tbuckley/cabot-search huggingface dataset:
Correlation between levels of adipokines and inflammatory mediators with spirometric parameters in individuals with obesity and symptoms of asthma: Cross-sectional study
Authors: L. Baltieri, E. Cazzo, D.A. Oliveira Modena, R.C. Gobato Rentel, L.C. Martins, E.A. Chaim
Journal: Pulmonology (2020)

The adipose tissue secretes adipokines and influences the release of inflammatory mediators contributing to a state of low-grade systemic inflammation that may change lung function.To correlate levels of adipokines and inflammatory mediators with lung function in individuals with obesity and bronchial asthma symptoms.A cross-sectional study, including women with obesity (grade II and III) with symptoms and clinical diagnosis of asthma. Anthropometric measurements (weight, height, BMI), pulmonary function test (spirometry), asthma control test questionnaire, collection of systemic inflammatory markers (blood collection) and pulmonary markers (sputum collection) were collected and were analyzed: IL-6, IL-8, TNF-α, adiponectin, resistin, leptin and C-reactive protein (CRP). The patients were stratified into two groups according to asthma control.80 women were analyzed and 40% had an ACT score greater than or equal to 18 and were classified as "controlled asthma". More than half of the patients of ACT<18 score obtaining measures of FEV1, PEF and FEF25-75% below and 80% of predicted. There was a significant and negative correlation between IL-6 in the sputum with FVC and FEF25-75% in the group ACT<18 and with FVC and FEV1 in the group ACT≥18.Therefore, we concluded that the increase of interleukin-6 in the sputum is related to worse pulmonary function even in patients with controlled asthma, especially in the translate airway permeability measures.
The lncRNA LAMP5-AS1 drives leukemia cell stemness by directly modulating DOT1L methyltransferase activity in MLL leukemia
Authors: Wen-Tao Wang, Tian-Qi Chen, Zhan-Cheng Zeng, Qi Pan, Wei Huang, Cai Han, Ke Fang, Lin-Yu Sun, Qian-Qian Yang, Dan Wang, Xue-Qun Luo, Yu-Meng Sun, Yue-Qin Chen
Journal: Journal of Hematology & Oncology (2020)

Abstract Background Mixed-lineage leukemia ( MLL ) gene rearrangements trigger aberrant epigenetic modification and gene expression in hematopoietic stem and progenitor cells, which generates one of the most aggressive subtypes of leukemia with an apex self-renewal. It remains a challenge to directly inhibit rearranged MLL itself because of its multiple fusion partners and the poorly annotated downstream genes of MLL fusion proteins; therefore, novel therapeutic targets are urgently needed. Methods qRT-PCR, receiver operating characteristic (ROC), and leukemia-free survival analysis were used to validate LAMP5-AS1 ( LAMP5 antisense 1) expression and evaluate its clinical value. We performed in vitro and in vivo experiments to investigate the functional relevance of LAMP5-AS1 in MLL leukemia progression and leukemia cell stemness. RNA electrophoretic mobility shift assays (EMSA), histone methyltransferase assay, RNA pull-down assay, and RNA fluorescence in situ hybridization (FISH) were used to validate the relationship between LAMP5-AS1 and the methyltransferase activity of DOT1L. The downstream ectopic target genes of LAMP5-AS1/DOT1L were validated by the chromatin immunoprecipitation (ChIP) and western blot. Results We discovered that a long noncoding RNA (lncRNA) LAMP5-AS1 can promote higher degrees of H3K79 methylation, followed by upregulated expression of the self-renewal genes in the HOXA cluster, which are responsible for leukemia stemness in context of MLL rearrangements. We found that LAMP5-AS1 is specifically overexpressed in MLL leukemia patients ( n = 58) than that in the MLL -wt leukemia ( n = 163) ( p &lt; 0.001), and the patients with a higher expression level of LAMP5-AS1 exhibited a reduced 5-year leukemia-free survival ( p &lt; 0.01). LAMP5-AS1 suppression significantly reduced colony formation and increased differentiation of primary MLL leukemia CD34+ cells. Mechanistically, LAMP5-AS1 facilitated the methyltransferase activity of DOT1L by directly binding its Lys-rich region of catalytic domain, thus promoting the global patterns of H3K79 dimethylation and trimethylation in cells. These observations supported that LAMP5-AS1 upregulated H3K79me2/me3 and the transcription of DOT1L ectopic target genes. Conclusions This is the first study that a lncRNA regulates the self-renewal program and differentiation block in MLL leukemia cells by facilitating the methyltransferase activity of DOT1L and global H3K79 methylation, showing its potential as a therapeutic target for MLL leukemia.
A common source for a trichinellosis outbreak reported in France and Serbia in 2017
Authors: Régine Barruet, Alice Devez, Jean Dupouy-Camet, Gregory Karadjian, Dragana Plavsa, Georges Chydériotis, Isabelle Vallée, Ljiljana Sofronic-Milosavljevic, Hélène Yera
Journal: Eurosurveillance (2020)

Trichinellosis is a rare parasitic zoonosis in the European Union. Meat from backyard pigs was the common source for a trichinellosis outbreak caused by Trichinella spiralis , which occurred in France and Serbia in the beginning of 2017. An epidemiological study was conducted in France and Serbia to determine the extent of the outbreak, to identify its source and to implement control measures. Three cases were exposed in Serbia and brought back to France pork delicatessen which they shared with relatives and friends. Around 47 individuals were exposed to the parasitised meat in France and Serbia and 20 cases of trichinellosis were reported (nine in France and 11 in Serbia). Nine of them were female. The diagnosis was delayed, in part because the parasitosis was not known by most physicians, which led to complications in the French cases such as facial paralysis and pulmonary embolism. Health alerts and survey networks are indispensable at a European level to control the disease.
Modeling the Hepatology Workforce in the United States: A Predicted Critical Shortage
Authors: Mark W. Russo, Oren K. Fix, Ayman A. Koteish, Katie Duggan, Marcia Ditmyer, Michael Fuchs, Raymond T. Chung, Gautham Reddy
Journal: Hepatology (2020)

Background and Aims Liver disease is prevalent in the United States, and as the population ages, an increasing number of patients are anticipated to present for care. The state of the current hepatology workforce and future demand for hepatology providers is not known. The aim of this study was to model future projections for hepatology workforce demand. Approach and Results A workforce study of hepatology providers in the United States was completed using primary and secondary data sources. An integrated workforce framework model was used that combined socioeconomic factors that drive economic demand, epidemiological factors that drive need, and utilization rates of health care services. Supply and demand projections were calculated for adult and pediatric hepatology professionals. Sensitivity analyses were conducted to cover the feasible range of these assumptions. An electronic survey of American Association for the Study of Liver Diseases (AASLD) members whose practice included 50% or more hepatology was conducted. In 2018, the adult and pediatric workforce included 7,296 and 824 hepatology providers, respectively, composed of hepatologists, gastroenterologists, and advanced practice providers whose practice was ≥50% hepatology. The modeling analysis projects that in 2023, 2028, and 2033, there will be shortages of 10%, 23%, and 35% adult hepatology providers, respectively, and 19%, 20%, and 16% pediatric hepatology providers, respectively. In sensitivity analyses, a shortage of hepatology providers is predicted even under optimistic assumptions. Among the respondents to the survey, the median age was higher among gastroenterologists and general hepatologists compared with transplant hepatologists. The most common category treated by transplant hepatologists was general hepatology. Conclusions There is an impending critical shortage of adult and pediatric hepatology providers. Strategies are needed to encourage clinicians to pursue hepatology, especially in areas outside of transplant centers.
Improved clinical symptoms and mortality among patients with severe or critical COVID-19 after convalescent plasma transfusion
Authors: Xinyi Xia, Kening Li, Lingxiang Wu, Zhihua Wang, Mengyan Zhu, Bin Huang, Jie Li, Ziyu Wang, Wei Wu, Min Wu, Wanlin Li, Lu Li, Yun Cai, Bakwatanisa Bosco, Aifang Zhong, Xiong Liu, Tangfeng Lv, Zhenhua Gan, Guang Chen, Yunhu Pan, Caidong Liu, Kai Zhang, Xiaoli Xu, Changjun Wang, Qianghu Wang
Journal: Blood (2020)
Combination of human umbilical cord mesenchymal stem (stromal) cell transplantation with IFN-γ treatment synergistically improves the clinical outcomes of patients with rheumatoid arthritis
Authors: Xiao He, Yi Yang, Mengwei Yao, Lei Yang, Luoquan Ao, Xueting Hu, Zhan Li, Xiaofeng Wu, Yan Tan, Wei Xing, Wei Guo, Joseph A Bellanti, Song Guo Zheng, Xiang Xu
Journal: Annals of the Rheumatic Diseases (2020)

Objectives To clarify the key role of circulating interferon-γ (IFN-γ) and to improve the clinical efficacy of mesenchymal stem cell (MSC) transplantation (MSCT) in patients with rheumatoid arthritis (RA). Methods Study of wild-type or IFN-γR -/- MSCT was first evaluated in a murine model of collagen-induced arthritis (CIA) following which a phase 1/2 randomised controlled study was conducted in 63 patients with RA who responded poorly to regular clinical treatments. Subjects were randomly assigned to an MSCT monotherapy group (n=32) or an MSCT plus recombinant human IFN-γ treatment group (n=31), with 1 year of follow-up. The primary end points consisted of efficacy as assessed as good or moderate EULAR response rates and the proportion of patients at 3 months attaining American College of Rheumatology 20 (ACR20) response rates. Results In the murine studies, wild-type MSCT significantly improved the clinical severity of CIA, while IFN-γR -/- MSCT aggravated synovitis, and joint and cartilage damage. Transitioning from the murine to the clinical study, the 3-month follow-up results showed that the efficacy and ACR20 response rates were attained in 53.3% patients with MSCT monotherapy and in 93.3% patients with MSCT combined with IFN-γ treatment (p&lt;0.05). No new or unexpected safety issues were encountered in 1-year follow-up for either treatment group. Conclusions The results of this study show that IFN-γ is a key factor in determining the efficacy of MSCT in the treatment of RA, and that an MSC plus IFN-γ combination therapeutic strategy can greatly improve the clinical efficacy of MSC-based therapy in RA patients.
Multicentre comparison of quantitative PCR-based assays to detect SARS-CoV-2, Germany, March 2020
Authors: Maximilian Muenchhoff, Helga Mairhofer, Hans Nitschko, Natascha Grzimek-Koschewa, Dieter Hoffmann, Annemarie Berger, Holger Rabenau, Marek Widera, Nikolaus Ackermann, Regina Konrad, Sabine Zange, Alexander Graf, Stefan Krebs, Helmut Blum, Andreas Sing, Bernhard Liebl, Roman Wölfel, Sandra Ciesek, Christian Drosten, Ulrike Protzer, Stephan Boehm, Oliver T Keppler
Journal: Eurosurveillance (2020)

Containment strategies and clinical management of coronavirus disease (COVID-19) patients during the current pandemic depend on reliable diagnostic PCR assays for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we compare 11 different RT-PCR test systems used in seven diagnostic laboratories in Germany in March 2020. While most assays performed well, we identified detection problems in a commonly used assay that may have resulted in false-negative test results during the first weeks of the pandemic.
Superior Vena Cava Syndrome Induced Collateral Circulation on 99mTc–Macroaggregated Albumin Lung Perfusion Scintigraphy
Authors: David Kersting, Nika Guberina, Lale Umutlu, Martin Stuschke, Hubertus Hautzel
Journal: Clinical Nuclear Medicine (2020)

Abstract Perfusion lung scintigraphy using SPECT/CT is one mainstay in diagnosing pulmonary embolism. Although typically almost all tracer will be accumulated in the lung capillaries, occasionally abnormal uptake can be detected. As superior vena cava syndrome leads to aberrant blood flow, tracer injected to an arm vein might partly circumvent the pulmonary capillary bed and accumulate in well-perfused anatomical structures. In this case, next to the commonly described liver enhancement, more prominent pseudo-uptake of various thoracic vertebrae was observable. However, a time-related FDG PET/CT demonstrated only the hepatic pseudo-uptake. Taken together, careful assessment of superior vena cava syndrome patient studies is highly recommended.
Neuronal codes for predictive processing in cortical layers
Authors: Lucy S. Petro, Lars Muckli
Journal: Behavioral and Brain Sciences (2020)

Abstract Predictive processing as a computational motif of the neocortex needs to be elaborated into theories of higher cognitive functions that include simulating future behavioural outcomes. We contribute to the neuroscientific perspective of predictive processing as a foundation for the proposed representational architectures of the mind.
Author Correction: Chimpanzee ethnography reveals unexpected cultural diversity
Authors: Christophe Boesch, Ammie K. Kalan, Roger Mundry, Mimi Arandjelovic, Simone Pika, Paula Dieguez, Emmanuel Ayuk Ayimisin, Amanda Barciela, Charlotte Coupland, Villard Ebot Egbe, Manasseh Eno-Nku, J. Michael Fay, David Fine, R. Adriana Hernandez-Aguilar, Veerle Hermans, Parag Kadam, Mohamed Kambi, Manuel Llana, Giovanna Maretti, David Morgan, Mizuki Murai, Emily Neil, Sonia Nicholl, Lucy Jayne Ormsby, Robinson Orume, Liliana Pacheco, Alex Piel, Crickette Sanz, Lilah Sciaky, Fiona A. Stewart, Nikki Tagg, Erin G. Wessling, Jacob Willie, Hjalmar S. Kühl
Journal: Nature Human Behaviour (2020)
Abstract A23: Ultrasensitive mutation detection in FFPE tissues and circulating tumor DNA using SiMSen-Seq
Authors: Stefan Filges, Daniel Andersson, Helena Kristiansson, Christoffer Vannas, Gustav Johansson, Junrui Li, Tony E. Godfrey, Max Levin, Barbro Linderholm, Anders Ståhlberg
Journal: Clinical Cancer Research (2020)

Abstract Novel diagnostic tools in oncology, prenatal diagnostics, and transplantation medicine depend on the detection of ultrarare variants. The analysis of cell-free DNA has the potential to revolutionize diagnosis, treatment monitoring, and recurrence and resistance of cancer. Yet these analysis remains challenging due to limited amounts of material and low allele frequencies of targeted variants. Simple, Multiplexed, PCR-based barcoding of DNA for Sensitive mutation detection using Sequencing (SiMSen-Seq) enables easy generation of libraries containing unique molecular identifiers (UMI) with minimal DNA input across several kilobases of DNA using two rounds of PCR and allows the detection of rare variants below 0.1% allele frequency. Clinical applications of ctDNA require highly optimized workflows to ensure high sensitivity and reproducibility. Here we present our state-of-the-art liquid biopsy workflow using SiMSen-Seq and simple quality control steps, applicable to almost any liquid biopsy protocol. In a series of case studies with melanoma patients we find that ctDNA mirrors the time-course of established protein markers such as S-100 and in some cases detects minimal residual months in advance of standard clinical diagnostics. SiMSen-Seq efficiently determined even rare mutations across multiple tumor forms in challenging sample types, such as FFPE tissue or cfDNA. We identified mutations in highly degraded FFPE tissue using a 60-plex SiMSen-Seq panel and then analyzed longitudinal cfDNA samples using patient-specific panels in a cohort of metastatic breast cancer patients. Our data indicate that ctDNA might be used as a biomarker for early detection of recurrence in these patients. We were able to detect treatment resistance variants as well as observe tumor recurrence well in advance of the onset of clinical symptoms. Thus, SiMSen-Seq offers an affordable, minimally invasive method for monitoring treatment efficiency and determination of drug resistance development in cancer. Citation Format: Stefan Filges, Daniel Andersson, Helena Kristiansson, Christoffer Vannas, Gustav Johansson, Junrui Li, Tony E. Godfrey, Max Levin, Barbro Linderholm, Anders Ståhlberg. Ultrasensitive mutation detection in FFPE tissues and circulating tumor DNA using SiMSen-Seq [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A23.
Vegetable Consumption and Progression of Prostate Cancer
Authors: Ilona Csizmadi, Pao-Hwa Lin, Stephen J. Freedland
Journal: JAMA (2020)

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Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike
Authors: Jiandong Huo, Yuguang Zhao, Jingshan Ren, Daming Zhou, Helen M.E. Duyvesteyn, Helen M. Ginn, Loic Carrique, Tomas Malinauskas, Reinis R. Ruza, Pranav N.M. Shah, Tiong Kit Tan, Pramila Rijal, Naomi Coombes, Kevin R. Bewley, Julia A. Tree, Julika Radecke, Neil G. Paterson, Piyada Supasa, Juthathip Mongkolsapaya, Gavin R. Screaton, Miles Carroll, Alain Townsend, Elizabeth E. Fry, Raymond J. Owens, David I. Stuart
Journal: Cell Host & Microbe (2020)

There are as yet no licensed therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric spike whose receptor binding domain (RBD) recognizes angiotensin-converting enzyme 2, initiating conformational changes that drive membrane fusion. We find that the monoclonal antibody CR3022 binds the RBD tightly, neutralizing SARS-CoV-2, and report the crystal structure at 2.4 Å of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilizing CR3022 epitope is inaccessible in the prefusion spike, suggesting that CR3022 binding facilitates conversion to the fusion-incompetent post-fusion state. Cryogenic electron microscopy (cryo-EM) analysis confirms that incubation of spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope could be useful therapeutically, possibly in synergy with an antibody that blocks receptor attachment.
Non-invasive monitoring of chronic liver disease via near-infrared and shortwave-infrared imaging of endogenous lipofuscin
Authors: Mari Saif, Wilhelmus J. Kwanten, Jessica A. Carr, Ivy X. Chen, Jessica M. Posada, Amitabh Srivastava, Juanye Zhang, Yi Zheng, Matthias Pinter, Sampurna Chatterjee, Samir Softic, C. Ronald Kahn, Klaus van Leyen, Oliver T. Bruns, Rakesh K. Jain, Moungi G. Bawendi
Journal: Nature Biomedical Engineering (2020)
A New Therapeutic Framework for Atrial Fibrillation Drug Development
Authors: Yen-Sin Ang, Sridharan Rajamani, Saptarsi M. Haldar, Jörg Hüser
Journal: Circulation Research (2020)

Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia and cause of significant morbidity and mortality. Its increasing prevalence in aging societies constitutes a growing challenge to global healthcare systems. Despite substantial unmet needs in AF prevention and treatment, drug developments hitherto have been challenging, and the current pharmaceutical pipeline is nearly empty. In this review, we argue that current drugs for AF are inadequate because of an oversimplified system for patient classification and the development of drugs that do not interdict underlying disease mechanisms. We posit that an improved understanding of AF molecular pathophysiology related to the continuous identification of novel disease-modifying drug targets and an increased appreciation of patient heterogeneity provide a new framework to personalize AF drug development. Together with recent innovations in diagnostics, remote rhythm monitoring, and big data capabilities, we anticipate that adoption of a new framework for patient subsegmentation based on pathophysiological, genetic, and molecular subsets will improve success rates of clinical trials and advance drugs that reduce the individual patient and public health burden of AF.
Representation and agency
Authors: Karl Friston
Journal: Behavioral and Brain Sciences (2020)

Abstract Gilead et al. raise some fascinating issues about representational substrates and structures in the predictive brain. This commentary drills down on a core theme in their arguments; namely, the structure of models that generate predictions. In particular, it highlights their factorial nature – both in terms of deep hierarchies over levels of abstraction and, crucially, time – and how this underwrites agency.
Emerging Treatment Paradigms for EGFR-Mutant Lung Cancers Progressing on Osimertinib: A Review
Authors: Andrew J. Piper-Vallillo, Lecia V. Sequist, Zofia Piotrowska
Journal: Journal of Clinical Oncology (2020)

Since its approval in April 2018, osimertinib has been widely adopted as first-line therapy for patients with advanced EGFR-mutant non -small cell lung cancer (NSCLC). Understanding osimertinib resistance mechanisms and currently available treatment options are essential to selecting optimal second line therapy for patients whose disease progresses during front-line osimertinib. Using data compiled from 6 osimertinib-resistance series, we describe here the heterogeneous profile of EGFR-dependent and independent mechanisms of osimertinib treatment failure. We identified MET alterations (7%-24%), EGFR C797X (0%-29%), SCLC transformation (2%-15%), and oncogene fusions (1%-10%) as the most common mechanisms of resistance. This review provides an evidence-based, algorithmic approach to the evaluation and management of post-osimertinib progression as well as a compendium of active, enrolling clinical trials for this population.