Vasculitis masquerading as a mass: a case report of Takayasu arteritis in a 28-year-old male

Takayasu arteritis is a chronic vasculitis mainly involving the aorta and its main branches most commonly subclavian and carotid. It induces clinically varied ischaemic symptoms due to stenotic lesions or thrombus formation, including blindness, retinal haemorrhage, pulselessness, aortic regurgitation and congestive heart failure due to dilatation of the ascending aorta. More acute progression causes destruction of arterial wall, leading to the formation of aneurysms and rupture of the involved arteries. Here we present a case of Takayasu’s arteritis in a 28-year-old male who presented with nonspecific symptoms of fever and neck pain with palpitations and feeling of pulsations in right side of neck since last 20 days and was eventually diagnosed as arteritis. This case shows that it can present with many non-specific symptoms and can be diagnosed with proper examination and a high index of suspicion due to its nonspecific overlapping features with many diseases

Fahr’s syndrome with hypoparathyroidism in a 65 year old: a case report

Fahr’s syndrome also known as idiopathic basal ganglia calcification (IBGC) is a notably rare neurological disease with an autosomal dominant pattern of inheritance and genetic heterogeneity, resulting from symmetric bilateral calcification commonly in basal nuclei and cerebellum. Regardless of being a rare disorder, Fahr's can have a dramatic effect on patients, and is characterized by spectrum of metabolic, biochemical, neuro-radiological, and neuro-psychiatric alterations leading to cognitive dysfunction, motor impairment and neurological manifestations. Our case of a 65-year male, deals with array of varied clinical symptoms and diagnostic difficulties of Fahr’s associated with hypoparathyroidism. The case report contributes to the expanding comprehension of the Fahr’s highlighting its genetic aspect and clinical heterogeneity and developing avenues for appropriate diagnostic and imaging modalities as-well-as intervention techniques. The motives of this article extend beyond the clinical case, influencing future research, diagnostic and prevention strategies

Multi-Environment Model Estimation for Motility Analysis of \u3cem\u3eCaenorhabditis elegans\u3c/em\u3e

The nematode Caenorhabditis elegans is a well-known model organism used to investigate fundamental questions in biology. Motility assays of this small roundworm are designed to study the relationships between genes and behavior. Commonly, motility analysis is used to classify nematode movements and characterize them quantitatively. Over the past years, C. elegans’ motility has been studied across a wide range of environments, including crawling on substrates, swimming in fluids, and locomoting through microfluidic substrates. However, each environment often requires customized image processing tools relying on heuristic parameter tuning. In the present study, we propose a novel Multi Environment Model Estimation (MEME) framework for automated image segmentation that is versatile across various environments. The MEME platform is constructed around the concept of Mixture of Gaussian (MOG) models, where statistical models for both the background environment and the nematode appearance are explicitly learned and used to accurately segment a target nematode. Our method is designed to simplify the burden often imposed on users; here, only a single image which includes a nematode in its environment must be provided for model learning. In addition, our platform enables the extraction of nematode ‘skeletons’ for straightforward motility quantification. We test our algorithm on various locomotive environments and compare performances with an intensity-based thresholding method. Overall, MEME outperforms the threshold-based approach for the overwhelming majority of cases examined. Ultimately, MEME provides researchers with an attractive platform for C. elegans’ segmentation and ‘skeletonizing’ across a wide range of motility assays

Integrated Molecular Characterization of Uterine Carcinosarcoma

SummaryWe performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

SummaryWe report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine

Integrated genomic characterization of pancreatic ductal adenocarcinoma

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine

Sex differences in oncogenic mutational processes.

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Classifying latent user attributes in Twitter

Social media outlets such as Twitter have become an important forum for peer interaction. Thus the ability to classify latent user attributes, including gender, age, regional origin, and political orientation solely from Twitter user language or similar highly informal content has important applications in advertising, personalization, and recommendation. This paper includes a novel investigation of stacked-SVM-based classification algorithms over a rich set of original features, applied to classifying these four user attributes. It also includes extensive analysis of features and approaches that are effective and not effective in classifying user attributes in Twitter-style informal written genres as distinct from the other primarily spoken genres previously studied in the userproperty classification literature. Our models, singly and in ensemble, significantly outperform baseline models in all cases. A detailed analysis of model components and features provides an often entertaining insight into distinctive language-usage variation across gender, age, regional origin and political orientation in modern informal communication