tbuckley/cabot-search huggingface dataset:
Functional Genomic Analysis of a <i>RUNX3</i> Polymorphism Associated With Ankylosing Spondylitis
Authors: Matteo Vecellio, Liye Chen, Carla J. Cohen, Adrian Cortes, Yan Li, Sarah Bonham, Carlo Selmi, Matthew A. Brown, Roman Fischer, Julian C. Knight, B. Paul Wordsworth
Journal: Arthritis & Rheumatology (2020)

Objective To investigate the functional consequences of the single‐nucleotide polymorphism rs4648889 in a putative enhancer upstream of the RUNX3 promoter associated with susceptibility to ankylosing spondylitis (AS). Methods Using nuclear extracts from Jurkat cells and primary human CD8+ T cells, the effects of rs4648889 on allele‐specific transcription factor (TF) binding were investigated by DNA pull‐down assay and quantitative mass spectrometry (qMS), with validation by electrophoretic mobility shift assay (EMSA), Western blotting of the pulled‐down eluates, and chromatin immunoprecipitation (ChIP)–quantitative polymerase chain reaction (qPCR) analysis. Further functional effects were tested by small interfering RNA knockdown of the gene for interferon regulatory factor 5 (IRF5), followed by reverse transcription–qPCR (RT‐qPCR) and enzyme‐linked immunosorbent assay (ELISA) to measure the levels of IFNγ messenger RNA (mRNA) and protein, respectively. Results In nuclear extracts from CD8+ T cells, results of qMS showed that relative TF binding to the AS‐risk A allele of rs4648889 was increased 3.7‐fold ( P &lt; 0.03) for Ikaros family zinc‐finger protein 3 (IKZF3; Aiolos) and components of the NuRD complex, including chromodomain helicase DNA binding protein 4 (CHD4) (3.6‐fold increase; P &lt; 0.05) and retinoblastoma binding protein 4 (RBBP4) (4.1‐fold increase; P &lt; 0.03). In contrast, IRF5 bound significantly more to the AS‐protective G allele compared to the AS‐risk A allele (fold change 8.2; P = 0.003). Validation with Western blotting, EMSA, and ChIP‐qPCR confirmed the differential allelic binding of IKZF3, CHD4, RBBP4, and IRF5. Silencing of IRF5 in CD8+ T cells increased the levels of IFNγ mRNA as measured by RT‐qPCR ( P = 0.03) and IFNγ protein as measured by ELISA ( P = 0.02). Conclusion These findings suggest that the association of rs4648889 with AS reflects allele‐specific binding of this enhancer‐like region to certain TFs, including IRF5, IKZF3, and members of the NuRD complex. IRF5 may have crucial influences on the functions of CD8+ lymphocytes, a finding that could reveal new therapeutic targets for the management of AS.
Bidirectional Genetic Control of Phenotypic Heterogeneity and Its Implication for Cancer Drug Resistance
Authors: Ning Mo, Xiaoyu Zhang, Wenjun Shi, Gongwang Yu, Xiaoshu Chen, Jian-Rong Yang
Journal: Molecular Biology and Evolution (2020)

Abstract Negative genetic regulators of phenotypic heterogeneity, or phenotypic capacitors/stabilizers, elevate population average fitness by limiting deviation from the optimal phenotype and increase the efficacy of natural selection by enhancing the phenotypic differences among genotypes. Stabilizers can presumably be switched off to release phenotypic heterogeneity in the face of extreme or fluctuating environments to ensure population survival. This task could, however, also be achieved by positive genetic regulators of phenotypic heterogeneity, or “phenotypic diversifiers,” as shown by recently reported evidence that a bacterial divisome factor enhances antibiotic resistance. We hypothesized that such active creation of phenotypic heterogeneity by diversifiers, which is functionally independent of stabilizers, is more common than previously recognized. Using morphological phenotypic data from 4,718 single-gene knockout strains of Saccharomyces cerevisiae, we systematically identified 324 stabilizers and 160 diversifiers and constructed a bipartite network between these genes and the morphological traits they control. Further analyses showed that, compared with stabilizers, diversifiers tended to be weaker and more promiscuous (regulating more traits) regulators targeting traits unrelated to fitness. Moreover, there is a general division of labor between stabilizers and diversifiers. Finally, by incorporating NCI-60 human cancer cell line anticancer drug screening data, we found that human one-to-one orthologs of yeast diversifiers/stabilizers likely regulate the anticancer drug resistance of human cancer cell lines, suggesting that these orthologs are potential targets for auxiliary treatments. Our study therefore highlights stabilizers and diversifiers as the genetic regulators for the bidirectional control of phenotypic heterogeneity as well as their distinct evolutionary roles and functional independence.
Evaluation of a novel navigation platform for laparoscopic liver surgery with organ deformation compensation using injected fiducials
Authors: Egidijus Pelanis, Andrea Teatini, Benjamin Eigl, Alois Regensburger, Amilcar Alzaga, Rahul Prasanna Kumar, Tobias Rudolph, Davit L. Aghayan, Carina Riediger, Niclas Kvarnström, Ole Jakob Elle, Bjørn Edwin
Journal: Medical Image Analysis (2020)

In laparoscopic liver resection, surgeons conventionally rely on anatomical landmarks detected through a laparoscope, preoperative volumetric images and laparoscopic ultrasound to compensate for the challenges of minimally invasive access. Image guidance using optical tracking and registration procedures is a promising tool, although often undermined by its inaccuracy. This study evaluates a novel surgical navigation solution that can compensate for liver deformations using an accurate and effective registration method. The proposed solution relies on a robotic C-arm to perform registration to preoperative CT/MRI image data and allows for intraoperative updates during resection using fluoroscopic images. Navigation is offered both as a 3D liver model with real-time instrument visualization, as well as an augmented reality overlay on the laparoscope camera view. Testing was conducted through a pre-clinical trial which included four porcine models. Accuracy of the navigation system was measured through two evaluation methods: liver surface fiducials reprojection and a comparison between planned and navigated resection margins. Target Registration Error with the fiducials evaluation shows that the accuracy in the vicinity of the lesion was 3.78±1.89 mm. Resection margin evaluations resulted in an overall median accuracy of 4.44 mm with a maximum error of 9.75 mm over the four subjects. The presented solution is accurate enough to be potentially clinically beneficial for surgical guidance in laparoscopic liver surgery.
Identifying early pulmonary arterial hypertension biomarkers in systemic sclerosis: machine learning on proteomics from the DETECT cohort
Authors: Yasmina Bauer, Simon de Bernard, Peter Hickey, Karri Ballard, Jeremy Cruz, Peter Cornelisse, Harbajan Chadha-Boreham, Oliver Distler, Daniel Rosenberg, Martin Doelberg, Sebastien Roux, Oliver Nayler, Allan Lawrie
Journal: European Respiratory Journal (2020)

Pulmonary arterial hypertension (PAH) is a devastating complication of systemic sclerosis (SSc). Screening for PAH in SSc has increased detection, allowed early treatment for PAH and improved patient outcomes. Blood-based biomarkers that reliably identify SSc patients at risk of PAH, or with early disease, would significantly improve screening, potentially leading to improved survival, and provide novel mechanistic insights into early disease. The main objective of this study was to identify a proteomic biomarker signature that could discriminate SSc patients with and without PAH using a machine learning approach and to validate the findings in an external cohort. Serum samples from patients with SSc and PAH (n=77) and SSc without pulmonary hypertension (non-PH) (n=80) were randomly selected from the clinical DETECT study and underwent proteomic screening using the Myriad RBM Discovery platform consisting of 313 proteins. Samples from an independent validation SSc cohort (PAH n=22 and non-PH n=22) were obtained from the University of Sheffield (Sheffield, UK). Random forest analysis identified a novel panel of eight proteins, comprising collagen IV, endostatin, insulin-like growth factor binding protein (IGFBP)-2, IGFBP-7, matrix metallopeptidase-2, neuropilin-1, N-terminal pro-brain natriuretic peptide and RAGE (receptor for advanced glycation end products), that discriminated PAH from non-PH in SSc patients in the DETECT Discovery Cohort (average area under the receiver operating characteristic curve 0.741, 65.1% sensitivity/69.0% specificity), which was reproduced in the Sheffield Confirmatory Cohort (81.1% accuracy, 77.3% sensitivity/86.5% specificity). This novel eight-protein biomarker panel has the potential to improve early detection of PAH in SSc patients and may provide novel insights into the pathogenesis of PAH in the context of SSc.
Exploring the Combination of Gabapentinoids and Opioids for Postoperative Analgesia
Authors: Joseph V. Pergolizzi
Journal: JAMA Network Open (2020)

Katsiaryna Bykov, PharmD, ScD; Brian T. Bateman, MD, MS; Jessica M. Franklin, PhD; Seanna M. Vine, MPH; Elisabetta Patorno, MD, DrPH
Counting publications and citations is not just irrelevant: it is an incentive that subverts the impact of clinical research
Authors: Fionn Büttner, Clare L Ardern, Paul Blazey, Serenna Dastouri, Heather A McKay, David Moher, Karim M Khan
Journal: British Journal of Sports Medicine (2020)

More than one million scientists publish peer-reviewed research each year.1 Health research strives to generate new discoveries or consolidate existing knowledge to benefit the lives of humans. But does published health research impact patients, policy, the economy, or society?

Common metrics that are purported to capture scientists’ contributions to their field include citations generated by peer-reviewed publications, journal impact factor, and indices that combine stand-alone metrics such as publication and citation count (eg, H-index).2 These metrics are frequently used by academic scientists and administrators to (1) inform faculty hiring and promotion, (2) rank grant funding applications, and (3) compare researchers’ perceived productivity.3 However, measures of academic output do not appear to capture the socioeconomic impact of health research, and fixating on academic metrics can lead scientists to neglect other important areas. As federal and international health research funding agencies increasingly demand that research should have impact beyond academia, researchers and academic institutions must adapt. We aim to draw the sport and exercise medicine community’s attention to the concept of research impact, highlight existing ways of assessing research impact, and outline the challenges of measuring research impact.

Research impact is considered the positive effect, influence, or benefit that …
An Essential Worker’s List of Pandemic Chores for the Kids
Authors: Wendy Stead
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 18716: Cardiovascular Benefits of Total and Domain Specific Physical Activity in Resource Poor Settings: Findings From a 7-Year Prospective Study of 0.5 Million Chinese Adults
Authors: Derrick Bennett, Liming Li, Huaidong Du, Yu Gou, Zheng Bian, Junshi Chen, Zhengming Chen
Journal: Circulation (2016)

Introduction: Previous studies of physical activities (PA) were mainly focused on recreational exercise and limited to high-income countries. In developing countries such as China recreational PA a...
The prospects of tumor chemosensitivity testing at the single-cell level
Authors: Chuan Yang, Caibo Yang, Yosef Yarden, Kenneth K.W. To, Liwu Fu
Journal: Drug Resistance Updates (2020)

Tumor chemosensitivity testing plays a pivotal role in the optimal selection of chemotherapeutic regimens for cancer patients in a personalized manner. High-throughput drug screening approaches have been developed but they failed to take into account intratumor heterogeneity and therefore only provided limited predictive power of therapeutic response to individual cancer patients. Single cancer cell drug sensitivity testing (SCC-DST) has been recently developed to evaluate the variable sensitivity of single cells to different anti-tumor drugs. In this review, we discuss how SCC-DST overcomes the obstacles of traditional drug screening methodologies. We outline critical procedures of SCC-DST responsible for single-cell generation and sorting, cell-drug encapsulation on a microfluidic chip and detection of cell-drug interactions. In SCC-DST, droplet-based microfluidics is emerging as an important platform that integrated various assays and analyses for drug susceptibility tests for individual patients. With the advancement of technology, both fluorescence imaging and label-free analysis have been used for detecting single cell-drug interactions. We also discuss the feasibility of integrating SCC-DST with single-cell RNA sequencing to unravel the mechanisms leading to drug resistance, and utilizing artificial intelligence to facilitate the analysis of various omics data in the evaluation of drug susceptibility. SCC-DST is setting the stage for better drug selection for individual cancer patients in the era of precision medicine.
COPD-associated miR-145-5p is downregulated in early-decline FEV1 trajectories in childhood asthma
Authors: Anshul Tiwari, Jiang Li, Alvin T. Kho, Maoyun Sun, Quan Lu, Scott T. Weiss, Kelan G. Tantisira, Michael J. McGeachie
Journal: Journal of Allergy and Clinical Immunology (2020)

Many microRNAs (miRNAs) have been associated with asthma and chronic obstructive pulmonary disease (COPD). Longitudinal lung function growth trajectories of children with asthma-normal growth, reduced growth (RG), early decline (ED), and RG with an ED (RGED)-have been observed, with RG and RGED associated with adverse outcomes, including COPD.Our aim was to determine whether circulating miRNAs from an early age in children with asthma would be prognostic of reduced lung function growth patterns over the next 16 years.We performed small RNA sequencing on sera from 492 children aged 5 to 12 years with mild-to-moderate asthma from the CAMP clinical trial, who were subsequently followed for 12 to 16 years. miRNAs were assessed for differential expression between previously assigned lung function growth patterns.We had 448 samples and 259 miRNAs for differential analysis. In a comparison of the normal and the most severe group (ie, normal growth compared with RGED), we found 1 strongly dysregulated miRNA, hsa-miR-145-5p (P < 8.01E-05). This miR was downregulated in both ED groups (ie, ED and RGED). We verified that miR-145-5p was strongly associated with airway smooth muscle cell growth in vitro.Our results showed that miR-145-5p is associated with the ED patterns of lung function growth leading to COPD in children with asthma and additionally increases airway smooth muscle cell proliferation. This represents a significant extension of our understanding of the role of miR-145-5p in COPD and suggests that reduced expression of miR-145-5p is a risk factor for ED of long-term lung function.
Seeking inspiration at the end of a turbulent year
Authors: Nikki Nabavi
Journal: BMJ (2020)

You might have noticed The BMJ in the news recently after our editor in chief, Fiona Godlee, wrote a joint editorial1 with Alastair McLellan, editor in chief of the Health Service Journal raising concern about relaxation of Christmas restrictions as the number of patients admitted to hospital with covid-19 rose. The article was especially meaningful because it’s only the second time in a century that The BMJ and HSJ have joined forces to write an editorial.

The editorial caps an extremely busy year at The BMJ as we’ve tried to keep readers informed of the ever changing covid-19 situation. Engaging in open conversation with experts is one way we’ve tried to communicate rapidly evolving knowledge. This has been a central aim of The BMJ ’s covid webinars, such as the one on long covid2 held in September, and the Known unknowns webinar that took place for a full day in November.3 As students, there is much …
Type 2 diabetes RCTs in mainland China: insights from a systematic review
Authors: Ruizhi Zheng, Yu Xu, Jingya Niu, Shujing Wu, Mian Li, Jieli Lu, Shanshan Wang, Yiping Xu, Weiqing Wang, Yufang Bi, Guang Ning
Journal: The Lancet Diabetes & Endocrinology (2020)
Unique challenges for glioblastoma immunotherapy—discussions across neuro-oncology and non-neuro-oncology experts in cancer immunology. Meeting Report from the 2019 SNO Immuno-Oncology Think Tank
Authors: Pavlina Chuntova, Frances Chow, Payal B Watchmaker, Mildred Galvez, Amy B Heimberger, Evan W Newell, Aaron Diaz, Ronald A DePinho, Ming O Li, E John Wherry, Duane Mitchell, Masaki Terabe, Derek A Wainwright, Jay A Berzofsky, Christel Herold-Mende, James R Heath, Michael Lim, Kim A Margolin, E Antonio Chiocca, Noriyuki Kasahara, Benjamin M Ellingson, Christine E Brown, Yvonne Chen, Peter E Fecci, David A Reardon, Gavin P Dunn, Linda M Liau, Joseph F Costello, Wolfgang Wick, Timothy Cloughesy, William C Timmer, Patrick Y Wen, Robert M Prins, Michael Platten, Hideho Okada
Journal: Neuro-Oncology (2020)

Abstract Cancer immunotherapy has made remarkable advances with over 50 separate Food and Drug Administration (FDA) approvals as first- or second-line indications since 2015. These include immune checkpoint blocking antibodies, chimeric antigen receptor-transduced T cells, and bispecific T-cell–engaging antibodies. While multiple cancer types now benefit from these immunotherapies, notable exceptions thus far include brain tumors, such as glioblastoma. As such, it seems critical to gain a better understanding of unique mechanistic challenges underlying the resistance of malignant gliomas to immunotherapy, as well as to acquire insights into the development of future strategies. An Immuno-Oncology Think Tank Meeting was held during the 2019 Annual Society for Neuro-Oncology Scientific Conference. Discussants in the fields of neuro-oncology, neurosurgery, neuro-imaging, medical oncology, and cancer immunology participated in the meeting. Sessions focused on topics such as the tumor microenvironment, myeloid cells, T-cell dysfunction, cellular engineering, and translational aspects that are critical and unique challenges inherent with primary brain tumors. In this review, we summarize the discussions and the key messages from the meeting, which may potentially serve as a basis for advancing the field of immune neuro-oncology in a collaborative manner.
Identification of risk factors associated with national transmission and late presentation of HIV-1, Denmark, 2009 to 2017
Authors: Maarten van Wijhe, Thea K Fischer, Jannik Fonager
Journal: Eurosurveillance (2021)

Background Despite availability of pre-exposure prophylaxis (PrEP), the incidence of HIV-1 in Europe remained stable the past decade. Reduction of new HIV-1 infections requires more knowledge about the profiles of high-risk transmitters and late presenters (LP). Aim We aimed to investigate risk factors associated with HIV-1 transmission clusters and late presentation with HIV-1 in Denmark. Methods Blood samples and epidemiological information were collected from newly diagnosed HIV-1 patients between 2009 and 2017. We genotyped pol genes and performed phylogenetic analyses to identify clusters. Risk factors for clustering and LP were investigated with partial proportional odds and logistic regression. Covariates included transmission mode, HIV-1 subtype, age, origin and cluster activity. Results We included 1,040 individuals in the analysis, 59.6% identified with subtype B and 48.4% in a cluster. Risk factors for clustering included Danish origin (odds ratio (OR): 2.95; 95% confidence interval (CI): 2.21–3.96), non-LP (OR: 1.44; 95% CI: 1.12–1.86), and men who have sex with men (MSM). Increasing age and non-B subtype infection decreased risk (OR: 0.69; 95% CI: 0.50–0.94). Risk for late presentation was lower for active clusters (OR: 0.60; 95% CI: 0.44–0.82) and Danish origin (OR: 0.43; 95% CI: 0.27–0.67). Non-Danish MSM had a lower risk than non-Danish heterosexuals (OR: 0.34; 95% CI: 0.21–0.55). Conclusion HIV-1 transmission in Denmark is driven by early diagnosed, young, subtype B infected MSM. These may benefit most from PrEP. Non-Danish heterosexual HIV-1 patients could benefit from improved communication to achieve earlier diagnosis and treatment.
AKI in Hospitalized Patients with COVID-19: A Mexican Population
Authors: Victor H. Gomez Johnson, Gina C. Gonzalez-Calderon, Antonio Camiro Zúñiga, José A. Garcĭa Gordillo, Adolfo Diaz Cabral, Alfredo Fonseca Chávez, Julio C. Arriaga, Jose S. Lopez Gil, Javier Zúñiga-Varga, Juan Pablo Herrera Felix
Journal: Journal of the American Society of Nephrology (2020)

Background: Although severe acute respiratory syndrome coronavirus (SARSCoV- 2) infection is primarily a respiratory disease, other organs are also affected  Several pathological studies confirm that SARS-CoV-2 invades kidney tissue causing endothelial damage, glomerular and vascular changes, extensive acute tubular injury and podocyte viral infection  AKI in COVID-19 appears to be frequent, with an AKI incidence of up to 46%, and a 20% requirement for renal replacement therapy (RRT)  Patients with AKI show a trend towards worse outcomes and increased mortality  Information on Latin- American population is scarce  Methods: We created a cohort to describe the incidence, risk factors, and outcomes associated with AKI in hospitalized patients with COVID-19 in Mexico City, excluding patients with a known chronic kidney disease  AKI was defined and classified according to KDIGO guidelines  Results: We included 127 patients  11 patients (8 66%) met the criteria for severe COVID-19, and were more likely to have AKI (81 82% vs  54 31%, p=0 078)  Of the 72 (56 69%) patients that had AKI, 48% were diagnosed at the time of admission  Patients with AKI were more likely to be men (61 7% vs  42 42%, p=0 043) and older (55 68 years vs  48 89 years, 0 018)  With regards disease severity, 72% of them had a grade 1 AKI  7 patients (9 72%) had grade 3 AKI, 4 of which needed renal replacement therapy  Overall length of stay was longer in patients with AKI (12 days vs  7 days, p=0 003)  A nonsignificant trend towards stay in critical care units was observed  3 out of 127 patients died, all 3 had AKI  Conclusions: Amongst our studied population, AKI was associated with a longer length of stay and with a trend towards a more use of critical care services  The lack of association of AKI with mortality could be due to the low overall in-hospital mortality of COVID-19 patients (2 40%)
Temozolomide in Relapse/Refractory Primary Vitreo-Retinal Lymphoma (R/R PVRL): A New Effective, Well-Tolerated and Cheap Reference. Result of a Study on Behalf of the LOC Network
Authors: Choquet Sylvain, Marine Baron, Anne Lavaud, Carole Soussain, Valerie Touitou, Christine Fardeau, Nathalie Cassoux, Magali Le Garff-Tavernier, Mirto Costopoulos, Caroline Houillier, Karim Maloum, Véronique Leblond, Emmanuel Gyan, Pierre Soubeyran
Journal: Blood (2017)