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Project description:Columbia University Irving Medical Center RNASeq of meningioma tumors
| PRJNA875140 | ENA
Project description:Many patients with SARS-CoV-2 infection develop neurological signs and symptoms; although, to date, little evidence exists that primary infection of the brain is a significant contributing factor. We present the clinical, neuropathological and molecular findings of 41 consecutive patients with SARS-CoV-2 infections who died and underwent autopsy in our medical centre. The mean age was 74 years (38-97 years), 27 patients (66%) were male and 34 (83%) were of Hispanic/Latinx ethnicity. Twenty-four patients (59%) were admitted to the intensive care unit. Hospital-associated complications were common, including eight patients (20%) with deep vein thrombosis/pulmonary embolism, seven (17%) with acute kidney injury requiring dialysis and 10 (24%) with positive blood cultures during admission. Eight (20%) patients died within 24 h of hospital admission, while 11 (27%) died more than 4 weeks after hospital admission. Neuropathological examination of 20-30 areas from each brain revealed hypoxic/ischaemic changes in all brains, both global and focal; large and small infarcts, many of which appeared haemorrhagic; and microglial activation with microglial nodules accompanied by neuronophagia, most prominently in the brainstem. We observed sparse T lymphocyte accumulation in either perivascular regions or in the brain parenchyma. Many brains contained atherosclerosis of large arteries and arteriolosclerosis, although none showed evidence of vasculitis. Eighteen patients (44%) exhibited pathologies of neurodegenerative diseases, which was not unexpected given the age range of our patients. We examined multiple fresh frozen and fixed tissues from 28 brains for the presence of viral RNA and protein, using quantitative reverse-transcriptase PCR, RNAscope® and immunocytochemistry with primers, probes and antibodies directed against the spike and nucleocapsid regions. The PCR analysis revealed low to very low, but detectable, viral RNA levels in the majority of brains, although they were far lower than those in the nasal epithelia. RNAscope® and immunocytochemistry failed to detect viral RNA or protein in brains. Our findings indicate that the levels of detectable virus in coronavirus disease 2019 brains are very low and do not correlate with the histopathological alterations. These findings suggest that microglial activation, microglial nodules and neuronophagia, observed in the majority of brains, do not result from direct viral infection of brain parenchyma, but more likely from systemic inflammation, perhaps with synergistic contribution from hypoxia/ischaemia. Further studies are needed to define whether these pathologies, if present in patients who survive coronavirus disease 2019, might contribute to chronic neurological problems.
| S-EPMC8083258 | biostudies-literature
Project description:We use a Master Regular-based precision cancer medicine framework to perform joint analysis of transcriptomic profiles from patients with distinct treatment refractory cancer and drug perturbation transcriptional profiles in cognate cell lines, to predict drug sensitivity. Validation of predictions was performed in patient-derived xenograft (PDX) mice. Pharmacodynamic samples were obtained from PDX mice after the third dose for RNASeq and downstream analysis.
2022-03-09 | GSE197763 | GEO
Project description:We use a Master Regular-based precision cancer medicine framework to predict drug sensitivity. The network based analysis uses RNASeq profiles of patient tumors, in conjunction with de novo drug mechanism analysis from high throughput drug screens with post-perturbation RNASeq profiles performed in cognate cell line models. The analysis aims to predict available antineoplastic drugs most likely to invert the aberrant protein activity state of individual tumors. Validation of predictions was performed in corresponding patient-derived xenograft (PDX) mice. Pharmacodynamic samples were obtained from PDX mice after the third dose for RNASeq and downstream analysis.
2022-09-10 | GSE212854 | GEO
Project description:We introduce OncoLoop, a highly-generalizable, precision medicine framework to triangulate between available mouse models, human tumors, and large-scale drug perturbational assays with in vivo validation to predict personalized treatment
2022-10-31 | GSE186566 | GEO
Project description:We profiled 116,314 cells using snRNA-seq of 20 frozen lungs obtained from 19 COVID-19 decedents and seven control patients with short postmortem interval (PMI) autopsies. The COVID-19 cohort comprises seven female and 12 male decedents, including 13 patients of Hispanic ethnicity, with an age range from 58 to >89 years who had acquired SARS-CoV-2 infection and succumbed to the disease. The average time from symptom onset to death was 27.5 days (range, 4–63 days). After rapid autopsy with a median PMI of 4 hours (range 2–9 hours) collected tissues were either flash-frozen or frozen following OCT (optimal cutting temperature) embedment and subjected to snRNA-seq using a droplet-based platform (10x Genomics). All included patients had underlying hypertensive disorder and frequently one or more additional co-morbidities associated with increased risk for severe COVID-19.
2021-04-29 | GSE171524 | GEO
Project description: Not available
| S-EPMC3650730 | biostudies-literature
Project description:We identified XPO1 as an aberrantly activated, non-oncogene encoded targetable vulnerability in pediatric renal tumors (Wilms and malignant rhabdoid tumor [MRT]) using OncoTarget, a Master Regular-based precision cancer medicine tool. We demonstrate significant anti-tumor activity of selinexor and eltanexor, two selective XPO1 inhibitors, in patient derived xenograft mice models of Wilms and MRT, and report on a case of successful treatment of a pediatric cancer patient.
2022-03-09 | GSE198000 | GEO
Project description:Organisation EGAO00000000913
| EGAO00000000913 | EGA
Project description:Enterocutaneous fistula is a challenging clinical condition with serious complications and considerable morbidity and mortality. Early nutritional support has been found to decrease these complications and to improve the clinical outcome. Location of the fistula and physiological status affect the nutrition management plan in terms of feeding route, calories, and protein requirements. This study investigated the nutritional management procedures at the Universiti Kebangsaan Malaysia Medical Center, and attempted to determine factors that affect the clinical outcome. Nutritional management was evaluated retrospectively in 22 patients with enterocutaneous fistula seen over a 5-year period. Medical records were reviewed to obtain data on nutritional status, biochemical indices, and route and tolerance of feeding. Calories and protein requirements are reported and categorized. The results show that surgery was the predominant etiology and low output fistula was the major physiological category; anatomically, the majority were ileocutaneous. The spontaneous healing rate was 14%, the total healing rate was 45%, and the mortality rate was 22%, with 14% due to fistula-associated complications. There was a significant relationship between body mass index/serum albumin levels and fistula healing; these parameters also had a significant relationship with mortality. Glutamine was used in 50% of cases; however, there was no significant relationship with fistula healing or mortality rate. The nutritional status of the patient has an important impact on the clinical outcome. Conservative management that includes nutrition support is very important in order to improve nutritional status before surgical repair of the fistula.
| S-EPMC4149450 | biostudies-other