tbuckley/cabot-search huggingface dataset:
Characteristics of Impaired Dendritic Cell Function in Patients With Hepatitis B Virus Infection
Authors: Atsushi Yonejima, Eishiro Mizukoshi, Toshikatsu Tamai, Hidetoshi Nakagawa, Masaaki Kitahara, Tatsuya Yamashita, Kuniaki Arai, Takeshi Terashima, Noriho Iida, Kazumi Fushimi, Hikari Okada, Taro Yamashita, Yoshio Sakai, Masao Honda, Shuichi Kaneko
Journal: Hepatology (2019)

Dendritic cells (DCs) are antigen‐presenting cells with a central role in host immune response. This study analyzed gene expression and DC function in hepatitis B virus (HBV) patients, functions impaired because of HBV, and identified the genes related to these functions. Peripheral blood mononuclear cells from 64 HBV patients and 19 healthy controls were analyzed. Peripheral blood DCs were stained with antibodies against human leukocyte antigen–DR/Lin‐1/CD123/CD11c and separated into plasmacytoid DCs (pDCs) and myeloid DCs by fluorescence‐activated cell sorting. Using an interferon‐gamma enzyme‐linked immunospot assay, we analyzed antigen‐specific response in HBV‐infected patients. Regarding DC function, we analyzed antigen‐presenting capacity, cell migration capacity, phagocytic capacity, and cytokine production capacity. DC gene expression was analyzed by microarray to identify genes related to DC function. No difference was found in the number of DCs in peripheral blood between healthy participants and HBV patients. In cell‐surface marker analysis, CD80, CD83, CD86, CD40, and C‐C motif chemokine receptor 7 expression levels in pDCs were related to the HBV‐specific T‐cell response. DCs from HBV patients exhibited decreases in antigen‐presenting capacity, migration capacity, and cytokine production capacity. In gene expression analysis, immune‐related genes with greatly reduced expression levels in chronic hepatitis B patients were identified. Of these genes, interleukin (IL)‐6 signal transducer (IL6ST) expression level positively correlated with DC surface marker expression level. Adjustment of IL6ST expression level in DCs and treatment with oncostatin M resulted in recovery of DC function. Conclusion : IL6ST expression was identified as one cause of decline in DC function in HBV patients. Adjustment of IL6 family cytokine signaling may be useful for recovering reduced DC function in HBV infection.
Demarcated thresholds of tumor-specific CD8 T cells elicited by MCMV-based vaccine vectors provide robust correlates of protection
Authors: Elham Beyranvand Nejad, Robert B. Ratts, Eleni Panagioti, Christine Meyer, Jennifer D. Oduro, Luka Cicin-Sain, Klaus Früh, Sjoerd H. van der Burg, Ramon Arens
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> The capacity of cytomegalovirus (CMV) to elicit long-lasting strong T cell responses, and the ability to engineer the genome of this DNA virus positions CMV-based vaccine vectors highly suitable as a cancer vaccine platform. Defined immune thresholds for tumor protection and the factors affecting such thresholds have not well been investigated in cancer immunotherapy. We here determined using CMV as a vaccine platform whether critical thresholds of vaccine-specific T cell responses can be established that relate to tumor protection, and which factors control such thresholds. <h3>Methods</h3> We generated CMV-based vaccine vectors expressing the E7 epitope and tested these in preclinical models of HPV16-induced cancer. Vaccination was applied via different doses and routes (intraperitoneal (IP), subcutaneous (SC) and intranasal (IN)). The magnitude, kinetics and phenotype of the circulating tumor-specific CD8<sup>+</sup> T cell response were determined. Mice were subsequently challenged with tumor cells, and the tumor protection was monitored. <h3>Results</h3> Immunization with CMV-based vaccines via the IP or SC route eliciting vaccine-induced CD8<sup>+</sup> T cell responses of &gt; 0.3% of the total circulating CD8 T cell population fully protects mice against lethal tumor challenge. However, low dose inoculations via the IP or SC route or IN vaccination elicited vaccine-induced CD8<sup>+</sup> T cell responses that did not reach protective thresholds for tumor protection. In addition, whereas weak pre-existing immunity did not alter the protective thresholds of the vaccine-specific T cell response following subsequent immunization with CMV-based vaccine vectors, strong pre-existing immunity inhibited the development of vaccine-induced T cells and their control on tumor progression. <h3>Conclusions</h3> This study highlight the effectiveness of CMV-based vaccine vectors, and shows that demarcated thresholds of vaccine-specific T cells could be defined that correlate to tumor protection. Together, these results may hold importance for cancer vaccine development to achieve high efficacy in vaccine recipients.
Abstract 15668: Mechanical Circulatory Support With Veno-Arterial Extracorporeal Membrane Oxygenation for Refractory Cardiogenic Shock in Elderly Patients: Results From the Extracorporeal Life Support Organization (ELSO) Registry
Authors: Roberto Lorusso, Sandro Gelsomino, Priya Mendiratta, Parthak Prodhan, Peter Rycus, Graeme MacLaren, Thomas Brogan, Yih-Sharng Chen, Jos Maessen, Xiaotong Hou, Orlando Parise, Ravi Thiagarajan
Journal: Circulation (2015)

Introduction: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for refractory acute cardiogenic shock is increasingly applied in adult patients. Patient age, however, represents still a controversial issue and data about VA-ECMO in elderly patients have been poorly reported in this setting. Hypothesis: The Extracorporeal Life Support Organization (ELSO) Registry was analysed to assess the in-hospital outcome of elderly patients (≥ 70 years) undergoing VA-ECMO because of acute refractory cardiogenic shock. Methods: Mean age of the total adult patient cohort (n=5,408) was 53.0±15.7 years (range 18-91 years). The elderly group included 735 patients (13.6%), with a mean age of 75.2±4.4 years, with pre-ECMO cardiac-related surgical or interventional procedures performed in 134 cases (18.9%). The mean duration of VA-ECMO in this group was 100.7± 90.9 hours (as compared to 137.7±146.1 hours, in younger group)(p&lt;0.001). Results: Overall survival to hospital discharge was 41.4% (2,657/5,408), with 30.5% (224/735) in the elderly, and 43.1% (2,016/4,673) in younger patients (p&lt;0.05), respectively. In terms of complications, older patients showed higher rates (p&lt;0.001) of bleeding, of infection, acute renal failure, renal replacement therapy, and need of inotropic drugs. Conclusions: Despite higher mortality and morbidity rates as compared to younger subjects, elderly patients undergoing VA-ECMO for refractory cardiogenic shock have still an acceptable outcome in such a challenging clinical scenario, indicating that patient age should not represent an absolute contraindication in the therapeutic decision-making.
FDG PET in Diffuse Spinal Carcinomatous Meningitis
Authors: Cécile Cuvilliers, Flora Ahrweiller, Elodie Vauléon, Joël Castelli, Xavier Palard-Novello
Journal: Clinical Nuclear Medicine (2019)

A 65-year-old man, diagnosed with right paranasal sinus neuroendocrine carcinoma with skull base invasion and ipsilateral lymph node involvement underwent chemotherapy. Six months later, the patient underwent radiation therapy for right cervical lymph node recurrence. Two months after the end of the radiation therapy, the patient was referred to our department to perform a whole-body FDG PET for therapeutic assessment. It showed diffuse intense FDG uptake of the whole spinal canal. The physical examination revealed walking disorders. Meningeal contrast enhancement on MRI of the brain and the spinal cord was leading to the diagnosis of carcinomatous meningitis.
The wheezy legacy of infant bronchiolitis
Authors: Fabio Midulla
Journal: Thorax (2019)

The association between bronchiolitis, recurrent wheeze (RW) and asthma is well known. Numerous studies have elucidated that respiratory syncytial virus (RSV) bronchiolitis is associated with RW, whereas disagreement remains regarding its association with asthma. RSV infection and RW may both be consequences of small airways dimensions,1 dysregulation of the innate immune response or they may be the results of post-RSV infection intense inflammation and airways remodelling.2

The Tucson group demonstrated the association between RSV infection and the development of different RW’s phenotypes, but not with asthma.1 On the contrary, Sigur et al demonstrated that RSV bronchiolitis was associated with the development atopy and asthma.3 Regarding the genetic characteristics of infants who developed asthma after bronchiolitis, two Danish studies performed on twins with RSV bronchiolitis, demonstrated that RSV is not responsible for the development of asthma, but that a strong genetic predisposition is crucial for the development of both bronchiolitis and asthma.4 5

The article …
Abstract P204: Growth and Moderators of Pulse Wave Velocity From Childhood to Adulthood
Authors: Xiaohua Liang, Shaoyong Su, Guang Hao, Harold Snieder, Frank Treiber, Gaston Kapuku, Xiaoling Wang
Journal: Circulation (2018)

Background: Increased arterial stiffness measured by pulse wave velocity (PWV) has been shown to be an important parameter in the assessment of cardiovascular risk. However little is known about its longitudinal development from childhood to adulthood and its possible sociodemographic, anthropometric, hemodynamic and behavioral moderators. Methods and Results: Individual growth curves of carotid-distal PWV across age were created for 559 African American and European American males and females with a maximum of 5 assessments over a 13-year period (age, 13.7-37.3). African Americans and males had significantly higher PWV than did European Americans and females (Ps&lt;0.01), respectively. A 3-way interaction (P&lt;0.01) between age, gender and ethnicity was observed with African American males displaying a larger rate of increase in PWV with age than the other 3 ethnic and gender groups. The ethnicity and gender effects on PWV persisted when controlling for other moderators. Waist circumstance was the strongest anthropometric predictor but its effect on PWV was only significant in females. Mean arterial pressure was the strongest hemodynamic predictor, marital status of parents was the strongest socioeconomic predictor, and illegal drug use was the strongest behavioral predictor of PWV. The best-fitting full model explained in total 61.6% of the between-subject variance in PWVwith ethnicity, genderand age explaining25%. Conclusion: We observed significant ethnic and gender differences in longitudinal trajectories of PWV in youth and young adults. Apart from these ethnicity and gender effects, individual differences in PWV growth can largely be explained by mean arterial pressure, waist circumstance, marital status and illegal drug use.
Epidemiology and implications of concurrent diagnosis of eosinophilic oesophagitis and IBD based on a prospective population-based analysis
Authors: Berkeley N Limketkai, Shailja C Shah, Ikuo Hirano, Emanuelle Bellaguarda, Jean-Frederic Colombel
Journal: Gut (2019)

Objective Eosinophilic oesophagitis (EoO) and IBD are immune-mediated diseases of the gastrointestinal tract with possible overlapping pathogenic mechanisms. Our aim was to define the epidemiology and clinical implications of concurrent EoO and IBD diagnoses. Design We conducted a prospective cohort analysis using the Truven MarketScan database (2009–2016) to estimate the incidence and prevalence of EoO in patients with Crohn’s disease (CD) or UC and vice versa. Cox proportional hazards and Kaplan-Meier methods were used to estimate the risk of EoO-related or IBD-related complications among patients with concurrent diagnoses. Results Among 134 013 536 individuals, the incidence of EoO, CD and UC were 23.1, 51.2 and 55.2 per 100 000 person-years, respectively. The risk of EoO was higher among patients with CD (incidence rate ratio [IRR] 5.4, p&lt;0.01; prevalence ratio (PR) 7.8, p&lt;0.01) or UC (IRR 3.5, p&lt;0.01; PR 5.0, p&lt;0.01), while the risk of IBD was higher among patients with EoO (CD: IRR 5.7, p&lt;0.01; PR 7.6, p&lt;0.01; UC: IRR 3.4, p&lt;0.01; PR 4.9, p&lt;0.01) versus individuals without either diagnosis. Concurrent diagnosis of EoO and IBD was associated with greater composite risk of IBD-related complications (CD: adjusted HR (aHR) 1.09, p=0.01; UC: aHR 1.10, p=0.04) but lower composite risk of EoO-related complications (aHR 0.59; p&lt;0.01). Conclusion Based on a population-based prospective cohort analysis, the risk of EoO is significantly higher among patients with IBD and vice versa. Concurrent diagnoses might modify the risk of IBD-related and EoO-related complications. Studies defining the mechanisms underlying these observations are needed.
Endoscopic destruction of a large intrajejunal biliary stone using a polypectomy snare and high Autocut mode
Authors: Jérôme Rivory, Florian Rostain, Mustapha Adham, Jean Christophe Saurin, Thierry Ponchon, Alexandru Lupu, Mathieu Pioche
Journal: Endoscopy (2019)

Biliary stones are usually found in the gallbladder or in the biliary ducts and are sometimes challenging to destroy with mechanical, electrohydraulic, or laser lithotripsy [1] [2]. Gallstone collections in the jejunal limb after duodenopancreatectomy have rarely been reported in the literature [3] [4].
Recurrent Stroke With Rivaroxaban Compared With Aspirin According to Predictors of Atrial Fibrillation
Authors: Jeff S. Healey, David J. Gladstone, Balakumar Swaminathan, Jens Eckstein, Hardi Mundl, Andrew E. Epstein, Karl Georg Haeusler, Robert Mikulik, Scott E. Kasner, Danilo Toni, Antonio Arauz, George Ntaios, Graeme J. Hankey, Kanjana Perera, Jorge Pagola, Ashfaq Shuaib, Helmi Lutsep, Xiaomeng Yang, Shinichiro Uchiyama, Matthias Endres, Shelagh B. Coutts, Michal Karlinski, Anna Czlonkowska, Carlos A. Molina, Gustavo Santo, Scott D. Berkowitz, Robert G. Hart, Stuart J. Connolly
Journal: JAMA Neurology (2019)

The NAVIGATE ESUS randomized clinical trial found that 15 mg of rivaroxaban per day does not reduce stroke compared with aspirin in patients with embolic stroke of undetermined source (ESUS); however, it substantially reduces stroke risk in patients with atrial fibrillation (AF).OBJECTIVE To analyze whether rivaroxaban is associated with a reduction of recurrent stroke among patients with ESUS who have an increased risk of AF.DESIGN, SETTING, AND PARTICIPANTS Participants were stratified by predictors of AF, including left atrial diameter, frequency of premature atrial contractions, and HAVOC score, a validated scheme using clinical features.Treatment interactions with these predictors were assessed.Participants were enrolled between December 2014 and September 2017, and analysis began March 2018. INTERVENTION Rivaroxaban treatment vs aspirin.MAIN OUTCOMES AND MEASURES Risk of ischemic stroke.RESULTS Among 7112 patients with a mean (SD) age of 67 (9.8) years, the mean (SD) HAVOC score was 2.6 (1.8), the mean (SD) left atrial diameter was 3.8 (1.4) cm (n = 4022), and the median (interquartile range) daily frequency of premature atrial contractions was 48 (13-222).Detection of AF during follow-up increased for each tertile of HAVOC score: 2.3% (score, 0-2), 3.0% (score, 3), and 5.8% (score, >3); however, neither tertiles of the HAVOC score nor premature atrial contractions frequency impacted the association of rivaroxaban with recurrent ischemic stroke (P for interaction = .67and .96,respectively).Atrial fibrillation annual incidence increased for each tertile of left atrial diameter (2.0%, 3.6%, and 5.2%) and for each tertile of premature atrial contractions frequency (1.3%, 2.9%, and 7.0%).Among the predefined subgroup of patients with a left atrial diameter of more than 4.6 cm (9% of overall population), the risk of ischemic stroke was lower among the rivaroxaban group (1.7% per year) compared with the aspirin group (6.5% per year) (hazard ratio, 0.26; 95% CI, 0.07-0.94;P for interaction = .02). CONCLUSIONS AND RELEVANCEThe HAVOC score, left atrial diameter, and premature atrial contraction frequency predicted subsequent clinical AF.Rivaroxaban was associated with a reduced risk of recurrent stroke among patients with ESUS and moderate or severe left atrial enlargement; however, this needs to be independently confirmed before influencing clinical practice.
Abstract 18605: Alterations in Cardiac Transcriptome Induced Dilated Cardiomyopathy and Noncompaction in Mlp-K69R Knock-In Mice
Authors: Ryan Hiltenbrand, Undral Munkhsaikhan, Lauren Leiden, Lu Lu, Jeffrey A Towbin, Enkhsaikhan Purevjav
Journal: Circulation (2017)

Introduction: The Cysteine and Glycine-Rich Protein 3 (CSRP3) gene encoding muscle LIM protein (MLP) is a master regulator of cardiac muscle myogenesis and mechanosensing. We previously reported th...
Bloom syndrome protein restrains innate immune sensing of micronuclei by cGAS
Authors: Matthieu Gratia, Mathieu P. Rodero, Cécile Conrad, Elias Bou Samra, Mathieu Maurin, Gillian I. Rice, Darragh Duffy, Patrick Revy, Florence Petit, Russell C. Dale, Yanick J. Crow, Mounira Amor-Gueret, Nicolas Manel
Journal: The Journal of Experimental Medicine (2019)

Cellular innate immune sensors of DNA are essential for host defense against invading pathogens. However, the presence of self-DNA inside cells poses a risk of triggering unchecked immune responses. The mechanisms limiting induction of inflammation by self-DNA are poorly understood. BLM RecQ–like helicase is essential for genome integrity and is deficient in Bloom syndrome (BS), a rare genetic disease characterized by genome instability, accumulation of micronuclei, susceptibility to cancer, and immunodeficiency. Here, we show that BLM-deficient fibroblasts show constitutive up-regulation of inflammatory interferon-stimulated gene (ISG) expression, which is mediated by the cGAS–STING–IRF3 cytosolic DNA–sensing pathway. Increased DNA damage or down-regulation of the cytoplasmic exonuclease TREX1 enhances ISG expression in BLM-deficient fibroblasts. cGAS-containing cytoplasmic micronuclei are increased in BS cells. Finally, BS patients demonstrate elevated ISG expression in peripheral blood. These results reveal that BLM limits ISG induction, thus connecting DNA damage to cellular innate immune response, which may contribute to human pathogenesis.
Reimagining Health—Flourishing
Authors: Tyler J. VanderWeele, Eileen McNeely, Howard K. Koh
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Male GPs earn 33% more than female GPs, finds pay review
Authors: Abi Rimmer
Journal: BMJ (2019)

Male doctors in the NHS earn £1.17 (€1.36; $1.53) for every £1 earned by female doctors, a review of the gender pay gap in medicine has found.1

This represents an improvement on 2016, when the gender pay gap for all doctors was 34%.2

But in primary care the gap remains large with male GPs earning 33% more than female GPs, interim findings from the Gender Pay Gap in Medicine Review, led …
Sexual and reproductive self care among women and girls: insights from ethnographic studies
Authors: Anita Hardon, Christopher Pell, Efenita Taqueban, Manjulaa Narasimhan
Journal: BMJ (2019)

Self Care InterventIonS for Sexual and reproduCtIve HealtHSexual and reproductive self care among women and girls: insights from ethnographic studies Ethnographic studies examining how women manage their sexual and reproductive health can inform strategies to address unmet needs, say Anita Hardon and colleagues P eople often choose to manage their sexual and reproductive health outside health facilities, sometimes using modern medicines obtained from pharmacies, drug stores, and markets.Ethnographic studies of self care practices reveal opportunities to reduce unmet needs and advance human rights based approaches to sexual and reproductive health.We highlight findings from ethnographic studies that show how healthcare professionals could better meet the priorities of women and girls for improved sexual and reproductive health. Anthropologists' studies of self careWith rising prevalence of non-communicable diseases and chronic health problems associated with ageing populations, definitions of health are expanding to include capabilities to adapt and self manage. 1 Public health initiatives increasingly promote healthy eating and exercise, and healthcare providers support patients to monitor and manage their health problems.Medical anthropologists have long sought to understand factors influencing how people take care of themselves.In the 1980s, Kleinman's influential book Patients and Healers in the Context of Culture 2 emphasised the importance of self care and its relation to the medical and traditional healthcare sectors (fig 1).Fo l l o w i n g K l e i n m a n , m e d i c a l anthropologists have shown how self on 12 July