bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of community types and features in a case–control analysis of new onset type 2 diabetes across a diverse geography in Pennsylvania
Authors: Schwartz B S , Pollak Jonathan , Poulsen Melissa N , Bandeen-Roche Karen , Moon Katherine , DeWalle Joseph , Siegel Karen , Mercado Carla , Imperatore Giuseppina , Hirsch Annemarie G 
Published: January 2021

ObjectivesTo evaluate associations of community types and features with new onset type 2 diabetes in diverse communities. Understanding the location and scale of geographic disparities can lead to community-level interventions.DesignNested case–control study within the open dynamic cohort of health system patients.SettingLarge, integrated health system in 37 counties in central and northeastern Pennsylvania, USA.Participants and analysisWe used electronic health records to identify persons with new-onset type 2 diabetes from 2008 to 2016 (n=15 888). Persons with diabetes were age, sex and year matched (1:5) to persons without diabetes (n=79 435). We used generalised estimating equations to control for individual-level confounding variables, accounting for clustering of persons within communities. Communities were defined as (1) townships, boroughs and city census tracts; (2) urbanised area (large metro), urban cluster (small cities and towns) and rural; (3) combination of the first two; and (4) county. Community socioeconomic deprivation and greenness were evaluated alone and in models stratified by community types.ResultsBorough and city census tract residence (vs townships) were associated (OR (95% CI)) with higher odds of type 2 diabetes (1.10 (1.04 to 1.16) and 1.34 (1.25 to 1.44), respectively). Urbanised areas (vs rural) also had increased odds of type 2 diabetes (1.14 (1.08 to 1.21)). In the combined definition, the strongest associations (vs townships in rural areas) were city census tracts in urban clusters (1.41 (1.22 to 1.62)) and city census tracts in urbanised areas (1.33 (1.22 to 1.45)). Higher community socioeconomic deprivation and lower greenness were each associated with increased odds.ConclusionsUrban residence was associated with higher odds of type 2 diabetes than for other areas. Higher community socioeconomic deprivation in city census tracts and lower greenness in all community types were also associated with type 2 diabetes.
Characteristics, physiology and mortality of intubated patients in an emergency care population in sub-Saharan Africa: a prospective cohort study from Kigali, Rwanda
Authors: Mbanjumucyo Gabin , Aluisio Adam , Cattermole Giles N 
Published: January 2021

BackgroundFormalised emergency departments (ED) are in early development in sub-Saharan Africa and there are limited data on emergency airway management in those settings. This study evaluates characteristics and outcomes of ED endotracheal intubation, as well as risk factors for mortality, at a teaching hospital in Rwanda.MethodsThis was a prospective observational study of consecutive patients requiring endotracheal intubation at the University Teaching Hospital of Kigali ED conducted between 1 January and 31 December 2017. A standardised data collection tool was used to record patient demographics, preintubation clinical presentation, indication for intubation, vital signs. medications and equipment used, and periintubation complications. The primary outcome was in-hospital mortality. Univariate associations were determined for risks of mortality.ResultsOf 198 intubations were analysed, 72.7% were male and the median age was 35 years (IQR 23–51). Airway protection was the most common indication for intubation (73.7%). Rapid sequence intubation was performed in 74.2% of cases; sedative-only facilitated intubation in 20.6% and non-drug assisted in 5.2%. The most common agents used were Ketamine for sedation (85.4%) and vecuronium for paralysis (65.7%). All patients were successfully intubated within three attempts, 85.4% on the first attempt. During intubation, 23.1% of patients experienced hypoxia, 6.7% aspiration and 3.6% cardiac arrest. Median ED length of stay was 2 days. Outcome data were available for 164 patients of whom 67.7% died. Bonferroni-corrected univariate analysis demonstrated that mortality was associated with higher postintubation shock index (p=0.0007) and lower postintubation systolic blood pressure (SBP) (p=0.0006).ConclusionThe first-attempt and overall success rates for intubation in this ED in Rwanda were comparable to those in high-income countries (HIC). Mortality postintubation is associated with lower postintubation SBP and higher postintubation shock index. The high complication and mortality rates suggest the need for better resources and training to address differences in compared with HIC.
Global burden of disease: acute-on-chronic liver failure, a systematic review and meta-analysis
Authors: Mezzano Gabriel , Juanola Adria , Cardenas Andres , Mezey Esteban , Hamilton James P , Pose Elisa , Graupera Isabel , Ginès Pere , Solà Elsa , Hernaez Ruben 
Published: January 2021

Background and aimsAcute-on-chronic liver failure (ACLF) is characterised by acute decompensation of cirrhosis associated with organ failures. We systematically evaluated the geographical variations of ACLF across the world in terms of prevalence, mortality, aetiology of chronic liver disease (CLD), triggers and organ failures.MethodsWe searched EMBASE and PubMed from 3/1/2013 to 7/3/2020 using the ACLF-EASL-CLIF (European Association for the Study of the Liver-Chronic Liver Failure) criteria. Two investigators independently conducted the abstract selection/abstraction of the aetiology of CLD, triggers, organ failures and prevalence/mortality by presence/grade of ACLF. We grouped countries into Europe, East/South Asia and North/South America. We calculated the pooled proportions, evaluated the methodological quality using the Newcastle-Ottawa Scale and statistical heterogeneity, and performed sensitivity analyses.ResultsWe identified 2369 studies; 30 cohort studies met our inclusion criteria (43 206 patients with ACLF and 140 835 without ACLF). The global prevalence of ACLF among patients admitted with decompensated cirrhosis was 35% (95% CI 33% to 38%), highest in South Asia at 65%. The global 90-day mortality was 58% (95% CI 51% to 64%), highest in South America at 73%. Alcohol was the most frequently reported aetiology of underlying CLD (45%, 95% CI 41 to 50). Infection was the most frequent trigger (35%) and kidney dysfunction the most common organ failure (49%). Sensitivity analyses showed regional estimates grossly unchanged for high-quality studies. Type of design, country health index, underlying CLD and triggers explained the variation in estimates.ConclusionsThe global prevalence and mortality of ACLF are high. Region-specific variations could be explained by the type of triggers/aetiology of CLD or grade. Health systems will need to tailor early recognition and treatment of ACLF based on region-specific data.
Prescription opioid use among drivers in British Columbia, 1997–2016
Authors: Staples John A , Erdelyi Shannon , Moe Jessica , Khan Mayesha , Chan Herbert , Brubacher Jeffrey R 
Published: January 2021

BackgroundOpioids increase the risk of traffic crash by limiting coordination, slowing reflexes, impairing concentration and producing drowsiness. The epidemiology of prescription opioid use among drivers remains uncertain. We aimed to examine population-based trends and geographical variation in drivers’ prescription opioid consumption.MethodsWe linked 20 years of province-wide driving records to comprehensive population-based prescription data for all drivers in British Columbia (Canada). We calculated age- and sex-standardised rates of prescription opioid consumption. We assessed temporal trends using segmented linear regression and examined regional variation in prescription opioid use using maps and graphical techniques.ResultsA total of 46 million opioid prescriptions were filled by 3.0 million licensed drivers between 1997 and 2016. In 2016 alone, 14.7% of all drivers filled at least one opioid prescription. Prescription opioid use increased from 238 morphine milligram equivalents per driver year (MMEs/DY) in 1997 to a peak of 834 MMEs/DY in 2011. Increases in MMEs/DY were greatest for higher potency and long-acting prescription opioids. The interquartile range of prescription opioid dispensation by geographical region increased from 97 (Q1=220, Q3=317) to 416 (Q1=591, Q3=1007) MMEs/DY over the study interval.ImplicationsPatterns of prescription opioid consumption among drivers demonstrate substantial temporal and geographical variation, suggesting they may be modified by clinical and policy interventions. Interventions to curtail use of potentially impairing prescription medications might prevent impaired driving.
Chromosome 10q-linked FSHD identifies DUX4 as principal disease gene
Authors: Lemmers Richard J L F , van der Vliet Patrick J , Blatnik Ana , Balog Judit , Zidar Janez , Henderson Don , Goselink Rianne , Tapscott Stephen J , Voermans Nicol C , Tawil Rabi , Padberg George W A M , van Engelen Baziel GM , van der Maarel Silvère M 
Published: January 2021

BackgroundFacioscapulohumeral dystrophy (FSHD) is an inherited muscular dystrophy clinically characterised by muscle weakness starting with the facial and upper extremity muscles. A disease model has been developed that postulates that failure in somatic repression of the transcription factor DUX4 embedded in the D4Z4 repeat on chromosome 4q causes FSHD. However, due to the position of the D4Z4 repeat close to the telomere and the complex genetic and epigenetic aetiology of FSHD, there is ongoing debate about the transcriptional deregulation of closely linked genes and their involvement in FSHD.MethodDetailed genetic characterisation and gene expression analysis of patients with clinically confirmed FSHD and control individuals.ResultsIdentification of two FSHD families in which the disease is caused by repeat contraction and DUX4 expression from chromosome 10 due to a de novo D4Z4 repeat exchange between chromosomes 4 and 10. We show that the genetic lesion causal to FSHD in these families is physically separated from other candidate genes on chromosome 4. We demonstrate that muscle cell cultures from affected family members exhibit the characteristic molecular features of FSHD, including DUX4 and DUX4 target gene expression, without showing evidence for transcriptional deregulation of other chromosome 4-specific candidate genes.ConclusionThis study shows that in rare situations, FSHD can occur on chromosome 10 due to an interchromosomal rearrangement with the FSHD locus on chromosome 4q. These findings provide further evidence that DUX4 derepression is the dominant disease pathway for FSHD. Hence, therapeutic strategies should focus on DUX4 as the primary target.
Rapid response team integration at a quaternary care academic centre: new paradigm for critical care organistions
Authors: Gupta Rohit R , Gonzalez Cristhian , Wang Jennifer , Martillo Miguel , Kohli-Seth Roopa 
Published: January 2021

ABSTRACTBackgroundDecompensating patients require expeditious and focused care at the bedside. This can be particularly challenging when there are multiple layers of providers, each with differing specialisation, experience and autonomy. We examined the impact of our intensivist-driven hospital-wide rapid response team (RRT) at our 1171-bed quaternary care centre.DesignSingle-centre retrospective cohort study.MethodsRRT service was implemented to assess, manage and triage acutely ill patients outside the intensive care unit (ICU). Criteria for consultation and workflow were established. The 24/7 team was led by an intensivist and included nurse practitioners and respiratory therapists. Over 3 years, we reviewed the impact of the RRT on patient outcomes and critical care support beyond the ICU.ResultsOver 3 years, the RRT received 31 392 consults for 12 122 individual patients averaging 30 consults over 24 hours. 58.9% of the calls received were for sepsis alerts/risk of decompensation and 41.1% of the consults were for reasons of acute decompensation. Among patients that were seen by the RRT, over the course of their hospital stay, 14% were upgraded to a step-down unit, 18% were upgraded to the ICU and 68% completed care without requiring any escalation. The average mortality rate for patients seen by the RRT service during their hospital stay was 11.3% with an average 30-day readmission rate of 16.5% and average hospital length of stay 16 days without significant variation between the 3 years.ConclusionsIntensivist-led RRT ensured consistent high value care. Early intervention and consistent supervision enabled timely and efficient delivery of critical care services.
Guidelines for mono, double and triple antithrombotic therapy
Authors: van Uden Renate C A E , Houtenbos Ilse , Griffioen-Keijzer Anita , Odekerken Diego A M , van den Bemt Patricia M L A , Becker Matthijs L 
Published: January 2021

ABSTRACTGuidelines for antithrombotic therapy are complex, especially if a patient has several indications that require antithrombotic therapy. In general, no patient should receive lifelong double or triple antithrombotic therapy. In this overview, we outline the most common indications for mono, double and triple antithrombotic therapy; the preferred antithrombotic therapy and the recommended duration of therapy. Both antiplatelet therapy and therapeutic anticoagulation therapy with vitamin K antagonists or direct oral anticoagulants were included. European guidelines were used or, if no European guidelines were available, the Dutch guidelines were used.
Determinants associated with viable genital or rectalChlamydia trachomatisbacterial load (FemCure)
Authors: Janssen Kevin J H , Wolffs Petra F G , Hoebe Christian J P A , Heijman Titia , Götz Hannelore M , Bruisten Sylvia M , Schim van der Loeff Maarten , de Vries Henry J , Dukers-Muijrers Nicole H T M 
Published: January 2021

BackgroundChlamydia trachomatis(CT) is routinely diagnosed by nucleic acid amplification tests (NAATs), which are unable to distinguish between nucleic acids from viable and non-viable CT organisms.ObjectivesWe applied our recently developed sensitive PCR (viability PCR) technique to measure viable bacterial CT load and explore associated determinants in 524 women attending Dutch sexual health centres (STI clinics), and who had genital or rectal CT.MethodsWe included women participating in the FemCure study (Netherlands, 2016–2017). At the enrolment visit (pre-treatment), 524 were NAAT positive (n=411 had genital and rectal CT, n=88 had genital CT only and n=25 had rectal CT only). We assessed viable rectal and viable genital load using V-PCR. We presented mean load (range 0 (non-viable) to 6.5 log10CT/mL) and explored potential associations with urogenital symptoms (coital lower abdominal pain, coital blood loss, intermenstrual bleeding, altered vaginal discharge, painful or frequent micturition), rectal symptoms (discharge, pain, blood loss), other anatomical site infection and sociodemographics using multivariable regression analyses.ResultsIn genital (n=499) CT NAAT-positive women, the mean viable load was 3.5 log10CT/mL (SD 1.6). Genital viable load was independently associated with urogenital symptoms—especially altered vaginal discharge (Beta=0.35, p=0.012) and with concurrent rectal CT (aBeta=1.79; p<0.001). Urogenital symptoms were reported by 50.3% of women; their mean genital viable load was 3.6 log10CT/mL (vs 3.3 in women without symptoms). Of 436 rectal CT NAAT-positive women, the mean rectal viable load was 2.2 log10CT/mL (SD 2.0); rectal symptoms were reported by 2.5% (n=11) and not associated with rectal viable load.ConclusionAmong women diagnosed with CT in an outpatient clinical setting, viable genital CT load was higher in those reporting urogenital symptoms, but the difference was small. Viable genital load was substantially higher when women also had a concurrent rectal CT.Trial registration numberClinicalTrials.govNCT02694497.
Diagnostic role of CXCL13 and CSF serology in patients with neurosyphilis
Authors: Li Dongdong , Huang Xiyue , Shi Mingqiao , Luo Lan , Tao Chuanmin 
Published: January 2021

BackgroundConsidering the unknown prevalence of neurosyphilis in West China, and the confusing diagnosis of neurosyphilis, the role of CSF_CXCL13 and syphilis serology was studied to provide a more accurate reference for the clinical detection and diagnosis of neurosyphilis.MethodsA retrospective data set I was used to investigate the prevalence of neurosyphilis, as well as the laboratory characteristics of 244 patients. Besides, to explore the diagnostic value of CSF_CXCL13 and syphilis serology for neurosyphilis, another 116 CSF_serum paired samples (data set II) were collected from 44 neurosyphilis and 72 non-neurosyphilis/syphilis patients.ResultsAbout 6.25% (156 out of 2494) syphilis was neurosyphilis. WhenTreponema palliduminfection occurs, syphilis serology (sero_TRUST ≥1:16 and sero_TPPA titre ≥1:10240) can be good predictors of neurosyphilis, as well as syphilis CSF serology (CSF_TPPA ≥1:320, CSF_TRUST and venereal disease research laboratory). The sensitivity of serology in neurosyphilis can be complemented by CSF_CXCL13, which could be the therapy monitor of neurosyphilis.ConclusionDue to the lack of ideal biomarkers for neurosyphilis, the importance of syphilis serology cannot be ignored, and their combination with CSF_CXCL13 or other biomarkers should be further investigated.
Impact of cigarette package warnings on attitudes towards sharing and gifting cigarettes in China: a nationwide study of smokers and non-smokers
Authors: Liao Yanhui , Tang Jinsong , McNeill Ann , Kelly Brian C , Cohen Joanna E 
Published: January 2021

BackgroundSharing and gifting cigarettes are common in China. These social practices promote cigarette consumption, and consequently may reduce quit rates in China. This study investigated sharing and gifting cigarettes, and the relationship of observing pictorial health warnings to attitudes towards sharing and gifting cigarettes in China.MethodsWe conducted an online nationwide cross-sectional study of 9818 adults in China. Experiences of sharing and gifting cigarettes, and attitudes towards sharing and gifting cigarettes before and after viewing text and pictorial health warnings on the packages were assessed, and compared between smokers and non-smokers.ResultsMost current smokers reported experiences of sharing (97%) and gifting (around 90%) cigarettes. Less than half of non-smokers reported sharing cigarettes and receiving gifted cigarettes, but over half (61.4%) gave cigarettes as a gift to others. More than half of non-smokers but less than 10% of smokers disagreed with sharing and gifting cigarettes. After observing both text and pictorial health warnings on the packages, disagreement with sharing and gifting cigarettes increased by more than 10 percentage points among both smokers and non-smokers.ConclusionHaving pictorial health warnings on cigarette packages may reduce sharing and gifting cigarettes in China.
Oncogenic N-Ras Mitigates Oxidative Stress–Induced Apoptosis of Hematopoietic Stem Cells
Authors: Ney Gina M. , Yang Kevin B. , Ng Victor , Liu Lu , Zhao Meiling , Kuk Wun , Alaka Lila , Sampang Leilani , Ross Adam , Jones Morgan A. , Jin Xi , McKay Laura M. , Evarts Hadie , Li Qing 
Published: January 2021

Abstract

Leukemic relapse is believed to be driven by transformed hematopoietic stem cells (HSC) that harbor oncogenic mutations or have lost tumor suppressor function. Recent comprehensive sequencing studies have shown that mutations predicted to activate Ras signaling are highly prevalent in hematologic malignancies and, notably, in refractory and relapsed cases. To better understand what drives this clinical phenomenon, we expressed oncogenic NrasG12D within the hematopoietic system in mice and interrogated its effects on HSC survival. N-RasG12D conferred a survival benefit to HSCs and progenitors following metabolic and genotoxic stress. This effect was limited to HSCs and early progenitors and was independent of autophagy and cell proliferation. N-RasG12D–mediated HSC survival was not affected by inhibition of canonical Ras effectors such as MEK and PI3K. However, inhibition of the noncanonical Ras effector pathway protein kinase C (PKC) ameliorated the protective effects of N-RasG12D. Mechanistically, N-RasG12D lowered levels of reactive oxygen species (ROS), which correlated with reduced mitochondrial membrane potential and ATP levels. Inhibition of PKC restored the levels of ROS to that of control HSCs and abrogated the protective effects granted by N-RasG12D. Thus, N-RasG12D activation within HSCs promotes cell survival through the mitigation of ROS, and targeting this mechanism may represent a viable strategy to induce apoptosis during malignant transformation of HSCs.

Significance:
Targeting oncogenic N-Ras–mediated reduction of ROS in hematopoietic stem cells through inhibition of the noncanonical Ras effector PKC may serve as a novel strategy for treatment of leukemia and other Ras-mutated cancers.
Association between Gene Promoter Methylation and Cervical Cancer Development: Global Distribution and A Meta-analysis
Authors: El Aliani Aissam , El-Abid Hassan , El Mallali Yassine , Attaleb Mohammed , Ennaji Moulay Mustapha , El Mzibri Mohammed 
Published: January 2021

Abstract
DNA methylation is the main epigenetic event for gene silencing and is associated with carcinogenesis. In this meta-analysis, we evaluated the association between the methylation of the promoter regions of APC, CADM1, CCNA1, CDH1, DAPK, FHIT, HIC1, MAL, MGMT, hMLH1, P16, PAX1, RAR-β, and RASSF1 genes and the risk of cervical cancer development and progression. Overall, 194 eligible studies were identified assessing the associations of promoter methylation status of aforementioned genes with low- and high-grade squamous intraepithelial lesions (LSIL and HSIL) and cervical cancer development. The majority of studies were conducted on Caucasian and Asian populations, whereas rare studies were available on the African population. Promoter methylation frequencies were shown to be significantly higher in LSIL and HSIL cervical cancer cases as compared to control specimens for CADM1, CCNA1, CDH1, DAPK1, FHIT, MAL, P16, PAX1, RAR-β, and RASSF1 genes. A moderate association was found between HIC promoter methylation, whereas APC, MGMT, and hMLH1 promoter methylation was not correlated with cervical cancer development. Promoter methylation could be considered as a noninvasive biomarker for early cervical lesions, making them highly promising targets for a personalized therapeutic approach.