tbuckley/cabot-search huggingface dataset:
AB0177 Some determinants of bone mass amd bone geometry in women over 50
Authors: O Lesnyak, Y Lesnyak, P Sarapultsev
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The exact influence of different risk factors of osteoporosis on bone need to be assessed. <h3>Objectives</h3> The aim of this study was to assess the influence of some anthropometric and lifestyle factors on bone parameters of forearm in women over 50. <h3>Methods</h3> This was a cross-sectional study included 117 women of 50–79 y.o. Volumetric BMD (trabecular, tBMD, and cortical, cBMD) cortical bone area (CBA) and strength sustained indices (SSI) of radius were measured using pQCT (Stratec-XCT960). The relationship among several factors influencing the bone parameters was assessed using a multiple regression analysis. <h3>Results</h3> The age was the independent determinant of cBMD and CBA. BMI positively influenced tBMD. SSI depended on age and height. The years since menopause were not significant after controlling for other covariables. Dietary intake of calcium and smoking contributed a little to variation in bone parameters. Strong predictor of tBMD was professional physical activity in youth (negative correlation), and cBMD, CBA and SSI were influenced positively by current professional physical activity. <h3>Conclusion</h3> Thus, different mechanisms might be involved in compact and trabecular bone loss and geometric parameters.
Clinical and Neurologic Outcomes in Acetaminophen-Induced Acute Liver Failure: A 21-Year Multicenter Cohort Study
Authors: Andrew J. MacDonald, Jaime L. Speiser, Daniel R. Ganger, Kathleen M. Nilles, Babak J. Orandi, Anne M. Larson, William M. Lee, Constantine J. Karvellas, William M. Lee, Anne M. Larson, Iris Liou, Oren Fix, Michael Schilsky, Timothy McCashland, J. Eileen Hay, Natalie Murray, A. Obaid S. Shaikh, Andres Blei, Daniel Ganger, Atif Zaman, Steven H.B. Han, None Robert Fontana, Brendan McGuire, Raymond T. Chung, Alastair Smith, Robert Brown, Jeffrey Crippin, Edwin Harrison, Adrian Reuben, Santiago Munoz, Rajender Reddy, R. Todd Stravitz, Lorenzo Rossaro, Raj Satyanarayana, Tarek Hassanein, Constantine J. Karvellas, Jodi Olson, Ram Subramanian, James Hanje, Bilal Hameed
Journal: Clinical Gastroenterology and Hepatology (2020)
Concomitant use of a dual Src/ABL kinase inhibitor eliminates the in vitro efficacy of blinatumomab against Ph+ ALL
Authors: Jessica T. Leonard, Yoko Kosaka, Pavani Malla, Dorian LaTocha, Adam Lamble, Brandon Hayes-Lattin, Kaelan Byrd, Brian J. Druker, Jeffrey W. Tyner, Bill H. Chang, Evan Lind
Journal: Blood (2020)
Haemoperfusion should only be used for COVID-19 in the context of randomized trials
Authors: Edward G. Clark, Swapnil Hiremath, Lauralyn McIntyre, Ron Wald, Gregory L. Hundemer, Michael Joannidis
Journal: Nature Reviews Nephrology (2020)

Interest in the use of haemoperfusion for severe COVID-19 has been spurred by anecdotal reports of its efficacy and expert reviews suggesting theoretical benefits. However, on the basis of the limited current evidence, haemoperfusion remains an experimental therapy that should only be applied within the context of well-designed randomized trials.
Inappropriate empirical antibiotic therapy for bloodstream infections based on discordant in-vitro susceptibilities: a retrospective cohort analysis of prevalence, predictors, and mortality risk in US hospitals
Authors: Sameer S Kadri, Yi Ling Lai, Sarah Warner, Jeffrey R Strich, Ahmed Babiker, Emily E Ricotta, Cumhur Y Demirkale, John P Dekker, Tara N Palmore, Chanu Rhee, Michael Klompas, David C Hooper, John H Powers, Arjun Srinivasan, Robert L Danner, Jennifer Adjemian
Journal: The Lancet Infectious Diseases (2020)
Targeting positive feedback between BASP1 and EGFR as a therapeutic strategy for lung cancer progression
Authors: Ching-Chan Lin, Yu-Kai Huang, Chia-Fong Cho, Yu-Sen Lin, Chia-Chien Lo, Ting-Ting Kuo, Guan-Chin Tseng, Wei-Chung Cheng, Wei-Chao Chang, Tzu-Hung Hsiao, Liang-Chuan Lai, Jin-Yuan Shih, Yu-Huei Liu, K.S. Clifford Chao, Jennifer L. Hsu, Pei-Chih Lee, Xian Sun, Mien-Chie Hung, Yuh-Pyng Sher
Journal: Theranostics (2020)

Rationale: Brain metastasis in patients with lung cancer is life-threatening. However, the molecular mechanism for this catastrophic disease remains elusive, and few druggable targets are available. Therefore, this study aimed to identify and characterize proteins that could be used as therapeutic targets. Methods: Proteomic analyses were conducted to identify differentially expressed membrane proteins between brain metastatic lung cancer cells and primary lung cancer cells. A neuronal growth-associated protein, brain acid soluble protein 1 (BASP1), was chosen for further investigation. The clinical relevance of BASP1 in lung adenocarcinoma was first assessed. Tyrosine kinase activity assays and in vitro and in vivo functional assays were conducted to explore the oncogenic mechanisms of BASP1. Results: The protein levels of BASP1 were positively associated with tumor progression and poor prognosis in patients with lung adenocarcinoma. Membrane-bound BASP1 increased EGFR signaling and stabilized EGFR proteins by facilitating their escape from the ubiquitin-proteasome pathway. Reciprocally, activation of EGFR recruited more BASP1 to the plasma membrane, generating a positive feedback loop between BASP1 and EGFR. Moreover, the synergistic therapeutic effects of EGFR tyrosine kinase inhibitor and arsenic trioxide led to a reduction in the level of BASP1 protein observed in lung cancer cells with acquired resistance to EGFR inhibitors. Conclusions: The reciprocal interaction between BASP1 and EGFR facilitates EGFR signaling in brain metastatic lung cancer. Targeting the newly identified BASP1-EGFR interaction could open new venues for lung cancer treatment.
CyTOF mass cytometry reveals phenotypically distinct human blood neutrophil populations differentially correlated with melanoma stage
Authors: Yanfang Peipei Zhu, Tobias Eggert, Daniel J Araujo, Pandurangan Vijayanand, Christian Hermann Ottensmeier, Catherine C Hedrick
Journal: Journal for ImmunoTherapy of Cancer (2020)

Understanding neutrophil heterogeneity and its relationship to disease progression has become a recent focus of cancer research. Indeed, several studies have identified neutrophil subpopulations associated with protumoral or antitumoral functions. However, this work has been hindered by a lack of widely accepted markers with which to define neutrophil subpopulations.To identify markers of neutrophil heterogeneity in cancer, we used single-cell cytometry by time-of-flight (CyTOF) coupled with high-dimensional analysis on blood samples from treatment-naïve patients with melanoma.Our efforts allowed us to identify seven blood neutrophil clusters, including two previously identified individual populations. Interrogation of these neutrophil subpopulations revealed a positive trend between specific clusters and disease stage. Finally, we recapitulated these seven blood neutrophil populations via flow cytometry and found that they exhibited diverse capacities for phagocytosis and reactive oxygen species production in vitro.Our data provide a refined consensus on neutrophil heterogeneity markers, enabling a prospective functional evaluation in patients with solid tumors.
Magnetic resonance imaging accurately tracks kidney pathology and heterogeneity in the transition from acute kidney injury to chronic kidney disease
Authors: Jennifer R. Charlton, Yanzhe Xu, Teresa Wu, Kim A. deRonde, Jillian L. Hughes, Shourik Dutta, Gavin T. Oxley, Aleksandra Cwiek, Helen P. Cathro, Nathan P. Charlton, Mark R. Conaway, Edwin J. Baldelomar, Neda Parvin, Kevin M. Bennett
Journal: Kidney International (2020)
CRISPR-Sunspot: Imaging of endogenous low-abundance RNA at the single-molecule level in live cells
Authors: Ning-He Sun, Dan-Yang Chen, Lu-Peng Ye, Gang Sheng, Jun-Jie Gong, Bao-Hui Chen, Ying-Mei Lu, Feng Han
Journal: Theranostics (2020)

CRISPR/Cas-based mRNA imaging has been developed to labeling of high-abundance mRNAs. A lack of non-genetically encoded mRNA-tagged imaging tools has limited our ability to explore the functional distributions of endogenous low-abundance mRNAs in cells. Here, we developed a CRISPR-Sunspot method based on the SunTag signal amplification system that allows efficient imaging of low-abundance mRNAs with CRISPR/Cas9.
Characterization of <i>ANGPT2</i> mutations associated with primary lymphedema
Authors: Veli-Matti Leppänen, Pascal Brouillard, Emilia A. Korhonen, Tuomas Sipilä, Sawan Kumar Jha, Nicole Revencu, Veerle Labarque, Elodie Fastré, Matthieu Schlögel, Marie Ravoet, Amihood Singer, Claudia Luzzatto, Donatella Angelone, Giovanni Crichiutti, Angela D’Elia, Jaakko Kuurne, Harri Elamaa, Gou Young Koh, Pipsa Saharinen, Miikka Vikkula, Kari Alitalo
Journal: Science Translational Medicine (2020)

Primary lymphedema is caused by developmental and functional defects of the lymphatic vascular system that result in accumulation of protein-rich fluid in tissues, resulting in edema. The 28 currently known genes causing primary lymphedema can explain <30% of cases. Angiopoietin 1 (ANGPT1) and ANGPT2 function via the TIE1-TIE2 (tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 and 2) receptor complex and α5β1 integrin to form an endothelial cell signaling pathway that is critical for blood and lymphatic vessel formation and remodeling during embryonic development, as well as for homeostasis of the mature vasculature. By screening a cohort of 543 individuals affected by primary lymphedema, we identified one heterozygous de novo ANGPT2 whole-gene deletion and four heterozygous ANGPT2 missense mutations. Functional analyses revealed three missense mutations that resulted in decreased ANGPT2 secretion and inhibited the secretion of wild-type (WT)-ANGPT2, suggesting that they have a dominant-negative effect on ANGPT2 signaling. WT-ANGPT2 and soluble mutants T299M and N304K activated TIE1 and TIE2 in an autocrine assay in human lymphatic endothelial cells. Molecular modeling and biophysical studies showed that amino-terminally truncated ANGPT subunits formed asymmetrical homodimers that bound TIE2 in a 2:1 ratio. The T299M mutant, located in the dimerization interphase, showed reduced integrin α5 binding, and its expression in mouse skin promoted hyperplasia and dilation of cutaneous lymphatic vessels. These results demonstrate that primary lymphedema can be associated with ANGPT2 mutations and provide insights into TIE1 and TIE2 activation mechanisms.
Targeted FGFR Blockade for the Treatment of Tumor-Induced Osteomalacia
Authors: Iris R. Hartley, Carole B. Miller, Georgios Z. Papadakis, Clemens Bergwitz, Jaydira del Rivero, Jenny E. Blau, Pablo Florenzano, Jason A. Berglund, Jing Tassone, Kelly L. Roszko, Susan Moran, Rachel I. Gafni, Randi Isaacs, Michael T. Collins
Journal: New England Journal of Medicine (2020)

Targeted FGFR Blockade for Tumor-Induced Osteomalacia This letter describes the treatment of a patient with tumor-induced osteomalacia due to a phosphaturic mesenchymal tumor. The discovery of FN1–...
UK’s economic recovery should include plans for net zero emissions, says report
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Actions taken by the UK government to help the economy recover from the covid-19 pandemic should also help achieve net zero carbon emissions, according to Climate Assembly UK.1

The assembly, commissioned by six House of Commons select committees, involved 108 members of the public that represent the UK population in terms of age, gender, ethnicity, educational level, where and how they live, and level of concern about climate change.

The report has called for “strong and clear leadership from government” and laid out several recommendations on travel, energy consumption, food, and businesses, among other matters.

The assembly met, initially in person and later virtually, for six weekends between January and May 2020. The members heard “balanced, accurate, and comprehensive” information about how the UK could meet its net zero target.

In June 2019, the …
Observational Study Design Challenges—The Case of Fluoroquinolones and Aortic Disease
Authors: Raphaela Lipinsky DeGette, Richard William Grant, MD MPH
Journal: JAMA Internal Medicine (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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Variation around the dominant viral genome sequence contributes to viral load and outcome in patients with Ebola virus disease
Authors: Xiaofeng Dong, Jordana Munoz-Basagoiti, Natasha Y. Rickett, Georgios Pollakis, William A. Paxton, Stephan Günther, Romy Kerber, Lisa F. P. Ng, Michael J. Elmore, N’faly Magassouba, Miles W. Carroll, David A. Matthews, Julian A. Hiscox
Journal: Genome biology (2020)

Abstract Background Viral load is a major contributor to outcome in patients with Ebola virus disease (EVD), with high values leading to a fatal outcome. Evidence from the 2013–2016 Ebola virus (EBOV) outbreak indicated that different genotypes of the virus can have different phenotypes in patients. Additionally, due to the error-prone nature of viral RNA synthesis in an individual patient, the EBOV genome exists around a dominant viral genome sequence. The minor variants within a patient may contribute to the overall phenotype in terms of viral protein function. To investigate the effects of these minor variants, blood samples from patients with acute EVD were deeply sequenced. Results We examine the minor variant frequency between patients with acute EVD who survived infection with those who died. Non-synonymous differences in viral proteins were identified that have implications for viral protein function. The greatest frequency of substitution was identified at three codon sites in the L gene—which encodes the viral RNA-dependent RNA polymerase (RdRp). Recapitulating this in an assay for virus replication, these substitutions result in aberrant viral RNA synthesis and correlate with patient outcome. Conclusions Together, these findings support the notion that in patients who survived EVD, in some cases, the genetic variability of the virus resulted in deleterious mutations that affected viral protein function, leading to reduced viral load. Such mutations may also lead to persistent strains of the virus and be associated with recrudescent infections.
How oral probiotics affect the severity of an experimental model of progressive multiple sclerosis? Bringing commensal bacteria into the neurodegenerative process
Authors: Leyre Mestre, Francisco J. Carrillo-Salinas, Ana Feliú, Miriam Mecha, Graciela Alonso, Carmen Espejo, Laura Calvo-Barreiro, José L. Luque-García, Héctor Estevez, Luisa María Villar, Carmen Guaza
Journal: Gut Microbes (2020)

A growing number of studies support that the bidirectional interactions between the gut microbiota, the immune system and the CNS are relevant for the pathophysiology of MS. Several studies have reported alterations in the gut microbiome of MS patients. In addition, a variety of studies in animal models of MS have suggested that specific members of the gut commensal microbiota can exacerbate or ameliorate neuroinflammation. Probiotics represent oral nontoxic immunomodulatory agents that would exert benefits when using in combination with current MS therapy. Here we investigate the effect of Vivomixx on the gut microbiome and central and peripheral immune responses in a murine model of primary progressive MS. Vivomixx administration was associated with increased abundance of many taxa such as Bacteroidetes, Actinobacteria, Tenericutes and TM7. This was accompanied by a clear improvement of the motor disability of Theiler's virus infected mice; in the CNS Vivomixx reduced microgliosis, astrogliosis and leukocyte infiltration. Notably, the presence of Breg cells (CD19+CD5+CD1dhigh) in the CNS was enhanced by Vivomixx, and while spinal cord gene expression of IL-1β and IL-6 was diminished, the probiotic promoted IL-10 gene expression. One of the most significant findings was the increased plasma levels of butyrate and acetate levels in TMEV-mice that received Vivomixx. Peripheral immunological changes were subtle but interestingly, the probiotic restricted IL-17 production by Th17-polarized CD4+ T-cells purified from the mesenteric lymph nodes of Theiler's virus infected mice. Our data reinforce the beneficial effects of oral probiotics that would be coadjuvant treatments to current MS therapies.
Absent B cells, agammaglobulinemia, and hypertrophic cardiomyopathy in folliculin-interacting protein 1 deficiency
Authors: Francesco Saettini, Cecilia Poli, Jaime Vengoechea, Sonia Bonanomi, Julio C. Orellana, Grazia Fazio, Fred H. Rodriguez, Loreani P. Noguera, Claire Booth, Valentina Jarur-Chamy, Marissa Shams, Maria Iascone, Maja Vukic, Serena Gasperini, Manuel Quadri, Amairelys Barroeta Seijas, Elizabeth Rivers, Mario Mauri, Raffaele Badolato, Gianni Cazzaniga, Cristina Bugarin, Giuseppe Gaipa, Wilma G. M. Kroes, Daniele Moratto, Monique M. van Oostaijen-ten Dam, Frank Baas, Silvère van der Maarel, Rocco Piazza, Zeynep H. Coban-Akdemir, James R. Lupski, Bo Yuan, Ivan K. Chinn, Lucia Daxinger, Andrea Biondi
Journal: Blood (2020)
Moving Back to the Marriage Bed
Authors: Deborah Scaperoth
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
Multi-task deep learning for cardiac rhythm detection in wearable devices
Authors: Jessica Torres-Soto, Euan A. Ashley
Journal: npj Digital Medicine (2020)

Wearable devices enable theoretically continuous, longitudinal monitoring of physiological measurements such as step count, energy expenditure, and heart rate. Although the classification of abnormal cardiac rhythms such as atrial fibrillation from wearable devices has great potential, commercial algorithms remain proprietary and tend to focus on heart rate variability derived from green spectrum LED sensors placed on the wrist, where noise remains an unsolved problem. Here we develop DeepBeat, a multitask deep learning method to jointly assess signal quality and arrhythmia event detection in wearable photoplethysmography devices for real-time detection of atrial fibrillation. The model is trained on approximately one million simulated unlabeled physiological signals and fine-tuned on a curated dataset of over 500 K labeled signals from over 100 individuals from 3 different wearable devices. We demonstrate that, in comparison with a single-task model, our architecture using unsupervised transfer learning through convolutional denoising autoencoders dramatically improves the performance of atrial fibrillation detection from a F1 score of 0.54 to 0.96. We also include in our evaluation a prospectively derived replication cohort of ambulatory participants where the algorithm performed with high sensitivity (0.98), specificity (0.99), and F1 score (0.93). We show that two-stage training can help address the unbalanced data problem common to biomedical applications, where large-scale well-annotated datasets are hard to generate due to the expense of manual annotation, data acquisition, and participant privacy.
Ecological Load and Balancing Selection in Circumboreal Barnacles
Authors: Joaquin C B Nunez, Stephen Rong, Alejandro Damian-Serrano, John T Burley, Rebecca G Elyanow, David A Ferranti, Kimberly B Neil, Henrik Glenner, Magnus Alm Rosenblad, Anders Blomberg, Kerstin Johannesson, David M Rand
Journal: Molecular Biology and Evolution (2020)

Abstract Acorn barnacle adults experience environmental heterogeneity at various spatial scales of their circumboreal habitat, raising the question of how adaptation to high environmental variability is maintained in the face of strong juvenile dispersal and mortality. Here, we show that 4% of genes in the barnacle genome experience balancing selection across the entire range of the species. Many of these genes harbor mutations maintained across 2 My of evolution between the Pacific and Atlantic oceans. These genes are involved in ion regulation, pain reception, and heat tolerance, functions which are essential in highly variable ecosystems. The data also reveal complex population structure within and between basins, driven by the trans-Arctic interchange and the last glaciation. Divergence between Atlantic and Pacific populations is high, foreshadowing the onset of allopatric speciation, and suggesting that balancing selection is strong enough to maintain functional variation for millions of years in the face of complex demography.