bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain structural covariance network differences in adults with alcohol dependence and heavy‐drinking adolescents
Authors: Ottino‐González Jonatan , Garavan Hugh ,   The ENIGMA‐Addiction and IMAGEN consortiums
Published: December 2021

AbstractBackground and aimsGraph theoretic analysis of structural covariance networks (SCN) provides an assessment of brain organization that has not yet been applied to alcohol dependence (AD). We estimated whether SCN differences are present in adults with AD and heavy‐drinking adolescents at age 19 and age 14, prior to substantial exposure to alcohol.DesignCross‐sectional sample of adults and a cohort of adolescents. Correlation matrices for cortical thicknesses across 68 regions were summarized with graph theoretic metrics.Setting and participantsA total of 745 adults with AD and 979 non‐dependent controls from 24 sites curated by the Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA)–Addiction consortium, and 297 hazardous drinking adolescents and 594 controls at ages 19 and 14 from the IMAGEN study, all from Europe.MeasurementsMetrics of network segregation (modularity, clustering coefficient and local efficiency) and integration (average shortest path length and global efficiency).FindingsThe younger AD adults had lower network segregation and higher integration relative to non‐dependent controls. Compared with controls, the hazardous drinkers at age 19 showed lower modularity [area‐under‐the‐curve (AUC) difference = −0.0142, 95% confidence interval (CI) = −0.1333, 0.0092; P‐value = 0.017], clustering coefficient (AUC difference = −0.0164, 95% CI = −0.1456, 0.0043; P‐value = 0.008) and local efficiency (AUC difference = −0.0141, 95% CI = −0.0097, 0.0034; P‐value = 0.010), as well as lower average shortest path length (AUC difference = −0.0405, 95% CI = −0.0392, 0.0096; P‐value = 0.021) and higher global efficiency (AUC difference = 0.0044, 95% CI = −0.0011, 0.0043; P‐value = 0.023). The same pattern was present at age 14 with lower clustering coefficient (AUC difference = −0.0131, 95% CI = −0.1304, 0.0033; P‐value = 0.024), lower average shortest path length (AUC difference = −0.0362, 95% CI = −0.0334, 0.0118; P‐value = 0.019) and higher global efficiency (AUC difference = 0.0035, 95% CI = −0.0011, 0.0038; P‐value = 0.048).ConclusionsCross‐sectional analyses indicate that a specific structural covariance network profile is an early marker of alcohol dependence in adults. Similar effects in a cohort of heavy‐drinking adolescents, observed at age 19 and prior to substantial alcohol exposure at age 14, suggest that this pattern may be a pre‐existing risk factor for problematic drinking.
Impact of the COVID‐19 pandemic on hospital admissions of nursing home residents
Authors: Tan Li Feng , Soh Rodney Yu Hang , Seetharaman Santhosh Kumar 
Published: December 2021

AbstractObjectiveThe coronavirus disease 2019 (COVID‐19) pandemic has impacted nursing home care and activities in profound ways. We sought to understand whether the COVID‐19 pandemic had any impact on hospital admissions of nursing home residents.MethodsA retrospective analysis of hospital admissions of nursing home residents to a tertiary general hospital in Singapore during the COVID‐19 pandemic in 2020 was conducted and compared to admissions in the preceding year. Patients' demographics, length of stay, primary diagnosis on admission, death and causes of death were recorded.ResultsOur study found reduced number of hospital admissions of nursing home residents to a tertiary hospital in Singapore. There was a significant decrease in pneumonia (p < 0.001) and fall (p = 0.001) as a primary diagnosis on admission and a decrease in pneumonia as the cause of death (p < 0.001) for nursing home residents admitted to hospital during the COVID‐19 pandemic.ConclusionsThis suggests that measures implemented during the pandemic may have impacted outcomes of nursing home residents. Further study is warranted to lead to practise changing outcomes for nursing home settings.
Identifying barriers and facilitators to implementing mindfulness‐based programmes into schools: A mixed methods study
Authors: Nguyen Dong , Kleeman Nicholas J. , Yager Zali , Parker Alexandra G. , Shean Mandie B. , Jefferies Willow , Wilson‐Evered Elisabeth , Pucinischi Christopher P. , Pascoe Michaela C. 
Published: December 2021

AbstractMindfulness‐based initiatives have been shown to improve psychological wellbeing and increase academic engagement in school settings. The current study explored barriers and facilitators to the implementation of mindfulness‐based (MB) programmes in schools. Ninety‐five teachers completed an online survey, and six principals were interviewed, with questions for both informed by the Theoretical Domains Framework (TDF). Quantitative data was analysed via descriptive statistics and independent sample t tests. Qualitative interview data were analysed via thematic analysis. Teachers reported facilitators to successful MB programme implementation as self‐efficacy and motivation, knowledge about MB programmes, acceptance of responsibility to deliver MB programmes and belief of negative consequences if MB programmes are not delivered. Principals reported organisational‐level facilitators as having a school‐wide positive education framework relevant to the school context, taking a long‐term approach, school leaders supporting the initiatives and understanding the evidence behind MB programmes and empowering staff to engage in mindfulness. Individual‐level facilitators included staff buy‐in and commitment to practice and understanding mindfulness. Barriers included time, resources/money, staff buy‐in and competing strategic priorities within the school. These findings are important for consideration by policymakers determining the way forward for more widespread implementation of MB programmes in Australia.
Potential drug–drug interactions when managing status epilepticus patients in intensive care: A cohort study
Authors: Le Roux Clémentine , Destère Alexandre , Hervy Sarah , Lloret‐Linares Célia , Reignier Jean , Caillet Pascal , Jolliet Pascale , Mégarbane Bruno , Boels David 
Published: December 2021

AimsThe risk for drug–drug interactions (DDIs) associated with antiseizure drugs (ASDs) used to manage status epilepticus (SE) patients in the intensive care unit (ICU) has been poorly investigated. We aimed to quantify and describe those potential DDIs and determine SE patient risk profiles.MethodsWe conducted an observational bi‐centric cohort study including all SE patients admitted to the ICU in the period 2016–2020.ResultsOverall, 431 SE patients were included and 5504 potential DDIs were identified including 1772 DDIs (33%) between ASDs, 2610 DDIs (47%) between ASDs and previous usual treatments (PUTs), and 1067 DDIs (20%) between ASDs and ICU treatments (ICUTs). DDIs were moderate (n = 4871), major (n = 562) or severe (n = 16). All patients exhibited potential DDIs, which were major‐to‐severe DDIs in 47% of the cases. DDIs were pharmacokinetic (n = 1972, 36%), mostly involving cytochrome P450 modulators, and pharmacodynamic (n = 3477, 64%), mainly leading to increased sedation. ASD/PUT DDIs were the most frequent and severe. Age, PUT and ASD drug numbers and length of ICU stay were significantly associated with increased DDI number. We identified four SE patient profiles with different DDI risks and outcomes including (1) epileptic or brain trauma patients, (2) withdrawal syndrome patients, (3) older patients with comorbidities and (4) self‐poisoned patients with psychiatric disorders and/or past epilepsy.ConclusionSE patients are subject to potential DDIs between ASDs, ASD/PUT and ASD/ICUT. Major‐to‐severe DDIs mostly occur between ASDs and PUTs. Physicians should pay attention to SE patient characteristics and history to limit DDI numbers and prevent their consequences.
Pharmacogenomic testing in paediatrics: Clinical implementation strategies
Authors: Barker Charlotte I. S. , Groeneweg Gabriella , Maitland‐van der Zee Anke H. , Rieder Michael J. , Hawcutt Daniel B. , Hubbard Tim J. , Swen Jesse J. , Carleton Bruce C. 
Published: December 2021

Pharmacogenomics (PGx) relates to the study of genetic factors determining variability in drug response. Implementing PGx testing in paediatric patients can enhance drug safety, helping to improve drug efficacy or reduce the risk of toxicity. Despite its clinical relevance, the implementation of PGx testing in paediatric practice to date has been variable and limited.As with most paediatric pharmacological studies, there are well‐recognised barriers to obtaining high‐quality PGx evidence, particularly when patient numbers may be small, and off‐label or unlicensed prescribing remains widespread. Furthermore, trials enrolling small numbers of children can rarely, in isolation, provide sufficient PGx evidence to change clinical practice, so extrapolation from larger PGx studies in adult patients, where scientifically sound, is essential.This review paper discusses the relevance of PGx to paediatrics and considers implementation strategies from a child health perspective. Examples are provided from Canada, the Netherlands and the UK, with consideration of the different healthcare systems and their distinct approaches to implementation, followed by future recommendations based on these cumulative experiences.Improving the evidence base demonstrating the clinical utility and cost‐effectiveness of paediatric PGx testing will be critical to drive implementation forwards. International, interdisciplinary collaborations will enhance paediatric data collation, interpretation and evidence curation, while also supporting dedicated paediatric PGx educational initiatives. PGx consortia and paediatric clinical research networks will continue to play a central role in the streamlined development of effective PGx implementation strategies to help optimise paediatric pharmacotherapy.
Proton pump inhibitors are associated with incident type 2 diabetes mellitus in a prospective population‐based cohort study
Authors: Czarniak Petra , Ahmadizar Fariba , Hughes Jeff , Parsons Richard , Kavousi Maryam , Ikram Mohammad , Stricker Bruno H. 
Published: December 2021

AimTo investigate the association between proton pump inhibitors (PPIs) and risk of incident diabetes in a follow‐up study and to investigate its potential mechanisms.MethodsA total of 9531 individuals without type 2 diabetes (T2DM) at baseline were included from the Rotterdam Study, a prospective population‐based cohort of 14 926 individuals aged 45 years or older. During the study period (1 April 1997 to 1 January 2012) all incident cases of T2DM were enrolled. We used multivariable linear regression analysis to investigate the associations of baseline PPI use and various serum biomarkers (eg, serum magnesium, insulin‐like growth factor 1) which might modify the association. Thereafter, we excluded prevalent PPI users and performed a Cox proportional hazard regression analysis to explore the time‐varying effect of incident PPI use on T2DM during follow‐up.ResultsBaseline use of a PPI was associated with increased serum levels of fasting insulin (0.091 pmoL/L, 95% confidence interval [CI] 0.049, 0.133), homeostasis model assessment‐insulin resistance (0.100, 95% CI 0.056, 0.145) and C‐reactive protein (0.29 mg/L, 95% CI 0.198, 0.384), but decreased levels of magnesium (−0.009 mmol/L, 95% CI −0.014, −0.004) and IGF‐1 (−0.805 nmoL/L, 95% CI −1.015, −0.595). After adjustment for risk factors such as physical activity and body mass index/waist‐to‐hip ratio, current use of PPI was associated with an increased risk of incident T2DM (hazard ratio [HR] 1.69, 95% CI 1.36‐2.10). The effect was dose‐dependent with the highest risk (HR 1.88, 95% CI 1.29‐2.75) in those on more than one defined daily dose.ConclusionNew users of PPIs during follow‐up had a significantly higher dose‐dependent risk of incident diabetes. We suggest vigilance regarding their potential adverse effect on glucose homeostasis.
Intra‐articular injection of triamcinolone acetonide sustains macrophage levels and aggravates osteophytosis during degenerative joint disease in mice
Authors: Ferrao Blanco Mauricio N. , Bastiaansen Jenniskens Yvonne M. , Kops Nicole , Chavli Athina , Narcisi Roberto , Botter Sander M. , Leenen Pieter J. M. , van Osch Gerjo J. V. M. , Fahy Niamh 
Published: December 2021

Background and purposeCorticosteroids such as triamcinolone acetonide (TAA) are potent drugs administered intra‐articularly as an anti‐inflammatory therapy to relieve pain associated with osteoarthritis (OA). However, the ability of early TAA intervention to mitigate OA progression and modulate immune cell subsets remains unclear. Here, we sought to understand the effect of early intra‐articular injection of TAA on OA progression, local macrophages, and peripheral blood monocytes.Experimental approachDegenerative joint disease was induced by intra‐articular injection of collagenase into the knee joint of male C57BL/6 mice. After 1 week, TAA or saline was injected intra‐articularly. Blood was taken throughout the study to analyse monocyte subsets. Mice were killed at days 14 and 56 post‐induction of collagenase‐induced OA (CiOA) to examine synovial macrophages and structural OA features.Key resultsThe percentage of macrophages relative to total live cells present within knee joints was increased in collagenase‐ compared with saline‐injected knees at day 14 and was not altered by TAA treatment. However, at day 56, post‐induction of CiOA, TAA‐treated knees had increased levels of macrophages compared with the knees of untreated CiOA‐mice. The distribution of monocyte subsets present in peripheral blood was not altered by TAA treatment during the development of CiOA. Osteophyte maturation was increased in TAA‐injected knees at day 56.Conclusion and implicationsIntra‐articular injection of TAA increases long‐term synovial macrophage numbers and osteophytosis. Our findings suggest that TAA accentuates the progression of osteoarthritis‐associated features when applied to an acutely inflamed knee.
Categorisation of serous effusions using the International System for Reporting Serous Fluid Cytopathology and assessment of risk of malignancy with diagnostic accuracy
Authors: Ahuja Sana , Malviya Avneesh 
Published: December 2021

AbstractContextThe International System for Reporting Serous Fluid Cytopathology (ISRSFC) standardises the reporting of serous effusion cytology under five categories: Non‐Diagnostic (ND), Negative for Malignancy (NFM), Atypia of Undetermined Significance (AUS), Suspicious for Malignancy (SFM), and Malignant (M). Very few studies have been conducted so far to confirm the risk of malignancy of the different categories.AimsThe main objectives of our study were to classify serous effusions according to the ISRSFC categories and assess their risk of malignancy (ROM) and performance parameters.Materials and MethodsAll serous effusion samples received from January 2019 to December 2020 were reclassified according to the ISRSFC. Using histopathological diagnosis as the gold standard, ROM and performance parameters were calculated.ResultsA total of 831 pleural effusion samples were reclassified as follows: ND, 3 (0.4%); NFM, 635 (76.4%); AUS, 65 (7.8%); SFM, 60 (7.2%); and M, 68 (8.2%). For 457 peritoneal effusion samples, the reclassifications were ND, 5 (1.1%); NFM, 368 (80.5%); AUS, 19 (4.2%); SFM, 17 (3.7%); and M, 48 (10.5%). All 12 (100%) pericardial effusions belonged to the NFM category. The ROM for the ND, NFM, AUS, SRM, and M categories was 0%, 2.1%, 33.3%, 94.1%, 100%, respectively, in pleural effusions, and 50%, 4.8%, 22.2%, 83.3%, 100%, respectively, in peritoneal effusions. The ROM was 0% for NFM in pericardial effusions.ConclusionThe ISRSFC is an excellent system for accurately classifying serous effusions with greater reproducibility of reports and better communication between pathologist and clinician.
Persistence of natural disasters on children's health: Evidence from the Great Kantō Earthquake of 1923
Authors: Ogasawara Kota 
Published: December 2021

AbstractThis study examines a catastrophic earthquake in 1923 to analyse the long‐term effects of a natural disaster on children's health. The findings show that foetal exposure to Japan's Great Kantō Earthquake had stunting effects on girls in the devastated area. Disaster relief spending helped remediate stunting among boys by late primary school age, whereas it did not ameliorate girls’ stunting, which suggests a prenatal selection mechanism and compensating investment after birth. While maternal mental stress due to the fear of vibrations and anticipation of future aftershocks played a role in the adverse health effects, maternal nutritional stress via physical disruption also enhanced those effects.
Size‐dependent mortality of corals during marine heatwave erodes recovery capacity of a coral reef
Authors: Speare Kelly E. , Adam Thomas C. , Winslow Erin M. , Lenihan Hunter S. , Burkepile Deron E. 
Published: December 2021

AbstractFor many long‐lived taxa, such as trees and corals, older, and larger individuals often have the lowest mortality and highest fecundity. However, climate change‐driven disturbances such as droughts and heatwaves may fundamentally alter typical size‐dependent patterns of mortality and reproduction in these important foundation taxa. Working in Moorea, French Polynesia, we investigated how a marine heatwave in 2019, one of the most intense marine heatwaves at our sites over the past 30 years, drove patterns of coral bleaching and mortality. The marine heatwave drove island‐wide mass coral bleaching that killed up to 76% and 65% of the largest individuals of the two dominant coral genera, Pocillopora and Acropora, respectively. Colonies of Pocillopora and Acropora ≥30 cm diameter were ~3.5× and ~1.3×, respectively, more likely to die than colonies <30‐cm diameter. Typically, annual mortality in these corals is concentrated on the smallest size classes. Yet, this heatwave dramatically reshaped this pattern, with heat stress disproportionately killing larger coral colonies and equalizing annual mortality rates across the size spectrum. This shift in the size‐mortality relationship reduced the overall fecundity of these genera by >60% because big corals are disproportionately important for reproduction on reefs. Additionally, the survivorship of microscopic coral recruits, critical for the recovery of corals following disturbances, declined to 2%, over an order of magnitude lower compared to a year without elevated thermal stress, where 33% of coral recruits survived. While other research has shown that larger corals can bleach more frequently than smaller corals, we show the severe impact this phenomenon can have at the reef‐wide scale. As marine heatwaves become more frequent and intense, disproportionate mortality of the largest, most fecund corals and near‐complete loss of entire cohorts of newly‐settled coral recruits will likely reduce the recovery capacity of these iconic ecosystems.
Histone variant H2A.Z plays multiple roles in the maintenance of heterochromatin integrity
Authors: Tsukii Kazuki , Takahata Shinya , Murakami Yota 
Published: December 2021

AbstractH2A.Z, an evolutionally well‐conserved histone H2A variant, is involved in many biological processes. Although the function of H2A.Z in euchromatic gene regulation is well known, its function and deposition mechanism in heterochromatin are still unclear. Here, we report that H2A.Z plays multiple roles in fission yeast heterochromatin. While a small amount of H2A.Z localizes at pericentromeric heterochromatin, loss of methylation of histone H3 at Lys9 (H3K9me) induces the accumulation of H2A.Z, which is dependent on the H2A.Z loader, SWR complex. The accumulated H2A.Z suppresses heterochromatic non‐coding RNA transcription. This transcriptional repression activity requires the N‐terminal tail of H2A.Z, which is involved in the regulation of euchromatic gene transcription. RNAi‐defective cells, in which a substantial amount of H3K9me is retained by RNAi‐independent heterochromatin assembly, also accumulate H2A.Z at heterochromatin, and the additional loss of H2A.Z in these cells triggers a further decrease in H3K9me. Our results suggest that H2A.Z facilitates RNAi‐independent heterochromatin assembly by antagonizing the demethylation activity of Epe1, an eraser of H3K9me. Furthermore, H2A.Z suppresses Epe1‐mediated transcriptional activation, which is required for subtelomeric gene repression. Our results provide novel evidence that H2A.Z plays diverse roles in chromatin silencing.
Glucolipids and lipoteichoic acids affect the activity of SigI, an alternative sigma factor, and WalKR, an essential two‐component system, in Bacillus subtilis
Authors: Matsuoka Satoshi , Shimizu Yoko , Nobe Kaori , Matsumoto Kouji , Asai Kei , Hara Hiroshi 
Published: December 2021

AbstractIn a Bacillus subtilis ugtP mutant lacking glucolipids, SigI was activated in the log phase, and the activation of SigI in the mutant was suppressed by the expression of native ugtP. By contrast, SigI was inhibited in a yfnI mutant lacking one of the lipoteichoic acid (LTA) synthase genes, and the inhibition was suppressed by the expression of yfnI. A series of mutation analyses of the sigI promoter revealed that the two WalR binding sites were involved in the increase of PsigI‐lacZ activity in the ugtP mutant and decrease of the lacZ activity in the yfnI mutant. Transcription from the SigI recognition sequence was enhanced in the ugtP mutant, whereas yfnI disruption inhibited the transcription from the SigA recognition sequence in the sigI promoter. We found that not only SigI but also WalKR, the essential two‐component system, was activated in the ugtP mutant and inhibited in the yfnI mutant. The walK mutants with activated WalR exhibited abnormal morphology, but this phenotype was suppressed by the addition of MgSO4. We conclude that glucolipids and LTA are key compounds in the maintenance of normal cell surface structure in B. subtilis.
The early start of hemoperfusion decreases the mortality rate among severe COVID‐19 patients: A preliminary study
Authors: Mikaeili Haleh , Taghizadieh Ali , Nazemiyeh Masoud , Rezaeifar Parisa , Zununi Vahed Sepideh , Safiri Saeid , Ardalan Mohammadreza , Ansarin Khalil 
Published: December 2021

AbstractBackgroundCoronavirus disease‐2019 (COVID‐19)‐related organ failure is partly related to a sepsis‐like syndrome and extreme pro‐inflammatory cytokine release, named cytokine storm. Therapeutic strategies that prevent the production of or remove the pro‐inflammatory cytokines could potentially be an effective therapy in critically afflicted COVID‐19 patients.MethodsIn this clinical trial study, from April until June 2020, 68 COVID‐19 patients (35 vs. 33 controls) with severe critical symptoms, and PaO2/FiO2 (P/F) ratio less than 200 mmHg either received a single standard therapy or a combination of standard treatment for COVID‐19 combined with hemoperfusion (hemofilter, HA330 D Javfron) for 4 h, in 3 consecutive days. The length of hospital stay and mechanical ventilation, the resolution of radiologic abnormalities, and the mortality rate were defined as the primary outcomes.ResultsDemographic characteristics, the acute physiology, and chronic health evaluation score of both groups were similar (p > 0.05). Importantly, we noticed a significant mortality rate reduction in the perfused group compared with controls (37.1% vs. 63.6%, p = 0.02), this positive effect was stronger among those with a P/F ratio higher than 75 (mortality rate of 84.7% for P/F ratio < 75 vs. 15.4% for P/F ratio ≥ 75, p = 0.02).ConclusionsThe results imply that early start of hemoperfusion could be more effective and significantly reduce the mortality rate among COVID‐19 patients with critical diseases.