tbuckley/cabot-search huggingface dataset:
Next-generation mapping: a novel approach for detection of pathogenic structural variants with a potential utility in clinical diagnosis
Authors: Hayk Barseghyan, Wilson Tang, Richard T. Wang, Miguel Almalvez, Eva Segura, Matthew S. Bramble, Allen Lipson, Emilie D. Douine, Hane Lee, Emmanuèle C. Délot, Stanley F. Nelson, Eric Vilain
Journal: Genome Medicine (2017)

Massively parallel DNA sequencing, such as exome sequencing, has become a routine clinical procedure to identify pathogenic variants responsible for a patient's phenotype. Exome sequencing has the capability of reliably identifying inherited and de novo single-nucleotide variants, small insertions, and deletions. However, due to the use of 100-300-bp fragment reads, this platform is not well powered to sensitively identify moderate to large structural variants (SV), such as insertions, deletions, inversions, and translocations.To overcome these limitations, we used next-generation mapping (NGM) to image high molecular weight double-stranded DNA molecules (megabase size) with fluorescent tags in nanochannel arrays for de novo genome assembly. We investigated the capacity of this NGM platform to identify pathogenic SV in a series of patients diagnosed with Duchenne muscular dystrophy (DMD), due to large deletions, insertion, and inversion involving the DMD gene.We identified deletion, duplication, and inversion breakpoints within DMD. The sizes of deletions were in the range of 45-250 Kbp, whereas the one identified insertion was approximately 13 Kbp in size. This method refined the location of the break points within introns for cases with deletions compared to current polymerase chain reaction (PCR)-based clinical techniques. Heterozygous SV were detected in the known carrier mothers of the DMD patients, demonstrating the ability of the method to ascertain carrier status for large SV. The method was also able to identify a 5.1-Mbp inversion involving the DMD gene, previously identified by RNA sequencing.We showed the ability of NGM technology to detect pathogenic structural variants otherwise missed by PCR-based techniques or chromosomal microarrays. NGM is poised to become a new tool in the clinical genetic diagnostic strategy and research due to its ability to sensitively identify large genomic variations.
Physical Activity Reduces Risk of Premature Mortality in Patients With Type 1 Diabetes With and Without Kidney Disease
Authors: Heidi Tikkanen-Dolenc, Johan Wadén, Carol Forsblom, Valma Harjutsalo, Lena M. Thorn, Markku Saraheimo, Nina Elonen, Heikki O. Tikkanen, Per-Henrik Groop
Journal: Diabetes Care (2017)

OBJECTIVE The aims of the study were to assess how baseline leisure-time physical activity (LTPA) and its exercise components intensity, duration, and frequency are associated with all-cause and cardiovascular mortality in patients with type 1 diabetes 1) overall, 2) stratified by presence or absence of chronic kidney disease (CKD), and 3) stratified by sex. RESEARCH DESIGN AND METHODS The study design was prospective and observational and included 2,639 patients with type 1 diabetes from the ongoing nationwide multicenter Finnish Diabetic Nephropathy (FinnDiane) Study. Mean follow-up time was 11.4 ± 3.5 years. LTPA was assessed by using a validated self-report questionnaire. Three hundred ten patients (11.7%) had CKD defined as an estimated glomerular filtration rate of ≤60 mL/min/1.73 m2. RESULTS During follow-up, 270 deaths occurred. LTPA and all its components were associated with all-cause mortality, even after adjustment for the potential confounders sex, diabetic nephropathy, duration of diabetes, age at onset of diabetes, systolic blood pressure, triglycerides, BMI, and HbA1c. Only exercise intensity was associated with cardiovascular mortality after adjustment for the confounders. Of the patients with CKD, 127 died during follow-up. The total amount of LTPA and exercise frequency were independently associated with lower risk of all-cause mortality when adjusted for covariates. CONCLUSIONS Exercise is associated with a lower risk of premature all-cause and cardiovascular mortality in patients with type 1 diabetes. This study also demonstrates that physical activity is associated with a lower risk of mortality in patients with type 1 diabetes and CKD.
Using Spatial and Temporal Mapping to Identify Nosocomial Disease Transmission of <i>Clostridium difficile</i>
Authors: Sara G. Murray, Joanne W. L. Yim, Rhiannon Croci, Alvin Rajkomar, Gabriela Schmajuk, Raman Khanna, Russell J. Cucina
Journal: JAMA Internal Medicine (2017)

This study evaluates the use of spatial and temporal mapping to identify nosocomial disease transmission of Clostridium difficile.
Prediabetes Prevalence in China—Reply
Authors: Pei Gao, Xun Tang, Yonghua Hu
Journal: JAMA (2017)

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
Deletion of Neuropilin 1 from Microglia or Bone Marrow–Derived Macrophages Slows Glioma Progression
Authors: Jeremy Tetsuo Miyauchi, Michael D. Caponegro, Danling Chen, Matthew K. Choi, Melvin Li, Stella E. Tsirka
Journal: Cancer Research (2017)

Abstract Glioma-associated microglia and macrophages (GAM), which infiltrate high-grade gilomas, constitute a major cellular component of these lesions. GAM behavior is influenced by tumor-derived cytokines that suppress initial antitumorigenic properties, causing them to support tumor growth and to convert and suppress adaptive immune responses to the tumor. Mice that lack the transmembrane receptor neuropilin-1 (Nrp1), which modulates GAM immune polarization, exhibit a decrease in glioma volumes and neoangiogenesis and an increase in antitumorigenic GAM infiltrate. Here we show that replacing the peripheral macrophage populations of wild-type mice with Nrp1-depleted bone marrow-derived macrophages (BMDM) confers resistance to the development of glioma. This resistance occurred in a similar fashion seen in mice in which all macrophages lacked Nrp1 expression. Tumors had decreased volumes, decreased vascularity, increased CTL infiltrate, and Nrp1-depleted BMDM adopted a more antitumorigenic phenotype relative to wild-type GAMs within the tumors. Mice with Nrp1-deficient microglia and wild-type peripheral macrophages showed resistance to glioma development and had higher microglial infiltrate than mice with wild-type GAMs. Our findings show how manipulating Nrp1 in either peripheral macrophages or microglia reprograms their phenotype and their pathogenic roles in tumor neovascularization and immunosuppression. Significance: This study highlights the proangiogenic receptor neuropilin 1 in macrophages and microglial cells in gliomas as a pivotal modifier of tumor neovascularization and immunosuppression, strengthening emerging evidence of the functional coordination of these two fundamental traits of cancer. Cancer Res; 78(3); 685–94. ©2017 AACR.
Nouvelles infections par l’HTLV diagnostiquées en Angleterre et Pays de Galles, 2002-2004
Authors: S Dougan, Alan Smith, J C Tosswill, K Davison, M Zuckerman, G P Taylor
Journal: Eurosurveillance (2005)

Les retrovirus humains (Human T cell lymphotropic viruses, HTLV) se transmettent par l’allaitement maternel, les relations sexuelles, les transfusions sanguines et l’utilisation de drogues injectables. Les HTLV sont endemiques dans les Caraibes et dans certaines zones d’Afrique, du Japon et d’Amerique du Sud, avec des foyers isoles dans d’autres regions du monde. L’infection est chronique. Moins de 5% des personnes contaminees developpent une des maladies liees au virus, mais celles-ci sont debilitantes et souvent mortelles. 
En Angleterre et au Pays de Galles, les declarations microbiologiques et cliniques des nouveaux diagnostics de HTLV sont recueillis en routine, incluant les infections identifiees par le service du sang depuis l’introduction du depistage de l’HTLV en aout 2002. 
Entre 2002 et 2004, 273 personnes ont ete confirmes positifs pour l’HTLV, dont 102 (37%) hommes et 169 femmes (le sexe n’etait pas precise pour deux cas). Au moment du diagnostic, l’âge median etait de 54 ans pour les hommes et 50 pour les femmes. Des rapports cliniques etaient disponibles pour 78% (212/273) des cas. Parmi ceux dont les donnees concernant l’appartenance ethnique etaient disponibles, 58% (116/199) etaient noirs d’origine caraibe et 29% (57/199) blancs ; 87% (128/147) ont probablement ete contamines lors de relations heterosexuelles ou par une transmission mere-enfant ; 45% (66/146) ont probablement ete contamines dans les Caraibes et 40% (59/146) au Royaume-Uni.
TCT-239 Comparison of safety and periprocedural complications of transfemoral aortic valve replacement in local anesthesia in reduced versus complete heart team
Authors: Michal Droppa, Thomas Katzenberger, Roland Krause, Oliver Borst, Dominik Rath, Karin Müller, Gawaz Meinrad, Tobias Geisler
Journal: Journal of the American College of Cardiology (2017)
Premier rapport de surveillance sur les Staphylococcus aureus résistants à la méthicilline acquis dans la communauté en Suisse
Authors: C Aramburu, S Harbarth, N Liassine, M Girard, A Gervaix, J Scherenzel, G Renzi, P Sudre
Journal: Eurosurveillance (2006)

Les SARM (Staphylococcus aureus resistants a la methicilline) sont un des pathogenes emergents dans la communaute. Les SARM acquis dans la communaute (co-SARM) ont ete associes a des souches virulentes produisant la leucocidine de Panton-Valentine (LPV) et plusieurs autres exotoxines. A Geneve, suite a l’identification en 2002 du premier co-SARM produisant la LPV, un systeme de surveillance base sur la declaration volontaire a ete mis en place. 
Toute culture positive pour SARM, dont le profil de resistance aux antibiotiques differe de celui de la souche endemique dominante dans les etablissements de soins de Geneve, et diagnostique chez un patient sans antecedent d’hospitalisation dans les 12 mois precedents, est declare au service local de sante publique. Le medecin traitant remplit un questionnaire contenant des informations demographiques, cliniques et sur l’exposition. 
De janvier 2002 a decembre 2004, les donnees de 58 cas ont ete notifiees, dont 26 cas groupes dans 13 foyers epidemiques distincts. La plupart d’entre eux etaient des membres de la meme famille, et pour deux d’entre eux, la colonisation a dure plus de 12 mois malgre le traitement. Trente-trois patients (57%) etaient des hommes. L’âge median etait de 32 ans et 22% avaient moins de 10 ans. Quarante-et-un cas (71%) etaient contamines et 17 (29%) colonises. Sur les 41 cas contamines, 40 presentaient des lesions dermatologiques symptomatiques, comme des furoncles, un impetigo ou des abces. La plupart des patients n’avaient pas de maladie sous-jacente. Trente-huit cas (65%) avaient voyage a l’etranger. Quarante (69%) des 58 isolats portaient le gene codant pour la LPV. 
Les infections a co-SARM sont un probleme emergent dans le canton de Geneve. La surveillance devrait se poursuivre e,t si possible, etre etendue aux autres parties du pays afin de mieux decrire les profils de transmission et la dissemination de ce pathogene. La prevention et le controle des infections a co-SARM sont un defi pour l’avenir, necessitant un suivi des contacts, des actions d’information et le traitement des contacts contamines et colonises.
TCT-506 An updated meta-analysis of randomized trials comparing complete versus culprit-only revascularization in patients undergoing primary percutaneous coronary intervention
Authors: Roisin Colleran, Robert Byrne, Himanshu Rai, Felix Voll, Daniele Giacoppo, Salvatore Cassese, Michael Joner, Heribert Schunkert, Adnan Kastrati
Journal: Journal of the American College of Cardiology (2017)
Lessons from the Latest ACA Battle
Authors: Jeanne M. Lambrew
Journal: New England Journal of Medicine (2017)

Interview with Dr. Linda Blumberg on proposals for stabilizing insurance markets and making nongroup insurance more affordable. (12:29)Download Obamacare has had multiple near-death experiences, but the most recent battle against repeal is notable for its unlikely heroes, who included GOP senators and governors, independent analysts, engaged citizens, past ACA critics, and comedian Jimmy Kimmel.
Intervention With Brief Cessation Advice Plus Active Referral for Proactively Recruited Community Smokers
Authors: Man Ping Wang, Yi Nam Suen, William Ho-cheung Li, Christina Oi-bun Lam, Socrates Yong-da Wu, Antonio Cho-shing Kwong, Vienna W. Lai, Sophia S. Chan, Tai Hing Lam
Journal: JAMA Internal Medicine (2017)

<h3>Importance</h3> Most smoking cessation (SC) clinics are costly, passive, and underused. <h3>Objective</h3> To compare the SC effect of a combined intervention involving brief, model-guided SC advice plus active referral to SC services (active referral group) with those of brief, model-guided SC advice only (brief advice group) and general SC advice only (control group). <h3>Design, Setting, and Participants</h3> A single-blind, 3-arm, pragmatic cluster randomized clinical trial was conducted including 1226 adult daily smokers in the general Hong Kong community proactively recruited to participate in the Quit-to-Win Contest held in 2015. The study was conducted from June 20 to September 24, 2015. Participants were randomly allocated to the active referral (n = 402), brief advice (n = 416), and control (n = 408) groups. Intention-to-treat analysis was used. <h3>Interventions</h3> Brief telephone counseling was offered to the active referral and brief advice groups at 1 and 2 months. Interventions were delivered by SC ambassadors who had undergone a short training period. <h3>Main Outcomes and Measures</h3> The primary outcome was the self-reported past 7-day point prevalence of abstinence (PPA) at 6 months. The secondary outcomes were carbon monoxide level–validated abstinence, smoking reduction, and SC service use. <h3>Results</h3> Participants included 991 (80.8%) men; mean (SD) age was 42.0 (14.8) years. The response rate was 68.2% at 3 and 72.3% at 6 months. The corresponding PPAs were 18.9% and 17.2% in the active referral group—higher than in the brief advice (8.9% and 9.4%; both<i>P</i> ≤ .001) or control (14.0% and 11.5%;<i>P</i> = .03 at 6 months) groups. Compared with the other 2 groups, the active referral group had significantly higher validated abstinence rates (10.2% at 3 months and 9.0% at 6 months, all<i>P</i> &lt; .05) with odds ratios of 2.84 (95% CI, 1.57-5.15) and 2.61 (95% CI, 1.46-4.68) at 3 months, and 1.85 (95% CI, 1.06-3.23) and 1.81 (95% CI, 1.04-3.16) at 6 months in the brief advice and control groups, respectively. The SC service use rate was significantly higher in the active referral group (25.1%) than in either brief advice (2.4%) or control (3.4%) groups at 6 months (<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> An intervention involving brief advice and active referral delivered to smokers in the community by volunteers can increase quitting in places where SC services are available but underused. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT02539875
Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease
Authors: Vicente E. Torres, Arlene B. Chapman, Olivier Devuyst, Ron T. Gansevoort, Ronald D. Perrone, Gary Koch, John Ouyang, Robert D. McQuade, Jaime D. Blais, Frank S. Czerwiec, Olga Sergeyeva
Journal: New England Journal of Medicine (2017)

In a previous trial involving patients with early autosomal dominant polycystic kidney disease (ADPKD; estimated creatinine clearance, ≥60 ml per minute), the vasopressin V2-receptor antagonist tolvaptan slowed the growth in total kidney volume and the decline in the estimated glomerular filtration rate (GFR) but also caused more elevations in aminotransferase and bilirubin levels. The efficacy and safety of tolvaptan in patients with later-stage ADPKD are unknown.We conducted a phase 3, randomized withdrawal, multicenter, placebo-controlled, double-blind trial. After an 8-week prerandomization period that included sequential placebo and tolvaptan run-in phases, during which each patient's ability to take tolvaptan without dose-limiting side effects was assessed, 1370 patients with ADPKD who were either 18 to 55 years of age with an estimated GFR of 25 to 65 ml per minute per 1.73 m2 of body-surface area or 56 to 65 years of age with an estimated GFR of 25 to 44 ml per minute per 1.73 m2 were randomly assigned in a 1:1 ratio to receive tolvaptan or placebo for 12 months. The primary end point was the change in the estimated GFR from baseline to follow-up, with adjustment for the exact duration that each patient participated (interpolated to 1 year). Safety assessments were conducted monthly.The change from baseline in the estimated GFR was -2.34 ml per minute per 1.73 m2 (95% confidence interval [CI], -2.81 to -1.87) in the tolvaptan group, as compared with -3.61 ml per minute per 1.73 m2 (95% CI, -4.08 to -3.14) in the placebo group (difference, 1.27 ml per minute per 1.73 m2; 95% CI, 0.86 to 1.68; P<0.001). Elevations in the alanine aminotransferase level (to >3 times the upper limit of the normal range) occurred in 38 of 681 patients (5.6%) in the tolvaptan group and in 8 of 685 (1.2%) in the placebo group. Elevations in the aminotransferase level were reversible after stopping tolvaptan. No elevations in the bilirubin level of more than twice the upper limit of the normal range were detected.Tolvaptan resulted in a slower decline than placebo in the estimated GFR over a 1-year period in patients with later-stage ADPKD. (Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization; REPRISE ClinicalTrials.gov number, NCT02160145 .).
TCT-839 Prognostic Significance of Established CAD in Patients with Left Main Disease Undergoing Revascularization: Analysis from EXCEL Trial
Authors: Matias Yudi, Roxana Mehran, Usman Baber, Aaron Crowley, Ori Ben-Yehuda, A. Pieter Kappetein, Joseph Sabik, Patrick Serruys, Gregg Stone
Journal: Journal of the American College of Cardiology (2017)
TCT-317 Propensity Score-Matched Analysis of Operator Radiation Exposure in Percutaneous Coronary Intervention with Radial versus Femoral Approach
Authors: Adriano Caixeta, Ana Leoncio, Breno Almeida, Fabio Brito, José Mariani, Carlos Campos, Marco Tulio Souza, Paula Gomes, Stella Pedrini, Pedro A. Lemos, Ivanise Gomes, Marcelo Franken
Journal: Journal of the American College of Cardiology (2017)
Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia
Authors: Robert O. Opoka, Christopher M. Ndugwa, Teresa S. Latham, Adam Lane, Heather A. Hume, Phillip Kasirye, James S. Hodges, Russell E. Ware, Chandy C. John
Journal: Blood (2017)
Abstract 11287: The Relationship of All-Cause Mortality to Average On-Treatment Systolic Blood Pressure is Significantly Related to Baseline Systolic Blood Pressure: Implications for Interpretation of the SPRINT Study
Authors: Peter M Okin, Sverre E Kjeldsen, Richard B Devereux
Journal: Circulation (2016)

Background: The SPRINT study demonstrated that targeting systolic blood pressure (SBP) &lt;120 mm Hg was associated with lower cardiovascular event and mortality rates. However, in the LIFE study, a lower achieved SBP (&lt;130 mm Hg) was associated with increased mortality. Mean baseline SBP in SPRINT was 140 and a third of the population had a baseline SBP ≤132, raising the question of whether the lower baseline SBP in SPRINT could in part account for these differences. Methods: All-cause mortality in relation to tertiles of on-treatment average SBP achieved was examined in patients with baseline SBP ≤ or &gt; 25 th percentile value of 164 mm Hg during 4.8±0.9 years follow-up in 7998 non-diabetic hypertensive patients with ECG left ventricular hypertrophy randomly assigned to losartan- or atenolol-based treatment. Average on-treatment SBP &lt;142 (lowest tertile) and average SBP 142 to &lt;152 (middle tertile) were compared with average SBP ≥152 (highest tertile and reference group). Results: In the overall population, there was a highly significant interaction between baseline SBP ≤164 and average on-treatment SBP &lt;142 in Cox analysis (χ 2 =15.48, p&lt;0.001). Among patients with baseline SBP &gt;164, in multivariate Cox analyses adjusting for other potential predictors of mortality and a propensity score for having baseline SBP ≤164, compared with average on-treatment SBP ≥152 an average on-treatment SBP &lt;142 was associated with 32% increased risk of mortality (HR 1.32, 95% CI 1.01-1.65), whereas average SBP of 142 to &lt;152 was associated with 24% lower mortality risk (HR 0.76, 95% CI 0.59-0.98). In contrast, in parallel Cox analyses among patients with baseline SBP ≤164, both an average on-treatment SBP &lt;142 (HR 0.60, 95% CI 0.36-0.99) and average SBP of 142 to &lt;152 (HR 0.51, 95% CI 0.30-0.89) were associated with statistically significant lower risks of mortality compared with average SBP ≥152. Conclusions: All-cause mortality risk associated with achievement of an average SBP &lt;142 is strongly related to baseline SBP level in LIFE. These findings suggest that the lower mortality associated with a lower targeted SBP in SPRINT may not be applicable to patients with considerably higher baseline SBP than SPRINT patients. Further study is necessary to better understand these findings.
The role of liver biopsy in chronic hepatitis C
Authors: S Saadeh
Journal: Hepatology (2001)

Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide, affecting 175 million people globally. Over 80% of acutely infected patients go on to develop chronicity, but only 20% to 25% will develop end-stage liver disease and its complications. The sequelae of HCV-induced chronic liver disease accounts for 8,000 to 10,000 deaths annually in the United States and is currently the leading indication for liver transplantation. To date, there are no accurate noninvasive markers of disease activity and fibrosis. Liver biopsy is indicated to exclude other forms of liver pathologies and to establish the stage of liver disease. In this study, the role of liver biopsy in chronic hepatitis C was evaluated. Additionally, we calculated a discriminant score to predict cirrhosis in chronic hepatitis C infection. Our results showed that additional diagnoses or unsuspected diagnoses are less frequent than clinicians' suspected. We confirmed that the discriminant score for predicting cirrhosis is inferior to liver biopsy. In conclusion, the majority of patients with chronic hepatitis C will require a liver biopsy, which has an important implication on staging of the liver disease, prognosis, and possibly further management options.
TCT-743 Clinical Impact of Stent Diameter and Length of First-Generation and Contemporary Drug-Eluting Stents: Evidence From Prospective, Stent-Specific, Observational Registries
Authors: Cheol Hyun Lee, Yong-Hoon Yoon, Sang Yong Om, Minsoo Kim, Hanbit Park, Sang-Cheol Cho, Ungjeong Do, Kyusup Lee, Osung Kwon, Do-yoon Kang, Pil Hyung Lee, Jung-Min Ahn, Duk-Woo Park, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2017)