tbuckley/cabot-search huggingface dataset:
Abstract 11092: Higher Risk Prognosis for Major Cardiac Events in Hypertrophic Cardiomyopathy with Myocardial Fibrosis by CT Following a Median of 32 Months Using Kaplan-Meier and Cox Proportional Hazard Regression
Authors: Hiroyuki Takaoka, Nobusada Funabashi, Masae Uehara, Yoshio Kobayashi
Journal: Circulation (2011)

Purpose:  To evaluate the prognosis of hypertrophic cardiomyopathy (HCM) patients after cardiac CT and compare the risk of major adverse cardiac events (MACE) between HCM patients with and without focal myocardial fibrosis (MF) on CT using a Kaplan-Meier and Cox proportional hazard model.   Material and methods:  A total of 57 consecutive patients with HCM by transthoracic echocardiogram, (39 male, mean age 62.2 ± 14.4 years, Maron type 1 (8), type 2 (1), type 3 (32), and type 5 (16)), who had suspected coronary artery disease without old myocardial infarction and who underwent cardiac CT on which no significant luminal stenosis (>50%) was observed, were included. Enhanced ECG gated MSCT was performed at 30 seconds and 6 minutes after contrast injection to detect MF as contrast defects in the early phase and abnormal enhancement in late phase. Patients were followed for a median of 43.0 ± 29.8 months after cardiac CT. The incidence of MACE was compared with a Kaplan -Meier analysis and the log rank statistic.   Result:  MF on CT was detected in 31 subjects. Patients with MF had a higher risk of MACE (22.6%) than those without (3.8%; p=0.04) during the observation period. Significant differences between HCM subjects with and without MF were also seen at each time point and when the whole period of follow-up was compared with a Kaplan-Meier and log rank test (p=0.02; Figure). A Cox proportional hazards model was used to test the significance of MF on CT as a predictor of MACE considering the influence of male sex, left ventricular asynergy, hypertrophic obstructive cardiomyopachy, apical hypertrophy, and time duration from the onset of HCM. This analysis revealed that the presence of MF on CT was a predictor of MACE (Hazard ratio 17.0, p=0.03).   Conclusion:  HCM patients without coronary luminal stenosis but with MF on cardiac CT had a higher risk of MACE than those without following a median of 32 months using a Kaplan-Meier analysis and Cox proportional hazard regression with a hazard ratio of 16.6.
Gut-liver interactions in celiac disease: FGF-19 and GLP-1 link disease activity to hepatic steatosis and liver injury
Authors: S. Sydor, P.P. Manka, J. Schänzer, I. Messerschmidt, S. Kinner, A. Link, H. Moshage, K.N. Faber, G. Gerken, A. Canbay, L.P. Bechmann
Journal: Journal of Hepatology (2018)
Communication About Prognosis With Adolescent and Young Adult Patients With Cancer: Information Needs, Prognostic Awareness, and Outcomes of Disclosure
Authors: Jennifer W. Mack, Karen M. Fasciano, Susan D. Block
Journal: Journal of Clinical Oncology (2018)

Purpose Communication about prognosis affects decisions patients and family members make about cancer care, and most patients say they want to know about their chances of cure. We sought to evaluate experiences with prognosis communication among adolescents and young adults (AYAs) with cancer. Patients and Methods We surveyed 203 AYAs with cancer age 15 to 29 years (response rate, 74%) treated at Dana-Farber Cancer Institute and their oncologists. Patients were approached within 6 weeks of diagnosis and asked to report on their prognosis communication preferences and experiences, their beliefs about likelihood of cure, and psychosocial outcomes of communication, such as trust (using an item from the Trust in Physician Scale), peace of mind (using select items from the Functional Assessment of Chronic Illness Therapy–Spiritual Well-Being Scale), and anxiety and depression (using the Hospital Anxiety and Depression Scale). Oncologists were asked to report the patient’s likelihood of cure. Results Most patients (83%, 167 of 203 patients) considered prognostic information to be extremely or very important. Patients who reported having received more extensive prognostic disclosure had higher odds of trust in the oncologist (odds ratio [OR], 1.30; 95% CI, 1.01 to 1.67; P = .05), peace of mind (OR, 2.13; 95% CI, 1.29 to 3.51; P = .002), and hope related to physician communication (OR, 1.27; 95% CI, 1.01 to 1.59; P = .04), after adjusting for patient sex, age, race or ethnicity, prognosis, and diagnosis. Disclosure was also associated with lower distress related to knowing about prognosis (OR, 0.65; 95% CI, 0.44 to 0.95; P = .03). However, a majority of patients (62%) reported prognostic estimates that exceeded those reported by physicians (McNemar P &lt; .001). Conclusion Most AYAs with cancer value receiving prognostic information, which is positively associated with aspects of well-being. However, most overestimate chances of cure relative to oncologists, highlighting the importance of efforts to improve communication with this young population.
The Impact of proton pump inhibitors on the intestinal microbiota in chronic hepatitis C patients
Authors: F. Wellhöner, N. Döscher, V. Marius, I. Plumeier, S. Kahl, A. Potthoff, M.P. Manns, P. Dietmar, H. Wedemeyer, M. Cornberg, B. Heidrich
Journal: Journal of Hepatology (2018)
Mitochondrial cyclophilin D regulates T cell metabolic responses and disease tolerance to tuberculosis
Authors: Fanny Tzelepis, Julianna Blagih, Nargis Khan, Joshua Gillard, Laura Mendonca, Dominic G. Roy, Eric H. Ma, Philippe Joubert, Russell G. Jones, Maziar Divangahi
Journal: Science Immunology (2018)

Mycobacterium tuberculosis (Mtb) is one of the most ancient human pathogens, yet the exact mechanism(s) of host defense against Mtb remains unclear. Although one-third of the world's population is chronically infected with Mtb, only 5 to 10% develop active disease. This indicates that, in addition to resistance mechanisms that control bacterial burden, the host has also evolved strategies to tolerate the presence of Mtb to limit disease severity. We identify mitochondrial cyclophilin D (CypD) as a critical checkpoint of T cell metabolism that controls the expansion of activated T cells. Although loss of CypD function in T cells led to enhanced Mtb antigen-specific T cell responses, this increased T cell response had no impact on bacterial burden. Rather, mice containing CypD-deficient T cells exhibited substantially compromised disease tolerance and succumbed to Mtb infection. This study establishes a mechanistic link between T cell-mediated immunity and disease tolerance during Mtb infection.
TCTAP A-044 Mid-term Angiographic Performance of a Self-expanding Sirolimus-eluting Stent for Left Main Percutaneous Coronary Intervention: A Substudy of the MATISSE Registry
Authors: Bernardo Cortese, Gaetano Di Palma, Paolo Sganzerla, Gioel G. Secco, Giuseppe Ando, Pedro silva Orrego, Romano G. Seregni
Journal: Journal of the American College of Cardiology (2018)
HIV-1 replicates and persists in vaginal epithelial dendritic cells
Authors: Victor Pena-Cruz, Luis M. Agosto, Hisashi Akiyama, Alex Olson, Yvetane Moreau, Jean-Robert Larrieux, Andrew Henderson, Suryaram Gummuluru, Manish Sagar
Journal: Journal of Clinical Investigation (2018)

HIV-1 acquisition occurs most commonly after sexual contact. To establish infection, HIV-1 must infect cells that support high-level replication, namely CD4+ T cells, which are absent from the outermost genital epithelium. Dendritic cells (DCs), present in mucosal epithelia, potentially facilitate HIV-1 acquisition. We show that vaginal epithelial DCs, termed CD1a+ VEDCs, are unlike other blood- and tissue-derived DCs because they express langerin but not DC-SIGN, and unlike skin-based langerin+ DC subset Langerhans cells (LCs), they do not harbor Birbeck granules. Individuals primarily acquire HIV-1 that utilizes the CCR5 receptor (termed either R5 or R5X4) during heterosexual transmission, and the mechanism for the block against variants that only use the CXCR4 receptor (classified as X4) remains unclear. We show that X4 as compared with R5 HIV-1 shows limited to no replication in CD1a+ VEDCs. This differential replication occurs after fusion, suggesting that receptor usage influences postentry steps in the virus life cycle. Furthermore, CD1a+ VEDCs isolated from HIV-1-infected virologically suppressed women harbor HIV-1 DNA. Thus, CD1a+ VEDCs are potentially infected early during heterosexual transmission and also retain virus during treatment. Understanding the interplay between HIV-1 and CD1a+ VEDCs is important for future prevention and cure strategies.
Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis
Authors: Pengcheng Bu, Kai-Yuan Chen, Kun Xiang, Christelle Johnson, Scott B. Crown, Nikolai Rakhilin, Yiwei Ai, Lihua Wang, Rui Xi, Inna Astapova, Yan Han, Jiahe Li, Bradley B. Barth, Min Lu, Ziyang Gao, Robert Mines, Liwen Zhang, Mark Herman, David Hsu, Guo-Fang Zhang, Xiling Shen
Journal: Cell Metabolism (2018)
The Association of Mediterranean and DASH Diets with Mortality in Adults on Hemodialysis: The DIET-HD Multinational Cohort Study
Authors: Valeria M. Saglimbene, Germaine Wong, Jonathan C. Craig, Marinella Ruospo, Suetonia C. Palmer, Katrina Campbell, Vanessa Garcia-Larsen, Patrizia Natale, Armando Teixeira-Pinto, Juan-Jesus Carrero, Peter Stenvinkel, Letizia Gargano, Angelo M. Murgo, David W. Johnson, Marcello Tonelli, Rubén Gelfman, Eduardo Celia, Tevfik Ecder, Amparo G. Bernat, Domingo Del Castillo, Delia Timofte, Marietta Török, Anna Bednarek-Skublewska, Jan Duława, Paul Stroumza, Susanne Hoischen, Martin Hansis, Elisabeth Fabricius, Paolo Felaco, Charlotta Wollheim, Jörgen Hegbrant, Giovanni F.M. Strippoli
Journal: Journal of the American Society of Nephrology (2018)

Background Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets associate with lower cardiovascular and all-cause mortality in the general population, but the benefits for patients on hemodialysis are uncertain.Methods Mediterranean and DASH diet scores were derived from the GA2LEN Food Frequency Questionnaire within the DIET-HD Study, a multinational cohort study of 9757 adults on hemodialysis. We conducted adjusted Cox regression analyses clustered by country to evaluate the association between diet score tertiles and all-cause and cardiovascular mortality (the lowest tertile was the reference category).Results During the median 2.7-year follow-up, 2087 deaths (829 cardiovascular deaths) occurred. The adjusted hazard ratios (95% confidence intervals) for the middle and highest Mediterranean diet score tertiles were 1.20 (1.01 to 1.41) and 1.14 (0.90 to 1.43), respectively, for cardiovascular mortality and 1.10 (0.99 to 1.22) and 1.01 (0.88 to 1.17), respectively, for all-cause mortality. Corresponding estimates for the same DASH diet score tertiles were 1.01 (0.85 to 1.21) and 1.19 (0.99 to 1.43), respectively, for cardiovascular mortality and 1.03 (0.92 to 1.15) and 1.00 (0.89 to 1.12), respectively, for all-cause mortality. The association between DASH diet score and all-cause death was modified by age (P=0.03); adjusted hazard ratios for the middle and highest DASH diet score tertiles were 1.02 (0.81 to 1.29) and 0.70 (0.53 to 0.94), respectively, for younger patients (≤60 years old) and 1.05 (0.93 to 1.19) and 1.08 (0.95 to 1.23), respectively, for older patients.Conclusions Mediterranean and DASH diets did not associate with cardiovascular or total mortality in hemodialysis.
Do highly physically active workers die early? A systematic review with meta-analysis of data from 193 696 participants
Authors: Pieter Coenen, Maaike A Huysmans, Andreas Holtermann, Niklas Krause, Willem van Mechelen, Leon M Straker, Allard J van der Beek
Journal: British Journal of Sports Medicine (2018)

Recent evidence suggests the existence of a physical activity paradox, with beneficial health outcomes associated with leisure time physical activity, but detrimental health outcomes for those engaging in high level occupational physical activity. This is the first quantitative systematic review of evidence regarding the association between occupational physical activity and all-cause mortality.Systematic review with meta-analysis.A literature search was performed in electronic databases PubMed, Embase, CINAHL, PsycINFO and Cochrane.We screened for peer reviewed articles from prospective studies assessing the association of occupational physical activity with all-cause mortality. A meta-analysis assessed the association of high (compared with low) level occupational physical activity with all-cause mortality, estimating pooled hazard ratios (HR) (with 95% CI).2490 unique articles were screened and 33 (from 26 studies) were included. Data from 17 studies (with 193 696 participants) were used in a meta-analysis, showing that men with high level occupational physical activity had an 18% increased risk of early mortality compared with those engaging in low level occupational physical activity (HR 1.18, 95% CI 1.05 to 1.34). No such association was observed among women, for whom instead a tendency for an inverse association was found (HR 0.90, 95% CI 0.80 to 1.01).The results of this review indicate detrimental health consequences associated with high level occupational physical activity in men, even when adjusting for relevant factors (such as leisure time physical activity). These findings suggest that research and physical activity guidelines may differentiate between occupational and leisure time physical activity.
Dysregulated phosphorylation of Rab GTPases by LRRK2 induces neurodegeneration
Authors: Ga Ram Jeong, Eun-Hae Jang, Jae Ryul Bae, Soyoung Jun, Ho Chul Kang, Chi-Hu Park, Joo-Ho Shin, Yukio Yamamoto, Keiko Tanaka-Yamamoto, Valina L. Dawson, Ted M. Dawson, Eun-Mi Hur, Byoung Dae Lee
Journal: Molecular Neurodegeneration (2018)

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial and sporadic Parkinson's disease (PD). Elevated kinase activity is associated with LRRK2 toxicity, but the substrates that mediate neurodegeneration remain poorly defined. Given the increasing evidence suggesting a role of LRRK2 in membrane and vesicle trafficking, here we systemically screened Rab GTPases, core regulators of vesicular dynamics, as potential substrates of LRRK2 and investigated the functional consequence of such phosphorylation in cells and in vivo. In vitro LRRK2 kinase assay with forty-five purified human Rab GTPases was performed to identify Rab family proteins as substrates of LRRK2. We identified the phosphorylation site by tandem mass-spectrometry and confirmed it by assessing phosphorylation in the in vitro LRRK2 kinase assay and in cells. Effects of Rab phosphorylation on neurodegeneration were examined in primary cultures and in vivo by intracranial injection of adeno-associated viral vectors (AAV) expressing wild-type or phosphomutants of Rab35. Our screening revealed that LRRK2 phosphorylated several Rab GTPases at a conserved threonine residue in the switch II region, and by using the kinase-inactive LRRK2-D1994A and the pathogenic LRRK2-G2019S along with Rab proteins in which the LRRK2 site was mutated, we verified that a subset of Rab proteins, including Rab35, were authentic substrates of LRRK2 both in vitro and in cells. We also showed that phosphorylation of Rab regulated GDP/GTP-binding property in cells. Moreover, in primary cortical neurons, mutation of the LRRK2 site in several Rabs caused neurotoxicity, which was most severely induced by phosphomutants of Rab35. Furthermore, intracranial injection of the AAV-Rab35 -T72A or AAV-Rab35-T72D into the substantia nigra substantially induced degeneration of dopaminergic neurons in vivo. Here we show that a subset of Rab GTPases are authentic substrates of LRRK2 both in vitro and in cells. We also provide evidence that dysregulation of Rab phosphorylation in the LRRK2 site induces neurotoxicity in primary neurons and degeneration of dopaminergic neurons in vivo. Our study suggests that Rab GTPases might mediate LRRK2 toxicity in the progression of PD.
Successful removal of a bezoar: treatment of a rare complication after Billroth II surgery
Authors: Yajun Shou, Yuyong Tan, Deliang Liu
Journal: Endoscopy (2018)

A 68-year-old man presented to our hospital with paroxysmal abdominal pain for 2 months. He had undergone a Billroth II operation 11 months previously, and esophagogastroduodenoscopy at another hospital 1 month ago had shown an anastomotic ulcer. However, his abdominal pain had not been relieved by administration of strong proton-pump inhibitors.
P551Effects of interferon gamma on endothelial barrier function: differential role of classical and non-classical pathways
Authors: S Mahmood, N Sevinc, C Troidl, R Schulz, B Schiefer, C Tanislav, D Guenduez, C W Hamm, M Aslam
Journal: Cardiovascular Research (2018)

in CON, reflected in an increased MO2ex (P<0.05), while it had no effect in DMþHFDþCKD, suggesting that loss of NO was principally responsible for the perturbation in myocardial oxygen delivery in DMþHFDþCKD (Figure).This was supported by lower myocardial levels of NO2-þNO3in DMþHFDþCKD compared to CON (0.2060.02 vs 0.3460.06mmol/mg protein, P<0.05).Isolated vessels of DMþHFDþCKD swine showed decreased endothelial dependent vasodilation to BK, mediated via a complete abolishment of the NO-dependent vasodilator pathway, consistent with the in vivo observations.Conclusion: Prolonged exposure to DM, HFD and CKD results in a pro-inflammatory state associated with impaired coronary microvascular NO production, thereby altering coronary microvascular dilation and hampering myocardial perfusion.
Abstract 16419: Healthcare Professionals' Perspectives on Implantable Cardioverter Defibrillator Deactivation: A Systematic Review
Authors: Donna Fitzsimons, Loreena Hill, Sonja McIlfatrick, Brian Taylor
Journal: Circulation (2017)

Introduction: In an era of advancing technology and clinical expertise, many dying patients with an Implantable Cardioverter Defibrillators (ICD) experience inappropriate shocks. Professional guidance to improve patient care is urgently needed.Aim: To evaluate the evidence on healthcare professionals’ perspectives on ICD deactivation at end-of-life.Methods: A systematic search of six electronic databases, using key terms identified from a preliminary scoping exercise. Empirical studies, as well as articles recommended by experts and citations, that met the inclusion criteria, were included. Twenty-two articles were selected and assessed for eligibility, resulting in 12 studies reviewed for quality (Hawker et al. 2002). Consensus from the research team was obtained before findings from all 12 studies were synthesised using narrative approach (Popay et al. 2006).Results: Studies included a total of 3535 professionals and representatives from 47 European centres. Majority (n=9) of studies were conducted in United States of America. Three main themes identified, Reluctance to initiate the discussion was found across all clinical practice settings. There was generalized agreement that the discussion should be initiated by a cardiologist, however there was diverse opinion (n=5) on the appropriateness of this discussion during pre-implantation consent process. Routinely, professionals associated the discussion with a Do-Not-Resuscitate order. Ethical and legal concerns were portrayed in most studies (n=7). Professionals agreed deactivation was ethically and legally permissible when the patient was terminally ill. Concerns were highlighted regarding the management of the patient with cognitive impairment. Desire for improved knowledge and guidance was mentioned by nine studies. Professionals not employed within a cardiac specialty requested additional knowledge and skills. Expert guidelines could be used to inform institutional protocols, flexible to meet the needs of individual patients.Conclusion: A paradigm shift in terms of who is responsible for this decision is overdue. A multidisciplinary team approach would encourage nursing staff to play a pivotal role concerning ICD deactivation.
P269Hearts subjected to ischemia-reperfusion benefit from adenine nucleotide translocase 1 overexpression
Authors: J Heger, O Lynetskiy, G Euler, K-D Schlueter, R Schulz, A Doerner
Journal: Cardiovascular Research (2018)

glibenclamide group (n¼11) spontaneously defibrillated within the time analyzed (v 2 (2)¼26,456, p<0.001).Conclusion: Activation of IKATP exerts arrhythmogenic and deleterious electrophysiological effects during normoxia and ischemic conditions.Blockade of KATP channels during ischemia has shown antiarrythmic properties.The electrophysiological effects of training on the events analyzed do not seem to be mediated by KATP opening.Further research must be taken in order to clarify the role of KATP chanels in the protective mechanisms elicited by physical training.
Retinopathy of prematurity
Authors: C. M Wilson, A. R Fielder
Journal: BMJ (2008)

The figure⇓ is a wide field image taken with a RetCam (Clarity Inc, Pleasanton, CA, USA) at 39+4 weeks’ postmenstrual age from a baby born at 27+5 weeks’ gestation (birth weight 940 g). He needed prolonged ventilation for respiratory distress syndrome, and he underwent surgery for necrotising enterocolitis. Now aged 5, he is seen regularly at the eye clinic for myopia and intermittent exotropia, which his mother reports is most obvious at the end of the day.





### Short answers



Fig 2 Retinopathy of prematurity pathology visible on image



### Long answers

#### 1 Which preterm babies should be screened?

Retinopathy of prematurity is a potentially preventable cause of blindness in children. The proportion of childhood blindness …
PML Recruits TET2 to Regulate DNA Modification and Cell Proliferation in Response to Chemotherapeutic Agent
Authors: Chengli Song, Lina Wang, Xiaoyan Wu, Kai Wang, Dan Xie, Qi Xiao, Songyu Li, Kui Jiang, Lujian Liao, John R. Yates, Jiing-Dwan Lee, Qingkai Yang
Journal: Cancer Research (2018)

Abstract Aberrant DNA methylation plays a critical role in the development and progression of cancer. Failure to demethylate and to consequently reactivate methylation-silenced genes in cancer contributes to chemotherapeutic resistance, yet the regulatory mechanisms of DNA demethylation in response to chemotherapeutic agents remain unclear. Here, we show that promyelocytic leukemia (PML) recruits ten–eleven translocation dioxygenase 2 (TET2) to regulate DNA modification and cell proliferation in response to chemotherapeutic agents. TET2 was required by multiple chemotherapeutic agents (such as doxorubicin) to prmote 5-hydroxymethylcytosine (5hmC) formation. Stable isotope labeling with amino acids in cell culture, followed by immunoprecipitation–mass spectrometry, identified potential binding partners of TET2, of which PML mostly enhanced 5hmC formation. PML physically bound to TET2 via the PML C-terminal domain and recruited TET2 to PML-positive nuclear bodies. This interaction was disrupted by the PML-RARA t(15;17) mutation, which stems from chromosomal translocation between DNA encoding the C-terminal domain of PML and the retinoic acid receptor alpha (RARA) gene. In response to chemotherapeutic drugs, PML recruited TET2, regulated DNA modification, reactivated methylation-silenced genes, and impaired cell proliferation. Knockout of PML abolished doxorubicin-promoted DNA modification. In addition, PML and TET2 levels positively correlated with improved overall survival in patients with head and neck cancer. These findings shed insight into the regulatory mechanisms of DNA modification in response to chemotherapeutic agents. Significance: Promyeloctic leukemia protein recruits TET2, regulating DNA modification and cell proliferation in response to chemotherapeutic agents. Cancer Res; 78(10); 2475–89. ©2018 AACR.