Small-Molecule-Directed Endogenous Regeneration of Visual Function in a Mammalian Retinal Degeneration Model.

Degenerative retinal diseases associated with photoreceptor loss are a leading cause of visual impairment worldwide, with limited treatment options. Phenotypic profiling coupled with medicinal chemistry were used to develop a small molecule with proliferative effects on retinal stem/progenitor cells, as assessed in vitro in a neurosphere assay and in vivo by measuring Msx1-positive ciliary body cell proliferation. The compound was identified as having kinase inhibitory activity and was subjected to cellular pathway analysis in non-retinal human primary cell systems. When tested in a disease-relevant murine model of adult retinal degeneration (MNU-induced retinal degeneration), we observed that four repeat intravitreal injections of the compound improved the thickness of the outer nuclear layer along with the regeneration of the visual function, as measured with ERG, visual acuity, and contrast sensitivity tests. This serves as a proof of concept for the use of a small molecule to promote endogenous regeneration in the eye.

The Impact of Contemporary Antiretroviral Drugs on Atherosclerosis and Its Complications in People Living With HIV: A Systematic Review.

With the advent of modern antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection has been modified into a chronic manageable condition, prolonging the lifespan of people living with HIV (PLHIV). This has resulted in an increased non-AIDS-related morbidity in the HIV-infected population. Our aim is to study the role of contemporary ART in tackling the risk of atherosclerosis and cardiovascular disease (CVD) in PLHIV. We searched through the databases of PubMed, PubMed Central, and Cochrane Library for pertinent articles using the medical subject headings (MeSH) "HIV infection", "Atherosclerosis", and "Antiretroviral agents". The articles published in the past five years were retrieved, screened for relevance, and assessed for quality before being included in the review. This review was performed following the PRISMA 2020 guidelines. The results indicate that the incidence of dyslipidemia with integrase strand transfer inhibitors (INSTIs) is greater than with non-nucleoside reverse transcriptase inhibitors (NNRTIs) and lesser than with protease inhibitors (PIs). INSTIs are indispensably associated with weight gain and obesity. High triglyceride (TG) and oxidized low-density lipoproteins to low-density lipoproteins (oxLDL/LDL) ratio levels and low high-density lipoprotein (HDL) levels are seen in patients taking PIs. A higher incidence of hypertension and metabolic syndrome (MetS) was noticed with INSTIs compared to NNRTIs. PI intake for >5 years increases the risk of subclinical atherosclerosis. Increased risk of myocardial infarction with INSTIs was observed in a study, while another study reported decreased risk. HIV infection independently increases the risk for atherosclerosis and CVD. Although contemporary ART decreases this enhanced risk, it inherently increases the risk for abnormal lipid profile, MetS, weight gain, and obesity. Further research into the risk of atherosclerosis and CVD with newer ART drugs is essential for decoding the underlying mechanisms and preventing adverse cardiac outcomes in PLHIV.

Comparison between peripheral nerve stimulator-guided serratus anterior plane block versus transversus abdominis plane block for postoperative analgesia in laparoscopic cholecystectomy under general anaesthesia: A double-blind randomised controlled trial.

Background and Aims: Laparoscopic cholecystectomy (LC) is a widely accepted surgical procedure associated with postoperative pain. This study was done to compare peripheral nerve stimulator (PNS)-guided serratus anterior plane block (SAP) and transversus abdominis plane (TAP) block for postoperative analgesia for patients undergoing LC. Methods: Following approval from the ethical committee, 70 patients for LC were randomly assigned to Group S: SAP block and Group T: TAP block. The blocks were performed under PNS guidance, and 20 ml of 0.375% ropivacaine was administered. The severity of pain was measured using a visual analogue scale (VAS). The study's primary objective was the evaluation of the postoperative VAS score. The time of the first dose of rescue analgesia and total tramadol consumption for 24 h postoperatively were secondary objectives. All the statistical calculation was done using statistical analyses for Social Sciences for Windows version 23.0 (IBM Corp, NY, USA). Results: Lower VAS score was seen in patients of TAP block at rest as well as movement at 6 h (P = 0.001), 12 h (P = 0.001) and 18 h (P = 0.001) postoperatively compared with SAP. The TAP group showed a significantly increased time of first rescue analgesic compared to the SAP group (7.97 ± 0.51 vs. 5.89 ± 1.45, P = 0.001). Tramadol usage was significantly higher in the SAP group than in the TAP group (128.9 ± 36.22 vs. 72.43 ± 44.80, P = 0.001). Conclusion: TAP block guided by the PNS improves postoperative pain with less tramadol consumption and during the postoperative period without significant complications.

Adult Brainstem Astroblastoma: Unusual Presentation of a Rare Tumor.

Astroblastoma is a rare tumor, which is mostly found in pediatric population. Due to scarcity of literature, the data about treatment is lacking. We are reporting case of brainstem astroblastoma in an adult female. A 45-year-old lady presented with complaint of headache, vertigo, vomiting, and nasal regurgitation for 3 months. On examination, she had weak gag, left hemiparesis. Magnetic resonance imaging brain reported medulla oblongata mass, dorsally exophytic. She underwent suboccipital craniotomy and decompression of mass. Histopathology confirmed diagnosis of astroblastoma. She underwent radiotherapy and recovered well. Brainstem astroblastoma is an extremely rare entity. The surgical resection is possible due to well-defined plane. For best outcome, maximum resection and radiation are indicated.

OpenPBTA: The Open Pediatric Brain Tumor Atlas.

Pediatric brain and spinal cancers are collectively the leading disease-related cause of death in children; thus, we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, the Children's Brain Tumor Network (CBTN) and Pacific Pediatric Neuro-Oncology Consortium (PNOC) created a systematic process for tumor biobanking, model generation, and sequencing with immediate access to harmonized data. We leverage these data to establish OpenPBTA, an open collaborative project with over 40 scalable analysis modules that genomically characterize 1,074 pediatric brain tumors. Transcriptomic classification reveals universal TP53 dysregulation in mismatch repair-deficient hypermutant high-grade gliomas and TP53 loss as a significant marker for poor overall survival in ependymomas and H3 K28-mutant diffuse midline gliomas. Already being actively applied to other pediatric cancers and PNOC molecular tumor board decision-making, OpenPBTA is an invaluable resource to the pediatric oncology community.

Which Is Better? Rate Versus Rhythm Control in Atrial Fibrillation: A Systematic Review.

Atrial fibrillation (AF) is a common arrhythmia associated with significant morbidity and mortality. The optimal approach to managing AF, specifically rate control versus rhythm control, remains a topic of debate in clinical practice. This systematic review aims to compare the rate control and rhythm control strategies based on their clinical outcomes, quality of life, and adverse events associated with them. A comprehensive search was conducted using PubMed, Google Scholar, Science Direct, Research Gate, MEDLINE (Medical Literature Analysis and Retrieval System Online), Scopus, and Embase (Excerpta Medica dataBASE) databases. A total of 1657 research papers were identified through the search strategy, and after applying the eligibility criteria, 28 studies were selected for the analysis. The studies encompassed a range of methodologies, including randomized controlled trials, observational studies, and meta-analyses. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for study selection, data extraction, and analysis. The outcomes of interest included all: cause mortality, stroke, bleeding events, cardiovascular hospitalizations, quality of life, and adverse effects of treatment. Data were synthesized and presented in tables, charts, and forest plots for meta-analysis where appropriate. The results indicate that both rate control and rhythm control strategies have their own merits and limitations, with the outcomes varying based on patient characteristics and comorbidities. While rhythm control strategies may lead to better symptom control and improved quality of life, rate control strategies may be associated with lower risks of adverse events and complications. This systematic review provides a comprehensive overview of the current evidence regarding rate and rhythm control strategies in AF management, offering insights for clinical decision-making and highlighting the need for individualized treatment approaches.

Discovery and functional characterization of the oncogenicity and targetability of a novel NOTCH1-ROS1 gene fusion in pediatric angiosarcoma.

Angiosarcomas are rare, malignant soft tissue tumors in children that arise in a wide range of anatomical locations and have limited targeted therapies available. Here, we report a rare case of a pediatric angiosarcoma (pAS) with Li-Fraumeni syndrome (LFS) expressing a novel NOTCH1-ROS1 gene fusion. Although both NOTCH1 and ROS1 are established proto-oncogenes, our study is the first to describe the mechanistic role of NOTCH1-ROS1 fusion arising via intrachromosomal rearrangement. NOTCH1-ROS1 displayed potent neoplastic transformation propensity in vitro, and harbors tumorigenic potential in vivo, where it induced oncogenic activation of the MAPK, PI3K/mTOR, and JAK-STAT signaling pathways in a murine allograft model. We found an unexpected contribution of the NOTCH1 extracellular region in mediating NOTCH1-ROS1 activation and oncogenic function, highlighting the contribution of both NOTCH1 and ROS1 fusion partners in driving tumorigenicity. Interestingly, neither membrane localization nor fusion protein dimerization were found to be essential for NOTCH1-ROS1 fusion oncogenicity. To target NOTCH1-ROS1-driven tumors, we tested both NOTCH1-directed inhibitors and ROS1-targeted tyrosine kinase inhibitors (TKI) in heterologous models (NIH3T3, Ba/F3). Although NOTCH1 inhibitors did not suppress NOTCH1-ROS1-driven oncogenic growth, we found that oral entrectinib treatment effectively suppressed the growth of NOTCH-ROS1-driven tumors. Taken together, we report the first known pAS case with a novel NOTCH1-ROS1 alteration along with a detailed report on the function and therapeutic targeting of NOTCH1-ROS1. Our study highlights the importance of genomic profiling of rare cancers such as pAS to reveal actionable drivers and improve patient outcomes.

Upfront Biology-Guided Therapy in Diffuse Intrinsic Pontine Glioma: Therapeutic, Molecular, and Biomarker Outcomes from PNOC003.

PURPOSE: PNOC003 is a multicenter precision medicine trial for children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG). PATIENTS AND METHODS: Patients (3-25 years) were enrolled on the basis of imaging consistent with DIPG. Biopsy tissue was collected for whole-exome and mRNA sequencing. After radiotherapy (RT), patients were assigned up to four FDA-approved drugs based on molecular tumor board recommendations. H3K27M-mutant circulating tumor DNA (ctDNA) was longitudinally measured. Tumor tissue and matched primary cell lines were characterized using whole-genome sequencing and DNA methylation profiling. When applicable, results were verified in an independent cohort from the Children's Brain Tumor Network (CBTN). RESULTS: Of 38 patients enrolled, 28 patients (median 6 years, 10 females) were reviewed by the molecular tumor board. Of those, 19 followed treatment recommendations. Median overall survival (OS) was 13.1 months [95% confidence interval (CI), 11.2-18.4] with no difference between patients who followed recommendations and those who did not. H3K27M-mutant ctDNA was detected at baseline in 60% of cases tested and associated with response to RT and survival. Eleven cell lines were established, showing 100% fidelity of key somatic driver gene alterations in the primary tumor. In H3K27-altered DIPGs, TP53 mutations were associated with worse OS (TP53mut 11.1 mo; 95% CI, 8.7-14; TP53wt 13.3 mo; 95% CI, 11.8-NA; P = 3.4e-2), genome instability (P = 3.1e-3), and RT resistance (P = 6.4e-4). The CBTN cohort confirmed an association between TP53 mutation status, genome instability, and clinical outcome. CONCLUSIONS: Upfront treatment-naïve biopsy provides insight into clinically relevant molecular alterations and prognostic biomarkers for H3K27-altered DIPGs.

A retrospective study of association of CT severity with clinical profile and outcomes of patients with COVID-19 in the second wave.

Objectives: This study aimed to find out the association of CT severity score with demographic and clinical characteristics as well as mortality in the patients who were confirmed to have COVID-19 disease in the second wave. Material and Methods: This retrospective study included collection and assessment of the demographic, clinical, laboratory data, and mortality of the patients, suspected with COVID-19 infection who underwent chest HRCT scan during March to April 2021. The findings of the chest HRCT were retrieved manually from the Medical Records section. Determination of the severity was done by the scoring system that involved the visual evaluation of the affected lobes. Results: CT severity score was mild, moderate, and severe in 21.94%, 41.60%, and 30.48% patients, respectively. Mortality rate was 5.70%. Age of the patients with mild, moderate, and severe CT severity score was significantly more than those with normal severity score (50 vs. 50 vs. 50 vs. 31, P=0.0009). When compared to patients with normal score, those with mild, moderate, and severe CT severity score had significantly higher dyspnoea (10.39% vs. 67.81% vs. 97.20% vs. 0%), significantly more cases with diabetes mellitus (16.88% vs. 25.34% vs. 31.78% vs. 9.52%, P=0.044), hypertension (27.27% vs. 21.23% vs. 32.71% vs. 4.76%, P=0.026), and obesity (6.49% vs. 8.90% vs. 23.36% vs. 0%, P=0.0005). Total leucocyte counts, absolute neutrophil counts, creatinine, serum glutamic pyruvic transaminase (SGPT), lactate dehydrogenase (LDH), ferritin, and D-dimer were deranged in significantly more patients of severe score (53.27%, 62.62%, 60.75%, 85.05%, 90.65%, 97.20%, and 95.35%, respectively). Interleukin-6 (IL-6) and C-reactive protein were deranged in significantly more patients with moderate disease (98.18% and 98.63%, respectively). Increasing severity scores were associated with increased mortality (mild vs. moderate vs. severe: 1.30% vs. 1.37 vs. 15.89%, P<.0001). Oxygen saturation (SpO2) was significantly lowest in severe score followed by moderate, mild and normal scores (87 vs. 90 vs. 96 vs. 97, P<.0001). Duration of non-rebreather mask (NRBM), noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), Venture/face mask, and intubation was also associated with increasing severity scores (P<0.0001). Conclusion: CT scans play an important role in guiding physicians with their management plans and can serve as a predictor of disease severity and outcomes.

The use of mandibular nerve block in unilateral mandibular fracture to evaluate the mouth opening for assessment of airway.

Background: Facial area is one of the most frequently injured area of the body, accounting for 23-97% of all facial fractures. Treatments under general anesthesia as those for maxillofacial fractures or infections is a highly complicated and a major challenging task in trismus associated patients. The main culprit in trismus is the increase muscle tone of masticatory muscles which are supplied via the mandibular nerve, blocking which could help increase the mouth opening thus, changing the whole of airway management. Material and Method: A prospective study was done on 50 patients of ASA grade I-II with unilateral mandibular fracture with trismus posted for maxillofacial surgery. Mandibular nerve block was given via extraoral approach with 5 ml of 0.5% bupivacaine using peripheral nerve stimulator to determine the difference in Pre block and Post block mouth opening and the VAS score at 2, 5, 10, 15, 20, 25, and 30 minutes. Results: The Interincisor distance measured Pre block was 1.20 ± 0.32 mm and was significantly increased after 5 mins onwards from the block (P < 0.005). The VAS score determined Pre block was 5.14 ± 1.37 which significantly decreased just 2 minutes after the application of block (P < 0.005). Conclusion: Mandibular nerve block decreases the pain and will aid in the decision making by an anesthetist regarding airway management as it helps in increasing the inter incisor distance significantly. Moreover, given the feasibility and effectiveness of the block it could be included in standard of care protocol for mandibular fracture patients.

Chest radiographic findings and their correlation with disease progression in COVID-19 patients in northern India.

Introduction: The present study was undertaken to describe and quantify the spectrum of radiographic findings on coronavirus disease 2019 (COVID-19) patients. The study also aimed to analyse the changes in chest X-ray (CXR) with disease progression. Methods: COVID-19 patients admitted between the period of 15 March 2020 and 1 July 2020 were retrospectively enrolled. CXR images were assessed and reported as 'Normal' or 'Abnormal'. A severity score was calculated using Warren et al.'s Radiographic Assessment of Lung Edema scoring. Correlations of the severity score thus calculated were sought with age, sex, clinical manifestations and presence of comorbidities. Results: Five hundred patients (342 males, 158 females) were enrolled, median age being 35 years. Fever and cough were the most common symptoms but significant correlation of an abnormal CXR was found with dyspnoea. CXRs were normal in 67% and abnormal in 33% patients. The commonest comorbidities were diabetes mellitus and cardiovascular disease including hypertension, coronary artery disease and congestive heart failure. Predominant pattern was ground glass opacities, reticular alteration and consolidation peaking in the second week from symptom onset. The most frequent distribution was bilateral, peripheral with middle/lower predominance. Increasing age, male sex, presence of dyspnoea and comorbidities correlated with abnormal findings on CXR. Critical illness and mortality correlated strongly with increasing age, male sex and presence of dyspnoea, less so with presence of comorbidities. Conclusion: In the current scenario with clinicians and radiologists working in tandem, CXR seems to be a promising tool in providing relevant information in a simplified way.

Ultrasonographic Changes in Transorbital Measurement of Optic Nerve Sheath Diameter in Magnesium Sulfate-Treated Severely Preeclamptic Patients: A Prospective Observational Study.

Introduction: Severe preeclampsia can lead to various complications including increased intracranial pressure (ICP) which can be catastrophic but difficult to detect because of variable nonspecific symptoms. Ultrasonography has been used as noninvasive measure to monitor optic nerve sheath diameter (ONSD) as a marker of raised ICP. Effect of MgSO4 on ICP can modify the management approach, need for additional monitoring, targeting hemodynamic goals, timing of delivery, and choice of anesthesia. We evaluated the effect of MgSO4 on raised ICP in severely preeclamptic patients using ultrasound-guided ONSD as a surrogate marker of ICP. Methodology: This prospective observational study was conducted after ethical committee approval and written informed consent from patients. Ultrasound-guided ONSD was measured and compared in 47 severe preeclamptic patients before and at 1 h, 4 h, 12 h, and 24 h after starting MgSO4 therapy. The analysis of data was done by one-way analysis of variance using Statistical Package for the Social Science. Results: Mean ONSD was 5.56 ± 0.30 mm in our study group. ONSD above 5.8 mm was seen in 17 (36.17%) patients and was considered as marker of raised ICP. There was a significant decrease in ONSD after 4 h of administration of MgSO4. No significant correlation was observed between mean arterial pressure, serum magnesium level, and ONSD. Conclusion: Ultrasound-guided ONSD measurement can be used as a quick, noninvasive bedside tool in severe preeclamptic patient on MgSO4 treatment as marker of ICP which help us in determining clinical severity, therapeutic response, and to decide further course of management.

Mortality in patients with Coronavirus disease 2019 (COVID- 19) and its clinicoradiological and laboratory correlates: A retrospective study.

Aim: To delineate and analyze the mortality from COVID -19 in our institute during the devastating second wave of pandemic. Settings and Design: A retrospective cohort analysis. Methods and Materials: A comprehensive mortality analysis of 142 laboratory-confirmed severe acute respiratory syndrome coronavirus 2-infected deceased patients from our hospital's medical records was done. These patients presented with severe disease at the time of admission and were managed in intensive care units. Statistical Analysis Used: Statistical Package for Social Sciences software, IBM manufacturer, Chicago, USA, version 21.0 was used. Results: The number of deceased males (82, 62.6%) was higher than females (53, 37.3%). Median age of deceased patient was 57 (44.25-69.75) years. Most frequent comorbidities were diabetes mellitus (42, 29.6%) and hypertension (41, 28.9%). Most common symptoms being shortness of breath (137, 96.5%), fever (94, 66.2%) and cough (73, 51.4%). Median peripheral capillary oxygen saturation (SpO2) at time of admission was 86% (77.25-90). Median time interval from symptom onset to admission in hospital was 3 (2.25-5) days. Neutrophil lymphocyte ratio was more than 5 in 117 (90.7%) patients. Complications seen were acute respiratory distress syndrome in 82.3%, acute liver injury in 58.4%, acute kidney injury in 26.7%, sepsis in 13.3% and acute cardiac injury in 12% patients. The median high-resolution computed tomography score was 20 (17-22). Conclusions: Male and elderly patients with underlying comorbidities had poorer outcome and involvement of multiple organ systems was common. A short time interval between symptom onset and admission/mortality, particularly encountered was worrisome.

Peripheral nerve stimulator guided erector spinae plane block for post-operative analgesia after total abdominal hysterectomies: A feasibility study.

BACKGROUND AND AIMS: The pain following total abdominal hysterectomy (TAH), a very commonly performed gynaecological surgery, is usually taken care of by various opioids, non-opioids, regional and peripheral nerve blocks. Erector spinae plane block (ESPB) under ultrasound guidance is a relatively new approach for postoperative analgesia in thoracic and abdominal surgeries. Ultrasound availability and expertise to use it is a limitation at times. The primary aim of this study was to determine the analgesic efficacy of ESPB using peripheral nerve stimulation (PNS) technique in patients undergoing TAH. METHODS: A total of 60 American Society of Anesthesiologists physical status I and II female patients were posted for abdominal hysterectomy after obtaining ethical committee clearance in a tertiary care centre. Group I (n = 30) received spinal anaesthesia, whereas Group II (n = 30) received ESPB under peripheral nerve stimulator (PNS) guidance with 20 mL of 0.375% ropivacaine before spinal anaesthesia. Post-operative pain intensity reported using the Visual Analogue Scale (VAS) was considered as the primary outcome. The haemodynamic variables, total duration before the first rescue analgesia, total consumption of tramadol, level of satisfaction regarding analgesia and any complications were considered as secondary outcomes. The data were recorded in an excel sheet, and analysis was performed using the Statistical Package for the Social Sciences version 23.0. RESULTS: VAS score was significantly lower (P < 0.001) in Group II at 0, 1, 2, 3, 4, 6, 12, 18 and 24 h post-operatively. The total dose of rescue analgesia was significantly reduced in the ESPB group. CONCLUSION: PNS-guided ESPB is effective in relieving pain in patients undergoing TAH.

BRAF fusions in pediatric histiocytic neoplasms define distinct therapeutic responsiveness to RAF paradox breakers.

Pediatric histiocytic neoplasms are hematopoietic disorders frequently driven by the BRAF-V600E mutation. Here, we identified two BRAF gene fusions (novel MTAP-BRAF and MS4A6A-BRAF) in two aggressive histiocytic neoplasms. In contrast to previously described BRAF fusions, MTAP-BRAF and MS4A6A-BRAF do not respond to the paradox breaker RAF inhibitor (RAFi) PLX8394 due to stable fusion dimerization mediated by the N-terminal fusion partners. This highlights a significant and clinically relevant shift from the current dogma that BRAF-fusions respond similarly to BRAF-inhibitors. As an alternative, we show suppression of fusion-driven oncogenic growth with the pan-RAFi LY3009120 and MEK inhibition.

annoFuse: an R Package to annotate, prioritize, and interactively explore putative oncogenic RNA fusions.

BACKGROUND: Gene fusion events are significant sources of somatic variation across adult and pediatric cancers and are some of the most clinically-effective therapeutic targets, yet low consensus of RNA-Seq fusion prediction algorithms makes therapeutic prioritization difficult. In addition, events such as polymerase read-throughs, mis-mapping due to gene homology, and fusions occurring in healthy normal tissue require informed filtering, making it difficult for researchers and clinicians to rapidly discern gene fusions that might be true underlying oncogenic drivers of a tumor and in some cases, appropriate targets for therapy. RESULTS: We developed annoFuse, an R package, and shinyFuse, a companion web application, to annotate, prioritize, and explore biologically-relevant expressed gene fusions, downstream of fusion calling. We validated annoFuse using a random cohort of TCGA RNA-Seq samples (N = 160) and achieved a 96% sensitivity for retention of high-confidence fusions (N = 603). annoFuse uses FusionAnnotator annotations to filter non-oncogenic and/or artifactual fusions. Then, fusions are prioritized if previously reported in TCGA and/or fusions containing gene partners that are known oncogenes, tumor suppressor genes, COSMIC genes, and/or transcription factors. We applied annoFuse to fusion calls from pediatric brain tumor RNA-Seq samples (N = 1028) provided as part of the Open Pediatric Brain Tumor Atlas (OpenPBTA) Project to determine recurrent fusions and recurrently-fused genes within different brain tumor histologies. annoFuse annotates protein domains using the PFAM database, assesses reciprocality, and annotates gene partners for kinase domain retention. As a standard function, reportFuse enables generation of a reproducible R Markdown report to summarize filtered fusions, visualize breakpoints and protein domains by transcript, and plot recurrent fusions within cohorts. Finally, we created shinyFuse for algorithm-agnostic interactive exploration and plotting of gene fusions. CONCLUSIONS: annoFuse provides standardized filtering and annotation for gene fusion calls from STAR-Fusion and Arriba by merging, filtering, and prioritizing putative oncogenic fusions across large cancer datasets, as demonstrated here with data from the OpenPBTA project. We are expanding the package to be widely-applicable to other fusion algorithms and expect annoFuse to provide researchers a method for rapidly evaluating, prioritizing, and translating fusion findings in patient tumors.

Telemedicine in India: A tool for transforming health care in the era of COVID-19 pandemic.

Although telemedicine has been used spottily in Indian health care so far, the 2020 Covid-19 pandemic provided the nation's health systems an unprecedented opportunity to make a concerted effort to increase access and coverage. Health-care providers can incorporate telemedicine systems to reduce doctor-patient visits and help in breaking the chain of transmission of infections. Anticipating the increased need of telemedicine by health-care providers, the Medical Council of India released practice guidelines in March 2020. In this article, the literature pertinent to telemedicine and its applications with special reference to recently released practice guidelines were reviewed and summarized in a historical and current context. Telemedicine is bound to grow and be adopted by more health-care practitioners and patients in a wide variety of forms due to ease and availability. At the same time, it cannot replace in-person consultation or emergency medicine.

PHF19 mediated regulation of proliferation and invasiveness in prostate cancer cells.

The Polycomb-like protein PHF19/PCL3 associates with PRC2 and mediates its recruitment to chromatin in embryonic stem cells. PHF19 is also overexpressed in many cancers. However, neither PHF19 targets nor misregulated pathways involving PHF19 are known. Here, we investigate the role of PHF19 in prostate cancer cells. We find that PHF19 interacts with PRC2 and binds to PRC2 targets on chromatin. PHF19 target genes are involved in proliferation, differentiation, angiogenesis, and extracellular matrix organization. Depletion of PHF19 triggers an increase in MTF2/PCL2 chromatin recruitment, with a genome-wide gain in PRC2 occupancy and H3K27me3 deposition. Transcriptome analysis shows that PHF19 loss promotes deregulation of key genes involved in growth, metastasis, invasion, and of factors that stimulate blood vessels formation. Consistent with this, PHF19 silencing reduces cell proliferation, while promotes invasive growth and angiogenesis. Our findings reveal a role for PHF19 in controlling the balance between cell proliferation and invasiveness in prostate cancer.

Smarcad1 mediates microbiota-induced inflammation in mouse and coordinates gene expression in the intestinal epithelium.

BACKGROUND: How intestinal epithelial cells interact with the microbiota and how this is regulated at the gene expression level are critical questions. Smarcad1 is a conserved chromatin remodeling factor with a poorly understood tissue function. As this factor is highly expressed in the stem and proliferative zones of the intestinal epithelium, we explore its role in this tissue. RESULTS: Specific deletion of Smarcad1 in the mouse intestinal epithelium leads to colitis resistance and substantial changes in gene expression, including a striking increase of expression of several genes linked to innate immunity. Absence of Smarcad1 leads to changes in chromatin accessibility and significant changes in histone H3K9me3 over many sites, including genes that are differentially regulated upon Smarcad1 deletion. We identify candidate members of the gut microbiome that elicit a Smarcad1-dependent colitis response, including members of the poorly understood TM7 phylum. CONCLUSIONS: Our study sheds light onto the role of the chromatin remodeling machinery in intestinal epithelial cells in the colitis response and shows how a highly conserved chromatin remodeling factor has a distinct role in anti-microbial defense. This work highlights the importance of the intestinal epithelium in the colitis response and the potential of microbial species as pharmacological and probiotic targets in the context of inflammatory diseases.