Journal articles on the topic 'Vibhakti'

ABSTRACT Dwividhopakramaneeya Adhyaya is a specialty of Acharya Vagbhatt being a part of both the treatises Ashtang Hridaya and Ashtang Sangraha. It paves the way for the understanding of treatment protocol for any disease. In the present study, the analysis of the chapter considers the different technical, literary, and grammatical aspects that can help widen the knowledge base. The detailed analysis of a chapter can be useful in better understanding other chapters in the texts. The objective of this article is to analyze the Dwividhopakramaneeya Adhyaya mentioned in the A. H and A. S. texts in light of conceptual and critical domains. The analysis and discussion are done considering the domains of the grammatical aspects of chapter etymology, authorship, position, number of verses mentioned in both A. H. and A. S, type of Sutra, Chanda, Samaasa, Vibhakti in the Adhyaya, analysis of chapter based on the literary tools Tantrayukti (Arthashraya, Vyakhya, Tacchilya, Upama, Nyaya), technical Ayurveda terms (Ashtavidha Prashna, Dasha Prakarana, Adhyayana-Adhyapan-Tadvidya Sambhasha, Pada-Paada-Shloka, Vakyasha-Vakyarthasha-Artha-Avayavasha) along with navigating the different concepts mentioned in Adhyaya such as Trisutra, Pramana, and Siddhant. It can be concluded that Adhyaya is pivotal for understanding all the diseases and treatment modalities as per Ayurveda. The methodology adopted to analyze the Adhyaya can be beneficial to understand the different aspects of the text as a whole. The present article can aid in learning and understanding of other Adhyaya in Ayurveda texts thus opening future areas of research to establish and assess the fundamental principles of Ayurveda.

Machine translation is important application in natural language processing. Machine translation means translation from source language to target language to save the meaning of the sentence. A large amount of research is going on in the area of machine translation. However, research with machine translation remains highly localized to the particular source and target languages as they differ syntactically and morphologically. Appropriate inflections result correct translation. This paper elaborates the rules for inflecting the parts-of-speech and implements the inflection for Marathi to English translation. The inflection of nouns, pronouns, verbs, adjectives are carried out on the basis of semantics of the sentence. The results are discussed with examples.

Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Short Talks from Proffered Abstracts section (PR004) of the Conference Proceedings. Citation Format: Daniel Spakowicz, Rebecca Hoyd, Caroline E. Wheeler, Nyelia Williams, Amna Bibi, Marium Husain, Srichandhana Rajamouli, Shankar Suman, Joseph Amann, Madison Grogan, Pooja Vibhakar, Dwight H. Owen, David P. Carbone, Ashley Rosko, Christin E. Burd, Carolyn J. Presley. Older adult-specific microbes correlate with treatment response and markers of T-cell senescence in NSCLC [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A021.

Hindi is the third most-spoken language in the world (615 million speakers) and has the fourth highest native speakers (341 million). It is an inflectionally rich and relatively free word-order language with an immense vocabulary set. Despite being such a celebrated language across the globe, very few Natural Language Processing (NLP) applications and tools have been developed to support it computationally. Moreover, most of the existing ones are not efficient enough due to the lack of semantic information (or contextual knowledge). Hindi grammar is based on Paninian grammar and derives most of its rules from it. Paninian grammar very aggressively highlights the role of karaka theory in free-word order languages. In this article, we present an application that extracts all possible karakas from simple Hindi sentences with an accuracy of 84.2% and an F1 score of 88.5%. We consider features such as Parts of Speech tags, post-position markers (vibhaktis), semantic tags for nouns and syntactic structure to grab the context in different-sized word windows within a sentence. With the help of these features, we built a rule-based inference engine to extract karakas from a sentence. The application takes in a text file with clean (without punctuation) simple Hindi sentences and gives back karaka tagged sentences in a separate text file as output.

Abstract Medulloblastoma (MB) is the most common malignant pediatric brain tumor. The most aggressive MB subtype Group 3, is characterized by Myc amplifications. However, targeting Myc has proven unsuccessful, necessitating alternative therapies for MB. The histone methyltransferase, enhancer of zeste homolog 2 (EZH2), is well-known for its role in catalyzing the tri-methylation of H3K27 (H3K27me3). Recent studies have demonstrated that EZH2 is overexpressed in Group 3 MB and that Myc and EZH2 regulate the expression of the B7 homolog 3 (B7-H3). As we previously showed the oncogenic functions of B7-H3 in Group 3 MB, this study aims to investigate the efficacy of EZH2 inhibition to reduce B7-H3 levels in an effort to improve treatment options and patient survival. Datamining studies conducted using MB patient datasets showed a positive correlation between EZH2 and B7-H3 transcripts. Additionally, we showed that inhibition of EZH2 using EPZ005687 in Myc-amplified MB cell lines downregulated B7-H3 and Myc expression. Furthermore, targeting EZH2 through shRNA and pharmacological inhibition reduced the viability and augmented apoptosis, as indicated by LDH, MTT, clonogenic, and FACS assays. We additionally tested the consequences of EZH2 inhibition on the C17.2, murine neural stem cells, and C17.2 NSC transformed with EZH2 oncogene (C17.2_EZH2OX). Furthermore, the C17.2_EZH2OXcells were susceptible to EPZ005687 treatment compared to C17.2 control cells, as demonstrated by MTT and FACS. Collectively, our study highlights the therapeutic benefits of targeting EZH2 in Myc-amplified MB cell survival. Citation Format: Katherine Shishido, Sujatha Venkataraman, Rajeev Vibhakar, Kiran Velpula, Swapna Asuthkar. EZH2 inhibition targets B7-H3 in Myc amplified medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5667.

Abstract Atypical Teratoid Rhabdoid Tumor (ATRT) is a highly aggressive pediatric brain tumor and characterized by SMARCB1 deletion. SMARCB1 is a member of the SWI/SNF chromatin remodeling complex that is responsible for determining cellular pluripotency and lineage commitment. We performed an RNAi-based functional genomic screen to identify key epigenetic regulators that co-operate with SMARCB1 loss and contribute to tumorigenesis in ATRT. 406 genes associated with epigenetic regulation in patient derived ATRT cell lines were targeted. This screen identified BMI1, a component of the Polycomb Repressive Complex 1 (PRC1), as one of the top targets essential for ATRT cell growth. Using RNA-seq and ChIP-Seq analysis we demonstrated that BMI1 co-operates with SMARCB1 deletion to suppress transcription of pro-differentiation pathways and promote self-renewal of tumor stem cells. In SMARCB1 deficient cells BMI1 forms a partial PRC1 complex devoid of DNA binding components. We found that genetic inactivation of BMI1 suppresses ATRT cell clonogenicity in vitro and decreases S-phase length. By Doxycycline-inducible SMARCB1 re-expression system we revealed activation of proapoptotic proteins p16 and p21. With immunoprecipitation for BMI1, followed by mass spectrometry analysis we demonstrated that re-expression of SMARCB1 activates two PRC1 chromatin localizing components CBX4 and CBX8. Moreover, inhibition of BMI1 significantly prolongs mice survival and decreases tumor size as evaluated by IVIS imaging system and T2-MRI. Thus, we demonstrated that SMARCB1 deletion results in reprograming of BMI1 chromatin occupancy away from lineage specification by altering the components of the PRC1 complex and that PRC1/BMI1 inhibition is a novel therapeutic approach in ATRT. Citation Format: Irina Irina Alimova, Gillian Murdock, Angela M. Pierce, Dong Wang, Nathan Dahl, Sujatha Venkataraman, Rajeev Vibhakar. PRC1/BMI1 activity alters chromatin accessibility to regulate differentiation in atypical teratoid rhabdoid tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A080.

Abstract Background: Dynamic regulation of gene expression is fundamental for cellular adaptation to exogenous stressors. PTEFb-mediated promoter proximal pause-release of Pol II is a conserved regulatory mechanism for synchronous transcriptional induction best described in response to heat shock, but this pro-survival role has not been examined in the applied context of cancer therapy. Design/Method: In order to examine the dynamics of chromatin reorganization following radiotherapy, we performed a combination of ChIP-, ATAC-, and RNA-seq in model systems of diffuse intrinsic pontine glioma (DIPG) and other pediatric high-grade gliomas (pHGG) following IR exposure. We interrogated IR-induced gene expression in the presence or absence of PTEFb blockade, including both mechanistic and functional consequences of concurrent inhibition or genetic depletion. We utilized culture models with live cell imaging to assess the therapeutic synergy of PTEFb inhibition with IR, as well as the therapeutic index of this intervention relative to normal controls. Finally, we employed orthotopic models of pHGG treated with conformal radiotherapy and CNS-penetrant PTEFb inhibitors in order to assess tolerability and anti-tumor effect in vivo. Results: Rapid genome-wide redistribution of active chromatin features and PTEFb facilitates Pol II pause-release to drive nascent transcriptional induction within hours of exposure to therapeutic ionizing radiation. Concurrent inhibition of PTEFb imparts a transcription elongation defect, abrogating canonical adaptive programs such as DNA damage repair and cell cycle regulation. This combination demonstrates a potent, synergistic therapeutic potential agnostic of glioma subtype, leading to a marked induction of tumor cell apoptosis and prolongation of xenograft survival.Conclusion: These studies reveal a central role for PTEFb underpinning the early adaptive response to radiotherapy, opening new avenues for combinatorial treatment in these lethal malignancies. Citation Format: Faye M. Walker, Lays Martin Sobral, Etienne Danis, Bridget Sanford, Ilango Balakrishnan, Dong Wang, Angela Pierce, Sana Karam, Natalie J. Serkova, Nicholas K. Foreman, Sujatha Venkataraman, Robin Dowell, Rajeev Vibhakar, Nathan A. Dahl. Rapid PTEFb-dependent transcriptional reorganization underpins the glioma adaptive response to radiotherapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr B078.

Moore, David R., Vibhakar C. Kotak, and Dan H. Sanes. Commissural and lemniscal synaptic input to the gerbil inferior colliculus. J. Neurophysiol. 80: 2229–2236, 1998. The central nucleus of the inferior colliculus (ICC) receives direct inputs, bilaterally, from all auditory brain stem nuclear groups. To evaluate the contribution made to gerbil ICC neuron physiology by two major afferent pathways, we examined the synaptic responses evoked by direct stimulation of the commissure of the inferior colliculus (CIC) and the ipsilateral lateral lemniscus (LL). Frontal midbrain slices were obtained from postnatal day (P) 9–P19 gerbils, and whole cell recordings were made under current- ( n = 22) or voltage-clamp ( n = 52) conditions. Excitatory and inhibitory synaptic responses were characterized by sequentially exposing the slice to ionotropic glutamate receptor antagonists [6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) + aminophosphonpentanoic acid (AP-5), or kynurenic acid)], a γ-aminobutryic acid type A receptor antagonist (bicuculline), and a glycine receptor antagonist (strychnine). In current clamp, LL stimulation typically produced a short latency depolarization followed by a longer duration hyperpolarization. The depolarization was abolished by AP-5 + CNQX, and the remaining inhibitory potential displayed either bicuculline or strychnine sensitivity. In voltage clamp, 79% of ICC neurons displayed synaptic currents after stimulation of each pathway. The synaptic currents were typically complex waveforms, and ionotropic glutamate receptor antagonists reduced inward currents at a holding potential of −80 mV in the majority of neurons. In addition, this treatment reduced outward synaptic currents at a holding potential of −20 mV, indicating that inhibitory interneuronal input was often activated by LL or CIC afferents. A minority of neurons had synaptic currents that were unaffected by glutamate receptor antagonists, but it was more common for CIC-evoked currents to be unaffected (38%) rather than LL-evoked currents (22%). The CIC provided a strong inhibitory input that was almost exclusively GABAergic, whereas the LL inhibition often included a glycinergic component. These experiments have shown that the CIC provides a major glutamatergic and GABAergic input to most ICC neurons. However, much of the inhibitory input from both the CIC and the LL appears to be mediated by interneuronal connections.

Abstract Medulloblastoma (MB) is the most prevalent malignant brain tumor in children that demonstrates clinical and genomic heterogeneity. Of the four major subgroups, Group 3 tumors (MYC-MB), and particularly the 3gsubtype, exhibit high levels of MYC, high rates of metastasis, and have the worst prognosis. Despite treatment with surgery, radiation and chemotherapy, Group 3 medulloblastoma patients are more likely to develop recurrent tumors which are far more aggressive resulting in a 5-year survival rate after recurrence of 12%. Thus, there is an imperative need to examine the underlying mechanisms mediating treatment resistance. Recent evidence has identified cellular plasticity, as a major driver of therapy resistance. To investigate whether epigenetic mediated cell plasticity contributes to Myc-MB therapy response we performed Single Nuclei Multiome ATAC + Gene Expression analysis of paired primary and relapsed tumors. We identified the emergence of novel progenitor populations in resistant tumors with stem-like gene expression networks and altered chromatin accessibility. These emergent popuoations demostrated new enhancer-promoer interactions and exhibited increased metabolic reprogramming with potential for theraputic targeting. Because radiation is one of the key treatment modalities for Myc-MB, we chose to model radiation resistance in further studies. Single-cell RNA sequencing of outgrown in vivo irradiated orthotopic xenograft MB tumors showed an overall upregulation of metabolic pathways with the enhancement of genes that mediate oxidative phosphorylation and glutamate metabolism centering on wild-type IDH1 (wtIDH1), consistent with our patient data. IR-resistant cells showed altered chromatin occupancy of H3K3me3 and H3K27Ac. Disruption of IDH1 activity in IR resistant cells in vitro altered the epigenomic landscape, facilitating reversion to the pre-irradiated state. Interestingly, we observed that pluripotent genes with bivalent regions (H3K4me3 and H3K27me3) were enhanced in radiation-resistant cells and suppressed by IDH1 inhibition. Metabolic mass spectrometry reveled that metabolites from the citric acid cycle and synthesis of unsaturated fatty acids were among the main metabolically elevated molecules in radiation-resistant cells consistnat with the observed epigenomic reprograming. IDH1 inhibition reversed the metabolic reprograming and resensitized MB cells to radiation. In total our data identify a novel mechanism of radiation resistance in medulloblastoma with potential theraputic implications. Citation Format: Bethany Veo, Dong Wang, John Desisto, Rajeev Vibhakar. Mechanisms of radiation resistance in medulloblastoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A071.

Abstract Medulloblastoma (MB) is a prevalent malignant pediatric brain tumor with high mortality rates despite currentmultimodal therapies. MYC-driven Group 3 MB represents a highly aggressive subgroup with poor prognosis and limited treatment options. To systematically identify genes representing therapeutic vulnerabilities in MYC-driven MB, we performed a CRISPR-Cas9 screen with a specific focus on 1140 druggable genes across three MB cell lines. CDK8 emerged as a significantly selected gene crucial for MYC-driven MB growth, for which clinically relevant inhibitors are in early phase trials. CDK8 gene expression is high in group 3 MB (Colorado cohort) and specifically high in MYC driven MB subtypes and elevated expression of CDK8 is an adverse prognostic marker even in high-risk group 3 tumors. CDK8 is highly expressed in progenitor populations identified in our recent single-cell RNA-seq analysis and similarly expressed in cycling progenitors in murine models of MB. CDK8 depletion in MB cells using CRISPR-Cas9-induced knockout and lentivirus-mediated CDK8 shRNAs resulted in decreased i cell proliferation and MYC protein. Additionally, CDK8 depletion significantly decreased neurosphere growth in MB cells and supressed orthotopic xenograft growth in vivo. Evaluation of eight CDK8 selective inhibitors demonstrated a broad range of half-maximal inhibitory concentrations (IC50) across three G3-MB cell lines with RVU120 showing the maximum potency, RVu120 supressed colony growth in vitro in MB cells but not normal astrocytes. In vivo RVU120 potently supressed growth of orthotopic xenografts as evaluated by MRI and prolonged survival. RNA-seq analysis revelaed that CDK8 depletion leads to repression of mRNA translation and ribosome biogenesis. GSEA indicated that the loss of CDK8 resulted in strong negative enrichment in the transcriptomic profile associated with stemness gene sets and positive enrichment in differentiation gene sets. We performed a genome-wide analysis to map the occupancy of CDK8 and key histone markers using CUT&RUN in three G3-MB cell lines. We found that CDK8 functions as a transcriptional activator affecting the translation program. In vitro, inhibition of protein tranlation via mTOR supression was synergistic with CDK8 inhibition. We found that this synthetic lethality was relevant in vivo,where CDK8i and mTORi combined to supress xenograft growth and prolong survival. Taken together, these studies established the therapeutic efficacy of combination treatment with mTOR and CDK8 inhibitors in vivo and in vitro, opening an alternate path for biologically based therapeutic trials in MYC-driven MB. Citation Format: Dong Wang, Breunna Brunt, Bethany Veo, Milena Mazan, Tomasz Rzmyski, Sujatha Venkataraman, Nathan Dahl, Rajeev Vibhakar. Understanding the role of CDK8 in protein synthesis for treating MYC-driven medulloblastoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A082.

Abstract Despite recent efforts to expand clinical trial eligibility criteria to involve traditionally underserved patient populations, less than 5% of patients diagnosed with cancer choose to participate in clinical trials (lifestyle, behavioral or pharmaceutical), of which only a small fraction represents underserved or vulnerable populations. The barriers that contribute to these trends are multifactorial. Examining sociodemographic and clinical characteristics may provide insight into successful participant recruitment and retention of underrepresented groups in clinical trials. The NutriCare study (NCT04986670) is a national, multisite, randomized controlled trial evaluating the impact of medically tailored meals plus weekly nutritional counseling on the outcomes of vulnerable patients with treatment-naïve lung cancer initiating treatment. Eligibility criteria defining vulnerability included: ≥65 years of age; underrepresented minority; rural resident; no health insurance; or income ≤130% of federal poverty line. To remain on study, eligible participants also completed a 90-minute baseline assessment within 8 weeks of study consent. A comprehensive list of screened patients was maintained throughout the course of the study, including approach attempts and refusal reasons for participation. Strategies to improve recruitment included obtaining referrals from the treating physician and inclusion of the study dietitian during the informed consent process. Descriptive statistics were used to summarize the recruitment and retention of vulnerable patients. Overall, 438 participants were screened in Phase I of this study at The Ohio State University and MD Anderson (Nov, 2020 – Aug, 2022), of which 116 (26%) participants consented to the study. Of these 116 participants, 76 (66%) were 65 years of age or older, 42 (36%) lived in a rural area, 21 (18%) identified as a racial or ethnic minority, and 27 (23%) met federal poverty levels. As the study progressed, 44 (38%) patients withdrew between baseline to 3-months,18 (16%) patients withdrew between the 3-month to 8-month timepoints, and a total of 54 (47%) participants completed the study. The highest retention rates were identified among those <65 years (58%), males (52%), early-stage lung cancer (69%), racial or ethnic minorities (62%), non-rural residents (50%) and those above the federal poverty line (48%). Barriers to completing the study included rapid decline in performance status among those diagnosed with late/extensive stage lung cancers (16%), treatment impacting taste and appetite (8%), and logistical complications with the meal intervention (3%). Barriers to recruitment and willingness to participate during the NutriCare trial were similar across recruiting sites. Future trials should consider implementation of a crossover study design, local and customized food delivery services, and measurements of time toxicity related to survey completion as an outcome. These efforts may improve clinical trial participation and provide more supportive care needs for vulnerable patients with lung cancer. Citation Format: Hazel M. Antao, Kenneth Kwan Ho Chui, Jade Smith, Pooja Vibhakar, Mary Kathryn Cohen, Jessica Bauman, Saumil Gandhi, Joya Chandra, Lori Pai, Fang Fang Zhang, Colleen Spees, Carolyn Presley. Overcoming barriers in recruiting medically underserved patients with lung cancer: The NutriCare study, a "Food is Medicine" intervention [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B116.

Abstract Background: DIPG (Diffuse Intrinsic Pontine Glioma) is an aggressive pediatric brain tumor that infiltrates the pons and is uniformly fatal. Curative surgery is not possible, radiation therapy provides only temporary relief, and chemotherapy is not effective. There is a great interest in applying Chimeric Antigen Receptor (CAR) expressing T cells and CAR-T cell strategies to solid tumors like DIPG; however, doing so will require novel approaches in CAR-T cell design to make this therapy effective. We recently identified CD99 as a highly expressed antigen in DIPG cells and an immunotherapy target in DIPG. A major obstacle in CAR-T cell therapy for solid tumors is the absence of true “tumor only” antigens, as most antigens are shared among multiple normal cells. CD99 is expressed in other normal cells. Therefore, combinatorial targeting of numerous antigens has the potential to overcome the lack of tumor-specific antigens. Hypothesis: Given that DIPG cells uniquely express the combination of B7-H3 and CD99 at high levels, we propose that CAR-T cells capable of specifically recognizing this combination will offer specificity to DIPG cells while safeguarding normal tissues expressing either antigen alone. We then developed a novel bicistronic CAR construct that employs Boolean logic to 'gate' the function of CAR-T cells according to 'AND' rules, where two distinct antigens are necessary for CAR-T cell activation. In our model, we used our novel CD99 CAR (based on 10D1-antibody-based ScFv) in conjunction with B7-H3 CAR (enoblituzumab antibody-based scFv). We created two 'AND' CAR-T cells using different co-stimulatory domains and successfully tested the specificity and functionality of our 'AND' CARs. Results: The “AND” CAR-T cells 1) showed enhanced tumor cell killing when co-cultured with DIPG tumor cells; 2) demonstrated no functionality against either single antigen-expressing cells, suggesting the specificity of the AND CAR-T in targeting dual-antigen-expressing tumor cells and 3) a single low dose of “AND” CAR-T cells delivered either IV or intrathecally completely cleared DIPG in the murine models with a significant increase in animal survival while either antigen targeting monovalent CAR-T cells showed only temporary clearance of tumor as the tumor relapsed after treatment. In addition, during the meeting, we will discuss the results obtained concerning the potency of the “AND” CARs developed against DIPG tumors. Topics will include the engineering design of the “AND” CAR-T cells to overcome CD99-driven fratricide, increased CAR-T persistence in vivo, and the mechanism behind the enhanced efficacy of our “AND” CAR-T cells against heterogeneously expressed tumor target antigens. Conclusion: The results from this study will significantly advance the development of effective immunotherapy for patients with DIPG. It emphasizes the importance of target antigen density heterogeneity and employs logic-gating to enhance tumor clearance and increase specificity, thereby reducing the risks associated with targeting shared antigens. Citation Format: Sujatha Venkataraman, Ilango Balakrishnan, Lillie Leach, Krishna Madhavan, Angela Pierce, Joshua Michlin, Joshua Obrecht, Breauna Brunt, Terry Fry, Rajeev Vibhakar, Eric.M Kohler. Developing a safe and potent tumor-targeting gated CAR-T cell therapy for DIPG: A deadly pediatric brain tumor [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr PR010.

Abstract The gut microbiome changes with age and affects many aspects of human health, including response to cancer treatments. Cancer survival rates have improved with new treatment options, including immune checkpoint blockade (ICB); however, the objective response rate remains low. Manipulation of the microbiome is a promising approach to improving cancer outcomes, but the effect of age is understudied. Here, we sought to understand whether (1) specific microbes are associated with treatment response in older adults with non-small cell lung cancer (NSCLC) and (2) whether these microbes are the same as for younger adults. Next, we explored the causal effects of the microbiome on ICB response in mouse models and the relationship with blood-based markers of T-cell senescence. We conducted a prospective cohort study of adults ≥60 years with a new diagnosis of NSCLC who received any treatment modality. Stool was collected, and metagenomic whole-genome shotgun sequencing was performed. Blood T-cells were isolated, the RNA purified and then assessed for markers of senescence by nanostring. Response to treatment was determined by RECIST v1.1 criteria. Generalized linear regression was used to relate baseline microbiome abundances to treatment response and non-parametric correlations associated with CDKN2A (p16) expression to microbe abundances. To assess the causal role of the gut microbiome in ICB response, we gavaged gut microbiome samples from responders and non-responders into C57BL/6 mice to create human-microbiome avatar models. The mice were then injected with MC38 cancer cells and treated with anti-PD1 or isotype control antibodies, and tumor volume was measured over time. Biospecimens and best response data at three months were captured from 23 patients, of which five had a complete response, eight had a partial response, eight had stable disease, and two had progressive disease. Over 50 microbes were associated with a response after p-value adjustment. Responder stool was enriched for microbes associated with youth and ICB response (Bifidobacterium adolescentis, p = 2.64e-20). However, microbial taxa associated with response differed from those reported in younger populations (Firmicutes sp. CAG 145, p = 1.58e-20, Oscillibacter sp. 57-20, p = 7.96e-24). Stool from non-responders (NRs) was enriched in taxa previously linked to treatment-related toxicities and shorter progression-free survival (Streptococcus lutetiensis, p = 4.55E-24) but also contained microbes previously linked to response in younger adults (e.g., Roseburia sp. CAG 309, p = 5.16e-15). The T cell senescence marker, p16, correlated with the most enriched taxon in non-responders NRs (Streptococcus thermophilus, r = 0.45, p = 0.02), suggesting a connection between immune aging and the microbiome. Preliminary fecal transplant studies in mice showed improved ICB response in mice engrafted with stool from responders versus non-responders. Together, these data identify potential differences in the gut microbiomes of young and older adult NSCLC patients who respond to ICB. Citation Format: Daniel Spakowicz, Rebecca Hoyd, Caroline E. Wheeler, Nyelia Williams, Amna Bibi, Marium Husain, Srichandhana Rajamouli, Shankar Suman, Joseph Amann, Madison Grogan, Pooja Vibhakar, Dwight H. Owen, David P. Carbone, Ashley Rosko, Christin E. Burd, Carolyn J. Presley. Older adult-specific microbes correlate with treatment response and markers of T-cell senescence in NSCLC [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr PR004.

Sushruta samhita as the best one in sharira. Sushruta has explained anatomy of sira in Sharir sthana 7th chapter ‘Siravarna Vibhakti Shariropkram’. Sira is also one of the important structural concepts which are described by Acharya Sushruta. Siravedhan is an ancient method of treatment. Sushruta considered siravedhan as Chikitsardha i.e. half treatment of disease. Sushruta has mentioned specific sites for siravedhan as well as sites for Avedhya sira. Vedhan of Avedhya sira may cause severe harmful effect to body. Siravedhan is curative treatment in many diseases. So it becomes essential for siravedhan knowledge to find out the anatomical structure to which one can label as Avedhya sira and also to avoid complications due to puncture of Avedhya sira. Aim- To study Urdhwa shakhagat avedhya sira and its anatomical consideration. Conclusion- Avedhya sira are anatomical structures which are either deep vessels or vessels which can lead to harmful effects by puncturing them.

<strong>Abstract &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </strong> The research paper explores the impact of grammar in the treatment of words and sentences in Sanskrit. The study analyses the importance of grammar in understanding and interpreting Sanskrit texts, and how knowledge of grammar can aid in the correct pronunciation and intonation of Sanskrit words. The paper also delves into the historical and cultural significance of Sanskrit grammar, and how it has been used as a tool for preserving and transmitting knowledge in ancient India. Through a detailed examination of Sanskrit grammar rules and their practical applications, the paper highlights the vital role of grammar in the study and practice of Sanskrit language and literature. The research paper investigates the impact of grammar in the treatment of words and sentences in Sanskrit. The study delves into the importance of understanding the rules of grammar in order to effectively interpret and communicate in Sanskrit. The researchers conducted a thorough analysis of various texts and grammatical rules, and observed that a strong foundation in grammar is essential for accurately conveying meaning and context in Sanskrit. The paper highlights the significance of incorporating grammar as an integral part of Sanskrit language learning, and recommends that educators emphasize its importance to students. The findings of this study contribute to the broader understanding of the role of grammar in language learning and its impact on communication. <strong>Key words: </strong>Vākya, Pada, Nāma, Ākhyāta, Nipāta, Upasarga, Taddhita, Samāsa, Sandhi and Vibhakti.

This paper is an attempt in building a rule-based dependency parser for Telugu which can parse simple sentences. This study adopts Pāṇini’s Grammatical (PG) tradition i.e., the dependency model to parse sentences. A detailed description of mapping semantic relations to vibhaktis (case suffixes and postpositions) in Telugu using PG is presented. The paper describes the algorithm and the linguistic knowledge employed while developing the parser. The research further provides results, which suggest that enriching the current parser with linguistic inputs can increase the accuracy and tackle ambiguity better than existing data-driven methods.

Золь-гель метод применен для получения одно- и двойнослойных оксидно-алюминиевых пленок на поверхности конструкционной стали 08кп для защиты от коррозии. Золь-гель систему готовили по методу Йолдаса путем гидролитической поликонденсации изопропоксида алюминия в присутствии уксусной кислоты при температуре 85-90 °С. Измерены рН, размер и дзета-потенциал частиц бемита, а также изучено коррозионное поведение стали в полученных коллоидах. При комнатной температуре слой гидрогеля бемита наносили путем погружения образцов стали в гель, выдержки в нем и последующей сушки в присутствии паров аммиака с целью подавления коррозии.Термообработку при 500 °С в атмосфере воздуха применяли для разложения бемита с образованием оксида алюминия и закрепления пленки на поверхности субстрата. Второй слой пленки наносили аналогичным образом поверх полностью сформированного первого слоя. Морфология поверхности полученных пленок изучена методами сканирующей электронной и атомно-силовой микроскопии. 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