tbuckley/cabot-search huggingface dataset:
Health of 1.8 billion children is at serious risk from air pollution, says WHO
Authors: Zosia Kmietowicz
Journal: BMJ (2018)

The World Health Organization has made an urgent call to action to reduce air pollution in order to protect children’s health.

Health professionals have a central role to play in this effort, says a report on the effects of air pollution on children.1

“Health effects experienced early in life can increase a child’s future risk of disease and lead to lifelong consequences. A child who is exposed to unsafe levels of pollution early in life can thus suffer a ‘life sentence’ of illness,” it says. “Health professionals are well positioned to communicate with families, communities, …
Polyvascular disease, type 2 diabetes, and long-term vascular risk: a secondary analysis of the IMPROVE-IT trial
Authors: Marc P Bonaca, J Antonio Gutierrez, Christopher Cannon, Robert Giugliano, Michael Blazing, Jeong-Gun Park, Jennifer White, Andrew Tershakovec, Eugene Braunwald
Journal: The Lancet Diabetes & Endocrinology (2018)
Redirected T Cell Cytotoxicity in Cancer Therapy
Authors: Raphael A. Clynes, John R. Desjarlais
Journal: Annual Review of Medicine (2018)

Bispecific antibodies that recruit and redirect T cells to attack tumor cells have tremendous potential for the treatment of various malignancies. In general, this class of therapeutics, known as CD3 bispecifics, promotes tumor cell killing by cross-linking a CD3 component of the T cell receptor complex with a tumor-associated antigen on the surface of the target cell. Importantly, this mechanism does not rely on a cognate interaction between the T cell receptor and a peptide:HLA complex, thereby circumventing HLA (human leukocyte antigen) restriction. Hence, CD3 bispecifics may find a key role in addressing tumors with low neoantigen content and/or low inflammation, and this class of therapeutics may productively combine with checkpoint blockade. A wide array of formats and optimization approaches has been developed, and a wave of CD3 bispecifics is proceeding into human clinical trials for a range of indications, with promising signs of therapeutic activity.
Transcription Factor 21 Is Required for Branching Morphogenesis and Regulates the Gdnf-Axis in Kidney Development
Authors: Shintaro Ide, Gal Finer, Yoshiro Maezawa, Tuncer Onay, Tomokazu Souma, Rizaldy Scott, Kana Ide, Yoshihiro Akimoto, Chengjin Li, Minghao Ye, Xiangmin Zhao, Yusuke Baba, Takuya Minamizuka, Jing Jin, Minoru Takemoto, Koutaro Yokote, Susan E. Quaggin
Journal: Journal of the American Society of Nephrology (2018)

Background The mammalian kidney develops through reciprocal inductive signals between the metanephric mesenchyme and ureteric bud. Transcription factor 21 (Tcf21) is highly expressed in the metanephric mesenchyme, including Six2-expressing cap mesenchyme and Foxd1-expressing stromal mesenchyme. Tcf21 knockout mice die in the perinatal period from severe renal hypodysplasia. In humans, Tcf21 mRNA levels are reduced in renal tissue from human fetuses with renal dysplasia. The molecular mechanisms underlying these renal defects are not yet known. Methods Using a variety of techniques to assess kidney development and gene expression, we compared the phenotypes of wild-type mice, mice with germline deletion of the Tcf21 gene, mice with stromal mesenchyme–specific Tcf21 deletion, and mice with cap mesenchyme–specific Tcf21 deletion. Results Germline deletion of Tcf21 leads to impaired ureteric bud branching and is accompanied by downregulated expression of Gdnf-Ret-Wnt11 , a key pathway required for branching morphogenesis. Selective removal of Tcf21 from the renal stroma is also associated with attenuation of the Gdnf signaling axis and leads to a defect in ureteric bud branching, a paucity of collecting ducts, and a defect in urine concentration capacity. In contrast, deletion of Tcf21 from the cap mesenchyme leads to abnormal glomerulogenesis and massive proteinuria, but no downregulation of Gdnf-Ret-Wnt11 or obvious defect in branching. Conclusions Our findings indicate that Tcf21 has distinct roles in the cap mesenchyme and stromal mesenchyme compartments during kidney development and suggest that Tcf21 regulates key molecular pathways required for branching morphogenesis.
A Phase 1 Dose Escalation Study of ARQ 531 in Selected Patients with Relapsed or Refractory Hematologic Malignancies
Authors: Jennifer A. Woyach, Ian W. Flinn, Deborah M. Stephens, Farrukh T. Awan, Kerry A. Rogers, Sean D. Reiff, Ron E. Savage, Sudharshan Eathiraj, Lyndsey A. Szuszkiewicz, Kate Tith, John C. Byrd
Journal: Blood (2018)
Carcinogenicity of some nitrobenzenes and other industrial chemicals
Authors: M Van den Berg, R Cattley, J W Cherrie, D C Dorman, J K Dunnick, J M Gohlke, J Jinot, H U Käfferlein, L Kopylev, M Matsumoto, T Nomiyama, K Ogawa, L Perbellini, H Sone, Y Grosse, K Z Guyton, M K Schubauer-Berigan, F El Ghissassi, V Bouvard, L Benbrahim-Tallaa, A Hall, A Paul, H Mattock, K Straif
Journal: The Lancet Oncology (2018)
Cellular Plasticity in Liver Regeneration: Spotlight on Cholangiocytes
Authors: Janina E.E. Tirnitz‐Parker, Stuart J. Forbes, John K. Olynyk, Grant A. Ramm
Journal: Hepatology (2018)

Tirnitz‐Parker, Janina E.E. M.Sc., Ph.D.; Forbes, Stuart J. M.B.Ch.B., B.Sc., M.R.C.P., Ph.D., F.R.C.P.; Olynyk, John K. B.Med.Sc., M.B.B.S., F.R.A.C.P., M.D., F.A.A.S.L.D., A.G.A.F.; Ramm, Grant A. B.Sc., Ph.D., F.A.A.S.L.D.Editor(s): Corey, Kathleen E.8; Malhi, Harmeet9 Author Information
Landscape of genomic alterations in high-grade serous ovarian cancer from exceptional long- and short-term survivors
Authors: S. Y. Cindy Yang, Stephanie Lheureux, Katherine Karakasis, Julia V. Burnier, Jeffery P. Bruce, Derek L. Clouthier, Arnavaz Danesh, Rene Quevedo, Mark Dowar, Youstina Hanna, Tiantian Li, Lin Lu, Wei Xu, Blaise A. Clarke, Pamela S. Ohashi, Patricia A. Shaw, Trevor J. Pugh, Amit M. Oza
Journal: Genome Medicine (2018)

Patients diagnosed with high-grade serous ovarian cancer (HGSOC) who received initial debulking surgery followed by platinum-based chemotherapy can experience highly variable clinical responses. A small percentage of women experience exceptional long-term survival (long term (LT), 10+ years), while others develop primary resistance to therapy and succumb to disease in less than 2 years (short term (ST)). To improve clinical management of HGSOC, there is a need to better characterize clinical and molecular profiles to identify factors that underpin these disparate survival responses. To identify clinical and tumor molecular biomarkers associated with exceptional clinical response or resistance, we conducted an integrated clinical, exome, and transcriptome analysis of 41 primary tumors from LT (n = 20) and ST (n = 21) HGSOC patients. Younger age at diagnosis, no residual disease post debulking surgery and low CA125 levels following surgery and chemotherapy were clinical characteristics of LT. Tumors from LT survivors had increased somatic mutation burden (median 1.62 vs. 1.22 non-synonymous mutations/Mbp), frequent BRCA1/2 biallelic inactivation through mutation and loss of heterozygosity, and enrichment of activated CD4+, CD8+ T cells, and effector memory CD4+ T cells. Characteristics of ST survival included focal copy number gain of CCNE1, lack of BRCA mutation signature, low homologous recombination deficiency scores, and the presence of ESR1-CCDC170 gene fusion. Our findings suggest that exceptional long- or short-term survival is determined by a concert of clinical, molecular, and microenvironment factors.
Response to: ‘Comment on: ‘Lupus Low Disease Activity State(LLDAS) attainment discriminates responders in a systemic lupus erythematosus trial: post-hocanalysis of the Phase IIb MUSE trial of anifrolumab’ by Eric Morand et al’ by Isenberg
Authors: Eric F Morand, Teodora Trasieva, Anna Berglind, Gabor Illei, Raj Tummala
Journal: Annals of the Rheumatic Diseases (2018)

error occurred, which was a discussion of the need for evidence that the physician global assessment adequately captures gastrointestinal activity in SLE.
Health Care in the 2018 Election
Authors: Robert J. Blendon, John M. Benson, Caitlin L. McMurtry
Journal: New England Journal of Medicine (2018)

Health Care in the 2018 Election Polls indicate that health care is the number one issue for Democrats in deciding their votes in the 2018 elections, but it is not among the top five for Republicans. Most Democrats support the ACA and “Medicare for all,” and most Republicans oppose these policies.
Assessing Patient-Reported Outcomes in People with Myelodysplastic Syndromes: Can a Customized Selection of Items from the EORTC Library Enhance the EORTC QLQ-C30?
Authors: Jill A Bell, Farrah A Pompilus, Anna Christian, Flora Mazerolle, Fatima Scipione, Rafael Bejar, Aaron Galaznik, Robert J. Fram, Douglas V. Faller, Stefan Cano, Antoine Regnault
Journal: Blood (2018)
Role of liver and spleen stiffness in predicting the recurrence of hepatocellular carcinoma after resection
Authors: Giovanni Marasco, Antonio Colecchia, Agostino Colli, Federico Ravaioli, Giovanni Casazza, Maria Letizia Bacchi Reggiani, Alessandro Cucchetti, Matteo Cescon, Davide Festi
Journal: Journal of Hepatology (2018)
Frailty, Psychoactive Medications, and Cognitive Dysfunction Are Associated With Poor Patient‐Reported Outcomes in Cirrhosis
Authors: Elliot B. Tapper, Jad Baki, Neehar D. Parikh, Anna S. Lok
Journal: Hepatology (2018)

Cirrhosis is associated with disabling symptoms and diminished health-related quality of life (HRQOL). However, for patients with compensated disease, data are limited regarding associations with poor patient-reported outcomes (PROs). We prospectively enrolled 300 patients with cirrhosis and portal hypertension without a history of hepatic encephalopathy (HE) and reviewed medical and pharmacy records. We characterized determinants of PROs using the 8-item Short-Form Health Survey (SF-8) scale (0-100) and sleep quality using the Pittsburgh Sleep Quality Index (PSQI; poor sleep >5). Disability and frailty measures were assessed using activities of daily living (ADLs), falls, hand-grip, and chair-stands. Cognitive function was measured using weighted-lures from the Inhibitory Control Test (ICT). The median age of our cohort was 60 (interquartile range [IQR], 52-66) years, 56.3% were male, and 70% Child class A. All patients had portal hypertension, 76% had varices, and 41% had a history of ascites (predominantly well controlled). The median Model for End-Stage Liver Disease with Sodium (MELD-Na) score was 9 (IQR, 7-13). The overall median SF-8 was 70 (IQR, 54-86). Multivariate analysis showed that after adjusting for age, sex, education, and MELD-Na, performance on chair-stands (9.28 HRQOL points [95% confidence interval {CI}, 4.76-13.8] per 10-stands), ADL dependence (-6.06 [-10.8 to -1.36]), opiate use (-5.01 [-7.84 to -2.19]), benzodiazepine use (-3.50 [-6.58 to -0.42]), and ICT performance (-0.10 [-0.20 to 0.001] per weighted-lure) were significantly associated with HRQOL. Among patients completing the ICT, poor HRQOL (score <50) was significantly associated with chair-stands (odds ratio [OR] per 10-stands, 0.24; 95% CI [0.11-0.56]) and weighted lures (OR per weighted-lure, 1.01 [1.00-1.03]). Poor sleep quality was associated with opiate use (OR, 2.85 [1.11-7.29]) and lures (OR per-lure, 1.03 [1.00-1.05]). Conclusion: Disability, chair-stand performance, cognitive dysfunction, as well as psychoactive medication use are significantly associated with PROs in patients with clinically stable cirrhosis.
Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With Outcomes After Acute Kidney Injury
Authors: Sandeep Brar, Feng Ye, Matthew T. James, Brenda Hemmelgarn, Scott Klarenbach, Neesh Pannu
Journal: JAMA Internal Medicine (2018)

Patients with acute kidney injury (AKI) are at an increased long-term risk of death. Effective strategies that improve long-term outcomes in patients with AKI are unknown.To evaluate whether the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) after hospital discharge is associated with better outcomes in patients with AKI.This retrospective cohort study used data from the Alberta Kidney Disease Network population database to evaluate 46 253 adults 18 years or older with an episode of AKI during a hospitalization between July 1, 2008, and March 31, 2015, in Alberta, Canada. All patients who survived to hospital discharge were followed up for a minimum of 2 years.Use of an ACEI or ARB within 6 months after hospital discharge.The primary outcome was mortality; secondary outcomes included hospitalization for a renal cause, end-stage renal disease (ESRD), and a composite outcome of ESRD or sustained doubling of serum creatinine concentration. An AKI was defined as a 50% increase between prehospital and peak in-hospital serum creatinine concentrations. Propensity scores were used to construct a matched-pairs cohort of patients who did and did not have a prescription for an ACEI or ARB within 6 months after hospital discharge.The study evaluated 46 253 adults (mean [SD] age, 68.6 [16.4] years; 24 436 [52.8%] male). Within 6 months of discharge, 22 193 (48.0%) of the participants were prescribed an ACEI or ARB. After adjustment for comorbidities, ACEI or ARB use before admission, demographics, baseline kidney function, other factors related to index hospitalization, and prior health care services, ACEI or ARB use was associated with lower mortality in patients with AKI after 2 years (adjusted hazard ratio, 0.85; 95% CI, 0.81-0.89). However, patients who received an ACEI or ARB had a higher risk of hospitalization for a renal cause (adjusted hazard ratio, 1.28; 95% CI, 1.12-1.46). No association was found between ACEI or ARB use and progression to ESRD.Among patients with AKI, ACEI or ARB therapy appeared to be associated with lower mortality but a higher risk of hospitalization for a renal cause. These results suggest a potential benefit of ACEI or ARB use after AKI, but cautious monitoring for renal-specific complications may be warranted.
The Trump Administration’s Actions to Address the Opioid Public Health Crisis
Authors: Elinore F. McCance-Katz, Brett P. Giroir
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Reflecting health: smart mirrors for personalized medicine
Authors: Riccardo Miotto, Matteo Danieletto, Jerome R. Scelza, Brian A. Kidd, Joel T. Dudley
Journal: npj Digital Medicine (2018)

Inexpensive embedded computing and the related Internet of Things technologies enable the recent development of smart products that can respond to human needs and improve everyday tasks in an attempt to make traditional environments more "intelligent". Several projects have augmented mirrors for a range of smarter applications in automobiles and homes. The opportunity to apply smart mirror technology to healthcare to predict and to monitor aspects of health and disease is a natural but mostly underdeveloped idea. We envision that smart mirrors comprising a combination of intelligent hardware and software could identify subtle, yet clinically relevant changes in physique and appearance. Similarly, a smart mirror could record and evaluate body position and motion to identify posture and movement issues, as well as offer feedback for corrective actions. Successful development and implementation of smart mirrors for healthcare applications will require overcoming new challenges in engineering, machine learning, computer vision, and biomedical research. This paper examines the potential uses of smart mirrors in healthcare and explores how this technology might benefit users in various medical environments. We also provide a brief description of the state-of-the-art, including a functional prototype concept developed by our group, and highlight the directions to make this device more mainstream in health-related applications.
Single-Arm Phase II Study of MOR208 Combined with Lenalidomide in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: L-Mind
Authors: Gilles Andre Salles, Johannes Duell, Eva González-Barca, Wojciech Jurczak, Anna Marina Liberati, Zsolt Nagy, Aleš Obr, Gianluca Gaidano, Marc Andre, Nagesh Kalakonda, Martin Dreyling, Pier Luigi Zinzani, Maren Dirnberger-Hertweck, Johannes Weirather, Sumeet Ambarkhane, Kami J. Maddocks
Journal: Blood (2018)
Transcatheter Aortic Valve Replacement With a Repositionable Self-Expanding Prosthesis
Authors: Lars Søndergaard, Josep Rodés-Cabau, Axel Hans-Peter Linke, Stephan Fichtlscherer, Ulrich Schäfer, Karl-Heinz Kuck, Joerg Kempfert, Dabit Arzamendi, Francesco Bedogni, Federico M. Asch, Stephen Worthley, Francesco Maisano
Journal: Journal of the American College of Cardiology (2018)
Abstract 12754: Infused CD34 Cell Dose, not Bone Marrow CD34+ Cell Content, Improves Clinical Outcomes and LVEF in Patients With Left Ventricular Dysfunction post STEMI: Results of the PreSERVE-AMI Trial
Authors: Arshed Quyyumi, Dean J Kereiakes, David M Shavelle, Timothy D Henry, Ahmed Abdel-Latif, Catalin Toma, Gregory Barsness, Steve C Frohwein, Richartd A Schatz, Martin Cohen, Charles Davidson, Nabil Dib, Marc Klapholz, Gary L Schaer, Alejandro Vasquez, Thomas J Moss, AnnaMaria Kanakaraj, Vitaly Druker, Ken Harper, Amy Chung, Candice Junge, Robert Preti, Robin Smith, David J Mazzo, Andrew Pecora, Douglas W Losordo
Journal: Circulation (2015)

Background: Prior studies suggest an association between naturally high circulating levels of CD34+ cells (CD34) and better outcomes following ischemic events. Pts in the treatment arm of the PreSERVE-AMI study were infused with all CD34 yielded from their bone marrow harvest, resulting in pts with naturally higher CD34 cell counts being infused with a higher cell dose. To determine whether selection bias may have influenced results, we performed an analysis of the relationship between BM CD34 content and outcomes in PreSERVE-AMI. Methods: PreSERVE-AMI is a Phase 2, randomized, double-blind, placebo-controlled trial of autologous, BM derived CD34 (CLBS10) in pts with LV dysfunction (LVEF ≤48% by MRI) ≥4 days post-STEMI. All pts underwent mini BM harvest and were randomized 1:1 to intracoronary infusion of CD34 (minimum dose 10M±20% cells) or placebo (cell diluent). Primary safety endpoints included AEs, SAEs and MACE (CV mortality, HF hospitalization, reinfarction, revascularization). Secondary endpoints included LVEF change from baseline. Regression analyses were performed to assess the influence of BM CD34 content on outcomes. Results: 161 patients were randomized and received intracoronary infusion (Jan 2013-Dec 2014). Mean age was 57±10 and 82% were men. Mean follow-up time was 18 mo, and safety data are accruing. BM CD34 content was not associated with differences in baseline characteristics with the exception of diabetes prevalence being higher in those with higher BM CD34 count (p=0.03). In controls, regression analyses showed no association of BM CD34 content with rates of MACE (p=0.2), SAEs (p=0.4), or change in LVEF (p=0.9). However, in CD34 treated pts, there was a dose-dependent improvement in LV function (p=0.045) and dose-dependent trends in MACE and SAE reduction compared to controls. As previously reported SPECT perfusion improved to a similar degree in control and treated pts. Conclusions: These data suggest that intracoronary infusion of CD34 cells, rather than BM CD34 cell content, is responsible for the benefit observed in the CD34 treatment group. The finding of a dose-response relationship is an important advance for defining the CD34 as an active agent for tissue repair. Future studies will further define CD34 dosimetry.
Inhibition of HIF1α Signaling: A Grand Slam for MDS Therapy?
Authors: Jiahao Chen, Ulrich Steidl
Journal: Cancer Discovery (2018)

Abstract Summary: The recent focus on genomics in myelodysplastic syndromes (MDS) has led to important insights and revealed a daunting genetic heterogeneity, which is presenting great challenges for clinical treatment and precision oncology approaches in MDS. Hayashi and colleagues show that multiple mutations frequently found in MDS activate HIF1α signaling, which they also found to be sufficient to induce overt MDS in mice. Furthermore, both genetic and pharmacologic inhibition of HIF1α suppressed MDS development with only mild effects on normal hematopoiesis, implicating HIF1α signaling as a promising therapeutic target to tackle the heterogeneity of MDS. Cancer Discov; 8(11); 1355–7. ©2018 AACR. See related article by Hayashi et al., p. 1438.
Scandinavian sports medicine congress with high impact
Authors: Karen Kotila, Thomas Bandholm, Kristian Thorborg, Carsten B Juhl, Merete Møller, Heidi Klakk
Journal: British Journal of Sports Medicine (2018)

Welcome to this year’s Danish Society of Sports Physical Therapy issue. We highlight some of the researchers whose work we had the privilege of presenting at the Scandinavian Congress of Medicine and Science in Sports in Copenhagen, February 2018. You can find, republished from the BMJ , the paper: ‘ Education plus exercise versus corticosteroid injection use versus a wait and see approach on global outcome and pain from gluteal tendinopathy prospective single blinded randomised clinical trial’ ( see page 1464 ). The first author is Rebecca Mellor, the senior author Sports Physiotherapy Professor Bill ‘ Veni, Vidi, Vici ’ Vicenzino. Watch a short interview with Professor Bill Vicenzino, the winner of the oral presentation competition of Scandinavian Congress of Medicine and Science in Sports (SCMSS) 2018 in Copenhagen, online (https://youtu.be/B_ygENDeIy0). 

In addition, in this issue we also dig into the topic of how to make research relevant for stakeholders and end-users such as the clinicians, coaches or athletes. As a follow-up editorial to ‘ Slow down to strengthen sport and exercise medicine research ’ ( Br J Sports Med 2017;51:1453), Professor Thomas Bandholm et al (Copenhagen) give their take on how to keep research REAL with an emphasis on identifying stakeholders and end-users as well as considering their …