Hilbert modular forms and Galois representations

In this expository article, we present a brief introduction to the theory of Hilbert modular forms and Galois representations, and describe what it means to attach a compatible system of Galois representations to a Hilbert modular form.Comment: 30 pages. This article will be published in the second trimester proceedings of the yearlong program on 'Triangle groups, Belyi uniformisation and Modularity' organized by Bhaskaracharya Pratishthana, Pune in 2021-2

Type and mode of diagnosis of carcinoma lung in a tertiary care centre: one year experience

Background: Lung cancer is one of the commonest cancers and cause of cancer related deaths all over the world. The reported incidence of adenocarcinoma is increasing globally and now reported to be the most common type of lung cancer. A panel of investigations are used for the diagnosis of lung cancer. Hence a study was planned to find out the pattern of malignancy and the most appropriate investigation for diagnosis. Objective of present study was to find out the type of carcinoma lung and to find out the best and easy method for diagnosis of carcinoma lung in a tertiary care centre.Methods: A hospital based cross sectional study was conducted in one unit of the Department of Pulmonary Medicine, Government Medical college, Thiruvananthapuram for a period of one year.148 diagnosed cases of carcinoma lung were enrolled. The type and the methods used for diagnosis were analysed.Results: Adenocarcinoma was the commonest malignancy 57 (38.5%), followed by squamous cell carcinoma 44 (29.7%) and small cell carcinoma 10 (6.75%). Rest of the cases 37 (25%) include non small cell carcinoma, poorly differentiated carcinoma and lymphoma. Diagnosis was established by FNA Lung in 46 (31.1%) patients and bronchoscopy and biopsy in 41 (27.7%). Other methods include TBNA 12 (8.1%), lymph node FNA/biopsy 11 (7.4%), pleural fluid cytology 24 (16.2%), sputum cytology and tru cut biopsy 14 (9.5%).Conclusions: The most common type of lung malignancy in present study was adenocarcinoma. Ultra sound guided FNAC lung and bronchoscopy biopsy were the best methods in present study to confirm the diagnosis

A large Indian family with rearrangement of chromosome 4p16 and 3p26.3 and divergent clinical presentations

BACKGROUND: The deletion of the chromosome 4p16.3 Wolf-Hirschhorn syndrome critical region (WHSCR-2) typically results in a characteristic facial appearance, varying intellectual disability, stereotypies and prenatal onset of growth retardation, while gains of the same chromosomal region result in a more variable degree of intellectual deficit and dysmorphism. Similarly the phenotype of individuals with terminal deletions of distal chromosome 3p (3p deletion syndrome) varies from mild to severe intellectual deficit, micro- and trigonocephaly, and a distinct facial appearance.METHODS AND RESULTS: We investigated a large Indian five-generation pedigree with ten affected family members in which chromosomal microarray and fluorescence in situ hybridization analyses disclosed a complex rearrangement involving chromosomal subregions 4p16.1 and 3p26.3 resulting in a 4p16.1 deletion and 3p26.3 microduplication in three individuals, and a 4p16.1 duplication and 3p26.3 microdeletion in seven individuals. A typical clinical presentation of WHS was observed in all three cases with 4p16.1 deletion and 3p26.3 microduplication. Individuals with a 4p16.1 duplication and 3p26.3 microdeletion demonstrated a range of clinical features including typical 3p microdeletion or 4p partial trisomy syndrome to more severe neurodevelopmental delay with distinct dysmorphic features.CONCLUSION: We present the largest pedigree with complex t(4p;3p) chromosomal rearrangements and diverse clinical outcomes including Wolf Hirschorn-, 3p deletion-, and 4p duplication syndrome amongst affected individuals.<br/

Myocardial Recovery and the Failing Heart: Medical, Device and Mechanical Methods

Background: Cardiac remodeling describes the molecular, cellular, and interstitial changes that cause the ventricle to develop pathologic geometry as heart failure progresses. Reverse remodeling, or the healing of a failing heart, leads to improved mortality and quality of life. Findings: Therapies that lead to reverse remodeling include medications such as β-blockers and angiotensin-converting enzyme inhibitors; cardiac resynchronization therapy with biventricular pacing; and mechanical support with left ventricular assist devices. Conclusions: Further study is needed to better predict which patients will benefit most from these therapies and will then go on to experience reverse remodeling and myocardial recovery

Neprilysin Inhibitors in Heart Failure: The Science, Mechanism of Action, Clinical Studies, and Unanswered Questions

This article provides a contemporary review and a new perspective on the role of neprilysin inhibition in heart failure (HF) in the context of recent clinical trials and addresses potential mechanisms and unanswered questions in certain HF patient populations. Neprilysin is an endopeptidase that cleaves a variety of peptides such as natriuretic peptides, bradykinin, adrenomedullin, substance P, angiotensin I and II, and endothelin. It has a broad role in cardiovascular, renal, pulmonary, gastrointestinal, endocrine, and neurologic functions. The combined angiotensin receptor and neprilysin inhibitor (ARNi) has been developed with an intent to increase vasodilatory natriuretic peptides and prevent counterregulatory activation of the angiotensin system. ARNi therapy is very effective in reducing the risks of death and hospitalization for HF in patients with HF and New York Heart Association functional class II to III symptoms, but studies failed to show any benefits with ARNi when compared with angiotensin-converting enzyme inhibitors or angiotensin receptor blocker in patients with advanced HF with reduced ejection fraction or in patients following myocardial infarction with left ventricular dysfunction but without HF. These raise the questions about whether the enzymatic breakdown of natriuretic peptides may not be a very effective solution in advanced HF patients when there is downstream blunting of the response to natriuretic peptides or among post-myocardial infarction patients in the absence of HF when there may not be a need for increased natriuretic peptide availability. Furthermore, there is a need for additional studies to determine the long-term effects of ARNi on albuminuria, obesity, glycemic control and lipid profile, blood pressure, and cognitive function in patients with HF

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN