bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allopurinol hepatotoxicity is associated with human leukocyte antigen Class I alleles
Authors: Fontana Robert J. , Li Yi‐Ju , Phillips Elizabeth , Saeed Naba , Barnhart Huiman , Kleiner David , Hoofnagle Jay ,   the Drug Induced Liver Injury Network
Published: April 2021

AbstractBackground/AimsAllopurinol can cause HLA class I‐associated life‐threatening severe skin reactions. However, HLA risk and association with clinical features in allopurinol hepatotoxicity are unknown.MethodsEleven of 17 patients with suspected allopurinol hepatotoxicity enrolled into the Drug‐Induced Liver Injury Network were adjudicated as definite, highly likely, or probable. High‐resolution HLA sequencing was undertaken in cases and compared with population and other DILI controls.ResultMedian age was 60 years, 54% were male, and 63% African‐ American, 27% Caucasian, and 9% Hispanic. Patients presented at a median of 52 days after starting allopurinol, all were hospitalized and six were jaundiced. The median peak ALT, alkaline phosphatase, and total bilirubin were 525 U/L, 521 U/L, and 7.8 mg/dl, respectively, with a median R ratio of 2.7 at onset. During follow‐up, nine patients were treated with corticosteroids including five of the six with suspected DRESS. Three patients died including two from liver failure at 38 and 45 days after onset, and the remaining eight recovered. Three HLA alleles were found to be overrepresented in allopurinol cases, particularly in African Americans: HLA‐B*58:01, which has been previously linked to severe skin reactions, and HLA‐B*53:01 and HLA‐A*34:02, all of which are more frequently found in African Americans than European Americans or Latinos.ConclusionsAllopurinol hepatotoxicity is associated with systemic hypersensitivity, a short latency to onset, African‐American race and three HLA risk alleles, HLA‐B*58:01, HLA‐B*53:01, and HLA‐A*34:02‐58:01 testing may help confirm a diagnosis of hepatotoxicity in allopurinol‐treated patients.
DNA methylation status of MutS genes in ameloblastoma
Authors: do Amaral‐Silva Gleyson Kleber , Pereira Thaís dos Santos Fontes , Rocha André Caroli , Mariz Bruno Augusto Linhares Almeida , Prado‐Ribeiro Ana Carolina , Fonseca Felipe Paiva , Gomez Ricardo Santiago , Vargas Pablo Agustin 
Published: April 2021

AbstractObjectivesAmeloblastoma is an odontogenic epithelial tumour with a low expression of mismatch repair system components. We aimed to investigate the methylation status of the genes MSH2, MSH3 and MSH6 (MutS group) in conventional ameloblastomas.Materials and MethodsThe ameloblastoma and dental follicle samples (n = 10 each) were collected from 20 different patients. Each ameloblastoma sample was sectioned into two fragments: one was paraffin‐embedded while the other one, likewise the dental follicle samples, was fixed in RNAlater and frozen at −196°C. All frozen samples were investigated for the MutS genes methylation levels, using the enzymatic restriction digestion and quantitative real‐time PCR (qPCR) assay. The ameloblastoma paraffin‐embedded samples were submitted to immunohistochemical reactions for MutS proteins detection and digitally quantification. Correlation analyses were performed between the immunohistochemical results and the respective gene methylation percentage.ResultsThere are no significant differences between the MutS genes methylation levels in the ameloblastoma and the dental follicle. However, a strong negative correlation was found between MSH2 and MSH6 gene methylation status and their respective proteins expressions evaluated by immunohistochemistry.ConclusionOur results show that the genes methylations is in part responsible for decreasing the expression of MSH2 and MSH6 genes in ameloblastoma.
Assessing public value failure in government adoption of artificial intelligence
Authors: Schiff Daniel S. , Schiff Kaylyn Jackson , Pierson Patrick 
Published: April 2021

AbstractIn the context of rising delegation of administrative discretion to advanced technologies, this study aims to quantitatively assess key public values that may be at risk when governments employ automated decision systems (ADS). Drawing on the public value failure framework coupled with experimental methodology, we address the need to measure and compare the salience of three such values—fairness, transparency, and human responsiveness. Based on a preregistered design, we administer a survey experiment to 1460 American adults inspired by prominent ADS applications in child welfare and criminal justice. The results provide clear causal evidence that certain public value failures associated with artificial intelligence have significant negative impacts on citizens' evaluations of government. We find substantial negative citizen reactions when fairness and transparency are not realized in the implementation of ADS. These results transcend both policy context and political ideology and persist even when respondents are not themselves personally impacted.
Effect of low temperature and high humidity stress on physiology of cucumber at different leaf stages
Authors: Amin B. , Atif M. J. , Wang X. , Meng H. , Ghani M. I. , Ali M. , Ding Y. , Li X. , Cheng Z. 
Published: April 2021

Abstract

Low temperature (LT) and high humidity (HH) are important environmental factors in greenhouses and plastic tunnels during the cold season, as they hamper plant growth and development.

Here, we studied the effect of LT (day/night: 9/5 °C, 25/18 °C as control) and HH (95%, 80% as control) on young cucumber plants at the 2, 4 or 6 leaf stages.

LT+HH stress resulted in a decline in shoot, root and total fresh and dry weights, and decreased Pn, gs, Tr, Fv/Fm, qP, ETR and chlorophyll, and increased MDA, H2O2, O2‐, NPQ and Ci as compared to the control at the 2 leaf stage. SOD, POD, CAT, APX and GR were upregulated under LT+HH stress as compared to the control at the 6 leaf stage. ABA and JA increased under LT+HH stress as compared to the control at the 6 leaf stage, while IAA and GA decreased under LT+HH stress as compared to the control at the 2 leaf stage.

Our results show that LT+HH stress affects young cucumber plant photosynthetic efficiency, PSII activity, antioxidant defence system, ROS and hormone profile. Plants at the 6 leaf stage were more tolerant than at the 2 and 4 leaf stages under stress conditions.
Jama'at‐e‐Islami and Trust Building in Bangladesh
Authors: Mostofa Shafi Md 
Published: April 2021

Bangladesh is the third‐largest Muslim country in the world where Islamic ideals inherently influence people's thought and actions. One of the Islamist political parties that has been trying to influence the Bangladeshi population is the Jama'at‐e‐Islami (JeI). The JeI is one of the oldest and largest Islamist political parties in the country and has continuously exerted its influence on the social ethos and state policy. JeI's unconditional support for Islamization and a society based on Sharia law undoubtedly attracts some sections of the Bangladeshi population. Apart from promoting an Islamist totalitarian ideology, it also maintains a requirement of religious purification for choosing its party members; a strategy that has earned a reputation as a party with robust intraparty discipline. To enhance its trust‐based relationships with its members (at both the horizontal and vertical levels), JeI helps its members through various means, including the provision of financial support, social welfare programs, and charity activities. Although the targeted population are their members, these schemes have had an impact, however minimal, on the Bangladeshi population to redress its anti‐independence stance in 1971, on the failure to send an apology message for what JeI did in 1971, and on the worldwide failure of political Islam.Related ArticlesBarton, Greg. 2010. “Indonesia: Legitimacy, Secular Democracy, and Islam.” Politics & Policy 38 (3): 471‐496. https://doi.org/10.1111/j.1747‐1346.2010.00244.xMarinov, Robert, and Daniel Stockemer. 2020. “The Spread of Anti‐Islamic Sentiment: A Comparison between the United States and Western Europe.” Politics & Policy 48 (3): 402‐441. https://doi.org/10.1111/polp.12354Spalek, Basia. 2010. “Community Policing, Trust, and Muslim Communities in Relation to ‘New Terrorism.’” Politics & Policy 38 (4): 789‐815. https://doi.org/10.1111/j.1747‐1346.2010.00258.x
Generation of Cretaceous high-silica granite by complementary crystal accumulation and silicic melt extraction in the coastal region of southeastern China
Authors: Chen Jing-Yuan , Yang Jin-Hui , Zhang Ji-Heng , Sun Jin-Feng , Zhu Yu-Sheng , Hartung Eva 
Published: April 2021

AbstractIt is generally hypothesized that high-silica (SiO2 &gt; 75 wt%) granite (HSG) originates from crystal fractionation in the shallow crust. Yet, identifying the complementary cumulate residue of HSG within plutons remains difficult. In this work, we examine the genetic links between the porphyritic monzogranite and HSG (including porphyritic granite, monzogranite, and alkali feldspar granite) from the coastal area of southeastern China using detailed zircon U-Pb ages, trace elements, Hf-O isotopes, and whole-rock geochemistry and Nd-Hf isotopic compositions. Zircon U-Pb ages indicate that the porphyritic monzogranite and HSG are coeval (ca. 96–99 Ma). The HSG and porphyritic monzogranite have similar formation ages within analytic error, identical mineral assemblages, similar Nd-Hf isotopic compositions, and consistent variations in their zircon compositions (i.e., Eu/Eu*, Zr/Hf, and Sm/Yb), which suggests that their parental magma came from a common silicic magma reservoir and that the lithological differences are the result of melt extraction processes. The porphyritic monzogranite has relatively high SiO2 (70.0–73.4 wt%), Ba (718–1070 ppm), and Sr (493–657 ppm) contents, low K2O and Rb concentrations and low Rb/Sr ratios (0.1–0.2), and it displays weak Eu anomalies (Eu/Eu* = 0.57–0.90). Together with the petrographic features of the porphyritic monzogranite, these geochemical variations indicate that the porphyritic monzongranite is the residual silicic cumulate of the crystal mush column. The HSG (SiO2 = 75.0–78.4) has variable Rb/Sr ratios (2–490) and very low Sr (1–109 ppm) and Ba (9–323 ppm) contents. Zircon from the HSG and porphyritic monzogranite overlap in Eu/Eu*, Zr/Hf, and Sm/Yb ratios and Hf contents; however, some zircon from the HSG show very low Eu/Eu* (&lt;0.1) and Zr/Hf ratios. These features suggest that the HSG represents the high-silica melt that was extracted from a crystal-rich mush. The injection of mantle-derived hotter mafic magma into the mush column and the exsolution of F/Cl−-enriched volatiles (or fluids) from the interstitial melt rejuvenated the pre-existing highly crystalline mush. Subsequent extraction and upward migration of silicic melt resulting from compaction of the mush column formed the HSG at shallow crustal levels, which left the complementary crystal residue solidified as porphyritic monzogranite at the bottom.
Associations between attainment of incentivized primary care indicators and incident lower limb amputation among those with type 2 diabetes: a population-based historical cohort study
Authors: Gunn Laura H , Vamos Eszter P , Majeed Azeem , Normahani Pasha , Jaffer Usman , Molina German , Valabhji Jonathan , McKay Ailsa J 
Published: April 2021

IntroductionEngland has invested considerably in diabetes care through such programs as the Quality and Outcomes Framework (QOF) and National Diabetes Audit (NDA). Associations between program indicators and clinical endpoints, such as amputation, remain unclear. We examined associations between primary care indicators and incident lower limb amputation.Research design and methodsThis population-based retrospective cohort study, spanning 2010–2017, was comprised of adults in England with type 2 diabetes and no history of lower limb amputation. Exposures at baseline (2010–2011) were attainment of QOF glycated hemoglobin (HbA1c), blood pressure and total cholesterol indicators, and number of NDA processes completed. Propensity score matching was performed and multivariable Cox proportional hazards models, adjusting for disease-related, comorbidity, lifestyle, and sociodemographic factors, were fitted using matched samples for each exposure.Results83 688 individuals from 330 English primary care practices were included. Mean follow-up was 3.9 (SD 2.0) years, and 521 (0.6%) minor or major amputations were observed (1.62 per 1000 person-years). HbA1c and cholesterol indicator attainment were associated with considerably lower risks of minor or major amputation (adjusted HRs; 95% CIs) 0.61 (0.49 to 0.74; p<0.0001) and 0.67 (0.53 to 0.86; p=0.0017), respectively). No evidence of association between blood pressure indicator attainment and amputation was observed (adjusted HR 0.88 (0.73 to 1.06; p=0.1891)). Substantially lower amputation rates were observed among those completing a greater number of NDA care processes (adjusted HRs 0.45 (0.24 to 0.83; p=0.0106), 0.67 (0.47 to 0.97; p=0.0319), and 0.38 (0.20 to 0.70; p=0.0022) for comparisons of 4–6 vs 0–3, 7–9 vs 0–3, and 7–9 vs 4–6 processes, respectively). Results for major-only amputations were similar for HbA1c and blood pressure, though cholesterol indicator attainment was non-significant.ConclusionsComprehensive primary care-based secondary prevention may offer considerable protection against diabetes-related amputation. This has important implications for diabetes management and medical decision-making for patients, as well as type 2 diabetes quality improvement programs.
Exploring the GLP-1–GLP-1R axis in porcine pancreas and gastrointestinal tract in vivo by ex vivo autoradiography
Authors: Manell Elin , Puuvuori Emmi , Svensson Anna , Velikyan Irina , Hulsart-Billström Gry , Hedenqvist Patricia , Holst Jens Juul , Jensen Waern Marianne , Eriksson Olof 
Published: April 2021

IntroductionGlucagon-like peptide-1 (GLP-1) increases insulin secretion from pancreatic beta-cells and GLP-1 receptor (GLP-1R) agonists are widely used as treatment for type 2 diabetes mellitus. Studying occupancy of the GLP-1R in various tissues is challenging due to lack of quantitative, repeatable assessments of GLP-1R density. The present study aimed to describe the quantitative distribution of GLP-1Rs and occupancy by endogenous GLP-1 during oral glucose tolerance test (OGTT) in pigs, a species that is used in biomedical research to model humans.Research design and methodsGLP-1R distribution and occupancy were measured in pancreas and gastrointestinal tract by ex vivo autoradiography using the GLP-1R-specific radioligand177Lu-exendin-4 in two groups of pigs, control or bottle-fed an oral glucose load. Positron emission tomography (PET) data from pigs injected with68Ga-exendin-4 in a previous study were used to retrieve data on biodistribution of GLP-1R in the gastrointestinal tract.ResultsHigh homogenous uptake of177Lu-exendin-4 was found in pancreas, and even higher uptake in areas of duodenum. Low uptake of177Lu-exendin-4 was found in stomach, jejunum, ileum and colon. During OGTT, there was no increase in plasma GLP-1 concentrations and occupancy of GLP-1Rs was low. The ex vivo autoradiography results were highly consistent with to the biodistribution of68Ga-exendin-4 in pigs scanned by PET.ConclusionWe identified areas with similarities as well as important differences regarding GLP-1R distribution and occupancy in pigs compared with humans. First, there was strong ligand binding in the exocrine pancreas in islets. Second, GLP-1 secretion during OGTT is minimal and GLP-1 might not be an important incretin in pigs under physiological conditions. These findings offer new insights on the relevance of porcine diabetes models.
Quality of life support in advanced cancer—web and technological interventions: systematic review and narrative synthesis
Authors: Kane Kathleen , Kennedy Fiona , Absolom Kate L , Harley Clare , Velikova Galina 
Published: April 2021

BackgroundAs treatments continue to progress, patients with advanced cancer are living longer. However, ongoing physical side-effects and psychosocial concerns can compromise quality of life (QoL). Patients and physicians increasingly look to the internet and other technologies to address diverse supportive needs encountered across this evolving cancer trajectory.Objectives1. To examine the features and delivery of web and technological interventions supporting patients with advanced cancer. 2. To explore their efficacy relating to QoL and psychosocial well-being.MethodsRelevant studies were identified through electronic database searches (MEDLINE, PsychINFO, Embase, CINAHL, CENTRAL, Web of Science and ProQuest) and handsearching. Findings were collated and explored through narrative synthesis.ResultsOf 5274 identified records, 37 articles were included. Interventions were evaluated within studies targeting advanced cancer (13) or encompassing all stages (24). Five subtypes emerged: Interactive Health Communication Applications (n=12), virtual programmes of support (n=11), symptom monitoring tools (n=8), communication conduits (n=3) and information websites (n=3). Modes of delivery ranged from self-management to clinically integrated. Support largely targeted psychosocial well-being, alongside symptom management and healthy living. Most studies (78%) evidenced varying degrees of efficacy through QoL and psychosocial measures. Intervention complexity made it challenging to distinguish the most effective components. Incomplete reporting limited risk of bias assessment.ConclusionWhile complex and varied in their content, features and delivery, most interventions led to improvements in QoL or psychosocial well-being across the cancer trajectory. Ongoing development and evaluation of such innovations should specifically target patients requiring longer-term support for later-stage cancer.PROSPERO registration numberCRD42018089153.
Integrative study of diet-induced mouse models of NAFLD identifies PPARα as a sexually dimorphic drug target
Authors: Smati Sarra , Polizzi Arnaud , Fougerat Anne , Ellero-Simatos Sandrine , Blum Yuna , Lippi Yannick , Régnier Marion , Laroyenne Alexia , Huillet Marine , Arif Muhammad , Zhang Cheng , Lasserre Frederic , Marrot Alain , Al Saati Talal , Wan JingHong , Sommer Caroline , Naylies Claire , Batut Aurelie , Lukowicz Celine , Fougeray Tiffany , Tramunt Blandine , Dubot Patricia , Smith Lorraine , Bertrand-Michel Justine , Hennuyer Nathalie , Pradere Jean-Philippe , Staels Bart , Burcelin Remy , Lenfant Françoise , Arnal Jean-François , Levade Thierry , Gamet-Payrastre Laurence , Lagarrigue Sandrine , Loiseau Nicolas , Lotersztajn Sophie , Postic Catherine , Wahli Walter , Bureau Christophe , Guillaume Maeva , Mardinoglu Adil , Montagner Alexandra , Gourdy Pierre , Guillou Hervé 
Published: April 2021

ObjectiveWe evaluated the influence of sex on the pathophysiology of non-alcoholic fatty liver disease (NAFLD). We investigated diet-induced phenotypic responses to define sex-specific regulation between healthy liver and NAFLD to identify influential pathways in different preclinical murine models and their relevance in humans.DesignDifferent models of diet-induced NAFLD (high-fat diet, choline-deficient high-fat diet, Western diet or Western diet supplemented with fructose and glucose in drinking water) were compared with a control diet in male and female mice. We performed metabolic phenotyping, including plasma biochemistry and liver histology, untargeted large-scale approaches (liver metabolome, lipidome and transcriptome), gene expression profiling and network analysis to identify sex-specific pathways in the mouse liver.ResultsThe different diets induced sex-specific responses that illustrated an increased susceptibility to NAFLD in male mice. The most severe lipid accumulation and inflammation/fibrosis occurred in males receiving the high-fat diet and Western diet, respectively. Sex-biased hepatic gene signatures were identified for these different dietary challenges. The peroxisome proliferator-activated receptor α (PPARα) co-expression network was identified as sexually dimorphic, and in vivo experiments in mice demonstrated that hepatocyte PPARα determines a sex-specific response to fasting and treatment with pemafibrate, a selective PPARα agonist. Liver molecular signatures in humans also provided evidence of sexually dimorphic gene expression profiles and the sex-specific co-expression network for PPARα.ConclusionsThese findings underscore the sex specificity of NAFLD pathophysiology in preclinical studies and identify PPARα as a pivotal, sexually dimorphic, pharmacological target.Trial registration numberNCT02390232.
Real-life survey of pitfalls and successes of precision medicine in genetic epilepsies
Authors: Balestrini Simona , Chiarello Daniela , Gogou Maria , Silvennoinen Katri , Puvirajasinghe Clinda , Jones Wendy D , Reif Philipp , Klein Karl Martin , Rosenow Felix , Weber Yvonne G , Lerche Holger , Schubert-Bast Susanne , Borggraefe Ingo , Coppola Antonietta , Troisi Serena , Møller Rikke S , Riva Antonella , Striano Pasquale , Zara Federico , Hemingway Cheryl , Marini Carla , Rosati Anna , Mei Davide , Montomoli Martino , Guerrini Renzo , Cross J Helen , Sisodiya Sanjay M 
Published: April 2021

ObjectiveThe term ‘precision medicine’ describes a rational treatment strategy tailored to one person that reverses or modifies the disease pathophysiology. In epilepsy, single case and small cohort reports document nascent precision medicine strategies in specific genetic epilepsies. The aim of this multicentre observational study was to investigate the deeper complexity of precision medicine in epilepsy.MethodsA systematic survey of patients with epilepsy with a molecular genetic diagnosis was conducted in six tertiary epilepsy centres including children and adults. A standardised questionnaire was used for data collection, including genetic findings and impact on clinical and therapeutic management.ResultsWe included 293 patients with genetic epilepsies, 137 children and 156 adults, 162 females and 131 males. Treatment changes were undertaken because of the genetic findings in 94 patients (32%), including rational precision medicine treatment and/or a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms. There was a rational precision medicine treatment for 56 patients (19%), and this was tried in 33/56 (59%) and was successful (ie, >50% seizure reduction) in 10/33 (30%) patients. In 73/293 (25%) patients there was a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms, and this was successful in 24/73 (33%).SignificanceOur survey of clinical practice in specialised epilepsy centres shows high variability of clinical outcomes following the identification of a genetic cause for an epilepsy. Meaningful change in the treatment paradigm after genetic testing is not yet possible for many people with epilepsy. This systematic survey provides an overview of the current application of precision medicine in the epilepsies, and suggests the adoption of a more considered approach.