bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone H3K27 demethylase KDM6A is an epigenetic gatekeeper of mTORC1 signalling in cancer
Authors: Revia Steffie , Seretny Agnieszka , Wendler Lena , Banito Ana , Eckert Christoph , Breuer Kersten , Mayakonda Anand , Lutsik Pavlo , Evert Matthias , Ribback Silvia , Gallage Suchira , Chikh Bakri Ismaiel , Breuhahn Kai , Schirmacher Peter , Heinrich Stefan , Gaida Matthias M , Heikenwälder Mathias , Calvisi Diego F , Plass Christoph , Lowe Scott W , Tschaharganeh Darjus F 
Published: September 2021

ObjectiveLarge-scale genome sequencing efforts of human tumours identified epigenetic modifiers as one of the most frequently mutated gene class in human cancer. However, how these mutations drive tumour development and tumour progression are largely unknown. Here, we investigated the function of the histone demethylase KDM6A in gastrointestinal cancers, such as liver cancer and pancreatic cancer.DesignGenetic alterations as well as expression analyses of KDM6A were performed in patients with liver cancer. Genetic mouse models of liver and pancreatic cancer coupled with Kdm6a-deficiency were investigated, transcriptomic and epigenetic profiling was performed, and in vivo and in vitro drug treatments were conducted.ResultsKDM6A expression was lost in 30% of patients with liver cancer. Kdm6a deletion significantly accelerated tumour development in murine liver and pancreatic cancer models. Kdm6a-deficient tumours showed hyperactivation of mTORC1 signalling, whereas endogenous Kdm6a re-expression by inducible RNA-interference in established Kdm6a-deficient tumours diminished mTORC1 activity resulting in attenuated tumour progression. Genome-wide transcriptional and epigenetic profiling revealed direct binding of Kdm6a to crucial negative regulators of mTORC1, such as Deptor, and subsequent transcriptional activation by epigenetic remodelling. Moreover, in vitro and in vivo genetic epistasis experiments illustrated a crucial function of Deptor and mTORC1 in Kdm6a-dependent tumour suppression. Importantly, KDM6A expression in human tumours correlates with mTORC1 activity and KDM6A-deficient tumours exhibit increased sensitivity to mTORC1 inhibition.ConclusionKDM6A is an important tumour suppressor in gastrointestinal cancers and acts as an epigenetic toggle for mTORC1 signalling. Patients with KDM6A-deficient tumours could benefit of targeted therapy focusing on mTORC1 inhibition.
Association of carbohydrate and saturated fat intake with cardiovascular disease and mortality in Australian women
Authors: Gribbin Sarah , Enticott Joanne , Hodge Allison M , Moran Lisa , Thong Eleanor , Joham Anju , Zaman Sarah 
Published: September 2021

BackgroundConflicting evidence surrounds the effect of dietary macronutrient intake (fat, carbohydrate and protein) on cardiovascular disease (CVD), particularly in women.MethodsWomen (aged 50–55 years) were recruited into the Australian Longitudinal Study on Women’s Health. Women were divided into quintiles according to their carbohydrate and saturated fat intake as a percentage of total energy intake (TEI). The primary endpoint was new-onset CVD (heart disease/stroke). Secondary endpoints included all-cause mortality, incident hypertension, obesity and/or diabetes mellitus. Multivariate logistic regression models assessed for associations with the primary and secondary endpoints, with adjustment for confounders.ResultsA total of 9899 women (mean age 52.5±1.5 years) were followed for 15 years, with 1199 incident CVD and 470 deaths. On multivariable analysis, higher carbohydrate intake was associated with lower CVD risk (ptrend<0.01), with the lowest CVD risk for quintile 3 (41.0%–44.3% energy as carbohydrate) versus quintile 1 (<37.1% energy as carbohydrate) (OR 0.56, 95% CI 0.35 to 0.91, p=0.02). There was no significant association between carbohydrate intake and mortality (ptrend=0.69) or between saturated fat intake and CVD (ptrend=0.29) or mortality (ptrend=0.25). Both increasing saturated fat and carbohydrate intake were significantly inversely associated with hypertension, diabetes mellitus and obesity (ptrend<0.01 for all).ConclusionsIn middle-aged Australian women, moderate carbohydrate intake (41.0%–44.3% of TEI) was associated with the lowest risk of CVD, without an effect on total mortality. Increasing saturated fat intake was not associated with CVD or mortality and instead correlated with lower rates of diabetes, hypertension and obesity.
Hydration for prevention of kidney injury after primary coronary intervention for acute myocardial infarction: a randomised clinical trial
Authors: Liu Yong , Tan Ning , Huo Yong , Chen Shiqun , Liu Jin , Chen Yun-Dai , Wu Keng , Wu Guifu , Chen Kaihong , Ye Jianfeng , Liang Yan , Feng Xinwu , Dong Shaohong , Wu Qiming , Ye Xianhua , Zeng Hesong , Zhang Minzhou , Dai Min , Duan Chong-Yang , Sun Guoli , He Yibo , Song Feier , Guo Zhaodong , Chen Ping-Yan , Ge Junbo , Xian Ying , Chen Jiyan 
Published: September 2021

ObjectiveTo evaluate the efficacy of aggressive hydration compared with general hydration for contrast-induced acute kidney injury (CI-AKI) prevention among patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI).MethodsThe Aggressive hydraTion in patients with STEMI undergoing pPCI to prevenT Contrast-Induced Acute Kidney Injury study is an open-label, randomised controlled study at 15 teaching hospitals in China. A total of 560 adult patients were randomly assigned (1:1) to receive aggressive hydration or general hydration treatment. Aggressive hydration group received preprocedural loading dose of 125/250 mL normal saline within 30 min, followed by postprocedural hydration performed for 4 hours under left ventricular end-diastolic pressure guidance and additional hydration until 24 hours after pPCI. General hydration group received ≤500 mL 0.9% saline at 1 mL/kg/hour for 6 hours after randomisation. The primary end point is CI-AKI, defined as a >25% or 0.5 mg/dL increased in serum creatinine from baseline during the first 48–72 hours after primary angioplasty. The safety end point is acute heart failure.ResultsFrom July 2014 to May 2018, 469 patients were enrolled in the final analysis. CI-AKI occurred less frequently in aggressive hydration group than in general hydration group (21.8% vs 31.1%; risk ratio (RR) 0.70, 95% CI 0.52 to 0.96). Acute heart failure did not significantly differ between the aggressive hydration group and the general hydration group (8.1% vs 6.4%, RR 1.13, 95% CI 0.66 to 2.44). Several subgroup analysis showed the better effect of aggressive hydration in CI-AKI prevention in male, renal insufficient and non-anterior myocardial infarction participants.ConclusionsComparing with general hydration, the peri-operative aggressive hydration seems to be safe and effective in preventing CI-AKI among patients with STEMI undergoing pPCI.
Predictors of short-term impulsive and compulsive behaviour after subthalamic stimulation in Parkinson disease
Authors: Sauerbier Anna , Loehrer Philipp , Jost Stefanie T. , Heil Shania , Petry-Schmelzer Jan N. , Herberg Johanna , Bachon Pia , Aloui Salima , Gronostay Alexandra , Klingelhoefer Lisa , Baldermann J. Carlos , Huys Daniel , Nimsky Christopher , Barbe Michael T. , Fink Gereon R. , Martinez-Martin Pablo , Ray Chaudhuri K. , Visser-Vandewalle Veerle , Timmermann Lars , Weintraub Daniel , Dafsari Haidar S. 
Published: September 2021

BackgroundThe effects of subthalamic stimulation (subthalamic nucleus-deep brain stimulation, STN-DBS) on impulsive and compulsive behaviours (ICB) in Parkinson’s disease (PD) are understudied.ObjectiveTo investigate clinical predictors of STN-DBS effects on ICB.MethodsIn this prospective, open-label, multicentre study in patients with PD undergoing bilateral STN-DBS, we assessed patients preoperatively and at 6-month follow-up postoperatively. Clinical scales included the Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS), PD Questionnaire-8, Non-Motor Symptom Scale (NMSS), Unified PD Rating Scale in addition to levodopa-equivalent daily dose total (LEDD-total) and dopamine agonists (LEDD-DA). Changes at follow-up were analysed with Wilcoxon signed-rank test and corrected for multiple comparisons (Bonferroni method). We explored predictors of QUIP-RS changes using correlations and linear regressions. Finally, we dichotomised patients into ‘QUIP-RS improvement or worsening’ and analysed between-group differences.ResultsWe included 55 patients aged 61.7 years±8.4 with 9.8 years±4.6 PD duration. QUIP-RS cut-offs and psychiatric assessments identified patients with preoperative ICB. In patients with ICB, QUIP-RS improved significantly. However, we observed considerable interindividual variability of clinically relevant QUIP-RS outcomes as 27.3% experienced worsening and 29.1% an improvement. In post hoc analyses, higher baseline QUIP-RS and lower baseline LEDD-DA were associated with greater QUIP-RS improvements. Additionally, the ‘QUIP-RS worsening’ group had more severe baseline impairment in the NMSS attention/memory domain.ConclusionsOur results show favourable ICB outcomes in patients with higher preoperative ICB severity and lower preoperative DA doses, and worse outcomes in patients with more severe baseline attention/memory deficits. These findings emphasise the need for comprehensive non-motor and motor symptoms assessments in patients undergoing STN-DBS.Trial registration numberDRKS00006735.
Temporal association of prostate cancer incidence with World Trade Center rescue/recovery work
Authors: Goldfarb David G , Zeig-Owens Rachel , Kristjansson Dana , Li Jiehui , Brackbill Robert M , Farfel Mark R , Cone James E , Yung Janette , Kahn Amy R , Qiao Baozhen , Schymura Maria J , Webber Mayris P , Dasaro Christopher R , Shapiro Moshe , Todd Andrew C , Prezant David J , Boffetta Paolo , Hall Charles B 
Published: September 2021

BackgroundThe World Trade Center (WTC) attacks on 11 September 2001 created a hazardous environment with known and suspected carcinogens. Previous studies have identified an increased risk of prostate cancer in responder cohorts compared with the general male population.ObjectivesTo estimate the length of time to prostate cancer among WTC rescue/recovery workers by determining specific time periods during which the risk was significantly elevated.MethodsPerson-time accruals began 6 months after enrolment into a WTC cohort and ended at death or 12/31/2015. Cancer data were obtained through linkages with 13 state cancer registries. New York State was the comparison population. We used Poisson regression to estimate hazard ratios and 95% CIs; change points in rate ratios were estimated using profile likelihood.ResultsThe analytic cohort included 54 394 male rescue/recovery workers. We observed 1120 incident prostate cancer cases. During 2002–2006, no association with WTC exposure was detected. Beginning in 2007, a 24% increased risk (HR: 1.24, 95% CI 1.16 to 1.32) was observed among WTC rescue/recovery workers when compared with New York State. Comparing those who arrived earliest at the disaster site on the morning of 11 September 2001 or any time on 12 September 2001 to those who first arrived later, we observed a positive, monotonic, dose-response association in the early (2002–2006) and late (2007–2015) periods.ConclusionsRisk of prostate cancer was significantly elevated beginning in 2007 in the WTC combined rescue/recovery cohort. While unique exposures at the disaster site might have contributed to the observed effect, screening practices including routine prostate specific antigen screening cannot be discounted.
COVID-19 infection among bartenders and waiters before and after pub lockdown
Authors: Methi Fredrik , Telle Kjetil , Magnusson Karin 
Published: September 2021

ObjectiveTo assess how different bans on serving alcohol in Norwegian bars and restaurants were related to the detection of SARS-CoV-2 in bartenders and waiters and in persons in any occupation.MethodsIn 25 392 bartenders and waiters and 1 496 328 persons with other occupations (mean (SD) age 42.0 (12.9) years and 51.8% men), we examined the weekly rates of workers tested and detected with SARS-CoV-2, 1–10 weeks before and 1–5 weeks after implementation of different degrees of bans on serving alcohol in pubs and restaurants, across 102 Norwegian municipalities with: (1) full blanket ban, (2) partial ban with hourly restrictions (eg, from 22:00 hours) or (3) no ban, adjusted for age, sex, testing behaviour and population size.ResultsBy 4 weeks after the implementation of ban, COVID-19 infection among bartenders and waiters had been reduced by 60% (from 2.8 (95% CI 2.0 to 3.6) to 1.1 (95% CI 0.5 to 1.6) per 1000) in municipalities introducing full ban, and by almost 50% (from 2.5 (95% CI 1.5 to 3.5) to 1.3 (95% CI 0.4 to 2.2) per 1000) in municipalities introducing partial ban. A similar reduction within 4 weeks was also observed for workers in all occupations, both in municipalities with full (from 1.3 (95% CI 1.3 to 1.4) to 0.9 (95% CI 0.9 to 1.0)) and partial bans (from 1.2 (95% CI 1.1 to 1.3) to 0.5 (95% CI 0.5 to 0.6)).ConclusionPartial bans on serving alcohol in bars and restaurants may be similarly associated with declines in confirmed COVID-19 infection as full bans.
No widespread dissemination of Chlamydia trachomatis diagnostic-escape variants and the impact of Neisseria gonorrhoeae positivity on the Aptima Combo 2 assay
Authors: Cole Michelle Jayne , Davis Grahame S , Fifer Helen , Saunders John Michael , Unemo Magnus , Hadad Ronza , Roberts David J , Fazal Mohammed , Day Michaela Joanne , Minshull Jack , Muir Peter , Horner Paddy J , Gill Noel O , Folkard Kate 
Published: September 2021

ObjectivesA Finnish Chlamydia trachomatis (CT) new variant was detected in 2019 that escaped detection in the Hologic Aptima Combo 2 (AC2) assay due to a C1515T mutation in the CT 23S rRNA target region. Reflex testing of CT-negative/CT-equivocal specimens as well as those positive for Neisseria gonorrhoeae (NG) with the Hologic Aptima CT (ACT) assay was recommended to identify any CT variants.MethodsFrom June to October 2019, specimens with discrepant AC2/ACT CT results were submitted to Public Health England and screened for detectable CT DNA using an inhouse real-time (RT)-PCR. When enough DNA was present, partial CT 23S rRNA gene sequencing was performed. Analysis of available relative light units and interpretative data was performed.ResultsA total of 317 discordant AC2/ACT specimens were collected from 315 patients. Three hundred were tested on the RT-PCR; 53.3% (n=160) were negative and 46.7% (n=140) were positive. Due to low DNA load in most specimens, sequencing was successful for only 36 specimens. The CT 23S rRNA wild-type sequence was present in 32 specimens, and two variants with C1514T or G1523A mutation were detected in four specimens from three patients. Of the discordant specimens with NG interpretation, 36.6% of NG-negative/CT-negative AC2 specimens had detectable CT DNA on the inhouse RT-PCR vs 53.3% of NG-positive/CT-negative specimens.ConclusionsNo widespread dissemination of AC2 diagnostic-escape CT variants has occurred in England. We however identified the impact of NG positivity on the discordant AC2/ACT specimens; a proportion appeared due to NG positivity and the associated NG signal, rather than any diagnostic-escape variants or low DNA load. Several patients with gonorrhoea may therefore receive false-negative AC2 CT results. Single diagnostic targets and multiplex diagnostic assays have their limitations such as providing selection pressure for escape mutants and potentially reduced sensitivity, respectively. These limitations must be considered when establishing diagnostic pathways.
Social mobility and gonorrhoea in Germany during 2020
Authors: Sulyok Mihály , Walker Mark 
Published: September 2021

ObjectivesThe incidence of STIs is likely to be related to levels of social activity and mobility. Novel datasets detailing levels of social activity were made widely available during the COVID-19 pandemic. These allow the relationship between activity and STI incidence to be examined.MethodsThe correlation between social activities and the reported number of gonorrhoea cases between March and December 2020 in Germany was studied. Regression through Autoregressive Integrated Moving Average (ARIMA) time series modelling identified those activities associated with case numbers.ResultsARIMA regression identified a significant association with ‘transit’ activity within the Apple data and ‘parks’ within Google.ConclusionsThis study illustrates the potential newly available measures of social activity provided for STI research. Reductions in STI incidence are likely to have occurred due to COVID-19 social restrictions. Although other studies report reductions in infectious diseases during this period, few examine the potential social factors mediating this. The results illustrate the continual need for sexual health services throughout the pandemic.
Endoplasmic reticulum-unfolded protein response signalling is altered in severe eosinophilic and neutrophilic asthma
Authors: Pathinayake Prabuddha S , Waters David W , Nichol Kristy S , Brown Alexandra C , Reid Andrew T , Hsu Alan Chen-Yu , Horvat Jay C , Wood Lisa G , Baines Katherine J , Simpson Jodie L , Gibson Peter G , Hansbro Philip M , Wark Peter A B 
Published: September 2021

IntroductionThe significance of endoplasmic reticulum (ER) stress in asthma is unclear. Here, we demonstrate that ER stress and the unfolded protein response (UPR) are related to disease severity and inflammatory phenotype.MethodsInduced sputum (n=47), bronchial lavage (n=23) and endobronchial biopsies (n=40) were collected from participants with asthma with varying disease severity, inflammatory phenotypes and from healthy controls. Markers for ER stress and UPR were assessed. These markers were also assessed in established eosinophilic and neutrophilic murine models of asthma.ResultsOur results demonstrate increased ER stress and UPR pathways in asthma and these are related to clinical severity and inflammatory phenotypes. Genes associated with ER protein chaperone (BiP, CANX, CALR), ER-associated protein degradation (EDEM1, DERL1)and ER stress-induced apoptosis (DDIT3, PPP1R15A) were dysregulated in participants with asthma and are associated with impaired lung function (forced expiratory volume in 1 s) and active eosinophilic and neutrophilic inflammation. ER stress genes also displayed a significant correlation with classic Th2 (interleukin-4, IL-4/13) genes, Th17 (IL-17F/CXCL1) genes, proinflammatory (IL-1b, tumour necrosis factor α, IL-8) genes and inflammasome activation (NLRP3) in sputum from asthmatic participants. Mice with allergic airway disease (AAD) and severe steroid insensitive AAD also showed increased ER stress signalling in their lungs.ConclusionHeightened ER stress is associated with severe eosinophilic and neutrophilic inflammation in asthma and may play a crucial role in the pathogenesis of asthma.
Myxobolus cerebralisestablishment and spread: a graphical synthesis
Authors: Ramazi Pouria , Fischer Samuel M. , Alexander Julie , James Clayton T. , Paul Andrew J. , Greiner Russell , Lewis Mark A. 
Published: September 2021

Myxobolus cerebralis is the parasite causing whirling disease, which has dramatic ecological impacts due to its potential to cause high mortality in salmonids. The large-scale efforts, necessary to underpin an effective surveillance program, have practical and economic constraints. There is, hence, a clear need for models that can predict the parasite spread. Model development, however, often heavily depends on knowing influential variables and governing mechanisms. We have developed a graphical model for the establishment and spread of M. cerebralis by synthesizing experts’ opinion and empirical studies. First, we conducted a series of workshops with experts to identify variables believed to impact the establishment and spread of the parasite M. cerebralis and visualized their interactions via a directed acyclic graph. Then we refined the graph by incorporating empirical findings from the literature. The final graph’s nodes correspond to variables whose considerable impact on M. cerebralis establishment and spread is either supported by empirical data or confirmed by experts, and the graph’s directed edges represent direct causality or strong correlation. This graphical model facilitates communication and education of whirling disease and provides an empirically driven framework for constructing future models, especially Bayesian networks.
Analysis of Glomerular Filtration Rate in Ischemic Cerebrovascular Diseases under the Magnetic Resonance Angiography Image Segmentation Algorithm
Authors: Ding Yong , Liu Yuebin , Peng Cong , Wang Huanmei , Xu Yuqin , Jiao Shengrong , Xu Huan , Zhao Yan , Liu Mingyu 
Published: September 2021

In order to discuss the segmentation effect of the magnetic resonance angiography (MRA) image segmentation algorithm based on the fuzzy clustering algorithm and DR-CV model and the prognostic value of glomerular filtration rate (GFR) in the ischemic cerebrovascular disease (ICVD), a total of 178 patients who were admitted to the hospital and received MRA due to ICVD were selected as the research objects of this study. Blood vessel segmentation was performed on the MRA image by fuzzy clustering algorithm and DR-CV model, and all patients were divided into a control group (group A), a single-vessel stenosis group (group B), a two-vessel stenosis group (group C), and a multiple-vessel stenosis group (group D). The GFR was estimated by using the dietary modification equation for kidney disease, and the correlation between GFR and the severity of arterial stenosis in patients with ICVD was analyzed. It was found that the results of the Dice similarity index (DSI) of the MRA image blood vessel segmentation algorithm based on the fuzzy clustering algorithm and the integrated model of boundary and regional information (DR-CV model) were all above 85%. The age and GFR values of the four groups of patients were significantly different (

P

< 0.05). The proportions of patients in groups C and D in the group with low DFR were significantly different from those in groups A and B (

P

< 0.01); the proportions of patients in groups A and B in the high-level GFR group had extremely significant differences compared with group D (

P

< 0.01). Age, GFR, total cholesterol (TC), and high-density lipoprotein-C (HDL-C) were correlated with the degree of arterial stenosis (

P

< 0.05). It showed that the segmentation effect of MRA image blood vessel segmentation algorithm based on the fuzzy clustering algorithm and DR-CV model was better, and the GFR level can be used as an independent risk factor for the ICVD.