tbuckley/cabot-search huggingface dataset:
Increased Interleukin-35 Levels in Patients With Type 1 Diabetes With Remaining C-Peptide
Authors: Daniel Espes, Kailash Singh, Stellan Sandler, Per-Ola Carlsson
Journal: Diabetes Care (2017)

OBJECTIVE Many patients with long-standing type 1 diabetes have remaining functional β-cells. This study investigated immunological differences between patients with or without measurable remaining endogenous insulin production after ≥10 years duration of disease. RESEARCH DESIGN AND METHODS Patients (n = 113; ≥18 years of age) with type 1 diabetes and with disease duration of ≥10 years were recruited at Uppsala University Hospital. Residual β-cell function was determined with an ultrasensitive C-peptide ELISA. Circulating cytokines, including interleukin-35 (IL-35), were determined in plasma. Additional blood samples were collected from 14 of the identified C-peptide–positive patients and 12 of the C-peptide–negative patients, as well as from 15 healthy control subjects, and were used for immediate investigation of peripheral blood mononuclear cells. RESULTS The blood concentration of the cytokine IL-35 was markedly lower in C-peptide–negative patients, and this was associated with a simultaneous decrease in the proportion of IL-35+ regulatory T cells (Tregs), IL-35+ regulatory B cells, and IL-35–producing CD8+Foxp3+ cells. IL-35 has previously been shown to maintain the phenotype of Tregs, block the differentiation of T-helper 17 cells, and thereby dampen immune assaults to β-cells. We found that the proportions of IL-17a+ cells among the Tregs, CD4+ T cells, and CD8+ T cells were lower in the C-peptide–positive patients. CONCLUSIONS Patients with remaining endogenous β-cell function after &amp;gt;10 years duration of type 1 diabetes differ immunologically from other patients with long-standing type 1 diabetes. In particular, they have a much higher IL-35 production.
Brain Amyloid Pathology and Cognitive Function
Authors: Pieter Jelle Visser, Betty Tijms
Journal: JAMA (2017)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Technical aspects of placing a second lumen-apposing metal stent at a separate session for a persistent walled-off pancreatic necrosis
Authors: Arvind Trindade, Yun Kim, Brian Markowitz, Petros Benias
Journal: Endoscopy (2017)

A 35-year-old man, presented with a 12 cm walled-off pancreatic necrosis (WON) ([Fig. 1] a). A 15 mm lumen-apposing metal stent (LAMS, Hot AXIOS; Boston Scientific, Marlborough, Massachusetts, USA) was placed from the duodenal bulb ([Fig. 2 a]). Computed tomography (CT) imaging 3 days later showed that the stent was in place ([Fig. 1 b]). A subsequent necrosectomy was performed, resulting in improved symptoms.
Erratum: Tumor necrosis factor-α-induced apoptosis in prostate cancer cells through inhibition of nuclear factor-κB by an IκBα "super-repressor," (Clinical Cancer Research (2002) 6 (1969-1977))
Authors: H. J. Muenchen, D. L. Lin, M. A. Walsh, E. T. Keller, K. J. Pienta
Journal: Clinical Cancer Research (2002)
Motor Vehicle Crash Risk Among Adolescents and Young Adults With Attention-Deficit/Hyperactivity Disorder
Authors: Allison E. Curry, Kristina B. Metzger, Melissa R. Pfeiffer, Michael R. Elliott, Flaura K. Winston, Thomas J. Power
Journal: JAMA Pediatrics (2017)

<h3>Importance</h3> Attention-deficit/hyperactivity disorder (ADHD) often persists into adolescence, when motor vehicle crash risk peaks. We know little about when adolescents with ADHD get licensed and, once they do, the extent to which they have increased crash risk compared with adolescents without ADHD. <h3>Objectives</h3> To examine the association between ADHD and both driver licensing and crash involvement and whether it varies by sex, licensing age, and/or being prescribed ADHD medication at licensure. <h3>Design, Setting, and Participants</h3> This retrospective cohort study was conducted at 6 primary care practices of the Children's Hospital of Philadelphia, a large pediatric health care network in southeastern Pennsylvania and southern New Jersey. Using electronic health records, we defined a cohort of 2479 adolescents and young adults with ADHD and 15 865 without ADHD who were (1) born from 1987 to 1997; (2) residents of New Jersey and patients at 1 of 6 New Jersey primary care practices at age 12 years or older; and (3) age-eligible to obtain a driver's license from 2004 through 2014. Electronic health records data were then linked with New Jersey's statewide driver licensing and crash databases for 2004 through 2014. <h3>Main Outcomes and Measures</h3> Acquisition of a driver's license and first involvement as a driver in a police-reported crash. Survival analysis was used to estimate adjusted hazard ratios for licensing and crash outcomes through age 25 years. <h3>Results</h3> The median age of individuals at the end of the study was 22.2 years (interquartile range, 19.7-24.8). Compared with individuals without ADHD, the licensing probability of individuals with ADHD 6 months after eligibility was 35% lower (for males: adjusted hazard ratio, 0.65; 95% CI, 0.61-0.70; females: adjusted hazard ratio, 0.64; 95% CI, 0.58-0.70). Among individuals with a driver's license, 764 of 1785 with ADHD (42.8%) and 4715 of 13 221 without ADHD (35.7%) crashed during the study period. The adjusted risk for first crash among licensed drivers with ADHD was 1.36 times higher than for those without ADHD (95% CI, 1.25-1.48) and did not vary by sex, licensing age, or over time. Only 129 individuals with ADHD (12.1%) were prescribed medication in the 30 days before licensure. <h3>Conclusions and Relevance</h3> Adolescents with ADHD get licensed less often and at an older age. Once licensed, this cohort has a greater risk of crashing. Additional research is needed to understand the specific mechanisms by which ADHD influences crash risk.
Intertumoral Heterogeneity within Medulloblastoma Subgroups
Authors: Florence M.G. Cavalli, Marc Remke, Ladislav Rampasek, John Peacock, David J.H. Shih, Betty Luu, Livia Garzia, Jonathon Torchia, Carolina Nor, A. Sorana Morrissy, Sameer Agnihotri, Yuan Yao Thompson, Claudia M. Kuzan-Fischer, Hamza Farooq, Keren Isaev, Craig Daniels, Byung-Kyu Cho, Seung-Ki Kim, Kyu-Chang Wang, Ji Yeoun Lee, Wieslawa A. Grajkowska, Marta Perek-Polnik, Alexandre Vasiljevic, Cecile Faure-Conter, Anne Jouvet, Caterina Giannini, Amulya A. Nageswara Rao, Kay Ka Wai Li, Ho-Keung Ng, Charles G. Eberhart, Ian F. Pollack, Ronald L. Hamilton, G. Yancey Gillespie, James M. Olson, Sarah Leary, William A. Weiss, Boleslaw Lach, Lola B. Chambless, Reid C. Thompson, Michael K. Cooper, Rajeev Vibhakar, Peter Hauser, Marie-Lise C. van Veelen, Johan M. Kros, Pim J. French, Young Shin Ra, Toshihiro Kumabe, Enrique López-Aguilar, Karel Zitterbart, Jaroslav Sterba, Gaetano Finocchiaro, Maura Massimino, Erwin G. Van Meir, Satoru Osuka, Tomoko Shofuda, Almos Klekner, Massimo Zollo, Jeffrey R. Leonard, Joshua B. Rubin, Nada Jabado, Steffen Albrecht, Jaume Mora, Timothy E. Van Meter, Shin Jung, Andrew S. Moore, Andrew R. Hallahan, Jennifer A. Chan, Daniela P.C. Tirapelli, Carlos G. Carlotti, Maryam Fouladi, José Pimentel, Claudia C. Faria, Ali G. Saad, Luca Massimi, Linda M. Liau, Helen Wheeler, Hideo Nakamura, Samer K. Elbabaa, Mario Perezpeña-Diazconti, Fernando Chico Ponce de León, Shenandoah Robinson, Michal Zapotocky, Alvaro Lassaletta, Annie Huang, Cynthia E. Hawkins, Uri Tabori, Eric Bouffet, Ute Bartels, Peter B. Dirks, James T. Rutka, Gary D. Bader, Jüri Reimand, Anna Goldenberg, Vijay Ramaswamy, Michael D. Taylor
Journal: Cancer Cell (2017)
Abstract 2: IL-10 Modulates Mobilization of Bone Marrow Endothelial Progenitor Cells and Enhances Their Survival and Angiogenic Properties in Ischemic Myocardium
Authors: Prasanna Krishnamurthy, Melissa Thal, Suresh Verma, Eneda Hoxha, Erin Lambers, Veronica Ramirez, Gangjian Qin, Douglas Losordo, Raj Kishore
Journal: Circulation Research (2011)

Endothelial progenitor cells (EPC) transplantation has been shown to enhance neovascularization and improve myocardial infarction (MI)-induced ventricular dysfunctions. However, persistent inflammation in the ischemic myocardium, adversely affect EPC survival and function, thereby compromising full benefits of EPC-mediated vascular repair. We hypothesized that modulation of IL-10 signaling in EPCs enhances their mobilization, survival and function in ischemic myocardium after MI. GFP-labeled EPC were transplanted intramyocardially after induction of MI, and the mice were treated with either saline or recombinant IL-10. EPC survival and EPC-mediated neovascularization and myocardial repair were evaluated. IL-10-treated mice showed increased number of GFP+EPCs retention that was associated with reduced EPC apoptosis in the myocardium (P&lt;0.05). The engraftment of EPC into the vascular structures and the associated capillaries density was significantly higher in IL-10-treated mice (P&lt;0.05). The above findings were corroborated with reduced infarct size, fibrosis and enhanced LV function (echocardiography) in IL-10+EPC group as compared to EPC+saline group. Invitro, IL-10-deficient EPCs showed higher LPS-induced apoptosis compared to WT-EPCs (P&lt;0.05). IL-10 treatment induced VEGF expression in WT-EPCs which was abrogated by STAT3 inhibition (using curcurbitacin I). Furthermore, microRNA (miR) profile experiments identified significant increases in a number of pro-apoptotic and anti-angiogenic-related miRs in EPCs from IL-10 deficient mice. Interestingly, IL-10-deficient mice showed impaired MI-induced mobilization of bone marrow EPCs (Sca1+Flk1+ cells) into the circulation and the associated SDF-1 mRNA expression in the myocardium. Bone marrow transplantation studies involving replacement of IL-10-deficient marrow with WT marrow attenuated these effects. Invitro, LPS-induced CXCR4 expression was lower in IL-10-deficient EPCs as compared to WT-EPC. Taken together, our studies suggest that IL-10 enhances EPC mobilization, possibly in an SDF1-CXCR4 dependent manner and increased their survival and neovascularization and the associated myocardial repair, in part via activation of STAT3 signaling cascades.
Supreme Court rejects Northern Irish woman’s appeal for NHS abortion in England
Authors: Clare Dyer
Journal: BMJ (2017)

Women from Northern Ireland, where abortion laws are among the most restrictive in Europe, are not entitled to free terminations on the NHS in England, the UK’s highest court has ruled.

The Supreme Court narrowly rejected an appeal by a resident of Northern Ireland who became pregnant at age 15 and obtained a private abortion in England at a total cost of around £900 (€1020; $1150).

The High Court originally ruled against her in 2014,1 as did the Court of Appeal in 2015, and she has now narrowly …
Erratum: Zidovudine compared with didanosine in patients with advanced HIV type 1 infection and little or no previous experience with zidovudine (Archives of Internal Medicine (May 8, 1995) 155 (961-974))
Authors: R. Dolin, D. A. Amato, M. A. Fischl, C. Pettinelli, M. Beltangady, S. H. Liou, M. J. Brown, A. P. Cross, M. S. Hirsch, W. D. Hardy, D. Mildvan, D. C. Blair, W. G. Powderly, M. F. Para, Kenneth Fife, R. T. Steigbigel, L. Smaldone
Journal: JAMA Internal Medicine (1995)
Quantifying patients’ motivations for phase I oncology trials and how expectations change at the first clinical consultation.
Authors: Saoirse Olivia Dolly, Eleftheria Kalaitzaki, Sarah Jane Stimpson, Janet Hanwell, Sonia Serrano Fandos, Sarah Stapleton, Thushara Ansari, Clare Peckitt, Stan B Kaye, Johann S. De Bono, Udai Banerji
Journal: Journal of Clinical Oncology (2016)

10061 Background: In order to better inform our clinical practice in the Drug Development Unit, our aims were to capture patients’ motivations for phase I trials, quantify expectations of benefit, risks and commitment to clinical trials and the impact of the initial clinical consultation on these. Methods: A single centre, non-randomised prospective quantitative study of newly referred adult patients considering their first phase I trial. Participants completed questionnaires prior to being seen and an abbreviated follow-up version after the consultation. Results: Questionnaires were completed by 389 (98%) patients before and 302 (78%) after clinic. Patients ranked the most important motivation as hope for tumour shrinkage 84%, followed by perception of no alternative treatments 56%, following their doctor’s recommendation 44% and lastly that research may benefit others 38%. Patients had high therapeutic expectations with 43% predicting tumour shrinkage at the outset. Following the first consultation this increased to 47% with 14% expecting a cure. Participants’ perceptions about adverse events were reasonable with 11% expecting severe side effects. Prior to attendance patients did not appreciate the weekly time commitment, this was well understood by 93% post consultation. Overall patients were keen to consider trials with 72% pre- and 84% of post-clinic patients willing to enroll. Conclusions: This study confirmed unrealistically high patient expectations of benefit from early phase trials, in which the actual response rate is around 10%. The first consultation does not alter this or the willingness to participate but does improve understanding of the time commitment required. These data will help healthcare professionals tailor future patient consultations.
Design of ALTA-1L (ALK in lung cancer trial of brigatinib in first-line), a randomized phase 3 trial of brigatinib (BRG) versus crizotinib (CRZ) in tyrosine kinase inhibitor (TKI)-naive patients (pts) with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).
Authors: Marcello Tiseo, Sanjay Popat, Scott N. Gettinger, Solange Peters, Jeff Haney, David Kerstein, D. Ross Camidge
Journal: Journal of Clinical Oncology (2017)

TPS9098 Background: BRG is an investigational, next-generation ALK inhibitor with potent preclinical activity against rearranged ALK and CRZ-resistant mutants. In an ongoing phase 1/2 trial, BRG has shown promising intracranial and whole-body activity in ALK+ NSCLC pts with or without prior CRZ therapy ( Lancet Oncol. 2016;17:1683-96). In an ongoing pivotal randomized phase 2 trial (ALTA) evaluating 2 BRG regimens (90 mg qd and 180 mg qd with a 7-d lead-in at 90 mg), BRG has shown substantial objective response rates (ORRs) and robust progression-free survival (PFS) in pts with CRZ-resistant ALK+ NSCLC, particularly at 180 mg (with lead-in), and acceptable safety ( J Thorac Oncol. 2017;12:S612-3). Based on these results, the ALTA-1L trial was designed to assess the efficacy and safety of BRG vs CRZ in pts with advanced ALK+ NSCLC naive to TKI therapy (including ALK inhibitors). Methods: ALTA-1L (NCT02737501) is an open-label, multicenter, randomized phase 3 trial. Pts (≥18 y of age) are required to have locally advanced or metastatic ALK+ NSCLC, no prior TKI therapy, and ≤1 prior systemic anticancer regimen in the advanced setting. Approximately 270 pts will be stratified by presence of brain metastases at baseline and prior chemotherapy (yes/no) and randomized 1:1 to receive oral BRG (180 mg qd with a 7-d lead-in at 90 mg) or CRZ (250 mg bid). The primary endpoint is PFS per RECIST v1.1 assessed by a blinded independent review committee (BIRC); secondary endpoints include ORR, duration of response, overall survival, safety/tolerability, pt-reported outcomes, and intracranial ORR/PFS. The primary endpoint will be analyzed with the Kaplan-Meier method and a 2-sided stratified log-rank test after 198 events; 2 interim analyses are planned after approximately 50% and 75% of expected events. CRZ-treated pts may cross over to BRG (180 mg [with lead-in]) after BIRC-assessed disease progression. ALTA-1L was initiated in April 2016; 150 sites are planned in North America, Europe, and the Asia-Pacific region. 97 pts were enrolled as of February 6, 2017. Clinical trial information: NCT02737501.
A TNF–JNK–Axl–ERK signaling axis mediates primary resistance to EGFR inhibition in glioblastoma
Authors: Gao Guo, Ke Gong, Sonia Ali, Neha Ali, Shahzad Shallwani, Kimmo J Hatanpaa, Edward Pan, Bruce Mickey, Sandeep Burma, David H Wang, Santosh Kesari, Jann N Sarkaria, Dawen Zhao, Amyn A Habib
Journal: Nature Neuroscience (2017)
Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA analysis in metastatic breast cancer
Authors: C. Fribbens, I. Garcia Murillas, M. Beaney, S. Hrebien, B. O’Leary, L. Kilburn, K. Howarth, M. Epstein, E. Green, N. Rosenfeld, A. Ring, S. Johnston, N. Turner
Journal: Annals of Oncology (2017)
Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes
Authors: Bruce Neal, Vlado Perkovic, Kenneth W. Mahaffey, Dick de Zeeuw, Greg Fulcher, Ngozi Erondu, Wayne Shaw, Gordon Law, Mehul Desai, David R. Matthews
Journal: New England Journal of Medicine (2017)

Canagliflozin is a sodium–glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes.
Monocytes inhibit NK activity<i>via</i>TGF-β in patients with obstructive sleep apnoea
Authors: Enrique Hernández-Jiménez, Carolina Cubillos-Zapata, Victor Toledano, Rebeca Pérez de Diego, Isabel Fernández-Navarro, Raquel Casitas, Carlos Carpio, Jose Casas-Martín, Jaime Valentín, Anibal Varela-Serrano, Jose Avendaño-Ortiz, Enrique Alvarez, Luis A. Aguirre, Antonio Pérez-Martínez, Maria P. De Miguel, Cristobal Belda-Iniesta, Francisco García-Río, Eduardo López-Collazo
Journal: European Respiratory Journal (2017)

Obstructive sleep apnoea (OSA) is associated with cancer incidence and mortality. The contribution of the immune system appears to be crucial; however, the potential role of monocytes and natural killer (NK) cells remains unclear. Quantitative reverse transcriptase PCR, flow cytometry and in vitro assays were used to analyse the phenotype and immune response activity in 92 patients with OSA (60 recently diagnosed untreated patients and 32 patients after 6 months of treatment with continuous positive airway pressure (CPAP)) and 29 healthy volunteers (HV). We determined that monocytes in patients with OSA exhibit an immunosuppressive phenotype, including surface expression of glycoprotein-A repetitions predominant protein (GARP) and transforming growth factor-β (TGF-β), in contrast to those from the HV and CPAP groups. High levels of TGF-β were detected in OSA sera. TGF-β release by GARP + monocytes impaired NK cytotoxicity and maturation. This altered phenotype correlated with the hypoxic severity clinical score (CT90). Reoxygenation eventually restored the altered phenotypes and cytotoxicity. This study demonstrates that GARP + monocytes from untreated patients with OSA have an NK-suppressing role through their release of TGF-β. Our findings show that monocyte plasticity immunomodulates NK activity in this pathology, suggesting a potential role in cancer incidence.
Presenilins regulate synaptic plasticity and mitochondrial calcium homeostasis in the hippocampal mossy fiber pathway
Authors: Sang Hun Lee, David Lutz, Mohanad Mossalam, Vadim Y. Bolshakov, Michael Frotscher, Jie Shen
Journal: Molecular Neurodegeneration (2017)

Presenilins play a major role in the pathogenesis of Alzheimer's disease, in which the hippocampus is particularly vulnerable. Previous studies of Presenilin function in the synapse, however, focused exclusively on the hippocampal Schaffer collateral (SC) pathway. Whether Presenilins play similar or distinct roles in other hippocampal synapses is unknown.To investigate the role of Presenilins at mossy fiber (MF) synapses we performed field and whole-cell electrophysiological recordings and Ca2+ imaging using acute hippocampal slices of postnatal forebrain-restricted Presenilin conditional double knockout (PS cDKO) and control mice at 2 months of age. We also performed quantitative electron microscopy (EM) analysis to determine whether mitochondrial content is affected at presynaptic MF boutons of PS cDKO mice. We further conducted behavioral analysis to assess spatial learning and memory of PS cDKO and control mice at 2 months in the Morris water maze.We found that long-term potentiation and short-term plasticity, such as paired-pulse and frequency facilitation, are impaired at MF synapses of PS cDKO mice. Moreover, post-tetanic potentiation (PTP), another form of short-term plasticity, is also impaired at MF synapses of PS cDKO mice. Furthermore, blockade of mitochondrial Ca2+ efflux mimics and occludes the PTP deficits at MF synapses of PS cDKO mice, suggesting that mitochondrial Ca2+ homeostasis is impaired in the absence of PS. Quantitative EM analysis showed normal number and area of mitochondria at presynaptic MF boutons of PS cDKO mice, indicating unchanged mitochondrial content. Ca2+ imaging of dentate gyrus granule neurons further revealed that cytosolic Ca2+ increases induced by tetanic stimulation are reduced in PS cDKO granule neurons in acute hippocampal slices, and that inhibition of mitochondrial Ca2+ release during high frequency stimulation mimics and occludes the Ca2+ defects observed in PS cDKO neurons. Consistent with synaptic plasticity impairment observed at MF and SC synapses in acute PS cDKO hippocampal slices, PS cDKO mice exhibit profound spatial learning and memory deficits in the Morris water maze.Our findings demonstrate the importance of PS in the regulation of synaptic plasticity and mitochondrial Ca2+ homeostasis in the hippocampal MF pathway.
Burnout—There’s an App for That
Authors: Noa Holoshitz, Samuel Wann
Journal: JAMA Cardiology (2017)

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 Cardiology 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 Cardiology journal