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1
Gribin, Nikolai. "Strategic planning and foresight in Russian foreign policy amid growing threats and challenges." Diplomatic Service, no. 1 (February 1, 2020): 35–44. http://dx.doi.org/10.33920/vne-01-2001-05.
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The article observes some aspects of strategic planning and prognostication in the context of increasing effectiveness of the Russian Federation international activity. The author examines main reasons for drawing attention to the subject of strategic planning at post-soviet planning. In this connection, the author takes up some practical works of the leading western countries. The focus is on practical significance of the legislative basis, which has been created in the Russian Federation. This legislative has given for the Russian Ministry for Foreign Affairs ability to work up its own system of long-distance planning, monitoring and prognostication. The article contains some proposals toward improving the mechanism of strategic planning in the interests of Russian international policy.
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Гуськова, Надежда, Nadezhda Guskova, Сергей Вдовин, Sergey Vdovin, Ирина Иванова, and Irina Ivanova. "MODELING OF SUSTAINABLE DEVELOPMENT INDICATORS: REGIONAL ASPECT." Russian Journal of Management 4, no. 4 (2016): 465–73. http://dx.doi.org/10.12737/22541.
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Strategic management is aimed at socio-economic development of region at the effective use of his potential. Questions of development of strategy of increase of stability of regional development and forming of mechanism of its realization are actual. Transformation of the territorial systems, development and acceptance of the administrative decisions aimed at providing of their competitive edges and stability of development must be reasonable mathematical and instrumental methods. In this research the methodical approach to prognostication of basic indicators of steady development of the regional systems and ground of administrative decisions on the increase of stability of development of region are worked out, the integral indexes of stability of socio-economic development of subjects of Russian are built, complex estimation is conducted with the use of econometrics design (systems of simultaneous equalizations). Attained results of research allow using the worked out model for an estimation, comparative analysis and prognostication of the regional systems on the level of stability of their development.
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Shlykov, Ilya V., Alexey E. Kovalenko, and Maria V. Rushakova. "Criminological prognostication of the emergence of new types of narcotic drugs." Butlerov Communications 64, no. 12 (2020): 88–97. http://dx.doi.org/10.37952/roi-jbc-01/20-64-12-88.
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The article presents the results of studying the algorithms for the emergence of new types of narcotic drugs, identifies the patterns of changes in the chemical structures of new psychoactive substances, and proposes a mechanism for criminological prognostication of the emergence of new types of substances with narcogenic potential. Analytical studies of the emergence of new psychostimulants have confirmed the correctness of the chosen model of state control of new psychoactive substances – the introduction of “derivative narcotic substances and psychotropic substances” into Russian legislation. An objective and comprehensive study of the chemical structures of molecules of new psychoactive substances also confirmed the legitimacy of establishing state control over the illegal traffic of analogues of narcotic drugs and psychotropic substances. In general, the conducted analytical study suggests considering from the scientific and analytical point of view the possible introduction into law enforcement practice of a new direction "Criminological prognostication of the emergence of new types of narcotic drugs". The general algorithms and patterns found in the process of analytical research in the new structures of molecules of psychoactive substances have confirmed both the forensic search and the logical and stepwise development of science in the field of psychoactive substances.
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Rice, Jill, Linda Hunter, Amy T. Hsu, et al. "Using the “Surprise Question” in Nursing Homes." Journal of Palliative Care 33, no. 1 (2017): 9–18. http://dx.doi.org/10.1177/0825859717745728.
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Background: The “Surprise Question” (SQ) is often used to identify patients who may benefit from a palliative care approach. The time frame of the typical question (a 12-month prognosis) may be unsuitable for identifying residents in nursing homes since it may not be able to differentiate between those who have a more imminent risk of death within a cohort of patients with high care needs. Objective: To examine the accuracy and acceptability of 3 versions of the SQ with shortened prognostication time frames (3 months, 6 months, and “the next season”) in the nursing home setting. Design: A prospective mixed-methods study. Setting/Participants: Forty-seven health-care professionals completed the SQ for 313 residents from a nursing home in Ontario, Canada. A chart audit was performed to evaluate the accuracy of their responses. Focus groups and interviews were conducted to examine the participants’ perspectives on the utility of the SQ. Results: Of the 301 residents who were included in the analysis, 74 (24.6%) deaths were observed during our follow-up period. The probability of making an accurate prediction was highest when the seasonal SQ was used (66.7%), followed by the 6-month (58.9%) and 3-month (57.1%) versions. Despite its high accuracy, qualitative results suggest the staff felt the seasonal SQ was ambiguous and expressed discomfort with its use. Conclusion: The SQ with shortened prognostication periods may be useful in nursing homes and provides a mechanism to facilitate discussions on palliative care. However, a better understanding of palliative care and increasing staff’s comfort with prognostication is essential to a palliative care approach.
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Kuznetsov, N. A. "Classifications in medicine: principles of their structure and clinical significance." Clinical Medicine (Russian Journal) 95, no. 5 (2017): 474–80. http://dx.doi.org/10.18821/0023-2149-2017-95-5-474-480.
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The article deals with theoretical aspects of medical classification research and quantitative perioperative prognostication for the purpose of planned surgical treatment. Classification is regarded as a cultural phenomenon related to all sides of everyday life. Also, it is part of the modern experience exchange mechanism. Under the term classification is understood both the classification proper and the development of classification. The natural classification is built up based on the inherent properties of objects and the relationships between them. The essential properties are identified with the use of a specialized mathematical apparatus (correlation, factorial and cluster analysis).
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Padayachee, Jananee, Aliscia Daniels, Adhika Balgobind, Mario Ariatti, and Moganavelli Singh. "HER-2/neu and MYC gene silencing in breast cancer: therapeutic potential and advancement in nonviral nanocarrier systems." Nanomedicine 15, no. 14 (2020): 1437–52. http://dx.doi.org/10.2217/nnm-2019-0459.
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Globally, breast cancer is the second leading cause of cancer-related mortality among women, with approximately 1.4 million new cases diagnosed annually. Associated genetic perturbations are emerging in the face of intense scientific enquiry, facilitating its classification, prognostication and treatment. RNAi, utilizing siRNA, is a powerful treatment strategy to silence disease-causing genes. However, therapeutic siRNA instability and poor cellular uptake have limited its clinical application, necessitating the use of nanocarriers. In this review, we highlight the RNAi mechanism, HER-2/neu and MYC as breast cancer gene targets, and nonviral nanocarriers as potentially safe and efficient delivery systems.
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Bonou, Maria, Sophie Mavrogeni, Chris J. Kapelios, et al. "Cardiac Adiposity and Arrhythmias: The Role of Imaging." Diagnostics 11, no. 2 (2021): 362. http://dx.doi.org/10.3390/diagnostics11020362.
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Increased cardiac fat depots are metabolically active tissues that have a pronounced pro-inflammatory nature. Increasing evidence supports a potential role of cardiac adiposity as a determinant of the substrate of atrial fibrillation and ventricular arrhythmias. The underlying mechanism appears to be multifactorial with local inflammation, fibrosis, adipocyte infiltration, electrical remodeling, autonomic nervous system modulation, oxidative stress and gene expression playing interrelating roles. Current imaging modalities, such as echocardiography, computed tomography and cardiac magnetic resonance, have provided valuable insight into the relationship between cardiac adiposity and arrhythmogenesis, in order to better understand the pathophysiology and improve risk prediction of the patients, over the presence of obesity and traditional risk factors. However, at present, given the insufficient data for the additive value of imaging biomarkers on commonly used risk algorithms, the use of different screening modalities currently is indicated for personalized risk stratification and prognostication in this setting.
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Kishore, Amit, Jana Borucka, Jana Petrkova, and Martin Petrek. "Novel Insights into miRNA in Lung and Heart Inflammatory Diseases." Mediators of Inflammation 2014 (2014): 1–27. http://dx.doi.org/10.1155/2014/259131.
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MicroRNAs (miRNAs) are noncoding regulatory sequences that govern posttranscriptional inhibition of genes through binding mainly at regulatory regions. The regulatory mechanism of miRNAs are influenced by complex crosstalk among single nucleotide polymorphisms (SNPs) within miRNA seed region and epigenetic modifications. Circulating miRNAs exhibit potential characteristics as stable biomarker. Functionally, miRNAs are involved in basic regulatory mechanisms of cells including inflammation. Thus, miRNA dysregulation, resulting in aberrant expression of a gene, is suggested to play an important role in disease susceptibility. This review focuses on the role of miRNA as diagnostic marker in pathogenesis of lung inflammatory diseases and in cardiac remodelling events during inflammation. From recent reports, In this context, the information about the models in which miRNAs expression were investigated including types of biological samples, as well as on the methods for miRNA validation and prediction/definition of their gene targets are emphasized in the review. Besides disease pathogenesis, promising role of miRNAs in early disease diagnosis and prognostication is also discussed. However, some miRNAs are also indicated with protective role. Thus, identifications and usage of such potential miRNAs as well as disruption of disease susceptible miRNAs using antagonists, antagomirs, are imperative and may provide a novel therapeutic approach towards combating the disease progression.
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Baker, Cordell M., Andrew Parker Cox, Joshua C. Hunsaker, Jonathan Scoville, and Robert J. Bollo. "Postoperative magnetic resonance imaging may predict poor outcome in children with severe traumatic brain injuries who undergo cranial surgery." Journal of Neurosurgery: Pediatrics 29, no. 4 (2022): 407–11. http://dx.doi.org/10.3171/2021.11.peds21486.
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OBJECTIVE Multiple studies have evaluated the use of MRI for prognostication in pediatric patients with severe traumatic brain injury (TBI) and have found a correlation between diffuse axonal injury (DAI)–type lesions and outcome. However, there remains a limited understanding about the use of MRI for prognostication after severe TBI in children who have undergone cranial surgery. METHODS Children with severe TBI who underwent craniectomy or craniotomy at Primary Children’s Hospital in Salt Lake City, Utah, between 2010 and 2019 were identified retrospectively. Of these 92 patients, 43 underwent postoperative brain MRI within 4 months of surgery. Susceptibility-weighted imaging (SWI) and FLAIR sequences were used to designate areas of hemorrhagic and nonhemorrhagic cerebral lesions related to DAI. Patients were then stratified based on the location of the DAI as read by a neuroradiologist as superficial, deep, or brainstem. The location of the DAI and other variables associated with poor outcome, including Glasgow Coma Scale (GCS) score, pediatric trauma score, mechanism of injury, and time to surgery, were analyzed for correlation with poor outcome. Outcomes were reported using the King’s Outcome Scale for Childhood Head Injury (KOSCHI). RESULTS In the 43 children with severe TBI who underwent postoperative brain MRI, the median GCS score on arrival was 4. The most common cause of injury was falls (14 patients, 33%). The most common primary intracranial pathology was subdural hematoma in 26 patients (60%), followed by epidural hematoma in 9 (21%). Fifteen patients (35%) had cerebral herniation and 31 (72%) had evidence of contusion. Variables associated with poor outcome included cerebral herniation (r = 0.338, p = 0.027) and location of DAI (r = 0.319, p = 0.037). In a separate analysis, brainstem DAI was shown to predict poor outcome, whereas location (no, superficial, or deep DAI) did not. Logistic regression showed that brainstem DAI (OR 22.3, p = 0.020) had a higher odds ratio than cerebral herniation (OR 10.5, p = 0.044) for poor outcome. Thirty-six children (84%) had a satisfactory outcome at last follow-up; 3 (7%) children died. CONCLUSIONS The majority of children in this series who presented with a severe TBI and underwent craniectomy or craniotomy made a satisfactory recovery. In patients in whom there is a concern for poor outcome, the location of DAI-type lesions with SWI and FLAIR may assist in prognostication. The authors’ results revealed that DAI-type lesions in the brainstem and evidence of cerebral herniation may indicate a poorer prognosis; however, more studies with larger cohorts are needed to make definitive conclusions.
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Khambhati, Ankit N., Alia Shafi, Vikram R. Rao, and Edward F. Chang. "Long-term brain network reorganization predicts responsive neurostimulation outcomes for focal epilepsy." Science Translational Medicine 13, no. 608 (2021): eabf6588. http://dx.doi.org/10.1126/scitranslmed.abf6588.
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Responsive neurostimulation (RNS) devices, able to detect imminent seizures and to rapidly deliver electrical stimulation to the brain, are effective in reducing seizures in some patients with focal epilepsy. However, therapeutic response to RNS is often slow, is highly variable, and defies prognostication based on clinical factors. A prevailing view holds that RNS efficacy is primarily mediated by acute seizure termination; yet, stimulations greatly outnumber seizures and occur mostly in the interictal state, suggesting chronic modulation of brain networks that generate seizures. Here, using years-long intracranial neural recordings collected during RNS therapy, we found that patients with the greatest therapeutic benefit undergo progressive, frequency-dependent reorganization of interictal functional connectivity. The extent of this reorganization scales directly with seizure reduction and emerges within the first year of RNS treatment, enabling potential early prediction of therapeutic response. Our findings reveal a mechanism for RNS that involves network plasticity and may inform development of next-generation devices for epilepsy.
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Chahin, Michael, Zachery Branham, Ashley Fox, Christian Leurinda, and Amany R. Keruakous. "Clinical Considerations for Immunoparesis in Multiple Myeloma." Cancers 14, no. 9 (2022): 2278. http://dx.doi.org/10.3390/cancers14092278.
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Multiple myeloma is a relatively common clonal plasma cell disorder, comprising 17% of hematologic malignancies. One of the hallmark features of this disease is immunoparesis, which is characterized by the suppression of immunoglobulin polyclonality. Though not entirely elucidated, the mechanism behind this process can be attributed to the changes in the tumor microenvironment. All treating clinicians must consider potential complications related to immunoparesis in the management of multiple myeloma. Though not explicitly described in large data series, the increased risk of infection in multiple myeloma is likely, at least in part, due to immunoglobulin suppression. Additionally, the presence of immunoparesis serves as a prognostic factor, conveying poorer survival and a higher risk of relapse. Even in the era of novel agents, these findings are preserved, and immunoglobulin recovery also serves as a sign of improved outcome following autologous HSCT. Though not within the diagnostic criteria for multiple myeloma, the presence and degree of immunoparesis should be at diagnosis for prognostication, and immunoglobulin recovery should be tracked following myeloablative therapy and autologous HSCT.
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Okadigwe, Mary Nkechi. "Modeling Ritual and Performance for Political Change: An Examination of Igu-Aro Ndi-Umueri in Anambra State." UJAH: Unizik Journal of Arts and Humanities 22, no. 2 (2022): 108–26. http://dx.doi.org/10.4314/ujah.v22i2.5.
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This research studied the performance of the Igu-Aro ritual of the Umueri people of Anambra state to investigate its processes in terms of its viability as a model of active and positive social change. Igu-Aro is the Igbo annual communal festival of the prognostication of the year’s events. The performance of the Igu-Aro of the Umueri people was perceived as an essential mechanism for transmitting the people’s cultural identity and a route to collective participation in the structuring of fair leadership and a progressive economy. Victor Turner’s ideologies on rituals, liminality, and social change were adopted for the research. The researcher believes that the understanding and integration of the insights gained from the transitory and collective nature of the performance of Igu-Aro Ndi-Umueri will be beneficial to the understanding of how the Nigerian political system could be bettered. This is because in recent times there seems to be an increasing clamour for the restructuring of the Nigerian political system with a major emphasis on the devolution of powers, duties, and responsibilities to component states. This study has provided insight into the Umueri people and their historical links with others within their common communities.
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Sebastian, Sinto, Yuan Xiao Zhu, Esteban Braggio, et al. "Intracellular Accumulation Of Light Chains Caused By Lenalidomide, and Mediated Via CRBN, Causes Major ER Stress and Is Implicated In The Synergistic Combination Of Imids and Proteasome Inhibitors." Blood 122, no. 21 (2013): 4434. http://dx.doi.org/10.1182/blood.v122.21.4434.4434.
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Background The precise molecular mechanism and targets of lenalidomide specific anti-Multiple Myeloma (MM) activity remain largely unknown, although, cereblon (CRBN) has been identified as a central mediator of activity with IRF-4 acting as a downstream molecule. Lenalidomide resistance in MM cells which, despite CRBN depletion, are able to restore their IRF-4 levels suggests the existence of alternative pathways. Methods To measure apoptosis and gene expression analysis 1x 106cells were incubated with 10μm to 50μm of lenalidomide for 24 to 96 hours before they were examined by annexin-PI and FACS analysis. Gene and protein expression were measured by RT-PCR, western blot, and immunohistochemistry. For lenalidomide followed bortezomib serial studies, cells were incubated with 10μm of lenalidomide for 48 hours and later treated with bortezomib for 24 to 48 hrs. CRBN and immunoglobulin light chain knock-down were performed by lentiviral mediated shRNA. Results We found lenalidomide induces Endoplasmic reticulum stress (ERS) via accumulation of intracellular immunoglobulin proteins, but only in the presence of CRBN in a panel of MM cell lines. This accumulation of intracellular proteins resulted in ERS as documented by western blot and RT-PCR in OPM2 and MMIS cell lines. We next utilized OPM2 cells knocked down for CRBN and control, non-target (NT), and treated with different doses of lenalidomide. After three days of treatment an ERS response was occurring in OPM2-NT cells but not in CRBN knockdown cells. Using Western blot we found decreased XBP-1u and increased XBP-1s, ERS marker proteins, in CRBN positive (NT) cells after 72 hours of lenalidomide treatment, but not in CRBN knock-down cells. Another ERS marker GRP78/BiP was also clearly accumulated after lenalidomide treatment in CRBN positive cells. Inactivation of the tumor suppressor p53 by degradation is a mechanism utilized by cells to adapt to ERS has been reported. We also found that p53 protein down regulated after lenalidomide treatment in CRBN positive OPM2 and MMIS cells. We have analyzed other isogenic cell lines MM1.S (lenalidomide-sensitive) and isogenic MM1.Sres (lenalidomide-resistant) HMCLs and found that lenalidomide induces ERS in MM1.S but not MM1.Sres cells. CRBN is important for lenalidomide to induce immunoglobulin protein accumulation and ERS was further proved by over-expressing CRBN in OCI-My5 MM cell line and subsequent lenalidomide treatment. To test the effect of light chain accumulation as ER stressors, we knocked down immunoglobulin light chain lambda in human MM cell line OPM2. Knock-down of lambda light chain in OPM2 cells resulted in lenalidomide resistance and it induced endoplasmic reticulum stress mediated anti-myeloma activity. Our preliminary data reveals that lenalidomide mediated progressive ERS can positively enhance bortezomib induced apoptosis in an in-vitro MM model. We pre-treated myeloma cell lines with lenalidomide and subsequently treated with bortezomib. MM cells pre-treated with lenalidomide for two days and there after treated with bortezomib clearly shown increased sensitivity to bortezomib induced apoptosis than non-pre-lenalidomide treated cells. Conclusion Here we show that lenalidomide causes accumulation of immunoglobulin light chains, inducing progressive ER stress, resulting in anti-myeloma activity and that effect depends on the presence of CRBN. Proteasome inhibitors such as bortezomib also sensitize MM cells to endoplasmic reticulum stress-mediated apoptosis. Our data demonstrated the synergistic effect of lenalidomide and proteasome inhibitors, likely due to the augmented protein stress. This data support the use of serial therapy utilizing pre-lenalidomide treatment followed by bortezomib or carfilzomib treatment. Disclosures: Fonseca: Medtronic: Consultancy; Otsuka: Consultancy; Celgene: Consultancy; Genzyme: Consultancy; BMS: Consultancy; Lilly: Consultancy; Onyx: Consultancy, Research Funding; Binding Site: Consultancy; Millennium: Consultancy; AMGEN: Consultancy; Cylene: Research Funding; Prognostication of MM based on genetic categorization of the disease: Prognostication of MM based on genetic categorization of the disease, Prognostication of MM based on genetic categorization of the disease Patents & Royalties.
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Ow, Suet H., Pei J. Chua, and Boon H. Bay. "miR-149 as a Potential Molecular Target for Cancer." Current Medicinal Chemistry 25, no. 9 (2018): 1046–54. http://dx.doi.org/10.2174/0929867324666170718102738.
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Background: MicroRNAs (miRNAs) are frequently dysregulated in cancers and serve as attractive targets for prognostication and therapeutic applications. Besides cancer, the biological functions of miR-149 have been studied in various diseases. This review aims to summarize the reports available in the literature, regarding miR-149 as a molecular target for cancer therapeutics. Methods: An extensive literature search was conducted using the Pubmed database to sieve out articles related to the roles of miR-149 in carcinogenesis and cancer progression, and potential miRNA-based therapies. A total of 89 publications were selected for inclusion in this review. Results: Depending on the cancer type, miR-149 can behave either as a tumor suppressor or as an ‘onco-miR' that promotes tumorigenesis and cancer spread, suggesting that this miRNA has diverse functions. Potential miRNA-based therapies include the use of miRNA mimics, miRNA inhibitors, demethylating agents and circular RNAs. Conclusion: Although targeting miRNA is an attractive anti-cancer strategy, not all cancers can be treated by the same miRNA-based strategy. A comprehensive understanding of miRNA regulatory mechanism is also necessary to improve the design of miRNA-based therapeutics and there is a need for safe and efficient delivery methods when using this approach for anti-cancer treatment.
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Joffe, Ari R., Geoff Brin, and Sarah Farrow. "Unreliable Early Neuroprognostication After Severe Carbon Monoxide Poisoning Is Likely Due to Cytopathic Hypoxia: A Case Report and Discussion." Journal of Child Neurology 35, no. 2 (2019): 111–15. http://dx.doi.org/10.1177/0883073819879833.
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A 17-year-old girl was found unconscious in a running vehicle. She developed very severe acute respiratory distress syndrome (which was treated with rescue high-frequency oscillation), hemodynamic instability, acute kidney injury, rhabdomyolysis, and remained comatose with a Glasgow Coma Scale score of 3 and gasping respirations for 67 hours (when the Glasgow Coma Scale score improved to 6, with tachypnea to Paco 2 28 and pH 7.5). By 92 hours, she was obeying commands, and she was extubated at 96 hours, shortly after which she was conversing with family and texting on her phone. A magnetic resonance imaging (MRI) scan 6 days after being found showed subacute infarctions affecting the medial aspect of the globus pallidus bilaterally as well as a small cortical/subcortical infarction in the right parietal lobe. At a 7-week follow-up, she had no delayed-onset signs of brain injury. This case demonstrated that neurologic prognostication after carbon monoxide poisoning may be unreliable for more than 72 hours after injury. We discuss that it is possible that the mitochondrial dysfunction induced by carbon monoxide was responsible for a functional coma without irreversible brain injury, similar to the mechanism of cytopathic hypoxia in multiple-organ dysfunction that allows some other organ recovery without necrosis in survivors.
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Schellenberg, Morgan, Aaron Strumwasser, Daniel Grabo, et al. "Delta Shock Index in the Emergency Department Predicts Mortality and Need for Blood Transfusion in Trauma Patients." American Surgeon 83, no. 10 (2017): 1059–62. http://dx.doi.org/10.1177/000313481708301009.
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Shock Index (SI = heart rate/systolic blood pressure) predicts outcomes among trauma patients. Studies have also shown that the change in SI between the field and Emergency Department (ED) arrival (Delta SI) predicts mortality in trauma. Given the lack of reliable prehospital data, Delta SI may more accurately prognosticate if used within the ED. All trauma patients arriving to our Level I trauma center in 2014 were reviewed. Patients were matched for age, gender, mechanism of injury, and injury severity score. SI and ED Delta SI were calculated. ED Delta SI >0.1 and ≤0.1 defined the study groups. Pregnant patients, pediatric patients, and patients with incomplete data were excluded. Outcomes included intensive care unit (ICU) length of stay, blood products, and mortality. A total of 2591 patients were identified (n = 1294 patients analyzed). After matching, patients with ED Delta SI >0.1 had greater mortality (6.6 vs 2.6%, P = 0.010), need for blood transfusion (1764 vs 565 cc, P < 0.001), and ICU length of stay (5.6 vs 3.8 days, P = 0.014) compared with patients with ED Delta SI ≤0.1. In conclusion, ED Delta SI >0.1 is associated with increased mortality, need for blood transfusion, and ICU length of stay. Delta SI may be superior to traditional SI for trauma outcome prognostication.
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Tavoosi, Jafar, Amir Abolfazl Suratgar, Mohammad Bagher Menhaj, Amir Mosavi, Ardashir Mohammadzadeh, and Ehsan Ranjbar. "Modeling Renewable Energy Systems by a Self-Evolving Nonlinear Consequent Part Recurrent Type-2 Fuzzy System for Power Prediction." Sustainability 13, no. 6 (2021): 3301. http://dx.doi.org/10.3390/su13063301.
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A novel Nonlinear Consequent Part Recurrent Type-2 Fuzzy System (NCPRT2FS) is presented for the modeling of renewable energy systems. Not only does this paper present a new architecture of the type-2 fuzzy system (T2FS) for identification and behavior prognostication of an experimental solar cell set and a wind turbine, but also, it introduces an exquisite technique to acquire an optimal number of membership functions (MFs) and their corresponding rules. Using nonlinear functions in the “Then” part of fuzzy rules, introducing a new mechanism in structure learning, using an adaptive learning rate and performing convergence analysis of the learning algorithm are the innovations of this paper. Another novel innovation is using optimization techniques (including pruning fuzzy rules, initial adjustment of MFs). Next, a solar photovoltaic cell and a wind turbine are deemed as case studies. The experimental data are exploited and the consequent yields emerge as convincing. The root-mean-square-error (RMSE) is less than 0.006 and the number of fuzzy rules is equal to or less than four rules, which indicates the very good performance of the presented fuzzy neural network. Finally, the obtained model is used for the first time for a geographical area to examine the feasibility of renewable energies.
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Schuchardt, Eleanor L., Shelley D. Miyamoto, Timothy Crombleholme, et al. "Amniotic Fluid microRNA in Severe Twin-Twin Transfusion Syndrome Cardiomyopathy—Identification of Differences and Predicting Demise." Journal of Cardiovascular Development and Disease 9, no. 2 (2022): 37. http://dx.doi.org/10.3390/jcdd9020037.
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Twin-twin transfusion syndrome (TTTS) is a rare but serious cause of fetal cardiomyopathy with poorly understood pathophysiology and challenging prognostication. This study sought a nonbiased, comprehensive assessment of amniotic fluid (AF) microRNAs from TTTS pregnancies and associations of these miRNAs with clinical characteristics. For the discovery cohort, AF from ten fetuses with severe TTTS cardiomyopathy were selected and compared to ten normal singleton AF. Array panels assessing 384 microRNAs were performed on the discovery cohort and controls. Using a stringent q < 0.0025, arrays identified 32 miRNAs with differential expression. Top three microRNAs were miR-99b, miR-370 and miR-375. Forty distinct TTTS subjects were selected for a validation cohort. RT-PCR targeted six differentially-expressed microRNAs in the discovery and validation cohorts. Expression differences by array were confirmed by RT-PCR with high fidelity. The ability of these miRNAs to predict clinical differences, such as cardiac findings and later demise, was evaluated on TTTS subjects. Down-regulation of miRNA-127-3p, miRNA-375-3p and miRNA-886 were associated with demise. Our results indicate AF microRNAs have potential as a diagnostic and prognostic biomarker in TTTS. The top microRNAs have previously demonstrated roles in angiogenesis, cardiomyocyte stress response and hypertrophy. Further studies of the mechanism of actions and potential targets is warranted.
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Huang, Na, Siting Zheng, Yisheng Fang, Min Shi, and Wangjun Liao. "Epithelial circulating tumor cells in portal vein are associated with number of liver metastatic nodules of colorectal cancer." Journal of Clinical Oncology 35, no. 15_suppl (2017): e15026-e15026. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e15026.
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e15026 Background: Colorectal cancer has been one of the most diagnosed cancers worldwide, and circulating tumor cells (CTCs), resulting in colorectal liver metastases (CLM), relate to its mortality. Although the mechanism and prognostication of metastasis has attracted a broad interest, the definite relationship between CLM and different phenotype of CTC is still not sufficient. Our objective is to investigate the clinical implication of different phenotype of CTCs. Methods: Twenty-one patients with CLM were enrolled in this study. Peripheral venous (PeV) and portal vein (PoV) blood specimens were collected from each patient. Through real-time ultrasound-guided percutaneous portal vein access, Pov blood was collected. Then CTC detection technology was employed to isolate CTCs for categorization. Results: No difference in the number of total CTCs between PoV and PeV, while strikingly, the number of epithelial CTCs was higher in PoV. In patients with unresected primary lesions, epithelial CTCs in PoV were more than that in PeV, while there was no difference in resected ones. Furthermore, we demonstrate that the percentage of epithelial CTCs in PoV relate to the number of liver metastatic nodules. In addition, the increased percentage of epithelial CTCs in the PoV relates to low amounts of lymphocytes. Conclusions: Our study shows that high proportion of epithelial CTCs in Pov relates to increasing number of liver metastatic nodules in CLM.
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Beck, Jonathan, Gauthier Loron, Pierre-Yves Ancel, et al. "An Updated Overview of MRI Injuries in Neonatal Encephalopathy: LyTONEPAL Cohort." Children 9, no. 4 (2022): 561. http://dx.doi.org/10.3390/children9040561.
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Background: Brain magnetic resonance imaging (MRI) is a key tool for the prognostication of encephalic newborns in the context of hypoxic−ischemic events. The purpose of this study was to finely characterize brain injuries in this context. Methods: We provided a complete, descriptive analysis of the brain MRIs of infants included in the French national, multicentric cohort LyTONEPAL. Results: Among 794 eligible infants, 520 (65.5%) with MRI before 12 days of life, grade II or III encephalopathy and gestational age ≥36 weeks were included. Half of the population had a brain injury (52.4%); MRIs were acquired before 6 days of life among 247 (47.5%) newborns. The basal ganglia (BGT), white matter (WM) and cortex were the three predominant sites of injuries, affecting 33.8% (n = 171), 33.5% (n = 166) and 25.6% (n = 128) of participants, respectively. The thalamus and the periventricular WM were the predominant sublocations. The BGT, posterior limb internal capsule, brainstem and cortical injuries appeared more frequently in the early MRI group than in the late MRI group. Conclusion: This study described an overview of brain injuries in hypoxic−ischemic neonatal encephalopathy. The basal ganglia with the thalamus and the WM with periventricular sublocation injuries were predominant. Comprehensive identification of brain injuries in the context of HIE may provide insight into the mechanism and time of occurrence.
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Задорожная, Елена, Elena Zadorozhnaya, Игорь Мухортов, Igor Mukhortov, Ксения Почкайло, and Kseniya Pochkaylo. "Anti-wear additives influence upon hydrodynamic friction mode parameters in bearings of internal-combustion engines." Bulletin of Bryansk state technical university 2016, no. 3 (2016): 29–36. http://dx.doi.org/10.12737/22007.
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An essential condition to ensure an engine life having 300,000 – 1 000,000 km according to race consists in assurance of a minimum wear rate of crankshaft bearings. For such units as connectingrod bearings a maximum allowable value of bearing brass wear makes 100 mkm which corresponds to an integral linear wear intensity of 10-14 …10-13 that is possible only at a hydrodynamic mode of friction actually at all modes of engines operations. Ensuring liquid friction in all range of contact pressures is achieved both through design methods, and technological ones. To the latter belongs first of all the application of lubricants with high wearresistant properties. In this connection arises a problem to reveal a mechanism and degree of the effect of lubricant components upon a range of contact pressure where liquid friction is realized. This paper reports the experimental evidences of the increase of contact pressures at which is achieved a minimum value of a constant of friction at the introduction in lubricant a standard wear-resistant additive – dialkyldithiophosphate of zinc (ZDDP). So, at the introduction in coal oil without additives I-20A (viscosity type ISO 32) 1.25 and 2.5% ZGGP maxi-mum contact pressure at which is realized a hydrody-namic mode of friction increases by 1.8 and 2 times accordingly. Because of impossibility to explain experimental data by a chemical interaction of ZDDP with surface material of tribo-coupling there is offered and substantiated a mechanism of ZDDP influence upon rheological parameters of lubricant in a separation layer. A rheological model allowing the computation of the wearresistant additives influence upon a value of hydrodynamic pressures in a lubrication layer is of-fered. The idea of the initiation by a wearresistant additive of multimolecular adsorption of lubricant on the surface of tribocoupling may be used for the optimization of ZDDP structure and also for the prognostication of changes in pressure coefficient of viscosity in a lubrication layer.
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Choudhary, Madhur, Khursheed Alam Khan, Nandkishore Gora, Achal Sharma, and Virendra Deo Sinha. "Traumatic Brain Injury: Comparison of Computed Tomography Findings in Pediatric and Adult Populations." Indian Journal of Neurosurgery 9, no. 03 (2020): 151–56. http://dx.doi.org/10.1055/s-0040-1708066.
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Abstract Introduction Traumatic brain injury (TBI) is a global health issue, accounting for a significant number of adult and pediatric deaths and morbidity. Computed tomography (CT) is an important diagnostic modality for TBI. The primary goal of this study was to determine if there were any significant radiological differences in CT brain findings between adult and pediatric populations. Materials and Methods Data of individual patients were collected from admission to discharge/death, which included various parameters in terms of demographics, mechanism of injury, and patient outcome which were later analyzed. A total of 1,150 TBI patients were enrolled in the study. Results The most common mode of injury in adults is road traffic accident (RTA) followed by fall from height (FFH), while in pediatrics it is vice versa. Findings of basal cisterns on CT brain were found to be statistically significant in both groups; 65% adults and 71% pediatrics had only one abnormal CT finding. Most common combination CT finding in adults was acute subdural hematoma (ASDH) and basal cistern abnormality, while in pediatrics it was traumatic subarachnoid hemorrhage (SAH) and contusion. Rotterdam score (based on CT brain findings) was significantly lower for pediatric age group compared with adults. It was 2.2 ± 0.85 for adults and 1.99 ± 0.74 for pediatrics, which was statistically significant (p < 0.001). Conclusions The Rotterdam score has immense predictive power for prognostication of mortality status. Pediatric age group has better prognosis in terms of survival as compared with adults, thus justifying the role of Rotterdam CT score for mortality risk stratification in providing clinical care.
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Balatsky, Evgeny, and Nataly Ekimova. "Public administration tools: Forecasting vs Designing." Upravlenets 12, no. 1 (2021): 18–31. http://dx.doi.org/10.29141/2218-5003-2021-12-1-2.
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The article discusses the expediency of abandoning the tool of social forecasting in the practice of public administration in favor of planning and design methods. The methodological basis rests on the conceptual imperative of the impossibility to produce adequate forecasts in the modern world, which is supported by such respected researchers as Douglas North, George Soros, Nassim Taleb and Arnold Toynbee. The fairness of this thesis is illustrated using methods of comparison and analysis. The study analyses the main factors that cast doubt on the possibility and expediency of preserving the tool of social prognostics: the failure of the scenario forecast format; the need for foreknowledge of events rather than values of traditional macro-parameters; the extension of Arnold Toynbee’s principle from a historical retrospective to studying the prospects; the economic growth rate indicator (GDP) losing its indicative universality and the emergence of alternative measures of social development (Gross National Happiness, culture and environment preservation); critical attitude of the intellectual elite to the possibility of social forecasting; unreliability of the source statistics; the expectation of the end of economic growth, a change in the development regime and quantitative forecasting devaluation by the leading experts – Douglas North, Robert Lucas, Tom Piketty, Richard Heinberg; the completion of the mission of capitalism in the form of the Neo-Malthusian trap and robotomics (mass introduction of robots to the economy). The authors prove that amid fading interest in traditional forecasting, alternative prognostication methods are emerging, such as planning, designing, futurology, foresight and strategic intelligence. Devaluation of forecast tools leads to the need to change the old doctrine of public administration, based on forecast documents, to a new one implying a transition to active construction of the future through directive designing and planning. The theoretical and practical significance of the study lies in substantiating the principles of a new management system: expanding the planning and design horizon (up to 30 years); introducing a mechanism for implementing plans and projects; introducing mechanisms for pre-project foresight; creating a twolevel economic management system; and moving from the quantity paradigm to the quality one.
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Mercier, Eric, Pier-Alexandre Tardif, Marcel Emond, et al. "Characteristics of patients included and enrolled in studies on the prognostic value of serum biomarkers for prediction of postconcussion symptoms following a mild traumatic brain injury: a systematic review." BMJ Open 7, no. 9 (2017): e017848. http://dx.doi.org/10.1136/bmjopen-2017-017848.
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ObjectiveMild traumatic brain injury (mTBI) has been insufficiently researched, and its definition remains elusive. Investigators are confronted by heterogeneity in patients, mechanism of injury and outcomes. Findings are thus often limited in generalisability and clinical application. Serum protein biomarkers are increasingly assessed to enhance prognostication of outcomes, but their translation into clinical practice has yet to be achieved. A systematic review was performed to describe the adult populations included and enrolled in studies that evaluated the prognostic value of protein biomarkers to predict postconcussion symptoms following an mTBI.Data sourcesSearches of MEDLINE, Embase, CENTRAL, CINAHL, Web of Science, PsycBITE and PsycINFO up to October 2016.Data selection and extractionTwo reviewers independently screened for potentially eligible studies, extracted data and assessed the overall quality of evidence by outcome using the Grading of Recommendations Assessment, Development and Evaluation approach.ResultsA total of 23 298 citations were obtained from which 166 manuscripts were reviewed. Thirty-six cohort studies (2812 patients) having enrolled between 7 and 311 patients (median 89) fulfilled our inclusion criteria. Most studies excluded patients based on advanced age (n=10 (28%)), neurological disorders (n=20 (56%)), psychiatric disorders (n=17 (47%)), substance abuse disorders (n=13 (36%)) or previous traumatic brain injury (n=10 (28%)). Twenty-one studies (58%) used at least two of these exclusion criteria. The pooled mean age of included patients was 39.3 (SD 4.6) years old (34 studies). The criteria used to define a mTBI were inconsistent. The most frequently reported outcome was postconcussion syndrome using the Rivermead Post-Concussion Symptoms Questionnaire (n=18 (50%)) with follow-ups ranging from 7 days to 5 years after the mTBI.ConclusionsMost studies have recruited samples that are not representative and generalisable to the mTBI population. These exclusion criteria limit the potential use and translation of promising serum protein biomarkers to predict postconcussion symptoms.
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Salottolo, Kristin, Ripul Panchal, Robert M. Madayag, et al. "Incorporating age improves the Glasgow Coma Scale score for predicting mortality from traumatic brain injury." Trauma Surgery & Acute Care Open 6, no. 1 (2021): e000641. http://dx.doi.org/10.1136/tsaco-2020-000641.
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BackgroundThe Glasgow Coma Scale (GCS) score has been adapted into categories of severity (mild, moderate, and severe) and are ubiquitous in the trauma setting. This study sought to revise the GCS categories to account for an interaction by age and to determine the discrimination of the revised categories compared with the standard GCS categories.MethodsThe American College of Surgeons National Trauma Data Bank registry was used to identify patients with traumatic brain injury (TBI; ICD-9 codes 850–854.19) who were admitted to participating trauma centers from 2010 to 2015. The primary exposure variables were GCS score and age, categorized by decade (teens, 20s, 30s…, 80s). In-hospital mortality was the primary outcome for examining TBI severity/prognostication. Logistic regression was used to calculate the conditional probability of death by age decade and GCS in a development dataset (75% of patients). These probabilities were used to create a points-based revision of the GCS, categorized as low (mild), moderate, and high (severe). Performance of the revised versus standard GCS categories was compared in the validation dataset using area under the receiver operating characteristic (AUC) curves.ResultsThe final population included 539,032 patients with TBI. Age modified the performance of the GCS, resulting in a novel categorization schema for each age decile. For patients in their 50s, performance of the revised GCS categories mirrored the standard GCS categorization (3–8, 9–12, 13–15); all other revised GCS categories were heavily modified by age. Model validation demonstrated the revised GCS categories statistically significantly outperformed the standard GCS categories at predicting mortality (AUC: 0.800 vs 0.755, p<0.001). The revised GCS categorization also outperformed the standard GCS categories for mortality within pre-specified subpopulations: blunt mechanism, isolated TBI, falls, non-transferred patients.DiscussionWe propose the revised age-adjusted GCS categories will improve severity assessment and provide a more uniform early prognostic indicator of mortality following traumatic brain injury.Level of evidenceIII epidemiologic/prognostic.
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Malek, Sami, Brian Parkin, Peter Ouillette, et al. "A Pathobiological Role of the Insulin Receptor in Chronic Lymphocytic Leukemia." Blood 114, no. 22 (2009): 2324. http://dx.doi.org/10.1182/blood.v114.22.2324.2324.
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Abstract Abstract 2324 Poster Board II-301 The presence of genomic aberrations in CLL, including del17p and del11q, affects CLL patient survival, and thus an in-depth understanding of the genes influenced through these deletions is important. Further, genes affecting CLL disease progression that is observed in patients with recurrent genomic deletions, including del11q, remain incompletely characterized. Focusing therefore on del11q in CLL, we employed comparative expression array profiling (Affymetrix 133 2.0 plus arrays) of RNA from sorted CD19+ cells from 10 cases with and nine cases without del11q to identify stable transcriptome differences associated with del11q. Through these efforts we have identified for the first time differential expression of the insulin receptor (INSR) in CLL and predominant INSR expression in CLL with del11q. We have validated this finding in a cohort of 219 CLL cases. Our aggregate data suggest biologically and clinically meaningful INSR expression in a substantial subset of all CLL cases. INSR stimulation by insulin in CLL cells expressing the INSR resulted in the activation of canonical INSR signaling pathways, including the AKT-mTOR and Ras/Raf/Erk pathways, and INSR activation partially abrogated CLL cell apoptosis ex vivo. Clinically, CLL cases with INSR expression displayed larger lymphnodes and higher Rai stage at study enrollment and the disease progressed faster requiring repeat therapy earlier than CLL cases with low or absent INSR expression. This novel data provides the first description of a pathobiological role of the insulin receptor in CLL biology and disease progression, thus identifying a potential mediator and mechanism for del11q-associated CLL phenotypes. The identification of a transmembrane tyrosine kinase receptor with direct effects on CLL biology and clinical behavior offers opportunities for CLL prognostication and targeted therapy development and further strengthens the case for involvement of the INSR in cancer biology. Disclosures: Malek: Cephalon: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Affymetrix: Research Funding. Erba:Lilly: Research Funding; Antisoma: Research Funding; Wyeth: Research Funding; Cephalon: Honoraria, Research Funding; MGI Pharma: Honoraria; Pharmion: Honoraria; Celgene: Honoraria; BMS: Honoraria; Novartis: Honoraria, Research Funding; Genzyme: Consultancy, Honoraria, Research Funding; Gemin-X: Research Funding; Kanisa: Research Funding.
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Ahearne, Caroline E., Ruby Y. Chang, Brian H. Walsh, Geraldine B. Boylan, and Deirdre M. Murray. "Cord Blood IL-16 Is Associated with 3-Year Neurodevelopmental Outcomes in Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy." Developmental Neuroscience 39, no. 1-4 (2017): 59–65. http://dx.doi.org/10.1159/000471508.
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Activation of the inflammatory pathway is increasingly recognized as an important mechanism of injury following neonatal asphyxia and encephalopathy. This process may contribute to the poor prognosis seen in some cases, despite therapeutic hypothermia. Our group has previously identified raised interleukin (IL)-6 and IL-16, measured in umbilical cord blood at birth, to be predictive of grade of hypoxic-ischaemic encephalopathy (HIE). Our aim in this study was to examine the ability of these cytokines to predict the 3-year neurodevelopmental outcome in the same cohort. As part of a prospective, longitudinal cohort study set in a single tertiary maternity unit, term infants with biochemical and clinical evidence of perinatal asphyxia were recruited at birth. Umbilical cord blood was collected and analyzed for IL-6 and IL-16 using a Luminex assay. The neurodevelopmental outcome of these infants was assessed at 3 years using the Bayley Scales of Infant and Toddler Development (Edition 3). Early cord blood measurement of IL-6 and IL-16 and long-term outcome were available in 33/69 infants. Median (IQR) IL-16 differentiated infants with a severely abnormal outcome (n = 6) compared to all others (n = 27), (646 [466-1,085] vs. 383.5 [284-494] pg/mL; p = 0.012). IL-16 levels were able to predict a severe outcome with an area under the receiver-operating characteristic (ROC) curve of 0.827 (95% CI 0.628-1.000; p = 0.014). Levels ≥514 pg/mL predicted a severe outcome with a sensitivity of 83% and a specificity of 81%. IL-16 also outperformed other routine biochemical markers available at birth for the prediction of severe outcome. APGAR scores at 1 and 10 min were also predictive of a severe outcome (p = 0.022 and p = 0.036, respectively). A combination of IL-16 with these clinical markers did not improve predictive value, but IL-16 combined with electroencephalogram grading increased the area under the ROC curve. IL-6 did not show any association with 3-year outcome. This is the first report studying the association of IL-16 measured at birth with long-term outcome in a cohort of neonates with perinatal asphyxia. IL-16 may be an early biomarker of severe injury and aid in the long-term prognostication in infants with HIE.
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Guo, Jimmy, Hannah I. Hoffman, Peter G. Hwang, et al. "Identifying pan-cancer transcriptomic determinants of perineural and lymphovascular invasion using machine learning." Journal of Clinical Oncology 38, no. 15_suppl (2020): 3621. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.3621.
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3621 Background: Tumor invasion of nerves, blood vessels, and lymphatics are a primary means of local recurrence and escape from the local microenvironment, resulting in metastases and poor clinical outcomes. However, the genetic drivers that are most pertinent to these malignant processes are not well understood, and few therapeutics successfully target perineural invasion (PNI) and lympho-vascular invasion (LVI). Identifying genetic drivers and biomarkers can be valuable for therapeutic targeting and prognostication. Methods: We analyzed surgical pathology reports and bulk RNA-seq data of 1,624 patients across 12 cancer types from The Cancer Genome Atlas (TCGA). Differential gene expression analysis between patients with and without PNI/LVI was performed using DEseq2 in Python while adjusting for age, sex, race, and cancer type. Genes with an adjusted p-value < 0.001 were then used to derive parsimonious signatures using random forest classifier and recursive feature selection algorithms. Results: To assess whether these invasive histological phenotypes have clinical ramifications, we examined outcomes data and found that patients with PNI or LVI have reduced overall (OS) and disease-free survival (DFS) ( p < 0.05) relative to those without. In addition, patients with both PNI and LVI have the lowest DFS from our pan-cancer analysis, suggesting that each may have non-redundant contributions to poor outcomes. From the differential gene expression analysis, we identified a set of 621 and 606 genes that were highly associated with PNI and LVI, respectively (padj < 0.001). Many of these genes such as TEKT5 (padj = 3.18 x 10−64), which is canonically associated with ciliary and flagellar microtubules, and SCRIB (padj = 1.60 x 10−21), which helps establish apico-basal cell polarity, have not been described previously in relevance to PNI and LVI, and warrant further scientific and clinical investigation. These genes were ultimately condensed into a signature that optimizes for both model simplicity and goodness of fit with up to 90% accuracy as determined by trials on both a logistic regression and neural network model. Conclusions: We concluded from a pan-cancer analysis that PNI and LVI are associated with poor outcomes, and we were able to robustly identify sets of genes that characterize each invasive mechanism for further functional investigation.
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Шпилевский, В. В., and И. В. Крупов. "Methods prognostication for description dynamics of Electronic Navigational Charts." Automation of ship technical facilities 26, no. 1 (2020): 110–23. http://dx.doi.org/10.31653/1819-3293-2020-1-26-110-123.
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n presented research, there are some explanations about mechanisms of using natural processes to make forecast of changes in bottom topography in shallow water under navigation conditions. The key factor is the development of programs that can track changes in natural processes with displaying and fixation on electronic devices. Any research should preferably be carried out considering changes of the object over time and under the influence of various factors simultaneously and dynamically. In the article dynamic processes are divided into "significant" and "insignificant".
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Yang, Juan, Ying Li, Ya Zhang, et al. "NCAPD3 Regulates Tumor Growth and Predicts Prognosis in Diffuse Large B-Cell Lymphoma." Blood 134, Supplement_1 (2019): 5045. http://dx.doi.org/10.1182/blood-2019-123910.
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Introduction NCAPD3 (Non-SMC Condensin II Complex Subunit D3) is a regulatory subunit of the condensing-2 complex. Recent studies have shown that somatic mutations in genes encoding subunits of condensins associated with microcephaly, primary autosomal recessive and several cancers. NCAPD3 was highlighted as an outcome predictor in pancreatic ductal adenocarcinoma (PDAC) and a new biomarker for subtype-1 prostate cancer that improves prognostication. Yet, no literature has been reported regarding the expression and biological role of NCAPD3 in diffuse large B cell lymphoma (DLBCL). Hence, the aim of our study is to evaluate the functional significance and mechanism of NCAPD3 in DLBCL. Methods Peripheral blood mononuclear cells (PBMCs) were obtained from healthy volunteers with informed consents. Expression levels of NCAPD3 mRNA and protein in DLBCL cell lines and PBMCs were detected by quantitative RT-PCR and western blotting. Immunohistochemistry (IHC) was conducted to assess the expression of NCAPD3 on paraffin-embedded tissues from 70 de novo DLBCL patients (study group) and 35 reactive hyperplasia patients (control group) with informed contents. Microarray datasets GSE32918 and GSE83632 were obtained from Gene Expression Omnibus. Survival analysis, protein-protein interaction (PPI) and gene set enrichment analysis (GSEA) in gene expression profiles were performed. Lentivirus vectors either targeting NCAPD3 (shNCAPD3) or empty lentiviral vector (shControl) were stably transfected into DLBCL cells. Cell proliferation was analyzed by cell counting kit (CCK-8). The apoptosis and cell cycle assays were carried out by flow cytometry. p < 0.05 was considered statistically significant. Results Markedly increased expression of NCAPD3 was detected in DLBCL cell lines at mRNA and protein level compared to those in healthy volunteers' PBMCs (Fig. 1a-b). We also observed higher NCAPD3 expression levels in DLBCL tissues than in reactive hyperplasia upon IHC staining (Fig. 1c). Expression of NCAPD3 protein was revealed in significant positive correlation with advanced Ann Arbor stage (p=0.046) and IPI score (p=0.017, Fig. 1d). Bioinformatics analysis showed that high NCAPD3 expression in DLBCL was turned up to be correlate with shorter overall survival according to GSE32918 (p=0.013, Fig. 2a). PPI network and GSEA indicated that NCAPD3 was functional enriched in chromatin regulation, cell cycle, histone methylation, NF-κB signaling and Toll-like receptor signaling pathway (Fig. 2b-c). Relevant mechanism is now the focus of ongoing experiments. Lentivirus mediated loss-of-function assays were performed to further investigate the biological role of NCAPD3 in DLBCL. Effective knockdown (shNCAPD3) was confirmed by qRT-PCR and western blot (Fig. 3a-b). Stable expression of shNCAPD3 in DLBCL cells exhibited growth suppression, increased fast-onset apoptosis, and induced GO/G1 phase arrest when compared to the control group (Fig. 3c-e). Conclusion Our investigations identified for the first time the oncogenic role of NCAPD3 in DLBCL tumorigenesis by bioinformatics analysis and in vitro evaluation. Expression of NCAPD3 was upregulated, and associated with adverse outcome of DLBCL patients. NCAPD3 inhibition by RNAi exerted anti-tumor efficacy in inhibiting cell growth, promoting apoptosis and blocking cell cycle. This study suggests that Sirt6 could be a potential molecular target for the treatment of DLBCL. Further study on it is under way. Disclosures No relevant conflicts of interest to declare.
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Zucchetto, Antonella, Chiara Caldana, Dania Benedetti, et al. "CD49d is overexpressed by trisomy 12 chronic lymphocytic leukemia cells: evidence for a methylation-dependent regulation mechanism." Blood 122, no. 19 (2013): 3317–21. http://dx.doi.org/10.1182/blood-2013-06-507335.
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Key Points CD49d, a negative prognosticator with a key role for microenvironmental interactions in CLL, is near universally expressed in trisomy 12 CLL. CD49d overexpression in trisomy 12 CLL is regulated by a methylation-dependent mechanism.
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Shamkhalova, Minara Shamkhalovna, Kseniya Olegovna Kurumova, Inna Igorevna Klefortova, et al. "Factors promoting development of renal tubulointerstitial lesions in patients with diabetes mellitus." Diabetes mellitus 13, no. 3 (2010): 134–41. http://dx.doi.org/10.14341/2072-0351-5502.
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Aim. To identify profibrogenic mediators, markers of endothelial dysfunction and hemostasis in patients with diabetes mellitus (DM) and chronickidney disease (CKD). Materials and methods. The study included 120 patients with DM and 20 age-matched normotensive subjects without DM showing the glomerularfiltration rate (GFR) > 60 ml/min/1.73 m3. Four groups of patients were distinguished: 1 - DM2 patients without renal pathology (n=33), 2 - DM2 patients with diabetic nephropathy (n=24), 3 - DM2 patients with ischemic nephropathy (IN) (n=33) verified by contrast visualization techniques(multispiral CM of abdominal aorta and renal arteries, abdominal angiography of renal arteries or MR angiography of renal arteries and abdominal aorta), 4 - DM1 patients with DN (n=30). Clinical examination included assessment of complaints, analysis of medical history of the main diseaseand concomitant disorders, determination of the main clinical and biochemical characteristics of blood and urine, measurement of НbА1с and 24-hralbuminuria (AU) by standard methods, estimation of GFR by the MDRD formula, ECG, echocardiography, 24-hr AP monitoring, counseling bycardiologist and ophthalmologist (fundal examination by ophthalmoscopy). Standard kits were used to detect profibrogenic mediators and markersof endothelial dysfunction including transforming growth factor-beta (TGF-b), angiotensin II (AT II), monocyte chemoattractant protein (MCP-1),regulated on activation normal T cell expressed and secreted (RANTES), adhesion factors (intracellular adhesion molecule (ICAM-1), vascular celladhesion molecule (VCAM-1) vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), asymmetric dimethylargnine (ADMA), homocysteine(HCYST), metalloproteinases (MMP), von Willebrand factor (vWF), plasminogen activator inhibitor (PAI-I). Results. DM patients with CKD had elevated blood profibrogenic cytokine (MCP-1, TGF-1b, IL-6) and extracellular matrix degradation factor(MMP-9) levels compared with patients without CKD and healthy subjects. These changes were unrelated to the type of diabetes or the cause ofnephropathy, which suggests their contribution to renal pathology through the universal mechanism of tubulointerstitial fibrosis. Activation of profibrogeniccytokines in DM patients with CKD was closely associated with endothelial dysfunction manifest as enhanced production of blood adhesive angiogenic, thrombogenic factors (FW, PAI, VICAM, sICAM, VEGF), and endothelium-affecting factors (ADMA, homocysteine). Mediators of inflammationand fibrogenesis in these patients negatively correlated with GFR and positively with AU, the main markers of renal dysfunction. Hyperuricemia,TGF-1b, ADMA, and MCP-1 are considered to be the risk factors of impaired renal filtration function. Conclusion. The level of profibrogenic cytokines and ndothelial dysfunction factors in DM patients with different renal lesions reflects severity of tubulointerstitialfibrosis. It may be used for the purpose of prognostication and substantiation of intensification of secondary prophylaxis of renal insufficiency.
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Gay, Laura, Ann-Marie Baker, and Trevor A. Graham. "Tumour Cell Heterogeneity." F1000Research 5 (February 29, 2016): 238. http://dx.doi.org/10.12688/f1000research.7210.1.
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The population of cells that make up a cancer are manifestly heterogeneous at the genetic, epigenetic, and phenotypic levels. In this mini-review, we summarise the extent of intra-tumour heterogeneity (ITH) across human malignancies, review the mechanisms that are responsible for generating and maintaining ITH, and discuss the ramifications and opportunities that ITH presents for cancer prognostication and treatment.
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Raskova Kafkova, Leona, Diana Brokesova, Zbynek Novak, Milan Raska, Dagmar Pospisilova, and Jana Volejnikova. "Platelet Desialylation As a Predictive Marker in Childhood Immune Thrombocytopenia (ITP)." Blood 134, Supplement_1 (2019): 221. http://dx.doi.org/10.1182/blood-2019-122095.
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Background and aim: Immune thrombocytopenia (ITP) is the most common bleeding condition in children. Its prognosis is mostly superior, however, severe refractory disease remains diagnostic and therapeutic challenge. Low platelet counts (&lt;100× 109/L) are associated with increased platelet clearance by two parallel mechanisms: classical antibody-mediated pathway and a novel lectin-carbohydrate mediated pathway. The latter is based on platelet desialylation, where terminal sialic acids are cleaved from glycoconjugates, mainly glycoproteins (GPs), on the platelet surface. The loss of sialic acid enhances bond of the penultimate β-galactose to asialoglycoprotein receptors (ASGPRs, also called Ashwell-Morell receptors) on hepatocytes. Desialylated platelets are then captured and phagocytosed by ASGPR-expressing hepatocytes. Desialylation has been shown to be responsible for platelet destruction in many contexts, e.g., infection-related thrombocytopenia or clearance of senescent platelets. Loss of T-cell tolerance is another underlying mechanism in ITP; CD8+ regulatory T cells (Tregs) are able to inhibit overactive immune response and maintain immune homeostasis. Forkhead box P3 (FOXP3) and GATA3 are transcription factors crucial for development and proper function of Tregs limiting the Th2-type inflammatory response. Our aims were to distinguish contribution of the mentioned processes to ITP development and to characterize immune response in children with ITP during the course of disease (diagnosis, ongoing therapy, remission, refractory/persistent ITP). Patients and Methods: We examined 30 samples from 20 children with ITP (12 males, 8 females, age 3-17 years; 3 acute ITP, 17 chronic ITP) and 10 healthy controls (age 4-15). The degree of desialylation was determined by flow cytometry using FITC-labeled Ricinus communis agglutinin (RCA-I) specific for terminal galactose or N-acetylgalactosamine. Expression of platelet surface markers was given quantitatively as mean fluorescence intensity (MFI). Presence of platelet surface-bond antibodies (IgG, IgA and IgM) was examined by flow cytometry. Subpopulations of CD4+ and CD8+ T-cells were characterized based on intracellular expression of transcription factors T-bet (Th1 cells), GATA3 (Th2 cells), ROR gamma T (Th17 cells) and FOXP3 (for Tregs) using multicolor flow cytometry. Results: Patients with ITP showed significant increase in RCA-I reactivity in comparison with healthy controls (p&lt;0.001). Patients with newly diagnosed ITP showed the most aberrant sialylation (i.e., maximum desialylation) of platelet surface proteins. A decrease in desialylation intensity was noticeable as soon as at three days after therapy initiation. Sialylation levels returned to normal after one month of successful treatment and were similar to healthy controls in children with ITP remission. Platelet surface-bond immunoglobulins were increased in 10 (50%) patients independently on their sialylation level. We observed significant changes in T-cell subpopulations in ITP: T lymphocytes producing T-bet were decreased within both CD4+ and CD8+ populations. Percentage of CD4+ cells expressing ROR gamma T was also reduced. Proportions of cells expressing FOXP3 and GATA3 were decreased within the CD8+ but not within the CD4+ population. Conclusion: Our results highlight the importance of Fc-independent hepatic platelet clearance in ITP. Interindividual differences in ITP pathophysiology are reflected by treatment response and may improve therapeutic management and prognostication. E.g., intravenous immunoglobulins or splenectomy will be ineffective in patients with prevalent Fc-independent mechanisms, and contrarily, possibilities for novel targeted treatment (neuraminidase inhibitors) arise. Better understanding of immune-mediated processes involved in ITP pathogenesis may reduce adverse effects of immunosuppressive therapy and considerably improve quality of life in patients with ITP. Supported by: MH CZ - DRO (FNOl, 00098892), Project ENOCH (No. CZ.02.1.01/0.0/0.0/16_019/0000868) and Ministry of Education, Youth and Sports OPVVV CEREBIT CZ.02.1.01/0.0/0.0/16_025/0007397. Disclosures No relevant conflicts of interest to declare.
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Bouffard, Marc, and Sashank Prasad. "Advances in Neuro-Ophthalmic Imaging." Seminars in Neurology 37, no. 05 (2017): 566–79. http://dx.doi.org/10.1055/s-0037-1608765.
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AbstractRecent years have brought a rapid evolution of diagnostic imaging studies in neuro-ophthalmic practice. Optical coherence tomography (OCT) and several of its derivations (swept-source OCT, enhanced-depth imaging OCT, and OCT-angiography) are advancing diagnosis, and in some cases prognostication, in a variety of inflammatory, ischemic, and compressive optic neuropathies. These technologies hold potential in the laboratory as well, yielding insights into the mechanisms of a variety of neurological conditions. In addition, further developments in magnetic resonance imaging and ultrasonography techniques are shaping the approach to the diagnosis of giant cell arteritis.
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Kaganova, T. I., and A. A. Loginova. "ETIOLOGICAL AND PATHOGENETIC MECHANISMS OF LINGERING NEONATAL JAUNDICE. PROGNOSTICATOIN AND DIFFERENTIATED MANAGEMENT OF CHILDREN WITH HYPERBILIRUBINEMIA." Current pediatrics 11, no. 5 (2012): 29. http://dx.doi.org/10.15690/vsp.v11i5.425.
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Liotti, Federica, Nella Prevete, Giancarlo Vecchio, and Rosa Marina Melillo. "Recent advances in understanding immune phenotypes of thyroid carcinomas: prognostication and emerging therapies." F1000Research 8 (February 28, 2019): 227. http://dx.doi.org/10.12688/f1000research.16677.1.
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Tumors modulate the host immune cells within their microenvironment to avoid recognition and elimination by our immune system, a phenotype called cancer immune escape. Different mechanisms responsible for cancer immune escape that result either in decreased tumor immunogenicity or in increased tumor immunosuppressive activity have been identified. Recently, various immunotherapeutic approaches have been developed with the aim to revert tumor immune escape. The aims of this review are to explore the immunological aspects of thyroid cancer and to assess whether these features can be exploited in the prognosis and treatment of advanced forms of this disease. Therefore, we will describe the immune landscape and phenotypes of thyroid cancer, summarize studies investigating the expression of immunomodulatory molecules, and finally describe the preclinical and clinical trials investigating the utility of immunotherapies in the management of thyroid cancer. The aim of this review is to explore the immunological aspects of thyroid cancer and to assess whether these features can be exploited in the prognosis and treatment of advanced forms of this disease. Therefore, we will describe the immune-landscape and phenotypes of thyroid cancer, we will summarize studies investigating the expression of immunomodulatory molecules, and we will finally describe the preclinical and clinical trials investigating the utility of immunotherapies in the management of thyroid cancer.
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Giorgi, Carlotta, Esmaa Bouhamida, Alberto Danese, Maurizio Previati, Paolo Pinton, and Simone Patergnani. "Relevance of Autophagy and Mitophagy Dynamics and Markers in Neurodegenerative Diseases." Biomedicines 9, no. 2 (2021): 149. http://dx.doi.org/10.3390/biomedicines9020149.
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During the past few decades, considerable efforts have been made to discover and validate new molecular mechanisms and biomarkers of neurodegenerative diseases. Recent discoveries have demonstrated how autophagy and its specialized form mitophagy are extensively associated with the development, maintenance, and progression of several neurodegenerative diseases. These mechanisms play a pivotal role in the homeostasis of neural cells and are responsible for the clearance of intracellular aggregates and misfolded proteins and the turnover of organelles, in particular, mitochondria. In this review, we summarize recent advances describing the importance of autophagy and mitophagy in neurodegenerative diseases, with particular attention given to multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease. We also review how elements involved in autophagy and mitophagy may represent potential biomarkers for these common neurodegenerative diseases. Finally, we examine the possibility that the modulation of autophagic and mitophagic mechanisms may be an innovative strategy for overcoming neurodegenerative conditions. A deeper knowledge of autophagic and mitophagic mechanisms could facilitate diagnosis and prognostication as well as accelerate the development of therapeutic strategies for neurodegenerative diseases.
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Torres Viera, Marialejandra Alejandra, Luis Villela, Brady E. Beltran, et al. "Serum Albumin and Neutrophil-to-Lymphocyte Ratio, Two Independent Factor Predicting Survival in Patients with Follicular Lymphoma: A Multi-Institutional Retrospective Cohort of 741 FL, from the Latin American Lymphoproliferative Study Group (GELL)." Blood 138, Supplement 1 (2021): 4515. http://dx.doi.org/10.1182/blood-2021-149662.
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Abstract Introduction: The neutrophil-lymphocyte ratio (NLR) is a measure of systemic inflammation that appears prognostic in different cancers. Although the exact mechanism remains to be elucidated, reduced lymphocyte intra tumor infiltration coupled with the formation of neutrophil extracellular traps (or NETosis) have been postulated as endogenous mechanisms for tissue damage and inflammation. Along this line, serum albumin has also been studied as a biomarker of inflammation and has been associated to prognosis in certain cancers. We have previously reported on the prognostic value of the NLR and serum albumin in diffuse large B-cell lymphoma (Villela, ASH meeting, 2019; Castro, ASH meeting, 2019) and peripheral T-cell lymphoma, not otherwise specified (Idrobo, ASH meeting, 2019), but nothing on follicular lymphoma (FL) yet. Therefore, we aim to investigate the role of different biomarkers on the prognosis of patients with FL diagnosed and managed in Latin America. Methods: We analyzed patients with FL diagnosed between 2010 and 2020 from 30 centers in 10 Latin American countries. The study outcomes were overall survival (OS) and progression-free survival (PFS) in relation to different biomarkers. Kaplan-Meier and log-rank test were used for survival analysis. Univariate and multivariate Cox regression analysis were used to estimate hazard ratios (HR) with a 95% confidence interval (CI) and adjusted to the Follicular Lymphoma International Prognostic Index (FLIPI) score. Outcomes with a p-value &lt;0.05 were considered statistically significant. Results: We identified 939 FL patients; 741 were included for the final analysis (median age 58 y, female 52%). There was no significant correlation between the NLR and other clinical factors such as: age, clinical stage, histological FL grading, and chemotherapy regimen used. A cutoff of 2.15 for NLR was defined as the maximum point for sensitivity and specificity based on ROC analysis. Table 1 and 2 summarizes the results from the univariate and multivariate analysis for 2 years OS and PFS, respectively. Both, serum albumin &lt;3.5 g/dL and a NLR &gt;2.15 were independently associated with worse OS (adjusted, aHR 2.48 [1.26-4.91], p=0.009; and 2.55 [1.21-5.37], p=0.014) and PFS (aHR 1.62 [1.03-2.55], p=0.038; 2.22 [1.45-3.40], p&lt;0.001), respectively. The lymphocyte:monocyte ratio (LMR) was not found to be prognostic for OS or PFS, although with a trend for worse PFS with a LMR ≤2.5. With a median follow of 43 months, (95% CI: 40-47), the survival rates in patients with FL and albumin &lt;3.5 were OS of 83% (vs. 95%) and PFS of 70% (vs. 83%); whereas in patients with NLR &gt;2.15 the survival rates were OS of 91% (vs. 96%) and PFS of 75% (vs. 88%) (Figures 1 and 2; table 3). Conclusions: In this study, serum albumin and NLR emerge as reliable predictors for survival for FL patients in Latin America. Although these markers have been associated to an increased inflammatory state in cancer patients; other factors such as poor nutritional status, and advanced disease stage due to delayed access to specialized cancer care in our region may have contributed to the observed outcome. Further studies are needed to better understand the role of these biomarkers on lymphoma care and to validate our findings. Lastly, we are currently working on evaluating these biomarkers on existing prognostic models and to improve prognostication for FL patients in Latin America. Figure 1 Figure 1. Disclosures Otero: ASTRA ZENECA: Current Employment. Ramirez-Ibarguen: Asofarma: Consultancy; MSD: Consultancy; Abbvie: Speakers Bureau; Astra Zeneca: Speakers Bureau; Janssen: Speakers Bureau; Roche: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Perini: Roche: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Janssen: Consultancy, Other: Travel/Accommodations/Expenses, Speakers Bureau; Takeda: Speakers Bureau; Abbvie: Consultancy, Other: Travel/Accommodations/Expenses, Speakers Bureau. Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.
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Haddad, Abdo S., Lukasz P. Gondek, Araf Alkali, et al. "SNP Array Analysis in Refractory Anemia with Ringed Sideroblast Allows for Detection of a High Frequency of Previously Cryptic Chromosomal Defects with Possible Clinical Significance." Blood 108, no. 11 (2006): 2352. http://dx.doi.org/10.1182/blood.v108.11.2352.2352.
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Abstract Among WHO low-risk categories of MDS, refractory anemia with ringed sideroblasts (RARS) can be more precisely identified based on typical findings in the iron stain preparations of marrow aspirates. Clonal hematopoiesis and chromosomal (chr) abnormalities are features that reveal a clear pathogenetic relationship to MDS. However, despite characteristic morphology, chr defects in RARS are heterogeneous, RARS shows considerable variability in the clinical course even for patients with identical cytogenetic defects. We analyzed the results of metaphase cytogenetics (MC) in a cohort of patients classified as RARS, RCMD-RS, or more advanced forms of MDS associated with ringed sideroblasts. Similar proportions of defects (around 50%) were found in RARS patients (n=68) as in all other remaining MDS forms studied (n=288). The most commonly occurring defects associated with ringed sideroblasts, compared to other forms of MDS, included those of chr 5 (14% vs 31%), 7 (11% vs 14%) and 8 (17% vs 20%), respectively. However, due to the low resolution of MC and its dependence on cell growth in vitro, this test is often negative or non-informative in MDS. High-density SNP arrays (SNP-A) allow for a precise identification of unbalanced genomic lesions. We hypothesize that cryptic chr aberrations do exist in most, if not all, patients with RARS. Their detection may help to improve prognostication, distinguish distinct subgroups of patients and point towards unifying pathogenic defects. Consequently, we have applied 250K SNP-A to analyze the marrow (n=14) or blood (n=15) in RARS. Pathologic lesions were defined based on a study of 36 normal marrow specimens (O’Keefe at al ASH 2006). By traditional MC, a defective karyotype was present in 18 of 29 patients (34%). Monosomy 7/7q- was found in 5 patients; deletions involving chr 5 and 11 in 2 cases; and 5 patients showed a complex karyotypes. However, when SNP-A was applied as a karyotyping tool (copy number and LOH analysis), we were able to detect lesions in 65% of patients (vs 34% by cytogenetics, p<.01). All but 2 aberrations found by MC were confirmed. New, previously cryptic lesions were identified, including losses of a portion of chr 8 (n=4) and deletions (n=2) as well as gains (n=2) within chr 17q. We have also detected segmental uniparental disomy (UPD) in 2 patients. This type of lesion cannot be detected using MC and provides an additional mechanism that can lead to LOH. When comparing MC to SNP-A, 1 lesion was found in 7/29 patients vs 12/29; 2 lesions in 0/29 vs 5/29; and ≥3 lesions in 3/29 vs 2/29 patients, respectively. Most remarkably, we have identified shared lesions, including an invariant deletion involving 4q31-21 (n=3, with 2/3 diagnosed as RARSt), loss of 8q24.23 (n=2); and a UPD involving 1p21.3-22.2 (n=2). These lesions contain important genes, including IL-15 and GAB1 (4p) or DR1 and TGFBR3 (1p). Our results indicate that if more precise techniques are applied, chr abnormalities can be detected in a higher proportion of patients with RARS. Analysis of clinical outcomes associated with defects identified by A-SNP is currently ongoing in our laboratory.
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Ghazal, Theodore, Lukasz P. Gondek, Abdo S. Haddad, et al. "SNP Array Karyotyping Improves Detection Rate of Clonal Chromosomal Abnormalities in Refractory Anemia with Ringed Sideroblasts." Blood 110, no. 11 (2007): 4132. http://dx.doi.org/10.1182/blood.v110.11.4132.4132.
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Abstract Among WHO low-risk categories of MDS, refractory anemia with ringed sideroblasts (RARS) can be more accurately diagnosed by characteristic pathomorphology. Clonal hematopoiesis and chromosomal abnormalities exemplify a close pathogenetic relationship to other forms of MDS. RARS shows considerable clinical variability even for patients (pts) with identical cytogenetic defects. Due to the low resolution of metaphase cytogenetics (MC) and its dependence on cell growth in vitro, this test is often non-informative in MDS. High-density SNP arrays (SNP-A) allow for a precise identification of unbalanced genomic lesions and copy-neutral loss of heterozygozity. We hypothesize that cryptic chromosomal (chr) aberrations exist in most, if not all, pts with RARS. Their detection may help to improve prognostication, distinguish distinct phenotypes and point towards unifying pathogenic defects. Initially, we analyzed the results of MC in pts with MDS and MDS/MPD (N=455) and in a sub-cohort of RARS, RCMD-RS, RARSt and other MDS subtypes with >15% RS. When we compared pts with/without RS, chr defects were found at comparable frequencies (∼50%). The most commonly occurring defects associated with RS, compared to other forms of MDS, included those of chr 5 (9% vs. 16%, 7 (8% vs. 12%) and 20 (3% vs. 8%). DNA was available for 36 pts with RS and was subjected to 250K SNP-A karyotyping. Pathologic lesions were defined upon exclusion of normal copy number polymorphisms identified in 81 controls (O’Keefe at al ASH 2007), as well as the Database of Genomic Variants (http://projects.tcag.ca/variation). By MC, a defective karyotype was present in 16/36 pts (44%). Deletions involving chr 5, 7 and complex MC were found in 3, 5, and 2pts, respectively. However, when SNP-A was applied as a karyotyping tool (copy number and LOH analysis), all aberrations found by MC were confirmed, but also new lesions were detected so that an abnormal karyotype was established in 62% of pts. Several previously cryptic/recurrent lesions included losses of a portion of chr. 2 (N=2; 2p16.2, 2p16.3), and deletions (N=4; 7p11.1–14.1, 7p21.3, 7q11.23–21.11, 7q21.12-qter) as well as gains (N=1; 7q33) on chr 7. We have also detected segmental uniparental disomy (UPD) in chr 1 (N=2; 1p21.3–22.2, 1p). This type of lesion cannot be detected using MC and provides an additional mechanism leading to LOH. When both bone marrow and blood of 5 RARS patient were tested using SNP-A, blood analysis had 100% accuracy rate as compared to marrow; all defects seen in the marrow were also found in blood. We conclude that chromosomal defects are present in a majority of RARS patients and arrays with higher resolution will identify defects in most, if not all of the patients. Our study also demonstrates testing of peripheral blood by SNP-A can complement marrow MC, especially in cases in which marrow is not available. Detection of clonal marker aberrations in blood of RARS patients suggests that mostly clonal dysplastic progenitor cells contribute to blood production rather than residual “normal” progenitors.
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Padua*, Mary Tannia, Amitha Joy, and G. Deepa. "Performance Gauging of Discrete Classifiers by Prognostication of a Reported Bug." International Journal of Innovative Technology and Exploring Engineering 9, no. 6 (2020): 654–56. http://dx.doi.org/10.35940/ijitee.f3407.049620.
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Bugs are the frequently transpiring drawback in software’s, to prevent these problems; an in-depth study of bugs is required. Bug repositories are a significant supply of information. The bug repository helps the software team to have a better study about bugs and its related parameters. Often arising bugs helps the developers to get rid of them in upcoming releases. There is a huge variety of algorithms that facilitate in finding bugs. This paper intends to measure the performance of mining algorithms in predicting the bug severity by scrutinizing their capabilities. We propose a study of assorted algorithms in Lazy (IBK and KStar) and Tree (Random Forest) Classifiers with regard to different parameters. The case inspected here is Mozilla_Thunderbird, which is implemented in WEKA.
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Alachkar, Houda, Ramasamy Santhanam, David M. Lucas, et al. "Translational Research From the Tropical Forest: Silvestrol, a Natural Product From the Plant Aglaia Foveolata inhibits the Expression of Tyrosine Kinases and Shows a Significant In Vivo Activity in Acute Myeloid Leukemia (AML)." Blood 118, no. 21 (2011): 2616. http://dx.doi.org/10.1182/blood.v118.21.2616.2616.
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Abstract Abstract 2616 Despite the progress made in the diagnosis, classification, prognostication and treatment of AML, the majority of patients still fail to achieve long-term survival and die of their disease. Several cytogenetic and molecular markers including gene mutations and aberrant expression have been shown to impact the outcome of AML patients and some of these are also potential therapeutic targets. Receptor tyrosine kinases (RTKs) regulate cell survival, proliferation and differentiation in normal hematopoiesis. Gain-of-function mutations of genes encoding RTKs, such as internal tandem duplication of FLT3 (FLT3-ITD) and mutations of KIT, result in constitutive tyrosine kinase activity and have been associated with poor outcome in distinct cytogenetic (i.e., normal karyotype and core binding factor, respectively) subsets of AML. In addition, overexpression of FLT3 and wild type (wt) KIT was also found to negatively impact outcome. Tyrosine kinase (TK) inhibitors (Is) (e.g., imatinib, dasatinib or PKC412) have been shown to suppress the aberrant activity of these mutants, but their activities as single agents have been limited by their relatively elevated IC50 values for myeloid blasts and early onset of resistance. Indeed, even in combination with chemotherapy, TKIs have not yet been shown to impact favorably on AML patient outcome. This supports the need for development of novel strategies that effectively interfere with aberrant TK activity in leukemia blasts. Silvestrol, a cyclopenta[b]benzofuran derivative isolated from Aglaia foveolata, a plant that grows in the tropical rain forests of Southeast Asia, has been shown to exhibit potent inhibitory activity against a panel of human cancer cell lines and shows in vitro and in vivo efficacy in B-cell malignancies. The mechanism of action has been thought to involve inhibition of translation initiation, which in turn results in selective depletion of actively translated, short half-lives proteins. We hypothesized that silvestrol-mediated inhibition of the translation of mutated and/or overexpressed RTKs results in a significant antileukemic activity in AML cells that rely on the aberrant TK activity of these proteins. Silvestrol showed antiproliferative and proapoptotic activities in representative AML cell lines harboring activated TK proteins: FLT3-ITD-positive MV4-11, FLT3-overexpressing THP-1 KIT-mutated Kasumi-1 and also BCR-ABL-positive K562, an erythroblastic cell line notoriously resistant to chemotherapy. Importantly, silvestrol treatment reduced the expression levels of FLT3 in MV4-11 (92 %) and THP-1 (84 %), KIT in Kasumi-1 (46 %), and BCR-ABL in K562 (64 %), compared to the respective vehicle-treated controls. The silvestrol IC50 at 48 hr was less than 10nM for all cell lines (MTS assay). Silvestrol also showed antiproliferative activity in FLT3-ITD-positive AML patient blasts (IC50 24 nM at 48 hr). To evaluate in vivo activity, NOD-SCID Gamma (NSG) mice were engrafted with FLT3-ITD-positive MV4-11 cells. Twenty-one days post-engraftment, mice were treated intraperitoneally with vehicle or silvestrol (1.5 mg/kg every 48 hr for 3 weeks). After 3 doses (day 6 of treatment), spleens were obtained from three mice from each group. Spleens from silvestrol treated mice were 60% decreased in size (P=0.016) and showed 80% FLT3 protein downregulation (P=0.002) compared to vehicle-treated controls. Silvestrol treated leukemic mice (n=10) survived significantly longer than vehicle treated control (n=6) (median survival: 55.5 days vs. 29 days from engraftment day respectively; P<0.0001). All vehicle-treated mice died by day 31 from engraftment (day 11 from treatment start), while 50% of silvestrol-treated mice are still alive on day 60 from engraftment (day 40 from treatment start; updated survival curves will be provided). We conclude that silvestrol has a potent in vitro and in vivo antileukemic activity in AML through downregulation of the expression and activity of FLT3 and other TKs driving leukemia. Given the excellent antileukemic activity of silvestrol via a novel mechanism of TK inhibition that is potentially complementary to that of TKIs (i.e., silvestrol-induced suppression of TK protein expression vs. TKI-induced protein enzymatic inhibition), a rapid translation of this natural product to the clinic as a single agent or in combination with other TKIs ± chemotherapy seems warranted. Disclosures: No relevant conflicts of interest to declare.
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Shamkhalova, Minara Shamkhalovna, Kseniya Olegovna Kurumova, and Marina Vladimirovna Shestakova. "Factors of tubulointerstitial lesions in diabetic kidneys." Diabetes mellitus 12, no. 4 (2009): 61–65. http://dx.doi.org/10.14341/2072-0351-5707.
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As the number of cases with classical manifestations of diabetic nephropathy (DN), i.e. nodular or diffuse glomerulosclerosis, grows, an increasinglylarger number of DM patients especially those with DM2 present with renal pathology largely affecting interstitium and tubules (ischemic nephropathy,urinary infection, interstitial nephritis, etc.). The rate of renal filtration impairment in glomerular diseases (DN, glomerulonephritis) is also relatedto the severity of tubulointerstitial fibrosis (TIF). Intricate intercellular interactions activated by immune and non-immune factors have been shownto play an important role in the development of tubulointerstitial lesions. Studies of the most important factors contributing to remodeling tubulointerstitiumin DM patients may provide a deeper insight into the mechanisms of nephrosclerosis and extend possibilities for prognostication of renalfunction.
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Petushek, Erich J., Edward T. Cokely, Paul Ward, and Gregory D. Myer. "Injury Risk Estimation Expertise: Cognitive-Perceptual Mechanisms of ACL-IQ." Journal of Sport and Exercise Psychology 37, no. 3 (2015): 291–304. http://dx.doi.org/10.1123/jsep.2014-0315.
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Instrument-based biomechanical movement analysis is an effective injury screening method but relies on expensive equipment and time-consuming analysis. Screening methods that rely on visual inspection and perceptual skill for prognosticating injury risk provide an alternative approach that can significantly reduce cost and time. However, substantial individual differences exist in skill when estimating injury risk performance via observation. The underlying perceptual-cognitive mechanisms of injury risk identification were explored to better understand the nature of this skill and provide a foundation for improving performance. Quantitative structural and process modeling of risk estimation indicated that superior performance was largely mediated by specific strategies and skills (e.g., irrelevant information reduction), and independent of domain-general cognitive abilities (e.g., mental rotation, general decision skill). These cognitive models suggest that injury prediction expertise (i.e., ACL-IQ) is a trainable skill, and provide a foundation for future research and applications in training, decision support, and ultimately clinical screening investigations.
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Onishchenko, Valentin. "Tooth wear modeling and prognostication parameters of engagement of spur gear power transmissions." Mechanism and Machine Theory 43, no. 12 (2008): 1639–64. http://dx.doi.org/10.1016/j.mechmachtheory.2007.12.005.
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Emich-Widera, Ewa, Wirginia Likus, Beata Kazek, et al. "CYP3A5*3 and C3435T MDR1 Polymorphisms in Prognostication of Drug-Resistant Epilepsy in Children and Adolescents." BioMed Research International 2013 (2013): 1–7. http://dx.doi.org/10.1155/2013/526837.
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Drug-resistant epilepsies still remain one of the most profound problems of contemporary epileptology. Several mechanisms of drug resistance are possible; among them, genetic factors have a prominent place. Much importance is attached to genes, which encode enzymes that metabolize antiepileptic drugs CYP 3A, which belong to the family of cytochromes P450 and the genome of multidrug resistance, such as multidrug resistance 1 (MDR1) that expresses P-glycoprotein (P-gp), a drug transporter protein. The aim of the study was to assess the relation between polymorphism of gene CYP3A5 and polymorphism C3435T of MDR1 gene with the occurrence of focal, drug-resistant epilepsy in children and youths up to 18 years of age. The study comprised 85 patients, and their age range was from 33 months to 18 years of age, suffering from epilepsy, partly responding well to treatment, partly drug resistant. The polymorphism of both genes has been analysed using the PCR-RFLP method. The study failed to corroborate association between polymorphism CYP3A5*3 and C3435T polymorphism in MDR1 gene and pharmacoresistant epilepsy. The results of our research do not confirm the prognostic value of the polymorphisms examined in the prognostication of drug resistance in epilepsies.
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Pauletto, Eleonora, Nils Eickhoff, Nuno Padrão, Christine Blattner, and Wilbert Zwart. "TRIMming Down Hormone-Driven Cancers: The Biological Impact of TRIM Proteins on Tumor Development, Progression and Prognostication." Cells 10, no. 6 (2021): 1517. http://dx.doi.org/10.3390/cells10061517.
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The tripartite motif (TRIM) protein family is attracting increasing interest in oncology. As a protein family based on structure rather than function, a plethora of biological activities are described for TRIM proteins, which are implicated in multiple diseases including cancer. With hormone-driven cancers being among the leading causes of cancer-related death, TRIM proteins have been described to portrait tumor suppressive or oncogenic activities in these tumor types. This review describes the biological impact of TRIM proteins in relation to hormone receptor biology, as well as hormone-independent mechanisms that contribute to tumor cell biology in prostate, breast, ovarian and endometrial cancer. Furthermore, we point out common functions of TRIM proteins throughout the group of hormone-driven cancers. An improved understanding of the biological impact of TRIM proteins in cancer may pave the way for improved prognostication and novel therapeutics, ultimately improving cancer care for patients with hormone-driven cancers.
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Kurylo, Vitalii, Iryna Trubavinab, Olena Karamana, Viktoriia Stepanenkoa, and Yaroslava Yurkiva. "Pedagogic technology of formation of readiness for self-development in students from the occupied territories and delimitation line in the east of Ukraine in conditions of temporarily displaced higher education institutions." Journal of Educational Sciences & Psychology 11(73) (2021): 39–53. http://dx.doi.org/10.51865/jesp.2021.2.06.
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The topicality of the research is connected with the need to develop a technology of preparing students for learning for life, developing their professional self-development at a temporarily displaced higher education institution in conditions when students’ primary and basic needs are insufficiently satisfied. The methods of the research included analysis, synthesis, comparing, systemizing, interviewing, pedagogic experiment, modelling, prognostication, mathematic statistics methods. The level of the analyzed phenomenon turned out much lower than that in students from the safety zone by the following parameters: self-management, gnostic, motivation, moral-and-will, and communicative components of readiness, conditions, mechanisms, and general level of self-development. The scientific novelty: the efficiency of such a technology was proved and justified, and its content was revealed.
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Whelan, Daniel, and Ryan Khan CCRP Graeme Hoit. "Common peroneal nerve injury in the setting of multi-ligament knee injury: incidence and recovery in a prospective cohort." Orthopaedic Journal of Sports Medicine 8, no. 7_suppl6 (2020): 2325967120S0048. http://dx.doi.org/10.1177/2325967120s00486.
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Objectives: Multiligament knee injuries (MLKI’s) are rare, but life-altering injuries which can be made worse with the presence of a concomitant nerve palsy or drop foot. Common peroneal nerve (CPN) palsy has previously been reported to be present in 5-40% of MLKI patients. The purpose of this study was to identify factors that predict CPN palsy at the time of MLKI presentation as well as determine variables that impact likelihood of neurologic recovery. Methods: Between 2006-2017, adults with MLKIs were identified at an academic level 1-trauma center and those with CPN palsy symptoms at presentation were identified. Patients were enrolled in prospective data collection and followed routinely after surgery. The primary outcome was MRC score to analyze associations between age, gender, BMI, injury severity (Schenck classification), surgical timing and presence of fibular head fracture. Secondarily, those with CPN palsy were also compared to a matched cohort of MLKI patients without CPN palsy for demographic as well as functional outcome differences using multiligament quality of life scores (MLQoL). Results: 152 patients were identified with MLKIs, of which 57 presented with a CPN palsy (38%). When comparing those with CPN palsy to those without, there were significantly more males in the CPN palsy cohort (p=0.001), significantly more lateral sided injuries – 84% versus 36% (p<0.001), and significantly more fibular head fractures – 35% versus 12% (p=0.001). There was no difference in age, BMI or injury severity or sidedness. Percentage of full or near full recovery for patients with CPN palsy at presentation was 58% (MRC>/=4). In comparing those with permanent CPN palsies to those who recovered, there was a trend towards significance for those with fibula head fractures being more likely to recover (Chi-squared 3.21, p=0.07). There was no significant difference in age, sex, BMI, sidedness, laterality, or time from presentation to surgery in terms of nerve recovery. There was no significant difference in MLQoL scores between those without CPN palsy, those with CPN palsy which recovered (MRC>/=4) and those with permanent CPN palsy (MRC<4). Analysis of MRC grading and sensory grading at presentation and factors influencing the likelihood of recovery is pending. Conclusions: The rate of CPN palsy within MLKI identified in our study matches previously reported literature. Male gender, lateral sided injury and presence of a fibular head fracture were found to be risk factors for CPN palsy at the time of injury. We found no significant difference between demographic or injury mechanism between patients who developed permanent CPN palsy and those who recovered, though there was a trend towards better recovery in those with fibular head fracture. Additionally, we found no difference between patients with CPN palsy compared to those without with respect to MLQoL scores in any domain, which calls into question whether a MLKI patient report outcome measure should incorporate nerve specific questions given the high rate of nerve injuries. The authors intend to analyze the likelihood of recovery in partial versus complete CPN palsy at the time of presentation. To our knowledge this is the largest prospectively collected dataset on CPN palsies after MLKIs, and will provide important insight into neurologic prognostication, especially when combined with previously reported data elsewhere in the literature.