tbuckley/cabot-search huggingface dataset:
The curious case of vacuolar ATPase: regulation of signaling pathways
Authors: Sahithi Pamarthy, Arpita Kulshrestha, Gajendra K. Katara, Kenneth D. Beaman
Journal: Molecular Cancer (2018)

The Vacuolar ATPase (V-ATPase) is a proton pump responsible for controlling the intracellular and extracellular pH of cells. The structure of V-ATPase has been highly conserved among all eukaryotic cells and is involved in diverse functions across species. V-ATPase is best known for its acidification of endosomes and lysosomes and is also important for luminal acidification of specialized cells. Several reports have suggested the involvement of V-ATPase in maintaining an alkaline intracellular and acidic extracellular pH thereby aiding in proliferation and metastasis of cancer cells respectively. Increased expression of V-ATPase and relocation to the plasma membrane aids in cancer modulates key tumorigenic cell processes like autophagy, Warburg effect, immunomoduation, drug resistance and most importantly cancer cell signaling. In this review, we discuss the direct role of V-ATPase in acidification and indirect regulation of signaling pathways, particularly Notch Signaling.
Dynamic ErbB4 Activity in Hippocampal-Prefrontal Synchrony and Top-Down Attention in Rodents
Authors: Zhibing Tan, Heath L. Robinson, Dong-Min Yin, Yu Liu, Fang Liu, Hongsheng Wang, Thiri W. Lin, Guanglin Xing, Lin Gan, Wen-Cheng Xiong, Lin Mei
Journal: Neuron (2018)
Questionable Conclusions Regarding Blood Pressure End Points—Reply
Authors: Mattias Brunström, Bo Carlberg
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Abstract 12266: Treatment and Outcomes of Dual Medicare/Medicaid Eligible Older Adults With Myocardial Infarction
Authors: Jacob A Doll, Anne Hellkamp, Abhinav Goyal, Nadia Sutton, Eric D Peterson, Tracy Y Wang
Journal: Circulation (2015)

Introduction: Patients with dual Medicare-Medicaid eligibility typically have higher burden of chronic disease conditions and increased healthcare utilization than patients with Medicare coverage alone. For patients with acute MI, in-hospital treatment patterns and longitudinal outcomes of dual eligible patients are unknown. Methods: We linked MI patients 65 years or older in the ACTION Registry-GWTG from 2007 to 2009 to Medicare claims data. We used multivariable Cox regression to compare risks of all-cause readmission by 30 days and major adverse cardiovascular events (MACE: death, MI, stroke) by 1 year between dual eligible vs. Medicare-only patients. Results: Of 17,419 Medicare patients discharged after MI, 4,674 (27%) were dual eligible. Dual eligible patients were more likely to be female (64% vs. 49%) and non-white (29% vs. 6%), to have a greater prevalence of comorbid conditions (mean Charlson comorbidity index 3.7 vs. 3.0) and to present with non-STEMI (75% vs. 69%). Rates of reperfusion for STEMI (91 vs 93%, p=0.006) and revascularization for NSTEMI (58% vs. 65%, p&lt;0.001) were significantly lower for dual eligible compared with Medicare only patients in the absence of contraindications. Unadjusted rates of 30-day all-cause readmission and 1-year MACE were higher among dual eligible patients (Figure). After adjustment for differences in patient characteristics and in-hospital treatment, dual eligible status remained associated with higher risk of 30-day readmission (HR 1.16, 95% C.I. 1.06-1.26) and 1-year MACE (HR 1.21; 95% C.I. 1.12-1.31). Conclusions: Patients with dual Medicare/Medicaid eligibility were less likely receive reperfusion or revascularization during the index MI hospitalization and had worse short- and long-term outcomes than patients with Medicare coverage alone. Despite the additional support provided by Medicaid coverage, this is a vulnerable population that will benefit from interventions to optimize post-MI outcomes.
Individuals with filaggrin-related eczema and asthma have increased long-term medication and hospital admission costs
Authors: P. Soares, K. Fidler, J. Felton, R. Tavendale, A. Hövels, S.A. Bremner, C.N.A. Palmer, S. Mukhopadhyay
Journal: British Journal of Dermatology (2018)

Eczema and asthma are chronic diseases with onset usually before the age of 5 years. More than 50% of individuals with eczema will develop asthma and/or other allergic diseases. Several loss-of-function mutations in filaggrin (FLG) have been identified in patients with eczema. However, the association of FLG with healthcare use is unknown.To determine whether FLG mutations are associated with increased prescribing for eczema and asthma and whether increased prescribing is associated with increased healthcare costs.A secondary analysis of BREATHE, a cross-sectional study of gene-environment associations with asthma severity, was undertaken. BREATHE data was collected for 1100 participants with asthma, in Tayside and Fife, Scotland during the period 2003-2005. Through collaboration with the Health Informatics Centre in Dundee, BREATHE was linked to accident and emergency, community prescribing and Scottish morbidity records. The data linkage allowed longitudinal exploration of associations between genetic variation and prescribing.An association was found between FLG mutations and increased prescribing for mild and moderate eczema, asthma-reliever medicine and asthma exacerbations. A strong association was found between FLG mutations and prescribing of emollients [incidence rate ratio (IRR) 2·19, 95% confidence interval (CI) 1·36-3·52], treatment for severe eczema (IRR 2·18, 95% CI 1·22-3·91) and a combination of a long-acting β2 -agonist and corticosteroids (IRR 3·29, 95% CI 1·68-6·43).The presence of FLG mutations in this cohort is associated with increased prescribing for eczema and asthma. Randomized controlled trials are required to determine if these individuals could benefit from management strategies to reduce morbidity and treatment costs.
A Call for Open-Source Cost-Effectiveness Analysis
Authors: Christopher J. Sampson
Journal: Annals of Internal Medicine (2018)

Letters3 April 2018A Call for Open-Source Cost-Effectiveness AnalysisChristopher J. Sampson, BA, MScChristopher J. Sampson, BA, MScThe Office of Health Economics, London, United Kingdom (C.J.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L17-0693 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I agree with Cohen and colleagues' sentiment (1) and welcome the call for open-source cost-effectiveness analysis. However, the authors' apparent unawareness of the ongoing discussions outside of the United States is unfortunate and regrettably common, as I am sure that readers from other countries can attest. Ten years ago, The BMJ published a letter highlighting the need for decision models to be opened to scrutiny (2). Since then, although it is certainly not yet standard practice, many analysts have made their models open source. At least 1 small piece of research on the subject was published last ...References1. Cohen JT, Neumann PJ, Wong JB. A call for open-source cost-effectiveness analysis. Ann Intern Med. 2017;167:432-3. [PMID: 28847014]. doi:10.7326/M17-1153 LinkGoogle Scholar2. Poole C, Agrawal S, Currie CJ. Let cost effectiveness models be open to scrutiny [Letter]. BMJ. 2007;335:735. [PMID: 17932167] CrossrefMedlineGoogle Scholar3. Dunlop WCN, Mason N, Kenworthy J, Akehurst RL. Benefits, challenges and potential strategies of open source health economic models [Letter]. Pharmacoeconomics. 2017;35:125-8. [PMID: 27928759] doi:10.1007/s40273-016-0479-8 CrossrefMedlineGoogle Scholar4. Arnold RJG, Ekins S. Ahead of our time: collaboration in modeling then and now [Letter]. Pharmacoeconomics. 2017;35:975-6. [PMID: 28660474] doi:10.1007/s40273-017-0532-2 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: The Office of Health Economics, London, United Kingdom (C.J.S.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L17-0693. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoA Call for Open-Source Cost-Effectiveness Analysis Joshua T. Cohen , Peter J. Neumann , and John B. Wong A Call for Open-Source Cost-Effectiveness Analysis R. Brett McQueen , William V. Padula , and Jonathan D. Campbell A Call for Open-Source Cost-Effectiveness Analysis Joshua T. Cohen , Peter J. Neumann , and John B. Wong Metrics Cited byCan We Develop Sustainable and Sharable Cost-Effectiveness Models for Value Assessment in the U.S. Health Care System? 3 April 2018Volume 168, Issue 7Page: 528KeywordsConflicts of interestDisclosureHealth economics ePublished: 3 April 2018 Issue Published: 3 April 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Volumetric response quantified using T1 subtraction predicts long-term survival benefit from cabozantinib monotherapy in recurrent glioblastoma
Authors: Benjamin M Ellingson, Dana T Aftab, Gisela M Schwab, Colin Hessel, Robert J Harris, Davis C Woodworth, Kevin Leu, Ararat Chakhoyan, Catalina Raymond, Jan Drappatz, John de Groot, Michael D Prados, David A Reardon, David Schiff, Marc Chamberlain, Tom Mikkelsen, Annick Desjardins, Jaymes Holland, Jerry Ping, Ron Weitzman, Patrick Y Wen, Timothy F Cloughesy
Journal: Neuro-Oncology (2018)

To overcome challenges with traditional response assessment in anti-angiogenic agents, the current study uses T1 subtraction maps to quantify volumetric radiographic response in monotherapy with cabozantinib, an orally bioavailable tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 (VEGFR2), hepatocyte growth factor receptor (MET), and AXL, in an open-label, phase II trial in patients with recurrent glioblastoma (GBM) (NCT00704288). A total of 108 patients with adequate imaging data and confirmed recurrent GBM were included in this retrospective study from a phase II multicenter trial of cabozantinib monotherapy (XL184-201) at either 100 mg (N = 87) or 140 mg (N = 21) per day. Contrast enhanced T1-weighted digital subtraction maps were used to define volume of contrast-enhancing tumor at baseline and subsequent follow-up time points. Volumetric radiographic response (>65% reduction in contrast-enhancing tumor volume from pretreatment baseline tumor volume sustained for more than 4 wk) was tested as an independent predictor of overall survival (OS). Volumetric response rate for all therapeutic doses was 38.9% (41.4% and 28.6% for 100 mg and 140 mg doses, respectively). A log-linear association between baseline tumor volume and OS (P = 0.0006) and a linear correlation between initial change in tumor volume and OS (P = 0.0256) were observed. A significant difference in OS was observed between responders (median OS = 20.6 mo) and nonresponders (median OS = 8.0 mo) (hazard ratio [HR] = 0.3050, P < 0.0001). Multivariable analyses showed that continuous measures of baseline tumor volume (HR = 1.0233, P < 0.0001) and volumetric response (HR = 0.2240, P < 0.0001) were independent predictors of OS. T1 subtraction maps provide value in determining response in recurrent GBM treated with cabozantinib and correlated with survival benefit.
Breast Cancer Family History and Contralateral Breast Cancer Risk in Young Women: An Update From the Women’s Environmental Cancer and Radiation Epidemiology Study
Authors: Anne S. Reiner, Julia Sisti, Esther M. John, Charles F. Lynch, Jennifer D. Brooks, Lene Mellemkjær, John D. Boice, Julia A. Knight, Patrick Concannon, Marinela Capanu, Marc Tischkowitz, Mark Robson, Xiaolin Liang, Meghan Woods, David V. Conti, David Duggan, Roy Shore, Daniel O. Stram, Duncan C. Thomas, Kathleen E. Malone, Leslie Bernstein, Jonine L. Bernstein
Journal: Journal of Clinical Oncology (2018)

Purpose The Women’s Environmental Cancer and Radiation Epidemiology (WECARE) study demonstrated the importance of breast cancer family history on contralateral breast cancer (CBC) risk, even for noncarriers of deleterious BRCA1/2 mutations. With the completion of WECARE II, updated risk estimates are reported. Additional analyses that exclude women negative for deleterious mutations in ATM, CHEK2*1100delC, and PALB2 were performed. Patients and Methods The WECARE Study is a population-based case-control study that compared 1,521 CBC cases with 2,212 individually matched unilateral breast cancer (UBC) controls. Participants were younger than age 55 years when diagnosed with a first invasive breast cancer between 1985 and 2008. Women were interviewed about breast cancer risk factors, including family history. A subset of women was screened for deleterious mutations in BRCA1/2, ATM, CHEK2*1100delC, and PALB2. Rate ratios (RRs) were estimated using multivariable conditional logistic regression. Cumulative absolute risks (ARs) were estimated by combining RRs from the WECARE Study and population-based SEER*Stat cancer incidence data. Results Women with any first-degree relative with breast cancer had a 10-year AR of 8.1% for CBC (95% CI, 6.7% to 9.8%). Risks also were increased if the relative was diagnosed at an age younger than 40 years (10-year AR, 13.5%; 95% CI, 8.8% to 20.8%) or with CBC (10-year AR, 14.1%; 95% CI, 9.5% to 20.7%). These risks are comparable with those seen in BRCA1/2 deleterious mutation carriers (10-year AR, 18.4%; 95% CI, 16.0% to 21.3%). In the subset of women who tested negative for deleterious mutations in BRCA1/2, ATM, CHEK2*1100delC, and PALB2, estimates were unchanged. Adjustment for known breast cancer single-nucleotide polymorphisms did not affect estimates. Conclusion Breast cancer family history confers a high CBC risk, even after excluding women with deleterious mutations. Clinicians are urged to use detailed family histories to guide treatment and future screening decisions for young women with breast cancer.
Arthur J Moss: pioneered clinical research into long QT syndrome and sudden cardiac death
Authors: Ned Stafford
Journal: BMJ (2018)

Credit: University of Rochester Medical Center

Three months before his death at the age of 86, Arthur Moss received the last of his many honours, the American Heart Association’s James B Herrick award for outstanding achievement in clinical cardiology. The award was “in recognition of his wideranging scientific achievements elevating understanding of critical aspects of coronary disease.”

In presenting the award, Randal J Thomas, of the Mayo School of Medicine in Rochester, Minnesota, noted that “very few individuals have made such enormous contributions to clinical cardiology as Arthur Moss.”

For more than 60 years Moss worked to better understand electrical disturbances of the heart, helping to pioneer significant discoveries in the treatment and prevention of cardiac arrhythmias, sudden cardiac death, heart failure, and long QT syndrome (LQTS), a rare inherited disorder of the heart’s electrical activity that can cause uncontrollable arrhythmias and can be fatal.

In the early 1990s Moss founded the Multicenter Automatic Defibrillator Implantation Trial (known as MADIT)—which was not actually one but a series of trials over two decades, showing that use of implantable cardioverter defibrillators (ICDs) significantly lowers the risk of death after heart attack. A key MADIT paper in 2002 helped change medical guidelines in the US and led to ICD use by millions of patients.1 Dozens of other MADIT papers have been published up to the current day.2

“Arthur Moss has left behind an amazing legacy,” cardiologist Jagmeet P Singh of Harvard Medical School told The BMJ. “He was the ‘master clinical trialist.’ He had a commanding presence, and one learnt so much by just being around him and seeing the way he conducted the large MADIT steering committee meetings. He had a unique talent for tapping into the strengths of his colleagues …
Abstract 054: Diet Beverage Intake is Positively Associated With Incident Coronary Heart Disease in People With Type 2 Diabetes
Authors: Andrew O Odegaard, Lyn M Steffen, David R Jacobs, Katherine L Tucker, Kenneth J Mukamal, Mark A Pereira
Journal: Circulation (2018)

Introduction: Diet beverages are calorie free beverages sweetened with non-nutritive sweeteners. People with diabetes are the highest per-capita consumers of diet beverages, tending to consume them as a replacement for dietary sources of sugar, especially in place of sugar sweetened beverages. This behavior is endorsed by dietetic and scientific organizations and diet beverages are marketed synonymously with better health, weight loss, and thus, are considered advantageous for diabetes control. The underlying public health concern is the lack of data to support or refute this concept. Hypothesis: Higher diet beverage intake is positively associated with incident Coronary Heart Disease (CHD) Methods: We pooled the data sets of the Atherosclerosis Risk in Communities (ARIC) study (1987-2014), Cardiovascular Health Study (CHS) (1989-2014), Framingham Offspring Study (FOS) (1995-2014), Jackson Heart Study (JHS) (2000-2012), and Multi-Ethnic Study of Atherosclerosis (MESA (2000-2013) to conduct a prospective examination of the association of diet beverage intake with the incidence of CHD among participants with clinically ascertained type 2 diabetes (T2D) without prevalent CHD and with valid dietary data (N=3,947). We carried out a 2-step meta-analysis using individual level, cohort-specific Cox regression analyses with identical adjustment for demographic, lifestyle, overall diet quality and clinical risk factors to generate effect estimates that were pooled together using fixed and random effects meta-analysis. Results: 1,046 participants developed adjudicated CHD during follow-up. There was a positive, graded association between diet beverage intake and risk of incident CHD (Table). Results were consistent by sex, race and age. Conclusions: Diet beverage intake is associated with increased risk of developing CHD in a population with T2D. These results suggest the need to further evaluate dietary recommendations related to diet beverages and consider their role in this high risk population.
Toward an Integrative Theory of Thalamic Function
Authors: Rajeev V. Rikhye, Ralf D. Wimmer, Michael M. Halassa
Journal: Annual Review of Neuroscience (2018)

The thalamus has long been suspected to have an important role in cognition, yet recent theories have favored a more corticocentric view. According to this view, the thalamus is an excitatory feedforward relay to or between cortical regions, and cognitively relevant computations are exclusively cortical. Here, we review anatomical, physiological, and behavioral studies along evolutionary and theoretical dimensions, arguing for essential and unique thalamic computations in cognition. Considering their architectural features as well as their ability to initiate, sustain, and switch cortical activity, thalamic circuits appear uniquely suited for computing contextual signals that rapidly reconfigure task-relevant cortical representations. We introduce a framework that formalizes this notion, show its consistency with several findings, and discuss its prediction of thalamic roles in perceptual inference and behavioral flexibility. Overall, our framework emphasizes an expanded view of the thalamus in cognitive computations and provides a roadmap to test several of its theoretical and experimental predictions.
The effect of socioeconomic factors on the outcome of hepatocellular carcinoma.
Authors: Cortlandt Sellers, Johannes M Ludwig, Johannes Uhlig, Stacey Stein, Tamar Hamosh Taddei, Hyun S Kim
Journal: Journal of Clinical Oncology (2018)

466 Background: To investigate the impact of socioeconomic factors on overall survival (OS) for patients with hepatocellular carcinoma (HCC) at an inner-city tertiary care hospital. Methods: Consecutive patients treated for HCC diagnosed between 2005 and 2016 in the cancer registry were studied. Patients were stratified by demographic, socioeconomic variables and treatment course. Kaplan-Meier curves and Cox proportional hazard modeling were performed. Results: Patients were 79% male (770 pts) with mean age of 62.8 yrs (SD 10.2 yrs). 25% of patients (239 pts) had private insurance, 38% (363 pts) with Medicare, and 34% (239 pts) with Medicaid. Median OS stratified by primary insurance demonstrated a survival benefit for private insurance with 27.8 mo (95% CI 23.1–33.1) vs 21.0 mo (95% CI 16.5–26.5) for Medicare (HR 0.82, p = 0.0344) vs 13.3 mo (95% CI 10.2–19.7) for Medicaid (HR 0.80, p = 0.0002) (p = 0.0007). When further stratified by AJCC Stage, median OS in Stage II was 55.3 mo (95% CI: 32.4–67.1 mo) for private insurance vs 26.0 mo (95% CI: 18.7–36.3 mo) in Medicare vs 13.2 mo (95% CI: 9.0–38.1 mo) in Medicaid (p = 0.0309). Private insurance in Stage III had a median OS of 23.8 mo (95% CI: 10.9–39.8 mo) vs 14.6 mo (95% CI: 7.5–30.8 mo) in Medicare vs 6.7 mo in Medicaid (95% CI: 2.5–12.2 mo) (p = 0.0069). No differences were seen in Stage I and Stage IV. Cancer-directed treatments were utilized in 91% of private insurance vs 84% in Medicare vs 78% in Medicaid (p &lt; 0.0001). Median OS stratified by marital status showed 23.7 mo (95% CI: 21.0–28.1 mo) for married (720 pts, 76%) vs 5.2 mo (95% CI: 9.6–20.1 mo) for never-married (227 pts, 24%) (p = 0.0009) (HR 1.4, p = 0.0013). Cancer-directed treatments were utilized by 87% of married vs 77% of never-married (p = 0.0016). Increased age was associated with decreased median OS (correlation -0.14, p &lt; 0.0001). No differences in OS were seen with ethnicity or gender. Multivariate Cox proportional analysis demonstrated survival advantage for private insurance versus Medicaid (HR 1.3, p = 0.0435) and Medicare (HR 1.2, p = 0.0472). Conclusions: Primary insurance and social support appear to affect the OS of patients with HCC. Further investigations to elucidate the socioeconomic determinants to enhance survivals are warranted.