tbuckley/cabot-search huggingface dataset:
Exosomal long noncoding RNA HOTTIP as potential novel diagnostic and prognostic biomarker test for gastric cancer
Authors: Rui Zhao, Yanli Zhang, Xin Zhang, Yongmei Yang, Xin Zheng, Xiaohui Li, Yingjie Liu, Yi Zhang
Journal: Molecular Cancer (2018)

Long noncoding RNA HOTTIP plays important roles in the generation and progression of human cancers. Exosomes participate in cellular communication by transmitting moleculars between cells and are regarded as suitable candidates for non-invasive diagnosis. However, the existence of HOTTIP in the circulating exosomes and the potential roles of exosomal HOTTIP in gastric cancer (GC) was poorly understood. This study aims at investigating the clinical roles of exosomal HOTTIP in GC. Serum exosomal HOTTIP from 246 subjects (126 GC patients and 120 healthy people) were detected by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). Our results showed that expression levels of exosomal HOTTIP were typically upregulated in GC than in normal control (P < 0.001). And its expression levels were significantly correlated with invasion depth (P = 0.0298) and TNM stage (P < 0.001). The AUC for exosomal HOTTIP was 0.827, which demonstrated a higher diagnostic capability than CEA, CA 19–9 and CA72–4 (AUC = 0.653, 0.685 and 0.639, respectively) (P < 0.001). The Kaplan–Meier analysis showed a correlation between increased exosomal HOTTIP levels and poor overall survival (OS) (logrank P < 0.001). And univariate and multivariate COX analysis revealed exosomal HOTTIP overexpression was an independent prognostic factor in GC patients (P = 0.027). These findings demonstrated that exosomal HOTTIP may be a potential biomarker for GC in diagnosis and prognosis.
Opening windows for bone remodeling through a SLIT
Authors: Jameel Iqbal, Tony Yuen, Se-Min Kim, Mone Zaidi
Journal: Journal of Clinical Investigation (2018)

Bone formation and resorption are tightly coupled, and dysfunction of either process leads to bone diseases, such as osteoporosis. Bone-forming agents have been explored clinically to increase bone density; however, long-term efficacy of these strategies is limited due to the accompanying increase in resorption in response to increased bone formation. Axonal guidance molecules have recently been shown to regulate formation-resorption coupling and thus have the potential for osteoporosis therapy. In this issue of the JCI, Kim et al. demonstrate that osteoclast-secreted SLIT3 influences bone formation and resorption by promoting osteoblast migration and suppressing osteoclast differentiation. Activation of SLIT3/ROBO signaling in ovariectomized mice increased bone mass, suggesting that SLIT3 should be further explored as a therapeutic target.
Expression of immune checkpoints on circulating tumor cells in men with metastatic prostate cancer (mPC).
Authors: Tian Zhang, Rebecca Garland Austin, Sally E Park, Daniella Runyambo, Rengasamy Boominathan, Chandra Rao, Elizabeth Bronson, Monika Anand, Patrick Healy, Daniel J. George, Megan Ann McNamara, Andrew J. Armstrong
Journal: Journal of Clinical Oncology (2018)

191 Background: Most immune checkpoint inhibitors have shown limited efficacy in unselected men with mPC, and there is limited understanding about which immune checkpoints (ICs) are relevant in mPC. We evaluated ICs on the cell surface of circulating tumor cells (CTCs) in patients with mPC. Methods: Patients were enrolled prospectively at the Duke Cancer Center in three cohorts: A) mCRPC starting the novel androgen receptor inhibitors abiraterone acetate (AA) or enza with or without sipuleucel-T, B) mCRPC with disease progression after AA or enza, and C) metastatic castration sensitive PC. The Cellsearch platform was used to capture EpCAM- and CK-expressing CTCs and analyzed for PD-L1, PD-L2, B7-H3, and CTLA-4 expression at baseline, 12 weeks, and at further disease progression. Results: Through August 2017, we enrolled 4 subjects in cohort A, 7 in cohort B, and 3 in cohort C. CTCs were detectable in every cohort. At baseline, B7-H3 was the most prevalent IC on a per-patient basis (mean 96% in cohort A, and 100% in cohort B, and 88% in cohort C). PD-L1 was detected less frequently (cohort A mean 8%, cohort B mean 42%, and cohort C mean 67%), with evidence of heterogeneity of CTC PD-L1 expression between and within patients. PD-L1 was expressed on 8% of CTCs in cohort C and cohort A, as compared to 28% of CTCs in cohort B, while CTLA-4 expression was not identified in cohort C, 3% of cohort A, and 15% of cohort B. B7H3 was expressed on 68% of cohort C, 91% of cohort A, and 98% of cohort B. PD-L2 was expressed on 0-7% of CTCs overall. Conclusions: Patients with mPC can have detectable and heterogeneous ICs on CTCs, particularly PD-L1 and B7-H3, and these characteristics can be monitored over time. B7-H3 was the most prevalent IC on CTCs, regardless of disease state. Our preliminary data suggests that men with mCRPC post-enza/AA have higher levels of PD-L1 and CTLA-4 expression on their CTCs as compared with men with mHSPC and mCRPC prior to enza/AA. Patient enrollment and analysis are ongoing.
ICU Admission and Mortality Among Elderly Adults
Authors: Valentin Andre, Nadia Aissaoui, François Vincent
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
miR-508 Defines the Stem-like/Mesenchymal Subtype in Colorectal Cancer
Authors: Ting-Ting Yan, Lin-Lin Ren, Chao-Qin Shen, Zhen-Hua Wang, Ya-Nan Yu, Qian Liang, Jia-Yin Tang, Ying-Xuan Chen, Dan-Feng Sun, Witold Zgodzinski, Marek Majewski, Piotr Radwan, Ilona Kryczek, Ming Zhong, Jinxian Chen, Qiang Liu, Weiping Zou, Hao-Yan Chen, Jie Hong, Jing-Yuan Fang
Journal: Cancer Research (2018)

Colorectal cancer includes an invasive stem-like/mesenchymal subtype, but its genetic drivers, functional, and clinical relevance are uncharacterized. Here we report the definition of an altered miRNA signature defining this subtype that includes a major genomic loss of miR-508. Mechanistic investigations showed that this miRNA affected the expression of cadherin CDH1 and the transcription factors ZEB1, SALL4, and BMI1. Loss of miR-508 in colorectal cancer was associated with upregulation of the novel hypoxia-induced long noncoding RNA AK000053. Ectopic expression of miR-508 in colorectal cancer cells blunted epithelial-to-mesenchymal transition (EMT), stemness, migration, and invasive capacity in vitro and in vivo In clinical colorectal cancer specimens, expression of miR-508 negatively correlated with stemness and EMT-associated gene expression and positively correlated with patient survival. Overall, our results showed that miR-508 is a key functional determinant of the stem-like/mesenchymal colorectal cancer subtype and a candidate therapeutic target for its treatment.Significance: These results define a key functional determinant of a stem-like/mesenchymal subtype of colorectal cancers and a candidate therapeutic target for its treatment. Cancer Res; 78(7); 1751-65. ©2018 AACR.
NHS must try outside ideas to boost staff engagement, NHS Employers says
Authors: Matthew Limb
Journal: BMJ (2015)

NHS organisations should explore ideas from other sectors to improve staff engagement, the organisation NHS Employers has said.

A briefing paper by NHS Employers highlights examples from local authorities, social enterprises, and private sector businesses in manufacturing, retail, and finance.1 It says that the NHS has a “proud” record on staff engagement and that it was difficult to make direct exact comparisons with other sectors. Available indicators showed …
Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis
Authors: Y. Bareche, D. Venet, M. Ignatiadis, P. Aftimos, M. Piccart, F. Rothe, C. Sotiriou
Journal: Annals of Oncology (2018)

Recent efforts of genome-wide gene expression profiling analyses have improved our understanding of the biological complexity and diversity of triple-negative breast cancers (TNBCs) reporting, at least six different molecular subtypes of TNBC namely Basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL) and luminal androgen receptor (LAR). However, little is known regarding the potential driving molecular events within each subtype, their difference in survival and response to therapy. Further insight into the underlying genomic alterations is therefore needed.
Calcitonin gene-related peptide (receptor) antibodies: an exciting avenue for migraine treatment
Authors: Antoinette MaassenVanDenBrink, Gisela M. Terwindt, Arn M. J. M. van den Maagdenberg
Journal: Genome Medicine (2018)

Specific prophylactic migraine treatments are urgently needed because of the unmet needs of many migraine patients. Antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor have recently shown efficacy in episodic and chronic migraine and will be available soon.
Heterochromatin Protein 1α Mediates Development and Aggressiveness of Neuroendocrine Prostate Cancer
Authors: Xinpei Ci, Jun Hao, Xin Dong, Stephen Y. Choi, Hui Xue, Rebecca Wu, Sifeng Qu, Peter W. Gout, Fang Zhang, Anne M. Haegert, Ladan Fazli, Francesco Crea, Christopher J. Ong, Amina Zoubeidi, Housheng H. He, Martin E. Gleave, Colin C. Collins, Dong Lin, Yuzhuo Wang
Journal: Cancer Research (2018)

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer arising mostly from adenocarcinoma via neuroendocrine transdifferentiation following androgen deprivation therapy. Mechanisms contributing to both NEPC development and its aggressiveness remain elusive. In light of the fact that hyperchromatic nuclei are a distinguishing histopathologic feature of NEPC, we utilized transcriptomic analyses of our patient-derived xenograft (PDX) models, multiple clinical cohorts, and genetically engineered mouse models to identify 36 heterochromatin-related genes that are significantly enriched in NEPC. Longitudinal analysis using our unique, first-in-field PDX model of adenocarcinoma-to-NEPC transdifferentiation revealed that, among those 36 heterochromatin-related genes, heterochromatin protein 1α (HP1α) expression increased early and steadily during NEPC development and remained elevated in the developed NEPC tumor. Its elevated expression was further confirmed in multiple PDX and clinical NEPC samples.
Supramolecular self assembly of nanodrill-like structures for intracellular delivery
Authors: N. Ashwanikumar, Justin S. Plaut, Barmak Mostofian, Siddharth Patel, Peter Kwak, Conroy Sun, Kerry McPhail, Daniel M. Zuckerman, Sadik C. Esener, Gaurav Sahay
Journal: Journal of Controlled Release (2018)
Surgical training should be provided in a 48 hour week, says surgery college president
Authors: Abi Rimmer
Journal: BMJ (2014)

Surgical training should be provided within a 48 hour week, Ian Ritchie, president of the Royal College of Surgeons of Edinburgh, has said.

Ritchie said that surgical trainees should not have to opt out of the working time regulations to receive enough training. Earlier this year the government said that it would consider how to encourage more doctors to opt out of working time restrictions established to comply with the European Working Time Directive.1

Speaking to BMJ Careers, Ritchie said, “If the legal situation is …
EFFECT OF HOSPITAL VOLUME ON TRANSCATHETER MITRAL VALVE REPAIR (TMVR) OUTCOMES: A NATIONWIDE INPATIENT SAMPLE ANALYSIS
Authors: Nikhil Nalluri, Varun Kumar, Varunsiri Atti, Shilpkumar Arora, Nileshkumar Patel, Deepak Asti, Sushruth Edla, Emad Barsoum, Mohammad Zgheib, Munir Abdallah, Boutros Karam, Sainath Gaddam, Jonathan Spagnola, Roman Royzman, Frank Tamburrino, Gregory Maniatis, Ruben Kandov, James Lafferty, Chad Kliger
Journal: Journal of the American College of Cardiology (2018)
3D MITRAL VALVE QUANTITATION PREDICTS PROCEDURAL SUCCESS DURING TRANSCATHETER MITRAL VALVE REPAIR
Authors: Didem Oguz, Mackram Eleid, Sunil Mankad, Sorin Pislaru, Youssef Maalouf, Vuyisile Nkomo, David Holmes, Guy Reeder, Charanjit Rihal, Jeremy Thaden
Journal: Journal of the American College of Cardiology (2018)
Overnutrition among schoolchildren in India: a review and meta-analysis
Authors: Pratap K Jena, Baliyeri P Jeena
Journal: The Lancet Global Health (2018)

BackgroundObesity continues to be a significant public health concern in India. As half of overweight adults were also overweight during their childhood, estimates of the burden of overweight or obesity among Indian schoolchildren would help to forecast the obesity epidemic among adults. In this context, we did a review and meta-analysis of studies published during past 10 years.MethodsStudies done during 2005–15 that used WHO cut-off points to assess overnutrition (overweight and obesity) among Indian children aged 6–19 years from rural or urban schools were included. Studies that used other diagnostic criteria, focused on specific subgroups such as males, or were done in affluent schools were excluded. Considering the heterogeneity of the studies, random effects and inverse variance heterogeneity models were used for estimating pooled prevalence using MetaXL (version 2.2) software.Findings21 studies involving both boys and girls, covering 81 716 schoolchildren and 11 Indian states, were included. The prevalence of overnutrition in the individual studies ranged between 1·5% and 32·2%. The pooled prevalence estimates of overnutrition in the random effects and inverse variance heterogeneity models were 11·15% (95% CI 8·98–13·51) and 10·56% (5·09–16·74), respectively. In subgroup analysis, boys and urban students had a higher burden of overnutrition than their counterparts. However, the difference in overnutrition prevalence across gender groups was lower than the urban–rural difference. Most of the studies included were of moderate quality and there was heterogeneity among studies.InterpretationOne in nine schoolchildren suffering from overnutrition is a concern as India suffers a dual burden of undernutrition and overnutrition, representing the inequitable distribution of health. Interventions to reduce overnutrition burden and monitoring of overnutrition with the use of a country-specific standard tool is warranted.FundingNone.
Efficacy of Subthreshold Newborn Phototherapy During the Birth Hospitalization in Preventing Readmission for Phototherapy
Authors: Andrea C. Wickremasinghe, Michael W. Kuzniewicz, Charles E. McCulloch, Thomas B. Newman
Journal: JAMA Pediatrics (2018)

Treatment of jaundiced newborns with subthreshold phototherapy (phototherapy given to newborns with bilirubin levels below those recommended in American Academy of Pediatrics [AAP] guidelines) is common. However, the use of subthreshold phototherapy may have risks and increase costs, and, to date, it has not been systematically studied in newborns.To estimate the efficacy of subthreshold phototherapy for newborns with total serum bilirubin (TSB) levels from 0.1 to 3.0 mg/dL below the appropriate AAP phototherapy threshold during the birth hospitalization in preventing readmissions for phototherapy, and to identify predictors of readmission for phototherapy.Retrospective cohort study of 25 895 newborns born at 35 or more weeks' gestation, born in 1 of 16 Kaiser Permanente Northern California hospitals from January 1, 2010, through December 31, 2014, with at least 1 TSB level from 0.1 to 3.0 mg/dL below the appropriate AAP phototherapy threshold and not exceeding the threshold during the birth hospitalization. Data were analyzed from November 1, 2015, to November 28, 2017.Subthreshold phototherapy during the birth hospitalization.Readmission for phototherapy.Among 25 895 newborns with qualifying TSB levels from 0.1 to 3.0 mg/dL below the appropriate AAP phototherapy threshold, 4956 (19.1%) received subthreshold phototherapy and 241 of these (4.9%) were readmitted for phototherapy compared with 2690 of 20 939 untreated newborns (12.8%) (unadjusted odds ratio [OR], 0.35; 95% CI, 0.30-0.40). In a logistic regression model, adjustment for confounding variables, including gestational age, race/ethnicity, formula feedings per day, and the difference between the TSB level and the phototherapy threshold, strengthened the association (OR, 0.28; 95% CI, 0.19-0.40). Estimated numbers needed to treat ranged from 60.8 in the lowest quintile of predicted risk to 6.3 in the highest quintile. Newborns who received formula feedings had lower adjusted odds of readmission for phototherapy compared with exclusively breastfed newborns (OR, 0.58; 95% CI, 0.47-0.72 for >0 to <2 formula feedings per day; OR, 0.24; 95% CI, 0.21-0.27 for ≥6 formula feedings per day). Subthreshold phototherapy was associated with a 22-hour longer length of stay (95% CI, 16-28 hours).Subthreshold phototherapy during the birth hospitalization is effective in preventing readmissions for phototherapy; however, for each readmission prevented, many newborns require phototherapy who would otherwise not need it.
Critical role of phosphodiesterase 2A in mouse congenital heart defects
Authors: Maria Rita Assenza, Federica Barbagallo, Florencia Barrios, Marisa Cornacchione, Federica Campolo, Elisabetta Vivarelli, Daniele Gianfrilli, Luigi Auletta, Andrea Soricelli, Andrea M Isidori, Andrea Lenzi, Manuela Pellegrini, Fabio Naro
Journal: Cardiovascular Research (2018)

Phosphodiesterase 2 A (Pde2A), a cAMP-hydrolysing enzyme, is essential for mouse development; however, the cause of Pde2A knockout embryonic lethality is unknown. To understand whether Pde2A plays a role in cardiac development, hearts of Pde2A deficient embryos were analysed at different stage of development.At the stage of four chambers, Pde2A deficient hearts were enlarged compared to the hearts of Pde2A heterozygous and wild-type. Pde2A knockout embryos revealed cardiac defects such as absence of atrial trabeculation, interventricular septum (IVS) defects, hypertrabeculation and thinning of the myocardial wall and in rare cases they had overriding aorta and valves defects. E14.5 Pde2A knockouts showed reduced cardiomyocyte proliferation and increased apoptosis in the IVS and increased proliferation in the ventricular trabeculae. Analyses of E9.5 Pde2A knockout embryos revealed defects in cardiac progenitor and neural crest markers, increase of Islet1 positive and AP2 positive apoptotic cells. The expression of early cTnI and late Mef2c cardiomyocyte differentiation markers was strongly reduced in Pde2A knockout hearts. The master transcription factors of cardiac development, Tbx, were down-regulated in E14.5 Pde2A knockout hearts. Absence of Pde2A caused an increase of intracellular cAMP level, followed by an up-regulation of the inducible cAMP early repressor, Icer in fetal hearts. In vitro experiments on wild-type fetal cardiomyocytes showed that Tbx gene expression is down-regulated by cAMP inducers. Furthermore, Pde2A inhibition in vivo recapitulated the heart defects observed in Pde2A knockout embryos, affecting cardiac progenitor cells. Interestingly, the expression of Pde2A itself was dramatically affected by Pde2A inhibition, suggesting a potential autoregulatory loop.We demonstrated for the first time a direct relationship between Pde2A impairment and the onset of mouse congenital heart defects, highlighting a novel role for cAMP in cardiac development regulation.
Inequalities in life expectancy are widening, data confirm
Authors: Ingrid Torjesen
Journal: BMJ (2018)

Differences in life expectancy in England between the most and least deprived groups are increasing, particularly among women, data analysed by the Office for National Statistics (ONS) show.1

There was a 0.3 year increase in the difference in life expectancy at birth between the most and least deprived men between 2011 to …
GPs returning to work are offered free RCGP membership
Authors: Abi Rimmer
Journal: BMJ (2016)

GPs who return to work in the UK through a return to practice scheme will receive a year’s free membership of the Royal College of General Practitioners, the college has said.

Last year Health Education England launched an updated induction and refresher scheme for GPs returning to clinical practice, with the support of the RCGP, NHS England, …
Undergraduate course aims to “attract, train, and retain” doctors in Wales
Authors: Abi Rimmer
Journal: BMJ (2014)

Cardiff University has launched an undergraduate medical curriculum designed specifically to “attract, train, and retain the best doctors for Wales.”

Earlier this year Plaid Cymru announced plans to tackle the medical recruitment crisis in Wales, which included paying off student debts.1

Cardiff University trains around 300 medical students each year and hopes that its C21 curriculum will encourage more doctors to remain in …
BMA seeks doctors’ views on final pensions offer
Authors: Helen Jaques
Journal: BMJ (2012)

The BMA is surveying its 130 000 members across the United Kingdom on whether the government’s final offer on reform of the NHS pension scheme is satisfactory.

It is also asking doctors what action they would be prepared to take to defend their pensions should they consider the government’s final offer unacceptable. Possible options are full strike action (complete withdrawal of labour), action short of striking (such as providing an emergency service only), or some alternative action to protest against …
Reply to Soo Hoo and Esquinas: Risk Trajectories of Readmission and Death in the First Year after Hospitalization for Chronic Obstructive Pulmonary Disease: Don’t Shortchange Noninvasive Ventilation
Authors: Peter K. Lindenauer, Kumar Dharmarajan, Harlan M. Krumholz
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

difference between invasive and noninvasive ventilation.Whether the difference can be solely attributed to disease severity or explained by other factors, such as hospital characteristics, remains to be elucidated.
The prognostic value of acute-on-chronic liver failure during the course of severe alcoholic hepatitis
Authors: Thomas Sersté, Alexia Cornillie, Hassane Njimi, Marco Pavesi, Vicente Arroyo, Antonella Putignano, Laura Weichselbaum, Pierre Deltenre, Delphine Degré, Eric Trépo, Christophe Moreno, Thierry Gustot
Journal: Journal of Hepatology (2018)