bluuebunny/crossref_metadata_2025_split huggingface dataset:
The intermediate proteasome is constitutively expressed in pancreatic beta cells and upregulated by stimulatory, non-toxic concentrations of interleukin 1 β
Authors: Khilji Muhammad Saad , Verstappen Danielle , Dahlby Tina , Burstein Prause Michala Cecilie , Pihl Celina , Bresson Sophie Emilie , Bryde Tenna Holgersen , Klindt Kristian , Zivkovic Dusan , Bousquet-Dubouch Marie-Pierre , Tyrberg Björn , Billestrup Nils , Mandrup-Poulsen Thomas , Marzec Michal Tomasz 
Published: August 2019

AbstractA central and still open question regarding the pathogenesis of autoimmune diseases, such as type 1 diabetes, concerns the processes that underlie the generation of MHC-presented autoantigenic epitopes that become targets of autoimmune attack. Proteasomal degradation is a key step in processing of proteins for MHC class I presentation. Different types of proteasomes can be expressed in cells dictating the repertoire of peptides presented by the MHC class I complex. Of particular interest for type 1 diabetes is the proteasomal configuration of pancreatic β cells, as this might facilitate autoantigen presentation by β cells and thereby their T-cell mediated destruction. Here we investigated whether so-called inducible subunits of the proteasome are constitutively expressed in β cells, regulated by inflammatory signals and participate in the formation of active intermediate or immuno-proteasomes.We show that inducible proteasomal subunits are constitutively expressed in human and rodent islets and an insulin-secreting cell-line. Moreover, the β5i subunit is incorporated into active intermediate proteasomes that are bound to 19S or 11S regulatory particles. Finally, inducible subunit expression along with increase in total proteasome activities are further upregulated by non-toxic concentrations of IL-1β stimulating proinsulin biosynthesis. These findings suggest that the β cell proteasomal repertoire is more diverse than assumed previously and may be highly responsive to a local inflammatory islet environment.
Albumin inhibits the activation of hepatic stellate cells by suppressing TGF-β/Smad3 signaling via IL-1β
Authors: Park Ji Hoon , Kim Janghyun , Choi So-Young , Cha Kiweon , Park Heekyung , Lee Jung-Eun , Lee Boram , Moon Ji Wook , Park Sun-Hwa , Lee Jae Min , Lee Hong Sik , Oh Junseo 
Published: August 2019

AbstractActivated hepatic stellate cells (HSCs) play a key role in liver fibrosis and inactivating HSCs has been considered a promising therapeutic approach. We previously showed that albumin and its derivative, retinol binding protein (RBP)-albumin domain III fusion protein (named R-III), inhibit HSC activation. Here, we investigate the mode of action of albumin and R-III. NF-κB in activated HSCs was evenly distributed in the cytoplasm, but albumin expression and R-III treatment (albumin/R-III) induced NF-κB nuclear translocation via retinoic acid (RA) sequestration, resulting in increased expression of interleukin-1β (IL-1β). In an IL-1β dependent manner, albumin/R-III inhibited Smad3 nuclear translocation via TAK1-, JNK-mediated Smad3 linker phosphorylation and decreased expression of Smad3 target genes, such as α-smooth muscle actin and collagen type I. Mutation of the Smad3 linker phosphorylation sites abolished R-III effects on Smad3. In conclusion, our data suggest that the anti-fibrotic effects of albumin/R-III are due to RA sequestration which downregulates RAR-mediated signaling and also TGF-β/Smad3 signaling. This mechanistic elucidation of albumin function in HSCs provides clues to understanding the frequent albumin mutations found in hepatocellular carcinoma.
Leveraging host metabolism for bisdemethoxycurcumin production in Pseudomonas putida
Authors: Incha Matthew R. , Thompson Mitchell G. , Blake-Hedges Jacquelyn M. , Liu Yuzhong , Pearson Allison N. , Schmidt Matthias , Gin Jennifer W. , Petzold Christopher J. , Deutschbauer Adam M. , Keasling Jay D. 
Published: August 2019

ABSTRACTPseudomonas putida is a saprophytic bacterium with robust metabolisms and strong solvent tolerance making it an attractive host for metabolic engineering and bioremediation. Due to its diverse carbon metabolisms, its genome encodes an array of proteins and enzymes that can be readily applied to produce valuable products. In this work we sought to identify design principles and bottlenecks in the production of type III polyketide synthase (T3PKS)-derived compounds in P. putida. T3PKS products are widely used as nutraceuticals and medicines and often require aromatic starter units, such as coumaroyl-CoA, which is also an intermediate in the native coumarate catabolic pathway of P. putida. Using a randomly barcoded transposon mutant (RB-TnSeq) library, we assayed gene functions for a large portion of aromatic catabolism, confirmed known pathways, and proposed new annotations for two aromatic transporters. The 1,3,6,8-tetrahydroxynapthalene synthase of Streptomyces coelicolor (RppA), a microbial T3PKS, was then used to rapidly assay growth conditions for increased T3PKS product accumulation. The feruloyl/coumaroyl CoA synthetase (Fcs) of P. putida was used to supply coumaroyl-CoA for the curcuminoid synthase (CUS) of Oryza sativa, a plant T3PKS. We identified that accumulation of coumaroyl-CoA in this pathway results in extended growth lag times in P. putida. Deletion of the second step in coumarate catabolism, the enoyl-CoA hydratase-lyase (Ech), resulted in increased production of the type III polyketide bisdemethoxycurcumin.
Effectiveness, safety and acceptability of self‐assessment of the outcome of first‐trimester medical abortion: a systematic review and meta‐analysis
Authors: Baiju N , Acharya G , D'Antonio F , Berg RC 
Published: August 2019

BackgroundFor many women, the need for multiple clinical visits is a barrier to medical abortion.ObjectivesWe assessed the effectiveness, safety, and acceptability of self‐assessment of the outcome of medical abortion completed at home versus routine clinic follow up after medical abortion.Search strategyWe searched databases such as MEDLINE, Embase, and CENTRAL to find studies published in 1991–2018.Selection criteriaEligible studies included women of reproductive age who had undergone a medical abortion that was completed at home. The intervention and self‐assessment of the outcome of medical abortion done by urine pregnancy tests kits by women at home was compared with routine medical follow up at a clinic.Data collection and analysisTwo researchers completed the study selection, data extraction, critical appraisal, and assessment of the evidence. The outcomes were successful complete abortions, side effects and complications, and acceptability. We performed meta‐analyses when possible and GRADE to ascertain the certainty of the evidence. The protocol was registered in PROSPERO (CRD42017055316).Main resultsFour randomised controlled trials (RCTs; n = 5493) met our inclusion criteria. The pooled analysis from all studies showed no significant difference in complete abortion rates between self‐assessment and routine clinic follow up: RR = 1.00, 95% CI 0.99–1.01. The ongoing pregnancy rates were similar and the pooled results for the safety outcomes showed no significant differences between the groups. There was a significantly greater preference for self‐assessment as the follow‐up method.ConclusionsThe effectiveness, safety, and acceptability of self‐assessment of the outcome of medical abortion completed at home are not inferior to routine clinic follow up.Tweetable abstractThe effectiveness, safety, and acceptability of self‐assessment of the outcome of medical abortion are not inferior to routine clinic follow up.
Fructose tolerance test in obese people with and without type 2 diabetes
Authors: Al‐Ozairi Ebaa , Rivard Christopher J. , Sanchez Lozada Laura Gabriela , Lanaspa Miguel A. , Bjornstad Petter , Al Salem Danah , Alhubail Asma , Megahed Amira , Kuwabara Masanari , Johnson Richard J. , Asad Reem A. 
Published: August 2019

AbstractBackgroundFructose is distinct among common sugars in its ability to raise serum uric acid, and some studies suggest fructose‐induced uric acid production may have a role in the ability of this sugar to induce metabolic syndrome. A fructose tolerance test has been previously developed to evaluate the relative ability of fructose to raise uric acid in individuals. However, the effect of fructose to raise uric acid in people with diabetes has not been studied.MethodsPeople with type 2 diabetes (n = 143) and without diabetes controls (n = 132) with similar body mass index (BMI) underwent an oral fructose tolerance test. As a comparison, participants also had their uric acid levels measured after an oral glucose tolerance test on a different day.ResultsSerum uric acid was lower in people with type 2 diabetes compared to controls with a similar BMI, especially those with poor glucose control (glycosylated hemoglobin [HbA1c] ≥ 8%). Fructose administration raised serum uric acid in both groups, with a lower absolute rise in people with diabetes. People with diabetes with a blunted rise in serum uric acid had higher baseline serum uric acid concentrations and a higher BMI. People without diabetes with a higher BMI also showed a blunted serum uric acid response. Oral glucose administration lowered serum uric acid in both participants, with a greater fall in those with diabetes.ConclusionBoth the presence of diabetes and obesity blunt the serum uric acid response to fructose ingestion. These data demonstrate altered fructose‐dependent urate metabolism in type 2 diabetes.
Implications of the Joint Provision of CSR Assurance and Financial Audit for Auditors' Assessment of Going‐Concern Risk
Authors: Maso Lorenzo Dal , Lobo Gerald J. , Mazzi Francesco , Paugam Luc 
Published: August 2019

ABSTRACTWe examine whether the joint provision of corporate social responsibility (CSR) assurance services and financial audit by the same audit firm influences auditors' assessment of going‐concern risk. We predict that the provision of CSR assurance and financial audit by the same audit firm creates CSR‐related knowledge spillovers from the CSR assurance team to the financial audit engagement team, which helps in the auditor's assessment of going‐concern risk. Using more than 28,000 firm‐year observations from 55 countries, we document that, relative to audit firms that provide only the financial audit, audit firms that provide both CSR assurance and financial audit for the same client (i) issue more frequent going‐concern opinions and have lower Type II going‐concern errors, (ii) have clients that book larger environmental and litigation provisions, (iii) report earnings that are more persistent and value‐relevant and are less likely to book income‐decreasing earnings restatements, and (iv) do not charge higher audit fees or total fees. Our results are important especially because of firms' increasing exposure to CSR risks and the growing number of countries that require assurance of CSR reports.
Randomized Clinical Trial Examining Cognitive Behavioral Therapy for Individuals With a First‐Time DUI Offense
Authors: Osilla Karen Chan , Paddock Susan M. , McCullough Colleen M. , Jonsson Lisa , Watkins Katherine E. 
Published: August 2019

BackgroundDriving under the influence (DUI) programs are a unique setting to reduce disparities in treatment access to those who may not otherwise access treatment. Providing evidence‐based therapy in these programs may help prevent DUI recidivism.MethodsWe conducted a randomized clinical trial of 312 participants enrolled in 1 of 3 DUI programs in California. Participants were 21 and older with a first‐time DUI offense who screened positive for at‐risk drinking in the past year. Participants were randomly assigned to a 12‐session manualized cognitive behavioral therapy (CBT) or usual care (UC) group and then surveyed 4 and 10 months later. We conducted intent‐to‐treat analyses to test the hypothesis that participants receiving CBT would report reduced impaired driving, alcohol consumption (drinks per week, abstinence, and binge drinking), and alcohol‐related negative consequences. We also explored whether race/ethnicity and gender moderated CBT findings.ResultsParticipants were 72.3% male and 51.7% Hispanic, with an average age of 33.2 (SD = 12.4). Relative to UC, participants receiving CBT had lower odds of driving after drinking at the 4‐ and 10‐month follow‐ups compared to participants receiving UC (odds ratio [OR] = 0.37, p = 0.032, and OR = 0.29, p = 0.065, respectively). This intervention effect was more pronounced for females at 10‐month follow‐up. The remaining 4 outcomes did not significantly differ between UC versus CBT at 4‐ and 10‐month follow‐ups. Participants in both UC and CBT reported significant within‐group reductions in 2 of 5 outcomes, binge drinking and alcohol‐related consequences, at 10‐month follow‐up (p < 0.001).ConclusionsIn the short‐term, individuals receiving CBT reported significantly lower rates of repeated DUI than individuals receiving UC, which may suggest that learning cognitive behavioral strategies to prevent impaired driving may be useful in achieving short‐term reductions in impaired driving.
Life in linear habitats: the movement ecology of an endangered mammal in a peri‐urban landscape
Authors: Maclagan S. J. , Coates T. , Hradsky B. A. , Butryn R. , Ritchie E. G. 
Published: August 2019

AbstractAnimal movement can be significantly altered in human‐dominated landscapes such as urban and peri‐urban areas, where habitat is often fragmented and/or linear. Knowledge regarding how wildlife respond to anthropogenic change is vital for informing conservation efforts in such landscapes, including the design of nature reserves and wildlife corridors. To better understand how threatened species persist and behave within human‐dominated landscapes, we examined the home range and space use of the nationally endangered southern brown bandicoot Isoodon obesulus obesulus in peri‐urban Melbourne, Australia’s second‐largest city. Specifically, we examined whether: (1) bandicoots were confined to linear strips of remnant vegetation or also made use of the broader highly modified landscape matrix; (2) the configuration of the linear vegetated strips affected home range shape; and (3) home range area differed between bandicoots living in linear strips and those in larger remnant habitat patches. We found that: (1) 71% of adult males and 33% of adult females used the matrix, but non‐dispersing juveniles were entirely confined to the linear strips; males also travelled greater distances into the matrix (away from the vegetated strips) than females; (2) bandicoots had longer home ranges in narrower strips and males had longer home ranges than females; and (3) home range area for both sexes was smaller in linear strips than has been recorded in other studies in larger remnant habitats. Our study highlights the importance of retaining narrow, fragmented and modified vegetation to accommodate threatened biodiversity within human‐dominated landscapes, but suggests the surrounding matrix may also offer important resources for adaptable species, such as bandicoots. Supporting off‐reserve conservation of biodiversity in novel ecosystems is increasingly pertinent in our rapidly urbanizing world.
A bibliometric analysis of the conversion and reporting of pilot studies published in six anaesthesia journals
Authors: Charlesworth M. , Klein A. A. , White S. M. 
Published: August 2019

SummaryPilot and feasibility studies are preliminary investigations undertaken before a larger study. We hypothesised that only a small proportion of pilot or feasibility studies published in anaesthesia journals were correctly labelled as such. We searched for papers published between 2007 and 2017 in six anaesthesia journals using the text words ‘pilot’ OR ‘feasibility’ and included 266 original articles with 26,682 human participants. Only 34 (12.8%) were correctly labelled as a pilot or feasibility study. They were more likely to: have more median (IQR [range]) participants, 73 (40–130 [4–2716]) vs. 27 (15–60 [2–3305], p < 0.001; report feasibility outcomes, 82.4% vs. 4.3%, p < 0.001; and report an intention to convert, 100% vs. 39.7%, p < 0.001. They were less likely to test the efficacy of the primary outcome, 50% vs. 72.8%, p = 0.009; and report firm clinical conclusions 41.2% vs. 67.7%, p = 0.004. Of the studies published more than 5 years ago, correctly labelled pilot or feasibility studies were more likely to precede a published conversion study, 53.8% vs. 16%, p = 0.004. There was no difference between the number of citations 18 (9–44 [2–216]) vs. 20 (7–47 [0–251]), p = 0.865. These results have important consequences for patients, trialists, researchers and funders. We argue that correctly labelled pilot studies enhance the quality of scientific research by encouraging methodological rigour, ensuring scientific validity and reducing research waste. Authors, reviewers, editors and publishers should ensure they adhere to the contents of the 2016 CONSORT extension for pilot and feasibility studies.
Meta‐analysis found that studies may have overestimated Caesarean section risks for attention‐deficit hyperactivity disorder by ignoring confounding factors
Authors: Xu Lian‐lian , Zhang Xue , Zhou Guo‐lin , Jiang Chun‐min , Jiang Hai‐yin , Zhou Yuan‐yue 
Published: August 2019

AbstractAimEpidemiological studies on associations between Caesarean sections (C‐sections) and attention‐deficit hyperactivity disorder (ADHD) have been inconsistent, and we performed a meta‐analysis.MethodsWe systematically searched PubMed and Embase to December 2018 and included nine hospital‐based and population registry studies published in 2011‐2018. These covered a total study cohort of more than 2.5 million people in eight countries: Australia, Brazil, Denmark, Finland, Germany, Sweden, Turkey and the UK. The analysis provided summary odds ratios (ORs) and 95% confidence intervals (CI) while taking heterogeneity into account.ResultsWe found that that C‐sections were associated with a small increase in the risk of ADHD (OR 1.14, 95% CI 1.11, 1.17, I2 0%) in offspring. In subgroup analyses, the association remained for both infants born after elective C‐sections (OR, 1.15, 1.11, 1.19, I2 0%) and emergency C‐sections (OR, 1.13, 1.1, 1.17, I2 45.4%). However, these were only marginally significant when we pooled data from siblings from other pregnancies (OR, 1.06, 1.00‐1.13, I2 0%), implying that the association was due to confounding.ConclusionThe statistically significant association between C‐sections and ADHD in children can be partially explained by unmeasured confounding. Further research controlling for important confounders is required before firm conclusions can be drawn.
Survey of less Invasive Surfactant Administration in England, slow adoption and variable practice
Authors: Bhayat Sadaf , Kaur Avineet , Premadeva Irnthu , Reynolds Peter , Gowda Harsha 
Published: August 2019

AbstractAimNational survey to evaluate the uptake of Less Invasive Surfactant Administration (LISA) in neonatal units across England.MethodsA web‐based survey was sent out by email to all 150 neonatal units in England. It consisted of questions regarding indications for LISA, the practicalities of the procedure and reasons for not using this technique.ResultsThe response rate was 96% (144/150 units). Only 11% of units are using LISA, but majority (78%) would consider implementing LISA on their unit. 56% would also consider LISA on delivery suite. Challenges identified are having a guideline and staff training. 61% of units have set the target population ≥27 weeks. On sub‐analysis, for tertiary units, the trend for LISA is ≥26 weeks. The median FiO2 threshold for LISA is 0.3 (IQR 0.3‐0.4) in less than 28 weeks gestational age (GA), and 0.4 in higher gestations. The most common suggestion for premedication is fentanyl (32%).ConclusionThe uptake of LISA in England is low comparing to the rest of Europe. Even though many units are considering implementing LISA, there is lack of training and national guidelines. There is urgent need for standardisation of practice and clear indications for LISA.
Is the use of metformin in patients undergoing dialysis hazardous for life? A systematic review of the safety of metformin in patients undergoing dialysis
Authors: Abdel Shaheed Christina , Carland Jane E. , Graham Garry G. , Stocker Sophie L. , Smith Greg , Hicks Mark , Williams Kenneth M. , Furlong Timothy , Macdonald Peter , Greenfield Jerry R. , Smith Felicity C. , Chowdhury Gina , Day Richard O. 
Published: August 2019

AimsMetformin may have clinical benefits in dialysis patients; however, its safety in this population is unknown. This systematic review evaluated the safety of metformin in dialysis patients.MethodsMEDLINE, Embase, CENTRAL, PsycINFO and the Cochrane Library were searched for randomised controlled trials and observational studies evaluating metformin use in dialysis patients. Three authors reviewed the studies and extracted data. The primary outcomes were mortality, occurrence of lactic acidosis and myocardial infarction (MI) in patients taking metformin during dialysis treatment for ≥12 months (long term). Risk of bias was assessed using Risk Of Bias In Nonrandomised Studies of Interventions (ROBINS‐1). Overall quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).ResultsFifteen observational studies were eligible; 7 were prospective observational studies and 8 were case reports/case series. No randomised controlled trials were identified. The 7 prospective observational studies (n = 194) reported on cautious metformin use in patients undergoing maintenance dialysis. Only 3 provided long‐term follow‐up data. In 2 long‐term studies of metformin therapy (≤1000 mg/d) in patients undergoing peritoneal dialysis (PD), 1 reported 6 deaths (6/83; 7%) due to major cardiovascular events (3 MI) and the other reported no deaths (0/35). One long‐term study of metformin therapy (250 mg to 500 mg thrice weekly) in patients undergoing haemodialysis reported 4 deaths (4/61; 7%) due to major cardiovascular events (2 MI). These findings provide very low‐quality evidence as they come from small observational studies.ConclusionThe evidence regarding the safety of metformin in people undergoing dialysis is inconclusive. Appropriately designed randomised controlled trials are needed to resolve this uncertainty.