tbuckley/cabot-search huggingface dataset:
The walking dead: sequential nuclear and organelle destruction during hair development
Authors: L.A. Jones, D.P. Harland, B.B. Jarrold, J.E. Connolly, M.G. Davis
Journal: British Journal of Dermatology (2017)

Transition of hair shaft keratinocytes from actively respiring, nucleated cells to structural cells devoid of nucleus and cytoplasm is key to hair production. This form of cell 'death', or cornification, requires cellular organelle removal to allow the cytoplasm to become packed with keratin filament bundles that further require cross-linking to create a strong hair fibre. Although these processes are well described in epidermal keratinocytes, there is a lack of understanding of such mechanisms, specifically in the hair follicle.To gain insights into cornification mechanisms within the hair follicle and thus improve our understanding of normal hair physiology.Scalp biopsies and hair-pluck samples were obtained from healthy human donors and analysed microscopically after immunohistochemical staining.A focal point of respiratory activity was evident in keratogenous zone cells within the hair shaft, which also exhibited nuclear damage. Nuclear degradation occurred via both caspase-dependent and caspase-independent pathways. Conversely, mitophagy was driven by Bnip3L and restricted to the boundary of the keratogenous zone at Adamson's Fringe.We propose a model of stepwise living-dead transition within the first 1 mm of hair formation, whereby fully functional, nucleated cells first consolidate required functions by degrading nuclear DNA, yet continue to respire and provide the source of reactive oxygen species required for keratin cross-linking. Finally, as the cells become packed with keratin bundles, Bnip3L expression triggers mitophagy to rid the cells of the last remaining 'living' characteristic, thus completing the march from 'living' to 'dead' within the hair follicle.
PCSK9 Variants, Low-Density Lipoprotein Cholesterol, and Neurocognitive Impairment
Authors: Matthew T. Mefford, Robert S. Rosenson, Mary Cushman, Michael E. Farkouh, Leslie A. McClure, Virginia G. Wadley, Marguerite R. Irvin, Vera Bittner, Monika M. Safford, Ransi Somaratne, Keri L. Monda, Paul Muntner, Emily B. Levitan
Journal: Circulation (2017)

Despite concerns about adverse neurocognitive events raised by prior trials, pharmacological PCSK9 (proprotein convertase subtilisin/kexin type-9) inhibition was not associated with neurocognitive effects in a recent phase 3 randomized trial. PCSK9 loss-of-function (LOF) variants that result in lifelong exposure to lower levels of low-density lipoprotein cholesterol can provide information on the potential long-term effects of lower low-density lipoprotein cholesterol on neurocognitive impairment and decline.We investigated the association between PCSK9 LOF variants and neurocognitive impairment and decline among black REGARDS study (Reasons for Geographic and Racial Differences in Stroke) participants with (n=241) and without (n=10 454) C697X or Y142X LOF variants. Neurocognitive tests included the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery (Word List Learning, World List Delayed Recall, Semantic Animal Fluency) and Six-Item Screener (SIS) assessments, administered longitudinally during follow-up. Neurocognitive impairment was defined as a score ≥1.5 SD below age, sex, and education-based stratum-specific means on 2 or 3 CERAD assessments or, separately, a score <5 on any SIS assessment at baseline or during follow-up. Neurocognitive decline was assessed using standardized continuous scores on individual neurocognitive tests.The mean sample age was 64 years (SD, 9), 62% were women, and the prevalence of neurocognitive impairment at any assessment was 6.3% by CERAD and 15.4% by SIS definitions. Adjusted odds ratios for neurocognitive impairment for participants with versus without PCSK9 LOF variants were 1.11 (95% confidence interval [CI], 0.58-2.13) using the CERAD battery and 0.89 (95% CI, 0.61-1.30) using the SIS assessment. Standardized average differences in individual neurocognitive assessment scores over the 5.6-year (range, 0.1-9.1) study period ranged between 0.07 (95% CI, -0.06 to 0.20) and -0.07 (95% CI, -0.18 to 0.05) among participants with versus without PCSK9 LOF variants. Patterns of neurocognitive decline were similar between participants with and without PCSK9 LOF variants (all P>0.10). Odds ratios for neurocognitive impairment per 20 mg/dL low-density lipoprotein cholesterol decrements were 1.02 (95% CI, 0.96-1.08) and 0.99 (95% CI, 0.95-1.02) for the CERAD and SIS definitions of impairment, respectively.These results suggest that lifelong exposure to low PCSK9 levels and cumulative exposure to lower levels of low-density lipoprotein cholesterol are not associated with neurocognitive effects in blacks.
Early detection of acute tubulointerstitial nephritis in the genesis of Mesoamerican nephropathy
Authors: Rebecca S.B. Fischer, Chandan Vangala, Luan Truong, Sreedhar Mandayam, Denis Chavarria, Orlando M. Granera Llanes, Marcos U. Fonseca Laguna, Alvaro Guerra Baez, Felix Garcia, Ramón García-Trabanino, Kristy O. Murray
Journal: Kidney International (2017)
Review: Continuous compression and 30:2 compression-to-ventilation CPR ratio do not differ for survival
Authors: Benton R. Hunter
Journal: Annals of Internal Medicine (2017)

Source Citation Ashoor HM, Lillie E, Zarin W, et al; ILCOR Basic Life Support Task Force. Effectiveness of different compression-to-ventilation methods for cardiopulmonary resuscitation: A systematic review. Resuscitation. 2017;118:112-25. 28583860
β‐Catenin and interleukin‐1β–dependent chemokine (C‐X‐C motif) ligand 10 production drives progression of disease in a mouse model of congenital hepatic fibrosis
Authors: Eleanna Kaffe, Romina Fiorotto, Francesca Pellegrino, Valeria Mariotti, Mariangela Amenduni, Massimiliano Cadamuro, Luca Fabris, Mario Strazzabosco, Carlo Spirli
Journal: Hepatology (2017)

Congenital hepatic fibrosis (CHF), a genetic disease caused by mutations in the polycystic kidney and hepatic disease 1 (PKHD1) gene, encoding for the protein fibrocystin/polyductin complex, is characterized by biliary dysgenesis, progressive portal fibrosis, and a protein kinase A–mediated activating phosphorylation of β‐catenin at Ser675. Biliary structures of Pkhd1del4/del4 mice, a mouse model of CHF, secrete chemokine (C‐X‐C motif) ligand 10 (CXCL10), a chemokine able to recruit macrophages. The aim of this study was to clarify whether CXCL10 plays a pathogenetic role in disease progression in CHF/Caroli disease and to understand the mechanisms leading to increased CXCL10 secretion. We demonstrate that treatment of Pkhd1del4/del4 mice for 3 months with AMG‐487, an inhibitor of CXC chemokine receptor family 3, the cognate receptor of CXCL10, reduces the peribiliary recruitment of alternative activated macrophages (cluster of differentiation 45 + F4/80 + cells), spleen size, liver fibrosis (sirius red), and cyst growth (cytokeratin 19–positive area), consistent with a pathogenetic role of CXCL10. Furthermore, we show that in fibrocystin/polyductin complex–defective cholangiocytes, isolated from Pkhd1del4/del4 mice, CXCL10 production is mediated by Janus kinase/signal transducer and activator of transcription 3 in response to interleukin 1beta (IL‐1β) and β‐catenin. Specifically, IL‐1β promotes signal transducer and activator of transcription 3 phosphorylation, whereas β‐catenin promotes its nuclear translocation. Increased pro‐IL‐1β was regulated by nuclear factor kappa‐light‐chain‐enhancer of activated B cells, and increased secretion of active IL‐1β was mediated by the activation of Nod‐like receptors, pyrin domain containing 3 inflammasome (increased expression of caspase 1 and Nod‐like receptors, pyrin domain containing 3). Conclusion: In fibrocystin/polyductin complex–defective cholangiocytes, β‐catenin and IL‐1β are responsible for signal transducer and activator of transcription 3–dependent secretion of CXCL10; in vivo experiments show that the CXCL10/CXC chemokine receptor family 3 axis prevents the recruitment of macrophages, reduces inflammation, and halts the progression of the disease; the increased production of IL‐1β highlights the autoinflammatory nature of CHF and may open novel therapeutic avenues. (H epatology 2018;67:1903‐1919).
Palliative care in a community-based oncology private practice.
Authors: Loren L. Friedman, Paul Cronin, Muhammad M. Siddiqui, Marie A. Garcia, Linda C. Anderson
Journal: Journal of Clinical Oncology (2017)

107 Background: Integration of palliative care in the outpatient oncology clinic improves the quality of care for patients with advanced cancer. While models of outpatient palliative care (PC) in the academic oncology clinic have been demonstrated, the feasibility of PC in a private practice oncology clinic has not been established. Methods: In 2014 our 8 office oncology practice composed of 30 physicians and 10 advanced practice providers hired a full-time PC physician. Our questions included: 1) Would the PC physician be valued by the oncologists in the practice; 2) Would internal referrals and follow-up encounters provide sufficient activity for PC physician employment; 3) Would the revenue received for patient encounters offset the cost to the practice of the PC physicians? We emailed a survey to providers; we tallied data on patient encounters; and we reviewed the actual dollar amount of reimbursements received from payers for PC evaluation and management codes for a 1 year period. Results: In our second full year, a single palliative care physician saw 487 initial consultations and 1273 follow-up encounters for a total of 1760 encounters. The collected revenue for these encounters covered 102% of the palliative care physician’s combined salary and overhead. This data enabled the additional hiring of a second PC physician in 2016. Of 36 providers surveyed, 24 (67%) completed our 10 question survey. On a 1-5 point scale, when asked to rank the positive influence of the palliative care program on the culture of patient care in the practice, the aggregate score was 4.96. When asked questions on how helpful the palliative care program was to the providers in managing a variety of patient concerns, all items scored between 4.5 and 5. A question on how helpful the PC physicians were as a curbside resource received an aggregate score of 5.0. Conclusions: Based on referral numbers and surveyed attitudes, PC physicians were readily accepted into the fabric of a community based oncology practice. Analysis of financial data demonstrates that the PC physician can cover a substantial part of their salary requirement through billing for patient encounters.
Abstract 21118: A Systematic Review on the Risk of Mortality Related to the Timing of Coronary Artery Bypass Grafting Following Myocardial Infarction
Authors: George A Krakowski, Andrew J Foy
Journal: Circulation (2017)

Introduction: The optimal timing for coronary artery bypass grafting (CABG) following an acute myocardial infarction (MI) is a topic of controversy among cardiologists and cardiothoracic surgeons. We sought to perform a systematic review of the evidence. Methods: PubMed was searched for studies that compared mortality between patients who underwent CABG, at different time points, following an acute MI. The quality of evidence was assessed using the National Institute of Health (NIH) quality assessment tool for observational cohort and cross-sectional studies. Mortality was compared between groups who had CABG performed &lt;24 hours (acute), 24-72 hours (sub-acute), and &gt;72 hours (delayed) following MI. Results: Sixteen observational studies were identified (1 prospective, 15 retrospective) which included 94,841 patients. There were no randomized controlled trials (RCT). Five studies used data from official registries while 11 relied upon data from a single site. Two studies specified the MI type as NSTEMI, 2 as STEMI, and it was unspecified in 12. Mortality was assessed as ‘in-hospital’ in 10 studies, ‘perioperative’ in 5, and ‘one month’ in 1. Using the NIH quality assessment tool, we scored 12 domains on a dichotomous scale of ‘yes’, ‘no’, or ‘other’ and found the average number of ‘yes’ answers was 6.5/12 with a range of 4 to 8/12. A quantitative comparison of mortality risk between timing groups could not be performed due to heterogeneity between recorded baseline covariates across studies as well as heterogeneity between MI-type, timing cut-offs, and specific mortality endpoints across studies. Only 1 study used propensity-matching, most used some logistic regression but 4 did not adjust at all for baseline cofounders. Most studies found that mortality was increased when patients underwent CABG &lt;24 hours following MI but there was no consistent difference in mortality between sub-acute versus delayed groups. Conclusions: The current evidence base for timing of CABG post-MI is poor, being composed of low to fair quality observational studies and expert opinion. Selection bias is a major concern for all studies that were reviewed. Well-conducted RCTs are urgently needed to better inform this important clinical question.
Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density
Authors: Nerea Alonso, Karol Estrada, Omar M E Albagha, Lizbeth Herrera, Sjur Reppe, Ole K Olstad, Kaare M Gautvik, Niamh M Ryan, Kathryn L Evans, Carrie M Nielson, Yi-Hsiang Hsu, Douglas P Kiel, George Markozannes, Evangelia E Ntzani, Evangelos Evangelou, Bjarke Feenstra, Xueping Liu, Mads Melbye, Laura Masi, Maria Luisa Brandi, Philip Riches, Anna Daroszewska, José Manuel Olmos, Carmen Valero, Jesús Castillo, José A Riancho, Lise B Husted, Bente L Langdahl, Matthew A Brown, Emma L Duncan, Stephen Kaptoge, Kay-Tee Khaw, Ricardo Usategui-Martín, Javier Del Pino-Montes, Rogelio González-Sarmiento, Joshua R Lewis, Richard L Prince, Patrizia D’Amelio, Natalia García-Giralt, Xavier Nogués, Simona Mencej-Bedrac, Janja Marc, Orit Wolstein, John A Eisman, Ling Oei, Carolina Medina-Gómez, Katharina E Schraut, Pau Navarro, James F Wilson, Gail Davies, John Starr, Ian Deary, Toshiko Tanaka, Luigi Ferrucci, Fernando Gianfrancesco, Luigi Gennari, Gavin Lucas, Roberto Elosua, André G Uitterlinden, Fernando Rivadeneira, Stuart H Ralston
Journal: Annals of the Rheumatic Diseases (2017)

Objectives To identify genetic determinants of susceptibility to clinical vertebral fractures, which is an important complication of osteoporosis. Methods Here we conduct a genome-wide association study in 1553 postmenopausal women with clinical vertebral fractures and 4340 controls, with a two-stage replication involving 1028 cases and 3762 controls. Potentially causal variants were identified using expression quantitative trait loci (eQTL) data from transiliac bone biopsies and bioinformatic studies. Results A locus tagged by rs10190845 was identified on chromosome 2q13, which was significantly associated with clinical vertebral fracture (P=1.04×10 −9 ) with a large effect size (OR 1.74, 95% CI 1.06 to 2.6). Bioinformatic analysis of this locus identified several potentially functional SNPs that are associated with expression of the positional candidate genes TTL (tubulin tyrosine ligase) and SLC20A1 (solute carrier family 20 member 1). Three other suggestive loci were identified on chromosomes 1p31, 11q12 and 15q11. All these loci were novel and had not previously been associated with bone mineral density or clinical fractures. Conclusion We have identified a novel genetic variant that is associated with clinical vertebral fractures by mechanisms that are independent of BMD. Further studies are now in progress to validate this association and evaluate the underlying mechanism.
MYC Targeted Long Noncoding RNA DANCR Promotes Cancer in Part by Reducing p21 Levels
Authors: Yunqi Lu, Zhongyi Hu, Lingegowda S. Mangala, Zachary E. Stine, Xiaowen Hu, Dahai Jiang, Yan Xiang, Youyou Zhang, Sunila Pradeep, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Angelo M. DeMarzo, Anil K. Sood, Lin Zhang, Chi V. Dang
Journal: Cancer Research (2017)

Abstract The MYC oncogene broadly promotes transcription mediated by all nuclear RNA polymerases, thereby acting as a positive modifier of global gene expression. Here, we report that MYC stimulates the transcription of DANCR, a long noncoding RNA (lncRNA) that is widely overexpressed in human cancer. We identified DANCR through its overexpression in a transgenic model of MYC-induced lymphoma, but found that it was broadly upregulated in many human cancer cell lines and cancers, including most notably in prostate and ovarian cancers. Mechanistic investigations indicated that DANCR limited the expression of cell-cycle inhibitor p21 (CDKN1A) and that the inhibitory effects of DANCR loss on cell proliferation could be partially rescued by p21 silencing. In a xenograft model of human ovarian cancer, a nanoparticle-mediated siRNA strategy to target DANCR in vivo was sufficient to strongly inhibit tumor growth. Our observations expand knowledge of how MYC drives cancer cell proliferation by identifying DANCR as a critical lncRNA widely overexpressed in human cancers. Significance: These findings expand knowledge of how MYC drives cancer cell proliferation by identifying an oncogenic long noncoding RNA that is widely overexpressed in human cancers. Cancer Res; 78(1); 64–74. ©2017 AACR.
P3.02c-094 Italian Nivolumab Advanced Squamous NSCLC Expanded Access Program: Efficacy and Safety in Patients with Brain Metastases
Authors: Diego Cortinovis, Angelo Delmonte, Rita Chiari, Annamaria Catino, Francesco Grossi, Cristina Noberasco, Francesco Gelsomino, Marina Gilli, Claudia Proto, Hector Soto Parra, Maria Rita Migliorino, Lucia Bonomi, Davide Tassinari, Antonio Frassoldati, Valeria Albanese, Giovanni Fadda, Federica De Galitiis, Giovanna Finocchiaro, Francesco Cognetti
Journal: Journal of Thoracic Oncology (2017)
Increased Liver Fatty Acid Uptake Is Partly Reversed and Liver Fat Content Normalized After Bariatric Surgery
Authors: Heidi Immonen, Jarna C. Hannukainen, Nobuyuki Kudomi, Jussi Pihlajamäki, Virva Saunavaara, Jukka Laine, Paulina Salminen, Terho Lehtimäki, Tam Pham, Patricia Iozzo, Pirjo Nuutila
Journal: Diabetes Care (2017)

Changes in liver fatty acid metabolism are important in understanding the mechanisms of diabetes remission and metabolic changes after bariatric surgery.Liver fatty acid uptake (LFU), blood flow, and fat content (LFC) were measured in 25 obese subjects before bariatric surgery and 6 months after using positron emission tomography/computed tomography and MRS; 14 lean individuals served as the control subjects.The increased LFU in obese subjects was associated with body adiposity. LFU was reduced postoperatively but was still high compared with the control subjects. LFC was normalized. Liver blood flow (per unit volume) was higher in obese subjects than in the control subjects at baseline and was further increased postoperatively; however, the total organ blood flow was unchanged as the liver volume decreased.The findings suggest that in a postoperative state, intrahepatic fatty acids are not stored in the liver but are used for oxidation to provide energy. Changes in perfusion may contribute to improved liver metabolism postoperatively.
3-Dimensional Echocardiographic Analysis of the Tricuspid Annulus Provides New Insights Into Tricuspid Valve Geometry and Dynamics
Authors: Karima Addetia, Denisa Muraru, Federico Veronesi, Csaba Jenei, Giacomo Cavalli, Stephanie A. Besser, Victor Mor-Avi, Roberto M. Lang, Luigi P. Badano
Journal: JACC. Cardiovascular imaging (2017)
La rage des chiroptères est un problème de santé publique en Europe
Authors: Mirjana Stantic-Pavlinic
Journal: Eurosurveillance (2005)

La rage, due a deux genotypes de lyssavirus differents et independants - European bat lyssaviruses (EBLV) type 1 et type 2 – est presente dans de nombreux pays d’Europe. L’infection concerne generalement les chauve-souris qui constituent le reservoir primaire des virus, mais quelques rares infections ont ete observees dans d’autres especes : martres, moutons et homme. A l’exception des deux cas humains, ces infections etaient toutes dues a EBLV-1. Aucun cas derive de EBLV-2 n’a ete rapporte chez les animaux terrestres. 
La maladie, fatale chez l’homme, a ete decrite en Europe suite a une morsure par une chauve-souris. Cet article fait le point sur les cas documentes de rage par EBLV en Europe chez l’homme et les chiropteres, et sur les recommandations en matiere de prevention et de traitement de la rage chez l’homme. La vaccination anti-rabique pre-exposition et le traitement post-exposition sont recommandes pour les personnes exposees professionnellement. Certains pays d’Europe ont deja adopte des recommandations selon des protocoles specifiques. Une prophylaxie est egalement recommandee chez les voyageurs internationaux apres une morsure par un chiroptere. La promotion de programmes de recherche sur la rage transmise par les chiropteres en Europe est en cours. Les chauve-souris font partie des especes protegees en Europe.
A phase I randomized controlled trial to evaluate safety and clinical effect of topically applied GSK2981278 ointment in a psoriasis plaque test
Authors: E.G. Kang, S. Wu, A. Gupta, Y.-L. von Mackensen, H. Siemetzki, J.M. Freudenberg, W. Wigger-Alberti, Y. Yamaguchi
Journal: British Journal of Dermatology (2017)

RORγt, a truncated isoform of retinoic acid receptor-related orphan receptor gamma (RORγ), is a transcription factor involved in Th17 cell differentiation. It is expressed in a few distinct types of immune cells and described as the master regulator of Th17 cytokine expression1. RORγ has identical ligand-binding domains as RORγt2; consequently, compounds targeting RORγ are also expected to modulate Th17 cell activity.

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Rare PfCSP C-terminal antibodies induced by live sporozoite vaccination are ineffective against malaria infection
Authors: Stephen W. Scally, Rajagopal Murugan, Alexandre Bosch, Gianna Triller, Giulia Costa, Benjamin Mordmüller, Peter G. Kremsner, B. Kim Lee Sim, Stephen L. Hoffman, Elena A. Levashina, Hedda Wardemann, Jean-Philippe Julien
Journal: The Journal of Experimental Medicine (2017)

Antibodies against the central repeat of the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) inhibit parasite activity and correlate with protection from malaria. However, the humoral response to the PfCSP C terminus (C-PfCSP) is less well characterized. Here, we describe B cell responses to C-PfCSP from European donors who underwent immunization with live Pf sporozoites (PfSPZ Challenge) under chloroquine prophylaxis (PfSPZ-CVac), and were protected against controlled human malaria infection. Out of 215 PfCSP-reactive monoclonal antibodies, only two unique antibodies were specific for C-PfCSP, highlighting the rare occurrence of C-PfCSP–reactive B cells in PfSPZ-CVac–induced protective immunity. These two antibodies showed poor sporozoite binding and weak inhibition of parasite traversal and development, and did not protect mice from infection with PfCSP transgenic Plasmodium berghei sporozoites. Structural analyses demonstrated that one antibody interacts with a polymorphic region overlapping two T cell epitopes, suggesting that variability in C-PfCSP may benefit parasite escape from humoral and cellular immunity. Our data identify important features underlying C-PfCSP shortcomings as a vaccine target.
Cancer-Associated Fibroblasts Neutralize the Anti-tumor Effect of CSF1 Receptor Blockade by Inducing PMN-MDSC Infiltration of Tumors
Authors: Vinit Kumar, Laxminarasimha Donthireddy, Douglas Marvel, Thomas Condamine, Fang Wang, Sergio Lavilla-Alonso, Ayumi Hashimoto, Prashanthi Vonteddu, Reeti Behera, Marlee A. Goins, Charles Mulligan, Brian Nam, Neil Hockstein, Fred Denstman, Shanti Shakamuri, David W. Speicher, Ashani T. Weeraratna, Timothy Chao, Robert H. Vonderheide, Lucia R. Languino, Peter Ordentlich, Qin Liu, Xiaowei Xu, Albert Lo, Ellen Puré, Chunsheng Zhang, Andrey Loboda, Manuel A. Sepulveda, Linda A. Snyder, Dmitry I. Gabrilovich
Journal: Cancer Cell (2017)