tbuckley/cabot-search huggingface dataset:
Dementia with Lewy bodies: an update and outlook
Authors: Tiago Fleming Outeiro, David J. Koss, Daniel Erskine, Lauren Walker, Marzena Kurzawa-Akanbi, David Burn, Paul Donaghy, Christopher Morris, John-Paul Taylor, Alan Thomas, Johannes Attems, Ian McKeith
Journal: Molecular Neurodegeneration (2019)

Dementia with Lewy bodies (DLB) is an age-associated neurodegenerative disorder producing progressive cognitive decline that interferes with normal life and daily activities. Neuropathologically, DLB is characterised by the accumulation of aggregated α-synuclein protein in Lewy bodies and Lewy neurites, similar to Parkinson's disease (PD). Extrapyramidal motor features characteristic of PD, are common in DLB patients, but are not essential for the clinical diagnosis of DLB. Since many PD patients develop dementia as disease progresses, there has been controversy about the separation of DLB from PD dementia (PDD) and consensus reports have put forward guidelines to assist clinicians in the identification and management of both syndromes. Here, we present basic concepts and definitions, based on our current understanding, that should guide the community to address open questions that will, hopefully, lead us towards improved diagnosis and novel therapeutic strategies for DLB and other synucleinopathies.
A network meta-analysis of adjuvant systemic therapy in resected pancreatic cancer.
Authors: Jorge Chaves Porras, Kaitlyn Perry, Amanda Putri Rahmadian, Seanthel Delos Santos, Yoo-Joung Ko, Scott R. Berry, Mark Doherty, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2019)

396 Background: Multiple randomized controlled trials (RCTs) have established several systemic therapy regimens as adjuvant therapy treatment options for resected pancreatic cancer, including modified FOLFRINOX (mFFX), gemcitabine and capecitabine (GemCap) and S1, mostly based on comparison with gemcitabine (Gem) alone. Many of these regimens have not been directly compared in RCTs and their relative survival benefits are unknown. Methods: A systematic review was conducted using MEDLINE, EMBASE, Cochrane Central and ASCO abstracts to identify phase III RCTs up to June 2018 that examined adjuvant systemic therapy in resected pancreatic cancer. Two reviewers independently reviewed the studies and discrepancies were resolved either by discussion or by a third reviewer. Data including study characteristics and outcomes including overall survival (OS) and disease-free survival (DFS) were extracted. Indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analyses (NMA) (R package “netmeta”) which maintains randomization within trials. Results: Nine phase III RCTs involving 3,394 patients and 6 regimens (5-flourouracil and folinic acid, Gem, gemcitabine and erlotinib (GemErl), GemCap, mFFX and S1) were identified. Hazard ratios (HR) and 95% confidence intervals (CI) of OS and DFS of selected comparisons from the results of the NMA are shown in the table. Conclusions: Both mFFX and S1 appeared to be superior to GemCap and can be considered as reasonable standard treatment options for suitable patients and as control arm regimens of future adjuvant clinical trials. [Table: see text]
Inhibition of the Hedgehog Pathway Decreases the Quiescent CD34+CD38- Population in Acute Myeloid Leukemia
Authors: Alicia Arenas, Daniel Lainez, Cristina Serrano del Castillo, Rocio N Salgado, Carlos Blas, Mireia Atance, Raul Cordoba, Pilar Llamas, Juan Manuel Alonso Dominguez
Journal: Blood (2018)
Abstract 19231: N-acetylcysteine Inhibits Aortic Stenosis Progression in a Preclinical Murine Model: Role of Platelet TGF-β1
Authors: Rohan Varshney, Brennah Murphy, Shahrouz Ghafoory, Tyler Robison, Sean Woolington, Jasim Ahamed
Journal: Circulation (2017)

Aortic stenosis (AS) is an age-related disease characterized by fibrotic aortic valve narrowing, resulting in high shear stress (SS). We demonstrated that SS can activate TGF-β1 released from plate...
Abstract 20336: A Novel Risk Score That Includes Lipoprotein Sub-Particles Enhances the Prediction of Severe Coronary Artery Disease and Adverse Cardiovascular Outcomes: Validation From Jackson Heart Study
Authors: Rahul Chaudhary, Kevin Bliden, Eliano Navarese, Peter Toth, Udaya Tantry, Nancy Min, Robert Mentz, Michael Hall, Michael Griswold, Paul A Gurbel
Journal: Circulation (2017)

Background: Non-invasive tools for the prediction of coronary artery disease (CAD) (coronary artery stenosis ≥70%) may improve identification of high-risk individuals who would benefit from further...
Pharmacokinetics (PK) and tolerability of DN-101, a new formulation of calcitriol, in patients with cancer
Authors: Tomasz M. Beer, Milind M. Javle, W. David Henner, Donald L. Trump
Journal: Cancer Research (2004)

404  Calcitriol antineoplastic activity, seen in a broad range of tumor models, is dose-dependent and is most pronounced at supraphysiologic concentrations. Weekly dosing has allowed substantial dose escalation of calcitriol, however limited absorption above doses of 0.25 –0.5 mcg/kg and marked interpatient variability in absorption of the commercially available formulation precluded dose escalation to a maximum tolerated dose (MTD). DN-101 is a new high-dose oral formulation of calcitriol designed specifically for cancer therapy. We sought to determine the MTD of both a single dose of DN-101 and of repeat dosing of DN-101 administered weekly. MTD was defined as the highest dose at which no more than 1 patient experienced a dose limiting toxicity (DLT), defined as grade 2 (11.6 - 12.5 mg/dL) hypercalcemia or grade 3 or higher treatment-related toxicity that persisted and/or resulted in discontinuation of therapy. At least 3 patients were enrolled at each dose level. 38 patients with various advanced cancers, ECOG PS
GBR 830, an anti-OX40, improves skin gene signatures and clinical scores in patients with atopic dermatitis
Authors: Emma Guttman-Yassky, Ana B. Pavel, Lisa Zhou, Yeriel D. Estrada, Ning Zhang, Hui Xu, Xiangyu Peng, Huei-Chi Wen, Panayiota Govas, Girish Gudi, Vinu CA, Hui Fang, Yacine Salhi, Jonathan Back, Venkateshwar Reddy, Robert Bissonnette, Catherine Maari, Fred Grossman, Gerhard Wolff
Journal: Journal of Allergy and Clinical Immunology (2019)

BackgroundGBR 830 is a humanized mAb against OX40, a costimulatory receptor on activated T cells. OX40 inhibition might have a therapeutic role in T cell–mediated diseases, including atopic dermatitis (AD).ObjectiveThis exploratory phase 2a study investigated the safety, efficacy, and tissue effects of GBR 830 in patients with AD.MethodsPatients with moderate-to-severe AD (affected body surface area, ≥10%; Eczema Area and Severity Index score, ≥12; and inadequate response to topical treatments) were randomized 3:1 to 10 mg/kg intravenous GBR 830 or placebo on day 1 (baseline) and day 29. Biopsy specimens were collected (n = 40) at days 1, 29, and 71. Primary end points included treatment-emergent adverse events (TEAEs) and changes from baseline in biomarkers (epidermal hyperplasia/cytokines) at days 29 and 71.ResultsGBR 830 was well tolerated, with equal TEAE distribution (GBR 830, 63.0% [29/46]; placebo, 63.0% [10/16]). One serious TEAE in the GBR 830 group was deemed unrelated to study drug. At day 71, the proportion of intent-to-treat subjects achieving 50% or greater improvement in Eczema Area and Severity Index score was greater with GBR 830 (76.9% [20/26]) versus placebo (37.5% [3/8]). GBR 830 induced significant progressive reductions in TH1 (IFN-γ/CXCL10), TH2 (IL-31/CCL11/CCL17), and TH17/TH22 (IL-23p19/IL-8/S100A12) mRNA expression in lesional skin. Significant progressive reductions until day 71 in the drug group were seen in OX40+ T cells and OX40L+ dendritic cells (P < .001). Hyperplasia measures (thickness/keratin 16/Ki67) showed greater reductions with GBR 830 (P < .001).ConclusionsTwo doses of GBR 830 administered 4 weeks apart were well tolerated and induced significant progressive tissue and clinical changes until day 71 (42 days after the last dose), highlighting the potential of OX40 targeting in patients with AD.Graphical abstract
Cytochrome <i>c</i> Deficiency Confers Apoptosome and Mitochondrial Dysfunction in African-American Men with Prostate Cancer
Authors: Rahul Kumar, Tariq A. Bhat, Elise M. Walsh, Ajay K. Chaudhary, Jordan O'Malley, Johng S. Rhim, Jianmin Wang, Carl D. Morrison, Kristopher Attwood, Wiam Bshara, James L. Mohler, Neelu Yadav, Dhyan Chandra
Journal: Cancer Research (2019)

Although African-American (AA) patients with prostate cancer tend to develop greater therapeutic resistance and faster prostate cancer recurrence compared with Caucasian-American (CA) men, the molecular mechanisms of this racial prostate cancer disparity remain undefined. In this study, we provide the first comprehensive evidence that cytochrome c deficiency in AA primary tumors and cancer cells abrogates apoptosome-mediated caspase activation and contributes to mitochondrial dysfunction, thereby promoting therapeutic resistance and prostate cancer aggressiveness in AA men. In AA prostate cancer cells, decreased nuclear accumulation of nuclear respiration factor 1 (Nrf1) and its subsequent loss of binding to the cytochrome c promoter mediated cytochrome c deficiency. The activation of cellular Myc (c-Myc) and NF-κB or inhibition of AKT prevented nuclear translocation of Nrf1. Genetic and pharmacologic inhibition of c-Myc and NF-κB or activation of AKT promoted Nrf1 binding to cytochrome c promoter, cytochrome c expression, caspase activation, and cell death. The lack of p-Drp1S616 in AA prostate cancer cells contributed to defective cytochrome c release and increased resistance to apoptosis, indicating that restoration of cytochrome c alone may be insufficient to induce effective apoptosis. Cytochrome c deficiency promoted the acquisition of glycolytic phenotypes and mitochondrial dysfunction, whereas cytochrome c restoration via inhibition of c-Myc and NF-κB or activation of AKT attenuated glycolysis in AA prostate cancer cells. Inhibition of c-Myc and NF-κB enhanced the efficacy of docetaxel in tumor xenografts. Therefore, restoring cytochrome c may overcome therapeutic resistance and prostate cancer aggressiveness in AA men. Overall, this study provides the first comprehensive experimental, mechanistic, and clinical evidence for apoptosome and mitochondrial dysfunction in prostate cancer racial disparity. SIGNIFICANCE: Mechanistic insights on prostate cancer health disparity among American men provide novel approaches to restore mitochondrial function, which can address therapeutic resistance and aggressiveness in African-American men with prostate cancer.
Arterial Vascular Pruning, Right Ventricular Size, and Clinical Outcomes in Chronic Obstructive Pulmonary Disease. A Longitudinal Observational Study
Authors: George R. Washko, Pietro Nardelli, Samuel Y. Ash, Gonzalo Vegas Sanchez-Ferrero, Farbod N. Rahaghi, Carolyn E. Come, Mark T. Dransfield, Ravi Kalhan, MeiLan K. Han, Surya P. Bhatt, J. Michael Wells, Carrie Pistenmaa Aaron, Alejandro A. Diaz, James C. Ross, Michael J. Cuttica, Wassim W. Labaki, Gabriela Querejeta Roca, Amil M. Shah, Kendra Young, Gregory L. Kinney, John E. Hokanson, Alvar Agustí, Raúl San José Estépar
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Cor pulmonale (right ventricular [RV] dilation) and cor pulmonale parvus (RV shrinkage) are both described in chronic obstructive pulmonary disease (COPD). The identification of emphysema as a shared risk factor suggests that additional disease characterization is needed to understand these widely divergent cardiac processes.
Papillary dilation for bile duct stones: start big but proceed with caution
Authors: James Buxbaum
Journal: Endoscopy (2019)

In this issue of Endoscopy, Park et al. compare the safety of endoscopic papillary large balloon dilation (EPLBD) with vs. without preceding endoscopic sphincterotomy (EST) in patients with large ( ≥ 10 mm) bile duct stones [1]. There was no difference in adverse events for EPLBD with vs. without EST (4 % vs. 6 %, respectively), and specifically no difference in postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) (3 % vs. 1 %). There was also no difference in stone clearance between EPLBD with vs. without EST (88 % vs. 92 %). The study provides new data to fuel the longstanding controversy regarding the risk of papillary dilation without preceding sphincterotomy. Their work raises important questions about whether discrepant results among studies on this topic may be the consequence of differences in study population vs. patient selection. In the Park et al. study, only those with stones ≥ 10 mm in size were enrolled. Though counter-intuitive, papillary dilation without EST may be the safest and most efficacious approach when addressing larger stones.
Abstract 15310: Job Strain and Cardiovascular Health Score. Cross-Sectional Analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) Baseline
Authors: Priscila T Rocco, Isabela M Bensenor, Rosane H Griep, Alessandra C Goulart, Sandhi M Barreto, Arlinda B Moreno, Airlane P Alencar, Paulo A Lotufo, Itamar S Santos
Journal: Circulation (2016)

Introduction: To date, there are no studies about the association between job strain and the American Heart Association (AHA)’s cardiovascular health (CVH) score. Hypothesis: There is an associatio...
Can Maintenance of Certification Pass the Test?
Authors: Steven E. Weinberger
Journal: JAMA (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 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
Immunotherapy in Multiple Myeloma: Experience of the Multiple Myeloma Gimema Lazio Group
Authors: Federico Vozella, Agostina Siniscalchi, Manuela Rizzo, Tommaso Za, Giusy Antolino, Ugo Coppetelli, Alfonso Piciocchi, Alessandro Andriani, Ombretta Annibali, Luca De Rosa, Giuseppe Cimino, Giacinto La Verde, Valerio De Stefano, Maria Cantonetti, Tommaso Caravita di Toritto, Robin Foà, Maria Teresa Petrucci
Journal: Blood (2018)
Abstract PR13: MET copy number gain is associated with gefitinib resistance in leptomeningeal carcinomatosis of EGFR-mutant lung cancer
Authors: Shigeki Nanjo, Sachiko Arai, Wei Wang, Akito Hata, Nobuyuki Katakami, Seiji Yano
Journal: Clinical Cancer Research (2018)

Abstract Leptomeningeal carcinomatosis occurs frequently in EGFR-mutant lung cancer, and develops acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). This study aimed to clarify the mechanism of EGFR-TKI resistance in leptomeningeal carcinomatosis and seek a novel therapeutic strategy. We examined EGFR mutations, including the T790M gatekeeper mutation, in 32 re-biopsy specimens from 12 leptomeningeal carcinomatosis and 20 extracranial lesions of EGFR-mutant lung cancer patients who became refractory to EGFR-TKI treatment. All 32 specimens had the same baseline EGFR mutations, but the T790M mutation was less frequent in leptomeningeal carcinomatosis specimens than in extracranial specimens (8% vs. 55%, P &amp;lt; 0.01). To study molecular mechanisms of acquired EGFR-TKI resistance in leptomeningeal carcinomatosis, we utilized our previously developed mouse model of leptomeningeal carcinomatosis with the EGFR-mutant lung cancer cell line PC-9/ffluc cells, in which acquired resistance to gefitinib was induced by continuous oral treatment. Compared with subcutaneously inoculated gefitinib-resistant tumors, the T790M mutation was less frequent in leptomeningeal carcinomatosis that acquired resistance to gefitinib. PC-9/LMC-GR cells were established from the gefitinib-resistant leptomeningeal carcinomatosis model, and they were found to be intermediately resistant to gefitinib and osimertinib (third-generation EGFR-TKI). Although EGFR-T790M was negative, gefitinib resistance of PC-9/LMC-GR cells was related to MET copy number gain with MET activation. Moreover, combined use of EGFR-TKI and crizotinib, a MET inhibitor, dramatically regressed leptomeningeal carcinomatosis with acquired resistance to gefitinib or osimertinib. These findings suggest that combination therapy with MET inhibitors may be promising for controlling leptomeningeal carcinomatosis that acquires resistance to EGFR-TKIs. This abstract is also being presented as Poster B29. Citation Format: Shigeki Nanjo, Sachiko Arai, Wei Wang, Akito Hata, Nobuyuki Katakami, Seiji Yano. MET copy number gain is associated with gefitinib resistance in leptomeningeal carcinomatosis of EGFR-mutant lung cancer [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr PR13.
Comparison of Proteomic Profiles Influencing Pulmonary Immune Responses Following Repeated Exposure to Aspergillus and Stachybotrys species
Authors: Tara L. Croston, Mark A. Barnes, Angela R. Lemons, Ajay P. Nayak, Dori Germolec, Donald H. Beezhold, Brett J. Green
Journal: Journal of Allergy and Clinical Immunology (2019)
A systematic review and network meta-analysis of adjuvant therapy for curatively resected biliary tract cancers.
Authors: Maxine Kish, Kelvin K. Chan, Kaitlyn Perry, Yoo-Joung Ko
Journal: Journal of Clinical Oncology (2019)

247 Background: Although recently completed randomized controlled trials (RCTs) have added high-quality data regarding adjuvant therapy in curatively resected biliary tract cancer (BTC), there is still no standard approach to manage these patients. We conducted a systematic review and network meta-analysis to compare the efficacy of adjuvant therapy regimens in curatively resected BTC to help guide clinical decision making and the design of future prospective trials. Methods: We conducted a systematic review of published studies and abstracts up to and including June 2018. Studies were included if they were phase III RCTs on patients with histologically proven BTC receiving adjuvant chemotherapy after a complete surgical resection (R0 or R1). BTCs included gallbladder cancer, intrahepatic and extrahepatic cholangiocarcinoma. The endpoints of interest were overall survival (OS) and relapse-free survival (RFS). Network meta-analysis methods were used for indirect comparison between adjuvant therapy regimens. Results: Five RCTs were included in the qualitative synthesis and three RCTs (BILCAP, PRODIGE 12-ACCORD 18 and BCAT) included sufficient data to be included in the meta-analysis. Results from the indirect comparison demonstrated no significant difference in OS between any of the adjuvant therapy regimens, however there was a trend that favoured adjuvant therapy with capecitabine over gemcitabine or gemcitabine plus oxaliplatin (GEMOX), with hazard ratios (HRs) of 0.82 (95% CI, 0.53-1.27) and 0.86 (95% CI, 0.56-1.34), respectively. Similarly there was no significant improvement in RFS with capecitabine compared to gemcitabine or GEMOX with HRs of 0.82 (95% CI, 0.53-1.27) and 0.86 (95% CI, 0.56-1.34), respectively. Conclusions: Although capecitabine is considered to be standard of care in the adjuvant setting based on a single randomized phase III study, in this indirect comparison, we did not find a statistically significant improvement in OS or RFS with capecitabine compared to GEMOX or gemcitabine. Further prospective trials comparing adjuvant therapies to capecitabine are warranted.
Dynamic ploidy changes drive fluconazole resistance in human cryptococcal meningitis
Authors: Neil R.H. Stone, Johanna Rhodes, Matthew C. Fisher, Sayoki Mfinanga, Sokoine Kivuyo, Joan Rugemalila, Ella Shtifman Segal, Leor Needleman, Síle F. Molloy, June Kwon-Chung, Thomas S. Harrison, William Hope, Judith Berman, Tihana Bicanic
Journal: Journal of Clinical Investigation (2019)

BACKGROUND. Cryptococcal meningitis (CM) causes an estimated 180,000 deaths annually, predominantly in sub-Saharan Africa, where most patients receive fluconazole (FLC) monotherapy. While relapse after FLC monotherapy with resistant strains is frequently observed, the mechanisms and impact of emergence of FLC resistance in human CM are poorly understood. Heteroresistance (HetR) — a resistant subpopulation within a susceptible strain — is a recently described phenomenon in Cryptococcus neoformans (Cn) and Cryptococcus gattii (Cg), the significance of which has not previously been studied in humans.
Biomarkers Predicting Venetoclax Sensitivity and Strategies for Venetoclax Combination Treatment
Authors: Haijiao Zhang, Beth Wilmot, Daniel Bottomly, Stephen E Kurtz, Christopher A. Eide, Alisa Damnernsawad, Kyle Romine, Shyam Patel, Brian J. Druker, Schannon K Mcweeney, Ravi Majeti, Jeffrey W. Tyner
Journal: Blood (2018)
Prevalence and Likelihood of Meeting Sleep, Physical Activity, and Screen-Time Guidelines Among US Youth
Authors: Gregory Knell, Casey P. Durand, Harold W. Kohl, Ivan H. C. Wu, Kelley Pettee Gabriel
Journal: JAMA Pediatrics (2019)

2][3] Accordingly, it is recommended that children (age 6-12 years) sleep 9 to 12 hours and adolescents (age 14-18 years) sleep 8 to 10 hours a night and that both groups accumulate at least 1 hour of moderate-intensity or vigorous-Table.Prevalence and Adjusted Relative Odds of Meeting Recommendations for Sleep, Screen Time, and Physical Activity Among US Youth per Youth Risk Behavior Surveillance Survey, 2011-2017
Mast cell hyperplasia in human type 2 inflammation: insights from single cell RNA sequencing
Authors: Daniel F. Dwyer, Jose Ordovas-Montanes, Sarah K. Nyquist, Kathleen M. Buchheit, Howard R. Katz, Neil Bhattacharyya, Tanya M. Laidlaw, Joshua A. Boyce, Alex K. Shalek, Nora A. Barrett
Journal: Journal of Allergy and Clinical Immunology (2019)
When to Start Levodopa Therapy for Parkinson’s Disease
Authors: Susan Bressman, Rachel Saunders-Pullman
Journal: New England Journal of Medicine (2019)

Patients with Parkinson's disease and the neurologists who treat them have had a complicated relationship with levodopa. Despite the undisputed efficacy of levodopa in ameliorating the cardinal motor signs of bradykinesia and rigidity, how and when to initiate treatment have been controversial issues. The practice of delaying and restricting, or "sparing," treatment with levodopa by treating with other medications, such as monoamine oxidase type B inhibitors and dopamine agonists, evolved in the 1980s and 1990s. This approach was derived from concerns about the common complications associated with levodopa — involuntary movements (dyskinesia) and fluctuations of motor control, including a wearing-off . . .
Health Care Utilization and Costs for Patients With End-Stage Liver Disease Are Significantly Higher at the End of Life Compared to Those of Other Decedents
Authors: Erin M. Kelly, Paul D. James, Sanjay Murthy, Lilia Antonova, Florence Wong, Thomas Shaw-Stiffel, Mathieu Chalifoux, Misbah Salim, Peter Tanuseputro
Journal: Clinical Gastroenterology and Hepatology (2019)