tbuckley/cabot-search huggingface dataset:
Factors Associated With Suicide Ideation in US Army Soldiers During Deployment in Afghanistan
Authors: Robert J. Ursano, Holly B. Herberman Mash, Ronald C. Kessler, James A. Naifeh, Carol S. Fullerton, Pablo A. Aliaga, Cara M. Stokes, Gary H. Wynn, Tsz Hin Hinz Ng, Hieu M. Dinh, Oscar I. Gonzalez, Alan M. Zaslavsky, Nancy A. Sampson, Tzu-Cheg Kao, Steven G. Heeringa, Matthew K. Nock, Murray B. Stein
Journal: JAMA Network Open (2020)

Understanding suicide ideation (SI) during combat deployment can inform prevention and treatment during and after deployment.To examine associations of sociodemographic characteristics, lifetime and past-year stressors, and mental disorders with 30-day SI among a representative sample of US Army soldiers deployed in Afghanistan.In this survey study, soldiers deployed to Afghanistan completed self-administered questionnaires in July 2012. The sample was weighted to represent all 87 032 soldiers serving in Afghanistan. Prevalence of lifetime, past-year, and 30-day SI and mental disorders was determined. Logistic regression analyses examined risk factors associated with SI. Data analyses for this study were conducted between August 2018 and August 2019.Suicide ideation, lifetime and 12-month stressors, and mental disorders were assessed with questionnaires. Administrative records identified sociodemographic characteristics and suicide attempts.A total of 3957 soldiers (3473 [weighted 87.5%] male; 2135 [weighted 52.6%] aged ≤29 years) completed self-administered questionnaires during their deployment in Afghanistan. Lifetime, past-year, and 30-day SI prevalence estimates were 11.7%, 3.0%, and 1.9%, respectively. Among soldiers with SI, 44.2% had major depressive disorder (MDD) and 19.3% had posttraumatic stress disorder in the past 30-day period. A series of analyses of the 23 grouped variables potentially associated with SI resulted in a final model of sex; race/ethnicity; lifetime noncombat trauma; past 12-month relationship problems, legal problems, and death or illness of a friend or family member; and MDD. In this final multivariable model, white race/ethnicity (odds ratio [OR], 3.1 [95% CI, 1.8-5.1]), lifetime noncombat trauma (OR, 2.1 [95% CI, 1.1-4.0]), and MDD (past 30 days: OR, 31.8 [95% CI, 15.0-67.7]; before past 30 days: OR, 4.9 [95% CI, 2.5-9.6]) were associated with SI. Among the 85 soldiers with past 30-day SI, from survey administration through 12 months after returning from deployment, 6% (5 participants) had a documented suicide attempt vs 0.14% (6 participants) of the 3872 soldiers without SI.This study suggests that major depressive disorder and noncombat trauma are important factors in identifying SI risk during combat deployment.
Treatment for refractory pancreatic duct strictures should follow the guidelines
Authors: Yu Liu, Dan Wang, Zhao-Shen Li, Liang-Hao Hu
Journal: Endoscopy (2020)

See also: Long-term follow-up after multiple plastic stenting for refractory pancreatic duct strictures in chronic pancreatitisEndoscopy 2019; 51(10): 930-935DOI: 10.1055/a-0959-6163 See also: Reply to Liu et al.Endoscopy 2020; 52(02): 156-156DOI: 10.1055/a-1027-7015
Prolyl Hydroxylase Domain Inhibitor Protects against Metabolic Disorders and Associated Kidney Disease in Obese Type 2 Diabetic Mice
Authors: Mai Sugahara, Shinji Tanaka, Tetsuhiro Tanaka, Hisako Saito, Yu Ishimoto, Takeshi Wakashima, Masatoshi Ueda, Kenji Fukui, Akira Shimizu, Reiko Inagi, Toshimasa Yamauchi, Takashi Kadowaki, Masaomi Nangaku
Journal: Journal of the American Society of Nephrology (2020)

Prolyl hydroxylase domain (PHD) inhibitors, which stimulate erythropoietin production through the activation of hypoxia-inducible factor (HIF), are novel therapeutic agents used for treating renal anemia. Several PHD inhibitors, including enarodustat, are currently undergoing phase 2 or phase 3 clinical trials. Because HIF regulates a broad spectrum of genes, PHD inhibitors are expected to have other effects in addition to erythropoiesis, such as protection against metabolic disorders. However, whether such beneficial effects would extend to metabolic disorder-related kidney disease is largely unknown.We administered enarodustat or vehicle without enarodustat in feed to diabetic black and tan brachyury (BTBR) ob/ob mice from 4 to 22 weeks of age. To elucidate molecular changes induced by enarodustat, we performed transcriptome analysis of isolated glomeruli and in vitro experiments using murine mesangial cells.Compared with BTBR ob/ob mice that received only vehicle, BTBR ob/ob mice treated with enarodustat displayed lower body weight, reduced blood glucose levels with improved insulin sensitivity, lower total cholesterol levels, higher adiponectin levels, and less adipose tissue, as well as a tendency for lower macrophage infiltration. Enarodustat-treated mice also exhibited reduced albuminuria and amelioration of glomerular epithelial and endothelial damage. Transcriptome analysis of isolated glomeruli revealed reduced expression of C-C motif chemokine ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1) in enarodustat-treated mice compared with the vehicle-only group, accompanied by reduced glomerular macrophage infiltration. In vitro experiments demonstrated that both local HIF-1 activation and restoration of adiponectin by enarodustat contributed to CCL2/MCP-1 reduction in mesangial cells.These results indicate that the PHD inhibitor enarodustat has potential renoprotective effects in addition to its potential to protect against metabolic disorders.
MDA-MB-134乳癌細胞は線維芽細胞成長因子(FGF)受容体を過剰発現し,FGFリガンドでその増殖は抑制される | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Mcleskey S W, Ding I Y F, Lippman M E, Kern F G
Journal: Cancer Research (1994)
Apolipoprotein E and Alzheimer's Disease
Authors: Warren J. Strittmatter, Allen D. Roses
Journal: Annual Review of Neuroscience (1996)

The apolipoprotein E locus (APOE) is associated with variations in the age of onset and risk of Alzheimer's disease. The APOE4 allele increases the probability of disease at an earlier age. In contrasL the APOE3 and APOE2 alleles decrease the probability of disease and increase the age of onset. Therefore the metabolism of apolipoprotein E is relevant to Alzheimer's disease. Isoform-specific interactions of apolipoprotein E with other molecules may determine the rate of disease expression through molecular pathways that appear unique to the disease. In addition, some isoform-specific interactions of apolipoprotein E have been demonstrated with the defining pathological lesions of Alzheimer's disease, the neurofibrillary tangle and neuritic plaque. Several hypotheses of disease pathogenesis are now based on the relevance of apolipoprotein E.
International standards for the analysis of quality-of-life and patient-reported outcome endpoints in cancer randomised controlled trials: recommendations of the SISAQOL Consortium
Authors: Corneel Coens, Madeline Pe, Amylou C Dueck, Jeff Sloan, Ethan Basch, Melanie Calvert, Alicyn Campbell, Charles Cleeland, Kim Cocks, Laurence Collette, Nancy Devlin, Lien Dorme, Hans-Henning Flechtner, Carolyn Gotay, Ingolf Griebsch, Mogens Groenvold, Madeleine King, Paul G Kluetz, Michael Koller, Daniel C Malone, Francesca Martinelli, Sandra A Mitchell, Jammbe Z Musoro, Daniel O'Connor, Kathy Oliver, Elisabeth Piault-Louis, Martine Piccart, Chantal Quinten, Jaap C Reijneveld, Christoph Schürmann, Ashley Wilder Smith, Katherine M Soltys, Martin J B Taphoorn, Galina Velikova, Andrew Bottomley
Journal: The Lancet Oncology (2020)
Unilateral Facial Paralysis During an Airline Flight
Authors: Alan J. Hunter
Journal: Annals of Internal Medicine (2020)

Letters5 May 2020Unilateral Facial Paralysis During an Airline FlightAlan J. Hunter, MDAlan J. Hunter, MDOregon Health & Science University, Portland, Oregon (A.J.H.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0550 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: A medical emergency during a commercial airline flight may require an unplanned landing, which disrupts travel plans and is expensive.Objective: To alert clinicians to a condition that can mimic acute stroke but does not require an unplanned aircraft landing.Case Report: Shortly after reaching cruising altitude on a recent airline flight, I responded to a flight attendant's request for "a doctor on board." She reported that a passenger was probably having a stroke. When I met the passenger, I found him to be young and fit looking, with a complete right-sided facial droop. In addition to the facial ...References1. White R, Shackleton D. Plane palsy: a case of transient facial weakness during an aircraft flight. BMJ Case Rep. 2018;2018. [PMID: 29982181] doi:10.1136/bcr-2018-224593 CrossrefMedlineGoogle Scholar2. Ah-See KL, Shakeel M, Maini SK, et al. Facial paralysis during air travel: case series and literature review. J Laryngol Otol. 2012;126:1063-5. [PMID: 22831643] CrossrefMedlineGoogle Scholar3. Molvaer OI, Eidsvik S. Facial baroparesis: a review. Undersea Biomed Res. 1987;14:277-95. [PMID: 3307083] MedlineGoogle Scholar4. Ardehali MM, Yazdani N, Heidarali M. Transient facial nerve baroparesis: case report. Pak J Biol Sci. 2009;12:476-9. [PMID: 19579994] CrossrefMedlineGoogle Scholar5. Kung RW, Roche JP, Gantz BJ. Postoperative facial baroparesis while flying: a rare complication of decompressing a facial nerve schwannoma. JAMA Otolaryngol Head Neck Surg. 2018;144:457-459. [PMID: 29596587] doi:10.1001/jamaoto.2018.0048 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Oregon Health & Science University, Portland, Oregon (A.J.H.)Disclosures: Author has disclosed no conflicts of interest. Form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0550.This article was published at Annals.org on 28 January 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 5 May 2020Volume 172, Issue 9Page: 634-636KeywordsFacial nerveHeadachesNervesParalysisStrokeSwallowingTasteTrauma surgeryUpper respiratory tract infectionsVision ePublished: 28 January 2020 Issue Published: 5 May 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Impaired Death Receptor Signaling in Leukemia Causes Antigen-Independent Resistance by Inducing CAR T-cell Dysfunction
Authors: Nathan Singh, Yong Gu Lee, Olga Shestova, Pranali Ravikumar, Katharina E. Hayer, Seok Jae Hong, Xueqing Maggie Lu, Raymone Pajarillo, Sangya Agarwal, Shunichiro Kuramitsu, Elena J. Orlando, Karen Thudium Mueller, Charly R. Good, Shelley L. Berger, Ophir Shalem, Matthew D. Weitzman, Noelle V. Frey, Shannon L. Maude, Stephan A. Grupp, Carl H. June, Saar Gill, Marco Ruella
Journal: Cancer Discovery (2020)

Primary resistance to CD19-directed chimeric antigen receptor T-cell therapy (CART19) occurs in 10% to 20% of patients with acute lymphoblastic leukemia (ALL); however, the mechanisms of this resistance remain elusive. Using a genome-wide loss-of-function screen, we identified that impaired death receptor signaling in ALL led to rapidly progressive disease despite CART19 treatment. This was mediated by an inherent resistance to T-cell cytotoxicity that permitted antigen persistence and was subsequently magnified by the induction of CAR T-cell functional impairment. These findings were validated using samples from two CAR T-cell clinical trials in ALL, where we found that reduced expression of death receptor genes was associated with worse overall survival and reduced T-cell fitness. Our findings suggest that inherent dysregulation of death receptor signaling in ALL directly leads to CAR T-cell failure by impairing T-cell cytotoxicity and promoting progressive CAR T-cell dysfunction. SIGNIFICANCE: Resistance to CART19 is a significant barrier to efficacy in the treatment of B-cell malignancies. This work demonstrates that impaired death receptor signaling in tumor cells causes failed CART19 cytotoxicity and drives CART19 dysfunction, identifying a novel mechanism of antigen-independent resistance to CAR therapy.See related commentary by Green and Neelapu, p. 492.
Physical activity: a (mobile) call to action
Authors: Erno Harzheim, Lívia de Almeida Faller, Otávio Pereira D’Avila, Lucas Matturro, Lucas Pedebôs
Journal: BMJ (2020)

The need to take “urgent action to improve low levels of physical activity”1 seems true for most countries. Despite the health and economic burden of inactivity23 and the benefits of even light activity,4 policies—in high, middle, and low income countries—have not succeeded in making people move.5

In Brazil, where physical activity could prevent 15% of deaths …
Linking risk factors and outcomes in autism spectrum disorder: is there evidence for resilience?
Authors: Mayada Elsabbagh
Journal: BMJ (2020)

Abstract Autism spectrum disorder (referred to here as autism) is one of several overlapping neurodevelopmental conditions that have variable impacts on different individuals. This variability results from dynamic interactions between biological and non-biological risk factors, which result in increasing differentiation between individuals over time. Although this differentiation continues well into adulthood, the infancy period is when the brain and behavior develop rapidly, and when the first signs and symptoms of autism emerge. This review discusses advances in our understanding of the causal pathways leading to autism and overlapping neurodevelopmental conditions. Research is also mapping trajectories of brain and behavioral development for some risk groups, namely later born siblings of children with autism and/or infants referred because of developmental concerns. This knowledge has been useful in improving early identification and establishing the feasibility of targeted interventions for infant risk groups before symptoms arise. However, key knowledge gaps remain, such as the discovery of protective factors (biological or environmental) that may mitigate the impact of risk. Also, the dynamic mechanisms that underlie the associations between risk factors and outcomes need further research. These include the processes of resilience, which may explain why some individuals at risk for autism achieve better than expected outcomes. Bridging these knowledge gaps would help to provide tools for early identification and intervention that reflect dynamic developmental pathways from risk to outcomes.
Alzheimer Disease, Biomarkers, and Clinical Symptoms—Quo Vadis?—Reply
Authors: Clifford R. Jack
Journal: JAMA Neurology (2020)

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 Neurology 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 Neurology journal
High efficacy of venetoclax plus obinutuzumab in patients with complex karyotype and chronic lymphocytic leukemia
Authors: Othman Al-Sawaf, Esther Lilienweiss, Jasmin Bahlo, Sandra Robrecht, Anna-Maria Fink, Michaela Patz, Maneesh Tandon, Yanwen Jiang, William Schary, Matthias Ritgen, Eugen Tausch, Stephan Stilgenbauer, Barbara Eichhorst, Kirsten Fischer, Michael Hallek, Karl-Anton Kreuzer
Journal: Blood (2020)
Semaphorin 7A: A novel marker of disease activity in Gaucher disease
Authors: Mélanie Franco, Nelly Reihani, Lucie Dupuis, Emmanuel Collec, Thierry Billette de Villemeur, Marine de Person, Fathi Moussa, Marc G. Berger, Nadia Belmatoug, Caroline Le Van Kim
Journal: American Journal of Hematology (2020)

Gaucher disease (GD) is a recessively inherited lysosomal storage disorder in which sphingolipids accumulates in the macrophages that transform into Gaucher cells. A growing body of evidence indicates that red blood cells (RBCs) represent important actors in GD pathophysiology. We previously demonstrated that altered RBC properties including increased Lyso-GL1 levels, dyserythropoiesis, and iron metabolism defect in GD patients contribute to anemia and hyperferritinemia. Since RBC defects also correlated well with markers of GD severity and were normalized under enzyme replacement therapy (ERT), the identification of molecules that are deregulated in GD RBCs represents an important issue in the search of pertinent markers of the disease. Here, we found a decreased expression of the GPI-anchored cell surface protein Semaphorin 7A (Sema7A) in RBCs from untreated GD (GD UT) patients, in parallel with increased levels of the soluble form in the plasma. Sema7A plays a role in neural guidance, atherosclerosis, and inflammatory diseases and represents a promigratory cue in physiological and pathological conditions. We showed that the decreased expression of Sema7A in RBCs correlated with their abnormal properties and with markers of GD activity. Interestingly, ERT restored the level of Sema7A to normal values both in RBCs and in plasma from GD patients. We then proposed that SemaA7A represents a simple and pertinent marker of inflammation in GD. Finally, because Sema7A is known to regulate the activity of immune cells, the increased level of soluble Sema7A in GD patients could propagate inflammation in several tissues.
Effectiveness of Intrapleural Tissue Plasminogen Activator and Dornase Alfa vs Tissue Plasminogen Activator Alone in Children with Pleural Empyema
Authors: Michael H. Livingston, Sanjay Mahant, Bairbre Connolly, Ian MacLusky, Sophie Laberge, Lucia Giglia, Connie Yang, Ashley Roberts, Anna Shawyer, Mary Brindle, Simon Parsons, Cristina Stoian, J. Mark Walton, Kevin E. Thorpe, Yang Chen, Fei Zuo, Muhammad Mamdani, Carol Chan, Desmond Loong, Wanrudee Isaranuwatchai, Felix Ratjen, Eyal Cohen
Journal: JAMA Pediatrics (2020)

Clinical guidelines recommend that children with pleural empyema be treated with chest tube insertion and intrapleural fibrinolytics. The addition of dornase alfa (DNase) has been reported to improve outcomes in adults but remains unproven in children.To determine if intrapleural tissue plasminogen activator (tPA) and DNase is more effective than tPA and placebo at reducing hospital length of stay in children with pleural empyema.This multicenter, parallel-group, placebo-controlled, superiority randomized clinical trial included children diagnosed as having pleural empyema requiring drainage aged 6 months to 18 years treated at 6 tertiary Canadian children's hospitals. A total of 379 children were assessed for eligibility; 281 were excluded and 98 were randomized. One child was excluded after randomization for not meeting the inclusion criteria. Data were collected from March 4, 2013, to December 13, 2017.Participants underwent chest tube insertion and 3 daily administrations of intrapleural tPA, 4 mg, followed by DNase, 5 mg (intervention group), or 5 mL of normal saline (placebo; control group). Participants, families, clinical staff, and members of the study team were blinded to allocation.The primary outcome was hospital length of stay from chest tube insertion to discharge. Secondary outcomes included time to meeting discharge criteria, time to chest tube removal, mean fever duration, additional pleural drainage procedures, hospital readmissions, and total health care cost.Of the 97 analyzed children with pleural empyema, 52 (54%) were male, and the mean (SD) age was 5.1 (3.6) years. A total of 49 children were randomized to tPA and DNase and 48 were randomized to tPA and placebo. Treatment with tPA and DNase was not associated with decreased hospital length of stay compared with tPA and placebo (mean [SD] length of stay, 9.0 [4.9] vs 9.1 [5.3] days; mean difference, -0.1 days; 95% CI, -2.0 to 2.1; P = .96). Similarly, no significant differences were observed for any of the secondary outcomes. Of the 14 adverse events in the tPA and DNase group, 6 (43%) were serious; of the 21 adverse events in the tPA and placebo group, 8 (38%) were serious. There were no deaths.The addition of DNase to intrapleural tPA for children with pleural empyema had no effect on hospital length of stay or other outcomes compared with tPA with placebo. Clinical practice guidelines should continue to support the use of chest tube insertion and intrapleural fibrinolytics alone as first-line treatment for pediatric empyema.ClinicalTrials.gov identifier: NCT01717742.
Real-world clinical outcomes of pazopanib immediately following immunotherapy discontinuation for the treatment of advanced renal cell carcinoma.
Authors: Xiting Cao, Derek Tang, Barbara Elizabeth Ratto, Austin Poole, Shoba Ravichandran, Lixian Jin, Wei Gao, Elyse Swallow, Nicholas J. Vogelzang
Journal: Journal of Clinical Oncology (2019)

573 Background: In the first-line setting (1L), pazopanib (PAZ) is recommended by NCCN for treatment of advanced renal cell carcinoma (aRCC). In 2018, immuno-oncology (IO) therapy became commonly used 1L treatment option for aRCC. This study reports real-world clinical outcomes of PAZ following IO therapy among aRCC patients (pts) in an evolving treatment landscape. Methods: This retrospective chart review study used medical record data collected by medical oncologists. Included pts were those ≥ 18 at initiation of IO therapy who initiated 2L+ PAZ for clear cell aRCC before November 2017, and had complete medical records from the diagnosis of aRCC to discontinuation of PAZ, death, or the chart extraction date (May 2018), whichever occurred first. Primary outcome was PAZ duration of therapy (DOT). Secondary outcomes were progression-free survival (PFS) and overall survival (OS) since PAZ initiation, reasons for PAZ discontinuation, and adverse events (AEs). Time-to-event outcomes were analyzed by Kaplan-Meier method. Results: 258 eligible pts initiated the IO therapies before PAZ as follows: nivolumab (NIVO) (68%), NIVO+ipilimumab (IPI) (14%), pembrolizumab (12%), and IPI (3%). Ninety-seven (38%), 56 (22%), and 92 (36%) pts were grouped as favorable, intermediate, or poor risk by Heng criteria, respectively. Overall, the median PAZ DOT was 13.4 months (Ms) (95% confidence interval [CI] 10.1-16.0). When stratified by lines of therapy, pts who received PAZ as 2L (n=182) or 3L+ (n=76) had DOT of 13.4 Ms (95% CI 11.1-NR) and 9.6 Ms (95% CI 6.2-NR), respectively. The PFS and OS outcomes are shown in the Table. One hundred-nine (42%) pts reported an AE. The most frequently (&gt;10%) reported AEs were fatigue (29%), diarrhea (14%), decreased appetite (14%), and hypertension (13%). Conclusions: In this real-world study, 2+L PAZ following prior IO therapy was well-tolerated, effective, and non-cross-resistant with IO therapy for aRCC pts. [Table: see text]