tbuckley/cabot-search huggingface dataset:
Long-Term Outcomes of the ADRENAL Trial
Authors: Balasubramanian Venkatesh, Simon Finfer, John Myburgh, Jeremy Cohen, Laurent Billot
Journal: New England Journal of Medicine (2018)

Hydrocortisone or Placebo in Septic Shock In the ADRENAL trial, among adult patients with septic shock, hydrocortisone did not lead to lower mortality than placebo. Now, a prespecified secondary analysis shows that hydrocortisone did not affect mortality 6 months after randomization.
Longitudinal evaluation of clustering of chronic sinonasal and related symptoms using exploratory factor analysis
Authors: M. Cole, K. Bandeen‐Roche, A. G. Hirsch, J. R. Kuiper, A. S. Sundaresan, B. K. Tan, R. P. Schleimer, R. C. Kern, B. S. Schwartz
Journal: Allergy (2018)

Abstract Background Sinonasal symptoms are common and can have several underlying causes. When symptoms occur in specified patterns lasting 3 months or more they meet criteria for chronic rhinosinusitis ( CRS ). Approaches to CRS symptom measurement do not specify how to measure symptoms and treat specified sinonasal symptoms as generally interchangeable, suggesting that such symptoms should cluster on 1 or 2 latent factors. Methods We used questionnaire responses to 37 questions on the presence, severity, bother, and frequency of cardinal sinonasal and related symptoms lasting 3 months, from 3535 subjects at 3 time points over 16 months. We completed 5 exploratory factor analyses ( EFA ) to identify symptom clustering, 1 for each time point and 2 for the differences between adjacent questionnaires. The baseline EFA was used to provide factor scores that were described longitudinally and examined by CRS status. Results Five EFA s identified the same 5 factors (blockage and discharge, pain and pressure, asthma and cold/flu symptoms, smell loss, and ear and eye [mainly allergy] symptoms), with clustering determined by symptom frequency, severity, and degree of bother. Responses to individual questions showed changes over time but when combined into factor scores showed less longitudinal change. All symptom factor scores were progressively higher from never to past to current CRS status. Conclusions Although the current approaches to symptom characterization in CRS imply a single underlying latent construct, our results suggest that there are at least 3 latent constructs relevant to CRS . Further studies are needed to evaluate whether these clusters have identifiable underlying pathobiologies.
TCTAP A-151 Predictors for In-stent Restenosis at Chronic Total Occlusive Lesions
Authors: Kyusup Lee, Sangwoo Park, Tae-Oh Kim, Sun Hack Lee, Yong-Hoon Yoon, Sang Yong Om, Minsoo Kim, Hanbit Park, Sang-Cheol Cho, Osung Kwon, Pil Hyung Lee, Jung-Min Ahn, Soo-Jin Kang, Duk-Woo Park, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2018)
Phase I/II trial of primary chemotherapy with nonpegylated liposomal doxorubicin, paclitaxel, and lapatinib in patients with HER2-positive, early-stage breast cancer.
Authors: Sherko Kuemmel, Bahriye Aktas, Jutta Krocker, Dirk Elling, Tilmann Lantzsch, Joachim Bischoff, Nikos Fersis, Michael Boehme, Antje Belau, Dieter Lampe, Peter Schmid
Journal: Journal of Clinical Oncology (2012)

624 Background: Combinations of trastuzumab and anthracyclines in HER2-positive breast cancer are highly active but associated with a high incidence of cardiotoxicity. The risk of cardiac damage can be significantly reduced through liposomal encapsulation of anthracyclines. This phase I/II study was initiated to evaluate the combination of non-pegylated liposomal doxorubicin (NPLD), paclitaxel and lapatinib as primary treatment for patients with early stage, HER2-positive primary breast cancer. Methods: Patients with newly diagnosed HER2-positive (IHC 3+ or FISH+) early stage (T1c N1-2 or T2 N0-2) breast cancer were treated with NPLD (60mg/m 2 ; day 1), paclitaxel (175mg/m 2 , day 1) and lapatinib (750-1500 mg orally daily) in 3-week intervals for up to 6 cycles. The primary endpoints were dose-limiting toxicities (DLT) and pathological complete response (pCR). Secondary endpoints include safety, incidence of cardiac events, and clinical response. Exploratory endpoints include molecular markers for sensitivity or resistance to chemotherapy and/or lapatinib evaluated. Results: A total of 84 patients have been included to date.No DLTs were observed and the maximum tolerated doses were NPLD 60mg/m 2 , paclitaxel 175mg/m 2 and lapatinib 1500mg. Recommended phase 2 doses (P2D) were NPLD 60mg/m 2 , paclitaxel 175mg/m 2 and lapatinib 1250mg. The treatment was generally well tolerated and associated with toxicities that were consistent with the known side-effects of the individual agents. No cardiac event has been observed to date. Preliminary efficacy data confirm a pCR breast rate of 41.7% and pCR rate in breast and lymph nodes of 37.5%, in 24 evaluable patients treated at ≥P2D. Conclusions: The combination of NPLD, paclitaxel and lapatinib is well tolerated and has high antitumour activity in patients with HER2-positive primary breast cancer. The phase II part of the study is ongoing and updated results will be presented.
FRI0066 Leflunomide inhibits proliferation and differentiation of pro-inflammatory th1 cells
Authors: P Dimitrova, A Skapenko, R Schleyerbach, M Herrmann, JR Kalden, H Schulze-Koops
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Leflunomide has been recently introduced as a new treatment for rheumatoid arthritis. It has been shown that this immunomodulatory drug blocks the <i>de novo</i> pyrimidine synthesis by inhibiting the enzyme dihydroorotate dehydrogenase. However, the functional consequences of this action for T cells are still unclear. <h3>Objectives</h3> To evaluate the effect of leflunomide on the proliferation and differentiation of human naive CD4<sup>pos</sup> T cells isolated from cord blood and of memory CD4<sup>pos</sup> T cells isolated from peripheral blood of healthy individuals. <h3>Methods</h3> The proliferative response of naive and memory T cells activated with anti-CD3 and anti-CD28 was determined by incorporation of <sup>3</sup>H-thymidine into newly synthesised DNA. The impact of leflunomide on T cell differentiation was assessed in an <i>in vitro</i> system in which effector cells were generated after short term priming. T cell differentiation was induced by priming with anti-CD3 and anti-CD28 in the presence or absence of leflunomide. The phenotype of freshly isolated and primed T cells was determined by cytometric analysis of intracellular cytokines. <h3>Results</h3> Leflunomide inhibited T cell proliferation induced by stimulation with anti-CD3 and anti-CD28 in a dose-dependent manner in naive and memory CD4<sup>pos</sup> T cells. Moreover, the expression of the activation markers CD25, CD69 and CD40L was markedly suppressed. Leflunomide significantly decreased the frequencies of T cells capable of producing IFN-γ. Most interestingly, the generation of Th2 effectors was enhanced by leflunomide in some donors. <h3>Conclusion</h3> Leflunomide may exert its anti-inflammatory effect by preventing the proliferation of pro-inflammatory Th1 effectors and by switching the T cell differentiation from the Th1 to the Th2 direction.
Suggestions for Improving Conflict of Interest Processes in the US Food and Drug Administration Advisory Committees—Past Imperfect
Authors: Peter Lurie
Journal: JAMA Internal Medicine (2018)

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
Patient-Reported Symptoms and Impact of Treatment With Osimertinib Versus Chemotherapy in Advanced Non–Small-Cell Lung Cancer: The AURA3 Trial
Authors: Chee Khoon Lee, Silvia Novello, Anna Rydén, Helen Mann, Tony Mok
Journal: Journal of Clinical Oncology (2018)

Purpose Capturing patient-reported outcome data is important for evaluating the overall clinical benefits of new cancer therapeutics. We assessed self-reported symptoms of advanced non-small-cell lung cancer in patients treated with osimertinib or chemotherapy in the AURA3 phase III trial. Patients and Methods Patients completed the European Organisation for Research and Treatment of Cancer 13-item Quality of Life Questionnaire-Lung Cancer Module (EORTC QLQ-LC13) questionnaire on disease-specific symptoms and the EORTC 30-item Core Quality of Life Questionnaire (EORTC QLC-C30) on general cancer symptoms, functioning, global health status/quality of life. We assessed differences between treatments in time to deterioration of individual symptoms and odds of improvement (a deterioration or improvement was defined as a change in score from baseline of ≥ 10). Hazard ratios (HRs) were calculated using a log-rank test stratified by ethnicity; odds ratios (ORs) were assessed using logistic regression adjusted for ethnicity. Results At baseline, the questionnaires were completed by 82% to 88% of patients, and 30% to 70% had individual key symptoms. Time to deterioration was longer with osimertinib than with chemotherapy for cough (HR, 0.74; 95% CI, 0.53 to 1.05), chest pain (HR, 0.52; 95% CI, 0.37 to 0.73), and dyspnea (HR, 0.42; 95% CI, 0.31 to 0.58). The proportion of symptomatic patients with improvement in global health status/quality of life was higher with osimertinib (80 [37%] of 215) than with chemotherapy (23 [22%] of 105; OR, 2.11; 95% CI, 1.24 to 3.67; P = .007). Proportions were also higher for appetite loss (OR, 2.50; 95% CI, 1.31 to 4.84) and fatigue (OR, 1.96; 95% CI, 1.20 to 3.22). Conclusion Time to deterioration of key symptoms was longer with osimertinib than with chemotherapy, and a higher proportion of patients had improvement in global health status/quality of life, demonstrating improved patient outcomes with osimertinib.
Association of Mild Traumatic Brain Injury With and Without Loss of Consciousness With Dementia in US Military Veterans
Authors: Deborah E. Barnes, Amy L. Byers, Raquel C. Gardner, Karen H. Seal, W. John Boscardin, Kristine Yaffe
Journal: JAMA Neurology (2018)

Traumatic brain injury (TBI) is common in both veteran and civilian populations. Prior studies have linked moderate and severe TBI with increased dementia risk, but the association between dementia and mild TBI, particularly mild TBI without loss of consciousness (LOC), remains unclear.To examine the association between TBI severity, LOC, and dementia diagnosis in veterans.This cohort study of all patients diagnosed with a TBI in the Veterans Health Administration health care system from October 1, 2001, to September 30, 2014, and a propensity-matched comparison group. Patients with dementia at baseline were excluded. Researchers identified TBIs through the Comprehensive TBI Evaluation database, which is restricted to Iraq and Afghanistan veterans, and the National Patient Care Database, which includes veterans of all eras. The severity of each TBI was based on the most severe injury recorded and classified as mild without LOC, mild with LOC, mild with LOC status unknown, or moderate or severe using Department of Defense or Defense and Veterans Brain Injury Center criteria. International Classification of Diseases, Ninth Revision codes were used to identify dementia diagnoses during follow-up and medical and psychiatric comorbidities in the 2 years prior to the index date.Dementia diagnosis in veterans who had experienced TBI with or without LOC and control participants without TBI exposure.The study included 178 779 patients diagnosed with a TBI in the Veterans Health Administration health care system and 178 779 patients in a propensity-matched comparison group. Veterans had a mean (SD) age of nearly 49.5 (18.2) years at baseline; 33 250 (9.3%) were women, and 259 136 (72.5%) were non-Hispanic white individuals. Differences between veterans with and without TBI were small. A total of 4698 veterans (2.6%) without TBI developed dementia compared with 10 835 (6.1%) of those with TBI. After adjustment for demographics and medical and psychiatric comobidities, adjusted hazard ratios for dementia were 2.36 (95% CI, 2.10-2.66) for mild TBI without LOC, 2.51 (95% CI, 2.29-2.76) for mild TBI with LOC, 3.19 (95% CI, 3.05-3.33) for mild TBI with LOC status unknown, and 3.77 (95% CI, 3.63-3.91) for moderate to severe TBI.In this cohort study of more than 350 000 veterans, even mild TBI without LOC was associated with more than a 2-fold increase in the risk of dementia diagnosis. Studies of strategies to determine mechanisms, prevention, and treatment of TBI-related dementia in veterans are urgently needed.
Adjunctive Intranasal Esketamine in Treatment-Resistant Depression—Reply
Authors: Ella J. Daly, Jaskaran B. Singh
Journal: JAMA Psychiatry (2018)

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
PHF5A Epigenetically Inhibits Apoptosis to Promote Breast Cancer Progression
Authors: Yi-Zi Zheng, Meng-Zhu Xue, Hong-Jie Shen, Xiao-Guang Li, Ding Ma, Yue Gong, Yi-Rong Liu, Feng Qiao, Hong-Yan Xie, Bi Lian, Wei-Li Sun, Hai-Yun Zhao, Ling Yao, Wen-Jia Zuo, Da-Qiang Li, Peng Wang, Xin Hu, Zhi-Ming Shao
Journal: Cancer Research (2018)

Abstract Alternative splicing (AS) and its regulation play critical roles in cancer, yet the dysregulation of AS and its molecular bases in breast cancer development have not yet been elucidated. Using an in vivo CRISPR screen targeting RNA-binding proteins, we identified PHD finger protein 5A (PHF5A) as a key splicing factor involved in tumor progression. PHF5A expression was frequently upregulated in breast cancer and correlated with poor survival, and knockdown of PHF5A significantly suppressed cell proliferation, migration, and tumor formation. PHF5A was required for SF3b spliceosome stability and linked the complex to histones, and the PHF5A–SF3b complex modulated AS changes in apoptotic signaling. In addition, expression of a short truncated FAS-activated serine/threonine kinase (FASTK) protein was increased after PHF5A ablation and facilitated Fas-mediated apoptosis. This PHF5A-modulated FASTK–AS axis was widely present in breast cancer specimens, particularly those of the triple-negative subtype. Taken together, our findings reveal that PHF5A serves as an epigenetic suppressor of apoptosis and thus provides a mechanistic basis for breast cancer progression and may be a valuable therapeutic target. Significance: This study provides an epigenetic mechanistic basis for the aggressive biology of breast cancer and identifies a translatable therapeutic target. Cancer Res; 78(12); 3190–206. ©2018 AACR.
Clinical and genetic predictors of HCC occuring in caucasian compensated HBV cirrhotics treated by Entecavir or Tenofovir for 8 years
Authors: A. Loglio, E. Galmozzi, M. Iavarone, G. Grossi, M. Viganò, F. Facchetti, M.G. Rumi, A. Sangiovanni, P. Lampertico
Journal: Journal of Hepatology (2018)
Modulation of allergic responses by mitochondrial STAT3 inhibitors
Authors: T. H. Erlich, I. Sharkia, N. Landolina, M. Assayag, O. Goldberger, N. Berkman, F. Levi‐Schaffer, E. Razin
Journal: Allergy (2018)

Abstract Background Recently, we have shown that mast cell mitochondrial STAT 3 could serve as a new target for the regulation of the allergic response as it plays an essential role in immunologically mediated degranulation of mast cells. In the present work, we explored how two recently developed mitochondrial STAT 3 inhibitors (Mitocur‐1 and Mitocur‐3) modulate the allergic response. Methods Experiments were performed both in vitro in cultured human/mouse mast cells and with rat basophilic leukemia ( RBL ) cells and also in vivo in mice. The effect of mitochondrial STAT 3 inhibition on mast cell function was determined via checking degranulation and several cytokines secretion levels. Results Here, we show that treatment of rodent and human cultured mast cells with low concentrations of mitochondrial STAT 3 inhibitors had no effect on STAT 3 target gene expression. However, these inhibitors caused a significant reduction in mast cell exocytosis and cytokine release, due to a decrease in OXPHOS activity and STAT 3 serine 727 phosphorylation. It was also observed in an OVA mouse model of allergic asthma that one of the inhibitors used significantly reduced eosinophilia and neutrophilia compared to the control mice group. Furthermore, it was observed that treatment with this inhibitor resulted in a significant reduction in blood histamine levels in mice after IgE‐Ag challenge. Conclusion The present data strongly suggest that the development of mitochondrial STAT 3 inhibitors could serve as a potential treatment for allergy‐associated diseases.
Abstract 18037: Cardiac Myosin Binding Protein-C Phosphorylation Decreases the Super-Relaxed State of Myosin
Authors: James W McNamara, Mohit Kumar, Roger Cooke, Sakthivel Sadayappan
Journal: Circulation (2016)

Introduction: Cardiac myosin exists in three populations: the active, the disordered relaxed (DRX) and the super-relaxed (SRX) states. The latter represents an economical reserve that is not immedi...
Endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic lesions: striving for perfection
Authors: John Karstensen, Peter Vilmann
Journal: Endoscopy (2018)

See also: Stylet slow-pull versus standard suction for endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic lesions: a multicenter randomized trialEndoscopy 2018; 50(05): 497-504DOI: 10.1055/s-0043-122381
BALDR: a computational pipeline for paired heavy and light chain immunoglobulin reconstruction in single-cell RNA-seq data
Authors: Amit A. Upadhyay, Robert C. Kauffman, Amber N. Wolabaugh, Alice Cho, Nirav B. Patel, Samantha M. Reiss, Colin Havenar-Daughton, Reem A. Dawoud, Gregory K. Tharp, Iñaki Sanz, Bali Pulendran, Shane Crotty, F. Eun-Hyung Lee, Jens Wrammert, Steven E. Bosinger
Journal: Genome Medicine (2018)

B cells play a critical role in the immune response by producing antibodies, which display remarkable diversity. Here we describe a bioinformatic pipeline, BALDR (BCR Assignment of Lineage using De novo Reconstruction) that accurately reconstructs the paired heavy and light chain immunoglobulin gene sequences from Illumina single-cell RNA-seq data. BALDR was accurate for clonotype identification in human and rhesus macaque influenza vaccine and simian immunodeficiency virus vaccine induced vaccine-induced plasmablasts and naïve and antigen-specific memory B cells. BALDR enables matching of clonotype identity with single-cell transcriptional information in B cell lineages and will have broad application in the fields of vaccines, human immunodeficiency virus broadly neutralizing antibody development, and cancer. BALDR is available at https://github.com/BosingerLab/BALDR .
Peliosis Hepatis Simulating Metastatic Liver Disease on FDG PET/CT
Authors: Daniel Levin, Nir Hod, Reut Anconina, Dina Ezroh Kazap, Ruthy Shaco-Levy, Sophie Lantsberg
Journal: Clinical Nuclear Medicine (2018)

Abstract A 20-year-old man with gastrointestinal symptoms and weight loss underwent FDG PET/CT, which revealed multiple hypermetabolic hepatic lesions concerning for metastatic liver disease. The outcome of liver biopsy was consistent with the diagnosis of peliosis hepatis which is a rare benign disease characterized by multiple blood-filled cystic spaces in the hepatic parenchyma. The findings of peliosis on FDG PET/CT are not well reported in the literature. These interesting images emphasize the importance of including peliosis hepatis in the differential diagnosis of multiple hypermetabolic hepatic lesions on FDG PET/CT, which could simulate malignancy.
Genome-wide studies of heart failure and endophenotypes: lessons learned and future directions
Authors: Maaike Yldau van der Ende, Mir Abdullah Said, Dirk Jan van Veldhuisen, Niek Verweij, Pim van der Harst
Journal: Cardiovascular Research (2018)

Heart failure (HF) is a complex clinical syndrome resulting from structural or functional impairments of ventricular filling or ejection of blood. HF has a poor prognosis and the burden to society remains tremendous. The unfulfilled expectation is that expanding our knowledge of the genetic architecture of HF will help to quickly advance the quality of risk assessment, diagnoses, and treatment. To date, genome-wide association studies (GWAS) of HF have led to disappointing results with only limited progress in our understanding and tempering the earlier expectations. However, the analyses of traits closely related to HF (also called 'endophenotypes') have led to promising and novel findings. For example, GWAS of NT-proBNP levels not only identified variants in the NNPA-NPPB locus but also substantiated data suggesting that natriuretic peptides in itself are associated with a lower risk of hypertension and HF. Many other genetic associates currently await experimental follow-up in which genes are prioritized based on bioinformatic analyses and various model organisms are employed to obtain functional insights. Promising genes with identified function could later be used in personalized medicine. Also, targeting specific pathogenic gene mutations is promising to protect future generations from HF, such as recently done in human embryos carrying the cardiomyopathy-associated MYBPC3 mutation. This review discusses the current status of GWAS of HF and its endophenotypes. In addition, future directions such as functional follow-up and application of GWAS results are discussed.
Ultrasound assisted gene and photodynamic synergistic therapy with multifunctional FOXA1-siRNA loaded porphyrin microbubbles for enhancing therapeutic efficacy for breast cancer
Authors: Ranran Zhao, Xiaolong Liang, Bo Zhao, Min Chen, Renfa Liu, Sujuan Sun, Xiuli Yue, Shumin Wang
Journal: Biomaterials (2018)