tbuckley/cabot-search huggingface dataset:
Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection
Authors: Robert Belknap, David Holland, Pei-Jean Feng, Joan-Pau Millet, Joan A. Caylà, Neil A. Martinson, Alicia Wright, Ruth N. Moro, Nigel A. Scott, Bert Arevalo, José M. Miró, Margarita E. Villarino, Marc Weiner, Andrey S. Borisov
Journal: Annals of Internal Medicine (2017)

Background: Expanding latent tuberculosis treatment is important to decrease active disease globally. Once-weekly isoniazid and rifapentine for 12 doses is effective but limited by requiring direct observation. Objective: To compare treatment completion and safety of once-weekly isoniazid and rifapentine by self-administration versus direct observation. Design: An open-label, phase 4 randomized clinical trial designed as a noninferiority study with a 15% margin. Seventy-five percent or more of study patients were enrolled from the United States for a prespecified subgroup analysis. (ClinicalTrials.gov: NCT01582711) Setting: Outpatient tuberculosis clinics in the United States, Spain, Hong Kong, and South Africa. Participants: 1002 adults (aged ≥18 years) recommended for treatment of latent tuberculosis infection. Intervention: Participants received once-weekly isoniazid and rifapentine by direct observation, self-administration with monthly monitoring, or self-administration with weekly text message reminders and monthly monitoring. Measurements: The primary outcome was treatment completion, defined as 11 or more doses within 16 weeks and measured using clinical documentation and pill counts for direct observation, and self-reports, pill counts, and medication event–monitoring devices for self-administration. The main secondary outcome was adverse events. Results: Median age was 36 years, 48% of participants were women, and 77% were enrolled at the U.S. sites. Treatment completion was 87.2% (95% CI, 83.1% to 90.5%) in the direct-observation group, 74.0% (CI, 68.9% to 78.6%) in the self-administration group, and 76.4% (CI, 71.3% to 80.8%) in the self-administration–with–reminders group. In the United States, treatment completion was 85.4% (CI, 80.4% to 89.4%), 77.9% (CI, 72.7% to 82.6%), and 76.7% (CI, 70.9% to 81.7%), respectively. Self-administered therapy without reminders was noninferior to direct observation in the United States; no other comparisons met noninferiority criteria. A few drug-related adverse events occurred and were similar across groups. Limitation: Persons with latent tuberculosis infection enrolled in South Africa would not routinely be treated programmatically. Conclusion: These results support using self-administered, once-weekly isoniazid and rifapentine to treat latent tuberculosis infection in the United States, and such treatment could be considered in similar settings when direct observation is not feasible. Primary Funding Source: Centers for Disease Control and Prevention.
Cardiovascular Safety During Treatment With Baricitinib in Rheumatoid Arthritis
Authors: Peter C. Taylor, Michael E. Weinblatt, Gerd R. Burmester, Terence P. Rooney, Sarah Witt, Chad D. Walls, Maher Issa, Claudia A. Salinas, Chadi Saifan, Xin Zhang, Anabela Cardoso, Miguel A. González‐Gay, Tsutomu Takeuchi
Journal: Arthritis & Rheumatology (2019)

To assess the frequency of cardiovascular and venous thromboembolic events in clinical studies of baricitinib, an oral, selective JAK1 and JAK2 inhibitor approved in more than 50 countries for the treatment of moderately-to-severely active rheumatoid arthritis (RA).Data were pooled from 9 RA studies. Placebo comparison up to 24 weeks included data from 6 studies. Randomized dose comparison between baricitinib doses of 2 mg and 4 mg used data from 4 studies and from the associated long-term extension study. The data analysis set designated "All-bari-RA" included all baricitinib exposures at any dose.Overall, 3,492 RA patients received baricitinib (7,860 patient-years of exposure). No imbalance compared to the placebo group was seen in the incidence of major adverse cardiovascular events (MACE) (incidence rates [IRs] of 0.5 per 100 patient-years for placebo and 0.8 per 100 patient-years for 4 mg baricitinib), arterial thrombotic events (ATE) (IRs of 0.5 per 100 patient-years for placebo and 0.5 per 100 patient-years for 4 mg baricitinib), or congestive heart failure (CHF) broad term (IRs of 4.3 per 100 patient-years for placebo and 2.4 per 100 patient-years for 4 mg baricitinib). Deep vein thrombosis (DVT)/pulmonary embolism (PE) were reported in 0 of 1,070 patients treated with placebo and 6 of 997 patients treated with 4 mg baricitinib during the placebo-controlled period; these events were serious in 2 of 6 patients, while all 6 had risk factors and 1 patient developed DVT/PE after discontinuation of the study drug. In the 2 mg-4 mg-extended data analysis set, IRs of DVT/PE were comparable between the doses across event types (IRs of 0.5 per 100 patient-years in those receiving 2 mg baricitinib and 0.6 per 100 patient-years in those receiving 4 mg baricitinib). In the All-bari-RA data analysis set, the rates were stable over time, with an IR of DVT/PE of 0.5 per 100 patient-years.In RA clinical trials, no association was found between baricitinib treatment and the incidence of MACE, ATE, or CHF. With regard to incidence of DVT/PE, 6 events occurred in patients treated with 4 mg baricitinib, but no cases of DVT/PE were reported in the placebo group. During longer-term evaluation, the incidence of DVT/PE was similar between the baricitinib dose groups, with consistent IR values over time, and this was similar to the rates previously reported in patients with RA.
Gasdermin D plays a key role as a pyroptosis executor of non-alcoholic steatohepatitis in humans and mice
Authors: Bing Xu, Mingzuo Jiang, Yi Chu, Weijie Wang, Di Chen, Xiaowei Li, Zhao Zhang, Di Zhang, Daiming Fan, Yongzhan Nie, Feng Shao, Kaichun Wu, Jie Liang
Journal: Journal of Hepatology (2017)
Does pregnancy change the effect of methQTL on DNA methylation and alter the risk of eczema?
Authors: Su Chen, Wilfried Karmaus, Rumana Siddique, Nandini Mukherjee, Vimala D. Janjanam, Hasan Arshad, Hongmei Zhang, John W. Holloway
Journal: Journal of Allergy and Clinical Immunology (2018)
Intention‐to‐treat survival benefit in liver transplantation: Comments on Lai et al.
Authors: Audrey Winter, J. P. Daures, Paul Landais
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. TO THE EDITOR: We read with interest the article of Lai et al.1 which introduced an intention‐to‐treat (ITT) survival benefit of liver transplantation (LT) in patients with hepatocellular cancer (HCC). The researchers developed two models: a pre‐LT model (non‐LT survival model) and a post‐LT model (ITT LT survival model). This split into two models is not innovative as is stated, ignoring Merion et al.2 and Schaubel et al.3 The researchers underlined the importance of the informative censorship in the pre‐LT model. However, they did not retain methods such as the inverse probability of censoring weighting method,4 which overcomes dependent censoring, even in waiting list (WL) patients.3 They split their WL candidates into two subgroups according to LT. In the LT subgroup, they estimated the survival using the MESIAH (Model to Estimate the Survival In Ambulatory patients with HCC) score.5 This score was developed on HCC patients followed from the time of HCC assessment, which is different from the wait‐listing time. Therefore, this score appears inappropriate to estimate survival in the WL condition. Even if it had been, a past external validation of the MESIAH score would have been expected. The researchers estimated the survival benefit as the difference between ITT LT median and the non‐LT median survival estimations for each patient. Did the researchers estimate a survival curve and then the survival median for each patient, defined by his or her covariates vector, giving patients with the same vector of covariates the same median? Given that the estimations were truncated at month 120, was the median observable in each subgroup of patients? Of note, in France, the median survival is not observed at 10 years (regardless of the diagnosis). The researchers did not comment on Schaubel et al.,3 which used the “true” value of life expectancy (area under the curve). Would this latter method lead to the same results? Can the researchers comment on why they chose the same set of covariates in the survival models for LT and non‐LT patients? It is unclear whether the researchers used candidates on the WL in the multivariate least square regression (MLSR); was it the case? The selection process of only four prediction covariates among nine retained in the MLSR is not clearly explained. It would have been useful to have a summary of the model with only the selected covariates in order to justify the chosen subgroups.
Frequency and type of <i>JAK3</i> variants in adult patients with leukemia.
Authors: Christopher Brent Benton, Rita Assi, Feng Wang, Sherry Pierce, Keyur Patel, Steven Mitchell Kornblau, Ahmed AlRawi, Jianhua Zhang, Betty Ky Hamilton, Koichi Takahashi, Courtney Denton Dinardo, Andrew Futreal, Guillermo Garcia-Manero, Tapan M. Kadia, Hagop M. Kantarjian, Michael Andreeff, Srdan Verstovsek
Journal: Journal of Clinical Oncology (2017)

e13117 Background: Janus kinases (JAK) family members ( JAK1, JAK2, JAK3, TYK2) are involved in tumorigenesis. JAK3 activating variants, including V722I, demonstrably induce cellular transformation in vitro. The prevalence of JAK3 variants/mutations in leukemia, particularly in AML, and their role in leukemogenesis, remains unclear Methods: We retrospectively reviewed leukemia patients (pts) treated at MD Anderson Cancer Center between 2012 and 2016, whose marrow samples were tested for JAK3 variants/mutations by next generation sequencing. We evaluated the type and prevalence of variants, the demographics, laboratory, treatment, and clinical information for JAK3 pts. Results: A total of 28 leukemia pts with JAK3 variants were identified, and included: MDS/MPN (n = 4), CLL (n = 2) and B-cell ALL (n = 1). All 7 non-AML pts had V722I variant (in the pseudokinase domain). Twenty-one AML pts were identified; this included 15 pts with V722I (1.5%) out of total 977 AML pts tested, demonstrating this variant was significantly more prevalent in AML pts than in the general population (1.5 vs 0.9%, P= 0.04). Three pts (0.3%) had P151R (FERM domain), and 1 pt each (0.1%) had V718L (pseudokinase), R925L (kinase), and L940V (kinase), none of which have been previously described. A pt with T815M (between pseudokinase-kinase domains) was identified from outside genetic testing. For AML pts, median allelic frequency for variants was 52% (range, 41-88) and median marrow blasts was 42% (range 21-97); 10% of AML patients had complex karyotype. Concomitant mutations were most commonly found in IDH1/2 (n = 10), TP53 (n = 8), FLT3 (n = 5), NPM1 (n = 5), ASXL1 (n = 5), RUNX1 (n = 4), DNMT3A (3), and TET2 (n = 3). Conclusions: We report the largest survey of JAK3 variants among adult leukemia pts, with detailed and novel variants described for AML. Given allelic frequencies, JAK3 variants may represent germline polymorphisms in most cases; however the activating V722I variant has increased prevalence among AML pts. The existence of an FDA-approved JAK3 inhibitor tofacitinib, and the prevalence and location of JAK3 variants provide a basis for additional investigations.
Association Between Diastolic Blood Pressure During Pediatric In-Hospital Cardiopulmonary Resuscitation and Survival
Authors: Robert A. Berg, Robert M. Sutton, Ron W. Reeder, John T. Berger, Christopher J. Newth, Joseph A. Carcillo, Patrick S. McQuillen, Kathleen L. Meert, Andrew R. Yates, Rick E. Harrison, Frank W. Moler, Murray M. Pollack, Todd C. Carpenter, David L. Wessel, Tammara L. Jenkins, Daniel A. Notterman, Richard Holubkov, Robert F. Tamburro, J. Michael Dean, Vinay M. Nadkarni, Athena F. Zuppa, Katherine Graham, Carolann Twelves, William Landis, Mary Ann DiLiberto, Elyse Tomanio, Jeni Kwok, Michael J. Bell, Alan Abraham, Anil Sapru, Mustafa F. Alkhouli, Sabrina Heidemann, Ann Pawluszka, Mark W. Hall, Lisa Steele, Thomas P. Shanley, Monica Weber, Heidi J. Dalton, Aimee La Bell, Peter M. Mourani, Kathryn Malone, Russell Telford, Whitney Coleman, Alecia Peterson, Julie Thelen, Allan Doctor
Journal: Circulation (2017)

On the basis of laboratory cardiopulmonary resuscitation (CPR) investigations and limited adult data demonstrating that survival depends on attaining adequate arterial diastolic blood pressure (DBP) during CPR, the American Heart Association recommends using blood pressure to guide pediatric CPR. However, evidence-based blood pressure targets during pediatric CPR remain an important knowledge gap for CPR guidelines.
Mg–Al and Zn–Al Layered Double Hydroxides Promote Dynamic Expression of Marker Genes in Osteogenic Differentiation by Modulating Mitogen‐Activated Protein Kinases
Authors: Ha Ram Kang, Célio Junior da Costa Fernandes, Rodrigo Augusto da Silva, Vera Regina Leopoldo Constantino, Ivan Hong Jun Koh, Willian F. Zambuzzi
Journal: Advanced Healthcare Materials (2017)

The effect of LDH samples comprised of chloride anions intercalated between positive layers of magnesium/aluminum (Mg-Al LDH) or zinc/aluminum (Zn-Al LDH) chemical composition on pre-osteoblast performance is investigated. Non-cytotoxic concentrations of both LDHs modulated pre-osteoblast adhesion by triggering cytoskeleton rearrangement dependent on recruiting of Cofilin, which is modulated by the inhibition of the Protein Phosphatase 2A (PP2A), culminating in osteoblast differentiation with a significant increase of osteogenic marker genes. The alkaline phosphatase (ALP) and bone sialoprotein (BSP) are significantly up-modulated by both LDHs; however, Mg-Al LDH nanomaterial promoted even more significance than both experimental controls, while the phosphorylations of mitogen-activated protein kinase (MAPKs)- extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinase (JNK) significantly increased. MAPK signaling is necessary to activate Runt-related transcription factor 2 (RUNX2) gene. Concomitantly, it is also investigated whether challenged osteoblasts are able to modulate osteoclastogenesis by investigating both osteoprotegerin (OPG) and Receptor activator of nuclear factor kappa-ligand (RANKL) in this model; a dynamic reprogramming of both these genes is found, suggesting LDHs in modulating osteoclastogenesis. These results suggest that LDHs interfere in bone remodeling, and they can be considered as nanomaterials in graft-based bone healing or drug-delivery materials for bone disorders.
Respiratory irritants in e-cigarette refill liquids across nine European countries: a threat to respiratory health?
Authors: Constantine Vardavas, Charis Girvalaki, Alexander Vardavas, Sophia Papadakis, Manolis Tzatzarakis, Panagiotis Behrakis, Aristidis Tsatsakis
Journal: European Respiratory Journal (2017)

The rapid expansion of the e-cigarette market across European countries has raised a number of concerns within the scientific community [1, 2]. The most recent data from across the European Union revealed a substantial increase in e-cigarette experimentation, with 15% of European citizens reporting having tried e-cigarettes in 2017, representing a 7.0% increase since 2012 [3]. Annual e-cigarette sales in Europe have reached EUR 1.33 billion, and are projected to reach over EUR 10 billion by 2020 [4]. Respiratory irritants within e-cigarette refill liquids are a cause for concern for respiratory health <http://ow.ly/454g30gK09m>
Tramadol Extended-Release and Opioid Withdrawal Management—Legal Implications—Reply
Authors: Kelly E. Dunn, D. Andrew Tompkins, Eric C. Strain
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Degradable rhenium trioxide nanocubes with high localized surface plasmon resonance absorbance like gold for photothermal theranostics
Authors: Wenlong Zhang, Guoying Deng, Bo Li, Xinxin Zhao, Tao Ji, Guosheng Song, Zhiyin Xiao, Qing Cao, Jingbo Xiao, Xiaojuan Huang, Guoqiang Guan, Rujia Zou, Xinwu Lu, Junqing Hu
Journal: Biomaterials (2017)
Abstract 20291: Preservation of Generated Cardiac Spiral Flow Structures is Valve-Type Dependent
Authors: Pablo S Huang Zhang, Colin D Tkatch, J Yasha Kresh
Journal: Circulation (2016)

Introduction: Non-invasive imaging modalities (e.g. 3D echo, 4D MRI) have demonstrated prevalence of spiral blood flow in the cardiovascular system. Fluid spirality imparts flow stability, minimize...
Y a-t-il un besoin et une place pour une production publique de vaccins à l'échelle européenne ?
Authors: D Lévy-Bruhl
Journal: Eurosurveillance (2006)

Dans ce numero d’Eurosurveillance, Pascale Rouaud et ses collegues decrivent une epidemie prolongee d’infections invasives a meningocoques B dans le departement de la Seine-Maritime, au nord de la France, liee a la dissemination locale d’une souche clonale de phenotype B:14:P1.7,16, appartenant au complexe clonal ST32/ET5.
Abstract 17105: Dietary Pattern and Long-term Survival: a Cohort Study of Patients in a Preventive Medicine Clinic
Authors: Nilay S Shah, David Leonard, Carrie E Finley, Fatima Rodriguez, Ashish Sarraju, Carolyn E Barlow, Laura DeFina, Benjamin L Willis, William L Haskell, David Maron
Journal: Circulation (2016)

Introduction:  Dietary pattern is related to mortality in selected populations with comorbidities. The association of certain dietary patterns with mortality remains unclear in healthy populations. We sought to determine whether recommended dietary patterns are associated with long-term survival in a young, healthy population.   Methods:  A volunteer sample of 11,503 men and women examined at The Cooper Clinic in Dallas, Texas, with no history of myocardial infarction or stroke, completed a baseline 3-day dietary record from 1987-1999 to assess adherence to the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets. Deaths from all causes and cardiovascular disease were evaluated over a mean follow-up of 18 years.   Results:  Mean age was 47 years at baseline. Individuals with the highest DASH diet scores had 32% lower adjusted risk for all-cause mortality compared to those with the lowest DASH diet scores (P   Conclusions:  The DASH dietary pattern was associated with significantly lower all-cause mortality over nearly two decades of follow-up in a young, generally healthy population. High saturated fat intake was associated with a higher risk of cardiovascular mortality. These results suggest that promotion of a healthy dietary pattern should begin early in life.
AMPKα2 Protects Against the Development of Heart Failure by Enhancing Mitophagy via PINK1 Phosphorylation
Authors: Bei Wang, Jiali Nie, Lujin Wu, Yangyang Hu, Zheng Wen, Lingli Dong, Ming-Hui Zou, Chen Chen, Dao Wen Wang
Journal: Circulation Research (2017)

Rationale: Mitochondrial dysfunction plays an important role in heart failure (HF). However, the molecular mechanisms regulating mitochondrial functions via selective mitochondrial autophagy (mitophagy) are poorly understood. Objective: We sought to determine the role of AMPK (AMP-activated protein kinase) in selective mitophagy during HF. Methods and Results: An isoform shift from AMPKα2 to AMPKα1 was observed in failing heart samples from HF patients and transverse aortic constriction–induced mice, accompanied by decreased mitophagy and mitochondrial function. The recombinant adeno-associated virus Serotype 9-mediated overexpression of AMPKα2 in mouse hearts prevented the development of transverse aortic constriction–induced chronic HF by increasing mitophagy and improving mitochondrial function. In contrast, AMPKα2 −/− mutant mice exhibited an exacerbation of the early progression of transverse aortic constriction–induced HF via decreases in cardiac mitophagy. In isolated adult mouse cardiomyocytes, AMPKα2 overexpression mechanistically rescued the impairment of mitophagy after phenylephrine stimulation for 24 hours. Genetic knockdown of AMPKα2, but not AMPKα1, by short interfering RNA suppressed the early phase (6 hours) of phenylephrine-induced compensatory increases in mitophagy. Furthermore, AMPKα2 specifically interacted with phosphorylated PINK1 (PTEN-induced putative kinase 1) at Ser495 after phenylephrine stimulation. Subsequently, phosphorylated PINK1 recruited the E3 ubiquitin ligase, Parkin, to depolarized mitochondria, and then enhanced the role of the PINK1–Parkin–SQSTM1 (sequestosome-1) pathway involved in cardiac mitophagy. This increase in cardiac mitophagy was accompanied by the elimination of damaged mitochondria, improvement in mitochondrial function, decrease in reactive oxygen species production, and apoptosis of cardiomyocytes. Finally, Ala mutation of PINK1 at Ser495 partially suppressed AMPKα2 overexpression-induced mitophagy and improvement of mitochondrial function in phenylephrine-stimulated cardiomyocytes, whereas Asp (phosphorylation mimic) mutation promoted mitophagy after phenylephrine stimulation. Conclusions: In failing hearts, the dominant AMPKα isoform switched from AMPKα2 to AMPKα1, which accelerated HF. The results show that phosphorylation of Ser495 in PINK1 by AMPKα2 was essential for efficient mitophagy to prevent the progression of HF.