tbuckley/cabot-search huggingface dataset:
Variants with large effects on blood lipids and the role of cholesterol and triglycerides in coronary disease
Authors: Anna Helgadottir, Solveig Gretarsdottir, Gudmar Thorleifsson, Eirikur Hjartarson, Asgeir Sigurdsson, Audur Magnusdottir, Aslaug Jonasdottir, Helgi Kristjansson, Patrick Sulem, Asmundur Oddsson, Gardar Sveinbjornsson, Valgerdur Steinthorsdottir, Thorunn Rafnar, Gisli Masson, Ingileif Jonsdottir, Isleifur Olafsson, Gudmundur I Eyjolfsson, Olof Sigurdardottir, Maryam S Daneshpour, Davood Khalili, Fereidoun Azizi, Dorine W Swinkels, Lambertus Kiemeney, Arshed A Quyyumi, Allan I Levey, Riyaz S Patel, Salim S Hayek, Ingibjorg J Gudmundsdottir, Gudmundur Thorgeirsson, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Hilma Holm, Kari Stefansson
Journal: Nature Genetics (2016)
Abstract 284: Cyclic stretch of Embryonic Cardiomyocytes Increases Proliferation, Growth, and Expression While Repressing Tgf-β Signaling
Authors: Indroneal Banerjee, Katrina Carrion, Ricardo Serrano, Jeffrey Dyo, Sean Lund, Erik Willems, Seema Aceves, Rudolph Meili, Mark Mercola, Ju Chen, Alexander Zambon, Alexander Zambon, Gary Hardiman, Taylor A Doherty, Juan C del Álamo, Vishal Nigam
Journal: Circulation Research (2014)

Rationale: Perturbed biomechanical stimuli are critical for the pathogenesis of a number of congenital heart defects, including Hypoplastic Left Heart Syndrome (HLHS). While ventricular cardiomyocytes experience biomechanical stretch every heart beat, the molecular responses of embryonic cardiomyocytes to biomechanical stimuli are poorly understood. In this study, we examined how cyclic mechanical stretch modulates embryonic cardiomyocytes to improve understanding of normal and pathologic ventricular development. We hypothesize that biomechanical stimuli activates specific signaling pathways that impact proliferation, gene expression and myocyte contraction. Objective: The objective for this study was to examine key molecular and phenotypic responses of embryonic cardiomyocytes to cyclic stretch that will provide a deeper understanding of HLHS. Methods and Results: Embryonic mouse cardiomyocytes were exposed to cyclic stretch. Analysis of RNA-Sequencing data demonstrated that gene ontology (GO) groups associated with myofibril and cardiac development were significantly modulated. Stretch increased cardiomyocyte proliferation, size, and cardiac gene expression. Since the Tgf-β GO term was modulated by stretch, the role of Tgf-β in the cardiomyocyte response to stretch was examined. Stretched Cardiomyocytes had decreased Tgf-β expression, protein, and signaling. Functionally, Tgf-β signaling repressed cardiomyocyte proliferation, and both inotropic and chronotropic contractile function, which was assayed for confluent cell cultures by dynamic monolayer force microscopy (DMFM). Tgf-β inhibitor treatment resulted in increased cardiomyocyte size. Conclusions: Herein, we observed that cyclic stretch promotes cardiomyocyte proliferation, growth, and gene expression. Stretch-mediated repression of Tgf-β appears to play a key role. Together these findings advance the understanding of how the biomechanical/molecular axis modulates ventricular development.
De Novo Malignancy After Living Donor Liver Transplantation
Authors: Shinoda Masahiro, Itano Osamu, Obara Hideaki, Kitagao Minoru, Hibi Taizo, Yagi Hiroshi, Abe Yuta, Matsubara Kentaro, Katsuki Yusuke, Tomita Hiroshi, Fujino Akihiro, Hoshino Ken, Kuroda Tatsuo, Kitagawa Yuko
Journal: Annals of Oncology (2014)
Ultracytochemical Localization of Glucose-6-phosphatase in Chang Rat Hepatoma In Vivo and In Vitro 2
Authors: Peter C. Moller, Masao Yokoyama, Jeffrey P. Chang
Journal: JNCI Journal of the National Cancer Institute (1977)

The standard lead precipitation method was used for ultracytochemical localization of glucose-6-phosphatase (G-6-Pase) in the in vivo and in vitro forms of the Chang rat hepatoma and in the normal adult rat liver. Reaction product was visualized as very fine particulate within the cisternae of the nuclear envelope and endoplasmic reticulum. Cytochemically, the amount of the G-6-Pase reaction product in both forms of the tumor cells was obviously less than that in the normal hepatocytes. Apparently, the enzyme was not completely deleted from the hepatoma cells. The results supported some biochemical data of certain other hepatomas. The successful ultracytochemical localization of G-6-Pase in cultured hepatoma cells has not been reported previously.
Cetuximab (C), Fluorouracil (F) and Cisplatin (P) Alone or with Docetaxel (D) for Recurrent/Metastatic (Rm) Head and Neck Cancer (Hnscc). Final Analysis of Aio Trial # 1108 - Cefcid.
Authors: M. Knoedler, T. Gauler, A. Dietz, V. Grünwald, J. Stoehlmacher-Williams, S. Knipping, M. Schroeder, O. Guntinas-Lichius, N. Frickhofen, H. Lindemann, R. Fietkau, B. Haxel, C. Junghanß, G. Maschmeyer, M. Zipfel, P. Martus, U. Keilholz
Journal: Annals of Oncology (2014)
Concurrent and Sustained Cumulative Effects of Adolescent Marijuana Use on Subclinical Psychotic Symptoms
Authors: Jordan Bechtold, Alison Hipwell, David A. Lewis, Rolf Loeber, Dustin Pardini
Journal: American Journal of Psychiatry (2016)

Adolescents who regularly use marijuana may be at heightened risk of developing subclinical and clinical psychotic symptoms. However, this association could be explained by reverse causation or other factors. To address these limitations, the current study examined whether adolescents who engage in regular marijuana use exhibit a systematic increase in subclinical psychotic symptoms that persists during periods of sustained abstinence.The sample comprised 1,009 boys who were recruited in 1st and 7th grades. Self-reported frequency of marijuana use, subclinical psychotic symptoms, and several time-varying confounds (e.g., other substance use, internalizing/externalizing problems) were recorded annually from age 13 to 18. Fixed-effects (within-individual change) models examined whether adolescents exhibited an increase in their subclinical psychotic symptoms as a function of their recent and/or cumulative history of regular marijuana use and whether these effects were sustained following abstinence. Models controlled for all time-stable factors (default) and several time-varying covariates as potential confounds.For each year adolescent boys engaged in regular marijuana use, their expected level of subsequent subclinical psychotic symptoms rose by 21% and their expected odds of experiencing subsequent subclinical paranoia or hallucinations rose by 133% and 92%, respectively. The effect of prior regular marijuana use on subsequent subclinical psychotic symptoms persisted even when adolescents stopped using marijuana for a year. These effects were after controlling for all time-stable and several time-varying confounds. No support was found for reverse causation.These results suggest that regular marijuana use may significantly increase the risk that an adolescent will experience persistent subclinical psychotic symptoms.
Fitness and Coronary Artery Calcification
Authors: Vincent L. Aengevaeren, Maria T. E. Hopman, Thijs M. H. Eijsvogels
Journal: JAMA Internal Medicine (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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study
Authors: Rita Nanda, Laura Q.M. Chow, E. Claire Dees, Raanan Berger, Shilpa Gupta, Ravit Geva, Lajos Pusztai, Kumudu Pathiraja, Gursel Aktan, Jonathan D. Cheng, Vassiliki Karantza, Laurence Buisseret
Journal: Journal of Clinical Oncology (2016)

Purpose Immune checkpoint inhibition has been demonstrated to be an effective anticancer strategy. Several lines of evidence support the study of immunotherapy in triple-negative breast cancer (TNBC). We assessed the safety and antitumor activity of the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab in patients with advanced TNBC. Methods KEYNOTE-012 ( ClinicalTrials.gov identifier: NCT01848834) was a multicenter, nonrandomized phase Ib trial of single-agent pembrolizumab given intravenously at 10 mg/kg every 2 weeks to patients with advanced PD-L1–positive (expression in stroma or ≥ 1% of tumor cells by immunohistochemistry) TNBC, gastric cancer, urothelial cancer, and head and neck cancer. This report focuses on the TNBC cohort. Results Among 111 patients with TNBC whose tumor samples were screened for PD-L1 expression, 58.6% had PD-L1–positive tumors. Thirty-two women (median age, 50.5 years; range, 29 to 72 years) were enrolled and assessed for safety and antitumor activity. The median number of doses administered was five (range, 1 to 36 doses). Common toxicities were mild and similar to those observed in other tumor cohorts (eg, arthralgia, fatigue, myalgia, and nausea), and included five (15.6%) patients with grade ≥ 3 toxicity and one treatment-related death. Among the 27 patients who were evaluable for antitumor activity, the overall response rate was 18.5%, the median time to response was 17.9 weeks (range, 7.3 to 32.4 weeks), and the median duration of response was not yet reached (range, 15.0 to ≥ 47.3 weeks). Conclusion This phase Ib study describes preliminary evidence of clinical activity and a potentially acceptable safety profile of pembrolizumab given every 2 weeks to patients with heavily pretreated, advanced TNBC. A single-agent phase II study examining a 200-mg dose given once every 3 weeks ( ClinicalTrials.gov identifier: NCT02447003) is ongoing.
Implications of family history of alcoholism, antisocial personality, and sex differences in alcohol dependence
Authors: J R Stabenau
Journal: American Journal of Psychiatry (1984)

In this study of 210 male and female alcoholic inpatients, significant associations were found 1) between antisocial personality diagnosis and early onset of all stages in alcohol dependence; 2) between bilineal family history of alcoholism and greater frequency of the consequences of impaired control, withdrawal symptoms, and the pathologic symptoms associated with chronic alcoholism; and 3) between being female and older at onset of the initial, but not final, stages of alcoholism and having more symptoms associated with chronic alcohol use. Antisocial personality, type of family history, and sex of the proband were not interactive but contributed separate additive effects.
NK Cell KIR Ligand Mismatches Influence Engraftment Following Combined Haploidentical and Umbilical Cord Blood (UCB) Transplantation In Patients With Severe Aplastic Anemia (SAA)
Authors: Ritesh Kotecha, Xin Tian, Jennifer Wilder, Nicole Gormley, Hahn Khuu, David Stroncek, Susan F. Leitman, Roger Kurlander, Elena Cho, Lisa Cook, Catalina Ramos, Ladan Foruraghi, Charles D. Bolan, Richard W. Childs
Journal: Blood (2013)
Association Between Severity of Obstructive Sleep Apnea and Blood Markers of Liver Injury
Authors: Wojciech Trzepizur, Jérôme Boursier, Yasmina Mansour, Marc Le Vaillant, Sylvaine Chollet, Thierry Pigeanne, Acya Bizieux-Thaminy, Marie-Pierre Humeau, Claire Alizon, François Goupil, Nicole Meslier, Pascaline Priou, Paul Calès, Frédéric Gagnadoux, Christine Person, Olivier Molinier, Audrey Paris, Isabelle Caby, Maël Bellier, Marie Langelot-Richard, Laurence Leclair-Visonneau, Sandrine Jaffre, Frédéric Corne, Marc Normand de la Tranchade, Béatrice Rouault, Jean-Louis Racineux, Christelle Gosselin, Nathalie Pelletier-Fleury
Journal: Clinical Gastroenterology and Hepatology (2016)
Adverse Associations of both Prenatal and Postnatal Exposure to Organophosphorous Pesticides with Infant Neurodevelopment in an Agricultural Area of Jiangsu Province, China
Authors: Ping Liu, Chunhua Wu, Xiuli Chang, Xiaojuan Qi, Minglan Zheng, Zhijun Zhou
Journal: Environmental Health Perspectives (2016)

Prenatal exposure to organophosphorous (OP) pesticides has been found to be associated with adverse effects on child neurodevelopment, but evidence on potential effects induced by both prenatal and postnatal OP exposure in infants is limited.Our aim was to investigate the associations of both prenatal and postnatal OP exposure with birth outcomes and infant neurodevelopment.Exposure to OP in 310 mother-infant pairs was assessed by measuring dimethylphosphate (DM), diethylphosphate (DE), and total dialkylphosphate (DAP) metabolites in urines from pregnant women and their children at 2 years of age. The Gesell Developmental Schedules was administered to examine neurodevelopment of 2-year-old children.Based on the Gesell Developmental Schedules, the proportions of children with developmental delays were < 6%. Adverse associations between head circumference at birth and prenatal OP exposure were demonstrated. Both prenatal and postnatal OP exposure was significantly associated with increased risk of being developmentally delayed. Specifically, odds ratio (OR) value for prenatal DEs was 9.75 (95% CI: 1.28, 73.98, p = 0.028) in the adaptive area, whereas in the social area, OR values for postnatal DEs and DAPs were 9.56 (95% CI: 1.59, 57.57, p = 0.014) and 12.00 (95% CI: 1.23, 117.37, p = 0.033), respectively. Adverse associations were observed only in boys, not in girls.Both prenatal and postnatal OP exposure may adversely affect the neurodevelopment of infants living in the agricultural area. The present study adds to the accumulating evidence on associations of prenatal and postnatal OP exposure with infant neurodevelopment.Liu P, Wu C, Chang X, Qi X, Zheng M, Zhou Z. 2016. Adverse associations of both prenatal and postnatal exposure to organophosphorous pesticides with infant neurodevelopment in an agricultural area of Jiangsu Province, China. Environ Health Perspect 124:1637-1643; http://dx.doi.org/10.1289/EHP196.
Infections in first six months of life show link to type 1 diabetes
Authors: Jacqui Wise
Journal: BMJ (2016)

Recurrent viral respiratory tract infections in the first six months of life are associated with developing type 1 diabetes, a study published in JAMA has shown.1 The German researchers said their findings suggested that the first half year of life is crucial for the development of the immune system and autoimmunity.

The researchers examined the medical records of 295 420 infants born from 2005 to 2007 in Bavaria, Germany. Of …
Development of a circulating tumor cell assay for use in selecting patients for a novel antibody-drug conjugate therapy*.
Authors: Xiaolei Qiu, Hilda Beas, Madeleine Matias, Monalisa Ray, Sunil Pandit, Harwinder Sidhu, Albert Chmura, Rong Jiang, Sebastian Kronmueller, Julia Philip, Karen Marfurt, Michael Pugia, Omar Perez, Steven Robert Pirie-Shepherd, Arejas Uzgiris
Journal: Journal of Clinical Oncology (2015)

e22022 Background: Antigens that are expressed in various cancers and substantially absent from normal tissue are potential targets for high-affinity antibodies developed for use in targeting cytotoxic agents to treat patients with such antigen-positive cancers. The results of this research are intended to support a technical feasibility recommendation regarding the use of the developed assay in future clinical trials to identify patients with circulating tumor cells (CTC) positively expressing an antibody-drug conjugate (ADC) target. Methods: A rare-cell detection platform* utilized for automated isolation and characterization of CTC was developed by Siemens Healthcare Diagnostics Innovations (Elkhart, IN). The Siemens Clinical Laboratory (SCL) (Berkeley, CA) developed a quantitative antigen expression assay* for this platform in collaboration with Pfizer Oncology Research, which provided 25 non-small cell lung carcinoma (NSCLC) samples. Analytical performance data were evaluated with cancer cell lines spiked in normal blood. Clinical samples from cancer patients were drawn in blood collection tubes and shipped to SCL at ambient temperature. Cancer cells were isolated by filtration, stained fluorescently, and scanned microscopically. ADC target signal intensity was analyzed quantitatively for each positive cell. Results: Analytical performance data included greater than 79% recovery from controls ranging from 4 to 200 cancer cells spiked per 8 mL of whole blood. With formalin-fixed cell line controls, recovery was greater than 90%. Twenty-four out of 25 clinical samples were successfully processed, and 62.5% (15 out of 24) were positive for detection of the drug target. Conclusions: Detection of this circulating biomarker in late-stage (III and IV) NSCLC patients was sufficiently frequent that the test could potentially find wider application in the areas of diagnosis and monitoring of lung cancer. *The prototype CTC platform and assay are for research use only. They are not available for sale.
AB0039 Preferential Induction of 4IG B7-H3 on Synovial Monocytes in Rheumatoid Arthritis (RA): Possible Role of 4IG B7-H3 as a Co-Inhibitory Ligand
Authors: S.W. Kang, B.R. Yoon, S.-J. Yoo, J. Kim, I.S. Yoo, W.-W. Lee
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> B7-H3 (B7-H3), newly identified B7 family member, has functional duality as a T-cell costimulator or coinhibitor for fine-tuning T-cell mediated immune responses. Given that B7-H3 expression is enhanced in human monocyte and dendritic cells by inflammatory cytokines, it has been suggested their potential inmmunoregulatory function at sites of inflammation. Monocytes play a crucial role in the pathophysiology of various inflammatory disorders including autoimmune diseases. However, the immunological role of B7-H3 in rheumatoid arthritis (RA) has not been defined. <h3>Objectives</h3> We aimed to investigate the possible roles of B7-H3 on monocyte in pathogenesis of RA. <h3>Methods</h3> Synovial fluid and peripheral blood from 33 RA patients and peripheral blood from 19 healthy controls (HCs) were obtained. The expression of B7-H3 on monocytes in RA patients and HCs were analyzed using flow cytometic analysis and quantitative RT-PCR. Purified synovial and peripheral monocytes were used for immunoblotting and intracellular flow cytometic analysis to investigate the distinct expression and localization of two isoforms of B7-H3. B7-H3-expressing THP-1 cells were transfected with B7-H3-specific siRNA and subjected to coculture assay with CD4 T cells. Proliferation and cytokine production of the cocultured T cells were assessed by CFSE dilution and ELISA, respectively. Clinical relevance of enhanced B7-H3 expression in RA was tested by comparison with clinical parameters and disease severity in the patients and with synovial cytokine levels measured by multiplex cytokine assay. <h3>Results</h3> Synovial monocytes but not peripheral monocytes in RA patients predominantly induce surface B7-H3 expression. The induced B7-H3 is exclusively 4Ig isoform, whereas 2Ig B7-H3 isoform constitutively express the intracytoplasmic region both peripheral and synovial monocytes. The B7-H3 knockdown experiments provided the evidence that 4Ig B7-H3 isoform has an inhibitory effect on interferon-gamma (IFN-γ) production of CD4 memory cells. Moreover, the expression level of 4Ig B7-H3 on synovial monocytes was inversely correlated with clinical parameters such as C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), and Disease Activity Score in 28 joints (DAS28). <h3>Conclusions</h3> Our findings demonstrate that activation-induced B7-H3 expression on synovial monocytes has the potential to inhibit Th1-mediated immune response and immunomodulatory role affecting pathogenesis of RA. <h3>Disclosure of Interest</h3> None declared
Exome Sequencing Discerns Syndromes in Patients from Consanguineous Families with Congenital Anomalies of the Kidneys and Urinary Tract
Authors: Asaf Vivante, Daw-Yang Hwang, Stefan Kohl, Jing Chen, Shirlee Shril, Julian Schulz, Amelie van der Ven, Ghaleb Daouk, Neveen A. Soliman, Aravind Selvin Kumar, Prabha Senguttuvan, Elijah O. Kehinde, Velibor Tasic, Friedhelm Hildebrandt
Journal: Journal of the American Society of Nephrology (2016)

Congenital anomalies of the kidneys and urinary tract (CAKUT) are the leading cause of CKD in children, featuring a broad variety of malformations. A monogenic cause can be detected in around 12% of patients. However, the morphologic clinical phenotype of CAKUT frequently does not indicate specific genes to be examined. To determine the likelihood of detecting causative recessive mutations by whole-exome sequencing (WES), we analyzed individuals with CAKUT from 33 different consanguineous families. Using homozygosity mapping and WES, we identified the causative mutations in nine of the 33 families studied (27%). We detected recessive mutations in nine known disease–causing genes: ZBTB24 , WFS1 , HPSE2 , ATRX , ASPH , AGXT , AQP2 , CTNS , and PKHD1 . Notably, when mutated, these genes cause multiorgan syndromes that may include CAKUT as a feature (syndromic CAKUT) or cause renal diseases that may manifest as phenocopies of CAKUT. None of the above monogenic disease–causing genes were suspected on clinical grounds before this study. Follow-up clinical characterization of those patients allowed us to revise and detect relevant new clinical features in a more appropriate pathogenetic context. Thus, applying WES to the diagnostic approach in CAKUT provides opportunities for an accurate and early etiology–based diagnosis and improved clinical management.
Influence Of Antithymoglobulin Doses On The Outcome Of Hematopoietic Stem Cells Transplantations After a Flu-Bu2 Conditioning Regimen: A Retrospective Study On 168 Consecutive Patients
Authors: Jérôme Cornillon, Marie Balsat, Aurélie Cabrespine, Emmanuelle Tavernier, Eric Hermet, Karine Augeul-Meunier, Jacques-Olivier Bay
Journal: Blood (2013)
Hypnosis and related clinical behavior
Authors: F H Frankel
Journal: American Journal of Psychiatry (1978)

The essential aspect in the experience of the hypnotized person is the altered or distorted perception that is suggested to him. Not all people are capable of the experience, but it is possible that spontaneous distortions occur in those with high hypnotizability. These distortions are frequently experienced as frightening symptoms. The author draws attention to the similarity between hysterical symptoms and events in hypnosis and to the high hypnotic responsivity in hysterical subjects reported in the clinical literature of the nineteenth century. Phobic patients have relatively high hypnotic responsivity. The author believes that it is sometimes possible to predict hypnotizability from clinical behavior, and that hypnotic responsivity can be utilized in psychodynamically sensitive therapy to teach such patients that they can learn to gain control of their symptoms.