bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in prevalence of pre-existing diabetes and perinatal outcomes: a large, population-based study in Catalonia, Spain, 2006–2015
Authors: Gortazar Lucia , Goday Albert , Flores-Le Roux Juana Antonia , Sarsanedas Eugènia , Payà Antonio , Mañé Laura , Pedro-Botet Juan , Benaiges David 
Published: October 2020

IntroductionThis study aims to assess trends in the prevalence of pre-existing diabetes and whether the risk of adverse perinatal outcomes decreased in women between 2006 and 2015 in Catalonia, Spain.Research design and methodsA population-based study of 743 762 singleton deliveries between 2006 and 2015 in Catalonia, Spain, was conducted using data from the Spanish Minimum Basic Data Set. Cases of type 1 diabetes (T1DM) and ‘type 2 diabetes and other pre-existing diabetes’ (‘T2DM and other PGD’) were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Crude and age-adjusted annual prevalences were calculated. Poisson regression model was used to assess trends in prevalence and perinatal outcomes during the study period.ResultsOverall prevalences of pre-existing diabetes, T1DM and ‘T2DM and other PGD’ were 0.52% (95% CI 0.51 to 0.54), 0.17% (95% CI 0.17 to 0.18) and 0.35% (95% CI 0.33 to 0.36), respectively. From 2006 to 2015, rates increased for pre-existing diabetes (from 0.43 (95% CI 0.39 to 0.48) to 0.56% (0.50 to 0.62), p<0.001), T1DM (from 0.14 (0.11 to 0.17) to 0.20% (0.17 to 0.23), p<0.001) and ‘T2DM and other PGD’ (from 0.29 (0.25 to 0.33) to 0.36% (0.31 to 0.40), p<0.001). Pre-eclampsia rose in women with pre-existing diabetes (from 4.38% to 8.97%, adjusted p<0.001), T1DM (from 3.85% to 12.88%, p=0.005) and ‘T2DM and other PGD’ (from 4.63% to 6.78%, adjusted p=0.01). Prevalence of prematurity, cesarean section and small for gestational age remained stable in all diabetes groups. However, the prevalence of macrosomia fell in women with pre-existing diabetes (from 18.18% to 11.9%, adjusted p=0.011) and ‘T2DM and other PGD’ (from 14.71% to 11.06%, non-adjusted p=0.022, adjusted p=0.305) and large for gestational age decreased in all diabetes groups (from 39.73% to 30.25% in pre-existing diabetes, adjusted p=0.004).ConclusionsThe prevalence of pre-existing diabetes increased significantly in Catalonia between 2006 and 2015. Despite improvements in outcomes related to excessive birth weight, pre-eclampsia rates are rising and overall perinatal outcomes in women with pre-existing diabetes continue to be markedly worse than in the population without diabetes.
Validation analysis of Global Health Security Index (GHSI) scores 2019
Authors: Boyd Matthew J , Wilson Nick , Nelson Cassidy 
Published: October 2020

IntroductionThe COVID-19 pandemic powerfully demonstrates the consequences of biothreats. Countries will want to know how to better prepare for future events. The Global Health Security Index (GHSI) is a broad, independent assessment of 195 countries’ preparedness for biothreats that may aid this endeavour. However, to be useful, the GHSI’s external validity must be demonstrated. We aimed to validate the GHSI against a range of external metrics to assess how it could be utilised by countries.MethodsGlobal aggregate communicable disease outcomes were correlated with GHSI scores and linear regression models were examined to determine associations while controlling for a number of global macroindices. GHSI scores for countries previously exposed to severe acute respiratory syndrome (SARS), Middle East respiratory syndrome and Ebola and recipients of US Global Health Security Agenda (GHSA) investment were compared with matched control countries. Possible content omissions in light of the progressing COVID-19 pandemic were assessed.ResultsGHSI scores for countries had strong criterion validity against the Joint External Evaluation ReadyScore (rho=0.82, p<0.0001), and moderate external validity against deaths from communicable diseases (−0.56, p<0.0001). GHSI scores were associated with reduced deaths from communicable diseases (F(3, 172)=22.75, p<0.0001). The proportion of deaths from communicable diseases decreased 4.8% per 10-point rise in GHSI. Recipient countries of the GHSA (n=31) and SARS-affected countries (n=26), had GHSI scores 6.0 (p=0.0011) and 8.2 (p=0.0010) points higher than matched controls, respectively. Biosecurity and biosafety appear weak globally including in high-income countries, and health systems, particularly in Africa, are not prepared. Notably, the GHSI does not account for all factors important for health security.ConclusionThe GHSI shows promise as a valid tool to guide action on biosafety, biosecurity and systems preparedness. However, countries need to look beyond existing metrics to other factors moderating the impact of future pandemics and other biothreats. Consideration of anthropogenic and large catastrophic scenarios is also needed.
QRS complex characteristics and patient outcomes in out-of-hospital pulseless electrical activity cardiac arrest
Authors: Kim Jung Ho , Ryoo Hyun Wook , Kim Jong-yeon , Ahn Jae Yun , Moon Sungbae , Lee Dong Eun , Mun You Ho , Son Jang Won 
Published: October 2020

BackgroundPulseless electrical activity (PEA) is increasingly observed in out-of-hospital cardiac arrest (OHCA), but outcomes are still poor. We aimed to assess the relationship between QRS characteristics and outcomes of patients with OHCA with initial PEA (OHCA-P).MethodsThis prospective observational study included patients aged at least 18 years who developed OHCA-P between 1 January 2016 and 31 December 2018, and were enrolled in the Daegu Emergency Medical Services registry, South Korea. We performed multivariable logistic regression analyses to identify the associations between QRS characteristics and OHCA-P outcomes, in which QRS complexes were considered separately (model 1) and simultaneously (model 2). The primary outcome was survival to hospital discharge and the secondary outcome was a favourable neurological outcome.ResultsOf the 3659 patients with OHCA, 576 were enrolled (median age 73 years; 334 men). A higher QRS amplitude was associated with survival to hospital discharge and a favourable neurological outcome in model 1 (adjusted OR (aOR) 1.077 and 1.106, respectively; 95% CI 1.021 to 0.136 and 1.029 to 1.190, respectively) and model 2 (aOR 1.084 and 1.123, respectively; 95% CI 1.026 to 1.145 and 1.036 to 1.216, respectively). A QRS width of <120 ms was associated with survival to hospital discharge and a favourable neurological outcome in model 1 (aOR 3.371 and 4.634, respectively; 95% CI 1.633 to 6.960 and 1.562 to 13.144, respectively) and model 2 (aOR 3.213 and 5.103, respectively; 95% CI 1.568 to 6.584 and 1.682 to 15.482, respectively). Survival to hospital discharge and neurological outcome were not associated with QRS frequency.ConclusionOHCA-P outcomes were better when the initial QRS complex showed a higher amplitude or narrower width.
Discovery of biomarker candidates associated with the risk of short-term and mid/long-term relapse after infliximab withdrawal in Crohn’s patients: a proteomics-based study
Authors: Pierre Nicolas , Baiwir Dominique , Huynh-Thu Vân Anh , Mazzucchelli Gabriel , Smargiasso Nicolas , De Pauw Edwin , Bouhnik Yoram , Laharie David , Colombel Jean-Frédéric , Meuwis Marie-Alice , Louis Edouard 
Published: October 2020

ObjectiveA subset of Crohn’s disease (CD) patients experiences mid/long-term remission after infliximab withdrawal. Biomarkers are needed to identify those patients.DesignNew biomarkers of relapse were searched in the baseline serum of CD patients stopping infliximab when they were under combined therapy (antimetabolite and infliximab) and stable clinical remission (diSconTinuation in CrOhn’s disease patients in stable Remission on combined therapy with Immunosuppressors cohort, n=102). From shotgun proteomics experiment (discovery step), biomarker candidates were identified and further targeted by selected reaction monitoring (verification step). The dataset was stratified to search for markers of short-term (<6 months) or mid/long-term relapse (>6 months). The risk of relapse and the predicting capacity associated with biomarker candidates were evaluated using univariate Cox model and log-rank statistic, respectively. To test their complementary predicting capacity, biomarker candidates were systematically combined in pairs.ResultsDistinct biomarker candidates were associated with the risk (HR) of short-term (15 proteins, 2.9<HR<16.1, p<0.05) and mid/long-term (17 proteins, 2.1<HR<4.7, p<0.05) relapse, they reflect different pathophysiological processes. In stratified and non-stratified datasets, novel marker combinations exhibited a high predicting capacity as shown by their higher Z-scores (false discovery rate <0.001) than C reactive protein and faecal calprotectin (current references in predicting relapse).ConclusionWe identified for the first time circulating biomarker candidates associated with the risk of mid/long-term relapse in CD patients stopping infliximab. We also highlight a sequence of pathophysiological processes leading to relapse, this could help to better understand the disease progression. Our findings may pave the way for a better non-invasive evaluation of the risk of relapse when contemplating antitumour necrosis factor α withdrawal in CD patients.
Low-dose radiation treatment enhances systemic antitumor immune responses by overcoming the inhibitory stroma
Authors: Barsoumian Hampartsoum B , Ramapriyan Rishab , Younes Ahmed I , Caetano Mauricio S , Menon Hari , Comeaux Nathan I , Cushman Taylor R , Schoenhals Jonathan E , Cadena Alexandra P , Reilly Timothy P , Chen Dawei , Masrorpour Fatemeh , Li Ailin , Hong David S , Diab Adi , Nguyen Quynh-Nhu , Glitza Isabella , Ferrarotto Renata , Chun Stephen G , Cortez Maria Angelica , Welsh James 
Published: October 2020

BackgroundDespite some successes with checkpoint inhibitors for treating cancer, most patients remain refractory to treatment, possibly due to the inhibitory nature of the tumor stroma that impedes the function and entry of effector cells. We devised a new technique of combining immunotherapy with radiotherapy (XRT), more specifically low-dose XRT, to overcome the stroma and maximize systemic outcomes.MethodsWe bilaterally established 344SQ lung adenocarcinoma tumors in 129Sv/Ev mice. Primary and secondary tumors were irradiated with either high-dose or low-dose of XRT with systemic anti-programmed cell death protein 1 and anti-cytotoxic T-lymphocyte associated protein 4 administration. Survival and tumor growth were monitored for the various groups, and secondary tumors were phenotyped by flow cytometry for immune populations. Tumor growth factor-beta (TGF-β) cytokine levels were assessed locally after low-dose XRT, and specific immune-cell depletion experiments were conducted to identify the major contributors to the observed systemic antitumor effect.ResultsThrough our preclinical and clinical studies, we observed that when tumor burden was high, there was a necessity of combining high-dose XRT to ‘prime’ T cells at the primary tumor site, with low-dose XRT directed to secondary (metastatic) tumors to ‘modulate the stroma’. Low-dose XRT improved the antitumor outcomes of checkpoint inhibitors by favoring M1 macrophage polarization, enhancing natural killer (NK) cell infiltration, and reducing TGF-β levels. Depletion of CD4+T cells and NK cells abrogated the observed antitumor effect.ConclusionOur data extend the benefits of low-dose XRT to reprogram the tumor environment and improve the infiltration and function of effector immune cells into secondary tumors.
Biallelic cGMP-dependent type II protein kinase gene (PRKG2) variants cause a novel acromesomelic dysplasia
Authors: Díaz-González Francisca , Wadhwa Saruchi , Rodriguez-Zabala Maria , Kumar Somesh , Aza-Carmona Miriam , Sentchordi-Montané Lucia , Alonso Milagros , Ahmad Istaq , Zahra Sana , Kumar Deepak , Kushwah Neetu , Shamim Uzma , Sait Haseena , Kapoor Seema , Roldán Belen , Nishimura Gen , Offiah Amaka C , Faruq Mohammed , Heath Karen E. 
Published: October 2020

BackgroundC-type natriuretic peptide (CNP), its endogenous receptor, natriuretic peptide receptor-B (NPR-B), as well as its downstream mediator, cyclic guanosine monophosphate (cGMP) dependent protein kinase II (cGKII), have been shown to play a pivotal role in chondrogenic differentiation and endochondral bone growth. In humans, biallelic variants in NPR2, encoding NPR-B, cause acromesomelic dysplasia, type Maroteaux, while heterozygous variants in NPR2 (natriuretic peptide receptor 2) and NPPC (natriuretic peptide precursor C), encoding CNP, cause milder phenotypes. In contrast, no variants in cGKII, encoded by the protein kinase cGMP-dependent type II gene (PRKG2), have been reported in humans to date, although its role in longitudinal growth has been clearly demonstrated in several animal models.MethodsExome sequencing was performed in two girls with severe short stature due to acromesomelic limb shortening, brachydactyly, mild to moderate platyspondyly and progressively increasing metaphyseal alterations of the long bones. Functional characterisation was undertaken for the identified variants.ResultsTwo homozygous PRKG2 variants, a nonsense and a frameshift, were identified. The mutant transcripts are exposed to nonsense-mediated decay and the truncated mutant cGKII proteins, partially or completely lacking the kinase domain, alter the downstream mitogen activation protein kinase signalling pathway by failing to phosphorylate c-Raf 1 at Ser43 and subsequently reduce ERK1/2 activation in response to fibroblast growth factor 2. They also downregulate COL10A1 and upregulate COL2A1 expression through SOX9.ConclusionIn conclusion, we have clinically and molecularly characterised a new acromesomelic dysplasia, acromesomelic dysplasia, PRKG2 type (AMDP).
Prior antiplatelet therapy and haematoma expansion after primary intracerebral haemorrhage: an individual patient-level analysis of CLEAR III, MISTIE III and VISTA-ICH
Authors: Murthy Santosh , Roh David J , Chatterjee Abhinaba , McBee Nichol , Parikh Neal S , Merkler Alexander E , Navi Babak B , Falcone Guido J , Sheth Kevin N , Awad Issam , Hanley Daniel , Kamel Hooman , Ziai Wendy C 
Published: October 2020

ObjectiveTo evaluate the relationship between prior antiplatelet therapy (APT) and outcomes after primary intracerebral haemorrhage (ICH), and assess if it varies by haematoma location.MethodsWe pooled individual patient data from the Virtual International Stroke Trials Archive-ICH trials dataset, Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III trial and the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase III trial. The exposure was APT preceding ICH diagnosis. The primary outcome was haematoma expansion at 72 hours. Secondary outcomes were admission haematoma volume, all-cause mortality, death or major disability (modified Rankin Scale (mRS) score ≥4) and shift in mRS distribution. Mixed-effects models were used to assess the relationship between APT and outcomes. Secondary analyses were stratified by ICH location and study cohort.ResultsAmong 1420 patients with ICH, there were 782 (55.1%) lobar and 596 (42.0%) deep haemorrhages. APT was reported in 284 (20.0%) patients. In adjusted regression models, prior APT was not associated with haematoma expansion (OR, 0.97; 95% CI 0.60 to 1.57), major disability or death (OR, 1.05; 95% CI 0.61 to 1.63), all-cause mortality (OR, 0.89; 95% CI 0.47 to 1.85), admission haematoma volume (beta, −0.17; SE, 0.09; p=0.07) and shift in mRS (p=0.43). In secondary analyses, APT was associated with admission haematoma volume in lobar ICH (beta, 0.25; SE, 0.12; p=0.03), but there was no relationship with other ICH outcomes when stratified by haematoma location or study cohort.ConclusionsIn a large heterogeneous cohort of patients with ICH, prior APT was not associated with haematoma expansion or functional outcomes after ICH, regardless of haematoma location. APT was associated with admission haematoma volumes in lobar ICH.
Metabolomic profiling identifies plasma sphingosine 1-phosphate levels associated with welding exposures
Authors: Gao Shangzhi , Zhuo Zhu , Hutchinson John , Su Li , Christiani David C 
Published: October 2020

BackgroundDespite a number of known health hazards of welding fume exposure, it is unclear how exposure affects the human metabolome.ObjectiveWe assessed the metabolic profiles of welders before and after a 6-hour welding shift, controlling for circadian rhythm of metabolism on a non-welding day.MethodsWelders were recruited from a training centre in Quincy, Massachusetts, in 2006 and 2010–2012 and donated blood samples on a welding shift day before and after work, as well as on a non-welding day spent in an adjacent classroom. In total, we collected 509 samples from 74 participants. Liquid chromatography–mass spectrometry quantified 665 metabolites from thawed plasmas. Metabolites with significant time (afternoon compared with morning) and day (welding/classroom) interactions were identified by two-way analysis of variance, and the overnight changes were evaluated.ResultsSphingosine 1-phosphate (S1P) and sphingasine 1-phosphate (SA1P) exhibited significant interaction effects between day and time with false discovery rate-adjusted p values of 0.03 and <0.01, respectively. S1P, SA1P and sphingosine shared similar trends over time: high relative levels in the morning of a non-welding day declining by afternoon, but with lower starting levels on a welding day and no decline. There was no obvious pattern related to current smoking status.ConclusionS1P and SA1P profiles were different between welding day and classroom day. The S1P pathway was disrupted on the day of welding exposure. The levels of S1P, SA1P and sphingosine were highly correlated over time. S1P is a signalling lipid with many vital roles; thus, the underlying mechanism and clinical implications of this alteration need further investigation.
Transmuscular quadratus lumborum block reduces opioid consumption and prolongs time to first opioid demand after laparoscopic nephrectomy
Authors: Dam Mette , Hansen Christian , Poulsen Troels Dirch , Azawi Nessn Htum , Laier Gunnar Hellmund , Wolmarans Morné , Chan Vincent , Bendtsen Thomas Fichtner , Børglum Jens 
Published: October 2020

BackgroundRobotic and hand-assisted laparoscopic nephrectomies are often associated with moderate to severe postoperative pain. The aim of the current study was to investigate the analgesic efficacy of the transmuscular quadratus lumborum (TQL) block for patients undergoing robotic or hand-assisted laparoscopic nephrectomy.MethodsFifty patients were included in this single-center study. All patients were scheduled for elective hand-assisted or robotic laparoscopic nephrectomy under general anesthesia. Preoperatively, patients were randomly allocated to TQL block bilaterally with ropivacaine 60 mL 0.375% or 60 mL saline and all patients received standard multimodal analgesia and intravenous patient-controlled analgesia. Primary outcome was postoperative oral morphine equivalent (OME) consumption 0–12 hours. Secondary outcomes were postoperative OME consumption up to 24 hours, pain scores, time to first opioid, nausea/vomiting, time to first ambulation and hospital length of stay (LOS).ResultsMean (95% CI) OME consumption was significantly lower in the intervention group at 12 hours after surgery 50 (28.5 to 71.5) mg versus control 87.5 (62.7 to 112.3) mg, p=0.02. At 24 hours, 69.4 (43.2 to 95.5) mg versus 127 (96.7 to 158.6) mg, p<0.01. Time to first opioid was significantly prolonged in the intervention group median (IQR) 4.4 (2.8–17.6) hours compared with 0.3 (0.1–1.0) hours in the control group, p<0.001. No significant intergroup differences were recorded for time to first ambulation, pain scores, nausea/vomiting nor for LOS.ConclusionPreoperative bilateral TQL block significantly reduced postoperative opioid consumption by 43% and significantly prolonged time to first opioid.Trial registration numberNCT03571490.
Factors associated with lower knowledge of HIV and STI transmission, testing and treatment among MSM in Ireland: findings from the MSM Internet Survey Ireland (MISI) 2015
Authors: Carey Cian , O'Donnell Kate , Davoren Martin , Quinlan Mick , Igoe Derval , Barrett Peter 
Published: October 2020

BackgroundPoor knowledge regarding STI and HIV transmission, testing and treatment among men who have sex with men (MSM) may be contributing to their disproportionate burden of STIs. However, factors which predispose MSM to having this low knowledge are less understood.AimThe aim of this study was to identify factors associated with having lower knowledge of HIV and STI transmission, testing and treatment among MSM.MethodsThe MSM Internet Survey Ireland 2015 was a self-completed online national survey available to MSM living in Ireland. Thirteen factual statements were used to assess participants’ knowledge of HIV and STI transmission, testing and treatment. Respondents were defined as having ‘lower knowledge’ if they indicated prior knowledge of fewer than 11 true statements. Multivariable-adjusted logistic regression was used to identify factors associated with having lower knowledge.Results3090 MSM completed the survey, of whom 2905 (94%) were included in this study. Thirty-six per cent (n=1055) had lower knowledge of HIV and STI transmission, testing and treatment. The factors associated with having lower knowledge included being 18–24 years of age (vs >40 years; adjusted OR (aOR) 1.98, 95% CI 1.50 to 2.61), born in Ireland (vs outside Ireland; aOR 1.62, 95% CI 1.25 to 2.10) and being out to none of their contacts (vs out to most/all; aOR 1.69, 95% CI 1.20 to 2.37). Knowledge was also lower among those who never tested for HIV (vs tested negative within last 12 months; aOR 2.32, 95% CI 1.88 to 2.86) and among MSM who never visited an MSM-specific health promotion website (vs visited website; aOR 1.81, 95% CI 1.45 to 2.25).ConclusionA range of demographic factors, sexual health variables and use of MSM-specific sexual health promotion materials are associated with low knowledge regarding HIV and STI transmission, testing and treatment among MSM in Ireland. Engagement with the main national MSM-specific sexual health promotion website was associated with higher knowledge levels.
Carbon availability limits the denitrification potential of sandy loam soil from corn agroecosystems with long-term tillage and residue management
Authors: Ejack Leanne , Whalen Joann K. , Madramootoo Chandra A. 
Published: October 2020

Conservation tillage and crop residues should increase the soluble organic carbon and nitrate concentration in agricultural soil, which increases the denitrification potential. Basal denitrification (72 h laboratory incubation) was 2.1–2.7 times higher in a sandy loam soil under 15 yr of conservation tillage than conventional tillage and 1.8–2.0 times higher with high-residue (additional input 8.6–9.4 Mg dry matter·ha−1·yr−1) than low-residue inputs. Adding glucose and nitrate increased the soil denitrification potential 3- to 14-fold. Denitrification was limited by carbon availability, even in soil with 15 yr of conservation tillage and high-residue inputs.