tbuckley/cabot-search huggingface dataset:
The Need for Large-Scale Randomized Evidence Without Undue Emphasis on Small Trials, Meta-analyses, or Subgroup Analyses
Authors: Charles H. Hennekens
Journal: JAMA (2009)

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
ABC transporter inhibitors that are substrates enhance lentiviral vector transduction into primitive hematopoietic progenitor cells
Authors: Brian M. Davis, Laurent Humeau, Vladimir Slepushkin, Gwendolyn Binder, Lauren Korshalla, Yajin Ni, E. Oluwakemi Ogunjimi, Lan-Fei Chang, Xiaobin Lu, Boro Dropulic
Journal: Blood (2004)
A comparison of real‐time and store‐and‐forward teledermatology: a cost–benefit study
Authors: M.A. Loane, S.E. Bloomer, R. Corbett, D.J. Eedy, N. Hicks, H.E. Lotery, C. Mathews, J. Paisley, K. Steele, R. Wootton
Journal: British Journal of Dermatology (2000)

Background Increasing use of teledermatology should be based on demonstration of favourable accuracy and cost–benefit analysis for the different methods of use of this technique. Objectives To evaluate the clinical efficacy and cost-effectiveness of real-time and store-and-forward teledermatology. Methods Patients attended their own health centre and in the company of a general practitioner (GP) were seen by a hospital dermatologist over the videolink (real-time). Before the videolink consultation commenced, the GP took instant photographs of the skin lesion and posted them along with a standard referral letter to a different hospital dermatologist (store-and-forward). In total, 96 patients were seen by both real-time and store-and-forward teledermatology. Comparative diagnoses, clinical management plans, clinical outcomes and associated costs were made between the two types of teledermatology consultation. Results There was agreement between the videolink diagnosis and the still image diagnosis in 51% of cases. The same or similar management plan was recommended at both types of consultation in 44% of cases. Following the store-and-forward consultation the dermatologist recommended that 69% of patients required at least one hospital appointment compared with 45% of those patients seen in real-time. The net societal cost of the initial real-time consultation was £132·10 per patient compared with £26·90 per patient for the initial store-and-forward consultation. Conclusions The store-and-forward consultation was cheaper, but less clinically efficient, compared with the real-time consultation. The absence of interaction in a store-and-forward consultation limits the dermatologist's ability to obtain clinically useful information in order to diagnose and manage a patient satisfactorily.
Different Lipid Variables Predict Incident Coronary Artery Disease in Patients With Type 1 Diabetes With or Without Diabetic Nephropathy: The FinnDiane Study
Authors: Nina Tolonen, Carol Forsblom, Ville-Petteri Mäkinen, Valma Harjutsalo, Daniel Gordin, Maija Feodoroff, Niina Sandholm, Lena M. Thorn, Johan Wadén, Marja-Riitta Taskinen, Per-Henrik Groop
Journal: Diabetes Care (2014)

To study the ability of lipid variables to predict incident coronary artery disease (CAD) events in patients with type 1 diabetes at different stages of nephropathy.Patients (n = 3,520) with type 1 diabetes and available lipid profiles participating in the Finnish Diabetic Nephropathy Study (FinnDiane) were included in the study. During a follow-up period of 10.2 years (8.6-12.0), 310 patients suffered an incident CAD event.Apolipoprotein B (ApoB)/ApoA-I ratio was the strongest predictor of CAD in normoalbuminuric patients (hazard ratio 1.43 [95% CI 1.17-1.76] per one SD increase), and ApoB was the strongest in macroalbuminuric patients (1.47 [1.19-1.81]). Similar results were seen when patients were stratified by sex or glycemic control. LDL cholesterol was a poor predictor of CAD in women, normoalbuminuric patients, and patients with HbA1c below the median (8.3%, 67 mmol/L). The current recommended triglyceride cutoff of 1.7 mmol/L failed to predict CAD in normoalbuminuric patients, whereas the cohort median 0.94 mmol/L predicted incident CAD events.In patients with type 1 diabetes, the predictive ability of the lipid variables differed substantially depending on the patient's sex, renal status, and glycemic control. In normoalbuminuric patients, the ratios of atherogenic and antiatherogenic lipoproteins and lipids were the strongest predictors of an incident CAD event, whereas in macroalbuminuric patients, no added benefit was gained from the ratios. Current treatment recommendations may need to be revised to capture residual CAD risk in patients with type 1 diabetes.
Density of dendritic cells in the human tracheal mucosa is age dependent and site specific
Authors: T Tschernig, V C de Vries, A S Debertin, A Braun, T Walles, F Traub, R Pabst
Journal: Thorax (2006)

<b>Background:</b> The mucosal immune system undergoes extensive changes in early childhood in response to environmental stimuli. Dendritic cells (DC) play a major role in the development of the immune system. However, few data exist on the influence of continuous environmental stimulation on the distribution and phenotype of human airway DC. <b>Methods:</b> Human tissue samples are mostly paraffin embedded which limits the use of several antibodies, and respiratory tissue for cryopreservation is difficult to obtain. Human frozen post mortem tracheal tissue was therefore used for this study. Only samples with epithelial adherence to the basement membrane were included (n = 34). Immunohistochemical staining and sequential overlay immunofluorescence were performed with DC-SIGN and a panel of leucocyte markers co-expressed by DC. <b>Results:</b> DC detected in the human tracheal mucosa using DC-SIGN correlated with the expression of HLA-DR, co-stimulatory and adhesion molecules. Higher cell densities were found at the ventral tracheal site of patients older than 1 year than in infants in the first year of life. <b>Conclusion:</b> The increasing population of mucosal DC with age could reflect immunological maturation.
TNF-α/IL-17 synergy inhibits IL-13 bioactivity via IL-13Rα2 induction
Authors: Vahe Badalyan, Robert Thompson, Kezia Addo, Lee A. Borthwick, Andrew J. Fisher, Tatiana Ort, Timothy G. Myers, Thomas A. Wynn, Thirumalai R. Ramalingam
Journal: Journal of Allergy and Clinical Immunology (2014)
Emerging roles of junctophilin-2 in the heart and implications for cardiac diseases
Authors: David L. Beavers, Andrew P. Landstrom, David Y. Chiang, Xander H.T. Wehrens
Journal: Cardiovascular Research (2014)

Cardiomyocytes rely on a highly specialized subcellular architecture to maintain normal cardiac function. In a little over a decade, junctophilin-2 (JPH2) has become recognized as a cardiac structural protein critical in forming junctional membrane complexes (JMCs), which are subcellular domains essential for excitation–contraction coupling within the heart. While initial studies described the structure of JPH2 and its role in anchoring junctional sarcoplasmic reticulum and transverse-tubule (T-tubule) membrane invaginations, recent research has an expanded role of JPH2 in JMC structure and function. For example, JPH2 is necessary for the development of postnatal T-tubule in mammals. It is also critical for the maintenance of the complex JMC architecture and stabilization of local ion channels in mature cardiomyocytes. Loss of this function by mutations or down-regulation of protein expression has been linked to hypertrophic cardiomyopathy, arrhythmias, and progression of disease in failing hearts. In this review, we summarize current views on the roles of JPH2 within the heart and how JPH2 dysregulation may contribute to a variety of cardiac diseases.
DSM-5 Sleep-Wake Disorders Classification: Overview for Use in Clinical Practice
Authors: Charles F. Reynolds, Ruth O’Hara
Journal: American Journal of Psychiatry (2013)

Mental health clinicians should appreciate that sleep is a fundamental human behavior and that inadequate sleep has adverse medical, psychiatric, and psychosocial consequences. Sleep disturbances interact with common mental disorders; the two are mutually exacerbating, and both must be appropriately addressed to ensure optimal outcomes for our patients. Sleep is by the brain, of the brain, and for the brain.
Improvement of BMI, Body Composition, and Body Fat Distribution With Lifestyle Modification in Japanese Americans With Impaired Glucose Tolerance
Authors: David Liao, Pamela J. Asberry, Jane B. Shofer, Holly Callahan, Colleen Matthys, Edward J. Boyko, Donna Leonetti, Steven E. Kahn, Melissa Austin, Laura Newell, Robert S. Schwartz, Wilfred Y. Fujimoto
Journal: Diabetes Care (2002)

OBJECTIVE—To determine whether diet and endurance exercise improved adiposity-related measurements in Japanese Americans with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS—This study compared the effects of an American Heart Association (AHA) step 2 diet (&amp;lt;30% of total calories as fat, &amp;lt;7% saturated fat, 55% carbohydrate, and &amp;lt; 200 mg cholesterol daily) plus endurance exercise for 1 h three times a week (treatment group) with an AHA step 1 diet (30% of total calories as fat, 10% saturated fat, 50% carbohydrate, and &amp;lt;300 mg cholesterol) plus stretching exercise three times a week (control group) on BMI, body composition (% fat), and body fat distribution at 6 and 24 months of follow-up in 64 Japanese American men and women with IGT, 58 of whom completed the study. RESULTS—At 6 months, the treatment group showed significantly greater reduction in percent, body fat (−1.4 ± 0.4 vs. −0.3 ± 0.3%); BMI (−1.1 ± 0.2 vs. −0.4 ± 0.1 kg/m2); subcutaneous fat by computed tomography at the abdomen (−29.3 ± 4.2 vs. −5.7 ± 5.9 cm2), thigh (−13.2 ± 3.6 vs. −3.6 ± 3.0 cm2), and thorax (−19.6 ± 3.6 vs. −8.9 ± 2.6 cm2); and skinfold thickness at the bicep (−2.0 ± 0.6 vs. 1.1 ± 0.6 mm) and tricep (−3.7 ± 0.8 vs. −0.9 ± 0.6 mm), which continued despite moving to home-based exercise for the last 18 months. CONCLUSIONS—Diet and endurance exercise improved BMI, body composition, and body fat distribution and, thus, may delay or prevent type 2 diabetes in Japanese Americans with IGT.
Immunogenicity without Immunoselection: A Mutant but Functional Antioxidant Enzyme Retained in a Human Metastatic Melanoma and Targeted by CD8+ T Cells with a Memory Phenotype
Authors: Marialuisa Sensi, Gabriella Nicolini, Marina Zanon, Chiara Colombo, Alessandra Molla, Ilaria Bersani, Raffaella Lupetti, Giorgio Parmiani, Andrea Anichini
Journal: Cancer Research (2005)

Human melanomas can express unique tumor antigens, resulting from mutated proteins, and shared epitopes encoded for by normal genes, but these two classes of antigens have not been previously compared for immunogenicity and retention in metastatic cells. Here, we identified a new unique antigen generated by a point mutation in the peroxiredoxin 5 (Prdx5) gene in an HLA-A*0201(+) human metastatic melanoma lacking the wild-type allele. An antioxidant assay, with recombinant Prdx5 proteins, and evaluation of peroxide accumulation in transiently transfected cells, indicated that the mutant protein retained its enzymatic activity. The mutation in the Prdx5 protein did not generate a new HLA agretope but yielded an HLA-A*0201-restricted T cell epitope (Prdx5(110-119)). By HLA-tetramer analysis, in a tumor-invaded lymph node, >50% of mutant Prdx5-specific CD8(+) T cells (frequency 0.37%/CD8(+)) showed a CCR7(+/-) CD45RA(-) "T(CM)" or "T(EM)" phenotype, as found in Melan-A/MART-1-specific T cells (frequency 0.68%/CD8(+)) in the same tissue. In agreement with their memory phenotype, the Prdx5-specific T cells readily expanded in vitro in mixed lymphocyte-tumor culture, as did the Melan-/MART-1-specific T cells. By immunohistochemistry of the invaded lymph node, the mutant Prdx5 protein was expressed in all neoplastic cells, in contrast with the heterogeneous expression of shared antigens as Melan-A/MART-1, gp100 and tyrosinase. Thus, a unique tumor antigen can be as immunogenic as the melanoma differentiation antigens but, in contrast to the latter, may be retained in all metastatic cells possibly as result of the relevant cellular function exerted by the mutated protein.
Spontaneous Atherothrombosis and Medial Degradation in <i>Apoe</i> <sup>−/−</sup> , <i>Npc1</i> <sup>−/−</sup> Mice
Authors: Carrie L. Welch, Yu Sun, Brian J. Arey, Vincent Lemaitre, Naresh Sharma, Minako Ishibashi, Scott Sayers, Rong Li, Anna Gorelik, Nick Pleskac, Kadesha Collins-Fletcher, Yoshiyuki Yasuda, Dieter Bromme, Jeanine M. D’Armiento, Martin L. Ogletree, Alan R. Tall
Journal: Circulation (2007)

The formation of an occluding thrombus on a ruptured or eroded atherosclerotic plaque is the hallmark event leading to acute coronary syndromes, myocardial infarction, and sudden death in humans. However, other species are highly resistant to plaque complications, and the specific processes predisposing to plaque destabilization and thrombosis are poorly understood.Mice carrying a null mutation of a gene regulating intracellular cholesterol transport (the Niemann-Pick C1 [Npc1] gene) were crossed with apolipoprotein E (Apoe) knockout mice to examine the effect of Npc1 on atherosclerotic lesion formation. Double-mutant mice showed greater lesion area compared with Apoe-/- littermates. Remarkably, the double mutants also developed large, protruding thrombi associated with the plaques and prominent medial degradation with inflammatory cell infiltration into the adventitia. Genetic studies suggested that the BALB background was permissive for plaque complications compared with C57BL/6J, and a BALB susceptibility locus was mapped by linkage analysis to chromosome 6. Examination of clotting parameters in double-knockout mice revealed that native clotting times were shortened and thrombin-antithrombin complex and soluble CD40 ligand levels were elevated compared with wild-type controls. In addition, cathepsin K was induced in Npc1-/- macrophages, and cathepsin K immunostaining and elastase activity were increased in proximal aortas of double-mutant mice compared with controls.A defect in intracellular cholesterol trafficking caused by the Npc1 null mutation predisposes to increased lesion formation, atherothrombosis, and medial degradation. Plaque complications may require a procoagulant state and an increased protease activity, leading to plaque destabilization.
Th9 cell development requires a BATF-regulated transcriptional network
Authors: Rukhsana Jabeen, Ritobrata Goswami, Olufolakemi Awe, Aishwarya Kulkarni, Evelyn T. Nguyen, Andrea Attenasio, Daniel Walsh, Matthew R. Olson, Myung H. Kim, Robert S. Tepper, Jie Sun, Chang H. Kim, Elizabeth J. Taparowsky, Baohua Zhou, Mark H. Kaplan
Journal: Journal of Clinical Investigation (2013)

T helper 9 (Th9) cells are specialized for the production of IL-9, promote allergic inflammation in mice, and are associated with allergic disease in humans. It has not been determined whether Th9 cells express a characteristic transcriptional signature. In this study, we performed microarray analysis to identify genes enriched in Th9 cells compared with other Th subsets. This analysis defined a transcriptional regulatory network required for the expression of a subset of Th9-enriched genes. The activator protein 1 (AP1) family transcription factor BATF (B cell, activating transcription factor–like) was among the genes enriched in Th9 cells and was required for the expression of IL-9 and other Th9-associated genes in both human and mouse T cells. The expression of BATF was increased in Th9 cultures derived from atopic infants compared with Th9 cultures from control infants. T cells deficient in BATF expression had a diminished capacity to promote allergic inflammation compared with wild-type controls. Moreover, mouse Th9 cells ectopically expressing BATF were more efficient at promoting allergic inflammation than control transduced cells. These data indicate that BATF is a central regulator of the Th9 phenotype and contributes to the development of allergic inflammation.
Estrogen Receptor β Polymorphism Is Associated with Prostate Cancer Risk
Authors: Camilla Thellenberg-Karlsson, Sara Lindström, Beatrice Malmer, Fredrik Wiklund, Katarina Augustsson-Bälter, Hans-Olov Adami, Par Stattin, Maria Nilsson, Karin Dahlman-Wright, Jan-Åke Gustafsson, Henrik Grönberg
Journal: Clinical Cancer Research (2006)

Abstract Purpose: After cloning of the second estrogen receptor, estrogen receptor β (ERβ) in 1996, increasing evidence of its importance in prostate cancer development has been obtained. ERβ is thought to exert an antiproliferative and proapoptotic effect. We examined whether sequence variants in the ERβ gene are associated with prostate cancer risk. Experimental Design: We conducted a large population-based case-control study (CAncer Prostate in Sweden, CAPS) consisting of 1,415 incident cases of prostate cancer and 801 controls. We evaluated 28 single nucleotide polymorphisms (SNP) spanning the entire ERβ gene from the promoter to the 3′-untranslated region in 94 subjects of the control group. From this, we constructed gene-specific haplotypes and selected four haplotype-tagging SNPs (htSNP: rs2987983, rs1887994, rs1256040, and rs1256062). These four htSNPs were then genotyped in the total study population of 2,216 subjects. Results: There was a statistically significant difference in allele frequency between cases and controls for one of the typed htSNPs (rs2987983), 27% in cases and 24% in controls (P = 0.03). Unconditional logistics regression showed an odds ratio of 1.22 (95% confidence interval, 1.02-1.46) for men carrying the variant allele TC or CC versus the wild-type TT, and an odds ratio of 1.33 (95% confidence interval, 1.08-1.64) for localized cancer. No association of prostate cancer risk with any of the other SNPs or with any haplotypes were seen. Conclusion: We found an association with a SNP located in the promoter region of the ERβ gene and risk of developing prostate cancer. The biological significance of this finding is unclear, but it supports the hypothesis that sequence variation in the promoter region of ERβ is of importance for risk of prostate cancer.
MEDICATION COMPLIANCE AS A FEATURE IN DRUG DEVELOPMENT
Authors: H. Kastrissios and, T. F. Blaschke
Journal: The Annual Review of Pharmacology and Toxicology (1997)

▪ Abstract Well-designed clinical trials maximize the information that can be obtained regarding the clinical pharmacology of a drug and, in turn, can streamline and enhance the drug development process. Until recently, little emphasis has been placed on integrating the role of variability in individual patterns of drug-taking into the drug development process. With the use of electronic monitoring, the temporal relationship between an individual's pattern of dosing and the prescribed regimen may be examined, and individual drug exposure may be estimated based on the actual history of dosing. As a result, accurate estimation of exposure-response relationships (or surrogate markers of response) can be obtained. Considerations in the design of clinical trials must therefore be expanded to include appropriate methods to measure compliance, sufficient frequency of monitoring to allow the time course of response to be mapped, and the use of statistically valid methods of data analysis.
Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin
Authors: Edgar A Otto, Bart Loeys, Hemant Khanna, Jan Hellemans, Ralf Sudbrak, Shuling Fan, Ulla Muerb, John F O'Toole, Juliana Helou, Massimo Attanasio, Boris Utsch, John A Sayer, Concepcion Lillo, David Jimeno, Paul Coucke, Anne De Paepe, Richard Reinhardt, Sven Klages, Motoyuki Tsuda, Isao Kawakami, Takehiro Kusakabe, Heymut Omran, Anita Imm, Melissa Tippens, Pamela A Raymond, Jo Hill, Phil Beales, Shirley He, Andreas Kispert, Benjamin Margolis, David S Williams, Anand Swaroop, Friedhelm Hildebrandt
Journal: Nature Genetics (2005)
A Phase I/II Multicenter, Open-Label Study of the Oral Histone Deacetylase Inhibitor Abexinostat in Relapsed/Refractory Lymphoma
Authors: Andrew M. Evens, Sriram Balasubramanian, Julie M. Vose, Wael Harb, Leo I. Gordon, Robert Langdon, Julian Sprague, Mint Sirisawad, Chitra Mani, Jeanne Yue, Ying Luan, Sharon Horton, Thorsten Graef, Nancy L. Bartlett
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Additional targeted therapeutics are needed for the treatment of lymphoma. Abexinostat is an oral pan-histone deacetylase inhibitor (HDACi) displaying potent activity in preclinical models. We conducted a multicenter phase I/II study (N = 55) with single-agent abexinostat in relapsed/refractory lymphoma. Experimental Design: In phase I, 25 heavily pretreated patients with any lymphoma subtype received oral abexinostat ranging from 30 to 60 mg/m2 twice daily 5 days/week for 3 weeks or 7 days/week given every other week. Phase II evaluated abexinostat at the maximum tolerated dose in 30 patients with relapsed/refractory follicular lymphoma or mantle cell lymphoma. Results: The recommended phase II dose was 45 mg/m2 twice daily (90 mg/m2 total), 7 days/week given every other week. Of the 30 follicular lymphoma and mantle cell lymphoma patients enrolled in phase II, 25 (14 follicular lymphoma, 11 mantle cell lymphoma) were response-evaluable. Tumor size was reduced in 86% of follicular lymphoma patients with an investigator-assessed ORR of 64.3% for evaluable patients [intent-to-treat (ITT) ORR 56.3%]. Median duration of response was not reached, and median progression-free survival (PFS) was 20.5 months (1.2–22.3+). Of responding follicular lymphoma patients, 89% were on study/drug &amp;gt;8 months. In mantle cell lymphoma, the ORR was 27.3% for evaluable patients (ITT ORR 21.4%), and median PFS was 3.9 months (range, 0.1–11.5). Grade 3–4 treatment-related adverse events (phase II) with ≥10% incidence were thrombocytopenia (20%), fatigue (16.7%), and neutropenia (13.3%) with rare QTc prolongation and no deaths. Conclusions: The pan-HDACi, abexinostat, was overall well tolerated and had significant clinical activity in follicular lymphoma, including highly durable responses in this multiply relapsed patient population. Clin Cancer Res; 22(5); 1059–66. ©2015 AACR.