tbuckley/cabot-search huggingface dataset:
Up-regulation of miR-31 in human atrial fibrillation begets the arrhythmia by depleting dystrophin and neuronal nitric oxide synthase
Authors: Svetlana N. Reilly, Xing Liu, Ricardo Carnicer, Alice Recalde, Anna Muszkiewicz, Raja Jayaram, Maria Cristina Carena, Rohan Wijesurendra, Matilde Stefanini, Nicoletta C. Surdo, Oliver Lomas, Chandana Ratnatunga, Rana Sayeed, George Krasopoulos, Timothy Rajakumar, Alfonso Bueno-Orovio, Sander Verheule, Tudor A. Fulga, Blanca Rodriguez, Ulrich Schotten, Barbara Casadei
Journal: Science Translational Medicine (2016)

Atrial fibrillation (AF) is a growing public health burden, and its treatment remains a challenge. AF leads to electrical remodeling of the atria, which in turn promotes AF maintenance and resistance to treatment. Although remodeling has long been a therapeutic target in AF, its causes remain poorly understood. We show that atrial-specific up-regulation of microRNA-31 (miR-31) in goat and human AF depletes neuronal nitric oxide synthase (nNOS) by accelerating mRNA decay and alters nNOS subcellular localization by repressing dystrophin translation. By shortening action potential duration and abolishing rate-dependent adaptation of the action potential duration, miR-31 overexpression and/or disruption of nNOS signaling recapitulates features of AF-induced remodeling and significantly increases AF inducibility in mice in vivo. By contrast, silencing miR-31 in atrial myocytes from patients with AF restores dystrophin and nNOS and normalizes action potential duration and its rate dependency. These findings identify atrial-specific up-regulation of miR-31 in human AF as a key mechanism causing atrial dystrophin and nNOS depletion, which in turn contributes to the atrial phenotype begetting this arrhythmia. miR-31 may therefore represent a potential therapeutic target in AF.
Abstract 154: Interaction Between Nitroso-Redox Balance and Temperature Influences SR Ca <sup>2+</sup> Leak In Cardiomyocytes: Role of Neuronal NOS Signaling
Authors: Raul A Dulce, Vera Mayo, Erika B Rangel, Wayne Balkan, Joshua M Hare
Journal: Circulation Research (2014)

Sarcomeric reticulum (SR) Ca 2+ leak contributes to impaired Ca 2+ cycling and contractile dysfunction of the heart. Leak is thought to be regulated by post-translational modification of RyR2 associated with the nitroso-redox state. Ca 2+ cycling is affected by both nitric oxide (NO) signaling and temperature. We studied the effect of temperature and nitroso-redox state on Ca 2+ leak. We hypothesized that nitroso-redox balance modulates leak in a temperature–dependent manner. Tetracaine was used to estimate the leak in cardiomyocytes (CMs) in mouse models of nitroso-redox imbalance (NOS1 -/- ), hyper S-nitrosylation (GSNOR -/- ) and in WT mice. Reactive oxygen species (ROS) were measured. Experiments were carried out at 23°C – 37°C. In WT CMs, Ca 2+ leak was inversely proportional to temperature whereas, in NOS1 -/- CMs, the leak suddenly increased when the temperature surpassed 30°C. Supplementing the media with NO (1 microM SNAP), reduced leak in NOS1 -/- CMs at physiologic temperature while at low temperatures, there was a trend toward an increase, a pattern similar to that of GSNOR -/- rather than WT CMs. The xanthine oxidase inhibitor, oxypurinol (100 microM), diminished the leak in NOS1 -/- CMs. SR Ca 2+ content in NOS1 -/- CMs was reduced as the temperature decreased, whereas it was not affected in WT cells. Cooling from 37°C to 23 °C increased ROS generation in WT CMs; however there was an opposite effect observed in NOS1 -/- CMs, which was further reduced by oxypurinol. Expression of the NOS isoforms (by RT-PCR) was unaffected by temperature in WT. Therefore, Ca 2+ leak is temperature dependent, is affected by the absence of NOS1 activity and increases with the rise of ROS production. Defective denitrosylation activity keeps leak low, suggesting a protective effect of S-nitrosylation against the cooling-induced increase in SR Ca 2+ leak. These results suggest that Ca 2+ leak from the SR is regulated by a temperature-dependent balance between NO and ROS.
Surveillance of acute infectious gastroenteritis (1992–2009) and food-borne disease outbreaks (1996–2009) in Italy, with a focus on the Piedmont and Lombardy regions
Authors: L Mughini-Gras, C Graziani, F Biorci, A Pavan, R Magliola, A Ricci, G Gilli, E Carraro, L Busani
Journal: Eurosurveillance (2012)

We describe trends in the occurrence of acute infectious gastroenteritis (1992 to 2009) and food-borne disease outbreaks (1996 to 2009) in Italy. In 2002, the Piedmont region implemented a surveillance system for early detection and control of food-borne disease outbreaks; in 2004, the Lombardy region implemented a system for surveillance of all notifiable human infectious diseases. Both systems are internet based. We compared the regional figures with the national mean using official notification data provided by the National Infectious Diseases Notification System (SIMI) and the National Institute of Statistics (ISTAT), in order to provide additional information about the epidemiology of these diseases in Italy. When compared with the national mean, data from the two regional systems showed a significant increase in notification rates of non-typhoid salmonellosis and infectious diarrhea other than non-typhoid salmonellosis, but for foodborne disease outbreaks, the increase was not statistically significant. Although the two regional systems have different objectives and structures, they showed improved sensitivity regarding notification of cases of acute infectious gastroenteritis and, to a lesser extent, food-borne disease outbreaks, and thus provide a more complete picture of the epidemiology of these diseases in Italy.
ETHERINGTON-SMITH MEMORIAL.
Authors: AnthonyA. Bowlby, W.B. Close, G. Acton Davis, J.H. Gibbon, W.P. Herringham, R.C. Lehmann, Howard Marsh, S.D. Muttlebury, Guy Nickalls, G.D. Rowe, H.T. Steward
Journal: The Lancet (1913)
The right to treatment suit as an agent of change
Authors: E Kaufman
Journal: American Journal of Psychiatry (1979)

Right to treatment suits can serve as agents of change in the standards and function of psychiatric institutions. The author evaluated five state psychiatric institutions as an expert witness in right to treatment suits. He found that changes for the better were made in most of these institutions as a result of the suit, whether it was settled or unsettled. Although he enumerates the problems caused by such suits, he concludes that they can be a positive force for improving mental health care.
More on the Association of Glucose-6-Phosphate Dehydrogenase Deficiency with Hairy-Cell Leukemia
Authors: R V Clayman, L R Kavoussi, N J Soper, S M Dierks, K S Merety, M D Darcy, S R Long, F D Roemer, E D Pingleton, P G Thomson
Journal: New England Journal of Medicine (1991)
Informed consent and confidentiality: proposed new approaches in Illinois
Authors: R Shlensky
Journal: American Journal of Psychiatry (1977)

The author examines the basic background and definitions of the issues of consent and, more particularly, informed consent to relinquishing the privacy of mental health records. He sets these issues in the context of some of their specific inherent problems and describes possible solutions suggested by the State of Illinois Governor's Commission To Revise the Mental Health Code.
Identification of DNA rearrangements at the retinoic acid receptor- alpha (RAR-alpha) locus in all patients with acute promyelocytic leukemia (APL) and mapping of APL breakpoints within the RAR-alpha second intron. Italian Cooperative Study Group "GIMEMA"
Authors: D Diverio, F Lo Coco, F D'Adamo, A Biondi, M Fagioli, F Grignani, A Rambaldi, V Rossi, G Avvisati, MC Petti
Journal: Blood (1992)
Abstract 3906: Annexin A1 overexpression preferentially predicts poor prognosis of basal-like breast cancer patients by activating m TOR-S6 signaling
Authors: Kazunoshin Tachibana, Anjana Bhardwaj, Nivetha Ganesan, Kimal Rajapakshe, Constance T. Albarracin, Preethi H. Gunaratn, Cristian Coarfa, Isabelle Bedrosian
Journal: Cancer Research (2015)

Abstract Introduction: Annexin A1 is an anti-inflammatory protein reported to play a role in cell proliferation, apoptosis and to be deregulated in breast cancer. The role and regulation of annexin A1 in the biology and prognosis of breast cancer remain unclear because most of the studies did not consider specific differences between the different subtypes of breast cancer. Thus, in this study, we hypothesize that annexin A1 plays subtype-specific role in basal like breast cancer progression and metastasis. Methods: By mining The Cancer Genome Atlas-Breast Cancer Dataset (TCGA-BRCA) and manipulating annexin A1 levels in breast cancer cell lines, we studied the role of annexin A1 in breast cancer and underlying signaling pathways. Results: Our in-silico analysis of TCGA-BRCA dataset demonstrated that annexin A1 mRNA expression is higher in basal subtype compared to luminal and HER2 subtypes. Within the basal subtype, patients show significantly poorer survival associated with higher expression of annexin A1. In both TCGA patient samples and cell lines, annexin A1 levels were significantly higher in basal-like breast cancer tumors than luminal and Her2/neu-positive breast cancer tumors. Stable annexin A1 knockdown in TNBC cell lines suppressed the mTOR-S6 pathway. Specifically, annexin A1 knockdown inhibited phosphorylation of mTOR and S6 (18-73% inhibition in pmTOR and 50-60% inhibition in pS6). But annexin A1 knockdown had no impact on the MAPK, c-Met, and EGFR pathways. In cell migration assays, annexin A1-depleted TNBC cells showed delayed migration as compared to wild-type cells which we found to be through suppression of MMP9. Conclusions: Our data suggest that annexin A1 is prognostic only in patients with basal like breast cancer. This appears to be due in part to the role of annexin A1 in activating mTOR-pS6 pathway. Citation Format: Kazunoshin Tachibana, Anjana Bhardwaj, Nivetha Ganesan, Kimal Rajapakshe, Constance T. Albarracin, Preethi H. Gunaratn, Cristian Coarfa, Isabelle Bedrosian. Annexin A1 overexpression preferentially predicts poor prognosis of basal-like breast cancer patients by activating m TOR-S6 signaling. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3906. doi:10.1158/1538-7445.AM2015-3906
Abstract B2-23: A Big Bang model of human colorectal tumor growth
Authors: Andrea Sottoriva, Haeyoun Kang, Zhicheng Ma, Trevor A. Graham, Matthew Salomon, Junsong Zhao, Paul Marjoram, Kim Siegmund, Michael F. Press, Darryl Shibata, Christina Curtis
Journal: Cancer Research (2015)

Abstract What happens in the early and still undetectable human malignancy is unknown because direct observations are impractical. Here we present a “Big Bang” model, whereby a tumor grows predominantly as a single expansion producing numerous intermixed sub-clones, which are not subject to stringent clonal selection. In this model, both public and most detectable private mutations arise during the earliest phase of tumor growth. Multi-scale genomic profiling of 349 individual glands sampled from 15 colorectal tumors revealed the absence of selective sweeps, uniformly high intra-tumor heterogeneity, and sub-clone mixing in distant tumor regions, as postulated by the Big Bang. By integrating the data in a spatial model of tumor growth and statistical inference framework we also verified the most striking prediction of our model, namely that most detectable intra-tumor heterogeneity originates from private alterations acquired early during growth, and not from the later expansion of selected sub-clones. Hence, early sub-clones define the genomic profile of colorectal carcinomas and advanced adenomas, whereas potentially dangerous late-arising sub-clones will go undetected. Moreover, our results suggest that sub-clone mixing may be a biomarker of malignant potential. This new model provides a quantitative framework that explains the origins of intra-tumor heterogeneity and tumor growth dynamics with significant clinical implications. Citation Format: Andrea Sottoriva, Haeyoun Kang, Zhicheng Ma, Trevor A. Graham, Matthew Salomon, Junsong Zhao, Paul Marjoram, Kim Siegmund, Michael F. Press, Darryl Shibata, Christina Curtis. A Big Bang model of human colorectal tumor growth. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B2-23.
The face validity of the DSM-III and DSM-III-R criteria sets for borderline personality disorder
Authors: M C Zanarini, J G Gunderson, F R Frankenburg, D L Chauncey, J H Glutting
Journal: American Journal of Psychiatry (1991)

The main objective of this study was to determine the congruence between DSM-III and DSM-III-R diagnoses of borderline personality disorder derived through the use of semistructured research interviews or given by experienced clinicians after lengthy consultations with an interdisciplinary team.The presence of the DSM-III and DSM-III-R criteria sets for borderline personality disorder was assessed in a study group of 253 patients with personality disorders (148 inpatients and 105 outpatients) by raters who were blind to clinical diagnoses and who used information from two semistructured interviews of proven reliability. These diagnoses were then compared with "longitudinal expert all data" (LEAD) standard clinical diagnoses provided by therapists specifically asked to base their diagnoses on DSM criteria.Both criteria sets were found to be overinclusive when compared with the LEAD standard. Most criteria were also found to lack specificity. However, the three DSM-III-R criteria that are new or revisions of DSM-III criteria were found to be more specific, and raising the cutoff on the DSM-III-R criteria from five to six improved specificity.Both the DSM-III and DSM-III-R criteria sets for borderline personality disorder as assessed by semistructured interview lack face validity because they are nonspecific when compared with a rigorous but representative clinical standard, and the results of studies using these criteria sets may prove misleading to researchers and clinicians because they seem to define a nonspecific type of serious character pathology.
Abstract P3-07-14: Prosigna® intrinsic subtyping predicts response to neoadjuvant combination therapy in study that includes herceptin within HER2+ (IHC) patients
Authors: Á Santonja, N Ribelles, B Jiménez-Rodríguez, P Sánchez Rovira, M Álvarez, L Vicioso, A Isabel Fernandez, V de Luque, C Fernández de Sousa, E Villar, I Zarcos, C Ramírez, C González-Hermoso, A Jeiranian, N Dowidar, C Schaper, W Buckingham, S Ferree, A Jiménez, A Prat, E Alba
Journal: Cancer Research (2016)

Abstract Background: The role of the HER2-enriched (HER2E) subtype determined by the Prosigna Assay in the neoadjuvant setting has remained largely uncharacterized. In this study, we examine whether Prosigna can identify a subgroup of HER2+ patients for whom combination neoadjuvant therapy that includes trastuzumab (Herceptin) is associated with a greater likelihood of pathological complete response (pCR). Methods: In this single-arm retrospective analysis, 75 patients determined to be HER2+ by IHC were treated with a neoadjuvant regimen (NAC) consisting of 8-12 cycles of anthracyclines and taxanes as well as Herceptin. The Prosigna Assay was performed on the NanoString nCounter® Dx Analysis System at HU Virgende la Victoria de Málaga/CIMES-UMA. pCR was used as the endpoint for this study and was determined using the Miller &amp; Payne scoring criteria. Results: Mean patient age for this study population was 49 (±11.1yr) and all patients were determined to be HER2+ by IHC. The overall pCR rate in this patient population was 46.2%. Of the 75 patient samples analyzed for this study, 59 (78.6%) were HER2E, 4 (5.3%) were Luminal A and 12 (16.1%) were Luminal B, as identified by the Prosigna Assay. Of the 16 tumors classified as Luminal (A or B) by Prosigna within this HER2+ population, only 2 (12.5%) responders were observed. Categorical analysis revealed that Prosigna subtype predicted response to a NAC regimen combined with Herceptin (Odds ratio [Her2E vs. non-Her2E]=6.4, p=0.023). Further analysis of the Her2E subtype revealed that tumors with profile expression that correlated well with the prototypical Her2E centroid were significantly more likely to respond to combination NAC and Herceptin (Odds ratio [Unit increase of 1 in Her2E correlation]=88.2, p=0.004). Conclusions: The results of this study indicate that HER2+ patients with greater correlations to the HER2E subtype have an increased likelihood of response to combination neoadjuvant regimens that included HER2-targeted therapy. Citation Format: Santonja Á, Ribelles N, Jiménez-Rodríguez B, Sánchez Rovira P, Álvarez M, Vicioso L, Isabel Fernandez A, de Luque V, Fernández de Sousa C, Villar E, Zarcos I, Ramírez C, González-Hermoso C, Jeiranian A, Dowidar N, Schaper C, Buckingham W, Ferree S, Jiménez A, Prat A, Alba E. Prosigna® intrinsic subtyping predicts response to neoadjuvant combination therapy in study that includes herceptin within HER2+ (IHC) patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-14.
Late-onset schizophrenia
Authors: Manabu Yasuda, Satoshi Kato
Journal: American Journal of Psychiatry (1982)

We conducted clinical research at Jichi Medical University Hospital psychiatric ward on 38 patients over the age of 40 with late-onset schizophrenia and on 278 patients under the age of 40 with early-onset schizophrenia. Cases with onset after age 40 reported in 12% of the total population. Female cases were 20.4%, and the result was significantly higher than the male cases of 4.3%. Paranoid type was 55.3% of the total population of the late-onset cases, and it was significantly higher than the early-onset cases of younger than 40 years old. 55.3% of late-onset cases were combined with depressive symptoms, and they rated significantly higher than early-onset cases.
Hemorrhagic gastric ulcer after endoscopic ultrasound-guided fine needle aspiration of a pancreatic adenocarcinoma
Authors: Tomoya Iida, Takeya Adachi, Suguru Nakagaki, Takashi Yabana, Akira Goto, Yoshihiro Kondo
Journal: Endoscopy (2015)

A 64-year-old man presented with a chief complaint of back pain. A contrast-enhanced computed tomography (CT) scan showed a 3-cm hypovascular, irregular, tumorous lesion in the body of the pancreas invading the celiac, splenic, and common hepatic arteries ([Fig. 1 a]). Inferior vena cava (IVC) invasion was thought to be due to lymph node metastasis ([Fig. 1 b]), and thrombi in the peripheral veins were causing extensive blockage. An endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was performed (2 times, 10 strokes each) on the pancreatic lesion with a 22-gauge needle (Expect; Boston Scientific, Tokyo, Japan) ([Fig. 2]). Pathological findings indicated invasive pancreatic ductal cancer. The patient was diagnosed with stage IVB cancer of the pancreatic body (Union for International Cancer Control classification). Systemic chemotherapy was planned, and edoxaban was administered for the venous thrombi caused by the IVC invasion.
Health, Wealth, Social Integration, and Sexuality of Extremely Low-Birth-Weight Prematurely Born Adults in the Fourth Decade of Life
Authors: Saroj Saigal, Kimberly L. Day, Ryan J. Van Lieshout, Louis A. Schmidt, Katherine M. Morrison, Michael H. Boyle
Journal: JAMA Pediatrics (2016)

Although it has been previously reported that the transition of extremely low-birth-weight survivors (≤1000 g) in their mid-20s was similar to that of normal-birth-weight controls (>2500g), there was uncertainty as to whether this positive pattern would persist.To compare the social functioning of low-birth-weight prematurely born adults aged 29 to 36 years with that of normal-birth-weight term controls.A population-based longitudinal cohort study was conducted in Ontario, Canada, between March 14, 2011, and August 13, 2013, among 100 of 165 low-birth-weight survivors (60.6%) prematurely born between January 1, 1977, and December 31, 1982, and 89 of 144 sociodemographically matched normal-birth-weight term controls (61.8%) recruited at age 8 years. Neurologic impairments were present in 20 premature participants (20.0%).Extremely low birth weight.Information on health, educational level, employment, social integration, sexuality, and reproduction was obtained through standardized questionnaires completed by the participants.Participants included 100 (39 males) extremely low-birth-weight survivors and 89 (33 males) normal-birth-weight term controls. The groups did not differ in the highest educational level achieved or in family and partner relationships. However, a lower proportion of premature adults was employed (odds ratio [OR], 0.37; 95% CI, 0.15 to 0.93) and fewer were employed full time (OR, 0.49; 95% CI, 0.24 to 0.98). The premature group had a mean total personal income of $20 000 less than controls, and more required social assistance (OR, 4.16; 95% CI, 1.13 to 15.33). Compared with the control group, more members of the premature group remained single (OR, 1.95; 95% CI, 1.08 to 3.50), had never had sexual intercourse (OR, 11.30; 95% CI, 2.56 to 49.91), did not have children (OR, 0.52; 95% CI, 0.27 to 0.99), reported more chronic health conditions (β, 1.54; 95% CI, 0.79 to 2.30), had lower self-esteem (β, 8.40; 95% CI, 1.68 to 15.12), and were less likely to have current drug abuse or dependence (OR, 0.29; 95% CI, 0.90 to 0.92) or lifetime alcohol abuse or dependence (OR, 0.30; 95% CI, 0.15 to 0.59). A higher proportion of premature adults without neurosensory impairments identified themselves as nonheterosexual (OR, 4.87; 95% CI, 1.01 to 23.69). After exclusion of individuals with neurosensory impairments, differences in employment, social assistance, marital status, and reproduction were no longer significant.In the fourth decade of life, extremely low-birth-weight survivors achieved similar educational levels and family and partner relationships, and reported fewer risky behaviors compared with controls. However, they had lower levels of employment, income, and self-esteem, and fewer were married and had children. It is therefore essential that these individuals receive necessary support and continued monitoring throughout life.
New Morcellation System Does Not Eliminate Cancer Risk
Authors: Rebecca Voelker
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