bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of soy and fermented soy product intake with total and cause specific mortality: prospective cohort study
Authors: Katagiri Ryoko , Sawada Norie , Goto Atsushi , Yamaji Taiki , Iwasaki Motoki , Noda Mitsuhiko , Iso Hiroyasu , Tsugane Shoichiro 
Published: January 2020

AbstractObjectiveTo investigate the association between several types of soy products and all cause and cause specific mortality.DesignPopulation based cohort study.SettingJapan Public Health Centre-based Prospective Study, which includes 11 public health centre areas in Japan.Participants92 915 participants (42 750 men and 50 165 women) aged 45 to 74 years.ExposuresIntake of total soy products, fermented soy products (natto and miso), non-fermented soy products, and tofu from a five year survey questionnaire.Main outcome measuresAll cause and cause specific mortality (cancer, total cardiovascular disease, heart disease, cerebrovascular disease, respiratory disease, and injury) obtained from residential registries and death certificates.ResultsDuring 14.8 years of follow-up, 13 303 deaths were identified. In the multivariable adjusted models, intake of total soy products was not significantly associated with total mortality. Compared with the lowest fifth of total soy product intake, the hazard ratios in the highest fifth were 0.98 (95% confidence interval 0.91 to 1.06, Ptrend=0.43) in men and 0.98 (0.89 to 1.08, Ptrend=0.46) in women. Intake of fermented soy products was inversely associated with all cause mortality in both sexes (highest versus lowest fifth: 0.90 (0.83 to 0.97), Ptrend=0.05 in men, and 0.89 (0.80 to 0.98), Ptrend=0.01 in women). Natto showed significant and inverse associations with total cardiovascular disease related mortality in both sexes.ConclusionsIn this study a higher intake of fermented soy was associated with a lower risk of mortality. A significant association between intake of total soy products and all cause mortality was not, however, observed. The findings should be interpreted with caution because the significant association of fermented soy products might be attenuated by unadjusted residual confounding.
Training in endotherapy for acute upper gastrointestinal bleeding: a UK-wide gastroenterology trainee survey
Authors: Segal Jonathan , Siau Keith , Kanagasundaram Cynthia , Askari Alan , Dunckley Paul , Morris Allan John 
Published: January 2020

IntroductionCompetence in endoscopic haemostasis for acute upper gastrointestinal bleeding (AUGIB) is typically expected upon completion of gastroenterology training. However, training in haemostasis is currently variable without a structured training pathway. We conducted a national gastroenterology trainee survey on haemostasis exposure and on attitudes and barriers to training.MethodsA 24-item electronic survey was distributed to UK gastroenterology trainees covering the following domains: demographics, training setup, attitudes and barriers, confidence in managing AUGIB independently and exposure to individual haemostatic modalities (supervised and independent). Responses were analysed by region and training grade to assess potential variation in training.ResultsA total of 181 trainees completed the questionnaire (response rate 33.5%). There was significant variation in AUGIB training setup across the UK (p<0.001), with 22.7% of trainees declaring no access to structured or ad hoc training. 31.5% expressed confidence in managing AUGIB independently; this varied by trainee grade (0% of first-year specialty trainees (ST3s) to 60.7% of final-years (ST7s)) and by training setup (p=0.001). ST7 trainees reported lack of experience with independently applying glue (86%), Hemospray (54%), heater probe (36%) and variceal banding (36%). Overall, 88% of trainees desired additional haemostasis training and 89% indicated support for a national certification process to ensure competence in AUGIB.ConclusionAUGIB training in the UK is variable. The majority of gastroenterology trainees lacked confidence in haemostasis management and desired additional training. Training provision should be urgently reviewed to ensure that trainees receive adequate haemostasis exposure and are competent by completion of training.
SUMO pathway inhibition targets an aggressive pancreatic cancer subtype
Authors: Biederstädt Alexander , Hassan Zonera , Schneeweis Christian , Schick Markus , Schneider Lara , Muckenhuber Alexander , Hong Yingfen , Siegers Gerrit , Nilsson Lisa , Wirth Matthias , Dantes Zahra , Steiger Katja , Schunck Kathrin , Langston Steve , Lenhof H-P , Coluccio Andrea , Orben Felix , Slawska Jolanta , Scherger Anna , Saur Dieter , Müller Stefan , Rad Roland , Weichert Wilko , Nilsson Jonas , Reichert Maximilian , Schneider Günter , Keller Ulrich 
Published: January 2020

ObjectivePancreatic ductal adenocarcinoma (PDAC) still carries a dismal prognosis with an overall 5-year survival rate of 9%. Conventional combination chemotherapies are a clear advance in the treatment of PDAC; however, subtypes of the disease exist, which exhibit extensive resistance to such therapies. Genomic MYC amplifications represent a distinct subset of PDAC with an aggressive tumour biology. It is clear that hyperactivation of MYC generates dependencies that can be exploited therapeutically. The aim of the study was to find and to target MYC-associated dependencies.DesignWe analysed human PDAC gene expression datasets. Results were corroborated by the analysis of the small ubiquitin-like modifier (SUMO) pathway in a large PDAC cohort using immunohistochemistry. A SUMO inhibitor was used and characterised using human and murine two-dimensional, organoid and in vivo models of PDAC.ResultsWe observed that MYC is connected to the SUMOylation machinery in PDAC. Components of the SUMO pathway characterise a PDAC subtype with a dismal prognosis and we provide evidence that hyperactivation of MYC is connected to an increased sensitivity to pharmacological SUMO inhibition.ConclusionSUMO inhibitor-based therapies should be further developed for an aggressive PDAC subtype.
Liver transcriptomics highlights interleukin-32 as novel NAFLD-related cytokine and candidate biomarker
Authors: Baselli Guido Alessandro , Dongiovanni Paola , Rametta Raffaela , Meroni Marica , Pelusi Serena , Maggioni Marco , Badiali Sara , Pingitore Piero , Maurotti Samantha , Montalcini Tiziana , Taliento Alice Emma , Prati Daniele , Rossi Giorgio , Fracanzani Anna Ludovica , Mancina Rosellina Margherita , Romeo Stefano , Valenti Luca 
Published: January 2020

ObjectiveEfforts to manage non-alcoholic fatty liver disease (NAFLD) are limited by the incomplete understanding of the pathogenic mechanisms and the absence of accurate non-invasive biomarkers. The aim of this study was to identify novel NAFLD therapeutic targets andbiomarkers by conducting liver transcriptomic analysis in patients stratified by the presence of thePNPLA3I148M genetic risk variant.DesignWe sequenced the hepatic transcriptome of 125 obese individuals. ‘Severe NAFLD’ was defined as the presence of steatohepatitis, NAFLD activity score ≥4 or fibrosis stage ≥2. The circulating levels of the most upregulated transcript, interleukin-32 (IL32), were measured by ELISA.ResultsCarriage of thePNPLA3I148M variant correlated with the two major components of hepatic transcriptome variability and broadly influenced gene expression. In patients with severe NAFLD, there was an upregulation of inflammatory and lipid metabolism pathways. IL32 was the most robustly upregulated gene in the severe NAFLD group (adjusted p=1×10−6), and its expression correlated with steatosis severity, both in I148M variant carriers and non-carriers. In 77 severely obese, and in a replication cohort of 160 individuals evaluated at the hepatology service, circulating IL32 levels were associated with both NAFLD and severe NAFLD independently of aminotransferases (p<0.01 for both). A linear combination of IL32-ALT-AST showed a better performance than ALT-AST alone in NAFLD diagnosis (area under the curve=0.92 vs 0.81, p=5×10−5).ConclusionHepatic IL32 is overexpressed in NAFLD, correlates with hepatic fat and liver damage, and is detectable in the circulation, where it is independently associated with the presence and severity of NAFLD.
Oral human papillomavirus infection in HIV-infected and HIV-uninfected MSM: the OHMAR prospective cohort study
Authors: Giuliani Massimo , Rollo Francesca , Vescio Maria Fenicia , Pichi Barbara , Latini Alessandra , Benevolo Maria , Pellini Raul , Cristaudo Antonio , Dona' Maria Gabriella 
Published: January 2020

ObjectiveWe aimed to assess incidence and clearance of oral human papillomavirus (HPV) infection and the respective risk factors in HIV-infected and uninfected men who have sex with men (MSM).MethodsOral rinse and gargles were collected semiannually from 244 MSM (103, 42.2% HIV-infected). HPV-DNA testing was performed with the Linear Array HPV Genotyping test. A Markov model was used for estimation of incidence, clearance and risk factor analysis.ResultsIncidence rates for any HPV were 21.2 and 15.0×1000 person-months in HIV-infected and uninfected MSM, respectively. The respective figures for high-risk HPVs were 10.7 and 6.5×1000 person-months. The clearance rate was 4–12 times higher than the respective incidence rate. HIV-infected MSM with >95 lifetime oral sex partners showed increased incidence of any HPV (adjusted HR, aHR: 8.46, 95% CI 1.89 to 37.92). Condomless oral sex appeared the strongest predictor for incident infection by high-risk HPVs in this group (aHR: 13.40, 95% CI 2.55 to 70.53). Those aged >46 years (aHR: 0.30, 95% CI 0.12 to 0.74) and those with nadir CD4+ T count of <200 cells/mm3(aHR: 0.14, 95% CI 0.03 to 0.75) displayed a significantly reduced clearance of any and high-risk HPVs, respectively. HIV-uninfected MSM aged >46 years had increased risk of acquiring any HPV (aHR: 3.70, 95% CI 1.30 to 10.52) and high-risk HPV (aHR: 5.33, 95% CI 1.06 to 26.68). Any HPV clearance declined in those with more than six recent oral sex partners (aHR: 0.18, 95% CI 0.05 to 0.65).ConclusionsAcquisition of oral HPV infection in MSM seems to occur rarely, whereas clearance seems to be a frequent event. Oral HPV natural history in these at-risk subjects is differently influenced by age and sex behaviour, depending on HIV status.
Cosmological and thermodynamics analysis in Weyl gravity
Authors: Jawad Abdul , Khan Zoya , Rani Shamaila 
Published: January 2020

AbstractIn the framework of modified Weyl gravity, we observe the equilibrium picture of the thermodynamical laws for flat Friedmann–Robertson–Walker metric with chameleon scalar field and analyze the validity of the generalized second law of thermodynamics and thermal equilibrium condition for Hubble horizon along with Bekenstien–Hawking entropy. Also, we examine the effective equation of state parameter as well as the square speed of sound. By assuming four different choices of deceleration parameter, we investigate the behavior of equation of state parameter as well as the square speed of sound. The validity of generalized second law of thermodynamics and thermal equilibrium condition is also checked by taking the observational values of the model parameters from CC+$$H_o$$Ho dataset.
On Legendrian cobordisms and generating functions
Authors: Limouzineau Maÿlis 
Published: January 2020

This note concerns Legendrian cobordisms in one-jet spaces of functions, in the sense of Arnol’d [Lagrange and Legendre cobordisms. I, Funkt. Anal. Prilozhen. 14(3) (1980) 1–13, 96.] — consisting of big Legendrian submanifolds between two smaller ones. We are interested in such cobordisms which fit with generating functions, and wonder which structures and obstructions come with this notion. As a central result, we show that the classes of Legendrian concordances with respect to the generating function equipment can be given a group structure. To this construction, we add one of a homotopy with respect to generating functions.
Is Static Analysis Able to Identify Unnecessary Source Code?
Authors: Haas Roman , Niedermayr Rainer , Roehm Tobias , Apel Sven 
Published: January 2020

Grown software systems often contain code that is not necessary anymore. Such unnecessary code wastes resources during development and maintenance, for example, when preparing code for migration or certification. Running a profiler may reveal code that is not used in production, but it is often time-consuming to obtain representative data in this way.
We investigate to what extent a static analysis approach, which is based on code stability and code centrality, is able to identify unnecessary code and whether its recommendations are relevant in practice. To study the feasibility and usefulness of our approach, we conducted a study involving 14 open-source and closed-source software systems. As there is no perfect oracle for unnecessary code, we compared recommendations for unnecessary code with historical cleanups, runtime usage data, and feedback from 25 developers of five software projects. Our study shows that recommendations generated from stability and centrality information point to unnecessary code that cannot be identified by dead code detectors. Developers confirmed that 34% of recommendations were indeed unnecessary and deleted 20% of the recommendations shortly after our interviews. Overall, our results suggest that static analysis can provide quick feedback on unnecessary code and is useful in practice.
Muscle fiber typology substantially influences time to recover from high-intensity exercise
Authors: Lievens Eline , Klass Malgorzata , Bex Tine , Derave Wim 
Published: January 2020

Human fast-twitch muscle fibers generate high power in a short amount of time but are easily fatigued, whereas slow-twitch fibers are more fatigue resistant. The transfer of this knowledge to coaching is hampered by the invasive nature of the current evaluation of muscle typology by biopsies. Therefore, a noninvasive method was developed to estimate muscle typology through proton magnetic resonance spectroscopy in the gastrocnemius. The aim of this study was to investigate whether male subjects with an a priori-determined fast typology (FT) are characterized by a more pronounced Wingate exercise-induced fatigue and delayed recovery compared with subjects with a slow typology (ST). Ten subjects with an estimated higher percentage of fast-twitch fibers and 10 subjects with an estimated higher percentage of slow-twitch fibers underwent the test protocol, consisting of three 30-s all-out Wingate tests. Recovery of knee extension torque was evaluated by maximal voluntary contraction combined with electrical stimulation up to 5 h after the Wingate tests. Although both groups delivered the same mean power across all Wingates, the power drop was higher in the FT group (−61%) compared with the ST group (−41%). The torque at maximal voluntary contraction had fully recovered in the ST group after 20 min, whereas the FT group had not yet recovered 5 h into recovery. This noninvasive estimation of muscle typology can predict the extent of fatigue and time to recover following repeated all-out exercise and may have applications as a tool to individualize training and recovery cycles. NEW & NOTEWORTHY A one-fits-all training regime is present in most sports, though the same training implies different stimuli in athletes with a distinct muscle typology. Individualization of training based on this muscle typology might be important to optimize performance and to lower the risk for accumulated fatigue and potentially injury. When conducting research, one should keep in mind that the muscle typology of participants influences the severity of fatigue and might therefore impact the results.
Impaired Death Receptor Signaling in Leukemia Causes Antigen-Independent Resistance by Inducing CAR T-cell Dysfunction
Authors: Singh Nathan , Lee Yong Gu , Shestova Olga , Ravikumar Pranali , Hayer Katharina E. , Hong Seok Jae , Lu Xueqing Maggie , Pajarillo Raymone , Agarwal Sangya , Kuramitsu Shunichiro , Orlando Elena J. , Mueller Karen Thudium , Good Charly R. , Berger Shelley L. , Shalem Ophir , Weitzman Matthew D. , Frey Noelle V. , Maude Shannon L. , Grupp Stephan A. , June Carl H. , Gill Saar , Ruella Marco 
Published: January 2020

Abstract

Primary resistance to CD19-directed chimeric antigen receptor T-cell therapy (CART19) occurs in 10% to 20% of patients with acute lymphoblastic leukemia (ALL); however, the mechanisms of this resistance remain elusive. Using a genome-wide loss-of-function screen, we identified that impaired death receptor signaling in ALL led to rapidly progressive disease despite CART19 treatment. This was mediated by an inherent resistance to T-cell cytotoxicity that permitted antigen persistence and was subsequently magnified by the induction of CAR T-cell functional impairment. These findings were validated using samples from two CAR T-cell clinical trials in ALL, where we found that reduced expression of death receptor genes was associated with worse overall survival and reduced T-cell fitness. Our findings suggest that inherent dysregulation of death receptor signaling in ALL directly leads to CAR T-cell failure by impairing T-cell cytotoxicity and promoting progressive CAR T-cell dysfunction.

Significance:
Resistance to CART19 is a significant barrier to efficacy in the treatment of B-cell malignancies. This work demonstrates that impaired death receptor signaling in tumor cells causes failed CART19 cytotoxicity and drives CART19 dysfunction, identifying a novel mechanism of antigen-independent resistance to CAR therapy.
See related commentary by Green and Neelapu, p. 492.
Soluble Uric Acid Promotes Atherosclerosis via AMPK (AMP-Activated Protein Kinase)-Mediated Inflammation
Authors: Kimura Yoshitaka , Yanagida Tamiko , Onda Akiko , Tsukui Daisuke , Hosoyamada Makoto , Kono Hajime 
Published: January 2020

Objective:
Uric acid is supposed but not yet determined to be associated with atherosclerosis. Uric acid is released from damaged cells to form urate crystal, which is recognized by the immune system to produce IL (interleukin)-1. Danger signals and IL-1 have been shown to play an important role in atherosclerosis. We determined whether the physiological level of soluble uric acid promotes inflammation and develops atherosclerosis.

Approach and Results:
The secretion of IL-1β from human peripheral blood mononuclear cells mediated by NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome was promoted by physiological levels in serum uric acid. This augmentation of inflammation was mediated by the regulation of the AMPK (AMP-activated protein kinase)-mTOR (mammalian target of rapamycin) mitochondrial reactive oxygen species and HIF-1α (hypoxia-inducible factor-1α) pathway. In both of uricase transgenic and xanthine oxidase inhibitor–treated mice, decreased levels of uric acid resulted in the activation of AMPK and attenuation of the development of atherosclerotic plaques. Further, acute uric acid reduction by the administration of benzbromarone in healthy humans for 2 weeks significantly decreased plasma IL-18—an inflammasome-dependent cytokine.

Conclusions:
The data indicate that the development of atherosclerosis and inflammation is promoted by uric acid in vivo. Moreover, the lowering of uric acid levels attenuated inflammation via the activation of the AMPK pathway. This study provides mechanistic evidence of uric acid–lowering therapies for atherosclerosis.
Interleukin-1 Beta–Mediated Sex Differences in Kawasaki Disease Vasculitis Development and Response to Treatment
Authors: Porritt Rebecca A. , Markman Janet L. , Maruyama Daisuke , Kocaturk Begum , Chen Shuang , Lehman Thomas J.A. , Lee Youngho , Fishbein Michael C. , Noval Rivas Magali , Arditi Moshe 
Published: January 2020

Objective:
Kawasaki disease (KD) is the leading cause of acute vasculitis and acquired heart disease in children in developed countries. Notably, KD is more prevalent in males than females. We previously established a key role for IL (interleukin)-1 signaling in KD pathogenesis, but whether this pathway underlies the sex-based difference in susceptibility is unknown.

Approach and Results:

The role of IL-1 signaling was investigated in the
Lactobacillus casei
cell wall extract-induced experimental mouse model of KD vasculitis. Five-week-old male and female mice were injected intraperitoneally with PBS,
Lactobacillus casei
cell wall extract, or a combination of
Lactobacillus casei
cell wall extract and the IL-1 receptor antagonist Anakinra. Aortitis, coronary arteritis inflammation score and abdominal aorta dilatation, and aneurysm development were assessed. mRNA-seq (messenger RNA sequencing) analysis was performed on abdominal aorta tissue. Publicly available human transcriptomics data from patients with KD was analyzed to identify sex differences and disease-associated genes. Male mice displayed enhanced aortitis and coronary arteritis as well as increased incidence and severity of abdominal aorta dilatation and aneurysm, recapitulating the increased incidence in males that is observed in human KD. Gene expression data from patients with KD and abdominal aorta tissue of
Lactobacillus casei
cell wall extract-injected mice showed enhanced
Il1b
expression and IL-1 signaling genes in males. Although the more severe IL-1β–mediated disease phenotype observed in male mice was ameliorated by Anakinra treatment, the milder disease phenotype in female mice failed to respond.

Conclusions:
IL-1β may play a central role in mediating sex-based differences in KD, with important implications for the use of anti–IL-1β therapies to treat male and female patients with KD.
Effects of Polyethylene Glycol‐20k on Coronary Perfusion Pressure and Postresuscitation Myocardial and Cerebral Function in a Rat Model of Cardiac Arrest
Authors: Ge Weiwei , Zheng Guanghui , Ji Xianfei , He Fenglian , Hu Juntao , Bradley Jennifer L. , Moore Christine E. , Peberdy Mary A. , Ornato Joseph P. , Mangino Martin J. , Tang Wanchun 
Published: January 2020

Background

Epinephrine increases the rate of return of spontaneous circulation. However, it increases severity of postresuscitation myocardial and cerebral dysfunction and reduces duration of survival. We investigated the effects of aortic infused polyethylene glycol, 20 000 molecular weight (
PEG
‐20k) during cardiopulmonary resuscitation on coronary perfusion pressure, postresuscitation myocardial and cerebral function, and duration of survival in a rat model of cardiac arrest.

Methods and Results

Twenty‐four male rats were randomized into 4 groups: (1)
PEG
‐20k, (2) epinephrine, (3) saline control–intravenous, and (4) saline control–intra‐aortic. Cardiopulmonary resuscitation was initiated after 6 minutes of untreated ventricular fibrillation. In
PEG
‐20k and Saline‐A, either
PEG
‐20k (10% weight/volume in 10% estimated blood volume infused over 3 minutes) or saline was administered intra‐aortically after 4 minutes of precordial compression. In epinephrine and placebo groups, either epinephrine (20 μg/kg) or saline placebo was administered intravenously after 4 minutes of precordial compression. Resuscitation was attempted after 8 minutes of cardiopulmonary resuscitation. Sublingual microcirculation was measured at baseline and 1, 3, and 5 hours after return of spontaneous circulation. Myocardial function was measured at baseline and 2, 4, and 6 hours after return of spontaneous circulation. Neurologic deficit scores were recorded at 24, 48, and 72 hours after return of spontaneous circulation. Aortic infusion of
PEG
‐20k increased coronary perfusion pressure to the same extent as epinephrine. Postresuscitation sublingual microcirculation, myocardial and cerebral function, and duration of survival were improved in
PEG
‐20k (
P
<0.05) compared with epinephrine (
P
<0.05).

Conclusions

Aortic infusion of
PEG
‐20k during cardiopulmonary resuscitation increases coronary perfusion pressure to the same extent as epinephrine, improves postresuscitation myocardial and cerebral function, and increases duration of survival in a rat model of cardiac arrest.