tbuckley/cabot-search huggingface dataset:
Sixteen novel lineages of SARS-CoV-2 in South Africa
Authors: Houriiyah Tegally, Eduan Wilkinson, Richard J. Lessells, Jennifer Giandhari, Sureshnee Pillay, Nokukhanya Msomi, Koleka Mlisana, Jinal N. Bhiman, Anne von Gottberg, Sibongile Walaza, Vagner Fonseca, Mushal Allam, Arshad Ismail, Allison J. Glass, Susan Engelbrecht, Gert Van Zyl, Wolfgang Preiser, Carolyn Williamson, Francesco Petruccione, Alex Sigal, Inbal Gazy, Diana Hardie, Nei-yuan Hsiao, Darren Martin, Denis York, Dominique Goedhals, Emmanuel James San, Marta Giovanetti, José Lourenço, Luiz Carlos Junior Alcantara, Tulio de Oliveira
Journal: Nature Medicine (2021)

The first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in South Africa was identified on 5 March 2020, and by 26 March the country was in full lockdown (Oxford stringency index of 90)1. Despite the early response, by November 2020, over 785,000 people in South Africa were infected, which accounted for approximately 50% of all known African infections2. In this study, we analyzed 1,365 near whole genomes and report the identification of 16 new lineages of SARS-CoV-2 isolated between 6 March and 26 August 2020. Most of these lineages have unique mutations that have not been identified elsewhere. We also show that three lineages (B.1.1.54, B.1.1.56 and C.1) spread widely in South Africa during the first wave, comprising ~42% of all infections in the country at the time. The newly identified C lineage of SARS-CoV-2, C.1, which has 16 nucleotide mutations as compared with the original Wuhan sequence, including one amino acid change on the spike protein, D614G (ref. 3), was the most geographically widespread lineage in South Africa by the end of August 2020. An early South African-specific lineage, B.1.106, which was identified in April 2020 (ref. 4), became extinct after nosocomial outbreaks were controlled in KwaZulu-Natal Province. Our findings show that genomic surveillance can be implemented on a large scale in Africa to identify new lineages and inform measures to control the spread of SARS-CoV-2. Such genomic surveillance presented in this study has been shown to be crucial in the identification of the 501Y.V2 variant in South Africa in December 2020 (ref. 5).
COVID-19 pandemia: Atopy and prospective analysis of the clinical evolution of patients infected with the SARS-CoV-2 virus
Authors: Débora S. Guterres, Ana Carolina Dos Santos, Marina de Almeida Prado Meireles Laubi, Marina Laubi, Roselene Lourenço, Marcus Vinícius, Rosana Agondi, Ana Karolina Marinho, Valéria Brandão, Thais Saito, Grasiela Lima
Journal: Journal of Allergy and Clinical Immunology (2021)

A few scientific evidence is now available to date on the clinical evolution of COVID-19 in atopics. The aim of this study was to assess the frequency of atopy in patients hospitalized for COVID-19. A prospective study was carried out with hard descriptive data of 4 months. During this period, 300 patients were admitted with ARS and positive RT-PCR for SARS-CoV-2. Clinical features, history of atopy, total IgE and chest tomography were evaluated. Of all patients, 212 (70%) were male and the average age was 58 years old. Of the total, 37 patients (12.3%) had a history of atopy according to the following: 19 rhinitis (51.4%), 15 asthma (40.5%) and 3 (1%), atopic dermatitis. Obesity was present in 32% of the evaluated atopics. The mean of atopic patients was aged for 55, 92% O2 Sat, respiratory rate 27 per minute, CT > 50% in 22 patients (7.3%) and 3 patients died (1%). Of these who died, all were elderly (age over 60 years) and had comorbidities such as SH and obesity. Mean IgE total was 538UI/ml, and 3 patients presented IgE above 2000, all of them with clinical suggesting atopy (AD, asthma and rhinitis). The literature reports less severe outcomes in atopic patients affected by COVID-19. In the studied group, the frequency of atopy was lower than that observed in the literature for the general population and the tomographic impairment was lower than that of the non-atopic group. The atopic patients who died were elderly and had comorbidities.
Can simvastatin reduce COPD exacerbations? A randomised double-blind controlled study
Authors: Peter Schenk, Alexander O. Spiel, Felix Hüttinger, Micheline Gmeiner, Josefine Fugger, Martina Pichler, Gernot Pichler, Susanne Schmeikal, Wolfgang Janistyn, Stefan Schügerl, Constantin Sajdik, Harald Herkner
Journal: European Respiratory Journal (2021)

Background Several studies have shown that statins have beneficial effects in COPD regarding lung function decline, rates and severity of exacerbation, hospitalisation and need for mechanical ventilation. Methods We performed a randomised double-blind placebo-controlled single-centre trial of simvastatin at a daily dose of 40 mg versus placebo in patients with Global Initiative for Chronic Obstructive Lung Disease criteria grades 2–4 at a tertiary care pulmonology department in Austria. Scheduled treatment duration was 12 months and the main outcome parameter was time to first exacerbation. Results Overall, 209 patients were enrolled. In the 105 patients taking simvastatin, time to first exacerbation was significantly longer compared to the 104 patients taking placebo: median 341 versus 140 days (log-rank test p&lt;0.001). Hazard ratio for risk of first exacerbation for the simvastatin group was 0.51 (95% CI 0.34–0.75; p=0.001). Rate of exacerbations was significantly lower with simvastatin: 103 (41%) versus 147 (59%) (p=0.003). The annualised exacerbation rate was 1.45 events per patient-year in the simvastatin group and 1.9 events per patient-year in the placebo group (incidence rate ratio 0.77, 95% CI 0.60–0.99). We found no effect on quality of life, lung function, 6-min walk test and high-sensitivity C-reactive protein. More patients dropped out in the simvastatin group compared to the placebo group (39 versus 29). Conclusion In our single-centre RCT, simvastatin at a dose of 40 mg daily significantly prolonged time to first COPD exacerbation and reduced exacerbation rate.
Association of socioeconomic deprivation with asthma care, outcomes, and deaths in Wales: A 5-year national linked primary and secondary care cohort study
Authors: Mohammad A. Alsallakh, Sarah E. Rodgers, Ronan A. Lyons, Aziz Sheikh, Gwyneth A. Davies
Journal: PLoS Medicine (2021)

Socioeconomic deprivation is known to be associated with worse outcomes in asthma, but there is a lack of population-based evidence of its impact across all stages of patient care. We investigated the association of socioeconomic deprivation with asthma-related care and outcomes across primary and secondary care and with asthma-related death in Wales.We constructed a national cohort, identified from 76% (2.4 million) of the Welsh population, of continuously treated asthma patients between 2013 and 2017 using anonymised, person-level, linked, routinely collected primary and secondary care data in the Secure Anonymised Information Linkage (SAIL) Databank. We investigated the association between asthma-related health service utilisation, prescribing, and deaths with the 2011 Welsh Index of Multiple Deprivation (WIMD) and its domains. We studied 106,926 patients (534,630 person-years), 56.3% were female, with mean age of 47.5 years (SD = 20.3). Compared to the least deprived patients, the most deprived patients had slightly fewer total asthma-related primary care consultations per patient (incidence rate ratio [IRR] = 0.98, 95% CI 0.97-0.99, p-value < 0.001), slightly fewer routine asthma reviews (IRR = 0.98, 0.97-0.99, p-value < 0.001), lower controller-to-total asthma medication ratios (AMRs; 0.50 versus 0.56, p-value < 0.001), more asthma-related accident and emergency (A&E) attendances (IRR = 1.27, 1.10-1.46, p-value = 0.001), more asthma emergency admissions (IRR = 1.56, 1.39-1.76, p-value < 0.001), longer asthma-related hospital stay (IRR = 1.64, 1.39-1.94, p-value < 0.001), and were at higher risk of asthma-related death (risk ratio of deaths with any mention of asthma 1.56, 1.18-2.07, p-value = 0.002). Study limitations include the deprivation index being area based and the potential for residual confounders and mediators.In this study, we observed that the most deprived asthma patients in Wales had different prescribing patterns, more A&E attendances, more emergency hospital admissions, and substantially higher risk of death. Interventions specifically designed to improve treatment and outcomes for these disadvantaged groups are urgently needed.
Successful endoscopic retrieval of dislodged jejunostomy Foley catheter
Authors: Chu-Hsuan Kuo, Chia-Wei Yang, Hsu-Heng Yen
Journal: Endoscopy (2021)

A 56-year-old man who had undergone placement of a feeding jejunostomy secondary to esophageal cancer presented believing that his feeding tube had fallen out but he was unable to locate it in his home. He had not experienced any abdominal pain, tarry stool, intestinal obstruction, or peritonitis. Radiological examination revealed that the missing jejunostomy Foley tube had migrated into the small intestine. Endoscopy failed to find the migrated tube, which remained stuck over the terminal ileum with proximal small bowel dilatation after 3 days ([Fig. 1]). We decided to perform endoscopic retrieval and the migrated tube with inflated balloon was found in the terminal ileum ([Fig. 2]). Attempts using snare or forceps all failed to pull out the impacted catheter due to adhesion resistance. We deflated the balloon after puncturing it with an injection needle ([Video 1]), and the Foley tube was successfully removed without resistance ([Fig. 3], [Fig. 4]).
Abstract 16443: Effects of Dietary Salt Intakes on Blood Pressure, Renal Function and Oxidative Stress in Rats Treated With Candesartan
Authors: Gangyi Zhu, Yanting Yu, Xiaoyan Wang
Journal: Circulation (2020)

Candesartan is one of angiotensin II type1 receptor blockers(ARB) and commonly used as first-line antihypertensive treatment. Low salt diet is often recommended by clinicians to the patients with hypertension and kidney diseases. However,it is not clear whether salt restriction is beneficial to the patients taking ARB. In order to explore this problem, the impacts of different salt diets on blood pressure (BP),renal function and oxidative stress were determined in 2-3 months old male Sprague Dawley rats treated with candesartan. The rats were randomly divided into 4 groups fed agar-gelled food rationally with NaCl content at 0.01%, 0.8%, 2% and 4% respectively(4-7 rats/group) while all rats were intraperitoneally injected with candesartan at 1mg / kg / day for 7 days. SBP started to decline on day 2 in all except 4% NaCl groups relative to day 0 (recorded 5-6 hrs before the first injection). On day 6, systolic BP (mmHg, tail-cuff, Softron,BP-98A) was lower in 0.8% (103.7+2.3) &amp; 0.01% (101.6+3) groups than 2% (113.5+4.1) &amp; 4% (129.9+4.6) groups (one way ANOVA,LSD test, P&lt;0.05) and correlated positively with food NaCl intakes (R 2 =0.9832). DBP was changed in a similar pattern as SBP. Serum creatinine (μmol/L) was higher in 0.01% group (225+39) than groups of 0.8% (1328+350), 2% (2095+242) and 4% (1576+703) while creatinine clearance (ml/day) was lower in 0.01% group (69.3+9) than groups of 0.8% (43.7+9), 2%(27.7+2) and 4%(29+0.6). In order to determine whether oxidative stress plays any role in the BP regulation and renal function maintenance, we also checked renal protein expression of ROS components. Relative to 0.8% group, renal NOXs were not altered in 0.01% group while NOX1 (145+18,% of 0.8% group), NOX2 (240+54) and NOX4 (197+41) was higher in 2% group than other groups. Mn-SOD (77+7.8), not Cu-Zn SOD, was decreased while HO1 (170+16), not HO2, was increased in 0.01% group. Renal abundance of nitrotyrosine was lower in 0.01% than other groups indicating a decreased oxidative stress, possibly caused by increase in HO1. We concluded that salt restriction with candesartan is beneficial to antihypertensive effect of AT1R blockade but disadvantage to maintenance of renal function. Thus, cautions to choice of low salt intakes are necessary when taking ARB agents.
Enforced dimerization between XBP1s and ATF6f enhances the protective effects of the UPR in models of neurodegeneration
Authors: René L. Vidal, Denisse Sepulveda, Paulina Troncoso-Escudero, Paula Garcia-Huerta, Constanza Gonzalez, Lars Plate, Carolina Jerez, José Canovas, Claudia A. Rivera, Valentina Castillo, Marisol Cisternas, Sirley Leal, Alexis Martinez, Julia Grandjean, Donzelli Sonia, Hilal A. Lashuel, Alberto J.M. Martin, Veronica Latapiat, Soledad Matus, S. Pablo Sardi, R. Luke Wiseman, Claudio Hetz
Journal: Molecular Therapy (2021)

Alteration to endoplasmic reticulum (ER) proteostasis is observed in a variety of neurodegenerative diseases associated with abnormal protein aggregation. Activation of the unfolded protein response (UPR) enables an adaptive reaction to recover ER proteostasis and cell function. The UPR is initiated by specialized stress sensors that engage gene expression programs through the concerted action of the transcription factors ATF4, ATF6f, and XBP1s. Although UPR signaling is generally studied as unique linear signaling branches, correlative evidence suggests that ATF6f and XBP1s may physically interact to regulate a subset of UPR target genes. In this study, we designed an ATF6f/XBP1s fusion protein termed UPRplus that behaves as a heterodimer in terms of its selective transcriptional activity. Cell-based studies demonstrated that UPRplus has a stronger effect in reducing the abnormal aggregation of mutant huntingtin and α-synuclein when compared to XBP1s or ATF6 alone. We developed a gene transfer approach to deliver UPRplus into the brain using adeno-associated viruses (AAVs) and demonstrated potent neuroprotection in vivo in preclinical models of Parkinson's disease and Huntington's disease. These results support the concept in which directing UPR-mediated gene expression toward specific adaptive programs may serve as a possible strategy to optimize the beneficial effects of the pathway in different disease conditions.
Registering Clinical Trials--Reply
Authors: K. Dickersin
Journal: JAMA (2003)

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Blood-brain barrier alterations in human brain tumors revealed by genome-wide transcriptomic profiling
Authors: Johanna Schaffenrath, Tania Wyss, Liqun He, Elisabeth Jane Rushing, Mauro Delorenzi, Flavio Vasella, Luca Regli, Marian Christoph Neidert, Annika Keller
Journal: Neuro-Oncology (2021)

Abstract Background Brain tumors, whether primary or secondary, have limited therapeutic options despite advances in understanding driver gene mutations and heterogeneity within tumor cells. The cellular and molecular composition of brain tumor stroma, an important modifier of tumor growth, has been less investigated to date. Only few studies have focused on the vasculature of human brain tumors despite the fact that the blood-brain barrier (BBB) represents the major obstacle for efficient drug delivery. Methods In this study, we employed RNA sequencing to characterize transcriptional alterations of endothelial cells (EC) isolated from primary and secondary human brain tumors. We used an immunoprecipitation approach to enrich for EC from normal brain, glioblastoma (GBM), and lung cancer brain metastasis (BM). Results Analysis of the endothelial transcriptome showed deregulation of genes implicated in cell proliferation, angiogenesis, and deposition of extracellular matrix (ECM) in the vasculature of GBM and BM. Deregulation of genes defining the BBB dysfunction module was found in both tumor types. We identified deregulated expression of genes in vessel-associated fibroblasts in GBM. Conclusion We characterize alterations in BBB genes in GBM and BM vasculature and identify proteins that might be exploited for developing drug delivery platforms. In addition, our analysis on vessel-associated fibroblasts in GBM shows that the cellular composition of brain tumor stroma merits further investigation.
Pharmacogenomics of Fluoropyrimidines—a Personalized Approach for Treating and Preventing Keratinocyte Carcinomas—Reply
Authors: David M. Schauder, Rajiv I. Nijhawan
Journal: JAMA Dermatology (2021)

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Early discharge after acute pulmonary embolism: keep quality of life on the radar
Authors: Kevin Solverson, Leslie Skeith, Jason Weatherald
Journal: European Respiratory Journal (2021)

<b>Quality of life improves following early discharge for acute PE, but not for all patients. Clinicians need to understand factors affecting quality of life for a given patient and must identify patients needing more support after discharge.</b>https://bit.ly/35dWzgV
Rugby’s implementation lessons: the importance of a ‘compliance wedge’ to support successful implementation for injury prevention
Authors: Martin Raftery, Éanna Cian Falvey
Journal: British Journal of Sports Medicine (2021)

World Rugby (the world governing body for rugby) has been committed to evidence-based risk management of concussion since introducing an off-field assessment in 2012. That year, the Concussion in Sports consensus meeting recommended the SCAT3 as a standardised assessment for concussion in sport. The SCAT3 and SCAT5 are the basis for the World Rugby Head Injury Assessment (HIA) protocol.1

World Rugby faced two significant obstacles when aiming to implement a concussion risk management plan: (1) the global nature of the game—rugby is played in over 120 countries, and (2) rugby is a limited-interchange sport (players unable to return to play), rather than free-interchange sport (unlike many other team sports). As a limited-interchange sport, rugby needed to change the game’s laws (rules) to allow temporary substitution for head injury.

The World Rugby Research Unit (WRRU) comprises sports medicine doctors with significant on-field experience working with a team of sports scientists, academic researchers and rugby administrators. This tripartite approach is supported by Hanson et al 2 who proposed using three complementary expert groups, termed as content experts (researchers), process experts (clinicians) and context experts (members of sporting bodies) to close the gaps between injury prevention research and safety promotion practice.2

The WRRU has a primary goal to improve player welfare and safety in rugby. It has recognised …
Mortality 10 Years After Percutaneous or Surgical Revascularization in Patients With Total Coronary Artery Occlusions
Authors: Hideyuki Kawashima, Kuniaki Takahashi, Masafumi Ono, Hironori Hara, Rutao Wang, Chao Gao, Faisal Sharif, Michael J. Mack, David R. Holmes, Marie-Claude Morice, Stuart J. Head, Arie Pieter Kappetein, Daniel J.F.M. Thuijs, Milan Milojevic, Thilo Noack, Friedrich-Wilhelm Mohr, Piroze M. Davierwala, Patrick W. Serruys, Yoshinobu Onuma
Journal: Journal of the American College of Cardiology (2021)
<i>Gv1</i>, a Zinc Finger Gene Controlling Endogenous MLV Expression
Authors: George R Young, Aaron K W Ferron, Veera Panova, Urszula Eksmond, Peter L Oliver, George Kassiotis, Jonathan P Stoye
Journal: Molecular Biology and Evolution (2021)

Abstract The genomes of inbred mice harbor around 50 endogenous murine leukemia virus (MLV) loci, although the specific complement varies greatly between strains. The Gv1 locus is known to control the transcription of endogenous MLVs and to be the dominant determinant of cell-surface presentation of MLV envelope, the GIX antigen. Here, we identify a single Krüppel-associated box zinc finger protein (ZFP) gene, Zfp998, as Gv1 and show it to be necessary and sufficient to determine the GIX+ phenotype. By long-read sequencing of bacterial artificial chromosome clones from 129 mice, the prototypic GIX+ strain, we reveal the source of sufficiency and deficiency as splice-acceptor variations and highlight the varying origins of the chromosomal region encompassing Gv1. Zfp998 becomes the second identified ZFP gene responsible for epigenetic suppression of endogenous MLVs in mice and further highlights the prominent role of this gene family in control of endogenous retroviruses.
Combining pulmonary and cardiac computed tomography biomarkers for disease-specific risk modelling in lung cancer screening
Authors: Anton Schreuder, Colin Jacobs, Nikolas Lessmann, Mireille J.M. Broeders, Mario Silva, Ivana Išgum, Pim A. de Jong, Nicola Sverzellati, Mathias Prokop, Ugo Pastorino, Cornelia M. Schaefer-Prokop, Bram van Ginneken
Journal: European Respiratory Journal (2021)

Objectives Combined assessment of cardiovascular disease (CVD), COPD and lung cancer may improve the effectiveness of lung cancer screening in smokers. The aims were to derive and assess risk models for predicting lung cancer incidence, CVD mortality and COPD mortality by combining quantitative computed tomography (CT) measures from each disease, and to quantify the added predictive benefit of self-reported patient characteristics given the availability of a CT scan. Methods A survey model (patient characteristics only), CT model (CT information only) and final model (all variables) were derived for each outcome using parsimonious Cox regression on a sample from the National Lung Screening Trial (n=15 000). Validation was performed using Multicentric Italian Lung Detection data (n=2287). Time-dependent measures of model discrimination and calibration are reported. Results Age, mean lung density, emphysema score, bronchial wall thickness and aorta calcium volume are variables that contributed to all final models. Nodule features were crucial for lung cancer incidence predictions but did not contribute to CVD and COPD mortality prediction. In the derivation cohort, the lung cancer incidence CT model had a 5-year area under the receiver operating characteristic curve of 82.5% (95% CI 80.9–84.0%), significantly inferior to that of the final model (84.0%, 82.6–85.5%). However, the addition of patient characteristics did not improve the lung cancer incidence model performance in the validation cohort (CT model 80.1%, 74.2–86.0%; final model 79.9%, 73.9–85.8%). Similarly, the final CVD mortality model outperformed the other two models in the derivation cohort (survey model 74.9%, 72.7–77.1%; CT model 76.3%, 74.1–78.5%; final model 79.1%, 77.0–81.2%), but not the validation cohort (survey model 74.8%, 62.2–87.5%; CT model 72.1%, 61.1–83.2%; final model 72.2%, 60.4–84.0%). Combining patient characteristics and CT measures provided the largest increase in accuracy for the COPD mortality final model (92.3%, 90.1–94.5%) compared to either other model individually (survey model 87.5%, 84.3–90.6%; CT model 87.9%, 84.8–91.0%), but no external validation was performed due to a very low event frequency. Conclusions CT measures of CVD and COPD provides small but reproducible improvements to nodule-based lung cancer risk prediction accuracy from 3 years onwards. Self-reported patient characteristics may not be of added predictive value when CT information is available.