Notes

A stage 2a randomized clinical trial of iv vedolizumab for the treatment of steroid-refractory colon acute graft-versus-host disease.
Finally, whereas RNA-seq and ChIP-seq showed no concomitant changes in chromatin methylation or gene expression in Setd2SRI/wt mice, primary neurons exhibited structural deficits in axon length and dendritic arborization. These data provide the first demonstration microtubules of neurons are methylated, and reveals a heterozygous chromatin remodeler defect that specifically disables microtubule methylation is sufficient to drive an autism-associated phenotype.In non-alcoholic steatohepatitis (NASH), decreased nitric oxide and increased endothelin-1 (ET-1, also known as EDN1) released by sinusoidal endothelial cells (LSEC) induce hepatic stellate cell (HSC) contraction and contribute to portal hypertension (PH). Statins improve LSEC function, and ambrisentan is a selective endothelin-receptor-A antagonist. We aimed to analyse the combined effects of atorvastatin and ambrisentan on liver histopathology and hemodynamics, together with assessing the underlying mechanism in a rat NASH model. Diet-induced NASH rats were treated with atorvastatin (10 mg/kg/day), ambrisentan (30 mg/kg/day or 2 mg/kg/day) or a combination of both for 2 weeks. Hemodynamic parameters were registered and liver histology and serum biochemical determinations analysed. Expression of proteins were studied by immunoblotting. Conditioned media experiments were performed with LSEC. HSCs were characterized by RT-PCR, and a collagen lattice contraction assay was performed. Atorvastatin and ambrisentan act synergistically in combination to completely normalize liver hemodynamics and reverse histological NASH by 75%. Atorvastatin reversed the sinusoidal contractile phenotype, thus improving endothelial function, whereas ambrisentan prevented the contractile response in HSCs by blocking ET-1 response. Additionally, ambrisentan also increased eNOS (also known as Nos3) phosphorylation levels in LSEC, via facilitating the stimulation of endothelin-receptor-B in these cells. Furthermore, the serum alanine aminotransferase of the combined treatment group decreased to normal levels, and this group exhibited a restoration of the HSC quiescent phenotype. The combination of atorvastatin and ambrisentan remarkably improves liver histology and PH in a diet-induced NASH model. By recovering LSEC function, together with inhibiting the activation and contraction of HSC, this combined treatment may be an effective treatment for NASH patients.
The web platform 3DBionotes-WS integrates multiple Web Services and an interactive Web Viewer to provide a unified environment in which biological annotations can be analyzed in their structural context. Since the COVID-19 outbreak, new structural data from many viral proteins have been provided at a very fast pace. This effort includes many cryogenic Electron Microscopy (cryo-EM) studies, together with more traditional ones (X-rays, NMR), using several modeling approaches and complemented with structural predictions. At the same time, a plethora of new genomics and interactomics information (including fragment screening and structure-based virtual screening efforts) have been made available from different servers. In this context we have developed 3DBionotes-COVID-19 as an answer to (1) The need to explore multi-omics data in a unified context with a special focus on structural information and (2) the drive to incorporate quality measurements, especially in the form of advanced validation metrics for cryogenic Electron Microscopy.

https//3dbionotes.cnb.csic.es/ws/covid19.

Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.The 'cancer stem cell' hypothesis has pointed to a specific target for new cancer therapies. The hypothesis is based on the observation that only the 'cancer stem cell' among the other heterogeneous cancer cells can sustain the growth of the cancer. The goal is to identify biomarkers of 'cancer stem cells' to distinguish them from the 'cancer non-stem cells' and normal adult tissue-specific stem cells. This analyst posits a hypothesis that, although all cancers originated from a single cell, there exist two types of 'cancer stem cells' either by the 'Stem Cell hypothesis' or from the 'De-differentiation hypothesis'. It is proposed that there exist two different 'cancer stem cells'. Some 'cancer stem cells' (a) lack the expression of connexins or gap junction genes and lack any form of gap junctional intercellular communication (GJIC) or (b) they have the expressed connexin-coded proteins for functional GJIC but are dysfunctional by some expressed oncogene. This is consistent with the Loewenstein hypothesis that a universal characteristic of cancer cells is they do not have growth control, nor terminally differentiate. This review speculates the normal organ-specific adult stem cell, that is 'initiated', is the origin of the 'cancer stem cells' with expressed Oct4A gene and no expressed connexin genes; whereas the other cancer stem cell has no expressed Oct4A genes but expressed connexin gene, whose coded protein is dysfunctional. Hence. both types of 'cancer stem cells' lack GJIC, for two different reasons, the selective therapies have to be different for these different cell types.
Evidence indicates that screening for colorectal cancer (CRC) beginning at 50 years of age can detect early-stage CRC and premalignant neoplasms (eg, adenomas) and thus prevent CRC-related mortality. At present, the US Preventive Services Task Force recommends continuing CRC screening until 75 years of age and individualized decision-making for adults older than 75 years, while accounting for a patient's overall health and screening history. However, scant data exist to support these recommendations.

To examine the association of lower gastrointestinal tract screening endoscopy with the risk of CRC incidence and CRC-related mortality in older US adults.

This prospective cohort study of health care professionals in the US included data from the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS) from January 1, 1988, through January 31, 2016, for the HPFS and June 30, 2016, for the NHS. Data were analyzed from May 8, 2019, to July 9, 2020.

History of screening sigmoidoscopy or cots without a screening history. However, screening endoscopy after 75 years of age was not associated with risk reduction in CRC death among participants with cardiovascular disease (HR, 1.18; 95% CI, 0.59-2.35) or significant comorbidities (HR, 1.17; 95% CI, 0.57-2.43).

In this cohort study, endoscopy among individuals older than 75 years was associated with lower risk of CRC incidence and CRC-related mortality. These data support continuation of screening after 75 years of age among individuals without significant comorbidities.
In this cohort study, endoscopy among individuals older than 75 years was associated with lower risk of CRC incidence and CRC-related mortality. These data support continuation of screening after 75 years of age among individuals without significant comorbidities.
Influenza vaccine effectiveness (VE) against a spectrum of severe disease, including critical illness and death, remains poorly characterized.

We conducted a test-negative study in an intensive care unit (ICU) network at 10 United States hospitals to evaluate VE for preventing influenza-associated severe acute respiratory infection (SARI) during the 2019-2020 season, which was characterized by circulation of drifted A/H1N1 and B-lineage viruses. Cases were adults hospitalized in the ICU and a targeted number outside the ICU (to capture a spectrum of severity) with laboratory-confirmed influenza-associated SARI. Test-negative controls were frequency-matched based on hospital, timing of admission, and care location (ICU vs non-ICU). Estimates were adjusted for age, comorbidities, and other confounders.

Among 638 patients, the median (interquartile) age was 57 (44-68) years; 286 (44.8%) patients were treated in the ICU and 42 (6.6%) died during hospitalization. Forty-five percent of cases and 61% of controls were vaccinated, which resulted in an overall VE of 32% (95% CI 2 to 53%), including 28% (-9% to 52%) against influenza A, and 52% (13% to 74%) against influenza B. VE was higher in adults 18-49 years old (62%; 95% CI 27% to 81%) than those 50-64 years old (20%, -48% to 57%) and ≥65 years old (-3%; 95% CI -97% to 46%) (p=0.0789 for interaction). VE was significantly higher against influenza-associated death (80%, 95% CI 4% to 96%) than non-fatal influenza illness.

During a season with drifted viruses, vaccination reduced severe influenza-associated illness among adults by 32%. VE was high among young adults.
During a season with drifted viruses, vaccination reduced severe influenza-associated illness among adults by 32%. VE was high among young adults.
Long-duration spaceflight induces structural changes in the brain and eye. Identification of an association between cerebral and ocular changes could help determine if there are common or independent causes and inform targeted prevention strategies or treatments.

To determine if there is an association between quantitative changes in intracranial compartment volumes and peripapillary total retinal thickness after spaceflight.

This cohort study included healthy International Space Station crew members before and immediately after long-duration spaceflight. Data on race were not collected. Analysis was conducted from September to November 2020.

Long-duration spaceflight (mean [SD], 191 [55] days).

Optical coherence tomography-derived peripapillary total retinal thickness as a quantitative assessment and early sign of optic disc edema and magnetic resonance imaging-derived measures of lateral ventricle volume, white matter volume, and whole brain plus cerebrospinal fluid volume.

In 19 healthy crew mek association between increased total retinal thickness and lateral ventricle volume suggest that while weightlessness-induced fluid redistribution during spaceflight may be a common stressor to the brain and retina, the development of optic disc edema appears to be uncoupled with changes occurring in the intracranial compartment.
These results help characterize spaceflight-associated neuro-ocular syndrome and the physiologic associations of headward fluid shifts with outcomes during spaceflight on the central nervous system. The possibly weak association between increased total retinal thickness and lateral ventricle volume suggest that while weightlessness-induced fluid redistribution during spaceflight may be a common stressor to the brain and retina, the development of optic disc edema appears to be uncoupled with changes occurring in the intracranial compartment.
Identification of geographic population-based differences in genotype and phenotype heterogeneity are important for targeted and patient-specific diagnosis and treatment, counseling, and screening strategies.

To report disease-causing variants and their detailed phenotype in patients with bilateral congenital cataract from a single center in Switzerland and thereby draw a genetic map and perform a genotype-phenotype comparison of this cohort.

This clinical and molecular-genetic cohort study took place through the collaboration of the Department of Ophthalmology at the University Hospital Zurich and the Institute of Medical Molecular Genetics, University of Zurich, Schlieren, Switzerland. Thirty-seven patients from 25 families with different types of bilateral congenital cataract were included. All participating family members received a comprehensive eye examination. Smad2 signaling Whole exome sequencing was performed in the index patients, followed by a filtering process to detect possible disease-associated variants in genes previously described in association with congenital cataract.
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