tbuckley/cabot-search huggingface dataset:
Psychological and Behavioral Interventions for Managing Insomnia Disorder: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians
Authors: Michelle Brasure, Erika Fuchs, Roderick MacDonald, Victoria A. Nelson, Erin Koffel, Carin M. Olson, Imran S. Khawaja, Susan Diem, Maureen Carlyle, Timothy J. Wilt, Jeannine Ouellette, Mary Butler, Robert L. Kane
Journal: Annals of Internal Medicine (2016)

Background: Psychological and behavioral interventions are frequently used for insomnia disorder. Purpose: To assess benefits and harms of psychological and behavioral interventions for insomnia disorder in adults. Data Sources: Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and PsycINFO through September 2015, supplemented with hand-searching. Study Selection: Randomized, controlled trials of psychological or behavioral interventions that were published in English and enrolled adults with insomnia disorder lasting 4 or more weeks. Data Extraction: Data extraction by single investigator confirmed by a second reviewer; dual investigator assessment of risk of bias; consensus determination of strength of evidence. Data Synthesis: Sixty trials with low to moderate risk of bias compared psychological and behavioral interventions with inactive controls or other psychological and behavioral interventions. Cognitive behavioral therapy for insomnia (CBT-I) improved posttreatment global and most sleep outcomes, often compared with information or waitlist controls (moderate-strength evidence). Use of CBT-I improved several sleep outcomes in older adults (low- to moderate-strength evidence). Multicomponent behavioral therapy improved several sleep outcomes in older adults (low- to moderate-strength evidence). Stimulus control improved 1 or 2 sleep outcomes (low-strength evidence). Evidence for other comparisons and for harms was insufficient to permit conclusions. Limitations: A wide variety of comparisons limited the ability to pool data. Trials did not always report global outcomes and infrequently conducted remitter or responder analysis. Comparisons were often information or waitlist groups, and publication bias was possible. Conclusion: Use of CBT-I improves most outcomes compared with inactive controls. Multicomponent behavioral therapy and stimulus control may improve some sleep outcomes. Evidence on other outcomes, comparisons, and long-term efficacy were limited. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42014009908)
DREADD Modulation of Transplanted DA Neurons Reveals a Novel Parkinsonian Dyskinesia Mechanism Mediated by the Serotonin 5-HT6 Receptor
Authors: Patrick Aldrin-Kirk, Andreas Heuer, Gang Wang, Bengt Mattsson, Martin Lundblad, Malin Parmar, Tomas Björklund
Journal: Neuron (2016)
Chlormadinone contraceptive withdrawn. (Letter to the editor)
Authors: Daniel Gr
Journal: BMJ (1970)

We regret to announce the suspension from the market of Verton the low dose estrogen-free preparation containing chlormadinone acetate.  Doctors have already received letters making this announcement.  This decision is taken in view of overreaction to any adverse reports associated with oral contraceptives in the light of certain reported findings of breast nodules in dogs.  Long-term toxicity tests on such animals are required by the Food and Drug Administration of America but not by the Committee on Safety of Drugs in the United Kingdom.  The significance of these reported findings is unclear and it is known that the metabolism of certain sex steroids in the dog is significantly different from that in man and monkey.  In addition the reaction of dogs to progestins is markedly different from that in man and the natural history of these nodules which appeared in a significant proportion of dogs by the age of 6 bears little resemblance to that of breast  cancer in the human.  The Committee on Safety of Drugs required long-term toxicity studies in rats and mice and in these species no similar effects have been shown.  Further no similar findings have been observed in monkeys treated for a little over a year.  Nevertheless because of the recent alarmist publicity in relation to chlormadinone acetate we have decided to suspend it from the market.  This decision is taken in consultation with the Committee on the Safety of Drugs with whom we have been in almost daily contact over the past few weeks.(FULL TEXT)
Weights and Measures
Authors: Gaetan Sgro
Journal: JAMA (2016)

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
The microenvironment of classical Hodgkin lymphoma: heterogeneity by Epstein–Barr virus presence and location within the tumor
Authors: R Wu, A Sattarzadeh, B Rutgers, A Diepstra, A van den Berg, L Visser
Journal: Blood Cancer Journal (2016)

Correction to: Blood Cancer Journal (2016) 6, e417; doi:10.1038/bcj.2016.26 Since the publication of the paper the authors have noticed that R Wu was listed as the sole first author. This is incorrect; R Wu and A Sattarzadeh contributed equally to this paper and are co-first authors. The authors wish to apologize for any inconvenience caused.
Novel pathomechanisms of cardiomyocyte dysfunction in a model of heart failure with preserved ejection fraction
Authors: Uwe Primessnig, Patrick Schönleitner, Alexander Höll, Susanne Pfeiffer, Taja Bracic, Thomas Rau, Martin Kapl, Tatjana Stojakovic, Toma Glasnov, Kirsten Leineweber, Paulina Wakula, Gudrun Antoons, Burkert Pieske, Frank R. Heinzel
Journal: European Journal of Heart Failure (2016)
Development of a bile acid–based newborn screen for Niemann-Pick disease type C
Authors: Xuntian Jiang, Rohini Sidhu, Laurel Mydock-McGrane, Fong-Fu Hsu, Douglas F. Covey, David E. Scherrer, Brian Earley, Sarah E. Gale, Nicole Y. Farhat, Forbes D. Porter, Dennis J. Dietzen, Joseph J. Orsini, Elizabeth Berry-Kravis, Xiaokui Zhang, Janice Reunert, Thorsten Marquardt, Heiko Runz, Roberto Giugliani, Jean E. Schaffer, Daniel S. Ory
Journal: Science Translational Medicine (2016)

Niemann-Pick disease type C (NPC) is a fatal, neurodegenerative, cholesterol storage disorder. With new therapeutics in clinical trials, it is imperative to improve diagnostics and facilitate early intervention. We used metabolomic profiling to identify potential markers and discovered three unknown bile acids that were increased in plasma from NPC but not control subjects. The bile acids most elevated in the NPC subjects were identified as 3β,5α,6β-trihydroxycholanic acid and its glycine conjugate, which were shown to be metabolites of cholestane-3β,5α,6β-triol, an oxysterol elevated in NPC. A high-throughput mass spectrometry-based method was developed and validated to measure the glycine-conjugated bile acid in dried blood spots. Analysis of dried blood spots from 4992 controls, 134 NPC carriers, and 44 NPC subjects provided 100% sensitivity and specificity in the study samples. Quantification of the bile acid in dried blood spots, therefore, provides the basis for a newborn screen for NPC that is ready for piloting in newborn screening programs.
Concussion Symptoms and Return to Play Time in Youth, High School, and College American Football Athletes
Authors: Zachary Y. Kerr, Scott L. Zuckerman, Erin B. Wasserman, Tracey Covassin, Aristarque Djoko, Thomas P. Dompier
Journal: JAMA Pediatrics (2016)

To our knowledge, little research has examined concussion across the youth/adolescent spectrum and even less has examined concussion-related outcomes (ie, symptoms and return to play).To examine and compare sport-related concussion outcomes (symptoms and return to play) in youth, high school, and collegiate football athletes.Athletic trainers attended each practice and game during the 2012 to 2014 seasons and reported injuries. For this descriptive, epidemiological study, data were collected from youth, high school, and collegiate football teams, and the analysis of the data was conducted between July 2015 and September 2015. The Youth Football Surveillance System included more than 3000 youth football athletes aged 5 to 14 years from 118 teams, providing 310 team seasons (ie, 1 team providing 1 season of data). The National Athletic Treatment, Injury, and Outcomes Network Program included 96 secondary school football programs, providing 184 team seasons. The National Collegiate Athletic Association Injury Surveillance Program included 34 college football programs, providing 71 team seasons.We calculated the mean number of symptoms, prevalence of each symptom, and the proportion of patients with concussions that had long return-to-play time (ie, required participation restriction of at least 30 days). Generalized linear models were used to assess differences among competition levels in the mean number of reported symptoms. Logistic regression models estimated the odds of return to play at less than 24 hours and at least 30 days.Overall, 1429 sports-related concussions were reported among youth, high school, and college-level football athletes with a mean (SD) of 5.48 (3.06) symptoms. Across all levels, 15.3% resulted return to play at least 30 days after the concussion and 3.1% resulted in return to play less than 24 hours after the concussion. Compared with youth, a higher number of concussion symptoms were reported in high school athletes (β = 1.39; 95% CI, 0.55-2.24). Compared with college athletes, the odds of return to play at least 30 days after injury were larger in youth athletes (odds ratio, 2.75; 95% CI, 1.10- 6.85) and high school athletes (odds ratio, 2.89; 95% CI, 1.61-5.19). The odds of return to play less than 24 hours after injury were larger in youth athletes than high school athletes (odds ratio, 6.23; 95% CI, 1.02-37.98).Differences in concussion-related outcomes existed by level of competition and may be attributable to genetic, biologic, and/or developmental differences or level-specific variations in concussion-related policies and protocols, athlete training management, and athlete disclosure. Given the many organizational, social environmental, and policy-related differences at each level of competition that were not measured in this study, further study is warranted to validate our findings.
Busulphan-melphalan as a myeloablative therapy (MAT) for high-risk neuroblastoma: Results from the HR-NBL1/SIOPEN trial.
Authors: R. L. Ladenstein, U. Poetschger, R. Luksch, P. Brock, V. Castel, I. Yaniv, V. Papadakis, G. Laureys, J. Malis, W. Balwierz, E. Ruud, P. Kogner, H. Schroeder, A. Forjaz De Lacerda, M. Beck Popovic, P. Bician, M. Garami, T. Trahair, A. D. Pearson, D. Valteau Couanet
Journal: Journal of Clinical Oncology (2011)

2 The full, final text of this abstract will be available in Part II of the 2011 Annual Meeting Proceedings, distributed onsite at the Meeting on June 4, 2011, and as a supplement to the June 20, 2011, issue of Journal of Clinical Oncology.
BCAM and LAMA5 Mediate the Recognition between Tumor Cells and the Endothelium in the Metastatic Spreading of KRAS-Mutant Colorectal Cancer
Authors: Alice Bartolini, Sabrina Cardaci, Simona Lamba, Daniele Oddo, Caterina Marchiò, Paola Cassoni, Carla Azzurra Amoreo, Giorgio Corti, Alessandro Testori, Federico Bussolino, Renata Pasqualini, Wadih Arap, Davide Corà, Federica Di Nicolantonio, Serena Marchiò
Journal: Clinical Cancer Research (2016)

KRAS mutations confer adverse prognosis to colorectal cancer, and no targeted therapies have shown efficacy in this patient subset. Paracrine, nongenetic events induced by KRAS-mutant tumor cells are expected to result in specific deregulation and/or relocation of tumor microenvironment (TME) proteins, which in principle can be exploited as alternative therapeutic targets.A multimodal strategy combining ex vivo/in vitro phage display screens with deep-sequencing and bioinformatics was applied to uncover TME-specific targets in KRAS-mutant hepatic metastasis from colorectal cancer. Expression and localization of BCAM and LAMA5 were validated by immunohistochemistry in preclinical models of human hepatic metastasis and in a panel of human specimens (n = 71). The antimetastatic efficacy of two BCAM-mimic peptides was evaluated in mouse models. The role of BCAM in the interaction of KRAS-mutant colorectal cancer cells with TME cells was investigated by adhesion assays.BCAM and LAMA5 were identified as molecular targets within both tumor cells and TME of KRAS-mutant hepatic metastasis from colorectal cancer, where they were specifically overexpressed. Two BCAM-mimic peptides inhibited KRAS-mutant hepatic metastasis in preclinical models. Genetic suppression and biochemical inhibition of either BCAM or LAMA5 impaired adhesion of KRAS-mutant colorectal cancer cells specifically to endothelial cells, whereas adhesion to pericytes and hepatocytes was unaffected.These data show that the BCAM/LAMA5 system plays a functional role in the metastatic spreading of KRAS-mutant colorectal cancer by mediating tumor-TME interactions and as such represents a valuable therapeutic candidate for this large, currently untreatable patient group. Clin Cancer Res; 22(19); 4923-33. ©2016 AACR.
CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands
Authors: Bruno Lamas, Mathias L Richard, Valentin Leducq, Hang-Phuong Pham, Marie-Laure Michel, Gregory Da Costa, Chantal Bridonneau, Sarah Jegou, Thomas W Hoffmann, Jane M Natividad, Loic Brot, Soraya Taleb, Aurélie Couturier-Maillard, Isabelle Nion-Larmurier, Fatiha Merabtene, Philippe Seksik, Anne Bourrier, Jacques Cosnes, Bernhard Ryffel, Laurent Beaugerie, Jean-Marie Launay, Philippe Langella, Ramnik J Xavier, Harry Sokol
Journal: Nature Medicine (2016)
Serum Protein Electrophoresis in Tuberculosis
Authors: B FREIGANG, R P BOYD, G B ELLIOTT
Journal: JAMA (1963)

Serial serum protein electrophoretic determinations at two-month intervals were carried out on 84 tuberculous patients undergoing treatment in a sanatorium. An attempt was made to correlate changes in the albumin/alpha-2 globulin ratios and gamma globulin levels with clinical and roentgenographic status. It was observed that before treatment of the tuberculous process the albumin/alpha-2 globulin ratios were low and the gamma globulin levels were increased. As improvement occurred, albumin/alpha-2 globulin ratios increased and gamma globulin values decreased. A poor prognosis was indicated by decreasing albumin/alpha-2 globulin ratios. Electrophoretograms are of particular value in assessing the effect of surgery, especially when roentgenographic studies are not informative. They are also a valuable guide in deciding upon the duration of therapy necessary for individual cases.
EGFR inhibitor gefitinib in advanced pretreated non-small cell lung cancer patients: Experience from a centre in north India
Authors: V. Talvar, A. K. Vaid, D. C. Doval, S. Gupta, J. B. Sharma, J. Sarin
Journal: Journal of Clinical Oncology (2006)

17141 Background: Gefitinib is an orally active EGFR-TKI (Epidermal Growth Factor Tyrosine Kinase Inhibitor) that demonstrated, clinically meaningful anti tumor activity, favorable toxicity profile in phase II trials involving patients with advanced pretreated NSCLC. The aim of this study was to assess the antitumour activity (time to disease progression) and toxicity profile of Gefitinib. Methods: Twenty five patients of NSCLC advanced were included in this study who have failed at least one chemotherapy regimen and completed at least one month Gefitinib (250 mg/day) therapy. The study included 18 male and 7 female patients with, a median age of 60 years (32–80 years) and performance status ECOG 0-I 64%. The histologically included were Adenocarcinoma 56%, Squamous Cell Carcinoma 40% and Large Cell Carcinoma 1%. 64% patients had failed to response to 1 (CT) chemotherapy regimen, 28% to 2 CT and 8% to 3 CT regimens. Results: A total of 25 patients (18 male, 7 female) were evaluated for response. 2 Complete Response (CR) and 1 Partial Response (PR) were observed with an Overall Response Rate (ORR) of 12% (CR+PR). All the three patients were with Adenocarcinoma histology. A total of 14 patients (56%) had Stable Disease (SD). This led to an Overall Disease Control Rate (CR+PR+SD) of 68% (17 patients). The Median Time to Progression (TTP) was 3.8 months using the SAS method for statistical analysis (95% CI 4.4–9.3). The number of previous chemotherapy regimens did not alter the response to therapy. All the patients were evaluated for toxicity profile assessment (25 patients). The most frequent toxicity observed was Asthenia in 52% of patients. Other toxicities were Diarrhaea 24%, Skin Disorders 32%, Anorexia 32%, Vomitings 44%. Only 1 patient had grade IV skin related toxicity. No deaths related to Gefitinib treatment were reported. Conclusion: Gefitinib shows antitumour activity in pretreated patients of advanced NSCLC. Gefitinib therapy of (250 mg/day) has a favourable toxicity profile and is well tolerated. Gefitinib is a viable therapy in NSCLC patients who have limited treatment options. No significant financial relationships to disclose.
Lysosomal cathepsins and their regulation in aging and neurodegeneration
Authors: Veronika Stoka, Vito Turk, Boris Turk
Journal: Ageing Research Reviews (2016)

Lysosomes and lysosomal hydrolases, including the cathepsins, have been shown to change their properties with aging brain a long time ago, although their function was not really understood. The first biochemical and clinical studies were followed by a major expansion in the last 20 years with the development of animal disease models and new approaches leading to a major advancement of understanding of the role of physiological and degenerative processes in the brain at the molecular level. This includes the understanding of the major role of autophagy and the cathepsins in a number of diseases, including its critical role in the neuronal ceroid lipofuscinosis. Similarly, cathepsins and some other lysosomal proteases were shown to have important roles in processing and/or degradation of several important neuronal proteins, thereby having either neuroprotective or harmful roles. In this review, we discuss lysosomal cathepsins and their regulation with the focus on cysteine cathepsins and their endogenous inhibitors, as well as their role in several neurodegenerative diseases.
Global burden of diseases, injuries, and risk factors for young people's health during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013
Authors: Ali H Mokdad, Mohammad Hossein Forouzanfar, Farah Daoud, Arwa A Mokdad, Charbel El Bcheraoui, Maziar Moradi-Lakeh, Hmwe Hmwe Kyu, Ryan M Barber, Joseph Wagner, Kelly Cercy, Hannah Kravitz, Megan Coggeshall, Adrienne Chew, Kevin F O'Rourke, Caitlyn Steiner, Marwa Tuffaha, Raghid Charara, Essam Abdullah Al-Ghamdi, Yaser Adi, Rima A Afifi, Hanan Alahmadi, Fadia AlBuhairan, Nicholas Allen, Mohammad AlMazroa, Abdulwahab A Al-Nehmi, Zulfa AlRayess, Monika Arora, Peter Azzopardi, Carmen Barroso, Mohammed Basulaiman, Zulfiqar A Bhutta, Chris Bonell, Cecilia Breinbauer, Louisa Degenhardt, Donna Denno, Jing Fang, Adesegun Fatusi, Andrea B Feigl, Ritsuko Kakuma, Nadim Karam, Elissa Kennedy, Tawfik A M Khoja, Fadi Maalouf, Carla Makhlouf Obermeyer, Amitabh Mattoo, Terry McGovern, Ziad A Memish, George A Mensah, Vikram Patel, Suzanne Petroni, Nicola Reavley, Diego Rios Zertuche, Mohammad Saeedi, John Santelli, Susan M Sawyer, Fred Ssewamala, Kikelomo Taiwo, Muhammad Tantawy, Russell M Viner, Jane Waldfogel, Maria Paola Zuñiga, Mohsen Naghavi, Haidong Wang, Theo Vos, Alan D Lopez, Abdullah A Al Rabeeah, George C Patton, Christopher J L Murray
Journal: The Lancet (2016)
Bioavailability of the hedgehog pathway inhibitor GDC-0449 in a phase I pharmacokinetic (PK) study in healthy female subjects.
Authors: R. A. Graham, G. E. Morrison, I. Chang, K. Jorga, C. Hop, Y. Shin, V. Malhi, M. Xie, J. A. Low, B. L. Lum
Journal: Journal of Clinical Oncology (2010)

e13009 Background: In a phase I clinical trial, GDC-0449 was well tolerated in patients (pts) with solid tumors and showed promising efficacy in advanced basal cell carcinoma (Von Hoff et al., NEJM, 361:1164-72, 2009). Results suggested GDC-0449 had a long half-life (t) and nonlinear PK; semi-mechanistic modeling suggested nonlinear PK was due to prolonged absorption, slow metabolic elimination, plasma protein binding, or a combination of these factors. A study was conducted to evaluate GDC-0449 PK after a single oral and IV tracer-labeled microdose to understand its absorption and elimination characteristics, and to define absolute bioavailability. Methods: Six healthy female subjects of nonchildbearing potential were enrolled; each received GDC-0449 as a single 150 mg oral dose and as a C14-labeled (500 nCi, 10 μg) IV microdose bolus two hours later. Plasma was collected frequently during the initial 7 d then weekly for 56 d. Nonlabeled GDC-0449 plasma concentrations were assessed by liquid chromatography tandem mass spectrometry; radiolabeled GDC-0449 was measured by accelerator mass spectrometry. PK parameters were calculated by noncompartmental methods. Results: Following the 150 mg oral dose the mean ± SD maximum plasma concentration (Cmax), time to Cmax (Tmax), and t were: 5.95 ± 0.993 μM, 20.3 (range, 1-48) hrs, and 11.7 ± 2.58 d, respectively. Following the IV bolus dose GDC-0449 plasma concentrations decreased markedly over the first 30 minutes; this short distribution phase was followed by a slower elimination phase through the remainder of the study, with an average terminal t of 10.2 ± 2.06 d. Clearance was 47.2 ± 14.1 mL/hr; volume of distribution (Vss) was 16.1 ± 2.34 L; mean bioavailability was 34.7 ± 5.76%. Conclusions: GDC-0449 is absorbed slowly after a single oral dose; terminal elimination t was very long after both oral and IV administration, likely due to distribution and/or elimination processes, consistent with PK modeling. The Vss of 16.1 L suggests that GDC-0449 is distributed out of the plasma space. Mean bioavailability was moderate, 34.7%, with little inter-individual variability; micromolar plasma concentrations were achieved with a single 150 mg oral dose. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech, Roche