Detection of mecC-Methicillin-resistant Staphylococcus aureus isolates in river water : a potential role for water in the environmental dissemination

Methicillin-resistant Staphylococcus aureus (MRSA) is a public health concern due to limited treatment options. The recent description of a mecA homologue, mecC in human and cattle, led to studies to detect this new variant in human and other animal species. Detection of mecC in wild boar and fallow deer in a Spanish game estate led us to further investigate the presence of mecC-MRSA at this location. Samples from cattle, wild animals, workers and river water were tested. A further three mecC-MRSA isolates were obtained from river water. Molecular characterization (multilocus sequence typing and spa typing) and antimicrobial susceptibility testing (broth microdilution) showed that isolates were similar to those detected in wild animals. Whole genome sequencing confirmed that the isolates from the river water and wild animals in the same geographic area were all closely related isolates of ST425 mecC-MRSA. The presence of mecC-MRSA in the river water highlights the potential role of water in the dissemination of mecC-MRSA

Power Wheelchair Canopy

Some power wheelchair users can not drive and independently hold an umbrella at the time because they do not have much upper body strength. Therefore, users are unprotected from the rain and are getting soaking wet. One of the members of this group is in a wheelchair and faces this problem. He has previously searched for something to protect him from rain, but could not found something he could independently use. What users need is a powered umbrella that attaches to their power wheelchair. There is no such umbrella available in the market. In this project, the solution to this problem will be designed and built in the form of an umbrella for his wheelchair. Exploration of various methods of rain protect will be explored. Calculations will be performed to verify that everything will work when assembled. The prototype will then be built. Assuming there will be some issues, as there always seem to be, several iterations of the prototype will be built. This is assuming that there will still be money left in the budget to complete these other iterations. It is also desired to make it inexpensive. This will allow power wheelchair users all over the world to purchase it for themselves. In order to achieve this, the project will lean heavily on the 3-D printing capabilities that the University of Akron has to offer

Outpatient treatment with AZD7442 (tixagevimab/cilgavimab) prevented Covid-19 hospitalizations over 6 months and reduced symptom progression in the TACKLE randomized trial

Introduction We assessed effects of AZD7442 (tixagevimab/cilgavimab) on deaths from any cause or hospitalizations due to coronavirus disease 2019 (COVID-19) and symptom severity and longer-term safety in the TACKLE adult outpatient treatment study. Methods Participants received 600 mg AZD7442 (n = 452) or placebo (n = 451) ≤ 7 days of COVID-19 symptom onset. Results Death from any cause or hospitalization for COVID-19 complications or sequelae through day 169 (key secondary endpoint) occurred in 20/399 (5.0%) participants receiving AZD7442 versus 40/407 (9.8%) receiving placebo [relative risk reduction (RRR) 49.1%; 95% confidence interval (CI) 14.5, 69.7; p = 0.009] or 50.7% (95% CI 17.5, 70.5; p = 0.006) after excluding participants unblinded before day 169 for consideration of vaccination). AZD7442 reduced progression of COVID-19 symptoms versus placebo through to day 29 (RRR 12.5%; 95% CI 0.5, 23.0) and improved most symptoms within 1–2 weeks. Over median safety follow-up of 170 days, adverse events occurred in 174 (38.5%) and 196 (43.5%) participants receiving AZD7442 or placebo, respectively. Cardiac serious adverse events occurred in two (0.4%) and three (0.7%) participants receiving AZD7442 or placebo, respectively. Conclusions AZD7442 was well tolerated and reduced hospitalization and mortality through 6 months, and symptom burden through 29 days, in outpatients with mild-to-moderate COVID-19. Clinical Trial Registration Clinicaltrials.gov, NCT04723394. (https://beta.clinicaltrials.gov/study/NCT04723394)

Outpatient Treatment with AZD7442 (Tixagevimab/Cilgavimab) Prevented COVID-19 Hospitalizations over 6 Months and Reduced Symptom Progression in the TACKLE Randomized Trial

INTRODUCTION: We assessed effects of AZD7442 (tixagevimab/cilgavimab) on deaths from any cause or hospitalizations due to coronavirus disease 2019 (COVID-19) and symptom severity and longer-term safety in the TACKLE adult outpatient treatment study. METHODS: Participants received 600 mg AZD7442 (n = 452) or placebo (n = 451) ≤ 7 days of COVID-19 symptom onset. RESULTS: Death from any cause or hospitalization for COVID-19 complications or sequelae through day 169 (key secondary endpoint) occurred in 20/399 (5.0%) participants receiving AZD7442 versus 40/407 (9.8%) receiving placebo [relative risk reduction (RRR) 49.1%; 95% confidence interval (CI) 14.5, 69.7; p = 0.009] or 50.7% (95% CI 17.5, 70.5; p = 0.006) after excluding participants unblinded before day 169 for consideration of vaccination). AZD7442 reduced progression of COVID-19 symptoms versus placebo through to day 29 (RRR 12.5%; 95% CI 0.5, 23.0) and improved most symptoms within 1-2 weeks. Over median safety follow-up of 170 days, adverse events occurred in 174 (38.5%) and 196 (43.5%) participants receiving AZD7442 or placebo, respectively. Cardiac serious adverse events occurred in two (0.4%) and three (0.7%) participants receiving AZD7442 or placebo, respectively. CONCLUSIONS: AZD7442 was well tolerated and reduced hospitalization and mortality through 6 months, and symptom burden through 29 days, in outpatients with mild-to-moderate COVID-19. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT04723394. ( https://beta. CLINICALTRIALS: gov/study/NCT04723394 )

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 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

Modification of the FoxP3 Transcription Factor Principally Affects Inducible T Regulatory Cells in a Model of Experimental Autoimmune Encephalomyelitis

T regulatory (Treg) cells expressing the transcription factor FoxP3 play a key role in protection against autoimmune disease. GFP-FoxP3 reporter mice have been used widely to study the induction, function and stability of both thymically- and peripherally-induced Treg cells. The N-terminal modification of FoxP3, however, affects its interaction with transcriptional co-factors; this can alter Treg cell development and function in certain self-antigen specific animal models. Interestingly, Treg cell function can be negatively or positively affected, depending on the nature of the model. In this study, we focused on the effect of the GFP-FoxP3 reporter on Treg cell development and function in the Tg4 mouse model. In this model, T cells express a transgenic T cell receptor (TCR) specific for the Myelin Basic Protein (MBP) peptide Ac1-9, making the animals susceptible to experimental autoimmune encephalomyelitis (EAE), a disease akin to multiple sclerosis in humans. Unlike diabetes-susceptible mice, Tg4 FoxP3(gfp) mice did not develop spontaneous autoimmune disease and did not demonstrate augmented susceptibility to induced disease. Concurrently, thymic generation of natural Treg cells was not negatively affected. The induction of FoxP3 expression in naive peripheral T cells was, however, significantly impaired as a result of the transgene. This study shows that the requirements for the interaction of FoxP3 with co-factors, which governs its regulatory ability, differ not only between natural and inducible Treg cells but also between animal models of diseases such as diabetes and EAE

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

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Sensitivity of the West Antarctic Ice Sheet to +2 °C (SWAIS 2C)

The West Antarctic Ice Sheet (WAIS) presently holds enough ice to raise global sea level by 4.3 m if completely melted. The unknown response of the WAIS to future warming remains a significant challenge for numerical models in quantifying predictions of future sea level rise. Sea level rise is one of the clearest planet-wide signals of human-induced climate change. The Sensitivity of the West Antarctic Ice Sheet to a Warming of 2 ∘C (SWAIS 2C) Project aims to understand past and current drivers and thresholds of WAIS dynamics to improve projections of the rate and size of ice sheet changes under a range of elevated greenhouse gas levels in the atmosphere as well as the associated average global temperature scenarios to and beyond the +2 ∘C target of the Paris Climate Agreement. Despite efforts through previous land and ship-based drilling on and along the Antarctic margin, unequivocal evidence of major WAIS retreat or collapse and its causes has remained elusive. To evaluate and plan for the interdisciplinary scientific opportunities and engineering challenges that an International Continental Drilling Program (ICDP) project along the Siple coast near the grounding zone of the WAIS could offer (Fig. 1), researchers, engineers, and logistics providers representing 10 countries held a virtual workshop in October 2020. This international partnership comprised of geologists, glaciologists, oceanographers, geophysicists, microbiologists, climate and ice sheet modelers, and engineers outlined specific research objectives and logistical challenges associated with the recovery of Neogene and Quaternary geological records from the West Antarctic interior adjacent to the Kamb Ice Stream and at Crary Ice Rise. New geophysical surveys at these locations have identified drilling targets in which new drilling technologies will allow for the recovery of up to 200 m of sediments beneath the ice sheet. Sub-ice-shelf records have so far proven difficult to obtain but are critical to better constrain marine ice sheet sensitivity to past and future increases in global mean surface temperature up to 2 ∘C above pre-industrial levels. Thus, the scientific and technological advances developed through this program will enable us to test whether WAIS collapsed during past intervals of warmth and determine its sensitivity to a +2 ∘C global warming threshold (UNFCCC, 2015)