bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiplatelet therapy and outcome in COVID-19: the Health Outcome Predictive Evaluation Registry
Authors: Santoro Francesco , Nuñez-Gil Ivan Javier , Vitale Enrica , Viana-Llamas Maria C , Reche-Martinez Begoña , Romero-Pareja Rodolfo , Feltez Guzman Gisela , Fernandez Rozas Inmaculada , Uribarri Aitor , Becerra-Muñoz Víctor Manuel , Alfonso-Rodriguez Emilio , Garcia-Aguado Marcos , Huang Jia , Ortega-Armas María Elizabeth , Garcia Prieto Juan F , Corral Rubio Eva Maria , Ugo Fabrizio , Bianco Matteo , Mulet Alba , Raposeiras-Roubin Sergio , Jativa Mendez Jorge Luis , Espejo Paeres Carolina , Albarrán Adrián Rodríguez , Marín Francisco , Guerra Federico , Akin Ibrahim , Cortese Bernardo , Ramakrishna Harish , Macaya Carlos , Fernandez-Ortiz Antonio , Brunetti Natale Daniele 
Published: October 2021

BackgroundStandard therapy for COVID-19 is continuously evolving. Autopsy studies showed high prevalence of platelet-fibrin-rich microthrombi in several organs. The aim of the study was therefore to evaluate the safety and efficacy of antiplatelet therapy (APT) in hospitalised patients with COVID-19 and its impact on survival.Methods7824 consecutive patients with COVID-19 were enrolled in a multicentre international prospective registry (Health Outcome Predictive Evaluation-COVID-19 Registry). Clinical data and in-hospital complications were recorded. Data on APT, including aspirin and other antiplatelet drugs, were obtained for each patient.ResultsDuring hospitalisation, 730 (9%) patients received single APT (93%, n=680) or dual APT (7%, n=50). Patients treated with APT were older (74±12 years vs 63±17 years, p<0.01), more frequently male (68% vs 57%, p<0.01) and had higher prevalence of diabetes (39% vs 16%, p<0.01). Patients treated with APT showed no differences in terms of in-hospital mortality (18% vs 19%, p=0.64), need for invasive ventilation (8.7% vs 8.5%, p=0.88), embolic events (2.9% vs 2.5% p=0.34) and bleeding (2.1% vs 2.4%, p=0.43), but had shorter duration of mechanical ventilation (8±5 days vs 11±7 days, p=0.01); however, when comparing patients with APT versus no APT and no anticoagulation therapy, APT was associated with lower mortality rates (log-rank p<0.01, relative risk 0.79, 95% CI 0.70 to 0.94). On multivariable analysis, in-hospital APT was associated with lower mortality risk (relative risk 0.39, 95% CI 0.32 to 0.48, p<0.01).ConclusionsAPT during hospitalisation for COVID-19 could be associated with lower mortality risk and shorter duration of mechanical ventilation, without increased risk of bleeding.Trial registration numberNCT04334291.
Insight into intraindividual variability across neuropsychological tests and its association with cognitive dysfunction in patients with lupus
Authors: He Jennifer Wei , Diaz Martinez Juan Pablo , Bingham Kathleen , Su Jiandong , Kakvan Mahta , Tartaglia Maria Carmela , Ruttan Lesley , Beaton Dorcas , Wither Joan , Choi May Y , Fritzler Marvin J , Anderson Nicole , Bonilla Dennisse , Green Robin , Katz Patricia , Touma Zahi 
Published: October 2021

ObjectiveDispersion, or variability in an individual’s performance across multiple tasks at a single assessment visit, has been associated with cognitive dysfunction (CD) in many neurodegenerative and neurodevelopmental disorders. We aimed to compute a dispersion score using neuropsychological battery (NB) tests and determine its association with CD in patients with SLE.MethodsCD was defined as a z-score of ≤−1.5 on ≥2 domains of the NB. To compute a type of dispersion score known as the intraindividual SD (ISD), the SD of age-adjusted and sex-adjusted z-scores was calculated for each visit in each patient. To estimate the association between ISD and cognitive status (CD and non-CD), we used multilevel logistic regression, adjusting for clinically important covariates.ResultsA total of 301 adult patients with SLE completed the NB at baseline, 187 of whom were reassessed at 6 months and 189 at 12 months. CD was observed in 35.2% of patients at baseline, 27.8% at 6 months and 28.0% at 12 months. Prior to covariate adjustment, the mean ISD for non-CD was 1.10±0.31 compared with 1.50±0.70 for CD. After adjusting for ethnicity, education, employment, socioeconomic status and anxiety/depression, there was a statistically significant association between ISD and CD (OR for one-unit increase in ISD: 13.56, 95% CI 4.80 to 38.31; OR for 1/10th-unit increase in ISD: 1.30, 95% CI 1.17 to 1.44). Findings were valid across multiple sensitivity analyses.ConclusionThis is the first study to show that patients with SLE who were classified as having CD by the NB had more variability across the NB tests (ie, higher ISD score) compared with those who were not classified as having CD.
Extended cost–benefit analysis of tobacco taxation in Brazil
Authors: Divino Jose Angelo , Ehrl Philipp , Candido Osvaldo , Valadao Marcos Aurelio Pereira 
Published: October 2021

BackgroundBrazil has experienced a persistent and substantial reduction in the prevalence of smoking in the population since 2006 due to increased taxes on tobacco and other tobacco control policies. Despite the effectiveness of these measures, however, the socioeconomic costs of smoking are still very high. Tobacco taxation in Brazil plays an important role among the measures adopted to curb tobacco use.MethodsThe study combines data from the National Household Sample Survey of 2008 and the National Health Survey of 2013 and applies cross-section, pooled, and probit estimations, to estimate price elasticities of tobacco consumption by distinct population cohorts. The paper presents a comprehensive cost–benefit analysis resulting from a one-time tax increase on manufactured cigarettes using estimated conditional price elasticity of cigarette consumption and probability of smoking by income and age quartiles.FindingsEach 10% price increase (BRL 0.54), due to higher tobacco taxes, reduces cigarette consumption by about 5%, and for poor smokers, it would lead to net income gains by about BRL 39.00 per month (in 2019 values). The highest net income effects were observed for the younger, aged between 15 and 29 years, and for middle-aged individuals, between 40 and 59 years old. Higher tobacco taxes lead to lower medical expenses on tobacco-related diseases and a longer, healthier and more productive life. Most importantly, this policy is progressive, as its economic effects are stronger for the poorer than for the richer according to the income quartiles.ConclusionsA tax increase that rises cigarette prices generates significant social benefits by reducing tobacco spending and medical expenses on tobacco-related diseases and raising future years of life and net income. The total benefits for the individual and the society go way beyond the public finance improvement.
The effects of upstream flexible barrier on the debris flow entrainment and impact dynamics on a terminal barrier
Authors: Vicari Hervé , Ng Charles W.W. , Nordal Steinar , Thakur Vikas , De Silva W.A. Roanga K. , Liu Haiming , Choi Clarence E. 
Published: October 2021

The destructive nature of debris flows is mainly caused by flow bulking from entrainment of an erodible channel bed. To arrest these flows, multiple flexible barriers are commonly installed along the predicted flow path. Despite the importance of an erodible bed, its effects are generally ignored when designing barriers. In this study, three unique experiments were carried out in a 28 m long flume to investigate the impact of a debris flow on both single and dual flexible barriers installed in a channel with a 6 m long erodible soil bed. Initial debris volumes of 2.5 and 6 m3 were modelled. For the test setting adopted, a small upstream flexible barrier before the erodible bed separates the flow into several surges via overflow. The smaller surges reduce bed entrainment by 70% and impact force on the terminal barrier by 94% compared to the case without an upstream flexible barrier. However, debris overflowing the deformed flexible upstream barrier induces a centrifugal force that results in a dynamic pressure coefficient that is up to 2.2 times higher than those recommended in guidelines. This suggests that although compact upstream flexible barriers can be effective for controlling bed entrainment, they should be carefully designed to withstand higher impact forces.
On the domination number of a graph and its block graph
Authors: Murugan E. , Paulraj Joseph J. 
Published: October 2021

Let [Formula: see text] be a graph. A subset [Formula: see text] of [Formula: see text] is called a dominating set of [Formula: see text] if every vertex not in [Formula: see text] is adjacent to some vertex in [Formula: see text] The domination number [Formula: see text] of [Formula: see text] is the minimum cardinality taken over all dominating sets of [Formula: see text] The block graph [Formula: see text] of a graph [Formula: see text] is a graph whose vertex set is the set of blocks in [Formula: see text] and two vertices of [Formula: see text] are adjacent if and only if the corresponding blocks have a common cut vertex in [Formula: see text] In this paper, we investigate the lower and upper bounds for the sum of domination number of a graph and its block graph and characterize the extremal graphs.
The Rise of IGFBP4 in People with Obstructive Sleep Apnea and Multilevel Sleep Surgery Recovers Its Basal Levels
Authors: Alterki Abdulmohsen , Al Shawaf Eman , Al-Khairi Irina , Cherian Preethi , Sriraman Devarajan , Hammad Maha , Thanaraj Thangavel A. , Ebrahim Mahmoud A. K. , Al-Mulla Fahd , Abu-Farha Mohamed , Abubaker Jehad 
Published: October 2021

IGFBP4 is the smallest member of the insulin-like growth factor binding protein family (IGFBP). It is a hepatic protein that plays a role in modulating the activity and bioavailability of IGF-I. The expression of IGFBP4 was found to increase under conditions of hypoxia. Obstructive sleep apnea (OSA) is a common disorder, characterized by cyclic episodes of intermittent hypoxia and fragmented sleep. Our aim was to quantify levels of circulating IGFBP1, IGFBP2, IGFBP3, IGFBP4, and IGFBP7 in fasting plasma samples of 69 Kuwaiti participants and explore its correlation with indices of OSA. The quantification was performed using multiplexing assay. The study involved 28 controls and 41 patients with OSA. Levels of circulating IGFBP4 were significantly higher in people with OSA (

289.74
±
23.30

ng/ml) compared to the control group (

217.60
±
21.74

ng/ml,

p
=
0.028

). The increase in IGFBP4 correlated significantly and positively with AHI (

r
=
.574

,

p
=
.01

) and AI (

r
=
.794

,

p
=
.001

) in people with moderate and severe OSA. There was a significant decline in circulating IGFBP4 after 3 months of surgery (

225.89
±
18.16

ng/ml,

p
=
0.012

). This was accompanied by a prominent improvement in OSA (AHI

8.97
±
2.37

events/h,

p
=
0.001

). In this study, our data showed a significant increase in circulating IGFBP4 in people with OSA. We also report a significant positive correlation between IGFBP4 and indices of OSA at baseline, which suggests IGFBP4 as a potential diagnostic biomarker for OSA. There was a significant improvement in OSA after 3 months of surgical intervention, which concurred with a significant decline in IGFBP4 levels. Altogether, the detected change suggests a potential link between IGFBP4 and OSA or an OSA-related factor, whereby OSA might play a role in triggering the induction of IGFBP4 expression.
Corneal Subbasal Plexus in Eyes with Fuchs’ Endothelial Corneal Dystrophy after Two Different Endothelial Surgeries
Authors: Abicca Irene , Gilardi Marta , Giannini Daniela , Colabelli Gisoldi Rossella Anna Maria , Pocobelli Augusto , Schiano Lomoriello Domenico 
Published: October 2021

Purpose. To evaluate the morphological features and density of corneal subbasal plexus (SBP) using in vivo corneal confocal microscopy (IVCCM) in patients affected by Fuchs’ endothelial corneal dystrophy (FECD) six months after Descemet membrane endothelial keratoplasty (DMEK) and Descemet-stripping automated endothelial keratoplasty (DSAEK). Methods. We included patients affected by FECD, requiring corneal endothelial surgery due to corneal oedema occurred from 3 to 6 months. 7 eyes underwent DMEK and 7 eyes DSAEK. All patients performed IVCCM preoperative and in six months postoperative. We analyzed SBP parameters, using CS4 Nerves Tracking Tool, and we studied the differences between the two endothelial keratoplasties. Results. Comparing the eyes treated with DMEK with those treated with DSAEK, preoperative corneal thickness, corrected distance visual acuity (CDVA), and age were similar in both groups. SBP was not detectable at preoperative IVCCM in any eye. Postoperatively, the nerve fibers length, the nerve fibers density, the tortuosity, and the number of fibers and of branching did not differ in the eyes that underwent DMEK compared to DSAEK. The corneal beadings density was higher after DMEK than DSAEK, and this difference was statistically significant (

P

= 0.004). The type of endothelial keratoplasty was not associated with the presence or absence of postoperative corneal SBP (Pearson’ chi-square, 0.755). Conclusions. Postoperative corneal reinnervation should be easily and noninvasively studied using IVCCM. Morphological postoperative features of SBP did not differ between two different types of endothelial keratoplasty, DMEK and DSAEK, despite the different sizes of the corneal incision. The lower beading density in the DSAEK group should be the consequence of a different distribution of mitochondria along the nerve fibers, as expression of a supposed higher metabolic distress in the DSAEK group.
Density of CD3+ and CD8+ Cells in the Microenvironment of Colorectal Cancer according to Prediagnostic Physical Activity
Authors: Renman David , Gylling Björn , Vidman Linda , Bodén Stina , Strigård Karin , Palmqvist Richard , Harlid Sophia , Gunnarsson Ulf , van Guelpen Bethany 
Published: October 2021

Abstract

Background:
Physical activity is associated not only with a decreased risk of developing colorectal cancer but also with improved survival. One putative mechanism is the infiltration of immune cells in the tumor microenvironment. Experimental findings suggest that physical activity may mobilize immune cells to the tumor. We hypothesized that higher levels of physical activity prior to colorectal cancer diagnosis are associated with higher densities of tumor-infiltrating T-lymphocytes in colorectal cancer patients.

Methods:
The study setting was a northern Swedish population-based cohort, including 109,792 participants with prospectively collected health- and lifestyle-related data. For 592 participants who later developed colorectal cancer, archival tumor tissue samples were used to assess the density of CD3+ and CD8+ cytotoxic T cells by IHC. Odds ratios for associations between self-reported, prediagnostic recreational physical activity and immune cell infiltration were estimated by ordinal logistic regression.

Results:
Recreational physical activity &gt;3 times per week was associated with a higher density of CD8+ T cells in the tumor front and center compared with participants reporting no recreational physical activity. Odds ratios were 2.77 (95% CI, 1.21–6.35) and 2.85 (95% CI, 1.28–6.33) for the tumor front and center, respectively, after adjustment for sex, age at diagnosis, and tumor stage. The risk estimates were consistent after additional adjustment for several potential confounders. For CD3, no clear associations were found.

Conclusions:
Physical activity may promote the infiltration of CD8+ immune cells in the tumor microenvironment of colorectal cancer.

Impact:
The study provides some evidence on how physical activity may alter the prognosis in colorectal cancer.
Advances in Understanding Early-Onset Colorectal Cancer
Authors: Hayes Richard B. 
Published: October 2021

Abstract
Since the 1990s, the incidence of early-onset colorectal cancer (at &lt;50 years of age) in the US has increased by more than 50%; similar increases have also been observed internationally. These increases are found particularly among individuals born during and after the 1960s, raising the possibility that the increased rates of early-onset colorectal cancer are attributable to changes in risk-factor patterns throughout successive generations. The reasons for these alarming epidemiologic patterns for early-onset colorectal cancer worldwide are only recently being investigated and major gaps in our knowledge remain. In the current issue of this journal, Arif and colleagues differentiated characteristics and outcomes of early-onset colorectal cancer in patients with the predisposing conditions of inflammatory bowel disease or hereditary genetic syndromes, compared with patients who have sporadic disease. Also, in this issue, Schumacher and colleagues investigated risk factors for early-onset colorectal adenocarcinoma in a nested case-control study among Kaiser Permanente Southern California (KPSC) health plan members. The research presented on characteristics and outcomes points to the importance of sporadic disease in the rise of early-onset colorectal cancer, while the research presented on risk factors points to the importance of obesity as a potential explanatory factor for this rise.
See related articles by Arif et al., p. 1785 and by Schumacher et al., p. 1792
Genome-Wide Association Study of Peripheral Artery Disease
Authors: van Zuydam Natalie R. , Stiby Alexander , Abdalla Moustafa , Austin Erin , Dahlström Emma H. , McLachlan Stela , Vlachopoulou Efthymia , Ahlqvist Emma , Di Liao Chen , Sandholm Niina , Forsblom Carol , Mahajan Anubha , Robertson Neil R. , Rayner N. William , Lindholm Eero , Sinisalo Juha , Perola Markus , Kallio Milla , Weiss Emily , Price Jackie , Paterson Andrew , Klein Barbara , Salomaa Veikko , Palmer Colin N.A. , Groop Per-Henrik , Groop Leif , McCarthy Mark I. , de Andrade Mariza , Morris Andrew P. , Hopewell Jemma C. , Colhoun Helen M. , Kullo Iftikhar J. , Grétarsdóttir Sólveig , Þorleifsson Guðmar , þorsteinsdóttir Unnur , Stefansson Kari , Mark Michael , Kanninen Timo , Thorand Barbara , Remuzzi Giuseppe , Dunger David , Shore Angela , Smith Ulf , Ylä-Herttuala Seppo , Cobelli Claudio , Bellazzi Riccardo , Ferrannini Ele , Patrono Carlo , Nuutila Pirjo , McKeague Paul , Steckel-Hamann Birgit , Gan Li-ming , Nogoceke Everson , Tortoli Piero , Jablonka Bernd , Brosnan Mary-Julia 
Published: October 2021

Background:
Peripheral artery disease (PAD) affects >200 million people worldwide and is associated with high mortality and morbidity. We sought to identify genomic variants associated with PAD overall and in the contexts of diabetes and smoking status.

Methods:
We identified genetic variants associated with PAD and then meta-analyzed with published summary statistics from the Million Veterans Program and UK Biobank to replicate their findings. Next, we ran stratified genome-wide association analysis in ever smokers, never smokers, individuals with diabetes, and individuals with no history of diabetes and corresponding interaction analyses, to identify variants that modify the risk of PAD by diabetic or smoking status.

Results:

We identified 5 genome-wide significant (
P

association

≤5×10
−8
) associations with PAD in 449 548 (N
cases
=12 086) individuals of European ancestry near
LPA (lipoprotein [a]), CDKN2BAS1 (CDKN2B antisense RNA 1), SH2B3 (SH2B adaptor protein 3) - PTPN11 (protein tyrosine phosphatase non-receptor type 11), HDAC9 (histone deacetylase 9), and CHRNA3 (cholinergic receptor nicotinic alpha 3 subunit
) loci (which overlapped previously reported associations). Meta-analysis with variants previously associated with PAD showed that 18 of 19 published variants remained genome-wide significant. In individuals with diabetes, rs116405693 at the
CCSER1 (coiled-coil serine rich protein 1
) locus was associated with PAD (odds ratio [95% CI], 1.51 [1.32–1.74],
P

diabetes

=2.5×10
−9
,
P

interactionwithdiabetes

=5.3×10
−7
). Furthermore, in smokers, rs12910984 at the
CHRNA3
locus was associated with PAD (odds ratio [95% CI], 1.15 [1.11–1.19],
P

smokers

=9.3×10
−10
,
P

interactionwithsmoking

=3.9×10
−5
).

Conclusions:
Our analyses confirm the published genetic associations with PAD and identify novel variants that may influence susceptibility to PAD in the context of diabetes or smoking status.
Combined Associations of Changes in Noncombustible Nicotine or Tobacco Product and Combustible Cigarette Use Habits With Subsequent Short-Term Cardiovascular Disease Risk Among South Korean Men: A Nationwide Cohort Study
Authors: Choi Seulggie , Lee Kiheon , Park Sang Min 
Published: October 2021

Background:
The associations of changes in noncombustible nicotine or tobacco product (NNTP) and combustible cigarette (CC) use habits with subsequent cardiovascular disease (CVD) risk are still unclear.

Methods:
The study population consisted of 5 159 538 adult men who underwent health screening examinations during both the first (2014–2015) and second (2018) health screening periods from the Korean National Health Insurance Service database. All participants were divided into continual CC-only smokers, CC and NNTP users, recent (<5 years) CC quitters without NNTP use, recent CC quitters with NNTP use, long-term (≥5 years) CC quitters without NNTP use, long-term CC quitters with NNTP use, and never smokers. Propensity score matching analysis was conducted to further compare CVD risk among CC quitters according to NNTP use. Starting from the second health screening date, participants were followed up until the date of CVD event, death, or December 31, 2019, whichever came earliest. Multivariable Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% CIs for CVD risk according to changes in NNTP and CC smoking habits.

Results:
Compared with continual CC-only smokers, CC and NNTP users (aHR, 0.83 [95% CI, 0.79–0.88]) and initial CC smokers who quit CCs and switched to NNTP use only (recent CC quitters with NNTP use, aHR, 0.81 [95% CI, 0.78–0.84]) had lower risk for CVD. After propensity score matching, recent CC quitters with NNTP use (aHR, 1.31 [95% CI, 1.01–1.70]) had higher risk for CVD than recent CC quitters without NNTP use. Similarly, compared with long-term CC quitters without NNTP use, long-term CC quitters with NNTP use (aHR, 1.70 [95% CI, 1.07–2.72]) had higher CVD risk.

Conclusions:
Switching to NNTP use among initial CC smokers was associated with lower CVD risk than continued CC smoking. On CC cessation, NNTP use was associated with higher CVD risk than CC quitting without NNTPs. Compared with CC smokers who quit without NNTP use, CC quitters who use NNTPs may be at higher future CVD risk.