tbuckley/cabot-search huggingface dataset:
A Population-Based Longitudinal Study of Symptoms and Signs Before the Onset of Psychosis
Authors: Abigail Livny, Abraham Reichenberg, Eyal Fruchter, Rinat Yoffe, Shira Goldberg, Daphna Fenchel, Shimon Burshtein, Eitan Bachar, Michael Davidson, Mark Weiser
Journal: American Journal of Psychiatry (2017)

The authors sought to characterize the symptoms of patients later hospitalized for psychotic disorders in primary mental health outpatient settings, and to investigate whether these symptoms can be used to predict later onset of psychotic illness.This was a population-based historical prospective cohort study using national registers of clinical psychiatric services. The sample (N=114,983) comprised 18- to 21-year-olds serving in the Israeli military and examined in military mental health outpatient clinics across 72 consecutive months.Overall, 1,092 individuals (0.95%) not diagnosed with a psychotic disorder at the time of examination were hospitalized for nonaffective psychotic disorder up to 9 years after the index examination. A principal components analysis of symptoms presented at index examination found that a symptom cluster of thought disorder, perceptual abnormalities, poor orientation, and suicidality was associated with an increased risk for hospitalization for nonaffective psychotic disorder within 14 days after examination (hazard ratio=45.80, 95% CI=22.87-91.73), 15-111 days after examination, (hazard ratio=19.59, 95% CI=13.08-29.33), 112-365 days after examination (hazard ratio=4.94, 95% CI=2.59-9.40), and 1-3.5 years after examination (hazard ratio=3.42, 95% CI=2.21-5.28), but not for hospitalization 3.5 years or more after examination (hazard ratio=1.57, 95% CI=0.91-2.71). Despite the increased risk, the positive predictive values of this symptom cluster were low, ranging from 0.54% to 1.99%.In 18- to 21-year-olds, the presence of psychotic symptoms was associated with later hospitalization for a nonaffective psychotic disorder. However, the low positive predictive values of symptoms elicited in primary mental health care settings suggest that symptoms alone are not useful in predicting later hospitalization for nonaffective psychotic disorder.
Atheroprone flow activates inflammation via endothelial ATP-dependent P2X7-p38 signalling
Authors: Jack P Green, Celine Souilhol, Ioannis Xanthis, Laura Martinez-Campesino, Neil P Bowden, Paul C Evans, Heather L Wilson
Journal: Cardiovascular Research (2017)

Abstract Objective Atherosclerosis is a focal disease occurring at arterial sites of disturbed blood flow that generates low oscillating shear stress. Endothelial inflammatory signalling is enhanced at sites of disturbed flow via mechanisms that are incompletely understood. The influence of disturbed flow on endothelial adenosine triphosphate (ATP) receptors and downstream signalling was assessed. Methods and results Cultured human endothelial cells were exposed to atheroprotective (high uniform) or atheroprone (low oscillatory) shear stress for 72 h prior to assessment of ATP responses. Imaging of cells loaded with a calcium-sensitive fluorescent dye revealed that atheroprone flow enhanced extracellular calcium influx in response to 300 µM 2'(3')-O-(4-Benzoylbenzoyl) adenosine-5'-triphosphate. Pre-treatment with pharmacological inhibitors demonstrated that this process required purinergic P2X7 receptors. The mechanism involved altered expression of P2X7, which was induced by atheroprone flow conditions in cultured cells. Similarly, en face staining of the murine aorta revealed enriched P2X7 expression at an atheroprone site. Functional studies in cultured endothelial cells showed that atheroprone flow induced p38 phosphorylation and up-regulation of E-selectin and IL-8 secretion via a P2X7-dependent mechanism. Moreover, genetic deletion of P2X7 significantly reduced E-selectin at atheroprone regions of the murine aorta. Conclusions These findings reveal that P2X7 is regulated by shear forces leading to its accumulation at atheroprone sites that are exposed to disturbed patterns of blood flow. P2X7 promotes endothelial inflammation at atheroprone sites by transducing ATP signals into p38 activation. Thus P2X7 integrates vascular mechanical responses with purinergic signalling to promote endothelial dysfunction and may provide an attractive potential therapeutic target to prevent or reduce atherosclerosis.
Integration of end-of-life care in clinical trials for advanced malignancies.
Authors: Adi Joseph Klil-Drori, Karine Silva, Tracy Regimbald, Sarit E. Assouline
Journal: Journal of Clinical Oncology (2017)

67 Background: ASCO endorses early integration of palliative care in the treatment of patients with advanced cancers and encourages patient education with regards to prognosis and participation in medical decision making. We implemented a uniform process of discussing end of life and advance directives (AD) early in the course of experimental cancer treatment and assessed whether this process is aligned with our patients' perspectives. Methods: This was a pilot study in a research unit conducting early-phase trials for patients with no remaining standard of care. Accrual goal was 15 patients in four months. We identified patients with advanced malignancies who were screened for cancer trials and approached their physicians with a request to fill out an AD form in discussion with their patients. Upon initiation of treatment, we filled out a supportive care checklist for each patient. The patients filled out a structured questionnaire probing their views on end-of-life discussion and awareness to supportive care resources on cycle 2 day 1 (Q1) and on cycle 3 day 1 (Q2). Results: Out of 41 screened, we completed checklists for 36 patients. Of these, 26 filled out Q1 and 11 filled out Q1 + Q2. Response rate to the questionnaires was 100%. The patients were diagnosed with metastatic solid tumor (23) and hematologic malignancies (3) and had 2 (0-5) previous lines of treatment. Females and males were 14 and 12, respectively. AD forms were filled out in most patients (81%), but about half (54%) reported having had AD discussions with their physicians. Most patients (73%) were aware of supportive resources (palliative care, social worker, support groups), and most (62%) actually used them while on study. Agreement in Q1 and Q2 was comparable (Table), with some rise in agreement with the timing of AD discussion. Conclusions: In the context of treatment on clinical trials, a large-scale initiative is feasible. More patients agree with time that early discussion of AD meets their goals while almost half report having had no such discussion with their physicians. [Table: see text]
Abstract MP36: Anemia, Chronic Kidney Disease, and Incident Heart Failure: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Junichi Ishigami, Morgan E Grams, Rakhi P Naik, Melissa C Caughey, Laura R Loehr, Josef Coresh, Kunihiro Matsushita
Journal: Circulation (2016)

Background: Both chronic kidney disease (CKD) measures, estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR), are associated with incident heart failure (HF). Anemia is thought to play an important role in this association, particularly when eGFR is reduced, but this concept has not been rigorously evaluated. Methods: Using data from 5,539 participants in the Atherosclerosis Risk in Communities (ARIC) study at the fourth visit (1996-98), we first assessed the prevalence ratio (PrR) of anemia for eGFR and ACR using cross-sectional Poisson models, and then prospectively quantified the associations of eGFR, ACR, and anemia with incident HF using Cox proportional hazard models. Results: Based on the WHO definition, 477 (8.6%) participants had anemia at baseline. Both CKD measures were associated with increased prevalence of anemia independently of each other and other potential confounders (PrR, 1.22 [95% confidence interval, 1.11-1.34] with every 1SD decrease in eGFR; and 1.12 [1.03-1.23] with every 1SD increase in log 10 ACR). There were 724 (13.1%) cases of incident HF over median follow-up of 14.8 years. Lower eGFR and higher ACR were independently associated with increased risk of HF regardless of anemia status (Figure A for eGFR, and B for ACR). The association between anemia and HF risk was generally consistent in the range of eGFR below 90 ml/min/1.73m 2 and ACR between 5 and 300 mg/g, without significant interaction between both CKD measures and anemic status (e.g., hazard ratio for anemia vs. no anemia: 1.40 [0.81-2.41] at eGFR 60 ml/min/1.73m 2 and 1.37 [0.67-2.80] at ACR 30 mg/g). Conclusions: Reduced eGFR and elevated ACR were independently associated with higher prevalence of anemia and HF risk. The contribution of anemia to HF risk was overall consistent across CKD ranges of eGFR and ACR. Our results suggest the need of clinical attention on anemia and related HF risk in persons with low eGFR as well as those with high ACR.
Abstract 11896: Percutaneous Left Atrial Appendage Closure is Reasonable Option for the Treatment of Patients With Atrial Fibrillation at High Risk for Cerebrovascular Events
Authors: Emmanuel Teiger, Jean-Benoit Thambo, Pascal Defaye, Jean-Sylvain Hermida, Daniel Gras, Didier Klug, Jean-Michel Juliard, Jean-Luc Pasquie, Gilles Rioufol, Antoine Lepillier, Meyer Elbaz, Jerome Horvilleur, Philippe Brenot, Dominique Babuty, Philippe Le Corvoisier
Journal: Circulation (2016)

Introduction: Percutaneous left atrial appendage (LAA) closure is an emerging alternative intervention for anticoagulant treatment in patients with atrial fibrillation and high risk of cerebrovascular events. Only few data are available on the prognosis of patients treated with this new interventional strategy. Hypothesis: The aim of the multicenter prospective French national LAA Closure registry (FLAAC) was to report the results of this procedure in daily practice in France. Methods: Patients referred from October 2013 to September 2015 to 36 French centers for percutaneous LAA closure were prospectively included in this observational registry. We report here the results of the 436 first patients with one year follow-up. Results: The mean (±SEM) age of the study population was 75.5 ± 0.4 years and 62.2 percent were men. Their average CHA 2 DS 2 -VASc and HAS-BLED scores were 4.5 ± 0.1 and 3.1 ± 0.1, respectively. Fifty-height percent of patients were treated with an Amplatzer ™ LAA Occluder and 42% with a Watchman ™ device. LAA closure was successful in 98.4% of patients (including 9 patients requiring two procedures with a different device). The mean follow-up period was 12.7 ± 0.2 months after implantation of the device and only one patient was lost to follow-up. In patients with successful device implantation, ischemic stroke and cerebral hemorrhage rates were 0.22 and 0.11% per month during the follow-up period. The survival rate was 91.1% (38 deaths/429), with 7 (1.6 %) deaths related or possibly related to the device or to the procedure. Other causes of death were cerebral ischemic and hemorrhagic events (0.2% and 0.7%, respectively), major non-cerebral hemorrhagic events (0.7%), known or suspected cardiovascular diseases (2.3 %) and other preexisting non-cardiovascular comorbidities (3.3%). Conclusion: In conclusion, this national prospective registry shows that LAA closure is mainly used in patients with very high risk of cerebrovascular events. In this population, this procedure appears to be a reasonable option in daily practice. The high percentage of deaths related to comorbidities suggests that patient global clinical status should also be evaluated to assess patient eligibility before the procedure.
Abstract 13963: Evidence of Content-Dependent Functional and Electrical Coupling of Human Induced Pluripotent Stem Cell-Derived Engineered Cardiac Tissue With Chronic Infarct Rat Myocardium
Authors: Hiroko Iseoka, Shigeru Miyagawa, Satsuki Fukushima, Shin Yajima, Atsuhiro Saito, Shigeo Masuda, Emiko Ito, Jong-Kook Lee, Yoshiki Sawa
Journal: Circulation (2015)

Background: It has been shown that transplantation of engineered cardiac tissue (ECT) derived from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) into the infarct heart induces electrical communication between the ECT and the native myocardium; however, factors enhancing the electrical integrity and thus the therapeutic effects are not fully understood. We herein hypothesized that content of cardiomyocytes in the ECT may be a key to achieve efficient electrical coupling and functional contribution in chronic rat myocardial infarction (MI) heart. Methods and Results: Neonatal rat cardiomyocytes (NRCM), mimicking the host myocardium, were partially covered by the ECT containing iPSC-CMs produced by thermoresponsive culture dishes in vitro , to explore electrical communication of the ECT with myocardium. As a result, the NRCM and the ECT showed spontaneous, individual contractions for 2 hours, though they gradually showed electrical and motional synchronization, featuring transmitted electrical pulse from the NRCM to the ECT, as assessed by multi-electrode array. Subsequently, the ECT of different ratios (25, 50, 70, and 90%) of iPSC-CMs were generated by magnetic-activated cell sorting using cardiac specific cell surface marker. As a result, the 70% group exhibited the highest contractile and relaxation properties in vitro , as assessed by high-speed video microscopy image-based motion analysis and Ca transient measurement. Finally, the ECTs including 25, 50, 70% CMs were transplanted to immune deficient rat MI model (n=7 each). As a result, ejection fraction was significantly improved in the 50% (52±10%) and 70% (52±12%) groups, but not in the 25% group (35±5%), as compared to the control (35±10%; P &lt;0.05). Epicardial optical mapping of Langendorff perfused heart on day 3 showed that the ECTs of 50% and the 70% groups exhibited electrical activity and synchronization with the native myocardium. Conclusion: Transplantation of the ECT improved cardiac performance associated with synchronization with the myocardium in rat infarction model, dependent upon content of the cardiomyocytes in the ECT. It was thus suggested that transplanted ECT may behave “working cardiac construct” in the damaged heart.
Administration of the National Cancer Institute Act, August 5, 1937, to June 30, 1943
Authors: Ora Marshino
Journal: JNCI Journal of the National Cancer Institute (1944)

Administration of the National Cancer Institute Act, August 5, 1937, to June 30, 1943 Get access Ora Marshino Ora Marshino administrative assistant National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 5, April 1944, Pages 429–443, https://doi.org/10.1093/jnci/4.5.429 Published: 01 April 1944
Mutant JAK3 signaling is increased by loss of wild-type JAK3 or by acquisition of secondary JAK3 mutations in T-ALL
Authors: Sandrine Degryse, Simon Bornschein, Charles E. de Bock, Emilie Leroy, Marlies Vanden Bempt, Sofie Demeyer, Kris Jacobs, Ellen Geerdens, Olga Gielen, Jean Soulier, Christine J. Harrison, Stefan N. Constantinescu, Jan Cools
Journal: Blood (2017)
Tendencia de las infecciones por Salmonella Typhimurium multirresistente en Noruega
Authors: O Alvseike, T Leegaard, P Aavitsland, J Lassen
Journal: Eurosurveillance (2002)

En este articulo se describe la tendencia de las infecciones humanas por Salmonella Typhimurium resistente a multiples farmacos en Noruega, de 1998 a 2000. Casi todas las infecciones por S. Typhimurium multirresistente contraidas en Noruega fueron debidas al fagotipo definitivo DT104. Por consiguiente, cabe esperar un aumento de las infecciones primarias y secundarias, si cepas como el fagotipo DT104 con patron de resistencia ACSSuT llegan a ser endemicas.
Emergencia del linfogranuloma venéreo en hombres homosexuales en Alemania
Authors: V Bremer, T Meyer, U Marcus, O Hamouda
Journal: Eurosurveillance (2006)

En varios paises europeos se ha observado una resurgencia del linfogranuloma venereo (LGV). El LGV no estaba considerado como una enfermedad de declaracion obligatoria en Alemania. Desde 2004 se hizo una busqueda activa de casos de LGV por el Instituto Robert Koch para describir el brote y evaluar el amplitud del problema de esta enfermedad en Alemania. Se publicaron actualizaciones sobre el brote de LGV en el boletin epidemiologico nacional aleman. Se pidio a los medicos que enviaran sus muestras a un laboratorio para la genotipificacion. Un caso posible se definio como una persona con sintomas de proctitis y/o inflamacion de los ganglios inguinales y con serologia positiva para chlamydia. Un caso se consideraba probable si ademas era PCR positivo para chlamydia en muestras rectales o urinarias. Un caso era confirmado si se identificaba el genotipo L1-L3 por secuenciacion del gen omp1. 
Desde 2003, se declararon 78 casos de LGV en varones en Alemania, con el genotipo L2 confirmado en 61. De los 78 pacientes, 58 (74%) eran hombres homosexuales. Cincuenta y cinco (71%) de los pacientes tenian sintomas rectales y 49 (63%) conocian su estatus positivo para el VIH. Sesenta y dos (79%) pacientes vivian en Berlin o Hamburgo. 
La emergencia del LGV en los hombres homosexuales en Alemania se ha producido en el mismo periodo que en otros paises de Europa. Se piensa que el LGV podria pasar a ser endemico en la comunidad homosexual masculina de las metropolis alemanas, debido al continuo aumento del numero de casos de LGV declarados. Dicho aumento, asi como la alta prevalencia del VIH en los pacientes afectados por el LGV, representan un problema preocupante de salud publica. Con el fin de asegurar una buena informacion de los medicos y de los hombres homosexuales, es necesario que se refuercen las acciones de promocion y prevencion de las infecciones de transmision sexual y del VIH.
SnWO4-based nanohybrids with full energy transfer for largely enhanced photodynamic therapy and radiotherapy
Authors: Meng Zhang, Zhaowen Cui, Ruixue Song, Bin Lv, Zhongmin Tang, Xianfu Meng, Xiaoyan Chen, Xiangpeng Zheng, Jiawen Zhang, Zhenwei Yao, Wenbo Bu
Journal: Biomaterials (2017)
Matrix stiffness determines the phenotype of vascular smooth muscle cell in vitro and in vivo: Role of DNA methyltransferase 1
Authors: Si-An Xie, Tao Zhang, Jin Wang, Feng Zhao, Yun-Peng Zhang, Wei-Juan Yao, Sung Sik Hur, Yi-Ting Yeh, Wei Pang, Li-Sha Zheng, Yu-Bo Fan, Wei Kong, Xian Wang, Jeng-Jiann Chiu, Jing Zhou
Journal: Biomaterials (2017)
ADHFE1 is a breast cancer oncogene and induces metabolic reprogramming
Authors: Prachi Mishra, Wei Tang, Vasanta Putluri, Tiffany H. Dorsey, Feng Jin, Fang Wang, Donewei Zhu, Lauren Amable, Tao Deng, Shaofei Zhang, J. Keith Killian, Yonghong Wang, Tsion Z. Minas, Harry G. Yfantis, Dong H. Lee, Arun Sreekumar, Michael Bustin, Wei Liu, Nagireddy Putluri, Stefan Ambs
Journal: Journal of Clinical Investigation (2017)

Metabolic reprogramming in breast tumors is linked to increases in putative oncogenic metabolites that may contribute to malignant transformation. We previously showed that accumulation of the oncometabolite, 2-hydroxyglutarate (2HG), in breast tumors was associated with MYC signaling, but not with isocitrate dehydrogenase (IDH) mutations, suggesting a distinct mechanism for increased 2HG in breast cancer. Here, we determined that D-2HG is the predominant enantiomer in human breast tumors and show that the D-2HG–producing mitochondrial enzyme, alcohol dehydrogenase, iron-containing protein 1 (ADHFE1), is a breast cancer oncogene that decreases patient survival. We found that MYC upregulates ADHFE1 through changes in iron metabolism while coexpression of both ADHFE1 and MYC strongly enhanced orthotopic tumor growth in MCF7 cells. Moreover, ADHFE1 promoted metabolic reprogramming with increased formation of D-2HG and reactive oxygen, a reductive glutamine metabolism, and modifications of the epigenetic landscape, leading to cellular dedifferentiation, enhanced mesenchymal transition, and phenocopying alterations that occur with high D-2HG levels in cancer cells with IDH mutations. Together, our data support the hypothesis that ADHFE1 and MYC signaling contribute to D-2HG accumulation in breast tumors and show that D-2HG is an oncogenic metabolite and potential driver of disease progression.
Using CRISPR/Cas9 to explore the human kinome: A tool to identify new potential therapeutic targets for malignant rhabdoid tumors (MRT).
Authors: Simone Treiger Sredni, Dorina Veliceasa, Kashyap Patel, Alexandre de Andrade, Jian-Ping Yang, Ross Whittaker, Elaine Sobel, Maya Behn, Meredith Hollender, David R Piper, Tadanori Tomita
Journal: Journal of Clinical Oncology (2016)

10544 Background: MRTs are universally lethal embryonal tumors that occur mainly in early childhood. The CRISPR/Cas9 system for genome editing is a powerful tool to identify genes involved in vital biological processes. We hypothesized that a systematic functional screening of the human Kinome will reveal molecules that are essential for tumor survival, growth and migration which can function as potential therapeutic targets for MRT. Methods: We have screened 160 kinases in an MRT cell line (MON - Dr. Delattre, Institut Curie, Paris) using GeneArtLentiviral-CRISPR-library particles which contain up to 4 gRNAs per gene (Thermo Fisher Scientific). We first used a lenti-vector to permanently express Cas9 in the cells then infected these cells with the GeneArt Lentiviral-CRISPR-library particles and two controls (positive: gRNA for HPRT, negative: scrambled gRNA). After proper transduction and selection, genotypes were evaluated using Genomic Cleavage Detection (GCD) assays and phenotypes, by cell proliferation (MTT and Ki-67), viability (Trypan Blue) and migration (wound healing) assays. Results: The proportion of positive GFP-expressing cells indicated high transduction efficiencies (95%). GCD demonstrated successful gene editing levels in the positive control and in randomly selected kinases. In vitro studies allowed very precise monitoring of proliferation of each of the 160 mutated cell lines. Although the majority of mutated cell lines did not present changes in phenotypes, mutations in 15 kinases (9.37%), including the BRAF proto-oncogene, resulted in severe impairment of MRT cell proliferation. Conclusions: With the help ofCRISPR/Cas9 genome editing technology, we identified a set of kinases with the potential to serve as therapeutic targets for MRT. Acknowledgements: Sponsored by The Rally Foundation for Childhood Cancer Research in memory of Hailey Trainer and The Lurie Children's Neurosurgery Research Fund.
P2.03b-015 Efficacy of the Irreversible ErbB Family Blocker Afatinib in Treatment of an Intracerebral Non-Small Cell Lung Cancer in Mice
Authors: Lucheng Zhu, Shirong Zhang, Yanping Jiang, Jing Zhang, Yasi Xu, Bing Xia, Shenglin Ma
Journal: Journal of Thoracic Oncology (2017)
The vascular endothelial specific IL-4 receptor alpha–ABL1 kinase signaling axis regulates the severity of IgE-mediated anaphylactic reactions
Authors: Amnah Yamani, David Wu, Lisa Waggoner, Taeko Noah, Anthony J. Koleske, Fred Finkelman, Simon P. Hogan
Journal: Journal of Allergy and Clinical Immunology (2017)