tbuckley/cabot-search huggingface dataset:
THU-422-Referral, treatment uptake and self-reported barriers in drug users diagnosed with active hepatitis C attending a low-threshold methadone program in Lisbon
Authors: Mario Jorge Silva, Cláudia Pereira, Rafaela Loureiro, Paulo Lopes, Ivone Água-Doce, Elsa Belo, Helena Cores Martins, Rodrigo Coutinho, Filipe Calinas, Elizabeth Padua
Journal: Journal of Hepatology (2019)
Effect of combined parasite derived peptide GK1 and Programmed Death antibody (anti-PD-L1) therapy on survival in a melanoma mouse model.
Authors: Jesus Vera-Aguilera, Raul Martinez-Zaguilan
Journal: Journal of Clinical Oncology (2015)

e20090 Background: With the recent discovery of the Programmed Death-1 receptor (PD1) and its ligand (PD-L1), the immunotherapy of cancer entered a new era.GK1, an 18-aminoacid peptide derived from Taenia crassiceps cysticerci, stimulates proinflammatory cytokines IFN-γ, TNF-α and CCL2 (MCP-1) in a concentration-dependent fashion. Studies regarding the PD1/PDL1 pathway suggest that combining therapies targeting tumor mechanisms of immune evasion with activation of normal immune cell may provide an optimal treatment strategy. In this study, we evaluated the efficacy for GK1 in combination with Anti-PD-L1 as an adjuvant treatment in a melanoma mouse model. Methods: Forty mice, 6- to 8-week-old C57BL/6 were injected with 2 x105 B16-F10-luc2. Tumor-bearing mice (20 mm3) were separated in four different groups (10 mice per group) until sacrifice: GK1, Anti-PDL-1, GK1/anti-PDL-1, and control. GK1 group was injected every 5 days peritumorally. Anti-PD-L1 was injected intraperitoneally (IP) every 3 days. The combined immunotherapy group injected every 5 days with peritumoral injection of GK1 and anti-PDL-1 every 3 days. The control group injected with peritumoral or IP sterile saline. Mice were sacrificed when moribund or lethargic and day of death was recorded. All experimental procedures comply with the Guide for the Care and Use of Laboratory Animals (NIH publication No. 80-23, revised 1985) and by the University Laboratory Animal Care Committee at Texas Tech University Health Sciences Center. Results: The GK1 peptide in combination with Anti-PD-L1 treatment resulted in a significant increase in the mean survival time of the treated group of 34 days compared to 23 days in the control group (P < 0.01). Moreover, the combination group demonstrated significant increase of survival compared to GK1 or Anti-PD-L1 alone (P < 0.01). Conclusions: The potential for GK1 to be used as a primary or adjuvant component of chemotherapeutic cocktails for the treatment of experimental melanoma was demonstrated in this study for the first time. Further studies to evaluate the direct translational bench-to bed-side translational potential are being performed by our group.
Concerns Regarding Phase 1b Clinical Trial of Atezolizumab Plus Nab-Paclitaxel for Metastatic Breast Cancer—In Reply
Authors: Sylvia Adams, Luciana Molinero
Journal: JAMA Oncology (2019)

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 Oncology 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 Oncology journal
THU-254-Cumulative effects of western diet and alcohol abuse: A novel model of ASH/NASH-derived liver injury
Authors: Raquel Benedé, Olga Estévez, Laura Moran Blanco, Nuria López-Alcántara, Feifei Guo, Chaobo CHEN, Ricardo Macias-Rodriguez, Astrid Ruiz-Margain, kang Zheng, Pierluigi Ramadori, Francisco Javier Cubero, Yulia Nevzorova
Journal: Journal of Hepatology (2019)
Influence of “Not Relevant” Responses on the Dermatology Life Quality Index (DLQI) for Patients With Psoriasis in the United States
Authors: John S. Barbieri, Joel M. Gelfand
Journal: JAMA Dermatology (2019)

This cross-sectional study examines the overall subjective and objective evaluation of disease severity between patients with psoriasis who responded "not relevant" vs those who responded "not at all" on the Dermatology Life Quality Index.
Staphylococcus aureus drives expansion of low-density neutrophils in diabetic mice
Authors: Taylor S. Cohen, Virginia Takahashi, Jessica Bonnell, Andrey Tovchigrechko, Raghothama Chaerkady, Wen Yu, Omari Jones-Nelson, Young Lee, Rajiv Raja, Sonja Hess, C. Kendall Stover, John J. Worthington, Mark A. Travis, Bret R. Sellman
Journal: Journal of Clinical Investigation (2019)

Diabetic individuals are at considerable risk for invasive infection by Staphylococcus aureus, however, the mechanisms underlying this enhanced susceptibility to infection are unclear. We observed increased mortality following i.v. S. aureus infection in diabetic mice compared with nondiabetic controls, correlating with increased numbers of low-density neutrophils (LDNs) and neutrophil extracellular traps (NETs). LDNs have been implicated in the inflammatory pathology of diseases such as lupus, given their release of large amounts of NETs. Our goal was to describe what drives LDN increases during S. aureus infection in the diabetic host and mechanisms that promote increased NET production by LDNs. LDN development is dependent on TGF-β, which we found to be more activated in the diabetic host. Neutralization of TGF-β, or the TGF-β-activating integrin αvβ8, reduced LDN numbers and improved survival during S. aureus infection. Targeting S. aureus directly with MEDI4893*, an α toxin-neutralizing monoclonal antibody, blocked TGF-β activation, reduced LDNs and NETs, and significantly improved survival. A comparison of gene and protein expression in high-density neutrophils and LDNs identified increased GPCRs and elevated phosphatase and tensin homolog (PTEN) in the LDN subset. Inhibition of PTEN improved the survival of infected diabetic mice. Our data identify a population of neutrophils in infected diabetic mice that correlated with decreased survival and increased NET production and describe 3 therapeutic targets, a bacterial target and 2 host proteins, that prevented NET production and improved survival.
Heart failure in cardiomyopathies: a position paper from the Heart Failure Association of the European Society of Cardiology
Authors: Petar M. Seferović, Marija Polovina, Johann Bauersachs, Michael Arad, Tuvia Ben Gal, Lars H. Lund, Stephan B. Felix, Eloisa Arbustini, Alida L.P. Caforio, Dimitrios Farmakis, Gerasimos S. Filippatos, Elias Gialafos, Vladimir Kanjuh, Gordana Krljanac, Giuseppe Limongelli, Aleš Linhart, Alexander R. Lyon, Ružica Maksimović, Davor Miličić, Ivan Milinković, Michel Noutsias, Ali Oto, Öztekin Oto, Siniša U. Pavlović, Massimo F. Piepoli, Arsen D. Ristić, Giuseppe M.C. Rosano, Hubert Seggewiss, Milika Ašanin, Jelena P. Seferović, Frank Ruschitzka, Jelena Čelutkiene, Tiny Jaarsma, Christian Mueller, Brenda Moura, Loreena Hill, Maurizio Volterrani, Yuri Lopatin, Marco Metra, Johannes Backs, Wilfried Mullens, Ovidiu Chioncel, Rudolf A. de Boer, Stefan Anker, Claudio Rapezzi, Andrew J.S. Coats, Carsten Tschöpe
Journal: European Journal of Heart Failure (2019)
FRI-181-Efficacy and safety of switching therapy from tenofovir disoproxil fumarate to tenofovir alafenamide for hepatitis B virus infection
Authors: Shun Kaneko, Masayuki Kurosaki, Nobuharu Tamaki, Jun Itakura, Sakura Kirino, Keiya Watakabe, Leona Osawa, Mao Okada, Wang Wan, Takao Shimizu, Mayu Higuchi, Kenta Takaura, Yutaka Yasui, Kaoru Tsuchiya, Hiroyuki Nakanishi, Yuka Takahashi, Namiki Izumi
Journal: Journal of Hepatology (2019)
Combined treatment with HMGN1 and anti-CD4 depleting antibody reverses T cell exhaustion and exerts robust anti-tumor effects in mice
Authors: Chang-Yu Chen, Satoshi Ueha, Yoshiro Ishiwata, Shoji Yokochi, De Yang, Joost J. Oppenheim, Haru Ogiwara, Shigeyuki Shichino, Shungo Deshimaru, Francis H. W. Shand, Shiro Shibayama, Kouji Matsushima
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Transient depletion of CD4<sup>+</sup> T cells results in tumor suppression and survival benefit in murine models; however, the tumor progression and recurrence still occur over more long-term monitoring of mice. Thus, we explored an additional strategy to enhance endogenous immune responses by an alarmin, high mobility group nucleosome binding protein 1 (HMGN1). <h3>Methods</h3> The anti-tumor effects of HMGN1, anti-CD4 depleting antibody, and their combined treatment were monitored in the Colon26 or the B16F10 subcutaneous murine models. The tumor-infiltrating CD8<sup>+</sup> T cell proliferation, differentiation, exhaustion, and its gene expression were determined by flow cytometry, transcriptome analysis, and quantitative real-time PCR. <h3>Results</h3> Our results show that a systemic administration of low doses of HMGN1 with an&nbsp;anti-CD4 depleting antibody (HMGN1/αCD4) promoted expansion of CD8<sup>+</sup> T cell populations (e.g. CD137<sup>+</sup> PD-1<sup>+</sup> and CD44<sup>hi</sup> PD-1<sup>+</sup>), recruited CCR7<sup>+</sup> migratory dendritic cells to the tumor, and reduced co-inhibitory molecules (e.g. PD-1, LAG-3, and TIM-3) to counteract CD8<sup>+</sup> T cell exhaustion. <h3>Conclusion</h3> The&nbsp;HMGN1/αCD4 treatment expanded effector CD8<sup>+</sup> T cells and prolonged their anti-tumor activities by rescuing them from exhaustion, thus resulting in tumor regression and even rejection in long-term monitored mice.
FRI-501-Survival among patients with advanced hepatocellular carcinoma in the pre-TKI versus TKI eras
Authors: Miyuki Sensui, Sadahisa Ogasawara, Yoshihiko Ooka, Kazufumi Kobayashi, Susumu Maruta, Hiroaki Kanzaki, Kengo Kanayama, Takahiro Maeda, Yuko Kusakabe, Soichiro Kiyono, Masato Nakamura, Tomoko Saito, Eiichiro Suzuki, Shingo Nakamoto, Shin Yasui, Akinobu Tawada, Tetsuhiro Chiba, Makoto Arai, Tatsuo Kanda, Hitoshi Maruyama, Naoya Kato
Journal: Journal of Hepatology (2019)
Interrater Reliability of Clinical Grading Measures for Cutaneous Chronic Graft-vs-Host Disease
Authors: Adela R. Cardones, Keith M. Sullivan, Cindy Green, Nelson J. Chao, Krista Rowe-Nichols, Lionel L. Bañez, Claude S. Burton, Mitchell E. Horwitz, Gwynn D. Long, Caroline L. Rao, Stefanie Sarantopoulos, Navjeet Sidhu-Malik, Anthony D. Sung, Russell P. Hall
Journal: JAMA Dermatology (2019)

<h3>Importance</h3> Cutaneous chronic graft-vs-host disease (cGVHD) is common after allogeneic hematopoietic stem cell transplant and is often associated with poor patient outcomes. A reliable and practical method for assessing disease severity and response to therapy among these patients is urgently needed. <h3>Objective</h3> To evaluate the interrater agreement and reliability of skin-specific and range of motion (ROM) variables of the 2014 National Institutes of Health (NIH) response criteria for cGVHD and a skin sclerosis grading scale (SSG). <h3>Design, Setting, and Participants</h3> In this observational study performed at a single tertiary academic center, 6 academic blood and marrow transplant specialists and 4 medical dermatologists examined 8 patients with diagnosed cutaneous cGVHD on July 10, 2015. The patient cohort was enriched for patients with sclerotic features. Each patient was evaluated by using the skin-specific and ROM criteria of the 2014 NIH response criteria for cGVHD and an SSG ranging from 0 to 3. Each patient was also asked to complete quality-of-life scoring instruments. Interrater agreement and reliability were estimated by calculating the Krippendorff α and Cohen κ statistics. Data were analyzed from September 29, 2015, through November 22, 2018. <h3>Main Outcomes and Measures</h3> Estimation of interrater agreement by interclass coefficient (Krippendorff α and Cohen κ statistics) for the skin-specific and ROM components of the 2014 NIH Response Criteria for Chronic GVHD and for the SSG. <h3>Results</h3> The median age of the patients evaluated was 54 years (range, 46-58 years). Patients were predominantly male (6 [75%]). Six of the 8 patients had a predominantly sclerotic cutaneous phenotype. Interrater agreement among our experts was acceptable for NIH skin feature score (0.68; 95% CI, 0.30-0.86) and good for NIH ROM scoring (0.80; 95% CI, 0.68-0.86). Dermatologists had acceptable agreement for NIH skin GVHD score (0.69; 95% CI, 0.25-0.82) and skin feature score (0.78; 95% CI, 0.17-0.98), good agreement in ROM grading (0.85; 95% CI, 0.69-0.90), and near perfect agreement in identifying sclerosis (0.82; 95% CI, 0.27-0.97). <h3>Conclusions and Relevance</h3> Although dermatologists had acceptable agreement in NIH skin GVHD score and skin features score, near perfect agreement in identifying cutaneous sclerosis, better agreement in grading severity of cutaneous cGVHD, especially in the intermediate grades, appears to be needed.
High intake of dietary fructose in overweight/obese teenagers associated with depletion of <i>Eubacterium</i> and <i>Streptococcus</i> in gut microbiome
Authors: Roshonda B Jones, Tanya L Alderete, Jeniffer S Kim, Joshua Millstein, Frank D Gilliland, Michael I Goran
Journal: Gut Microbes (2019)

Background A western high fat, high carbohydrate diet has been shown to be associated with decreased gut bacterial diversity and reductions in beneficial bacteria. This gut bacteria dysbiosis could develop in early life and contribute to chronic disease risk such as obesity, type 2 diabetes and non-alcoholic fatty liver disease.Objective To determine how dietary macronutrients are associated with the relative abundance of gut bacteria in healthy adolescents.Methods Fifty-two obese participants (12–19 years) from two studies, many who were primarily of Hispanic background, provided fecal samples for 16S rRNA gene sequencing. Dietary macronutrients were assessed using 24-hour diet recalls and body composition was assessed using DEXA. General regression models assuming a negative binomial distribution were used to examine the associations between gut bacteria and dietary fiber, saturated fat, unsaturated fats, protein, added sugar, total sugar and free fructose after adjusting for age, gender, race/ethnicity, body fat percentage, study and caloric intake.Results The genera Eubacterium (Benjamini-Hochberg (BH) corrected p-value = 0.10) and Streptococcus (BH corrected p-value = 0.04) were inversely associated with dietary fructose intake. There were no other significant associations between abundances of gut microbes and other dietary macronutrients, including fiber, fat, protein, total sugar or added sugar.Conclusions High dietary fructose was associated with lower abundance of the beneficial microbes Eubacterium and Streptococcus, which are involved with carbohydrate metabolism.
Trends in Readmissions and Length of Stay for Patients Hospitalized With Heart Failure in Canada and the United States
Authors: Marc D. Samsky, Andrew P. Ambrosy, Erik Youngson, Li Liang, Padma Kaul, Adrian F. Hernandez, Eric D. Peterson, Finlay A. McAlister
Journal: JAMA Cardiology (2019)

Over the past decade, reducing 30-day readmission rates has been emphasized in the United States (including via the implementation of the Hospital Readmissions Reduction Program) but not Canada.To examine changes that occurred from April 1, 2005, to December 31, 2015, in the United States and Canada for hospitalization length of stay and 30-day readmission rates of patients with heart failure.This cohort study included patients admitted with a primary diagnosis of heart failure to Canadian and US hospitals between April 1, 2005, and December 31, 2015, using International Classification of Diseases, Ninth Revision code 428.xx and Tenth Revision code I50. The study examined secular trends in length of stay and readmissions in both countries and tested for changes after implementation of the Hospital Readmissions Reduction Program using segmented regression models and the association between length of stay and readmissions using patient-level and hospital-level multivariable logistic regression models. Data analysis was completed from February 2018 to August 2018.Thirty-day readmissions.Between 2005 and 2015, mean length of stay declined marginally in Canadian hospitals (from a mean [SD] of 7.5 [5.7] to 7.3 [5.6] days; P < .001) but remained stable in US hospitals (mean [SD], 4.9 [3.7] days to 4.9 [3.5] days). Thirty-day readmission rates declined similarly in Canada (from 4088 of 20 758 patients [19.7%] to 3823 of 21 733 patients [17.6%] for all-cause readmissions; P < .001; and from 1743 of 20 758 patients [8.4%] to 1490 of 21 733 patients [6.9%] for heart failure-specific readmissions; P < .001) and the United States (from 21.2% to 18.5% for all-cause readmissions; from 7.6% to 5.7% for heart failure-specific readmissions; both P < .001). There were small but statistically significant positive correlations between length of stay and 30-day readmissions in both Canada (odds ratio, 1.01 [95% CI, 1.01-1.01]) and the United States (odds ratio, 1.01 [95% CI, 1.01-1.01]). Interrupted time-series analysis comparing readmission rates before and after the Hospital Readmissions Reduction Program implementation revealed no significant difference in either country for all-cause readmission rates before and after October 2012. There was also no change in the slope of the temporal trends; in Canada, all-cause readmissions were decreasing 1.1% per year before implementation and 1.3% after implementation (P = .84 for slope change) compared with 1.6% per year in the United States before implementation and 1.8% per year after October 2012 (P = .60 for slope change).Both Canada and the United States exhibited similar temporal declines in 30-day all-cause readmissions over the past decade. These findings suggest that the Hospital Readmissions Reduction Program did not appear to be associated with this secular trend or length of stay for heart failure in the United States.
Abstract 14445: Reduced Expression of Let-7f Leads to Impaired Ischemia-Induced Neovascularization Following Cigarette Smoke Exposure: Role of ALK5/SMAD2/PAI-1 Pathway
Authors: Wahiba Dhahri, Sylvie Dussault, Paola Haddad, Julie Turgeon, Sophie Tremblay, Michel Desjarlais, Raphaël Mathieu, Alain Rivard
Journal: Circulation (2015)

Background: Exposure to cigarette smoke is associated with impaired formation of new blood vessels (neovascularization) in response to ischemia. Here we investigated the potential role of miRs in that physiopathology. Methods and Results: Using Affimetrix GeneChip miRNA array analysis, we identified let-7f as a pro-angiogenic miR which expression is reduced following cigarette smoke exposure. qRT-PCR analyses confirmed that the expression of let-7f is significantly reduced in HUVECs treated with cigarette smoke extracts (CSE), and in the ischemic muscles of mice that are exposed to cigarette smoke (MES). In a mouse model of hindlimb ischemia, intramuscular injection of let-7f mimic restored ischemia-induced neovascularisation in MES. At day 21 after ischemia, Doppler flow ratios and capillary density in ischemic muscles were significantly improved in MES treated with let-7f mimic compared to those treated with a mimic control. Clinically, mice treated with let-7f mimic also exhibited reduced ambulatory impairment and hindlimb ischemic damages. Interestingly, we found that treatment with let-7f mimic can rescue endothelial progenitor cell (EPC) number and function (migration, integration into tubules) in MES. Let-7f has previously been shown to target ALK5 (TGF-βRI), an important modulator of angiogenesis. We found that ALK5 is significantly increased in HUVECs exposed to CSE and in the ischemic muscles of MES. This is associated with a downstream activation of anti-angiogenic factors such as SMAD2 and PAI-1. Importantly, treatment with let-7f mimic reduces the expression of ALK5, SMAD2 and PAI-1 both in vitro and in vivo. Moreover, let-7f mimic can also rescue angiogenesis in HUVECs exposed to CSE. Conclusion: Cigarette smoke exposure is associated with reduced expression of let-7f, which leads to impaired neovascularization following ischemia. Our results suggest that the mechanism involves increased activation of ALK5, together with a downstream stimulation of the anti-angiogenic SMAD2/PAI-1 pathway. Overexpression of let-7f using a miR mimic could constitute a novel therapeutic strategy to improve ischemia-induced neovascularization in pathological conditions.
World Health Organization Treatment Recommendations for Nonsevere Fast-Breathing Pneumonia Need to Be Updated—Reply
Authors: Amy Sarah Ginsburg, Eric D. McCollum, Susanne J. May
Journal: JAMA Pediatrics (2019)

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 Pediatrics 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 Pediatrics journal
Keratin 6a mutations lead to impaired mitochondrial quality control
Authors: S.M. Lehmann, R.E. Leube, N. Schwarz
Journal: British Journal of Dermatology (2019)

BackgroundEpidermal differentiation is a multilevel process in which keratinocytes need to lose their organelles, including their mitochondria, by autophagy. Disturbed autophagy leads to thickening of the epidermis as seen in pachyonychia congenita (PC), a rare skin disease caused by mutations in keratins 6, 16 and 17.