tbuckley/cabot-search huggingface dataset:
Integrated transcriptomic and regulatory network analyses identify microRNA-200c as a novel repressor of human pluripotent stem cell-derived cardiomyocyte differentiation and maturation
Authors: Ellen Ngar-yun Poon, Baixia Hao, Daogang Guan, Mulin Jun Li, Jun Lu, Yong Yang, Binbin Wu, Stanley Chun-ming Wu, Sarah E Webb, Yan Liang, Andrew L Miller, Xiaoqiang Yao, Junwen Wang, Bin Yan, Kenneth R Boheler
Journal: Cardiovascular Research (2018)

MicroRNAs (miRNAs) are crucial for the post-transcriptional control of protein-encoding genes and together with transcription factors (TFs) regulate gene expression; however, the regulatory activities of miRNAs during cardiac development are only partially understood. In this study, we tested the hypothesis that integrative computational approaches could identify miRNAs that experimentally could be shown to regulate cardiomyogenesis.We integrated expression profiles with bioinformatics analyses of miRNA and TF regulatory programs to identify candidate miRNAs involved with cardiac development. Expression profiling showed that miR-200c, which is not normally detected in adult heart, is progressively down-regulated both during cardiac development and in vitro differentiation of human embryonic stem cells (hESCs) to cardiomyocytes (CMs). We employed computational methodologies to predict target genes of both miR-200c and five key cardiac TFs to identify co-regulated gene networks. The inferred cardiac networks revealed that the cooperative action of miR-200c with these five key TFs, including three (GATA4, SRF and TBX5) targeted by miR-200c, should modulate key processes and pathways necessary for CM development and function. Experimentally, over-expression (OE) of miR-200c in hESC-CMs reduced the mRNA levels of GATA4, SRF and TBX5. Cardiac expression of Ca2+, K+ and Na+ ion channel genes (CACNA1C, KCNJ2 and SCN5A) were also significantly altered by knockdown or OE of miR-200c. Luciferase reporter assays validated miR-200c binding sites on the 3' untranslated region of CACNA1C. In hESC-CMs, elevated miR-200c increased beating frequency, and repressed both Ca2+ influx, mediated by the L-type Ca2+ channel and Ca2+ transients.Our analyses demonstrate that miR-200c represses hESC-CM differentiation and maturation. The integrative computation and experimental approaches described here, when applied more broadly, will enhance our understanding of the interplays between miRNAs and TFs in controlling cardiac development and disease processes.
A Systematic Review of Tools to Measure Respiratory Rate in Order to Identify Childhood Pneumonia
Authors: Amy Sarah Ginsburg, Jennifer L. Lenahan, Rasa Izadnegahdar, J. Mark Ansermino
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Pneumonia is the leading infectious cause of death in children worldwide, with most deaths occurring in developing countries. Measuring respiratory rate is critical to the World Health Organization's guidelines for diagnosing childhood pneumonia in low-resource settings, yet it is difficult to accurately measure. We conducted a systematic review to landscape existing respiratory rate measurement technologies. We searched PubMed, Embase, and Compendex for studies published through September 2017 assessing the accuracy of respiratory rate measurement technologies in children. We identified 16 studies: 2 describing manual devices and 14 describing automated devices. Although both studies describing manual devices took place in low-resource settings, all studies describing automated devices were conducted in well-resourced settings. Direct comparison between studies was complicated by small sample size, absence of a consistent reference standard, and variations in comparison methodology. There is an urgent need for affordable and appropriate innovations that can reliably measure a child's respiratory rate in low-resource settings. Accelerating development or scale-up of these technologies could have the potential to advance childhood pneumonia diagnosis worldwide.
ERAP1-Dependent Antigen Cross-Presentation Determines Efficacy of Adoptive T-cell Therapy in Mice
Authors: Karin Schmidt, Christin Keller, Anja A. Kühl, Ana Textor, Ulrike Seifert, Thomas Blankenstein, Gerald Willimsky, Peter-Michael Kloetzel
Journal: Cancer Research (2018)

Cytotoxic T lymphocytes can reject established tumors if their target peptide is efficiently presented by MHC class I molecules (pMHC-I) on the surface of cancerous cells. Therapeutic success upon adoptive T-cell transfer (ATT), however, requires additional cross-presentation of the same pMHC-I on noncancerous cells. Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an enzyme that customizes the N-terminus of proteasome-generated peptides so they can be loaded onto MHC-I molecules in the endoplasmic reticulum (ER). We show here that ERAP1 is critically involved in the process of tumor rejection and assumes a dual role by independently operating on both sides. Direct presentation of two MHC-I-restricted epitopes of a cancer-driving transplantation rejection antigen through ERAP1 moderately affected tumor rejection by adoptively transferred T-cell receptor gene-modified T cells in each case. ERAP1 expression by antigen cross-presenting cells of the ATT recipients was critical for expansion of therapeutic monospecific T cells and correlated with tumor rejection. Specifically, lack of ERAP1 expression in the ATT recipient's noncancerous cells enabled progression of pMHC-I-positive, IFNγ-responsive tumors, despite the presence of antigen-specific functional cytotoxic T lymphocytes. These data reveal a decisive role for ERAP1 in T-cell-mediated tumor rejection and will enhance the choice of MHC-I-restricted epitopes targeted by adoptive T-cell transfer.Significance: This study demonstrates a role of ERAP1 in the efficacy of adoptive T-cell transfer and has potential to improve personalized T-cell therapy for solid tumors. Cancer Res; 78(12); 3243-54. ©2018 AACR.
In DMARD and steroid naïve early rheumatoid arthritis patients D-vitamin metabolites at baseline do not correlate with initial radiographic status or radiographic progression over 5 years (the CIMESTRA-cohort)
Authors: M. Herly, K. Stengaard-Pedersen, P. Vestergaard, Merete Lund Hetland, K. Hørslev-Petersen, T. Ellingsen
Journal: Annals of the Rheumatic Diseases (2011)
Progress of Multicompartmental Particles for Medical Applications
Authors: Asish C. Misra, Joerg Lahann
Journal: Advanced Healthcare Materials (2018)

Abstract Particulate materials are becoming increasingly used in the literature for medical applications, but translation to the clinical setting has remained challenging as many particle systems face challenges from in vivo barriers. Multicompartmental particles that can incorporate several materials in an individual particle may allow for more intricate control and addressing of issues that otherwise standard particles are unable to. Here, some of the advances made in the use of multicompartmental particles for medical applications are briefly described.
NEW IPSILATERAL BALLOON OCCLUSION TECHNIQUE FOR PERCUTANEOUS CLOSURE AFTER TRANSFEMORAL AORTIC VALVE REPLACEMENT AND COMPARISON WITH ROUTINE CROSSOVER BALLOON OCCLUSION TECHNIQUE
Authors: Sunny Goel, Sabah Siddiqui, Chirag Agarwal, Elliot Borgen, Jacob Shani, Robert Frankel
Journal: Journal of the American College of Cardiology (2018)
Detecting Intestinal Malrotation on Hepatobiliary Scintigraphy
Authors: Lane T. Miner, Mark Tulchinsky
Journal: Clinical Nuclear Medicine (2018)

Abstract Intestinal malrotation displays classic pattern of the small bowel activity on hepatobiliary scintigraphy that could lead to the diagnosis, but only if an interpreting physician looks for it. Presented are 2 cases, one demonstrates diagnostic findings during the first 60-minute phase, whereas the other reveals the diagnosis only on the later sincalide stimulation phase. The currently recommended structured reporting for hepatobiliary scintigraphy does not include examination of bowel activity pattern, which could result in a missed diagnosis. Including interrogation of the small bowel pattern into the structured reporting checklist would ensure consistent detection of this rare but most consequential diagnosis.
DIFFERENCES IN LATE CARDIOVASCULAR MORTALITY FOLLOWING ACUTE MYOCARDIAL INFARCTION AMONG THREE MAJOR ASIAN ETHNICITIES
Authors: Leonardo Carvalho, Fei Gao, Qifeng Chen, Mikael Hartman, Sim Ling Ling, Tian-Hai Koh, David Foo, Chee Tang Chin, Tong Khim Leng, Hean Yee Ong, Gerard Leong, Huay Cheem Tan, Chow Khuan Yew, Mark Richards, Eric Peterson, Terrance Chua, Mark Chan
Journal: Journal of the American College of Cardiology (2013)
Ever-Pregnant Female Blood Donors and Mortality Risk in Male Recipients—Reply
Authors: Rutger A. Middelburg, Camila Caram-Deelder, Johanna G. van der Bom
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Incidence and severity of prostate cancer (PCa) in 792 hypogonadal men with and without long-term testosterone therapy (TTh): Results from a controlled registry study.
Authors: Ahmad Haider, Karim Sultan Haider
Journal: Journal of Clinical Oncology (2018)

167 Background: There is no evidence that TTh in hypogonadal men increases PCa incidence or severity. A US-Scandinavian group recently found that men receiving TTh had lower risk of aggressive PCa (Loeb S et al., J Clin Oncol 2017; 35:1430-6). Methods: 412 men with testosterone ≤350 ng/dL and symptoms received testosterone undecanoate 1000 mg every 3 months for up to 12 years. 380 hypogonadal men (57-74) opted against TTh. Median follow-up: 9 years. Total observation time covered approximately 6,400 patient-years. Prostate volume (PV) and PSA were measured and digital rectal examination/transrectal ultrasound performed before treatment/observation initiation and then every 3-6 months (T-group) or once or twice per year (CTRL). Biopsies were performed when indicated according to EAU guidelines. Results: In the T-group, 11 men (2.7%) were diagnosed with PCa. In CTRL, 34 (8.9%) were diagnosed with PCa. The incidence per 10,000 years was 33 in the T-group and 108 in CTRL. The mean baseline age of PCa patients was 65.2 years in the T-group and 64.3 in CTRL. All PCa diagnoses in the T-group were made within the first 18 months of treatment initiation. In CTRL, PCa was diagnosed at any time during the observation time. In the T-group, radical prostatectomy was performed in all men. All but 1 patient had a Gleason score (GS) ≤6, and all but 1 a predominant GS of 3. Tumor grade was G2 in all 11 (100%), tumor stage T2a in 7 (64%), T2b in 3 (27%), and T2c in 1 (9%) patient(s). In CTRL, radical prostatectomy was performed in all but 6 patients. GS was &gt; 6 in all 34 patients. 7 men had a GS of 7, 17 a GS of 8, and 10 a GS of 9. 2 men had a predominant Gleason score of 3, 22 had 4, and 10 had 5. Tumor grade was G2 in 6 (17.6%) and G3 in 28 (82.4%) patients, tumor stage T2c in 1 (0.3%), T3a in 3 (8.8%), T3b in 13 (38.2%) and T3c in 17 (50%) patients. In CTRL, biochemical recurrence occurred in 8 (23.5%) patients. These patients received androgen deprivation therapy (ADT). 10 (29.4%) patients died of whom 5 were on ADT. In the T-group, there were no biochemical recurrences or deaths during the observation time. Conclusions: In hypogonadal men, TTh may decrease PCa incidence compared to CTRL. PCa was less severe in the T-group.
The Role of Autophagy in the Degradation of Misfolded <scp>HLA</scp>–B27 Heavy Chains
Authors: Fatemeh Navid, Gerlinde Layh‐Schmitt, Keith A. Sikora, Antony Cougnoux, Robert A. Colbert
Journal: Arthritis & Rheumatology (2018)

To determine whether autophagy is involved in the degradation of misfolded HLA-B27 in experimental spondyloarthritis.Bone marrow-derived macrophages from HLA-B27/human β2 -microglobulin (hβ2 m)-transgenic rats were incubated in the presence or absence of interferon-γ and proteasome or autophagy inhibitors. Immunoprecipitation, immunoblotting, and immunofluorescence analysis were used to measure HLA-B27 heavy chains and autophagy. Autophagy was induced using rapamycin. Macrophages from HLA-B7/hβ2 m-transgenic and wild-type rats were used as controls.HLA-B27-expressing macrophages showed phosphatidylethanolamine-conjugated microtubule-associated protein 1 light chain 3B levels similar to those in both control groups, before and after manipulation of autophagy. Blocking autophagic flux with bafilomycin resulted in the accumulation of misfolded HLA-B27 dimers and oligomers as well as monomers, which was comparable with the results of blocking endoplasmic reticulum-associated degradation (ERAD) with the proteasome inhibitor bortezomib. HLA-B7 monomers also accumulated after blocking each degradation pathway. The ubiquitin-to-heavy chain ratio was 2-3-fold lower for HLA-B27 than for HLA-B7. Activation of autophagy with rapamycin rapidly eliminated ~50% of misfolded HLA-B27, while folded HLA-B27 or HLA-B7 monomeric heavy chains were minimally affected.This study is the first to demonstrate that both autophagy and ERAD play roles in the elimination of excess HLA class I heavy chains expressed in transgenic rats. We observed no evidence that HLA-B27 expression modulated the autophagy pathway. Our results suggest that impaired ubiquitination of HLA-B27 may play a role in the accumulation of misfolded disulfide-linked dimers, the elimination of which can be enhanced by activation of autophagy. Manipulation of the autophagy pathway should be further investigated as a potential therapeutic target in spondyloarthritis.
The ABC of change: X, Y, Z
Authors: Susan E Kersley
Journal: BMJ (2004)

Are you part of Generation X? This might influence your attitude to being a doctor and to yourself. And remember, even if you want to reach your goal in a straight line, all too often progress is achieved only via a zigzag path. Do not lose heart, work on your people x ray, keep your zeal, and you will succeed. <b>Susan Kersley</b> explains how
Hemodialysis Induces an Acute Decline in Cerebral Blood Flow in Elderly Patients
Authors: Harmke A. Polinder-Bos, David Vállez García, Johanna Kuipers, Jan Willem J. Elting, Marcel J.H. Aries, Wim P. Krijnen, Henk Groen, Antoon T.M. Willemsen, Peter J. van Laar, Fijanne Strijkert, Gert Luurtsema, Riemer H.J.A. Slart, Ralf Westerhuis, Ron T. Gansevoort, Carlo A.J.M. Gaillard, Casper F.M. Franssen
Journal: Journal of the American Society of Nephrology (2018)

The initiation of hemodialysis is associated with an accelerated decline of cognitive function and an increased incidence of cerebrovascular accidents and white matter lesions. Investigators have hypothesized that the repetitive circulatory stress of hemodialysis induces ischemic cerebral injury, but the mechanism is unclear. We studied the acute effect of conventional hemodialysis on cerebral blood flow (CBF), measured by [ 15 O]H 2 O positron emission tomography–computed tomography (PET-CT). During a single hemodialysis session, three [ 15 O]H 2 O PET-CT scans were performed: before, early after the start of, and at the end of hemodialysis. We used linear mixed models to study global and regional CBF change during hemodialysis. Twelve patients aged ≥65 years (five women, seven men), with a median dialysis vintage of 46 months, completed the study. Mean (±SD) arterial BP declined from 101±11 mm Hg before hemodialysis to 93±17 mm Hg at the end of hemodialysis. From before the start to the end of hemodialysis, global CBF declined significantly by 10%±15%, from a mean of 34.5 to 30.5 ml/100g per minute (difference, −4.1 ml/100 g per minute; 95% confidence interval, −7.3 to −0.9 ml/100 g per minute; P =0.03). CBF decline (20%) was symptomatic in one patient. Regional CBF declined in all volumes of interest, including the frontal, parietal, temporal, and occipital lobes; cerebellum; and thalamus. Higher tympanic temperature, ultrafiltration volume, ultrafiltration rate, and pH significantly associated with lower CBF. Thus, conventional hemodialysis induces a significant reduction in global and regional CBF in elderly patients. Repetitive intradialytic decreases in CBF may be one mechanism by which hemodialysis induces cerebral ischemic injury.
In adults with <i>S aureus</i> bacteremia, adding rifampin to standard antibiotic therapy did not improve outcomes
Authors: Dennis G. Maki
Journal: Annals of Internal Medicine (2018)

Source Citation Thwaites GE, Scarborough M, Szubert A, et al; United Kingdom Clinical Infection Research Group (UKCIRG). Adjunctive rifampin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2017. [Epub ahead of print]. 29249276
Hospitals to be offered cash incentives to increase consultants’ presence out of hours
Authors: Helen Jaques
Journal: BMJ (2012)

Hospitals are to be offered cash incentives to increase the number of senior doctors working overnight and at weekends, the health secretary, Andrew Lansley, has announced.

Rather than insisting that hospitals provide care at weekends, the Department of Health is considering voluntary incentives for the NHS to make 24/7 care a priority, a department spokesman said.

The department plans to use the existing Commissioning for Quality and Innovation (CQUIN) payment framework to encourage service commissioners to strike deals with hospitals to provide more consultants at weekends and evenings.

Research by NHS London last year found that the hospital mortality rate in the city was 0.32% higher …
Mesenchymal stromal cell infusion modulates systemic immunological responses in stable COPD patients: a phase I pilot study
Authors: Jesse Armitage, Dino B.A. Tan, Russel Troedson, Paul Young, Kay-vin Lam, Kathryn Shaw, Marian Sturm, Daniel J. Weiss, Yuben P. Moodley
Journal: European Respiratory Journal (2018)

Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality due to limited therapeutic options for the persistent pulmonary and systemic inflammation that characterises this condition [1]. Recently, pre-clinical studies of mesenchymal stromal cells (MSCs) in COPD demonstrate efficacy in alleviating inflammation and reducing emphysema following either systemic or intra-tracheal administration [2, 3]. Human trials have demonstrated that MSCs did not improve spirometry following their administration to COPD patients; however, it was reported that C-reactive protein (CRP), a marker for systemic inflammation, was reduced 1–3 months after infusion. Earlier time-points were not assessed in detail in these trials, which limits further investigation of these changes [4, 5]. Identifying the fate of intravenously infused MSCs and the potential implications of their biodistribution, as well as short-term MSC-induced systemic changes that were not explored in previous trials will better delineate the utility of MSC treatment for COPD. Mesenchymal stromal cell infusion may provide an alternative immune-based therapeutic option for COPD patients <http://ow.ly/5DpA30hQS6y> The authors thank study participants and staff at Cell and Tissue Therapies WA at Royal Perth Hospital for the preparation and handling of MSCs used in the study. The authors also acknowledge the use of facilities, and the scientific and technical assistance of the Australian Microscopy and Microanalysis Research Facility at the Centre for Microscopy, Characterisation and Analysis, University of Western Australia, a facility funded by the University, State and Commonwealth Governments. We also thank the Medical Research Foundation at Royal Perth Hospital for the use of their laboratory facilities throughout the study. This study was supported by funding from Therapeutics Innovation Australia (TIA) and a National Health and Medical Research Council grant.
Abstract P3-12-11: Disparities in adjuvant hormone adherence in breast cancer patients within a universal healthcare model
Authors: ZW Veitch, OF Khan, D Tilley, X Kostaras, K King, S Lupichuk, P Tang
Journal: Cancer Research (2018)

Abstract Background: Patient adherence to adjuvant hormonal therapy for breast cancer (BC) is correlated with improved survival. Recent publications have demonstrated ethnic disparities in adjuvant hormone adherence (AHA) for privatized healthcare models. Objective: To identify disparities in AHA for BC patients within a universal healthcare system in Alberta, Canada. Methods: Patients diagnosed from 2007-2014 with stage I-III, ER+/HER2- BC receiving adjuvant FECD or DC chemotherapy and at least one month of adjuvant hormonal therapy in Alberta, Canada were retrospectively assessed. Hormone monotherapy (tamoxifen, AI), switch strategies (tam to AI), and treatment duration were collected. Compliance was assessed with central pharmacy data. Patient ethnicity was identified using patient first/last and parental last name via Onolytics® ethnographic software. Ethnicity was further verified using a centrally collected place of birth. Age, AJCC stage, psychiatric diagnoses (mood, bipolar), and comorbidity were collected. Log rank and Chi squared were used to assess difference between adjuvant hormonal therapy for variables at 1, 2, and 5 years. Log rank p-values at 2 years are reported. Results: A total of 2,399 ER+ patients were included for analysis. AHA was non-significant for ethnicity (p=0.797), comorbidity (p=0.623), psychiatric disorders (p=0.145), or elderly cohorts (p= 0.814). AHA by stage was significant with stage III &amp;gt; II &amp;gt; I (p=0.004) having the highest compliance rates. AHA was highest for planned hormonal switch strategies (p=0.004) compared to monotherapy. Hormone Adherence RatesCharacteristicsNo. of Patients% AdherenceEthnicity Caucasian211891.6Asian15293.4Middle Eastern/African9593.7Hispanic2491.7Age &amp;lt;65207791.8&amp;gt;6534192.1Comorbidity 096191.21-3134392.2&amp;gt;311493Psychiatric Dx Yes31189.7No210792.1Stage I45388.3II151292.1III45394.5Hormone Strategy Monotherapy173190.9Switch68794.2 Conclusion: AHA is not dependent on ethnicity, age, comorbidity, or psychiatric diagnosis in a universal healthcare model. Conversely, higher rates of AHA are seen with planned switch strategy compared to monotherapy, contradictory to the BIG I-98 trial. Patients with higher stage, and thus higher risk of BC recurrence have increased adherence compared to their low risk counterparts. Reinforcement of AHA for low/moderate risk BC patients, in addition to tamoxifen to AI switch strategies may improve overall adherence. Citation Format: Veitch ZW, Khan OF, Tilley D, Kostaras X, King K, Lupichuk S, Tang P. Disparities in adjuvant hormone adherence in breast cancer patients within a universal healthcare model [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-12-11.