tbuckley/cabot-search huggingface dataset:
Abstract P049: Mitochondrial DNA Copy Number and Diabetes in the ARIC Study
Authors: Bailey DeBarmore, Foram Ashar, Dan Arking, Rita Kalyani, Eliseo Guallar, YiYi Zhang, Elizabeth Selvin, J. Hunter Young
Journal: Circulation (2017)

Introduction: In the United States, the rising number of adults with type 2 diabetes (T2D) is thought to be associated with the rise in obesity. Obesity may be associated with T2D through biologic pathways where excess weight strains the body’s metabolic machinery, such as mitochondria. Mitochondria are dynamic organelles whose regulation and function respond to cell stress, such as insulin resistance. Previous research reveals that insulin resistance is associated with obesity prior to hyperglycemia. Mitochondrial DNA copy number is a measure of mitochondrial DNA content, and correlates with both the number and size of mitochondria. We assessed the hypothesis that mitochondrial DNA copy number is associated with T2D in a community-based, prospective cohort study. A lower mitochondrial DNA copy number in these analyses represents worse mitochondrial function. Methods: We included 6,633 white ARIC participants without coronary heart disease who had mitochondrial DNA copy number measured from visit 2 (1990-1992). Our sample had a mean age of 57 ± 5.6 years, was 43% male, average BMI of 27 ± 4.9 kg/m2, and 27% with hypertension. Those with diabetes had an average hemoglobin A 1c of 7.2 ± 1.8 (n=681). The mitochondrial DNA copy number value used in analyses represents a sample’s standard deviation (SD) from a mean of zero for age- and sex-adjusted distributions. The mitochondrial DNA copy number data was then divided into quintiles, with the most negative mitochondrial DNA copy number in quintile 1 (Q1), the mean of zero in Q3, and the most positive in Q5. We defined T2D as self-report of doctor diagnosis, current use of glucose-lowering medication, or fasting blood glucose ≥ 126 mg/dL or non-fasting blood glucose ≥ 200 mg/dL measured at study visits. We used logistic regression to estimate the odds of prevalent T2D for each quintile group compared to Q3. Confounders considered in the base model included age at sample collection, sex, education level, and medication use (thyroid and estrogen). All analyses were done in Stata 14.1. Results: The prevalence of T2D was higher in the lower mitochondrial DNA copy number quintiles: 15% in Q1 (mean copy number: -1.40 SD) 11% in Q2 (-0.46 SD), and 9% in Q3-Q5 (0.04 SD, 0.52 SD, 1.33 SD). There was increased odds of T2D in lower mitochondrial DNA copy number quintiles, but with no additional benefit of copy number above the mean. The odds of T2D in each quintile compared to Q3 was 1.9 in Q1 (95% CI 1.49, 2.46), 1.36 in Q2 (95% CI 1.05, 1.77), 0.99 in Q4 (95% CI 0.76, 1.30) and 0.96 in Q5 (95% CI 0.74, 1.26). Conclusion: Examining the association of mitochondrial dysfunction and diabetes in a large community-based cohort connects results from experimental studies to epidemiologic studies and provides the opportunity to characterize the complex pathogenesis of diabetes using cohort data.
Allergen‐specific IgG<sub>4</sub> over time: Observation among adults with hydrolyzed wheat protein allergy
Authors: Yuma Fukutomi, Yuya Teruuchi, Eiji Nakatani, Takafumi Minami, Yoshikiyo Sasagawa, Masao Fukushima, Yosuke Kamide, Kiyoshi Sekiya, Hirohisa Saito, Reiko Teshima, Reiko Adachi, Masami Taniguchi
Journal: Allergy (2019)

YF has received fees for lectures from Thermo Fisher Diagnostics KK, Torii Pharmaceutical Co., Ltd, Kyorin Pharmaceutical Company, Novartis Pharma KK, MSD KK, and Taiho Pharmaceutical Co., Ltd., outside the submitted work. YT, YS, and MF are employees of Nitto Boseki Co., Ltd. (parent company of Nittobo Medical Co., Ltd.). YT is the inventor of patent “Anti-human IgG4 monoclonal antibody and human IgG4 assay reagent using the antibody” in which Nitto Boseki Co., Ltd., is pending. HS reports personal fees from Shiseido Co., Ltd., and AstraZeneca, outside the submitted work. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Randomised controlled trial: effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months
Authors: Candice L Downey, Susan Bewley
Journal: BMJ (2012)

The paper

“Randomised controlled trial: effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months” by Ola Andersson and colleagues ( BMJ 2011;343:d7157, doi:10.1136/bmj.d7157)

Abstract

Objective— To investigate the effects of delayed umbilical cord clamping, compared with early clamping, on infant iron status at 4 months of age in a European setting.

Design— Randomised controlled trial.

Setting—Swedish county hospital.

Participants— 400 full term infants born after a low risk pregnancy.

Intervention— Infants were randomised to delayed umbilical cord clamping (≥180 seconds after delivery) or early clamping (≤10 seconds after delivery).

Main outcome measures— Haemoglobin and iron status at 4 months of age with the power estimate based on serum ferritin levels. Secondary outcomes included neonatal anaemia, early respiratory symptoms, polycythaemia, and need for phototherapy.

Results— At 4 months of age, infants showed no significant differences in haemoglobin concentration between the groups, but infants subjected to delayed cord clamping had 45% (95% confidence interval 23% to 71%) higher mean ferritin concentration (117 μg/L v 81 μg/L, P<0.001) and a lower prevalence of iron deficiency (1 (0.6%) v 10 (5.7%), P=0.01, relative risk reduction 0.90; number needed to treat=20 (17 to 67)). As for secondary outcomes, the delayed cord clamping group had lower prevalence of neonatal anaemia at 2 days of age (2 (1.2%) v 10 (6.3%), P=0.02, relative risk reduction 0.80, number needed to treat 20 (15 to 111)). There were no significant differences between groups in postnatal respiratory symptoms, polycythaemia, or hyperbilirubinaemia requiring phototherapy.

Conclusions— Delayed cord clamping, compared with early clamping, resulted in improved iron status and reduced prevalence of iron deficiency at 4 months of age, and reduced prevalence of neonatal anaemia, without demonstrable adverse effects. As iron deficiency in infants even without anaemia has been associated with impaired development, …
An American revolution?
Authors: Athalia Rachel Pyzer
Journal: BMJ (2010)

“Do you know what NICE is?” an enthusiastic protester asks me outside a library in Boston. “Yes I do,” I reply in the most proper English accent I can summon. “Oh,” he is taken aback, “So you know our president wants to give us the same socialised health care you folks suffer in England?” We enter into a heated debate over our imperialist monarch, who employs Tony Blair as her henchman, I’m told.

While abroad, enjoying the summer holiday before my fifth year, a healthcare revolution was being plotted in Washington, DC. President Barack Obama wants to make it easier and cheaper for US residents to buy health insurance, without …
Lifting the lid
Authors: Matthew Billingsley
Journal: BMJ (2015)

One in four people will have a mental health problem, yet the medical profession has difficulty in dealing with mental ill health within its own workforce. Mental health remains a taboo subject particularly among medical students. Anna Sayburn takes a look at why this is and the barriers to seeking help (doi:10.1136/sbmj.h722).

Hearing a medical student say “I’m struggling” might be perceived by some as an admission of failure after years of high achievement. You may worry that being exposed as someone who needs help might be penalised by your medical school or the General Medical Council, leaving your dream of being a doctor in tatters.

But this is not true. Your medical school has a duty to support you so that you succeed in becoming a doctor. …
Targeting monocyte-intrinsic enhancer reprogramming improves immunotherapy efficacy in hepatocellular carcinoma
Authors: Man Liu, Jingying Zhou, Xiaoyu Liu, Yu Feng, Weiqin Yang, Feng Wu, Otto Ka-Wing Cheung, Hanyong Sun, Xuezhen Zeng, Wenshu Tang, Myth T S Mok, John Wong, Philip Chun Yeung, Paul Bo San Lai, Zhiwei Chen, Hongchuan Jin, Jie Chen, Stephen Lam Chan, Anthony W H Chan, Ka Fai To, Joseph J Y Sung, Minhu Chen, Alfred Sze-Lok Cheng
Journal: Gut (2019)

Hepatocellular carcinoma (HCC), mostly developed in fibrotic/cirrhotic liver, exhibits relatively low responsiveness to immune checkpoint blockade (ICB) therapy. As myeloid-derived suppressor cell (MDSC) is pivotal for immunosuppression, we investigated its role and regulation in the fibrotic microenvironment with an aim of developing mechanism-based combination immunotherapy.Functional significance of MDSCs was evaluated by flow cytometry using two orthotopic HCC models in fibrotic liver setting via carbon tetrachloride or high-fat high-carbohydrate diet and verified by clinical specimens. Mechanistic studies were conducted in human hepatic stellate cell (HSC)-peripheral blood mononuclear cell culture systems and fibrotic-HCC patient-derived MDSCs. The efficacy of single or combined therapy with anti-programmed death-1-ligand-1 (anti-PD-L1) and a clinically trialled BET bromodomain inhibitor i-BET762 was determined.Accumulation of monocytic MDSCs (M-MDSCs), but not polymorphonuclear MDSCs, in fibrotic livers significantly correlated with reduced tumour-infiltrating lymphocytes (TILs) and increased tumorigenicity in both mouse models. In human HCCs, the tumour-surrounding fibrotic livers were markedly enriched with M-MDSC, with its surrogate marker CD33 significantly associated with aggressive tumour phenotypes and poor survival rates. Mechanistically, activated HSCs induced monocyte-intrinsic p38 MAPK signalling to trigger enhancer reprogramming for M-MDSC development and immunosuppression. Treatment with p38 MAPK inhibitor abrogated HSC-M-MDSC crosstalk to prevent HCC growth. Concomitant with patient-derived M-MDSC suppression by i-BET762, combined treatment with anti-PD-L1 synergistically enhanced TILs, resulting in tumour eradication and prolonged survival in the fibrotic-HCC mouse model.Our results signify how non-tumour-intrinsic properties in the desmoplastic microenvironment can be exploited to reinstate immunosurveillance, providing readily translatable combination strategies to empower HCC immunotherapy.
How to get the most out of your placement in general practice
Authors: Matilda Esan, Kamila Hawthorne, David Thomas
Journal: BMJ (2017)

A placement in primary care provides a great opportunity to see a wide range of conditions and to practise a patient centred approach to consultations #### This article contains... Working as a general practitioner requires a broad range of skills. You need to be able to diagnose a wide range of undifferentiated health problems, treat illness in the community, respond to risk safely and effectively, prevent disease, manage long term conditions, and coordinate care with allied healthcare professionals. Some of the major challenges of being a GP include having a large and diverse range of patients, managing patients with multiple health conditions who take numerous drugs, working independently, and using your clinical acumen rather than having quick access to tests and investigations. All this—as well as being a gatekeeper of NHS resources—requires a high volume of daily decision making. However, being able to help a variety of people of different ages and with different ailments, from cradle to grave, is a great privilege. One of the benefits of being a student on a GP placement is that general practice takes a holistic, patient centred approach to problem solving. This is one of the General Medical Council’s curriculum requirements, and all medical schools are required to ensure that their students are well equipped with this skill.1 In this article, we provide some advice on how to make the most of your GP placement. #### Box 1: Facts about general practice in the NHS
Convalescent plasma therapy for persistent hepatitis E virus infection
Authors: Michael Ankcorn, Jennifer Gallacher, Samreen Ijaz, Yusri Taha, Heli Harvala, Sheila Maclennan, Emma C. Thomson, Chris Davis, Joshua B. Singer, Ana da Silva Filipe, Katherine Smollett, Marc Niebel, Malcolm G. Semple, Richard S. Tedder, Stuart McPherson
Journal: Journal of Hepatology (2019)
Effect of domiciliary oxygen therapy on exercise capacity and quality of life in patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension: a randomised, placebo-controlled trial
Authors: Silvia Ulrich, Stéphanie Saxer, Elisabeth D. Hasler, Esther I. Schwarz, Simon R. Schneider, Michael Furian, Patrick R. Bader, Mona Lichtblau, Konrad E. Bloch
Journal: European Respiratory Journal (2019)

Study question We investigated whether domiciliary oxygen therapy (DOXT) increases exercise capacity and quality of life in patients with pulmonary arterial or distal chronic thromboembolic pulmonary hypertension (PAH/CTEPH) presenting with mild resting hypoxaemia and exercise-induced oxygen desaturation. Materials and methods 30 patients with PAH/CTEPH, mean± sd age 60±15 years, pulmonary artery pressure 39±11 mmHg, resting arterial oxygen saturation measured by pulse oximetry ( S pO 2 ) ≥90%, S pO 2 drop during a 6-min walk test ≥4%, on pulmonary hypertension-targeted medication, were randomised in a double-blind crossover protocol to DOXT and placebo (ambient air) treatment, each over 5 weeks, at 3 L·min −1 via nasal cannula overnight and when resting during the day. Treatment periods were separated by 2 weeks of washout. Co-primary outcomes were changes in 6-min walk distance (6MWD, breathing ambient air) and physical functioning scale of the 36-item short-form medical outcome questionnaire during treatment periods. Results DOXT increased the 6MWD from baseline 478±113 m by a mean (95% CI) of 19 (6–32) m, and physical functioning from 52±29 by 4 (0–8) points. Corresponding changes with placebo were 1 (−11–13) m in 6MWD and −2 (−6–2) points in physical functioning. Between-treatment differences in changes were 6MWD 18 (1–35) m (p=0.042) and physical functioning 6 (1–11) points (p=0.029). DOXT significantly improved the New York Heart Association functional class versus placebo. Answer to the question This first randomised trial in PAH/CTEPH patients with exercise-induced hypoxaemia demonstrates that DOXT improves exercise capacity, quality of life and functional class. The results support large long-term randomised trials of DOXT in PAH/CTEPH.
Can Circulating Tumor DNA in Early-Stage Colorectal Cancer Be More Than a Prognostic Biomarker?
Authors: Van Morris, Arvind Dasari, Scott Kopetz
Journal: JAMA Oncology (2019)

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 Oncology 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 Oncology journal
Addition of cyclic angiotensin-(1-7) to angiotensin-converting enzyme inhibitor therapy has a positive add-on effect in experimental diabetic nephropathy
Authors: Paola Cassis, Monica Locatelli, Daniela Corna, Sebastian Villa, Daniela Rottoli, Domenico Cerullo, Mauro Abbate, Giuseppe Remuzzi, Ariela Benigni, Carlamaria Zoja
Journal: Kidney International (2019)
Food, inglorious food: how hospital food is bad for patients
Authors: Alexander S Romain
Journal: BMJ (2010)

On my first clinical placement I encountered the National Health Service sausage hotpot, typical of a meal served thousands of times each week to patients throughout the United Kingdom: an orange lake of dehydrated sausages embedded in mashed potato. One junior doctor smiled at my fascination with the cuisine, “I hope your cat hasn’t gone missing.” Fortunately she hadn’t, but it turned out that the term “mystery meat” was used affectionately by doctors at the hospital.

Poor quality food is deeply entrenched in the NHS. As my …
Abstract P5-10-04: Exome sequencing in high breast and ovarian cancer incidence families which lack detectable mutations in established cancer susceptibility genes
Authors: PA Kenny, MA Girtman, JA Deviley, DR Meier, CR Vos, CS Richmond, KA Lofgren
Journal: Cancer Research (2019)

Abstract At our center, a standard 25 gene panel has proved useful for the identification of pathogenic germline mutations in many families with a high penetrance of breast and ovarian cancer, yet there remain several families with very high cancer incidence but from whom these assays have not identified pathogenic alleles. To attempt to define the genetic mechanism of susceptibility in such cases, are conducting germline whole exome sequencing in affected individuals. Here we describe the identification of strong candidate susceptibility variants in two such families. Both variants cause loss-of-function of DNA repair genes not previously implicated in breast cancer, but which share properties with genes with known roles in maintenance of genome integrity. In one individual, with a personal history of ovarian cancer and two independent breast tumors, we identified a novel point mutation in POLD2 which introduces a mutation at a residue which is biochemically conserved in all animal species thus far sequenced. In the second individual, a frameshift mutation was detected in ERCC4. In both cases, the variants found have not been observed in large exome datasets (e.g. ExAC) or reported in ClinVar. Our study highlights the potential utility of whole exome sequencing as a discovery tool in those families with high cancer incidence yet which lack mutations in known hereditary cancer predisposition genes. Citation Format: Kenny PA, Girtman MA, Deviley JA, Meier DR, Vos CR, Richmond CS, Lofgren KA. Exome sequencing in high breast and ovarian cancer incidence families which lack detectable mutations in established cancer susceptibility genes [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-10-04.
Christopher Roy Barraclough
Authors: Laura Barraclough, Evelith Barraclough
Journal: BMJ (2019)

Christopher Roy Barraclough was born in Dewsbury, Yorkshire, on 28 February 1948. He studied medicine at the University of St Andrews and graduated in 1970. His first house jobs were at the Doncaster Royal Infirmary. Subsequently, he moved to Birmingham and …
Translation of the circular RNA circβ-catenin promotes liver cancer cell growth through activation of the Wnt pathway
Authors: Wei-Cheng Liang, Cheuk-Wa Wong, Pu-Ping Liang, Mai Shi, Ye Cao, Shi-Tao Rao, Stephen Kwok-Wing Tsui, Mary Miu-Yee Waye, Qi Zhang, Wei-Ming Fu, Jin-Fang Zhang
Journal: Genome biology (2019)

Circular RNAs are a class of regulatory RNA transcripts, which are ubiquitously expressed in eukaryotes. In the current study, we evaluate the function of a novel circRNA derived from the β-catenin gene locus, circβ-catenin. Circβ-catenin is predominantly localized in the cytoplasm and displays resistance to RNase-R treatment. We find that circβ-catenin is highly expressed in liver cancer tissues when compared to adjacent normal tissues. Silencing of circβ-catenin significantly suppresses malignant phenotypes in vitro and in vivo, and knockdown of this circRNA reduces the protein level of β-catenin without affecting its mRNA level. We show that circβ-catenin affects a wide spectrum of Wnt pathway-related genes, and furthermore, circβ-catenin produces a novel 370-amino acid β-catenin isoform that uses the start codon as the linear β-catenin mRNA transcript and translation is terminated at a new stop codon created by circularization. We find that this novel isoform can stabilize full-length β-catenin by antagonizing GSK3β-induced β-catenin phosphorylation and degradation, leading to activation of the Wnt pathway. Our findings illustrate a non-canonical function of circRNA in modulating liver cancer cell growth through the Wnt pathway, which can provide novel mechanistic insights into the underlying mechanisms of hepatocellular carcinoma.
Abstract P3-07-03: Withdrawn
Authors: AL Rinkenbaugh, VC Sinha, X Zhang, J Shao, H Piwnica-Worms
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Rinkenbaugh AL, Sinha VC, Zhang X, Shao J, Piwnica-Worms H. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-07-03.
Abstract P3-07-11: Withdrawn
Authors: HW Jackson, JR Fischer, VR Zanotelli, SD Soysal, M Simone, WP Weber, B Bodenmiller
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Jackson HW, Fischer JR, Zanotelli VR, Soysal SD, Simone M, Weber WP, Bodenmiller B. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-07-11.
Association of Brain Atrophy and Masseter Sarcopenia With 1-Year Mortality in Older Trauma Patients
Authors: Christopher Tanabe, May J. Reed, Tam N. Pham, Kevin Penn, Itay Bentov, Stephen J. Kaplan
Journal: JAMA Surgery (2019)

Older adults are disproportionately affected by trauma and accounted for 47% of trauma fatalities in 2016. In many populations and disease processes, described risk factors for poor clinical outcomes include sarcopenia and brain atrophy, but these remain to be fully characterized in older trauma patients. Sarcopenia and brain atrophy may be opportunistically evaluated via head computed tomography, which is often performed during the initial trauma evaluation.
Cardiogenic Shock in Takotsubo Cardiomyopathy Versus Acute Myocardial Infarction
Authors: Saraschandra Vallabhajosyula, Shannon M. Dunlay, Dennis H. Murphree, Gregory W. Barsness, Gurpreet S. Sandhu, Amir Lerman, Abhiram Prasad
Journal: JACC Heart Failure (2019)