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1
Chui, Wing Hong, and Paul Vinod Khiatani. "Delinquency Among Members of Hong Kong Youth Street Gangs: The Role of the Organizational Structures of Gangs and Triad Affiliations." International Journal of Offender Therapy and Comparative Criminology 62, no. 9 (September 12, 2017): 2527–47. http://dx.doi.org/10.1177/0306624x17730616.
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This study explores the importance of organizational structures and formal affiliations with the Hong Kong triads to delinquency among youth street gang members in Hong Kong. More specifically, this study examines the relative importance of the number of organizational structures and triad affiliation to patterns of delinquency in a sample of active members of youth street gangs ( N = 201). With the aid of outreach social workers, a convenience sampling method was used to recruit a gender-balanced sample of at-risk youths. Logistic regression analysis of the survey data that was gathered indicated that formal affiliation to Hong Kong triads and the presence of organizational structures significantly increased the odds of delinquency (independently of each other). Suggestions for future research on gang membership and delinquency, with particular reference to the Asian context, are provided.
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Bichler, Gisela, Alexis Norris, and Citlalik Ibarra. "Evolving Patterns of Aggression: Investigating the Structure of Gang Violence during the Era of Civil Gang Injunctions." Social Sciences 9, no. 11 (November 11, 2020): 203. http://dx.doi.org/10.3390/socsci9110203.
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Mapping the structural characteristics of attack behavior, this study explores how violent conflict evolved with the implementation of civil gang injunctions (CGIs). Networks were generated by linking defendants and victims named in 963 prosecutions involving street gangs active in the City of Los Angeles (1998–2013). Aggregating directed ties to 318 groups associated with the combatants, we compare four observations that correspond with distinct phases of CGI implementation—development (1998–2001), assent (2002–2005), maturity (2006–2009), and saturation (2010–2013). Using a triad census to calculate a ratio of simple patterns (retaliation, directed lines, and out-stars) to complex three-way interactions, we observed that CGIs were associated with a substantive thickening of conflict—greater complexity was found in conflict relations over time. Dissecting the nature of change, stochastic actor-oriented models (SAOMs) show that enjoined gangs are more likely to initiate transitive closure. The findings suggest that crime control efforts must make regular adjustments in response to the evolving structure of gang interactions.
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Lo, T. Wing, and H. L. Tam. "Working With Chinese Triad Youth Gangs: Correct Diagnosis and Strategic Intervention." International Journal of Offender Therapy and Comparative Criminology 62, no. 12 (February 2, 2018): 3708–26. http://dx.doi.org/10.1177/0306624x18755482.
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Across the world, youth workers have been active in helping vulnerable youth groups. In Hong Kong, government-funded youth services are conducted by professional social workers to help vulnerable youths. This article adopted a case study approach to investigate a youth group who committed a murder. Nine murderers and two social workers were interviewed. It aims to uncover the structure and activities of the group and analyse the gang intervention prior to the murder to find out what had gone wrong and identify the lessons that social workers can learn from the murder. Four misconceptions in gang intervention have been identified. First, because of the Triad (Chinese-organised crime) affiliation, this is not just a group of deviant youths but a youth gang. Second, because it is a gang, the social workers should not group them but should instead degroup them to avoid contamination. Third, diagnosis is different from labelling. With the right diagnosis, services can be tailor-made to delabel them. Fourth, when the youths are diagnosed as a gang, outreach work instead of centre work should be provided—social workers should reach out to the gangland to uncover the youths’ gang participation and crime involvement.
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Morla, Shravan. "Glycosaminoglycans and Glycosaminoglycan Mimetics in Cancer and Inflammation." International Journal of Molecular Sciences 20, no. 8 (April 22, 2019): 1963. http://dx.doi.org/10.3390/ijms20081963.
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Glycosaminoglycans (GAGs) are a class of biomolecules expressed virtually on all mammalian cells and usually covalently attached to proteins, forming proteoglycans. They are present not only on the cell surface, but also in the intracellular milieu and extracellular matrix. GAGs interact with multiple ligands, both soluble and insoluble, and modulate an important role in various physiological and pathological processes including cancer, bacterial and viral infections, inflammation, Alzheimer’s disease, and many more. Considering their involvement in multiple diseases, their use in the development of drugs has been of significant interest in both academia and industry. Many GAG-based drugs are being developed with encouraging results in animal models and clinical trials, showcasing their potential for development as therapeutics. In this review, the role GAGs play in both the development and inhibition of cancer and inflammation is presented. Further, advancements in the development of GAGs and their mimetics as anti-cancer and anti-inflammatory agents are discussed.
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Ago, Yasuhiko, Estera Rintz, Krishna Musini, Zhengyu Ma, and Shunji Tomatsu. "Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy." International Journal of Molecular Sciences 25, no. 2 (January 17, 2024): 1113. http://dx.doi.org/10.3390/ijms25021113.
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Mucopolysaccharidoses (MPSs) are a group of inborn errors of the metabolism caused by a deficiency in the lysosomal enzymes required to break down molecules called glycosaminoglycans (GAGs). These GAGs accumulate over time in various tissues and disrupt multiple biological systems, including catabolism of other substances, autophagy, and mitochondrial function. These pathological changes ultimately increase oxidative stress and activate innate immunity and inflammation. We have described the pathophysiology of MPS and activated inflammation in this paper, starting with accumulating the primary storage materials, GAGs. At the initial stage of GAG accumulation, affected tissues/cells are reversibly affected but progress irreversibly to: (1) disruption of substrate degradation with pathogenic changes in lysosomal function, (2) cellular dysfunction, secondary/tertiary accumulation (toxins such as GM2 or GM3 ganglioside, etc.), and inflammatory process, and (3) progressive tissue/organ damage and cell death (e.g., skeletal dysplasia, CNS impairment, etc.). For current and future treatment, several potential treatments for MPS that can penetrate the blood–brain barrier and bone have been proposed and/or are in clinical trials, including targeting peptides and molecular Trojan horses such as monoclonal antibodies attached to enzymes via receptor-mediated transport. Gene therapy trials with AAV, ex vivo LV, and Sleeping Beauty transposon system for MPS are proposed and/or underway as innovative therapeutic options. In addition, possible immunomodulatory reagents that can suppress MPS symptoms have been summarized in this review.
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K.K, MATHAN. "Impact of biological wastes on soil physical properties and yield of maize and finger millet." Madras Agricultural Journal 87, December (2000): 618–20. http://dx.doi.org/10.29321/maj.10.a00522.
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Two field trials were conducted in red sandy loam soils with finger millet (Eleusine corecana Geartn. var. Co 10) and maize (Zea mays var. Ganga-1) as test crops to evaluate the influence of biological wastes on the soil physical properties and the yield of crops. The biological wastes tried were maize straw, pig manure, municipal compost, sugarcane bagasse and groundnut husk applied at 20 t ha'. In both the trials, organic wastes application increased the saturated hydraulic conductivity and aggregate stability significantly. Significantly higher grain and straw yield over control obtained in pig manure and municipal compost treated plots
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Lamotte, Martin. "Los Ñetas en quête de transformation ?" Swiss Journal of Sociocultural Anthropology 29, no. 1 (January 3, 2024): 69–84. http://dx.doi.org/10.36950/sjsca.2023.29.8901.
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Belonging to the gang Los Ñetas, it is in part observing a certain number of rules which are transcribed in the Liderato, the book of the Ñetas. These rules are accompanied of trials procedure, the mesas disciplinarias, and of sanctions for those transgressing them. Yet, while Ñetas have developed a complex legal order to resolve internal conflicts, trials are little used. Is the Ñetas rules little applied, or little effective? What is the nature of these rules? Can we speak of Ñetas Law? And what is its role, if it is not used in cases of conflict?
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Krieger, Joshua L. "Trials and Terminations: Learning from Competitors’ R&D Failures." Management Science 67, no. 9 (September 2021): 5525–48. http://dx.doi.org/10.1287/mnsc.2020.3775.
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I analyze project continuation decisions where firms may resolve uncertainty through news about competitors’ research and development (R&D) failures, as well as through their own results. I examine the tradeoffs and interactions between product-market competition and technological learning from parallel R&D projects. Leveraging the biopharmaceutical industry’s unique characteristics to overcome barriers to measuring project-level responses, I use a difference-in-differences strategy to evaluate how competitor exit news alters a firm’s own project discontinuation decisions. The findings reveal that technological learning dominates competition effects. Firms are most sensitive to competitor failure news from within the same market and same technology area—more than doubling their propensity to terminate drug development projects in the wake of this type of information. Finally, I explore how levels of competition, uncertainty, and opportunities to learn moderate the response to competitor failure news. This paper was accepted by Joshua Gans, business strategy.
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Michelutti, Luca, Alessandro Tel, Marco Zeppieri, Tamara Ius, Edoardo Agosti, Salvatore Sembronio, and Massimo Robiony. "Generative Adversarial Networks (GANs) in the Field of Head and Neck Surgery: Current Evidence and Prospects for the Future—A Systematic Review." Journal of Clinical Medicine 13, no. 12 (June 18, 2024): 3556. http://dx.doi.org/10.3390/jcm13123556.
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Background: Generative Adversarial Networks (GANs) are a class of artificial neural networks capable of generating content such as images, text, and sound. For several years already, artificial intelligence algorithms have shown promise as tools in the medical field, particularly in oncology. Generative Adversarial Networks (GANs) represent a new frontier of innovation, as they are revolutionizing artificial content generation, opening opportunities in artificial intelligence and deep learning. Purpose: This systematic review aims to investigate what the stage of development of such technology is in the field of head and neck surgery, offering a general overview of the applications of such algorithms, how they work, and the potential limitations to be overcome in the future. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in conducting this study, and the PICOS framework was used to formulate the research question. The following databases were evaluated: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, ClinicalTrials.gov, ScienceDirect, and CINAHL. Results: Out of 700 studies, only 9 were included. Eight applications of GANs in the head and neck region were summarized, including the classification of craniosynostosis, recognition of the presence of chronic sinusitis, diagnosis of radicular cysts in panoramic X-rays, segmentation of craniomaxillofacial bones, reconstruction of bone defects, removal of metal artifacts from CT scans, prediction of the postoperative face, and improvement of the resolution of panoramic X-rays. Conclusions: Generative Adversarial Networks may represent a new evolutionary step in the study of pathology, oncological and otherwise, making the approach to the disease much more precise and personalized.
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McAvoy, Theodore, Joshua H. Freeman, Steven L. Rideout, Stephen M. Olson, and Mathews L. Paret. "Evaluation of Grafting Using Hybrid Rootstocks for Management of Bacterial Wilt in Field Tomato Production." HortScience 47, no. 5 (May 2012): 621–25. http://dx.doi.org/10.21273/hortsci.47.5.621.
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Seven hybrid tomato rootstocks with possible resistance to bacterial wilt caused by Ralstonia solanacearum and a known resistant cultivar were tested as grafting rootstocks to impart resistance to a bacterial wilt-susceptible cultivar, BHN 602. Greenhouse studies showed resistance of all the rootstocks to bacterial wilt. The disease incidence and yield of ‘BHN 602’ grafted to these rootstocks were evaluated in open-field tomato production in Florida and Virginia over four seasons. Significant differences in bacterial wilt incidence were observed between grafted entries in three of the four trials. In these three trials, grafted entries consistently exhibited the least bacterial wilt incidence compared with the controls; the self-graft, and non-grafted entries. Over all the trials, tomato plants grafted onto ‘Cheong Gang’, ‘BHN 1054’, and ‘BHN 998’ displayed the least bacterial wilt incidence. Rootstocks had a significant effect on total marketable yield in all the trials with certain grafted entries yielding significantly greater than non-grafted ‘BHN 602’. Field studies show that grafting holds promise for decreasing the impact of bacterial wilt on tomato cultivars as well as increasing the overall productivity of tomato cultivars.
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Feng, Zhenpeng, Miloš Daković, Hongbing Ji, Xianda Zhou, Mingzhe Zhu, Xiyang Cui, and Ljubiša Stanković. "Interpretation of Latent Codes in InfoGAN with SAR Images." Remote Sensing 15, no. 5 (February 24, 2023): 1254. http://dx.doi.org/10.3390/rs15051254.
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Generative adversarial networks (GANs) can synthesize abundant photo-realistic synthetic aperture radar (SAR) images. Some modified GANs (e.g., InfoGAN) are even able to edit specific properties of the synthesized images by introducing latent codes. It is crucial for SAR image synthesis since the targets in real SAR images have different properties due to the imaging mechanism. Despite the success of the InfoGAN in manipulating properties, there still lacks a clear explanation of how these latent codes affect synthesized properties; thus, editing specific properties usually relies on empirical trials, which are unreliable and time-consuming. In this paper, we show that latent codes are almost disentangled to affect the properties of SAR images in a nonlinear manner. By introducing some property estimators for latent codes, we are able to decompose the complex causality between latent codes and different properties. Both qualitative and quantitative experimental results demonstrate that the property value can be computed by the property estimators; inversely, the required latent codes can be computed given the desired properties. Unlike the original InfoGAN, which only provides the visual trend between properties and latent codes, the properties of SAR images can be manipulated numerically by latent codes as users expect.
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Kubaski, Francyne, Fabiano de Oliveira Poswar, Kristiane Michelin-Tirelli, Maira Graeff Burin, Diana Rojas-Málaga, Ana Carolina Brusius-Facchin, Sandra Leistner-Segal, and Roberto Giugliani. "Diagnosis of Mucopolysaccharidoses." Diagnostics 10, no. 3 (March 22, 2020): 172. http://dx.doi.org/10.3390/diagnostics10030172.
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The mucopolysaccharidoses (MPSs) include 11 different conditions caused by specific enzyme deficiencies in the degradation pathway of glycosaminoglycans (GAGs). Although most MPS types present increased levels of GAGs in tissues, including blood and urine, diagnosis is challenging as specific enzyme assays are needed for the correct diagnosis. Enzyme assays are usually performed in blood, with some samples (as leukocytes) providing a final diagnosis, while others (such as dried blood spots) still being considered as screening methods. The identification of variants in the specific genes that encode each MPS-related enzyme is helpful for diagnosis confirmation (when needed), carrier detection, genetic counseling, prenatal diagnosis (preferably in combination with enzyme assays) and phenotype prediction. Although the usual diagnostic flow in high-risk patients starts with the measurement of urinary GAGs, it continues with specific enzyme assays and is completed with mutation identification; there is a growing trend to have genotype-based investigations performed at the beginning of the investigation. In such cases, confirmation of pathogenicity of the variants identified should be confirmed by measurement of enzyme activity and/or identification and/or quantification of GAG species. As there is a growing number of countries performing newborn screening for MPS diseases, the investigation of a low enzyme activity by the measurement of GAG species concentration and identification of gene mutations in the same DBS sample is recommended before the suspicion of MPS is taken to the family. With specific therapies already available for most MPS patients, and with clinical trials in progress for many conditions, the specific diagnosis of MPS as early as possible is becoming increasingly necessary. In this review, we describe traditional and the most up to date diagnostic methods for mucopolysaccharidoses.
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Malczewski, Krzysztof. "The development of a generative approach for joint super-resolution image reconstruction from highly sparse raw data in the context of MR-PET imaging." Machine Graphics and Vision 32, no. 3/4 (December 18, 2023): 161–91. http://dx.doi.org/10.22630/mgv.2023.32.3.9.
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The present study introduces a rapid and efficient approach for reconstructing high-resolution images in hybrid MRI-PET scanners. The application of sparsity, compressed sensing (CS), and super-resolution reconstruction (SRR) methodologies can significantly decrease the demands of data acquisition while concurrently attaining high-resolution output. G-guided generative multilevel networks for sparsely sampled MR-PET input are shown here. Compressed Sensing using conjugate symmetry and Partial Fourier methodology speeds up data collection over k-space sampling methods. GANs and k-space adjustments are used in this image domain technique. The employed methodology utilizes discrete preprocessing stages to effectively tackle the challenges associated with the deblurring, reducing motion artifacts, and denoising of layers. Initial trials offer contextual details and accelerate evaluations. Preliminary experiments provide contextual information and expedite assessments.
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Flexer, Carol, and Donald P. Gans. "Distribution of Auditory Response Behaviors in Normal Infants and Profoundly Multihandicapped Children." Journal of Speech, Language, and Hearing Research 29, no. 3 (September 1986): 425–29. http://dx.doi.org/10.1044/jshr.2903.425.
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Responsiveness (yes/no decisions) to sound has been found to be similar for normal infants and profoundly multihandicapped children of comparable developmental ages (Flexer & Gans, 1985). The purpose of this investigation is to extend the comparison of these two groups by examining the distribution of their response behaviors to sound. Ten normal and 10 multihandicapped children were videotaped while various auditory signals were presented. Without knowledge of stimulus type, five judges listed the behaviors that occurred during 24 sound and 24 catch trials for each child. The behaviors were then evaluated as a function of the stimulus parameters of meaningfulness, bandwidth, and intensity. Results revealed that the profoundly multihandicapped children displayed relatively more reflexive than attentive type behaviors and exhibited fewer behaviors per response. The effects of stimulus-type on the numbers and distribution of responses are discussed.
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Jacobs, Arnaud, Thomas Drouet, Thibault Sterckeman, and Nausicaa Noret. "Phytoremediation of urban soils contaminated with trace metals using Noccaea caerulescens: comparing non-metallicolous populations to the metallicolous ‘Ganges’ in field trials." Environmental Science and Pollution Research 24, no. 9 (January 31, 2017): 8176–88. http://dx.doi.org/10.1007/s11356-017-8504-9.
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Imran Ali, Md, Sirajam Monira, Tapan Kumar, Syed Najrul Islam, Md Alfatun Kabir Himel, and Md Asraful Islam. "ASSESSMENT OF OPTIMAL SOWING TIME OF SEED PRODUCTION OF BJRI DESHI PAT-10 UNDER GANGES TIDAL FLOODPLAIN OF BANGLADESH." Tropical Agrobiodiversity 4, no. 2 (June 26, 2023): 48–52. http://dx.doi.org/10.26480/trab.02.2023.48.52.
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An investigation was conducted at Jute Research Substation, Kalapara, Patuakhali from July 2022 to February, 2023 to find out the appropriate sowing time for BJRI Deshi pat-10. The study consisted of five different sowing time at 15 days interval starting from 1 July to 15 September by following Randomized Complete Block Design with three trials. Sowing date had substantial impact on growth, yield attributes, seed yield and quality of BJRI Deshi pat-10. The maximum plant population (563.33), base diameter (6.54 mm), branch plant-1 (5.20), seeds pod-1 (37.80), seed yield (677.00 kg ha-1), and percentage germination (98.00 %) were recorded in 16 July. After 16 July, decreasing trends of all parameters were recorded in the investigation. The least results were recorded at 15 September sowing treatments. BJRI Deshi pat-10 is the light sensitive crop, after subsequently reduced in day length, the seed yield and quality were hampered. Finally, it would be summarized that the sowing BJRI Deshi pat-10 at 16 July will be better practice for attaining maximum seed yield and ensuring quality of seed.
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Chang, Yu-Cheng, Yuan-Ju Lee, Jeff S. Chueh, and Shang-Jen Chang. "Glycosaminoglycan replacement therapy in preventing women’s recurrent urinary tract infections?: A systematic review and meta-analysis." Urological Science 35, no. 2 (June 2024): 59–66. http://dx.doi.org/10.1097/us9.0000000000000016.
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The aim of this study is to systematically review the published literature and pool the data to evaluate the effectiveness of glycosaminoglycans (GAGs) replacement therapy in preventing women’s recurrent urinary tract infections (rUTIs). A systematic search of PubMed was performed to identify comparative and randomized controlled trials that compared the efficacy of GAG replacement therapy with control groups (placebo/antibiotics/standard therapy) in preventing rUTI in women. The evaluated outcomes included risk of rUTI, rUTI episodes per patient-year, time to urinary tract infection recurrence, pelvic pain and urgency/frequency, and the quality of life (Short Form-36 questionnaire). The Cochrane Collaboration Review Manager software (RevMan, version 5.4) was used for statistical analysis. Seven trials, including 2 randomized control studies and 5 retrospective comparative trials, met the inclusion criteria and were enrolled into our meta-analysis. A total of 702 patients were included in the analysis. Five studies adopted intravesical instillations and 2 used oral-administered hyaluronic acid. The synthesized results revealed that GAG replacement therapy significantly reduced the risk of rUTI (odds ratio: 0.31), reduced urinary tract infection-associated symptoms on pelvic pain and urgency/frequency scores (WMD: −6.70), and contributed to nonsignificant influence in quality of life, prolongation of time to rUTI, and the risk of rUTI per patient-year. In conclusion, the current meta-analysis revealed that GAG replacement therapy might serve as an alternative treatment strategy for rUTI. Further studies should focus on the durability of the protective effect of hyaluronic acid and the optimal protocol for dosage and administration route for GAG replacement therapy.
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Wing, Heath. "The Sovereign Fool and Bare Life in Cormac McCarthy’s Blood Meridian." Cormac McCarthy Journal 20, no. 2 (October 1, 2022): 158–77. http://dx.doi.org/10.5325/cormmccaj.20.2.0158.
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ABSTRACT This article argues that violence in Cormac McCarthy’s Blood Meridian is attributed to an allegory of sovereignty found in the work. As such, Giorgio Agamben’s notion of state of exception—a sovereign space of suspended law—is the common denominator for violence in the novel, which reduces human life to an animalized existence known as bare life and accounts for the novel’s unanthropocentric viewpoint. The state of exception is first enacted by way of the illegal scalp-hunting contract exchanged between Governor Trias and the Glanton gang, which is mediated by the judge. Furthermore, Holden’s place of privilege at the governor’s side in his palace demonstrates allegorically the relationship of the king and his court jester-fool, thus signaling the sovereign’s need for chaos and violence for validation. Ultimately, this article interprets Blood Meridian as a novel that can be understood as a biopolitical metaphor for the modern nation-state.
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Wang, Winston, and Tun-Wen Pai. "Enhancing Small Tabular Clinical Trial Dataset through Hybrid Data Augmentation: Combining SMOTE and WCGAN-GP." Data 8, no. 9 (August 23, 2023): 135. http://dx.doi.org/10.3390/data8090135.
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This study addressed the challenge of training generative adversarial networks (GANs) on small tabular clinical trial datasets for data augmentation, which are known to pose difficulties in training due to limited sample sizes. To overcome this obstacle, a hybrid approach is proposed, combining the synthetic minority oversampling technique (SMOTE) to initially augment the original data to a more substantial size for improving the subsequent GAN training with a Wasserstein conditional generative adversarial network with gradient penalty (WCGAN-GP), proven for its state-of-art performance and enhanced stability. The ultimate objective of this research was to demonstrate that the quality of synthetic tabular data generated by the final WCGAN-GP model maintains the structural integrity and statistical representation of the original small dataset using this hybrid approach. This focus is particularly relevant for clinical trials, where limited data availability due to privacy concerns and restricted accessibility to subject enrollment pose common challenges. Despite the limitation of data, the findings demonstrate that the hybrid approach successfully generates synthetic data that closely preserved the characteristics of the original small dataset. By harnessing the power of this hybrid approach to generate faithful synthetic data, the potential for enhancing data-driven research in drug clinical trials become evident. This includes enabling a robust analysis on small datasets, supplementing the lack of clinical trial data, facilitating its utility in machine learning tasks, even extending to using the model for anomaly detection to ensure better quality control during clinical trial data collection, all while prioritizing data privacy and implementing strict data protection measures.
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Bicer, Metin, Andrew TM Phillips, Alessandro Melis, Alison McGregor, and Luca Modenese. "DEEP LEARNING FOR ENLARGING HUMAN MOTION CAPTURE (MOCAP) DATASETS." Orthopaedic Proceedings 105-B, SUPP_16 (November 17, 2023): 63. http://dx.doi.org/10.1302/1358-992x.2023.16.063.
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AbstractOBJECTIVESApplication of deep learning approaches to marker trajectories and ground reaction forces (mocap data), is often hampered by small datasets. Enlarging dataset size is possible using some simple numerical approaches, although these may not be suited to preserving the physiological relevance of mocap data. We propose augmenting mocap data using a deep learning architecture called “generative adversarial networks” (GANs). We demonstrate appropriate use of GANs can capture variations of walking patterns due to subject- and task-specific conditions (mass, leg length, age, gender and walking speed), which significantly affect walking kinematics and kinetics, resulting in augmented datasets amenable to deep learning analysis approaches.METHODSA publicly available (https://www.nature.com/articles/s41597-019-0124-4) gait dataset (733 trials, 21 women and 25 men, 37.2 ± 13.0 years, 1.74 ± 0.09 m, 72.0 ± 11.4 kg, walking speeds ranging from 0.18 m/s to 2.04 m/s) was used as the experimental dataset. The GAN comprised three neural networks: an encoder, a decoder, and a discriminator. The encoder compressed experimental data into a fixed-length vector, while the decoder transformed the encoder's output vector and a condition vector (containing information about the subject and trial) into mocap data. The discriminator distinguished between the encoded experimental data from randomly sampled vectors of the same size. By training these networks jointly using the experimental dataset, the generator (decoder) could generate synthetic data respecting specified conditions from randomly sampled vectors. Synthetic mocap data and lower limb joint angles were generated and compared to the experimental data, by identifying the statistically significant differences across the gait cycle for a randomly selected subset of the experimental data from 5 female subjects (73 trials, aged 26–40, weighing 57–74 kg, with leg lengths between 868–931 mm, and walking speeds ranging from 0.81–1.68 m/s). By conducting these comparisons for this subset, we aimed to assess the synthetic data generated using multiple conditions.RESULTSWe visually inspected the synthetic trials to ensure that they appeared realistic. The statistical comparison revealed that, on average, only 2.5% of the gait cycle showed significantly differences in the joint angles of the two data groups. Additionally, the synthetic ground reaction forces deviated from the experimental data distribution for an average of 2.9% of the gait cycle.CONCLUSIONSWe introduced a novel approach for generating synthetic mocap data of human walking based on the conditions that influence walking patterns. The synthetic data closely followed the trends observed in the experimental data, also in the literature, suggesting that our approach can augment mocap datasets considering multiple conditions, an approach unfeasible in previous work. Creation of large, augmented datasets allows the application of other deep learning approaches, with the potential to generate realistic mocap data from limited and non-lab-based data. Our method could also enhance data sharing since synthetic data does not raise ethical concerns. You can generate and download virtual gait data using our GAN approach from https://thisgaitdoesnotexist.streamlit.app/.Declaration of Interest(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
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Maguire, Muireann. "Aleksei N. Tolstoi and the Enigmatic Engineer: A Case of Vicarious Revisionism." Slavic Review 72, no. 2 (2013): 247–66. http://dx.doi.org/10.5612/slavicreview.72.2.0247.
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In this article, Muireann Maguire examines the cultural construction of the trope of the engineer-inventor in Russia during the 1920s and 1930s, focusing on the changing representation of this archetype in three science fiction novels by Aleksei Tolstoi: Aelita (1922-23), Soiuzpiati (The Gang of Five, 1925), and Giperboloid inzhenera Garina (Engineer Garin's Death Ray, 1925-26). Tolstoi's fiction portrays engineers as misguided and self-centred at best and as amoral, megalomaniacal, and irredeemably un-Soviet at worst. This increasingly negative portrayal of the engineers in these novels, and in their later redactions and cinema versions, helped to prepare the way for the alienation of engineer and technical specialist within Soviet society, providing cultural justification for Iosif Stalin's show trials and purges of both categories in the 1930s. Tolstoi's alienation of the engineer-inventor, the traditional hero of early Soviet nauchnaia fantastika (science fiction), prefigured the occlusion of science fiction as a mainstream literary genre. As a trained engineer, former aristocrat, and returned émigré whose own status in Soviet Russia was deeply compromised, Tolstoi's literary demonization of engineers effectively purchased his own acceptance within the Stalinist literary hierarchy.
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Silva, Zilmara Alves da, and Maria Helena Santana Cruz. "“Boys and girls of God”: the experience of re-socialization of adolescents and young people in conflict with the law in the Santa Filomena community." JOURNAL OF RESEARCH AND KNOWLEDGE SPREADING 2, no. 1 (May 30, 2021): e12433. http://dx.doi.org/10.20952/jrks2112433.
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This research aims to analyze the resocialization process of the second generation of adolescents and young people from the Meninos de Deus project and the contributions of socio-affective relationships in the resignification of individual trajectory in the context of violence in the Santa Filomena community. The study is necessary to understand the importance of strengthening the resocialization processes in an open space, which has the triad of public authorities, civil society and the community as the executing nucleus of socio-educational measures. The Meninos de Deus group was born in 2007 and was born from a pact, among youths in conflict with the law, based on the premise of mutual care, commitment to life and in the re-socializing walk with the community. In this group, the feeling of belonging is opposed to the feeling that young people and adolescents in conflict with the law had with the youth gang or the criminal faction they belonged. The methodology to be used is ethnography, where we will use field research, characterized as an integration of data obtained in the field and by bibliographic reading.
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Kolotaev, V. A., and E. V. Ulybina. "Structural Features of Film Narrative in Chaplin’s Early Comedies." Art & Culture Studies, no. 1 (March 2023): 12–29. http://dx.doi.org/10.51678/2226-0072-2023-1-12-29.
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The article studies the original way of an action developing, building a narrative in the early films of Charlie Chaplin. Compared to traditional models of film narration in which there is a trajectory of the main character moving through the spatial boundaries of the worlds with a series of trials, losses / gains, and the final return of the renewed hero, the great comedian develops and implements a structure based on the character’s ability to annihilate when he enters an unusual world for him meanings and rules on which the familiar world of other characters, ordinary people, is based. Almost from the first independent works, Chaplin uses the theatrical technique of the quirky quo, the confusion that arose as a result of erroneous recognition, both to achieve a comic effect and for the tasks of film narration, in order to show the main feature of his hero — this is a person who always finds himself out of place, not having an identity. He either pretends to be someone else, or he is not taken for who he really is, and thus penetrates into a strange space for him, the laws of organization of which he undermines with ridiculous behavior, gags, bringing the norms to the point of absurdity, hoatizing the established order.
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Ndlovu, Sebastian, Mumraiz Naqshband, Stanley Masunda, Kudzayi Ndlovu, Krissen Chettiar, and Anoop Anugraha. "Clinical effectiveness of the Ganga Hospital Open Injury Severity Score for limb salvage versus amputation in patients with complex limb injuries." Bone & Joint Journal 105-B, no. 1 (January 1, 2023): 21–28. http://dx.doi.org/10.1302/0301-620x.105b1.bjj-2022-0934.r1.
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Aims Clinical management of open fractures is challenging and frequently requires complex reconstruction procedures. The Gustilo-Anderson classification lacks uniform interpretation, has poor interobserver reliability, and fails to account for injuries to musculotendinous units and bone. The Ganga Hospital Open Injury Severity Score (GHOISS) was designed to address these concerns. The major aim of this review was to ascertain the evidence available on accuracy of the GHOISS in predicting successful limb salvage in patients with mangled limbs. Methods We searched electronic data bases including PubMed, CENTRAL, EMBASE, CINAHL, Scopus, and Web of Science to identify studies that employed the GHOISS risk tool in managing complex limb injuries published from April 2006, when the score was introduced, until April 2021. Primary outcome was the measured sensitivity and specificity of the GHOISS risk tool for predicting amputation at a specified threshold score. Secondary outcomes included length of stay, need for plastic surgery, deep infection rate, time to fracture union, and functional outcome measures. Diagnostic test accuracy meta-analysis was performed using a random effects bivariate binomial model. Results We identified 1,304 records, of which six prospective cohort studies and two retrospective cohort studies evaluating a total of 788 patients were deemed eligible for inclusion. A diagnostic test meta-analysis conducted on five cohort studies, with 474 participants, showed that GHOISS at a threshold score of 14 has a pooled sensitivity of 93.4% (95% confidence interval (CI) 78.4 to 98.2) and a specificity of 95% (95% CI 88.7 to 97.9) for predicting primary or secondary amputations in people with complex lower limb injuries. Conclusion GHOISS is highly accurate in predicting success of limb salvage, and can inform management and predict secondary outcomes. However, there is a need for high-quality multicentre trials to confirm these findings and investigate the effectiveness of the score in children, and in predicting secondary amputations. Cite this article: Bone Joint J 2023;105-B(1):21–28.
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Travis, Charles. "Blood Meridian's Chronotopic Gates: Reading Cormac McCarthy through the Lens of a Literary-Historical GIS." International Journal of Humanities and Arts Computing 17, no. 2 (October 2023): 187–222. http://dx.doi.org/10.3366/ijhac.2023.0312.
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This geographical information systems (GIS) reading of Cormac McCarthy’s Blood Meridian: Or the Evening Redness in the West (1985) provides a literary geography analysis that plots latitude and longitude coordinates in conjunction with Mikhail M. Bakhtin’s chronotopes of the Road, the Rabelaisian, the Petty-Bourgeois Provincial Town, the Threshold and the political cartography of the United States–Mexico border established by the 1849 Treaty of Guadalupe Hidalgo to map the emergence of an American Imperial chronotope. Blood Meridian is a fictionalized account of historical events carried out by the Glanton Gang, a band of mercenaries contracted by Governor Trias in 1849 to counter the threat of Apache raids in Chihuahua province, Mexico. Viewed through the lenses of a GIS/MAXQDA platform, Blood Meridian comes into focus as ‘cartographical novel’ illuminating its literary geography as a melange, spun from allusions to and spatial remediations of Classical, medieval and Indigenous mythologies. The GIS/MAXQDA platform frames Blood Meridian as deep chronotopic map that, in tracing the spiralling lifepath of its protagonist, the ‘Kid’, across the terra damnata of the American Southwest and northern Mexico, creates an analogy and spatial metaphor for the violent geographical teleology of US nineteenth-century westward expansion which unfolded between the 1830s and 1880s.
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Simanovic, Tia, Paul McFarlane, Iain Brennan, William Graham, and Alex Sutherland. "Focused deterrence: A protocol for a realist multisite randomised controlled trial for evaluating a violence prevention intervention in the UK." PLOS ONE 19, no. 3 (March 28, 2024): e0301023. http://dx.doi.org/10.1371/journal.pone.0301023.
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Introduction Focused deterrence (FD) is a frequently cited intervention for preventing violence, particularly against violent urban gangs. The Youth Endowment Fund (YEF) believes it could be effective in the UK, based primarily on research conducted in the US. However, we contend that these studies have inadequate methodological designs, lack of rigorous testing, and small sample sizes. Therefore, the evidence supporting focused deterrence as an effective method, particularly outside the US, is inconclusive. The aim of the protocol is to better understand the potential effects of FD in the context of the UK, using a multisite evaluation experimental design to more closely investigate the evidence of its likely impact. Methods We planned a realist randomised controlled trial. The design is focused on a multisite trial consisting of two-arm randomised experiments in five locations. Each trial location will test their implementation of a core programme specified by the funder. The multisite nature will allow us to understand differential impacts between locations, improving the external validity of the results. Participants will be randomly selected from a wider pool of eligible individuals for the intervention. We estimate a sample size of approximately N = 1,700 individuals is required. Based on this pooled sample size, a relative reduction of 26% would be detectable in 80% of trials. The trial is coupled with a formative process evaluation of delivery and fidelity. The formative evaluation will use a mixed methods design. The qualitative aspect will include semi-structured cross-sectional and longitudinal interviews with programme leads, programme delivery team, and programme participants, as well as observations of the meetings between the programme delivery team (i.e., community navigators/mentors) and programme participants. The quantitative data for the formative evaluation will be gathered by the sites themselves and consist of routine outcome performance monitoring using administrative data. Sampling for interviews and observations will vary, with the researchers aiming for a higher number of individuals included in the first round of cross-sectional interviews and retaining as many as possible for repeat interviews and observations. Discussion This protocol outlines the process and impact evaluation methodology for the most extensive multisite evaluation of focused deterrence to date in the UK. Spanning five distinct sites with seven trials, the evaluation includes a cohort of 2,000 individuals, marking it as the only multisite trial of focused deterrence. Employing an integrated realist evaluation framework, the study uses qualitative and quantitative research methods. The anticipated findings will offer pivotal insights for formulating future violence prevention policies in the UK. They are also expected to contribute significantly to the corpus of literature on violence prevention and intervention evaluation. Trial registration Protocol registration: ISRCTN: 11650008 4th June 2023.
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Wiesinger, Anna-Maria, Florian Lagler, Brian Bigger, Christoph Kampmann, Roberto Giugliani, and Maurizio Scarpa. "19 The inflammation in the pathology of patients with mucopolysaccharidosis." Archives of Disease in Childhood 108, no. 6 (May 18, 2023): A6.3—A7. http://dx.doi.org/10.1136/archdischild-2023-esdppp.19.
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IntroductionMucopolysaccharidoses (MPS) are a group of rare lysosomal storage diseases caused by different enzyme deficiencies that lead to accumulation of glycosaminoglycans (GAGs) in lysosomes and the extracellular matrix. This storage-induced inflammation is a key driver of cytopathology in MPS, and pharmacological immunomodulation can improve brain, cartilage and bone symptoms in rodents. As the approved enzyme replacement therapy cannot stop the progression of CNS involvement and several other symptoms, we develop a rational for personalized treatment to address the unmet clinical need in MPS patients.MethodsFirst, we conducted comprehensive literature reviews on MPS type specific inflammatory immune response and on the safety and efficacy of Adalimumab, Infliximab, Abatacept, Alemtuzumab, Anakinra. Second, by expert consensus top candidates for innovative personalized drug repurposing in MPS patients were identified and ranked.ResultsThe key process is the upregulation of toll-like receptor-4 (TLR4) pathway induced by the accumulation of heparan sulfate (HS) in MPS type I, II and III. This and other relevant mech-anisms indicate TNF-alpha and IL-1 as most promising targets. Systematic analysis of the clinical pharmacology of all relevant candidates and several expert focus group meetings identified Anakinra, Adalimumab, Cladribine and Abatacept as top candidate’s dependent on the individual clinical situation.ConclusionsThese results provide the rational for individual treatment trials (ITTs) with the aim to evaluate immunomodulatory molecules, repurposed in MPS. Furthermore, they will – together with the results of the ITTs – be utilized for the development of a decision tool for the personalized treatment of unmet clinical needs in these patients.
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Malczewski, Krzysztof. "A Framework for Reconstructing Super-Resolution Magnetic Resonance Images from Sparse Raw Data Using Multilevel Generative Methods." Applied Sciences 14, no. 4 (February 6, 2024): 1351. http://dx.doi.org/10.3390/app14041351.
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Super-resolution magnetic resonance (MR) scans give anatomical data for quantitative analysis and treatment. The use of convolutional neural networks (CNNs) in image processing and deep learning research have led to super-resolution reconstruction methods based on deep learning. The study offers a G-guided generative multilevel network for training 3D neural networks with poorly sampled MR input data. The author suggest using super-resolution reconstruction (SRR) and modified sparse sampling to address these issues. Image-based Wasserstein GANs retain k-space data sparsity. Wasserstein Generative Adversarial Networks (WGANs) store and represent picture space knowledge. The method obtains null-valued k-space data and repairs fill gaps in the dataset to preserve data integrity. The proposed reconstruction method processes raw data samples and is able to perform subspace synchronization, deblurring, denoising, motion estimation, and super-resolution image production. The suggested algorithm uses different preprocessing methods to deblur and denoise datasets. Preliminary trials contextualize and speed up assessments. Results indicate that reconstructed pictures have better high-frequency features than sophisticated multi-frame techniques. This is supported by rising PSNR, MAE, and IEM measurements. A k-space correction block improves GAN network refinement learning in the suggested method. This block improves the network’s ability to avoid unnecessary data, speeding reconstruction. A k-space correction module can limit the generator’s output to critical lines, allowing the reconstruction of only missing lines. This improves convergence and speeds rebuilding. This study shows that this strategy reduces aliasing artifacts better than contemporaneous and noniterative methods.
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Sunardi, Tasyia Juliana, and Irine Kurniastuti. "PENGEMBANGAN MEDIA BUSY BOOK UNTUK MENGEMBANGKAN KECERDASAN NATURALIS PADA ANAK USIA DINI." PAUDIA : Jurnal Penelitian dalam Bidang Pendidikan Anak Usia Dini 11, no. 2 (November 30, 2022): 501–9. http://dx.doi.org/10.26877/paudia.v11i2.11437.
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AbstractThis study was derived by the needs of the children to develop their naturalist intelligence. The importance of this research is to make children knowing the state of nature through the process of direct observation and playing busy book. The aim of this research is to develop the media that suited for the characteristics of the children in early age and discover the quality of the busy book products as a media to develop naturalist intelligence in children aged 3-5 years old. The method used in this research was research and development (R&D). There subject used in this study were eight children who were involved in the busy book media trial. This study took data on the analysis of research needs in the Yogyakarta and Sleman areas and product trials carried out on a limited basis at Jalan Affandi, Gang Kuwera No. 14, Caturtunggal Depok, Sleman, Yogyakarta. Data processing in this study used descriptive-qualitative techniques. The results of this study were as follows. 1) The busy book media equipped with a guidebook developed was beneficial to develop naturalist intelligence in early childhood based on the steps in ADDIE, Analyze, Design, Develop, Implement, and Evaluate. 2) The quality of the busy book and guidebook media products was “very good”. Thus, it can be concluded that the busy book media and guidebooks developed had very good quality and were useful for early childhoodKeywords: Research and development, busy book media, naturalist intelligence. AbstrakAbstrak Penelitian ini dilatarbelakangi oleh perlunya membantu anak usia dini khususnya pada anak usia 3-5 tahun dalam mengembangkan kecerdasan naturalis menggunakan media permainan. Pentingnya penelitian ini agar anak dapat mengetahui keadaan alam melalui proses observasi secara langsung serta bermain busy book. Tujuan penelitian adalah untuk mengembangkan media yang sesuai dengan karakteristik anak usia dini dan mengetahui kualitas produk media busy book untuk mengembangkan kecerdasan naturalis pada anak usia 3-5 tahun. Metode yang digunakan adalah penelitian dan pengembangan (R&D). Subjek yang digunakan dalam penelitian ini 8 anak dilibatkan untuk uji coba media busy book. Penelitian ini mengambil data analisis kebutuhan penelitian di daerah Yogyakarta dan Sleman dan uji coba produk yang dilaksanakan secara terbatas di Jalan Affandi, Gang Kuwera No. 14, Caturtunggal Depok, Sleman, Yogyakarta. Pengolahan data pada penelitian ini menggunakan teknik deskriptif-kualitatif. Hasil penelitian ini adalah sebagai berikut. 1) Media busy book untuk mengembangkan kecerdasan naturalis pada anak usia dini dilengkapi dengan buku panduan dikembangkan berdasarkan langkah-langkah dalam ADDIE, Analyze, Design, Develop, Implement, dan Evaluate. 2) Kualitas produk media busy book dan buku panduan adalah “sangat baik”. Dengan demikan dapat disimpulkan bahwa media busy book dan buku panduan yang dikembangkan memiliki kualitas sangat baik dan bermanfaat bagi anak usia dini. Kata kunci: Penelitian dan pengembangan, media busy book, kecerdasan naturalis
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Chauhan, Anmol, Sana Rabbani, Prof (Dr ). Devendra Agarwal, Dr Nikhat Akhtar, and Dr Yusuf Perwej. "Diffusion Dynamics Applied with Novel Methodologies." International Journal of Innovative Research in Computer Science and Technology 12, no. 4 (July 2024): 52–58. http://dx.doi.org/10.55524/ijircst.2024.12.4.9.
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An in-depth analysis of using stable diffusion models to generate images from text is presented in this research article. Improving generative models' capacity to generate high-quality, contextually appropriate images from textual descriptions is the main focus of this study. By utilizing recent advancements in deep learning, namely in the field of diffusion models, we have created a new system that combines visual and linguistic data to generate aesthetically pleasing and coherent images from given text. To achieve a clear representation that matches the provided textual input, our method employs a stable diffusion process that iteratively reduces a noisy image. This approach differs from conventional generative adversarial networks (GANs) in that it produces more accurate images and has a more consistent training procedure. We use a dual encoder mechanism to successfully record both the structural information needed for picture synthesis and the semantic richness of text. outcomes from extensive trials on benchmark datasets show that our model achieves much better outcomes than current state-of-the-art methods in diversity, text-image alignment, and picture quality. In order to verify the model's efficacy, the article delves into the architectural innovations, training schedule, and assessment criteria used. In addition, we explore other uses for our text-to-image production system, such as for making digital art, content development, and assistive devices for the visually impaired. The research lays the groundwork for future work in this dynamic area by highlighting the technical obstacles faced and the solutions developed. Finally, our text-to-image generation model, which is based on stable diffusion, is a huge step forward for generative models in the field that combines computer vision with natural language processing.
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Yang, Mei, Yuhan Liu, Yi-Ching Hsueh, Qiangzu Zhang, Yanhui Fan, Juntao Xu, Min Huang, et al. "Abstract LB_B19: Utilizing genome-informed modeling to assess CDK4/6 inhibitor response in breast cancer patients, simulate clinical trials, and result in novel CDK4/6 inhibitor treatment for chordoma patients." Molecular Cancer Therapeutics 22, no. 12_Supplement (December 1, 2023): LB_B19. http://dx.doi.org/10.1158/1535-7163.targ-23-lb_b19.
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Abstract Varied therapeutic responses were observed among cancer patients receiving the same treatment regimen, highlighting the challenge of identifying patients most likely to benefit from a given therapy. Here, we present an artificial intelligence-based approach, called CDK4/6 inhibitor Response Model (CRM), to address the complexity of predicting patient responses to treatment by a certain clinical scene on CDK4/6 inhibitors (CDK4/6i). To train the CRM, we transformed the genomic data of 980 breast cancer patients from the TCGA database into activity profiles of signaling pathways (APSP) by utilizing the modified Damage Assessment of Genomic Mutations (DAGM) algorithm. A scoring model was then established by random forest algorithm to classify the HR+/HER2- and HR-/HER2- breast cancer molecular subtypes by the differential APSP features between the two, which reasonably reflected the potential role played by CDK4/6 molecules in HR+/HER2- breast cancer cells. The effectiveness of CRM was then tested in a separate local patient cohort (n = 343) in Guangdong, China. Twin in-silico clinical trials (ICT) of previously disclosed clinical trials (NCT02246621, NCT02079636, NCT03155997, NCT02513394, NCT02675231) were performed to demonstrate the potential of CRM in generating concerted results as the real-world clinical outcomes. The CRM displayed high precision in classifying HR+/HER2- and HR-/HER2- breast cancer patients in TCGA (AUC=0.9956) and local patient cohorts (AUC=0.9795). Significantly, the scores were distinct (p = 0.025) between CDK4/6i-treated patients with different responses. Breast cancer patients from different subtypes were grouped into five distinct populations based on the scores assigned by the CRM. From twin ICT, the CRM scores reflected the differential responses of patient groups to CDK4/6i-based therapies. Thus, the CRM score showed not only a robust association with clinically observed CDK4/6i responses but also heterogenetic responses across subtypes. More than half of HR+/HER2+ patients may benefit from CDK4/6i-based treatment. The CRM empowered us to conduct ICT on different types of cancer patients responding to CDK4/6i-based therapies. We have discovered 131 subtypes of tumors that should respond to CDK4/6i-based therapies. Finally, one of our IIT demonstrated that chordoma patients, the only go-to treatment option is surgery, greatly responded to CDK4/6i treatment. Citation Format: Mei Yang, Yuhan Liu, Yi-Ching Hsueh, Qiangzu Zhang, Yanhui Fan, Juntao Xu, Min Huang, Xu Li, Su Chen, Jianfei Yang, Gang Niu. Utilizing genome-informed modeling to assess CDK4/6 inhibitor response in breast cancer patients, simulate clinical trials, and result in novel CDK4/6 inhibitor treatment for chordoma patients [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_B19.
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Nikolaev, S. V., I. G. Konopeltsev, M. V. Glukhova, F. A. Sapozhnikov, and A. G. Norkin. "TOXICITY ASSESSMENT OF THE DRUG BASED ON SILVER NANOPAR-TICLES AND PROTEOLYTIC EN-ZYME." International bulletin of Veterinary Medicine 3 (2020): 52–57. http://dx.doi.org/10.17238/issn2072-2419.2020.3.52.
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One of the most relevant areas of veteri-nary science is the search for new, environ-mentally safe, antimicrobial drugs. From this position, special attention should be paid to products based on ionized silver. As part of preclinical studies, the toxic properties of a new complex drug containing nanoserebro and a proteolytic enzyme as active substanc-es were determined. The toxicity study was performed on healthy sexually Mature out-bred white male mice with a live weight of 20-24 grams. The effect of a single dose was determined by intragastric (n=7) and intra-peritoneal administration (n=7), chronic tox-icity was determined by introperitoneal ad-ministration of the drug for 14 days (n=12). A control group of mice was given saline. The toxic effects of the drug were assessed by changes in behavioral response, appetite, body weight, and the number of fatalities. At the end of the experiment, the surviving mice were euthanized, the hematological properties of the blood and the state of inter-nal organs were evaluated. In the course of studies, it was not possible to establish a lethal dose of the drug, since the maximum allowable volume for intragastric and intra-peritoneal administration (1.0 ml) did not cause it. The tolerated dose of this drug with single and multiple administration was more than 40,000 mg/kg of body weight, which in accordance with GOST 12.1.007-76 allows it to be classified as class 4 toxicity (more than 5,000 mg/kg when administered in the stomach). The use of the drug for two weeks caused minor reversible morphological changes in the blood in mice: hyperchromia (an increase in hemoglobin by 2.3 PG / ml; P<0.05) and more pronounced anisocytosis of red blood cells (by 2.7%; P<0.001), with-out any macroscopic changes in internal or-gans. Thus, the results obtained reflect the weak toxic effect of the drug, which allows us to go directly to its clinical trials.
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Gasparella, Marco, Carola Cenzi, Monica Piccione, Valentina Noemi Madia, Roberto Di Santo, Valeria Tudino, Marco Artico, et al. "Effects of Modified Glucosamine on the Chondrogenic Potential of Circulating Stem Cells under Experimental Inflammation." International Journal of Molecular Sciences 24, no. 12 (June 20, 2023): 10397. http://dx.doi.org/10.3390/ijms241210397.
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Glucosamine (GlcN) is a glycosaminoglycan (GAGs) constituent in connective tissues. It is naturally produced by our body or consumed from diets. In the last decade, in vitro and in vivo trials have demonstrated that the administration of GlcN or its derivates has a protective effect on cartilage when the balance between catabolic and anabolic processes is disrupted and cells are no longer able to fully compensate for the loss of collagen and proteoglycans. To date, these benefits are still controversial because the mechanism of action of GlcN is not yet well clarified. In this study, we have characterized the biological activities of an amino acid (AA) derivate of GlcN, called DCF001, in the growth and chondrogenic induction of circulating multipotent stem cells (CMCs) after priming with tumor necrosis factor-alpha (TNFα), a pleiotropic cytokine commonly expressed in chronic inflammatory joint diseases. In the present work, stem cells were isolated from the human peripheral blood of healthy donors. After priming with TNFα (10 ng/mL) for 3 h, cultures were treated for 24 h with DCF001 (1 μg/mL) dissolved in a proliferative (PM) or chondrogenic (CM) medium. Cell proliferation was analyzed using a Corning® Cell Counter and trypan blue exclusion technique. To evaluate the potentialities of DCF001 in counteracting the inflammatory response to TNFα, we measured the amount of extracellular ATP (eATP) and the expression of adenosine-generating enzymes CD39/CD73, TNFα receptors, and NF-κB inhibitor IκBα using flow cytometry. Finally, total RNA was extracted to perform a gene expression study of some chondrogenic differentiation markers (COL2A1, RUNX2, and MMP13). Our analysis has shed light on the ability of DCF001 to (a) regulate the expression of CD39, CD73, and TNF receptors; (b) modulate eATP under differentiative induction; (c) enhance the inhibitory activity of IκBα, reducing its phosphorylation after TNFα stimulation; and (d) preserve the chondrogenic potentialities of stem cells. Although preliminary, these results suggest that DCF001 could be a valuable supplement for ameliorating the outcome of cartilage repair interventions, enhancing the efficacy of endogenous stem cells under inflammatory stimuli.
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Cheung, Brian C. H., Xingyu Chen, Hannah J. Davis, Joshua Toth, Vivek B. Shenoy, Jeffrey E. Segall, and Mingming Wu. "Abstract LB277: β1-integrin and CD44 may both be required in modulating traction force transmission in collagen-hyaluronic acid hydrogels." Cancer Research 83, no. 8_Supplement (April 14, 2023): LB277. http://dx.doi.org/10.1158/1538-7445.am2023-lb277.
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Abstract Mechanics of the tumor microenvironment (TME) has long been recognized as a key aspect of the tumor invasion cascade. The TME contains a mesh of fibrous proteins such as collagen fibers, elastin, and fibronectin, and glycosaminoglycans (GAGs) that fill the interstitial space. As tumor cells migrate and invade throughout the extracellular matrix (ECM), they can communicate with each other mechanically by utilizing biophysical cues such as contractile forces and fiber alignment. For example, leader cells emerging from tumor spheroids can align ECM fibers to guide follower cells. In breast cancer, hyaluronic acid (HA), one of the GAGs found in the tumor stroma, is often overexpressed in pathological tissues, and stromal HA has been correlated with poor survival. Mechanically, while cells can guide their way by aligning matrix fibers through traction force generation, it is reported that HA may impact force transmission by altering matrix microstructure in the TME. It is therefore crucial to understand how HA impacts the interaction between tumor cells and the TME. In this study, we first investigated the bulk mechanical properties and micro-architecture of collagen-HA hydrogels (Col-HA). Our rheology measurements show that HA softens the collagen network while increasing the onset strain for strain-stiffening. Structurally, together with smaller pore sizes and thinner fibers as revealed by reflectance confocal microscopy, fiber alignment in Col-HA becomes less favorable. We then questioned how MDA-MB-231 cells generate traction forces in Col-HA using 3-dimensional traction force microscopy (3D TFM). Along with less fiber alignment around cells in Col-HA, we found that force transmission distance is reduced in Col-HA, as revealed by a shorter propagation of matrix deformation. In Col-HA, while the matrix resists alignment as the fiber network becomes more isotropic, we hypothesized that force transmission is also adhesion-dependent. Specifically, we investigated the role of β1-integrin and CD44, the key adhesion molecules to collagen fiber and HA respectively, in traction force generation. Immunofluorescence staining shows a significant increase in colocalization between actin and the two adhesion molecules in Col-HA, compared to pure collagen matrix. Interestingly, CD44 is colocalized with β1-integrin in Col-HA, but not in pure collagen. While it is widely recognized that cells transmit forces via β1-integrin in collagen matrices, we suspect that, in parallel with β1-integrin, CD44 may also be involved in traction force transmission because of its linkage between actin and HA. To examine how β1-integrin and CD44 contribute to force transmission in Col-HA, we neutralized them with antibodies and performed 3D TFM experiments. Preliminary data shows that matrix deformation decreases significantly when either β1-integrin and CD44 is blocked. In conclusion, we have demonstrated that HA reduces the mechanical communication between breast tumor cells by reducing force transmission distance. And in addition to β1-integrin, CD44 may also be required in traction force transmission in Col-HA. In the future, we will explore the differential role of β1-integrin and CD44 on tumor invasion in the presence of HA. Citation Format: Brian C.H. Cheung, Xingyu Chen, Hannah J. Davis, Joshua Toth, Vivek B. Shenoy, Jeffrey E. Segall, Mingming Wu. β1-integrin and CD44 may both be required in modulating traction force transmission in collagen-hyaluronic acid hydrogels [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB277.
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Zhao, Xiaobei, and Gang Chen. "Abstract B075: Anti-human LIV-1 antibody drug conjugate for treatment of metastatic prostate cancer." Cancer Research 83, no. 11_Supplement (June 2, 2023): B075. http://dx.doi.org/10.1158/1538-7445.prca2023-b075.
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Abstract In the worldwide male population, prostate cancer has the most frequent malignancy; out of all the cancer-related causes of deaths, it is also one of the most common. With the advance of new therapies of androgen receptor pathway inhibitors, patient survival rates have improved significantly. There are still tremendous unmet needs, however, for the patients with treat-refractory metastatic castration-resistant prostate cancer (mCRPC). LIV-1, also known as SLC39A6 or ZIP6, is a member of the zinc transporter family and was first identified as an estrogen-inducible gene in breast cancer. Previous studies with immunohistochemical (IHC) analysis showed that LIV-1 is expressed by estrogen receptor-positive (ER+), hormone-treated tumors (both primary and metastatic sites) and ER-/PR-/Her2- (triple-negative) breast cancers. These studies also showed that in healthy human tissues, LIV-1 expression is limited to hormonally-regulated organs (prostate, uterus, and breast). The broad expression of LIV-1 in prostate and breast cancer tumors in combination with the limited expression in vital organs makes LIV-1 an excellent target for an antibody-drug conjugate (ADC). We generated an ADC, BRY812, consisting of a humanized anti-LIV-1 mAb conjugated to monomethyl auristatin E (MMAE), via a novel conjugation method that prevents MMAE from coming off of the antibody during the circulation. The PK studies in rat and monkey showed that the free MMAE released from ADC is 1 to 2 log lower compared with approved ADCs prepared by the standard conjugation method. Low free MMAE concentration significantly lowers the risk of off target toxicity by the ADC. In vitro and in vivo studies demonstrated the antitumor activity of BRY812 for the treatment of prostate and ER+ and triple-negative breast cancers with a better safety profile and a larger therapeutic window. The humanized LIV-1 ADC, BRY812 is currently in preclinical toxicity studies and will advance to First-in-Human trials in April, 2023. Citation Format: Xiaobei Zhao, Gang Chen. Anti-human LIV-1 antibody drug conjugate for treatment of metastatic prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B075.
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Zhao, Xiaobei, Jie Zhu, Zhenhua Wu, Jing Li, yaqiong zhou, Lei Nie, and Gang Chen. "Abstract LB218: Developing a bispecific anti-ROR1 antibody drug conjugate for hematological and solid tumor treatment." Cancer Research 83, no. 8_Supplement (April 14, 2023): LB218. http://dx.doi.org/10.1158/1538-7445.am2023-lb218.
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Abstract Developing a bispecific anti-ROR1 Antibody Drug Conjugate for hematological and solid tumor treatment Receptor tyrosine kinase ROR1 is a type I transmembrane protein belongs to the ROR family members. ROR1 is a receptor for Wnt family signaling molecules Wnt5a and is a key regulator of normal cellular process, including cell proliferation, survival, and migration. It is also involved in the development and progression of many types of cancer. Although being an oncofetal protein with limited expression in most of the normal tissues, ROR1 is expressed abnormally in various hematological and solid cancers, making it a highly attractive target for antibody-drug conjugate (ADC) therapy. The current clinical results of ROR1 ADC have been promising in treating patients with relapsed and/or refractory (R/R) hematologic malignancies. Utilizing our unique and innovated linker platform, we screened many anti-ROR1 ADCs, with defined DAR=4. Those unique ADCs consist of a humanized monoclonal antibody (mAb against single epitope) or a bispecific antibody (BsAb against two epitopes), stably conjugated to an antimitotic agent. The bispecific mAbs that target to two different epitopes of ROR1, are superior to those antibodies that target to single epitope in the binding to ROR1-expressing tumor cells, the induction of tumor cell death and anti-tumor immunity. Our novel linker structure prevents payloads from coming off of the antibody during the circulation, significantly reduced the off-target toxicity. In vitro and In vivo studies demonstrated the antitumor activity of anti-ROR1 ADCs outperformed the lead anti-ROR1 ADC currently in phase II/IIl trial, providing a promising treatment for hematological and solid cancers with a better safety profile and a larger therapeutic window. The lead candidate molecule, BR111A will start the preclinical studies soon. Citation Format: Xiaobei Zhao, Jie Zhu, Zhenhua Wu, Jing Li, yaqiong zhou, Lei Nie, Gang Chen. Developing a bispecific anti-ROR1 antibody drug conjugate for hematological and solid tumor treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB218.
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Pievani, Alice, Isabella Maria Rebecca Azario, Laura Antolini, Tsutomu Shimada, Pravin Patel, Cristina Remoli, Benedetta Rambaldi, et al. "Neonatal Bone Marrow Transplantation Prevents Bone Pathology in a Mouse Model of Mucopolysaccharidosis Type I." Blood 124, no. 21 (December 6, 2014): 649. http://dx.doi.org/10.1182/blood.v124.21.649.649.
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Abstract Neonatal bone marrow transplantation (nBMT) could offer a novel therapeutic opportunity for genetic disorders by providing sustainable levels of the missing protein at birth, thus preventing tissue damage. We tested this concept in Mucopolysaccharidosis type I (MPS IH, Hurler syndrome), a lysosomal storage disorder caused by deficiency of α-L-iduronidase (IDUA). MPS IH is characterized by a broad spectrum of clinical manifestations including severe progressive skeletal abnormalities. Although BMT increases the life span of MPS IH patients, musculoskeletal manifestations are only minimally responsive if the timing of BMT delays, suggesting already irreversible bone damage. In this study, we tested the hypothesis that transplanting normal bone marrow into newborn MPS I mice, soon after birth, can prevent skeletal dysplasia. 1- to 2-day-old mutant mice were conditioned using a single administration of 20 mg/kg busulfan and then injected via the superficial temporal vein with 2 x 106 bone marrow cells from wild type (WT) donors. Age-matched WT and untreated MPS I mice were used as controls. Transplantation of normal bone marrow cells into preconditioned MPS I and WT neonates led to a similar engraftment level at 37 weeks after nBMT (peripheral blood, median MPS I nBMT 81.30%, range from 0.80% to 95.80% vs. median WT nBMT 67.45%, range from 16.00% to 95.86%, p = 0.714). Spleen, PB and thymus cells of nBMT MPS I mice were repopulated with committed lymphoid and myeloid populations similar to the transplanted WT mice. The >50% replacement of the hematopoiesis resulted in a measurable increase in IDUA activity in visceral organs, especially in the spleen, showing a correlation between engraftment levels and enzyme activity with clearance of GAGs from blood and tissues. At the time of euthanasia (37-week-old), reconstitution of normal hematopoiesis in MPS I mice was associated with a consistent amelioration of bone pathology, as revealed by radiographic skeletal examination. Radiographic analysis has shown that the width of the humerus, radius/ulna, femur and tibia of untreated MPS I mice was significantly larger at comparison with WT littermates. For MPS I nBMT mice, long bone widths, including the humerus (p = 0.0014, vs. untreated MPS I mice), the radius/ulna (p = 0.0003, vs. untreated MPS I mice), the femur (p = 0.0003, vs. untreated MPS I mice), and the tibia (p = 0.0003, vs. untreated MPS I mice) significantly decreased, compared to untreated MPS I mice. Furthermore, several three-dimensional architectural parameters in femurs such as trabecular number and separation, cortical thickness and bone mineral volume were analyzed by micro-CT, resulting in a significant difference between untreated and nBMT MPS I mice. All examined nBMT MPS I mice displayed bone parameter values comparable to WT mice, confirming that nBMT mice had significant improvements in skeletal phenotype approaching complete normalization of each parameter tested. Histologically, in MPS I cortical bone, osteocytes were increased and contained vacuoles, likely reflecting GAGs storage. Histological amelioration of these features was consistently observed in femurs of all nBMT mice with a definite reduction in both hyperosteocytosis and lysosomal vacuolization, confirming that the perinatal treatment of the disease can positively impact the skeletal phenotype in MPS I. We also evaluated KS levels in the blood as a biomarker of MPS with skeletal dysplasia. Normalization of blood KS level strongly supports the notion that nBMT corrects the pathological and clinical bone lesions in nBMT MPS I mice. Our findings demonstrate that nBMT prevents some of the relevant abnormalities of the skeletal pathology in the MPS I mouse model. Moreover, improvements in bone parameters correlated with high levels of bone marrow-derived cell engraftment in multiple hematopoietic compartments, suggesting that the early and complete restoration of normal hematopoiesis can have significant impact on the bone development of newborn MPS I mice. Future clinical trials are needed to confirm our findings. Disclosures No relevant conflicts of interest to declare.
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Chen, Zirong, Gang Huang, Katy Torres, Fiona Stavros, Alessandra Ahmed, Jason Miller, Tian Zhao, Jinming Gao, and Ruolan Han. "Abstract LB245: ONM-501, a dual-activating polyvalent STING agonist, enhances tumor retention and demonstrates favorable preclinical safety profile." Cancer Research 83, no. 8_Supplement (April 14, 2023): LB245. http://dx.doi.org/10.1158/1538-7445.am2023-lb245.
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Abstract Background: The Stimulator of Interferon Genes (STING) plays a crucial role in the innate immune response. Several previous STING agonist development compounds have shown limited therapeutic efficacy in oncology clinical trials. ONM-501 is a novel STING agonist: the endogenous STING agonist 2’,3’-cyclic GMP-AMP (cGAMP) is encapsulated within PC7A micelles. PC7A induces polyvalent STING condensation and prolongs immune activation. cGAMP-PC7A nanoparticles offer a dual ‘burst’ and ‘sustained’ STING activation. The anti-tumor efficacy and pharmacodynamic analysis of ONM-501 in multiple tumor models have been demonstrated previously. Here we report the pharmacokinetic (PK) and biodistribution (BD) analysis of ONM-501 in mice and safety evaluation in mice, rats and primates. Methods: PC7A polymers conjugated with LiCOR 800CW were mixed with unlabeled PC7A in 1:9 ratio and cGAMP was encapsulated into micelles to generate an “always-on” fluorescently labelled ONM-501-CW800. Naïve or tumor-bearing mice were injected subcutaneously (SC) or intratumorally (IT) with ONM-501-CW800, respectively, and plasma and multiple organ samples were collected; the whole tissue specimens were first imaged ex vivo using LiCOR Pearl Imaging system, and then homogenized and the fluorescence quantified against standard curves prepared by spiking ONM-501-CW800 into a homogenate of the relevant matrix. PK parameters were calculated using non-compartmental methods. Safety and tolerability were evaluated by single- and multiple-dose SC injections in naïve animals up to the highest feasible doses. Results: The BD pattern of ONM-501-CW800 was similar after IT and SC injections. The highest concentrations were observed at the injection sites and draining lymph nodes at all timepoints for both routes of administration. The concentrations in the injection site were much higher in tumors following IT than in dermal tissue following SC injection. After a 50 µg dose, systemic exposure to ONM-501-CW800 was ~1.8- and 2.4-fold lower after IT than SC injection based on Cmax and AUC(inf), respectively. The plasma t½ after IT injection, 17.4 hours, was ~1.3-fold longer than after SC injection, 12.9 hours. The Cmax and AUC (inf) in tumors were ~144- and 120-fold higher than in plasma after IT injection, with a t½ of 25.2 hours in tumors. In single-dose toxicology studies, ONM-501 was well tolerated in mice, rats and monkeys without severe or irreversible systemic toxicities up to the maximum feasible SC doses at 74, 45 and 30 mg/kg, respectively. In the 4-week repeat-dose GLP toxicology studies, the highest non-severely toxic SC dose (HNSTD) was 30 and 7.5 mg/kg in rats and monkeys, respectively. Conclusions: Systemic exposure to ONM-501 was lower after IT than SC administration, which is consistent with increased ONM-501 retention in tumors. Combined with preclinical toxicology studies, ONM-501 showed a favorable pharmacokinetic, tolerability and safety profile that support its continued development in cancer patients. Citation Format: Zirong Chen, Gang Huang, Katy Torres, Fiona Stavros, Alessandra Ahmed, Jason Miller, Tian Zhao, Jinming Gao, Ruolan Han. ONM-501, a dual-activating polyvalent STING agonist, enhances tumor retention and demonstrates favorable preclinical safety profile [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB245.
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Chaudhry, Sadaf Amin, Nadia Ali Zafar, Rabia Hayat, Ayesha Noreen, Gulnaz Ali, Zain Ali Raza, and Muhammad Nadeem. "Efficacy and safety of oral dapsone in acne vulgaris – experience of a tertiary care teaching hospital in central Lahore." Journal of Fatima Jinnah Medical University 14, no. 2 (July 15, 2020): 87–90. http://dx.doi.org/10.37018/xqbw1463.
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Background: Acne is the eighth most prevalent disease affecting 9.4% of the population worldwide and its prevalence in our country is estimated to be around 5%. Severe inflammatory acne is most likely to leave scars and in order to prevent facial disfigurement due to acne scarring, early treatment is desirable. Various treatment options have been formulated for acne, and are tailored according to the severity of the disease. Numerous clinical trials have been conducted till now, to determine the usefulness and side effect profile of such therapies, making acne treatment a highly studied area in dermatology. Objective of this study is to highlight the fact that oral Dapsone could be used as a cheaper alternate to isotretinoin in recalcitrant severe acne, especially in females where retinoids are sometimes contraindicated.
Patients and methods: 51 patients, suffering from severe nodulocystic acne, fulfilling the criteria, were enrolled from the Department of Dermatology, Sir Ganga Ram Hospital, Lahore. All the study patients were given oral Dapsone 50mg for initial two weeks and then 100mg daily for the next 10 weeks along with oral cimetidine and topical clindamycin application twice daily. Investigator Global Assessment Scale (IGAS) was employed to measure effectiveness. The treatment was considered ʽeffectiveʹ if the patient achieves 2 or more than 2-grade improvement or almost clear or clear skin at the end of 12 weeks according to IGAS scale. The lesion counts were also done before the start of therapy (day 1) and at every two weeks follow up for 12 weeks. The change in lesion count observed between the baseline number and that seen at follow up visits was also used to evaluate the effectiveness of oral Dapsone. Safety was analyzed by fortnightly visits of the patients to look for any undesirable side effects and monitoring of the hematologic profile of the patients. Final follow up was done at the end of 16 weeks.
Results: The study was conducted on 51 patients, with a ratio of 1:3 for males and females and a mean age of 25.2 years (SD ±5.81). At 12th week, patients had significant reduction in their acne lesions; with 7 patients (13.7%) showing completely clear skin, 17 patients (33.3%) had almost clear skin, 5 patients (9.8%) had 3-grade improvement. Twelve patients (23.5%) had 2-grade improvement from baseline score and only 2 patients (3.9%) had 1-grade improvement from baseline. Based on percentage reduction of lesions, excellent response was seen in 32 patients (62.7%), good response in 9 patients (17.6%), moderate response in 2 patients (3.9%), while no patient showed poor response. Dapsone was discontinued in 8 patients due to derangement of hematologic profile.
Conclusion: Oral Dapsone, when given carefully, is a very effective therapeutic option in severe recalcitrant acne, with limited side effects.
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Yuan, Robert, Andrew McGeehan, Sihong Zhou, Jennifer Smith, Dayson Moreira, Krishna Bajjuri, Cuong Tran, et al. "Abstract C115: Preclinical characterization of STRO-002, a clinical-stage anti-FolRα antibody-drug conjugate." Molecular Cancer Therapeutics 22, no. 12_Supplement (December 1, 2023): C115. http://dx.doi.org/10.1158/1535-7163.targ-23-c115.
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Abstract STRO-002 is a novel folate receptor alpha (FolRα)-targeting antibody-drug conjugate (ADC) currently undergoing evaluation in clinical trials at various phases of development in ovarian and endometrial cancer and pediatric AML. Here, we describe the favorable properties of the STRO-002 ADC and summarize its activity in preclinical models. STRO-002 is an ADC composed of an anti-FolRα antibody conjugated to four tubulin-targeting hemiasterlin warheads. Incorporation of non-natural amino acids, using Sutro’s XpressCF® and XpressCF+® cell-free expression and conjugation systems, allows for site-specific conjugation of the hemiasterlin payload, yielding a homogenous and high-fidelity ADC. As an ADC, STRO-002 internalizes rapidly into FolRα+ tumor cells and exhibits potent target-dependent cell killing on xenograft tumor cell lines. Further characterization of STRO-002 and the hemiasterlin payload reveals significant ADC bystander activity and a lower sensitivity to drug efflux via the P-gp drug pump compared to other microtubule-targeting warheads. In addition to robust direct and bystander cell killing, STRO-002 is also capable of triggering immunogenic cell death (ICD). In in vitro cell killing assays, STRO-002 induces all three hallmarks of ICD—HMGB1 and ATP release and surface exposure of calreticulin—and in in vivo vaccination studies, injection of STRO-002-killed tumor cells was effective at establishing a protective immune response against subsequent tumor challenge, identifying STRO-002 as a bonafide ICD inducer.In vivo, STRO-002 treatment demonstrates robust efficacy in ovarian xenograft models, even when treatment is initiated in large, established tumors. In addition, combination therapy with STRO-002 and carboplatin, anti-VEGF, or anti-PD-L1 results in greater efficacy than treatment with single agents alone, demonstrating combination benefit with current standard-of-care therapies. To better understand the activity of STRO-002 in more-translatable preclinical models, we turned to patient-derived xenografts (PDX) and found that STRO-002 exhibits good anti-tumor activity in endometrial cancer and non-small cell lung cancer PDX studies, suggesting potential clinical benefit in these indications. In conclusion, STRO-002 exhibits multiple advantageous properties as an ADC and shows good anti-tumor activity, either in combination or as a single agent, in both cell-derived xenograft and PDX models. Citation Format: Robert Yuan, Andrew McGeehan, Sihong Zhou, Jennifer Smith, Dayson Moreira, Krishna Bajjuri, Cuong Tran, Gang Yin, Alice Yam, Helena Kiefel, Xiaofan Li. Preclinical characterization of STRO-002, a clinical-stage anti-FolRα antibody-drug conjugate [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C115.
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Yadav, Satya Prakash, Ruchira Misra, Kharya Gaurav, Sunil Dutt Sharma, and Anupam Sachdeva. "Rituximab Use in Children - A Single Center Experience." Blood 108, no. 11 (November 16, 2006): 3892. http://dx.doi.org/10.1182/blood.v108.11.3892.3892.
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Abstract Treatment of children with chronic refractory ITP often results in significant morbidity and current therapies induce remission in fewer than half of children with chronic ITP. Rituximab is a humanized mouse monoclonal antibody against the B cell antigen CD20 that results in the prolonged depletion of B cells. CD20 is relatively selectively expressed on pre-B and mature B cells and may selectively treat antibody-mediated disorders. Among the lymphomas that occur in children, diffuse large cell NHL (DLCL) and Burkitt’s lymphoma both express high levels of CD20. Data from adult clinical trials demonstrated that rituximab is active against B-cell low-grade lymphomas, particularly follicular center cell lymphoma, and is also active against diffuse large cell lymphoma. Rituximab has been safely combined with standard doxorubicin, cyclophosphamide, vincristine, prednisone (CHOP) chemotherapy, with no substantial increase in toxicity. This study examined the efficacy and safety of rituximab in children with chronic immune thrombocytopenic purpura (ITP) and Burkitt’s lymphoma. It was a retrospective analysis of all children who received one or more courses of Rituximab in Pediatric Hemato-Oncology unit at Sir Ganga Ram Hospital from January 2005 to January 2006, who met the criteria of minimum follow up of 6 months. Five children age ranging from 3 yr to 11 years received 18 courses of rituximab during the study period. Three patients had chronic ITP (mean duration 20 months) non-responsive to IVIG, prednisolone, cyclosporin etc. Baseline platelet count were 10,000–15000/mm3. Rituximab was tried in an effort to avoid splenectomy. Each patient received 375-mg/m2 dose per course weekly for 4 weeks except one patients who could afford only 2 courses. First patient had response with platelets > 100000/mm3 for 8 months after which they again dropped to 15000/mm3. In other 2 cases sustained response has been seen with platelets > l00000/mm3 till date after a follow up of more than 12 months. Fourth patient had developed ITP during treatment of Precursor B cell Acute lymphoblastic leukemia (ALL) and had no response to steroids and IVIG. He responded after 4 courses of weekly rituximab and has maintained his platelets >50,000 except during chemotherapy blocks with follow up of 10 months. Now he is in maintenance phase of treatment for ALL. Fifth patient had abdominal Burkitt’s lymphoma resected but had residual local mass. Bone marrow and CSF were negative. Child was treated as per MCP842 protocol for B cell lymphoma with 4 courses of chemotherapy and Rituximab. Rituximab was given 24 hr prior to start of chemotherapy in each course. Residual tumor cleared after 2 courses of chemotherapy and Rituximab. Child is in remission for 12 months after finishing chemotherapy. In regard to side effects, one patient of chronic ITP developed hypotension and drowsiness 15 min after start of infusion during 1st course which improved after stopping infusion but later it was restarted with no problems and tolerated following 3 courses well. However this same patient developed white matter changes on MRI head done for headache 12 months in follow up. She was also treated with cyclosporin in past and had no neurological problems. Patient with Burkitt’s lymphoma developed late onset asymptomatic neutropenia 5 weeks after last course and recovered in following 3 weeks. Rituximab has good efficacy in cases of chronic ITP and Burkitt’s lymphoma. However patients should be monitored for acute reactions, late onset neutropenia and long-term effect on brain with white matter changes.
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Zhang, Yang, Nan Ji, Gang Chen, Haiyang Wu, Yi Wang, Xiao’ou Li, Wei Xu, et al. "Abstract CT086: H3.3-K27M neoantigen vaccine elicits CD4+ and CD8+ T cells immunity and improved prognosis against diffuse intrinsic pontine glioma." Cancer Research 83, no. 8_Supplement (April 14, 2023): CT086. http://dx.doi.org/10.1158/1538-7445.am2023-ct086.
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Abstract Background: Diffuse intrinsic pontine glioma (DIPG) harboring H3.3-K27M mutation is a malignant pediatric brain tumor with a >90% mortality rate within two years of diagnosis. Aiming to improve therapeutic outcomes, we herein describe a neoantigen peptide vaccine against H3.3-K27M which effectively triggers both CD8+ and CD4+ T cell responses. Methods: A neoantigen vaccine was designed to trigger T cell immunity against DIPGs harboring the H3.3-K27M mutation. ENACTING (NCT04749641) was then initiated as an open-label, single center, two-armed phase 1 trial to assess T cell immune responses and vaccine safety. The vaccine was administered intramuscularly with poly-ICLC adjuvant until tumor progression or untolerated toxicity. PBMCs before and after each vaccine treatment were collected for TCR repertoire analysis and immune response assessment. Results: As of November 2022, 10 patients have been treated. No grade 3-4 treatment-related adverse events have been observed, with fever (80%) and injection site pain (60%) being the most common AEs. On a per patient basis, vaccines induce a landscape change of TCR repertoire in patients’ PBMC after 4-6 times of dosing, indicating multiple dosing is required to trigger extensive T cell responses. T cell responses against neoantigens were detected and H3.3-K27M mutation-specific CD4+ and two CD8+ clones were validated. Among 9 efficacy-assessable patients, the one-year overall survival rate was 71.4%. The mPFS has reached 11.7 months and increasing. One patient reached complete response. As this trial remains ongoing, subgroup analysis will be reported in the future. Conclusion: The H3.3-K27M neoantigen vaccine was well tolerated and elicited mutation-specific CD4+ and CD8+ T cell responses in patients. Initial results from this ongoing study suggest that, compared with other current immunotherapies against DIPG, H3.3-K27M peptide vaccination may provide superior patient outcomes, for both life qualities and survival outcomes. Table 1. Clinical efficacy and adverse events Efficacy Complete response (CR) 1 (11.1%) Partial response (PR) 0 (0) Stable disease (SD) 8 (88.9%) Progressive disease (PD) 0 (0) Disease control rate (DCR) 100% 12-month overall survival 71.4% Median progression-free survival (mPFS) 11.7 months (95% CI, 7.0-NR) Median overall survival (mOS) 15.7 months (95% CI, 10.0-NR) Treatment-Related Adverse Events All grades Grade 3 Grade 4 Fever 9 (90.0%) 0 0 Injection site pain 6 (60.0%) 0 0 Bloating 1 (10.0%) 0 0 Abdominal pain 1 (10.0%) 0 0 Vomiting 1 (10.0%) 0 0 Increased blood LDH 1 (10.0%) 0 0 Proteinuria 1 (10.0%) 0 0 Hypocalcemia 1 (10.0%) 0 0 Citation Format: Yang Zhang, Nan Ji, Gang Chen, Haiyang Wu, Yi Wang, Xiao’ou Li, Wei Xu, Ling Peng, Tian Li, Yi Wang, Li-Feng Zhang, Shengjun Sun, Xiaobing Zhao, Si Li, Peter Alexander, Liwei Zhang, Qi-Jing Li. H3.3-K27M neoantigen vaccine elicits CD4+ and CD8+ T cells immunity and improved prognosis against diffuse intrinsic pontine glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT086.
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Lemech, Charlotte, Chenfei Zhou, Xianbao Zhan, Yan Shi, Jieqiong Liu, Sarina A. Piha-Paul, Gary Richardson, et al. "Abstract CT178: GQ1001: A next generation HER2-targeting ADC that exhibits promising early clinical efficacy with excellent tolerance in a multi-center, Phase Ia study." Cancer Research 83, no. 8_Supplement (April 14, 2023): CT178. http://dx.doi.org/10.1158/1538-7445.am2023-ct178.
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Abstract Background: GQ1001 is a novel HER2-targeted antibody-drug conjugate (ADC) that was developed using innovative conjugation technologies coined intelligent Ligase-Dependent Conjugation (iLDC), that can significantly improves homogeneity and biostability of ADC. In preclinical studies, GQ1001 showed a robust anti-tumor response in multiple HER2+ models alone or in combination with HER2 TKIs and chemotherapeutics, and excellent pharmacokinetics and safety profiles in rats and monkeys due to low level of payload release. Herein we report the initial results of the ongoing phase Ia study, which aims to investigate the safety, tolerability, pharmacokinetics and antitumor activity of GQ1001 in subjects with HER2+ advanced solid tumors. Methods: In phase Ia dose escalation, a modified 3+3 model was adopted to assess the safety, dose-limiting toxicity (DLT) and maximal tolerable dose (MTD) or dose recommended for dose expansion (DRDE) of GQ1001. GQ1001 was administered intravenously as a monotherapy on Day 1 of 21-day cycles. The starting dose was 1.2 mg/kg, followed by 2.4, 3.6, 4.8, 6.0, 7.2 and 8.4 mg/kg. Results: As of Dec. 28th, 2022, 32 subjects with HER2-positive advanced solid tumors, predominantly in breast (9), gastric or gastro-esophageal junction (9) and salivary gland (4), were enrolled and received GQ1001 treatment. Patients had a median 3 (range, 0-11) prior lines of therapies, and 37.5% of those previously received ≥2 lines of anti-HER2 therapies. Median exposure time of GQ1001 was 18.5 weeks. The longest treatment duration exceeded 370 days. No DLT was observed in all doses, MTD was not reached up to 8.4 mg/kg, the highest dose tested. Treatment-related adverse events (TRAEs) occurred in 24 subjects (75%). The most common TRAEs (>10.0%) were aspartate aminotransferase (AST) increased (37.5%), thrombocytopenia (28.1%), alanine aminotransferase (ALT) increased (25.0%), pyrexia (21.9%), anemia (18.8%), alkaline phosphatase increased (12.5%), vomiting (12.5%) and nausea (12.5%). Grade ≥3 TRAEs occurred in 9 subjects (28.1%), including 5 myelosuppression, 2 abnormal liver function, 1 hypertension and 1 vomiting. There were no drug-related deaths. The pharmacokinetics analysis showed the concentration of GQ1001 and TAb generally peaked rapidly and declined in a roughly biphasic manner. Among 15 evaluable subjects who received ≥ 7.2 mg/kg, 6 cases achieved confirmed partial response, and 3 had stable disease, the median progression-free survival was 4.8 months Conclusions: GQ1001 demonstrates an excellent tolerability and promising antitumor activity in heavily pretreated HER2-positive advanced solid tumors, supporting further evaluation of the safety and efficacy of GQ1001 at DRDE of 8.4 mg/kg in the following phase Ib trial. (NCT04450732; sponsored by GeneQuantum Healthcare (Suzhou) Co., Ltd.) Citation Format: Charlotte Lemech, Chenfei Zhou, Xianbao Zhan, Yan Shi, Jieqiong Liu, Sarina A Piha-Paul, Gary Richardson, Gang Qin, Paul H. Song, Lili Shi, Yajun Sun, Yi Xia. GQ1001: A next generation HER2-targeting ADC that exhibits promising early clinical efficacy with excellent tolerance in a multi-center, Phase Ia study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT178.
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Lu, Si, Yu Chen, Meiyu Fang, Zhengyun Zou, Di Wu, Zhiguo Luo, Jian Zhang, et al. "Abstract CT208: Tebotelimab, a PD-1/LAG-3 bispecific antibody, in patients with untreated, unresectable, recurrent or metastatic, mucosal melanoma: An open-label, single-arm, Phase 1 study." Cancer Research 83, no. 8_Supplement (April 14, 2023): CT208. http://dx.doi.org/10.1158/1538-7445.am2023-ct208.
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Abstract Background: Immune checkpoint inhibitors (CPIs) targeting PD-(L)1 have become a standard of care for untreated, advanced melanoma, but demonstrated limited efficacy in mucosal melanoma. Tebotelimab, also known as MGD013, is a PD-1/LAG-3 bispecific tetravalent DART® molecule with synergistic antitumor activity shown in preclinical studies. We conducted an open-label, single-arm, multi-cohort phase 1 study (NCT04653038) to assess the efficacy and safety of tebotelimab in melanoma patients (pts) including those with CPI-naïve mucosal melanoma. Methods: The CPI-naïve cohort of this study enrolled pts with unresectable, recurrent or metastatic, mucosal or acral melanoma who had received no systemic therapy. Tebotelimab 600 mg was administered intravenously once every two weeks. The primary endpoint was overall response rate (ORR) assessed by independent radiologic review committee (IRC) per RECIST v1.1 in the efficacy analysis set consisting of pts who received ≥1 dose of tebotelimab. A post-hoc sensitivity analysis was conducted in the IRC-response evaluable set consisting of pts with IRC-assessed target lesions in the efficacy analysis set who received ≥1 post-baseline tumor assessment by IRC or died within 13 weeks after first dose. Results are reported for mucosal melanoma. Results: At data cut-off (January 19, 2022), 25 pts with mucosal melanoma were enrolled (median age, 61 years; male, 40%; ECOG 1, 40%; TNM Stage IV, 92%; metastatic, 80%). LAG-3 expression level was ≥1% in seven (28%), <1% in 15 (60%), and unknown in three (12%). PD-L1 expression was positive (CPS≥1) in three (12%), negative (CPS<1) in 19 (76%), and unknown in three (12%). All pts received ≥1 dose of tebotelimab. In the efficacy analysis set (n=25), three, three, and four pts achieved complete response (CR), partial response (PR), and stable disease (SD), respectively, leading to a confirmed ORR of 24% (95% confidence interval [CI], 9-45), with median duration of response (DOR) not reached, and a disease control rate (DCR) of 40% (95% CI, 21-61). In the IRC-response evaluable set (n=20), three, three, and four pts achieved CR, PR, and SD, respectively, leading to a confirmed ORR of 30% (95% CI, 12-54), with median DOR not reached, and a DCR of 50% (95% CI, 27-73). Immune-related treatment-emergent adverse events occurred in 11 (44%) pts, most commonly, hypothyroidism (20%), hyperthyroidism (16%), and white blood cell count decreased (12%). Grade ≥3 and serious treatment-related adverse events (TRAEs) were reported in three (12%) and four (16%) pts, respectively. TRAEs led to treatment discontinuation and death each in one (4%). Conclusions: Tebotelimab demonstrated preliminary but promising antitumor activity and a tolerable safety profile in pts with untreated, unresectable, recurrent or metastatic, mucosal melanoma. Citation Format: Si Lu, Yu Chen, Meiyu Fang, Zhengyun Zou, Di Wu, Zhiguo Luo, Jian Zhang, Jing Chen, Gang Huang, Hongming Pan, Xiubao Ren, Ying Cheng, Haichuan Su, Yuan Xin, Qiong Hua, Jianmei Hou, Jun Guo. Tebotelimab, a PD-1/LAG-3 bispecific antibody, in patients with untreated, unresectable, recurrent or metastatic, mucosal melanoma: An open-label, single-arm, Phase 1 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT208.
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Alfiah, Haura, and Sri Maslihah. "Pengaruh Kepribadian Extraversion terhadap Perilaku Narsisme di Media Sosial Dimoderasi Social Media Engagement pada Usia Dewasa Awal." JURNAL PSIKOLOGI INSIGHT 6, no. 1 (November 29, 2023): 75–84. http://dx.doi.org/10.17509/insight.v6i1.64701.
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This study aims to determine the effect of extraversion personality on narcissistic behavior in social media moderated by social media engagement in early adulthood. This research design used quantitative methods with a total of 390 subjects consisting of social media users in the age range of 18-25 years in Bandung. The instruments used in this research are BFI (Big Five Inventory) which has been adapted by Reza (2017), the instrument of narcissism behavior based on seven aspects of narcissism from Raskin and Terry (1988), social media engagement as measured by Social Media Engagement Questionnaire (Przybylski et al., 2013). The data analysis technique used is Moderated Regression analysis (MRA) using SPSS version 25. This study shows the results of social media engagement as a moderating variable of extraversion personality on narcissistic behavior with a significant value of 0,192. Based on these results, it can be concluded social media engagement does not moderate the effect of extraversion on narcissistic behavior.Keywords: extraversionpersonality, narcissistic, socialmediaengagement.Tujuanpenelitianiniyaknimengetahuipengaruhkepribadianextraversionterhadapperilaku narsisme di media sosial yang dimoderasi social media engagement pada usiadewasa awal. Desain penelitian ini menggunakan metode kuantitatif dengan jumlah subjeksebanyak 390 yang terdiri dari pengguna media sosial pada rentang usia 18 – 25 tahun diKotaBandung.InstrumenyangdigunakandalampenelitianiniyakniBFI(BigFiveInventory) yang telah diadaptasi oleh Reza (2015), instrumen perilaku narsismeberdasarkantujuh aspek narsisme dari Raskin dan Terry (1998),socialmediaengagementdiukurdenganmenggunakaninstrumenSocialMediaEngagementQuestionnaire(Przybylskiet al.,2013). Teknikanalisisdatayangdigunakanyaitu Moderated Regression analysis (MRA) menggunakan program SPSS versi 25. Penelitianinimenunjukkanhasilsocial mediaengagementsebagai variabelmoderatorpengaruhkepribadianextraversionterhadapperilakunarsismedengannilaisignifikansisebesar0,192. Berdasarkanhasil tersebut dapat disimpulkan bahwa social mediaengagementtidakmemoderasipengaruhkepribadianextraversionterhadapperilakunarsismedimedia sosial.Kata kunci: kepribadianextraversion, narsisme,socialmediaengagement.Andreassen, C. S., Pallesen, S., Griffiths, M. D. (2017). The relationship betweenaddictive use of social media, narcissism, and self-esteem: Findings from a largenationalsurvey. AddictiveBehaviors,64, 287-293.Bendau, A., Petzold, M. B., Pyrkosch, L., Mascarell Maricic, L., Betzler, F., Rogoll, J.,Große, J., Ströhle, A., Plag, J. (2021). Associations between COVID-19 relatedmediaconsumptionandsymptomsofanxiety,depressionandCOVID-19related fear in the general population in Germany. European Archives of Psychiatry andClinicalNeuroscience,271(2),283–291Boursier, V., Gioia, F., Griffiths, M. D. (2020). 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Gottschalk, Petter. "Money laundering prevention: the challenge of insurance termination for outlaw biker gangs’ club houses." Journal of Money Laundering Control, April 3, 2024. http://dx.doi.org/10.1108/jmlc-01-2024-0003.
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Purpose The purpose of this paper is to discuss the legal barriers to termination of an insurance arrangement where there is suspicion of money laundering when paying insurance premiums. Design/methodology/approach Trials in court between insurance firm and outlaw biker gangs regarding insurance of their clubhouses. Findings Protection of insured seems more important than prevention of money laundering. Research limitations/implications This is a case study that cannot be generalized. Practical implications Anti money laundering is difficult when competing with other considerations. Social implications Accusations of money laundering is not sufficient to terminate an insurance contract. Rather, solid evidence is needed. Originality/value This is a real case of failing anti-money laundering efforts.
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Chui, Wing Hong, and Paul Vinod Khiatani. "Mediating the Maltreatment–Delinquency Relationship: The Role of Triad Gang Membership." Journal of Interpersonal Violence, February 23, 2018, 088626051876060. http://dx.doi.org/10.1177/0886260518760607.
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Owusu-Bempah, Abenaa. "Prosecuting rap: what does the case law tell us?" Popular Music, November 3, 2022, 1–19. http://dx.doi.org/10.1017/s0261143022000575.
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Abstract This article explores the admissibility and use of rap music as evidence in English criminal trials. It presents findings from an analysis of over 30 appeal cases. As well as unpacking the link between rap, race and gangs that is prevalent in these cases, the article challenges the categorisation of rap as ‘bad character evidence’, and critiques the way in which questions of relevance and prejudicial effect have been addressed by the courts. In particular, when making admissibility decisions, the courts appear to give little consideration to the cultural context, artistic conventions or social influences within the rap music genre, or the racialised nature of rap evidence. It is argued that, if rap is to be admissible evidence, a much more rigorous and informed approach is required.
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Prasad, Suday. "Outdoor Hatchery Larval Biology and Seed Production of Ganga River Prawn Macrobrachium gangeticum (Bate)." Current Journal of Applied Science and Technology, March 5, 2019, 1–7. http://dx.doi.org/10.9734/cjast/2019/v33i330066.
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Macrobrachium gangeticum (Bate) the third largest freshwater prawn in habitat in the river Ganga and Brahmaputra, which drain into Bay of Bengal. Seed production of this species (M. gangeticum) in India is done in indoor hatcheries. An outdoor hatchery system has been developed by the author at ICAR Research Complex for Eastern Region, Patna, in which M. gangeticum post larvae are produced. Larval rearing trials for M. gangeticum were carried out during the year 2008. The hatchery shades were covered with non transparent polythene sheets at the roof top to avoid direct sunlight. Larvae were reared in brackish water of 8-14 ppt (part per thousand) salinity for growth and development. Ten thousand larvae were stocked in 300 L tank and fed with live nauplii of Artemia salina twice in a day and after that 1 or 2 days, green algae developed in the larval rearing tank due to open sunlight, these algae were found to be ingested by larvae. The larvae fed voraciously and grew faster because of availability of green algae in the larval rearing tanks. The larvae passed through 15 molts, showing the characteristics of 11 distinct larval stages. First occurrence of post larvae (PL) has been recorded within 20 days and trial was conducted on the 35 days. The water quality parameters viz. water temperature, salinity, pH, dissolved oxygen; total hardness and alkalinity were recorded. Production of PL in trials during rearing was 6,480 and 5,870 with 21.6 and 19.56 PL/L respectively. The result of the present trials, the post larval production and shorter larval duration in M. gangeticum indicated the potential of commercial culture and hatchery operation in inland region.
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Valsted, Sebastian Satkunasingam, Andreas Thesbjerg Larsen, Henriette Edemann Callesen, and Dan Dupont Hougaard. "A Comparison of the Efficacy of Four Repositioning Maneuvers in the Treatment of Posterior Benign Paroxysmal Positional Vertigo." American Journal of Audiology, June 20, 2024, 1–15. http://dx.doi.org/10.1044/2024_aja-23-00177.
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Purpose: The purpose of the present review was to report the effectiveness of Epley maneuver compared to other manual repositioning maneuvers (RM) for treatment of posterior benign paroxysmal positional vertigo (P-BPPV). A systematic search of PubMed, Embase, and the Cochrane Library was conducted up until June 30, 2023. Results: Primary outcomes focused on complete resolution of vertiginous symptoms measured by either a Visual Analog Scale (VAS) or the Dix–Hallpike (DH) test. Secondary outcomes included conversion of a positive DH test to a negative DH test exclusively looking at positional nystagmus and assessment of side effects (cervical/back pain, posttreatment dizziness, and nausea). Both outcomes were assessed within a maximum of 4-week follow-up. Following systematic search and review, nine randomized controlled trials (RCTs; p = .413) were found. The studies reported on the effectiveness of the Epley maneuver compared to three other specific RM: Semont, Li, and Gans maneuvers. Results revealed a low to very low certainty of evidence. With the primary outcomes, Epley maneuver was superior to Gans maneuver 24-hr posttreatment but not after 1 week. No significant differences were found between the remaining maneuvers. Conclusions: In summary, evidence of low to very low certainty indicates that Epley maneuver is comparable with Semont, Gans, and Li maneuvers for vertiginous symptoms in patients with P-BPPV. Further high-quality studies are needed.