tbuckley/cabot-search huggingface dataset:
Mapping a shared genetic basis for neurodevelopmental disorders
Authors: Matthew Jensen, Santhosh Girirajan
Journal: Genome Medicine (2017)

Distinct neurodevelopmental disorders have a common genetic etiology that explains the high degree of comorbidity among these disorders. A recent study sought to identify copy number variants across five neurodevelopmental disorders, and detected an enrichment for chromosome 9p24.3 duplication encompassing DOCK8 and KANK1 in affected individuals. Such large-scale studies will help uncover additional causative and modifier loci within common pathways, which will enable the development of therapeutic targets for the treatment of multiple disorders. See related research 10.1186/s13073-017-0494-1
Salt-Losing Tubulopathies in Children: What’s New, What’s Controversial?
Authors: Robert Kleta, Detlef Bockenhauer
Journal: Journal of the American Society of Nephrology (2017)

Renal tubulopathies provide insights into the inner workings of the kidney, yet also pose therapeutic challenges. Because of the central nature of sodium in tubular transport physiology, disorders of sodium handling may affect virtually all aspects of the homeostatic functions of the kidney. Yet, owing to the rarity of these disorders, little clinical evidence regarding treatment exists. Consequently, treatment can vary widely between individual physicians and centers and is based mainly on understanding of renal physiology, reported clinical observations, and individual experiences. Salt-losing tubulopathies can affect all tubular segments, from the proximal tubule to the collecting duct. But the more frequently observed disorders are Bartter and Gitelman syndrome, which affect salt transport in the thick ascending limb of Henle's loop and/or the distal convoluted tubule, and these disorders generate the greatest controversies regarding management. Here, we review clinical and molecular aspects of salt-losing tubulopathies and discuss novel insights provided mainly by genetic investigations and retrospective clinical reviews. Additionally, we discuss controversial topics in the management of these disorders to highlight areas of importance for future clinical trials. International collaboration will be required to perform clinical studies to inform the treatment of these rare disorders.
Overlapping Surgery—Perspectives From the Other Side of the Table
Authors: Alan L. Zhang
Journal: JAMA Internal Medicine (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 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
Long term hormonal treatment for transgender people
Authors: Martin den Heijer, Alex Bakker, Louis Gooren
Journal: BMJ (2017)

### What you need to know

The aim of hormone treatment in transgender people is to adjust their secondary sex characteristics to be more congruent with their experienced gender. Hormone treatment for transgender people is usually initiated by specialist gender clinics, but some people start hormone treatment of their own accord without a prescription. With growing numbers of transgender people presenting to healthcare services (estimated as 9.2 per 100 0001), general practitioners, general endocrinologists, and other doctors will become increasingly involved in their long term care, the prescription of hormones, and consideration of potential side effects. Several guidelines are available on the start of hormonal treatment234567; the focus of this article is the long term hormonal care for transgender people who might no longer attend a specialist clinic. It is aimed at a more general readership of physicians occasionally seeing adult transgender people.

### Transgender terminology

Language and terminology are sensitive. Some terms used in the past are no longer appropriate because they might have negative connotations. 

#### Sex/gender

The term gender has historically been used to refer to psychological, behavioural, and sociological characteristics, and their categorisation by society as “masculine” or “feminine.” The term sex has historically been used to refer to …
The Impact of Smoking and TP53 Mutations in Lung Adenocarcinoma Patients with Targetable Mutations—The Lung Cancer Mutation Consortium (LCMC2)
Authors: Dara L. Aisner, Lynette M. Sholl, Lynne D. Berry, Michael R. Rossi, Heidi Chen, Junya Fujimoto, Andre L. Moreira, Suresh S. Ramalingam, Liza C. Villaruz, Gregory A. Otterson, Eric Haura, Katerina Politi, Bonnie Glisson, Jeremy Cetnar, Edward B. Garon, Joan Schiller, Saiama N. Waqar, Lecia V. Sequist, Julie Brahmer, Yu Shyr, Kelly Kugler, Ignacio I. Wistuba, Bruce E. Johnson, John D. Minna, Mark G. Kris, Paul A. Bunn, David J. Kwiatkowski
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Multiplex genomic profiling is standard of care for patients with advanced lung adenocarcinomas. The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional effort to identify and treat oncogenic driver events in patients with lung adenocarcinomas. Experimental Design: Sixteen U.S. institutions enrolled 1,367 patients with lung cancer in LCMC2; 904 were deemed eligible and had at least one of 14 cancer-related genes profiled using validated methods including genotyping, massively parallel sequencing, and IHC. Results: The use of targeted therapies in patients with EGFR, ERBB2, or BRAF p.V600E mutations, ALK, ROS1, or RET rearrangements, or MET amplification was associated with a survival increment of 1.5 years compared with those with such mutations not receiving targeted therapy, and 1.0 year compared with those lacking a targetable driver. Importantly, 60 patients with a history of smoking derived similar survival benefit from targeted therapy for alterations in EGFR/ALK/ROS1, when compared with 75 never smokers with the same alterations. In addition, coexisting TP53 mutations were associated with shorter survival among patients with EGFR, ALK, or ROS1 alterations. Conclusion: Patients with adenocarcinoma of the lung and an oncogenic driver mutation treated with effective targeted therapy have a longer survival, regardless of prior smoking history. Molecular testing should be performed on all individuals with lung adenocarcinomas irrespective of clinical characteristics. Routine use of massively parallel sequencing enables detection of both targetable driver alterations and tumor suppressor gene and other alterations that have potential significance for therapy selection and as predictive markers for the efficacy of treatment. Clin Cancer Res; 24(5); 1038–47. ©2017 AACR.
Physiological Mitochondrial Fragmentation Is a Normal Cardiac Adaptation to Increased Energy Demand
Authors: Michael Coronado, Giovanni Fajardo, Kim Nguyen, Mingming Zhao, Kristina Kooiker, Gwanghyun Jung, Dong-Qing Hu, Sushma Reddy, Erik Sandoval, Aleksandr Stotland, Roberta A. Gottlieb, Daniel Bernstein
Journal: Circulation Research (2017)

Mitochondria play a dual role in the heart, responsible for meeting energetic demands and regulating cell death. Paradigms have held that mitochondrial fission and fragmentation are the result of pathological stresses, such as ischemia, are an indicator of poor mitochondrial health, and lead to mitophagy and cell death. However, recent studies demonstrate that inhibiting fission also results in decreased mitochondrial function and cardiac impairment, suggesting that fission is important for maintaining cardiac and mitochondrial bioenergetic homeostasis.
Etk Interaction with PFKFB4 Modulates Chemoresistance of Small-cell Lung Cancer by Regulating Autophagy
Authors: Qiongyao Wang, Fanrui Zeng, Yanqin Sun, Qianqian Qiu, Jian Zhang, Weimei Huang, Jie Huang, Xiaomin Huang, Linlang Guo
Journal: Clinical Cancer Research (2017)

Purpose: Epithelial and endothelial tyrosine kinase (Etk), also known as bone marrow X kinase (Bmx), was found to be critical in modulating the chemoresistance of small-cell lung cancer (SCLC) in our preliminary study. However, the molecular mechanisms of Etk in SCLC chemoresistance remain poorly understood.Experimental Design: We determined correlation of Etk with autophagy in SCLC. And direct inhibition of autophagy was performed to validate its effect on chemoresistance. Coimmunoprecipitation (co-IP) and GST-pull down experiments were conducted to verify the interaction of Etk and PFKFB4, after a microarray analysis. In vitro and in vivo gain or loss-of-function analyses and evaluation of PFKFB4 expression in SCLC specimens, were done to validate its role in chemoresistance. Ibrutinib was administrated in SCLC cells to verify its synergistic anti-tumor effect with chemotherapy using preclinical models including a PDX model.Results: Downregulation of Etk suppressed autophagy in chemoresistant SCLC cells, and direct inhibition of autophagy sensitized cells to chemotherapy. PFKFB4 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4) was identified as a downstream target of Etk and an Etk-interacting protein, which promoted chemoresistance in SCLC and was associated with poor therapeutic response and prognosis. Furthermore, ibrutinib was found to exhibit a synergistic anti-tumor effect with chemotherapy in targeting Etk.Conclusions: Our results demonstrated for the first time that Etk interacts with PFKFB4 to promote SCLC chemoresistance through regulation of autophagy. Aberrant Etk and PFKFB4 can be predictive factors for the chemotherapy response as well as potential therapeutic targets in SCLC. Clin Cancer Res; 24(4); 950-62. ©2017 AACR.
Erratum: Corrigendum: Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy
Authors: B Gerull, A Heuser, T Wichter, M Paul, C T Basson, D A McDermott, B B Lerman, S M Markowitz, P T Ellinor, C A MacRae, S Peters, K S Grossman, B Michely, S Sasse-Klaassen, M Birchmeier, R Dietz, G Breithardt, E Schulze-Bahr, L Thierfelder
Journal: Nature Genetics (2004)
Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin’s Lymphoma
Authors: Joseph M. Connors, Wojciech Jurczak, David J. Straus, Stephen M. Ansell, Won S. Kim, Andrea Gallamini, Anas Younes, Sergey Alekseev, Árpád Illés, Marco Picardi, Ewa Lech-Maranda, Yasuhiro Oki, Tatyana Feldman, Piotr Smolewski, Kerry J. Savage, Nancy L. Bartlett, Jan Walewski, Robert Chen, Radhakrishnan Ramchandren, Pier L. Zinzani, David Cunningham, Andras Rosta, Neil C. Josephson, Eric Song, Jessica Sachs, Rachael Liu, Hina A. Jolin, Dirk Huebner, John Radford
Journal: New England Journal of Medicine (2017)

Brentuximab vedotin is an anti-CD30 antibody-drug conjugate that has been approved for relapsed and refractory Hodgkin's lymphoma.We conducted an open-label, multicenter, randomized phase 3 trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma, in which 664 were assigned to receive brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) and 670 were assigned to receive doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). The primary end point was modified progression-free survival (the time to progression, death, or noncomplete response and use of subsequent anticancer therapy) as adjudicated by an independent review committee. The key secondary end point was overall survival.At a median follow-up of 24.6 months, 2-year modified progression-free survival rates in the A+AVD and ABVD groups were 82.1% (95% confidence interval [CI], 78.8 to 85.0) and 77.2% (95% CI, 73.7 to 80.4), respectively, a difference of 4.9 percentage points (hazard ratio for an event of progression, death, or modified progression, 0.77; 95% CI, 0.60 to 0.98; P=0.04). There were 28 deaths with A+AVD and 39 with ABVD (hazard ratio for interim overall survival, 0.73 [95% CI, 0.45 to 1.18]; P=0.20) [corrected]. All secondary efficacy end points trended in favor of A+AVD. Neutropenia occurred in 58% of the patients receiving A+AVD and in 45% of those receiving ABVD; in the A+AVD group, the rate of febrile neutropenia was lower among the 83 patients who received primary prophylaxis with granulocyte colony-stimulating factor than among those who did not (11% vs. 21%). Peripheral neuropathy occurred in 67% of patients in the A+AVD group and in 43% of patients in the ABVD group; 67% of patients in the A+AVD group who had peripheral neuropathy had resolution or improvement at the last follow-up visit. Pulmonary toxicity of grade 3 or higher was reported in less than 1% of patients receiving A+AVD and in 3% of those receiving ABVD. Among the deaths that occurred during treatment, 7 of 9 in the A+AVD group were associated with neutropenia and 11 of 13 in the ABVD group were associated with pulmonary-related toxicity.A+AVD had superior efficacy to ABVD in the treatment of patients with advanced-stage Hodgkin's lymphoma, with a 4.9 percentage-point lower combined risk of progression, death, or noncomplete response and use of subsequent anticancer therapy at 2 years. (Funded by Millennium Pharmaceuticals and Seattle Genetics; ECHELON-1 ClinicalTrials.gov number, NCT01712490 ; EudraCT number, 2011-005450-60 .).
ERS statement: interventional bronchoscopy in children
Authors: Ernst Eber, Juan L. Antón-Pacheco, Jacques de Blic, Iolo Doull, Al Faro, Raffaella Nenna, Thomas Nicolai, Petr Pohunek, Kostas N. Priftis, Paola Serio, Courtney Coleman, Sarah Masefield, Thomy Tonia, Fabio Midulla
Journal: European Respiratory Journal (2017)

Paediatric airway endoscopy is accepted as a diagnostic and therapeutic procedure, with an expanding number of indications and applications in children. The aim of this European Respiratory Society task force was to produce a statement on interventional bronchoscopy in children, describing the evidence available at present and current clinical practice, and identifying areas deserving further investigation. The multidisciplinary task force panel performed a systematic review of the literature, focusing on whole lung lavage, transbronchial and endobronchial biopsy, transbronchial needle aspiration with endobronchial ultrasound, foreign body extraction, balloon dilation and occlusion, laser-assisted procedures, usage of airway stents, microdebriders, cryotherapy, endoscopic intubation, application of drugs and other liquids, and caregiver perspectives. There is a scarcity of published evidence in this field, and in many cases the task force had to resort to the collective clinical experience of the committee to develop this statement. The highlighted gaps in knowledge underline the need for further research and serve as a call to paediatric bronchoscopists to work together in multicentre collaborations, for the benefit of children with airway disorders.
The Wait for High-Sensitivity Troponin Is Over—Proceed Cautiously
Authors: Frederick K. Korley
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Brief Report: Clinical Trials Aiming to Prevent Rheumatoid Arthritis Cannot Detect Prevention Without Adequate Risk Stratification: A Trial of Methotrexate Versus Placebo in Undifferentiated Arthritis as an Example
Authors: Leonie E. Burgers, Cornelia F. Allaart, Tom W. J. Huizinga, Annette H. M. van der Helm‐van Mil
Journal: Arthritis & Rheumatology (2017)

Prevention of rheumatoid arthritis (RA) was the aim of several trials in undifferentiated arthritis (UA), with overall negative results. As preparatory work has revealed that only ∼30% of UA patients progress to having RA, we hypothesized that inclusion of patients without imminent RA could lead to false-negative results. We undertook this study to evaluate this hypothesis by reinvestigating the Probable Rheumatoid Arthritis: Methotrexate versus Placebo Treatment (PROMPT) trial (a 1-year course of methotrexate [MTX] versus placebo in UA) after excluding patients without a high risk of developing RA.A validated prediction model was used to determine the risk of RA in all patients included in the PROMPT trial. Patients with a prediction score of ≥8 (positive predictive value of ≥84% for developing RA) were considered to have a high risk of developing RA. The effect of a 1-year course of MTX during 5 years of follow-up was reinvestigated in these patients.Twenty-two of the 110 patients in the PROMPT trial had a high risk of RA at baseline. In the MTX arm, 6 of 11 patients (55%) developed RA, compared to 11 of 11 patients (100%) in the placebo arm (P = 0.011). Time to RA development was longer in the MTX arm than in the placebo arm (median 22.5 months versus 3 months; P < 0.001). Drug-free remission was achieved by 4 of 11 patients (36%) in the MTX arm compared to 0 of 11 patients (0%) in the placebo arm (P = 0.031). These beneficial effects of MTX were observed both in anti-citrullinated protein antibody (ACPA)-positive and in ACPA-negative UA patients with a high risk of RA, but not in UA patients without a high risk of RA. In retrospect, 43 of 110 patients fulfilled the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria for RA at baseline. In addition, beneficial effects were observed only in patients with a high prediction score.A 1-year course of MTX delayed and prevented RA development in high-risk UA patients. This emphasizes the importance of adequate risk prediction in trials that aim to prevent RA.
Soft Tissue and Uterine Leiomyosarcoma
Authors: Suzanne George, César Serrano, Martee L. Hensley, Isabelle Ray-Coquard
Journal: Journal of Clinical Oncology (2017)

Leiomyosarcoma (LMS) is one of the most common subtypes of soft tissue sarcoma in adults and can occur in almost any part of the body. Uterine leiomyosarcoma is the most common subtype of uterine sarcoma. Increased awareness of this unique histology has allowed for the development of drugs that are specific to LMS and has begun to shed light on the similarities and possible unique aspects of soft tissue and uterine LMS. In this review, we summarize the current understanding of the epidemiology, diagnosis, genomics, and treatment options for LMS.
Abstract 20320: Late Gadolinium Enhancement at Interventricular Insertion Point Strongly Predicts Systolic and Diastolic Dysfunction of the Systemic Ventricle in Repaired Adult Patients With Complex Congenital Heart Disease
Authors: Yohsuke Hayama, Hideo Ohuchi, Jun Negishi, Kanae Noritake, Toru Iwasa, Aya Miyazaki, Etsuko Tsuda, Isao Shiraishi
Journal: Circulation (2016)

Background: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) at interventricular insertion points can often be detected in patients with hypertrophic cardiomyopathy. Some a...
Resposta às cartas : Surtos de parvovirus B19
Authors: G Gonçalves, A M Correia, P Palminha, Helena Rebelo-Andrade, A Alves
Journal: Eurosurveillance (2005)

We are grateful for the comments provided by Kelly and Leydon, and Bernard J Cohen. They seem to share our previously expressed opinion that ’in the context of measles and rubella elimination programs, study protocols should include data collection procedures and laboratory tests able to confirm or discard the diagnosis of B19 infections.’ [1]. They have provided a useful commentary with relevant information and references.
Video capsule endoscopy diagnosis of Takayasu’s arteritis
Authors: Carolina Olano, Henry Cohen
Journal: Endoscopy (2017)

An asymptomatic 62-year-old woman presented for a routine annual examination and was found to have elevated sedimentation rate and C-reactive protein. Physical examination was normal except for a difference in blood pressure between arms (120/74 on the right and 110/76 on the left). Computed tomography (CT) scan demonstrated an aortitis, and positron emission tomography–CT scan confirmed the presence of active inflammatory disease. She received prednisone 40 mg daily for 30 days, but discontinued the treatment because of multiple side effects.
Study links varicoceles to heart disease and diabetes
Authors: Jacqui Wise
Journal: BMJ (2017)

Men with varicoceles appear to be more likely to develop cardiovascular disease and diabetes than those without the condition, according to a study published in Andrology .1

Varicoceles occur in around 15% of men. The enlarged veins are thought to allow more blood to flow through the scrotum, raising the temperature above normal levels. This can lead to lower sperm and testosterone production. The condition is usually left untreated unless it causes pain or impairs reproductive function.

Researchers from Stanford School of Medicine examined a database containing the …