tbuckley/cabot-search huggingface dataset:
Abstract A21: TRIM29 promotes invasion and migration of bladder cancer cells by regulating myosin-intermediate filament network and focal adhesion
Authors: Yin Wang, Erica R. Gumkowski, Phillip L. Palmbos
Journal: Clinical Cancer Research (2020)

Abstract Development of invasive progression in human bladder cancer is a key determinant of patient outcomes. Therefore, understanding the drivers of bladder cancer invasive progression is critical to improving patient care. We have previously shown that TRIM29 (also known as ataxia-telangiectasia group D complementing gene, ATDC) is highly expressed in muscle-invasive bladder cancer and plays an important role in driving tumor formation and invasion in vitro and in vivo. TRIM29 is upregulated by TP63 in basal subtype tumors, but the mechanism by which TRIM29 promotes tumor invasion was unknown. To elucidate the mechanism by which TRIM29 drives bladder cancer invasion, we developed a 3-D bladder cancer spheroid invasion assay that allows observation of the invasive process of cancer spheroids in a real-time fashion and observation of protein expression using confocal microscopy. Using this system, we confirmed that TRIM29 is required for bladder cancer stromal invasion. To determine if TRIM29 is specifically required for cell migration, which is an important ability contributing to invasive behavior, scratch assays were performed and we found TRIM29 is required for migration. Cancer cell migration requires modulation of cell adhesion and actin/myosin activation. To examine the role of TRIM29 in cell adhesion and motility, gene knockout or knockdowns of TRIM29 were generated in human bladder cancer cell lines (UM-UC5, UC9, UC13, UC14). Interestingly, TRIM29 KO/KD downregulates the expression of keratin 14 (KRT14), a member of type I keratin family that constitutes intermediate filament (IF) network, as well as myosin IIA (MYH9), a non-muscle motor protein that is essential for cell adhesion and migration. Using immunofluorescent confocal microscopy, we found that TRIM29 also modulates formation of focal adhesion plaques in bladder cancer during cell migration. Taken together, these findings suggest a novel mechanism by which TRIM29 regulates bladder cancer cell motility and invasion. Citation Format: Yin Wang, Erica R. Gumkowski, Phillip L. Palmbos. TRIM29 promotes invasion and migration of bladder cancer cells by regulating myosin-intermediate filament network and focal adhesion [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr A21.
External Automated Defibrillator–Assisted Diagnosis of Patient After Bringing Him Back to Life
Authors: José de Almeida, Francisco Gonçalves, Lino Gonçalves
Journal: JAMA Internal Medicine (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 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
Abstract 14932: The Associations Between Physical Activity and Appetite in Patients With Heart Failure - A Prospective Observational Study
Authors: Christina Andreae, Lorraine S Evangelista, Kristofer Arestedt, Anna Stromberg
Journal: Circulation (2018)

Introduction: Physical activity and appetite both play a crucial role for health outcomes and quality of life in patients with heart failure. Nevertheless, both of these key functions are frequentl...
Abstract 16628: Improvement of LV-Strain in HFrEF-Patients at 12 Months Follow-Up Using the Revivent TM System (Bioventrix) Compared to Patients Treated by OMT- Results From a CMR-Multi-Center-Trial
Authors: Tomas Lapinskas, Christoph Klein, Gianni Pedrizzetti, Lukas Stoiber, Felix Hennig, Christoph Knosalla, Christoph Schmitz, David Schickling, Lon Annest, Sebastian Kelle
Journal: Circulation (2018)

Introduction: After an acute coronary syndrome many patients with ischemic cardiomyopathy (ICM) suffer from heart failure with reduced ejection fraction (HFrEF). Beside surgical ventricular reconst...
Phase I and Pharmacokinetic Study of Romidepsin in Patients with Cancer and Hepatic Dysfunction: A National Cancer Institute Organ Dysfunction Working Group Study
Authors: Roisin M. Connolly, Eric Laille, Ulka Vaishampayan, Vincent Chung, Karen Kelly, Afshin Dowlati, Olatunji B. Alese, R. Donald Harvey, Paul Haluska, Lillian L. Siu, Shivaani Kummar, Richard Piekarz, S. Percy Ivy, Nicole M. Anders, Melinda Downs, Ashley O'Connor, Angela Scardina, Jacqueline Saunders, Gary L. Rosner, Michael A. Carducci, Michelle A. Rudek
Journal: Clinical Cancer Research (2020)

Romidepsin dosing recommendations for patients with malignancy and varying degrees of hepatic dysfunction was lacking at the time of regulatory approval for T-cell lymphoma. We conducted a multicenter phase I clinical trial (ETCTN-9008) via the NCI Organ Dysfunction Working Group to investigate safety, first cycle MTD, and pharmacokinetic profile of romidepsin in this setting.Patients with select advanced solid tumors or hematologic malignancies were stratified according to hepatic function. Romidepsin was administered intravenously on days 1, 8, and 15 of a 28-day cycle and escalation followed a 3 + 3 design in moderate and severe impairment cohorts. Blood samples for detailed pharmacokinetic analyses were collected after the first dose.Thirty-one patients received one dose of romidepsin and were evaluable for pharmacokinetic analyses in normal (n = 12), mild (n = 8), moderate (n = 5), and severe (n = 6) cohorts. Adverse events across cohorts were similar, and dose-limiting toxicity occurred in two patients (mild and severe impairment cohorts). The MTD was not determined because the geometric mean AUC values of romidepsin in moderate (7 mg/m2) and severe (5 mg/m2) impairment cohort were 114% and 116% of the normal cohort (14 mg/m2).Data from the ETCTN-9008 trial led to changes in the romidepsin labeling to reflect starting dose adjustment for patients with cancer and moderate and severe hepatic impairment, with no adjustment for mild hepatic impairment.
Coordination of metabolism, arousal, and reward by orexin/hypocretin neurons
Authors: Natalie J. Michael, Joel K. Elmquist
Journal: Journal of Clinical Investigation (2020)

Orexin/hypocretin neurons located in the lateral hypothalamus play a critical role in the maintenance of arousal and contribute to the regulation of multiple homeostatic and behavioral processes. In this issue of the JCI, Tan and Hang et al. report that feeding a high-fat diet to mice compromised the function of the orexin system, leading to impairments in reward-seeking and active coping mechanisms. The researchers observed changes at the cellular and circuit levels suggesting that reduced excitability of orexin neurons affects behavior through induction of a hypoarousal state.
Mechanotransduction is a context-dependent activator of TGF-β signaling in mesenchymal stem cells
Authors: Steven Vermeulen, Nadia Roumans, Floris Honig, Aurélie Carlier, Dennie G.A.J. Hebels, Aysegul Dede Eren, Peter ten Dijke, Aliaksei Vasilevich, Jan de Boer
Journal: Biomaterials (2020)
OP0084 Peg stnf-ri improves health-related quality of life in patients with rheumatoid arthritis
Authors: JR Tesser, MH Schiff, MW Davis, JM Woolley
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To evaluate the effect of PEG sTNF-RI on the health related quality of life (HRQOL) of subjects with rheumatoid arthritis. <h3>Methods</h3> In a 12-week, multicenter, randomised, double-blind clinical trial, 194 subjects received either 400- or 800-mcg/kg of PEG sTNF-RI or placebo SC weekly (1:1:1). The study population included subjects with or without background DMARDs (combination therapy involving methotrexate with sulfasalazine or hydroxychloroquine, or sulfasalazine plus hydroxychloroquine). To measure HRQOL, the SF-36 was administered at baseline and at weeks 4 and 12. The SF-36 consists of 36 items designed to assess physical function (PF), role limitations due to physical problems (RP), body pain (BP), general health (GH), vitality/energy (VT), social function (SF), role limitations due to emotional problems (RE), and mental health (MH). The SF-36 is scored from 0 to 100, with higher scores indicating better HRQOL. Differences of 3 to 5 points are considered clinically and socially relevant. The mean change in each SF-36 scale score was compared between subjects receiving PEG sTNF-RI and those on placebo using a repeated measure mixed effect model analysis. The analysis set was a modified intent-to-treat sample, i.e. all patients who received at least one dose were included (n = 193). <h3>Results</h3> Subjects using either dose of PEG sTNF-RI experienced statistically significant, and clinically and socially relevant improvements in each SF-36 scale (see Table 1). These improvements exceeded those for subjects on placebo in every scale and were statistically significantly improved over placebo for 7 of 8 scales for the 800-mcg/kg dose, and 6 of 8 scales for the 400-mcg/kg dose. <h3>Conclusion</h3> Subjects receiving PEG sTNF-RI experienced statistically significant, clinically and socially relevant improvements in their SF-36 scores. These improvements occurred across a full range of health-related quality of life scales, from the physical to the psychosocial, and exceeded those for subjects on placebo. In this population of patients with rheumatoid arthritis, some of whom received DMARD or combination DMARD therapy, PEG sTNF-RI leads to significant and meaningful improvements in health-related quality of life.
Research in a time of enteroids and organoids: how the human gut model has transformed the study of enteric bacterial pathogens
Authors: Sridevi Ranganathan, Emily M. Smith, Jennifer D. Foulke-Abel, Eileen M. Barry
Journal: Gut Microbes (2020)

Enteric bacterial pathogens cause significant morbidity and mortality globally. Studies in tissue culture and animal models shaped our initial understanding of these host–pathogen interactions. However, intrinsic shortcomings in these models limit their application, especially in translational applications like drug screening and vaccine development. Human intestinal enteroid and organoid models overcome some limitations of existing models and advance the study of enteric pathogens. In this review, we detail the use of human enteroids and organoids to investigate the pathogenesis of invasive bacteria Shigella, Listeria, and Salmonella, and noninvasive bacteria pathogenic Escherichia coli, Clostridium difficile, and Vibrio cholerae. We highlight how these studies confirm previously identified mechanisms and, importantly, reveal novel ones. We also discuss the challenges for model advancement, including platform engineering to integrate environmental conditions, innate immune cells and the resident microbiome, and the potential for pre-clinical testing of recently developed antimicrobial drugs and vaccines.
Aerobic performance among healthy (non-asthmatic) adults using beta2-agonists: a systematic review and meta-analysis of randomised controlled trials
Authors: Amund Riiser, Trine Stensrud, Julie Stang, Lars Bo Andersen
Journal: British Journal of Sports Medicine (2020)

Objective To examine the effect of beta2-agonists on aerobic performance in healthy, non-asthmatic study participants. Design Systematic review and meta-analysis. Eligibility criteria We searched four databases (PubMed, Embase, SPORTDiscus and Web of Science) for randomised controlled trials published until December 2019. Studies examining the effect of beta2-agonists on maximal physical performance lasting longer than 1 min were included in the meta-analysis. Data are presented as standardised difference in mean (SDM) with 95% CI. Results The present meta-analysis includes 47 studies. The studies comprise 607 participants in cross-over trials, including 99 participants in three-way cross-over trials and 27 participants in a four-way cross-over trial. Seventy-three participants were included in parallel trials. Beta2-agonists did not affect aerobic performance compared with placebo (SDM 0.051, 95% CI −0.020 to 0.122). The SDM for the included studies was not heterogeneous (I 2 =0%, p=0.893), and the effect was not related to type of beta2-agonist, dose, administration route, duration of treatment or performance level of participants. Beta2-agonists had no effect on time trial performance, time to exhaustion or maximal oxygen consumption (p&lt;0.218). Conclusion/implication The present study shows that beta2-agonists do not affect aerobic performance in non-asthmatic subjects regardless of type, dose, administration route, duration of treatment or performance level of participants. The results of the present study should be of interest to WADA and to anyone who is interested in equal opportunities in competitive sports. Systematic review registration PROSPERO CRD42018109223.
Long-term Trends in Mental Health Disorders After the 2011 Great East Japan Earthquake and Tsunami
Authors: Shiho Kino, Jun Aida, Katsunori Kondo, Ichiro Kawachi
Journal: JAMA Network Open (2020)

Posttraumatic stress symptoms (PTSS) and depressive symptoms are common among survivors of a major disaster, yet few longitudinal studies have documented their long-term persistence at the community level.To examine the trajectories of PTSS and depressive symptoms for as long as 5.5 years after the 2011 Great East Japan earthquake and tsunami.This cohort study used data from 2781 participants in 3 waves of the Iwanuma Study (2010, 2013, and 2016), a cohort of community-dwelling older adults (≥65 years in August 2010) in Iwanuma, Japan, who were directly affected by the 2011 disaster. The baseline assessment of mental health predated the disaster by 7 months, and survivors were followed up for 5.5 years after the disaster. Data analysis was performed from October 2019 to February 2020.The March 11, 2011, Great East Japan earthquake and tsunami.PTSS were measured by 9 questions on the Screening Questionnaire for Disaster Mental Health, while depressive symptoms were measured by 15 items on the Geriatric Depression Scale short form.The analytic samples for trajectories of PTSS and depressive symptoms included 2275 and 1735 respondents, respectively. In the study population at baseline, there were slightly more women (1262 of 2275 [55.5%] and 882 of 1735 [50.8%]), and most participants were aged 65 to 74 years (1533 [67.4%] and 1224 [70.5%]) and married (1664 [76.2%] and 1319 [77.7%]). Overall, there was a 13.6% (95% CI, 11.7%-15.6%) incidence of depression among individuals who did not have depression before the disaster, while a further 11.1% (95% CI, 9.8%-12.4%) reported PTSS after the disaster. By 5.5 years of follow-up, approximately half of the survivors with new depressive symptoms in 2013 (85 of 168 [50.6%]) and PTSS (147 of 253 [58.1%]) had recovered. The prevalence of depression in the community remained remarkably stable (between 504 participants [29.0%] and 506 participants [29.2%]) comparing predisaster and postdisaster data.In this study, mental illness symptoms persisted for more than 5 years among half of disaster survivors, but the community-wide prevalence of depression remained stable, suggesting that the community itself was resilient.
Mutation affecting the conserved acidic WNK1 motif causes inherited hyperkalemic hyperchloremic acidosis
Authors: Hélène Louis-Dit-Picard, Ilektra Kouranti, Chloé Rafael, Irmine Loisel-Ferreira, Maria Chavez-Canales, Waed Abdel-Khalek, Eduardo R. Argaiz, Stéphanie Baron, Sarah Vacle, Tiffany Migeon, Richard Coleman, Marcio Do Cruzeiro, Marguerite Hureaux, Nirubiah Thurairajasingam, Stéphane Decramer, Xavier Girerd, Kevin O’Shaugnessy, Paolo Mulatero, Gwenaëlle Roussey, Ivan Tack, Robert Unwin, Rosa Vargas-Poussou, Olivier Staub, Richard Grimm, Paul A. Welling, Gerardo Gamba, Eric Clauser, Juliette Hadchouel, Xavier Jeunemaitre
Journal: Journal of Clinical Investigation (2020)

Gain-of-function mutations in with no lysine (K) 1 (WNK1) and WNK4 genes are responsible for familial hyperkalemic hypertension (FHHt), a rare, inherited disorder characterized by arterial hypertension and hyperkalemia with metabolic acidosis. More recently, FHHt-causing mutations in the Kelch-like 3–Cullin 3 (KLHL3-CUL3) E3 ubiquitin ligase complex have shed light on the importance of WNK's cellular degradation on renal ion transport. Using full exome sequencing for a 4-generation family and then targeted sequencing in other suspected cases, we have identified new missense variants in the WNK1 gene clustering in the short conserved acidic motif known to interact with the KLHL3-CUL3 ubiquitin complex. Affected subjects had an early onset of a hyperkalemic hyperchloremic phenotype, but normal blood pressure values"Functional experiments in Xenopus laevis oocytes and HEK293T cells demonstrated that these mutations strongly decrease the ubiquitination of the kidney-specific isoform KS-WNK1 by the KLHL3-CUL3 complex rather than the long ubiquitous catalytically active L-WNK1 isoform. A corresponding CRISPR/Cas9 engineered mouse model recapitulated both the clinical and biological phenotypes. Renal investigations showed increased activation of the Ste20 proline alanine–rich kinase–Na+-Cl– cotransporter (SPAK-NCC) phosphorylation cascade, associated with impaired ROMK apical expression in the distal part of the renal tubule. Together, these new WNK1 genetic variants highlight the importance of the KS-WNK1 isoform abundance on potassium homeostasis.
Policy Implications of the Orphan Drug Designation for Remdesivir to Treat COVID-19
Authors: Kao-Ping Chua, Rena M. Conti
Journal: JAMA Internal Medicine (2020)

Christoph D. Spinner, MD; Robert L. Gottlieb, MD, PhD; Gerard J. Criner, MD; José Ramón Arribas López, MD; Anna Maria Cattelan, MD; Alex Soriano Viladomiu, MD; Onyema Ogbuagu, MD; Prashant Malhotra, MD; Kathleen M. Mullane, DO; Antonella Castagna, MD; Louis Yi Ann Chai, MD; Meta Roestenberg, MD; Owen Tak Yin Tsang, MD; Enos Bernasconi, MD; Paul Le Turnier, MD; Shan-Chwen Chang, MD; Devi SenGupta, MD; Robert H. Hyland, DPhil; Anu O. Osinusi, MD; Huyen Cao, MD; Christiana Blair, MS; Hongyuan Wang, PhD; Anuj Gaggar, MD, PhD; Diana M. Brainard, MD; Mark J. McPhail, MD; Sanjay Bhagani, MD; Mi Young Ahn, MD; Arun J. Sanyal, MD; Gregory Huhn, MD; Francisco M. Marty, MD; for the GS-US-540-5774 Investigators
Real-world mepolizumab in the prospective severe asthma REALITI-A study: initial analysis
Authors: Tim Harrison, Giorgio Walter Canonica, Geoffrey Chupp, Jason Lee, Florence Schleich, Tobias Welte, Antonio Valero, Kim Gemzoe, Aoife Maxwell, Sandra Joksaite, Shibing Yang, Peter Howarth, Melissa K. Van Dyke
Journal: European Respiratory Journal (2020)

Introduction Efficacy of mepolizumab, an anti-interleukin-5 monoclonal antibody, was demonstrated in randomised controlled trials; data on its real-world impact in routine clinical practice are starting to emerge. We assessed the effectiveness and safety of mepolizumab prescribed for patients in the real world. Methods REALITI-A is a global, prospective, observational cohort study, collecting data from routine healthcare visits from patients with asthma. Patients newly prescribed mepolizumab for severe asthma with 12 months of relevant medical history pre-mepolizumab (collected retrospectively) were enrolled. An initial analysis of data from early initiators who had completed 1 year of follow-up (as of February 28, 2019) was conducted. The primary objective was to compare the rate of clinically significant exacerbations (requiring oral corticosteroids (OCS) and/or hospitalisation and/or emergency department visit) before and after mepolizumab; exacerbations requiring hospitalisation and/or emergency department visit and change in maintenance OCS use were secondary objectives. Treatment-related adverse events were reported. Results Overall, 368 mepolizumab-treated patients were included. Rates of clinically significant exacerbations were reduced by 69% from 4.63 per person per year pre-treatment to 1.43 per person per year during follow-up (p&lt;0.001), as were those requiring hospitalisation and/or emergency department visit (from 1.14 to 0.27 per person per year; 77% reduction). In 159 patients with maintenance OCS dose data available during the pre-treatment period, median daily dose decreased from 10.0 (pre-treatment) to 5.0 mg·day −1 by week 21–24 of follow-up, sustained until week 53–56. No new safety signals were reported. Conclusion These data demonstrate that the effectiveness of mepolizumab is consistent with clinical trial results under real-world settings, with significant reductions in exacerbations and daily maintenance OCS dose.
FRI0140 Relatonship between mhc ii class allele polymorphism and clinical characteristics of systemic lupus erythematosus
Authors: A Kovács, E Endreffy, L Kovács, J Eller, G Pokorny
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To examine the possible correlations between the genetic background and clinical characteristics of the disease in patients with systemic lupus erythematosus (SLE). <h3>Methods</h3> Distributions of MHC II Class (DRB1, DQA1 and DQB1) alleles were studied with molecular genetic methods (polymerase chain reaction and restriction fragment length polymorphism) in 50 SLE patients and 50 healthy blood donors as controls. The statistical significance of differences between the examined groups were analysed with Fisher's exact test. <h3>Results</h3> In our SLE patients, the DR2 (1501 subtype) – DQA1 0102 – DQB1 0602 (p = 0.045), the DR3 – DQA1 05011 – DQB1 0201 (p = 0.022), and the DR7 – DQA1 0201 – DQB1 0202 (p = 0.005) haplotypes occurred significantly more frequently than in controls. Evaluating the connexion between the genetic and clinical characteristics of the disease, we found that DR2 positivity was less frequent in patients with lupus nephritis (LN) than in those without LN (3/16 vs 16/34, p = 0.05). In contrast, DR3- and DR7-associated haplotypes were more common in LN than in patients without renal manifestation (8/16 vs 11/34 and 7/16 vs 8/34, respectively). In patients with pericarditis and/or pleuritis, DR7 positivity was more frequent than in patients without serositis (12/27 vs 3/23, p = 0.016). Similarly, the DR7-associated haplotype was detected more frequently in patients with one or more severe (renal, cardiopulmonary, central nervous system) manifestations as compared to patients without these major features (15/36 vs 0/14, p = 0.002). <h3>Conclusion</h3> We conclude that there are three different MHC II Class haplotypes of susceptibility in Hungarian patients with SLE. In our experience, the DR7-positive cases exhibited more severe disease manifestations, while patients with DR2-positivity had a milder clinical course.