tbuckley/cabot-search huggingface dataset:
Exercise training increases levels of the anti-ageing Klotho protein: health-related cardiometabolic implications. The FIT-AGEING randomised controlled trial (PhD Academy Award)
Authors: Francisco J Amaro-Gahete
Journal: British Journal of Sports Medicine (2020)

The main aims of this PhD were (1) to study the association of the shed form of the α-Klotho gene (S-Klotho) with physical fitness, energy metabolism and cardiometabolic health, and (2) to study the effect of different exercise training programmes on S-Klotho, as well as on physical fitness, energy metabolism and cardiometabolic health in sedentary middle-aged adults.1 

Since the discovery of the Klotho gene as a suppressor of several ageing phenotypes, numerous studies have focused on elucidating the molecular pathways that mediate the effects of its expression on cellular ageing–related processes.1 However, the role of the S-Klotho protein in different healthy ageing–related outcomes has not been deeply studied. Moreover, there is a biological base supporting the hypothesis that exercise training could induce an increment of S-Klotho, resulting in one of the still unrecognised physiological mechanisms that can explain the exercise benefits on the ageing process. …
Adaptive evolution of virulence and persistence in carbapenem-resistant Klebsiella pneumoniae
Authors: Christoph M. Ernst, Julian R. Braxton, Carlos A. Rodriguez-Osorio, Anna P. Zagieboylo, Li Li, Alejandro Pironti, Abigail L. Manson, Anil V. Nair, Maura Benson, Kaelyn Cummins, Anne E. Clatworthy, Ashlee M. Earl, Lisa A. Cosimi, Deborah T. Hung
Journal: Nature Medicine (2020)
Lymphocyte subset (CD4+, CD8+) counts reflect the severity of infection and predict the clinical outcomes in patients with COVID-19
Authors: Zeming Liu, Wei Long, Mengqi Tu, Sichao Chen, Yihui Huang, Shipei Wang, Wei Zhou, Danyang Chen, Ling Zhou, Min Wang, Meng Wu, Qi Huang, Haibo Xu, Wen Zeng, Liang Guo
Journal: Journal of Infection (2020)
C-Met targeted fluorescence molecular endoscopy in Barrett's esophagus patients and identification of outcome parameters for phase-I studies
Authors: Steven J. de Jongh, Floris J. Voskuil, Iris Schmidt, Arend Karrenbeld, Gursah Kats-Ugurlu, Gert Jan Meersma, Jessie Westerhof, Max J.H. Witjes, Gooitzen M. van Dam, Dominic J. Robinson, Wouter B. Nagengast
Journal: Theranostics (2020)

Rationale & aim: Various types of cell therapies are currently under investigation for the treatment of ischemic stroke patients.To bridge the gap between cell administration and therapeutic outcome, there is a need for non-invasive monitoring of these innovative therapeutic approaches.Spectral photon counting computed tomography (SPCCT) is a new imaging modality that may be suitable for cell tracking.SPCCT is the next generation of clinical CT that allows the selective visualization and quantification of multiple contrast agents.The aims of this study are: (i) to demonstrate the feasibility of using SPCCT to longitudinally monitor and quantify therapeutic cells, i.e. bone marrow-derived M2-polarized macrophages transplanted in rats with brain damage; and (ii) to evaluate the potential of this approach to discriminate M2-polarized macrophages from their encapsulating scaffold.Methods: Twenty one rats received an intralesional transplantation of bone marrow-derived M2-polarized macrophages.In the first set of experiments, cells were labeled with gold nanoparticles and tracked for up to two weeks post-injection in a monocolor study via gold K-edge imaging.In the second set of experiments, the same protocol was repeated for a bicolor study, in which the labeled cells are embedded in iodine nanoparticle-labeled scaffold.The amount of gold in the brain was longitudinally quantified using gold K-edge images reconstructed from SPCCT acquisition.Animals were sacrificed at different time points post-injection, and ICP-OES was used to validate the accuracy of gold quantification from SPCCT imaging.Results: The feasibility of therapeutic cell tracking was successfully demonstrated in brain-damaged rats with SPCCT imaging.The imaging modality enabled cell monitoring for up to 2 weeks post-injection, in a specific and quantitative manner.Differentiation of labeled cells and their embedding scaffold was also feasible with SPCCT imaging, with a detection limit as low as 5,000 cells in a voxel of 250 × 250 × 250 µm in dimension in vivo. Conclusion:Multicolor SPCCT is an innovative translational imaging tool that allows monitoring and quantification of therapeutic cells and their encapsulating scaffold transplanted in the damaged rat brain.
The molecular landscape and microenvironment of salivary duct carcinoma reveal new therapeutic opportunities
Authors: Melissa Alame, Emmanuel Cornillot, Valère Cacheux, Guillaume Tosato, Marion Four, Laura De Oliveira, Stéphanie Gofflot, Philippe Delvenne, Evgenia Turtoi, Simon Cabello-Aguilar, Masahiko Nishiyama, Andrei Turtoi, Valérie Costes-Martineau, Jacques Colinge
Journal: Theranostics (2020)

de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Clonal Progression during First Course of Chemotherapy in Acute Myeloid Leukemia Suboptimal Responders Heralds Reinduction Failure and Early Death
Authors: Anita Tranberg Simonsen, Manja Meggendorfer, Sarah Koch, Annette Fasan, Wolfgang Kern, Line Nederby, Peter Hokland, Hans Beier Ommen
Journal: Blood (2017)
Association of Cigarette Smoking With Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Authors: Greg McDermott, Xiaoqing Fu, John H. Stone, Rachel Wallwork, Yuqing Zhang, Hyon K. Choi, Zachary S. Wallace
Journal: JAMA Internal Medicine (2020)

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic small vessel vasculitis characterized by circulating ANCAs targeting proteinase 3 (PR3) or myeloperoxidase (MPO) and associated with excess morbidity and mortality. Myeloperoxidase-ANCA-positive AAV and PR3-ANCA-positive AAV are increasingly recognized to have differences in genetic risk, pathogenesis, and response to treatment. Risk factors for AAV, including cigarette smoking, are poorly understood.To examine the association between cigarette smoking and AAV.This case-control study included a consecutive inception cohort of 484 patients with AAV diagnosed from 2002 to 2017 compared with a cohort of sex-, race-, and age-matched controls. Eleven cases were excluded owing to discordant smoking information in the electronic health record. Controls were randomly selected from participants recruited to the Partners HealthCare Biobank between its inception in 2010 and 2018 and who completed a smoking questionnaire and were not diagnosed with AAV (n = 30 536).Smoking status (current, former, never) and pack-years of cigarette smoking were determined from review of the electronic medical record and smoking questionnaires.Patients with AAV were individually matched with 3 randomly-selected controls based on sex, race, and age (within 2 years difference). Conditional logistic regression was performed to examine the association between cigarette smoking and AAV using odds ratios (OR) and 95% confidence intervals (CIs).Overall, 473 cases were matched with 1419 controls (mean [SD] age, 59 [16] years; 281 women [59%], 396 white [84%]). Patients with AAV were more likely to be former (OR, 1.6; 95% CI, 1.3-2.0) or current smokers (OR, 2.7; 95% CI, 1.8-4.1); there was a dose-response relationship according to pack-years of exposure (P < .001). These associations were especially strong among participants with MPO-ANCA-positive disease (former smokers: OR, 1.7; 95% CI, 1.3-2.3; current smokers: OR, 3.5; 95% CI, 2.1-6.1) but not in participants with PR3-ANCA-positive AAV (former smokers: OR, 1.3; 95% CI, 0.9-2.0; current smokers: OR, 1.7; 95% CI, 0.8-3.5). After stratifying by selected demographics and disease manifestations, these associations remained strong.Cigarette smoking was associated with AAV, especially MPO-ANCA-positive AAV. Further studies are needed to investigate a potential pathogenic mechanism.
Lethal Infectious Diseases as Inborn Errors of Immunity: Toward a Synthesis of the Germ and Genetic Theories
Authors: Jean-Laurent Casanova, Laurent Abel
Journal: Annual Review of Pathology Mechanisms of Disease (2020)

It was first demonstrated in the late nineteenth century that human deaths from fever were typically due to infections. As the germ theory gained ground, it replaced the old, unproven theory that deaths from fever reflected a weak personal or even familial constitution. A new enigma emerged at the turn of the twentieth century, when it became apparent that only a small proportion of infected individuals die from primary infections with almost any given microbe. Classical genetics studies gradually revealed that severe infectious diseases could be driven by human genetic predisposition. This idea gained ground with the support of molecular genetics, in three successive, overlapping steps. First, many rare inborn errors of immunity were shown, from 1985 onward, to underlie multiple, recurrent infections with Mendelian inheritance. Second, a handful of rare and familial infections, also segregating as Mendelian traits but striking humans resistant to other infections, were deciphered molecularly beginning in 1996. Third, from 2007 onward, a growing number of rare or common sporadicinfections were shown to result from monogenic, but not Mendelian, inborn errors. A synthesis of the hitherto mutually exclusive germ and genetic theories is now in view.
Phase I trial and pharmacokinetic study of Tanibirumab, a fully human monoclonal antibody to the vascular endothelial growth factor receptor 2 in patients with refractory solid tumors.
Authors: Su Jin Lee, Jun Soo Ham, Hee Kyung Kim, Seonggyu Byeon, Seon Young Lee, Weon Sup Lee, Jin San Yoo, Jong Mu Sun, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Myung-Ju Ahn, Ho Yeong Lim, Won Ki Kang, Young Suk Park
Journal: Journal of Clinical Oncology (2015)

2522 Background: Tanibirumab is a fully human monoclonal antibody to the vascular endothelial growth factor receptor 2 (VEGFR-2). We conducted a first-in-human phase I study of Tanibirumab in patients with solid tumors which were refractory to standard chemotherapy. Primary endpoints are evaluating safety, pharmacokinetics (PKs), estimating maximum-tolerated dose (MTD) and recommended phase II dose (RP2D). Methods: We designed to escalate Tanibirumab at 9 different dose levels with 3+3 method and Tanibirumab (1-28mg/kg) was administered intravenously on D1, 8, 15 in 28-day courses. Dose limiting toxicities (DLTs) were assessed in only first cycle of treatment and response evaluation was performed every 2 cycles. The effects of Tanibirumab on serum VEGF, soluble VEGFR-2, PlGF and correlation between VEGF, VEGFR-2 expression in archival tumor tissue and efficacy were planned. Results: From October 2011 to September 2013, a total of 26 patients with refractory solid tumors were enrolled. The median age was 58 years (range, 27-75) and 20 patients were male. Most common tumor type was colorectal cancer (N = 18) and 7 patients had history of previous bevacizumab treatment. As hemangioma continued to occur, last dose level, 28m/kg was not performed. DLTs were not found, and MTD was confirmed as 24mg/kg. Hemangioma was observed in 50% of patients, but most of those were grade 1-2 which disappeared after discontinuation of study drug. Among 18 patients of efficacy set, no objective response was observed, but 11 patients showed stable disease. PKs were characterized by dose-dependent linear exposure and mean trough concentrations exceeded biologically relevant target levels at 12mg/kg and above. Serum VEGF, soluble VEGFR-2, PlGF increased at 4mg/kg dose level and above. Conclusions: Treatment with Tanibirumab showed tolerable toxicity profile and modest clinical efficacy in patients with refractory solid tumors. We have a plan to conduct phase II trial in patients with glioma. Clinical trial information: NCT01660360.
Effect of Smoking on Outcomes of Primary PCI in Patients With STEMI
Authors: Björn Redfors, Ariel Furer, Harry P. Selker, Holger Thiele, Manesh R. Patel, Shmuel Chen, James E. Udelson, E. Magnus Ohman, Ingo Eitel, Christopher B. Granger, Akiko Maehara, Ajay J. Kirtane, Philippe Généreux, Paul L. Jenkins, Ori Ben-Yehuda, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2020)
Genetic evolution of invasive emm28 Streptococcus pyogenes strains and significant association with puerperal infections in young women in Finland
Authors: K. Gröndahl-Yli-Hannuksela, S.B. Beres, H.-L. Hyyryläinen, T. Kallonen, J.M. Musser, J. Vuopio
Journal: Clinical Microbiology and Infection (2020)

ObjectivesStreptococcus pyogenes or group A streptococcus (GAS) is a human specific pathogen that annually infects over 700 million individuals. GAS strains of type emm28 are an abundant cause of invasive infections in Europe and North America.MethodsWe conducted a population-based study on bacteraemic emm28 GAS cases in Finland, from 1995 to 2015. Whole-genome sequencing (WGS) was used to genetically characterize the bacterial isolates. Bayesian analysis of the population structure was used to define genetic clades. Register-linkage analysis was performed to test for association of emm28 GAS with delivery- or postpartum-related infections. A genome-wide association study was used to search for DNA sequences associated with delivery or puerperal infections.ResultsAmong 3060 bacteraemic cases reported during the study period, 714 were caused by emm28. Women comprised a majority of cases (59 %, 422/714), and were significantly over-represented (84.4 %, 162/192, p < 0.0001) among cases in the childbearing age group (20–40 years). Register-linkage analysis revealed strong association (p < 0.0001) of emm28 bacteraemias with delivery and puerperium. In this register-linkage analysis, 120 women with GAS bacteraemia were identified and linked to delivery, infections during delivery or puerperium time. Among these the proportion of cases caused by emm28 was significantly higher than any other emm type (55.8%, 67/120, p < 0.0001). Among the four genetic subclades identified, SC1B has dominated among the bacteraemic cases since 2000. Altogether 620 of 653 (94.9%) isolates belonged to SC1B. No specific sequence or genetic clade was found nonrandomly associated with delivery or puerperal infections.ConclusionsWomen of childbearing age were significantly overrepresented among bacteraemic emm28 GAS cases, and in particular were strongly associated with delivery and puerperium cases over the 21 years studied. The molecular mechanisms behind these associations are unclear and warrant further investigation.
Starvation-induced suppression of DAZAP1 by miR-10b integrates splicing control into TSC2-regulated oncogenic autophagy in esophageal squamous cell carcinoma
Authors: Yunsong Chen, Yan Lu, Yanli Ren, Jupeng Yuan, Nasha Zhang, Hannah Kimball, Liqing Zhou, Ming Yang
Journal: Theranostics (2020)

Esophageal squamous cell carcinoma (ESCC) accounts for about 90% of all incident esophageal cancers, with a 5-year survival rate of < 20%. Autophagy is of particular importance in cancers; however, the detailed regulatory mechanisms of oncogenic autophagy in ESCC have not been fully elucidated. In the present study, we address how splicing control of TSC2 is involved in mTOR-regulated oncogenic autophagy. Methods: Alternative splicing events controlled by DAZAP1 in ESCC cells were identified via RNAseq. Differential phosphorylation of short or long TSC2 splicing variants by AKT and their impacts on mTOR signaling were also examined. Results: We found that starvation-induced miR-10b could enhance autophagy via silencing DAZAP1, a key regulator of pre-mRNA alternative splicing. Intriguingly, we observed a large number of significantly changed alternative splicing events, especially exon skipping, upon RNAi of DAZAP1. TSC2 was verified as one of the crucial target genes of DAZAP1. Silencing of DAZAP1 led to the exclusion of TSC2 exon 26 (from Leu947 to Arg988), producing a short TSC2 isoform. The short TSC2 isoform cannot be phosphorylated at Ser981 by AKT, which resulted in continuous activation of TSC2 in ESCC. The active TSC2 inhibited mTOR via RHEB, leading to continually stimulated oncogenic autophagy of ESCC cells. Conclusions: Our data revealed an important physiological function of tumor suppressor DAZAP1 in autophagy regulation and highlighted the potential of controlling mRNA alternative splicing as an effective therapeutic application for cancers.
Clinical outcomes in men of diverse ethnic backgrounds with metastatic castration-resistant prostate cancer
Authors: S. Halabi, S. Dutta, C.M. Tangen, M. Rosenthal, D.P. Petrylak, I.M. Thompson, K.N. Chi, J.S. De Bono, J.C. Araujo, C. Logothetis, M.A. Eisenberger, D.I. Quinn, K. Fizazi, M.J. Morris, C.S. Higano, I.F. Tannock, E.J. Small, W.K. Kelly
Journal: Annals of Oncology (2020)
Abstract 225: Hands-off Fraction Is Not Negatively Impacted by Deployment of the AutoPulse During Out-of-Hospital Cardiac Arrest
Authors: Lars Wik, Jan-Aage Olsen, David Persse, Fritz Sterz, Michael Lozano, Marc A Brouwer, Mark Westfall, Chris M Souders, Reinhard Malzer, Pierre M van Grunsven, David Travis, Anne Whitehead, Ulrich R Herken, E Brooke Lerner
Journal: Circulation (2011)

Background: Deployment of mechanical chest compression devices is suspected to increase hands-off fraction. A potential benefit of mechanical devices is defibrillation during compressions, but it is unknown if this is utilized in the field. Our objectives were to compare hands-off fraction between manual CPR (M-CPR) and integrated AutoPulse CPR (iA-CPR), and to determine if providers will defibrillate during mechanical compressions. Methods: An international randomized clinical trial of EMS treated adult cardiac arrests of cardiac origin was conducted at 5 sites from March 2009 to January 2011. All EMS providers received 4 hours of training in providing high quality CPR and AutoPulse deployment. After initial manual compressions, patients were randomized to iA-CPR or M-CPR. ECG and impedance or accelerometer data were analyzed to determine the number of compressions per minute, and hands-off fraction was calculated at 10 and 20 minutes. Descriptive statistics and 95% CI were calculated. Results: A total of 4,232 subjects were enrolled. Electronic data were available for 4,135 (98%) cases (2,055 M-CPR, 2,080 iA-CPR). There were 117 (3%) cases with no compression data (69 M-CPR, 48 iA-CPR). There were more compressions per minute in the M-CPR arm (table). The mean hands-off fraction at 10 minutes was 20.4% M-CPR and 21.5% iA-CPR (difference 1.1%; 95% CI 0.5% to 1.7%) and at 20 minutes was 20.2% M-CPR and 19.6% iA-CPR (difference -0.6%; 95% CI -1.2% to 0.1%). Average time to AutoPulse start after defibrillator on was 172 seconds (±183). In 84% of the iA-CPR cases the device was not stopped during the first cycle of resuscitation. 74% of the defibrillated iA-CPR cases were shocked during compressions. Conclusion: This is the first study to document operational deployment of the AutoPulse. There was no difference in hands-off fraction between M-CPR and iA-CPR. Providers without prior experience using the AutoPulse shocked through compressions in the majority of cases.
Resident Burnout
Authors: Ira S. Nash
Journal: Annals of Internal Medicine (2002)

Letters15 October 2002Resident BurnoutIra S. Nash, MDIra S. Nash, MDMount Sinai School of Medicine; New York, NY 10029-6574Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-137-8-200210150-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Although the articles on housestaff burnout by Shanafelt and colleagues (1, 2) and the accompanying editorial by Clever (3) present a disturbing snapshot of the mental health of trainees, they do not take important related issues into account. First, none notes that the difficult working conditions of residents are time limited. One would certainly approach the question of altering working conditions differently if residents were permanently consigned to the demands of a training environment, rather than experiencing them, as they now do, for a few years.Second, none of the pieces addresses the potential consequences of substantial ...Reference1. Shanafelt TD, Bradley KA, Wipf JE, Back AL. Burnout and self-reported patient care in an internal medicine residency program. Ann Intern Med. 2002;136:358-67. [PMID: 11874308] LinkGoogle Scholar2. Collier VU, McCue JD, Markus A, Smith L. Stress in medical residency: status quo after a decade of reform? Ann Intern Med. 2002;136:384-90. [PMID: 11874311] LinkGoogle Scholar3. Clever LH. Who is sicker: patients—or residents? Residents' distress and the care of patients [Editorial]. Ann Intern Med. 2002;136:391-3. [PMID: 11874312] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Ira S. Nash, MDAffiliations: Mount Sinai School of Medicine; New York, NY 10029-6574 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoBurnout and Self-Reported Patient Care in an Internal Medicine Residency Program Tait D. Shanafelt , Katharine A. Bradley , Joyce E. Wipf , and Anthony L. Back Stress in Medical Residency: Status Quo after a Decade of Reform? Virginia U. Collier , Jack D. McCue , Allan Markus , and Lawrence Smith Who Is Sicker: Patients—or Residents? Residents' Distress and the Care of Patients Linda Hawes Clever Resident Burnout W. Robert Graham Resident Burnout Troy Madsen Resident Burnout Anthony L. Back , Joyce E. Wipf , and Tait D. Shanafelt Metrics Cited byBurnout in oral medicine and orofacial pain residentsThe Impact of Duty Hours Restrictions on Job Burnout in Internal Medicine ResidentsResident Burnout 15 October 2002Volume 137, Issue 8Page: 698-699KeywordsForecastingHealth care qualityInstinctPatient advocacyPsychiatry and mental healthResidency ePublished: 15 October 2002 Issue Published: 15 October 2002 Copyright & PermissionsCopyright © 2002 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Roll-out of SARS-CoV-2 testing for healthcare workers at a large NHS Foundation Trust in the United Kingdom, March 2020
Authors: Alexander J Keeley, Cariad Evans, Hayley Colton, Michael Ankcorn, Alison Cope, Amy State, Tracy Bennett, Prosenjit Giri, Thushan I de Silva, Mohammad Raza
Journal: Eurosurveillance (2020)

Healthcare workers (HCW) are potentially at increased risk of infection with coronavirus disease (COVID-19) and may transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to vulnerable patients. We present results from staff testing at Sheffield Teaching Hospitals NHS Foundation Trust, United Kingdom. Between 16 and 29 March 2020, 1,533 symptomatic HCW were tested, of whom 282 (18%) were positive for SARS-CoV-2. Testing HCW is a crucial strategy to optimise staffing levels during this outbreak.
Delay in Retreatment of Helicobacter pylori Infection Increases Risk of Upper Gastrointestinal Bleeding
Authors: Chuan-Guo Guo, Ka Shing Cheung, Feifei Zhang, Esther W. Chan, Lijia Chen, Ian C.K. Wong, Wai K. Leung
Journal: Clinical Gastroenterology and Hepatology (2020)
Adhesion to fibronectin via α5β1 integrin supports expansion of the megakaryocyte lineage in primary myelofibrosis
Authors: Shinobu Matsuura, Cristal Reyna Thompson, Seng Kah Ng, Christina Marie Ward, Aikaterini Karagianni, Carla Mazzeo, Alessandro Malara, Alessandra Balduini, Katya Ravid
Journal: Blood (2020)