bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of childhood-onset systemic lupus erythematosus in pregnancy and its association with pregnancy outcomes: a retrospective comparative cohort study
Authors: Li Zhi-Ju , Hu Hao-Yue , Ding Zi-Ling , Bian Zi-Wei , Xu Ying-Hua , Wen Hui-Ting , Qu Ya-Li , Wang Jin-Dong , Huang Xiao-Li , Li Dong , Li Jing , Hu Gui-Fang 
Published: May 2022

Abstract
Background
Disease situations are more aggressive in patients with childhood-onset systemic lupus erythematosus (cSLE) than in those with adult-onset SLE (aSLE). However, information on pregnant women with cSLE and its association with pregnancy outcomes is limited. This study aimed to compare pregnancies in patients with cSLE vs. aSLE, and further analyse the characteristics of cSLE in pregnant women and explore its association with adverse pregnancy outcomes.

Methods
Altogether, data of 167 pregnancies from 150 women, including 22 pregnancies with cSLE and 145 pregnancies with aSLE, were retrospectively analysed. Characteristics and disease activity were compared between the cSLE and aSLE groups during pregnancy. Associations between cSLE and the risk of active SLE (SLEPDAI > 4), active lupus nephritis (LN), and adverse pregnancy outcomes were analysed using logistic regression.

Results
The cSLE group had a higher incidence of active SLE (12/22 vs. 30/145, P = 0.001) and active LN (11/22 vs. 26/145, P = 0.001) than the aSLE group. In the multivariable analysis, cSLE was a risk factor for active SLE and active LN during pregnancy, with ORs of 4.742 (95%CI 1.678–13.405, P = 0.003) and 4.652 (95%CI 1.630–13.279, P = 0.004), respectively. No significant association between cSLE and the risk of composite adverse gestational outcomes was identified after sequentially adjusting pre-pregnancy characteristics and pregnancy factors (P > 0.05).

Conclusion
Disease activity of women with cSLE in pregnancy was more aggressive than that of women with aSLE, which was similar to the characteristics of non-pregnant women with SLE. cSLE might have indirect effects on the risk of adverse pregnancy outcomes through LN and active disease. Therefore, closely monitoring patients with cSLE during pregnancy is crucial.
Longitudinal changes in objectively-measured physical activity and sedentary time among school-age children in Central Texas, US during the COVID-19 pandemic
Authors: Ganzar Leigh Ann , Salvo Deborah , Burford Katie , Zhang Yuzi , Kohl Harold W. , Hoelscher Deanna M. 
Published: May 2022

Abstract
Background
Most available evidence on the effects of the COVID-19 pandemic on child movement behaviors is from cross-sectional studies using self-report measures. This study aimed to identify change trajectories and their associated factors for objectively-assessed physical activity and sedentary time among an ethnically and socioeconomically diverse sample of school-age children from Central Texas, U.S.A., during COVID-19.

Methods
Pre- (Sept. 2019 – Feb. 2020) and during- (Oct. 2020 – March 2021) COVID-19 physical activity and sedentary behavior data were collected for school-age children (8–11 years) enrolled in the Safe Travel Environment Evaluation in Texas Schools (STREETS) cohort study. Daily time spent in moderate- to vigorous-intensity physical activity (MVPA) and sedentary time were assessed using GT3X-wBT Actigraph accelerometers. Parent surveys were used to assess socio-ecological factors. Latent class linear mixed models were used to identify change trajectories of MVPA and sedentary time. Logistic regression models were used to assess the association between socio-ecological characteristics with physical activity and sedentary time change trajectory groups.

Results
There was a significant decrease in mean daily MVPA (− 9.4 mins, SD = 18.54) and an increase in sedentary behavior (0.83 hrs, SD = 1.18). Two trajectory groups were identified for MVPA (‘decrease MPVA’ and ‘maintain high MVPA’), with the majority (82.1%) being in the ‘decrease MVPA’ group. Three trajectory groups were identified for sedentary behavior (‘moderate increase sedentary, ‘steep increase sedentary,’ and ‘decrease sedentary’), with most children (78.5%) being in the ‘moderate increase’ group. Girls had significantly lower odds of being in the ‘maintain high MVPA’ group than boys (OR = 0.27, 95% CI = 0.11, 0.61). Children living in neighborhoods with higher perceived social cohesion had significantly higher odds of being in the ‘maintain high MVPA’ group (OR = 1.22, 95% CI = 1.06, 1.41), while those in neighborhoods with higher social cohesion had lower odds of being in the ‘decrease sedentary’ group (OR = 0.86, 95% CI = 0.74, 0.99).

Conclusions
Declines in physical activity and increases in sedentary time among most school-age children during COVID-19 in a socioeconomically and ethnically diverse U.S. sample, were observed in our study, especially among girls. These findings highlight the need to counteract the short-term negative changes in movement behaviors in response to COVID-19 among children.
SORBS2 as a molecular target for atherosclerosis in patients with familial hypercholesterolemia
Authors: Liu Ming-Ming , Peng Jia , Guo Yuan-Lin , Zhu Cheng-Gang , Wu Na-Qiong , Xu Rui-Xia , Dong Qian , Cui Chuan-Jue , Li Jian-Jun 
Published: May 2022

Abstract
Background
Familial hypercholesterolemia (FH) is a metabolic disease in which patients are prone to develop premature atherosclerosis (AS). Sorbin and SH3 Domain Containing 2 (SORBS2) is known to play a role in coronary heart disease (CHD). However, the mechanism underlying SORBS2 involvement in the development of hypercholesterolemia remains unknown. Here, we investigated the effects of SORBS2 on inflammation and foam cell formation and its underlying mechanisms.

Methods
Using Bioinformatics analysis, we established that SORBS2 is upregulated in patients with FH. Circulating concentrations of SORBS2 were measured using ELISA kit (n = 30). The association between circulating SORBS2 levels and inflammatory factors or lipid indexes were conducted using Spearman correlation analysis. We further conducted in vitro experiments that the expression of SORBS2 were analyzed, and SORBS2 siRNA were transfected into oxidized LDL (OxLDL)-induced macrophages, followed by western blot and immunofluorescence.

Results
Circulating SORBS2 levels were positively associated with inflammatory factors and lipid indexes. We also observed that high in vitro expression of SORBS2 in OxLDL-induced macrophages. After SORBS2 silencing, Nod like receptor family pyrin domain-containing 3 protein(NLRP3)-Caspase1 activation and NF-κB activation were attenuated, and secretion of pro-inflammatory cytokines (IL-1β and IL-18) was decreased. Moreover, SORBS2 silencing blocked reactive oxygen species (ROS) production and lipid accumulation, and promoted cholesterol efflux through ABCG1-PPARγ pathway.

Conclusions
SORBS2 regulates lipid-induced inflammation and foam cell formation, and is a potential therapeutic target for hypercholesterolemia.
Cardiometabolic diseases, total mortality, and benefits of adherence to a healthy lifestyle: a 13-year prospective UK Biobank study
Authors: Xu Chenjie , Cao Zhi 
Published: May 2022

Abstract
Background
Cardiometabolic disease (CMD) increases the risk of mortality, but the extent to which this can be offset by adherence to a healthy lifestyle is unknown. We aimed to investigate whether and to what extent a combination of healthy lifestyle is associated with lower risk of total mortality that related to CMD.

Methods
Data for this prospective analysis was sourced from the UK Biobank with 356,967 participants aged 37 to 73 years between 2006 and 2010. Adherence to a healthy lifestyle was determined on the basis of four factors: no smoking, healthy diet, body mass index < 30 kg/m2, and regular physical activity. CMD was defined as any of incidence of diabetes, coronary heart disease and stroke at baseline. Cox proportional hazards models were used to calculate hazard ratios (HRs) and confidence intervals (CIs) of the associations of CMDs and lifestyle factors with total mortality.

Results
During a median follow-up of 13 years, a total of 21,473 death events occurred. The multivariable-adjusted HRs of mortality were 1.49 (95% CI 1.53–1.56) for one, 2.17 (95% CI 2.01–2.34) for two, and 3.75 (95% CI 3.04–4.61) for three CMDs. In joint exposure analysis, compared with CMDs-free and a favorable lifestyle, the HRs of mortality were 2.57 (95% CI 2.38–2.78) for patients with CMDs plus an unfavorable lifestyle and 1.58 (95% CI 1.50–1.66) for those with CMDs plus a favorable lifestyle. A favorable lifestyle attenuates the CMDs-related risk of mortality by approximately 63%. The mortality risk of CMDs-free people but have unfavorable lifestyle was higher than those who have over one CMDs but have favorable lifestyle.

Conclusion
The potential effect of an increasing number of CMDs on total mortality appears additive, adherence to a healthy lifestyle may attenuate the CMDs-related mortality risk by more than 60%. These findings highlight the potential importance of lifestyle interventions to reduce risk of mortality across entire populations, even in patients with CMDs.
Connecting DCX, COMT and FMR1 in social behavior and cognitive impairment
Authors: Delprato Anna , Xiao Emily , Manoj Devika 
Published: May 2022

AbstractGenetic variants of DCX, COMT and FMR1 have been linked to neurodevelopmental disorders related to intellectual disability and social behavior. In this systematic review we examine the roles of the DCX, COMT and FMR1 genes in the context of hippocampal neurogenesis with respect to these disorders with the aim of identifying important hubs and signaling pathways that may bridge these conditions. Taken together our findings indicate that factors connecting DCX, COMT, and FMR1 in intellectual disability and social behavior may converge at Wnt signaling, neuron migration, and axon and dendrite morphogenesis. Data derived from genomic research has identified a multitude of genes that are linked to brain disorders and developmental differences. Information about where and how these genes function and cooperate is lagging behind. The approach used here may help to shed light on the biological underpinnings in which key genes interface and may prove useful for the testing of specific hypotheses.
The influence of poly-drug use patterns on the association between opioid agonist treatment engagement and injecting initiation assistance
Authors: Meyers-Pantele Stephanie A. , Mittal Maria Luisa , Jain Sonia , Sun Shelly , Rammohan Indhu , Fairbairn Nadia , Milloy M-J , DeBeck Kora , Hayashi Kanna , Werb Dan 
Published: May 2022

Abstract
Background
Evidence suggests people who inject drugs (PWID) prescribed opioid agonist treatment (OAT) are less likely to provide injection drug use (IDU) initiation assistance. We investigated the association between OAT engagement and providing IDU initiation assistance across poly-drug use practices in Vancouver, Canada.

Methods
Preventing Injecting by Modifying Existing Responses (PRIMER) is a prospective study seeking to identify structural interventions that reduce IDU initiation. We employed data from linked cohorts of PWID in Vancouver and extended the findings of a latent profile analysis (LPA). Multivariable logistic regression models were performed separately for the six poly-drug use LPA classes. The outcome was recently assisting others in IDU initiation; the independent variable was recent OAT engagement.

Results
Among participants (n = 1218), 85 (7.0%) reported recently providing injection initiation assistance. When adjusting for age and sex, OAT engagement among those who reported a combination of high-frequency heroin and methamphetamine IDU and low-to-moderate-frequency prescription opioid IDU and methamphetamine non-injection drug use (NIDU) was associated with lower odds of IDU initiation assistance provision (Adjusted Odds Ratio [AOR]: 0.18, 95% CI: 0.05–0.63, P = 0.008). Significant associations were not detected among other LPA classes.

Conclusions
Our findings extend evidence suggesting that OAT may provide a population-level protective effect on the incidence of IDU initiation and suggest that this effect may be specific among PWID who engage in high-frequency methamphetamine and opioid use. Future research should seek to longitudinally investigate potential causal pathways explaining the association between OAT and initiation assistance provision among PWID to develop tailored intervention efforts.
Embedding gene trees into phylogenetic networks by conflict resolution algorithms
Authors: Wawerka Marcin , Dąbkowski Dawid , Rutecka Natalia , Mykowiecka Agnieszka , Górecki Paweł 
Published: May 2022

Abstract
Background
Phylogenetic networks are mathematical models of evolutionary processes involving reticulate events such as hybridization, recombination, or horizontal gene transfer. One of the crucial notions in phylogenetic network modelling is displayed tree, which is obtained from a network by removing a set of reticulation edges. Displayed trees may represent an evolutionary history of a gene family if the evolution is shaped by reticulation events.

Results
We address the problem of inferring an optimal tree displayed by a network, given a gene tree G and a tree-child network N, under the deep coalescence and duplication costs. We propose an O(mn)-time dynamic programming algorithm (DP) to compute a lower bound of the optimal displayed tree cost, where m and n are the sizes of G and N, respectively. In addition, our algorithm can verify whether the solution is exact. Moreover, it provides a set of reticulation edges corresponding to the obtained cost. If the cost is exact, the set induces an optimal displayed tree. Otherwise, the set contains pairs of conflicting edges, i.e., edges sharing a reticulation node. Next, we show a conflict resolution algorithm that requires $$2^{r+1}-1$$

2

r
+
1

-
1

invocations of DP in the worst case, where r is the number of reticulations. We propose a similar $$O(2^kmn)$$

O
(

2
k

m
n
)

-time algorithm for level-k tree-child networks and a branch and bound solution to compute lower and upper bounds of optimal costs. We also extend the algorithms to a broader class of phylogenetic networks. Based on simulated data, the average runtime is $$\Theta (2^{{0.543}k}mn)$$

Θ
(

2

0.543

k

m
n
)

under the deep-coalescence cost and $$\Theta (2^{{0.355}k}mn)$$

Θ
(

2

0.355

k

m
n
)

under the duplication cost.

Conclusions
Despite exponential complexity in the worst case, our algorithms perform significantly well on empirical and simulated datasets, due to the strategy of resolving internal dissimilarities between gene trees and networks. Therefore, the algorithms are efficient alternatives to enumeration strategies commonly proposed in the literature and enable analyses of complex networks with dozens of reticulations.
Different electrophysiology patterns in GNE myopathy
Authors: Liu Xiangyi , Zhang Yingshuang , Zhang Shuo , Sun Aping , Zheng Danfeng , Fan Dongsheng , Liu Xiaoxuan 
Published: May 2022

Abstract
Background
GNE myopathy is a rare distal myopathy caused by mutations of the GNE gene. A few cases of GNE myopathy accompanied by neurogenic features of electrophysiology mimicking hereditary motor neuropathy were reported recently. We confirmed this feature and described the clinical phenotype and mutations of GNE myopathy in these rare cases.

Results
The absence of lower limb tendon reflexes, decreased compound muscle action potentials in lower leg motor nerves, and neurogenic pattern of electromyography suggested neuropathy in four patients. However, muscle pathology revealed a predominantly myogenic pattern. The follow-up electroneurography results implied that the compound motor action potential amplitudes deteriorated over time. Next-generation sequencing identified three novel variants of the GNE gene, c.2054T > C (p.Val685Ala), c.424G > A (p.Gly142Arg) and c.944T > C (p.Phe315Ser), as well as two hotspot mutations, c.115C > T(p.Arg39*) and c.620A > T(p.Asp207Val), in these patients. These novel mutations cosegregated with disease in the family.

Conclusions
These rare cases supported the existence of neurogenic features of electrophysiology different from the typical myopathic pattern of GNE myopathy.
Statistical analysis plan for the randomized controlled trial Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST)
Authors: Eltoft Agnethe , Wilsgaard Tom , Roaldsen Melinda B. , Søyland Mary-Helen , Lundström Erik , Petersson Jesper , Indredavik Bent , Putaala Jukka , Christensen Hanne , Kõrv Janika , Jatužis Dalius , Engelter Stefan T. , De Marchis Gian Marco , Werring David J. , Robinson Thompson , Tveiten Arnstein , Mathiesen Ellisiv B. 
Published: May 2022

Abstract
Background
Patients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings.

Objective
To publish the detailed statistical analysis plan for TWIST prior to unblinding.

Methods
The TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CONSORT) statement and provides clear and open reporting.

Discussion
Publication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses.

Trial registration
ClinicalTrials.govNCT03181360. EudraCT Number 2014-000096-80. WHO ICRTP registry number ISRCTN10601890.
Randomized double-blind, placebo-controlled study of topical diclofenac in the prevention of hand-foot syndrome in patients receiving capecitabine (the D-TORCH study)
Authors: Santhosh Akhil , Kumar Akash , Pramanik Raja , Gogia Ajay , Prasad Chandra Prakash , Gupta Ishaan , Gupta Nishkarsh , Cheung Winson Y. , Pandey Ravindra Mohan , Sharma Atul , Batra Atul 
Published: May 2022

AbstractIntroductionHand-foot syndrome (HFS) is a common cutaneous side effect of capecitabine therapy. Apart from oral cyclooxygenase-2 (COX-2) inhibitor (celecoxib), there are no proven strategies for the prevention of HFS. However, celecoxib is associated with significant cardiotoxicity. To date, no study has evaluated the role of topical COX inhibitor, diclofenac. In this study, we aim to compare topical 1% diclofenac gel with placebo in the prevention of capecitabine-induced HFS.MethodsThis is a randomized, placebo-controlled, double-blind, parallel-group superiority trial: the Diclofenac Topical in Reducing Capecitabine induced HFS (D-TORCH) study. A total of 264 patients with breast and gastrointestinal malignancies will be randomly allocated (stratified by sex and type of therapy [monotherapy or combination regimen with capecitabine]) to receive either 1% topical diclofenac or placebo that will be applied over the palmar and dorsal surface of the hands twice daily whilst taking capecitabine for 12 weeks. The patients will be followed up until the end of four cycles. The primary objective of this study is to compare the effect of topical diclofenac with placebo in preventing HFS (incidence of NCI CTCAEv5.0 grade 2 or higher HFS). The secondary objective is to compare the effect of topical diclofenac with placebo on preventing all grades of HFS (incidence of NCI CTCv5.0 all grade HFS), time to develop HFS (from the start of capecitabine), patient-reported outcomes (PROs) (HF-HRQoL questionnaire), adherence with the application (self-reported), capecitabine dose changes (number of patients with dose modifications due to HFS) and safety profile (NCICTCv5.0 all grade HFS)DiscussionThe D-TORCH study aims to determine if 1% topical diclofenac reduces the incidence of grade 2 or higher HFS in patients receiving capecitabine. To date, there have been a lot of trials for hand-foot syndrome prevention using agents like pyridoxine, vitamin E, carvedilol, and various polyherbal formulations, but none has been found successful. If the trial meets the primary end point, 1% topical diclofenac will be the new standard of care for HFS prevention.Trial registrationClinical Trials Registry of India CTRI/2021/01/030592. Prospectively registered on January 19, 2021
Multiple biochemical indices and metabolomics of Clonorchis sinensis provide a novel interpretation of biomarkers
Authors: Qiu Yang-Yuan , Chang Qiao-Cheng , Gao Jun-Feng , Bao Ming-Jia , Luo Hai-Tao , Song Jin-Ho , Hong Sung-Jong , Mao Rui-Feng , Sun Yun-Yi , Chen Ying-Yu , Liu Ming-Yuan , Wang Chun-Ren , Liu Xiao-Lei 
Published: May 2022

Abstract
Background
Clonorchiasis, an infectious disease caused by the liver fluke Clonorchis sinensis, may lead to the development of liver and gallbladder diseases, and even cholangiocarcinoma (CCA). However, the pathogenesis, host-pathogen interaction, and diagnostic markers for clonorchiasis remain unclear.

Methods
Eighteen rabbits were randomly divided into control group (n = 9) and C. sinensis-infected group (n = 9), and their plasma samples were collected at 7, 14, 28, and 63 days post-infection (dpi). Biochemical indices and metabolites in different infection periods were detected. A non-targeted ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach was employed to investigate the metabolic profiles of plasma in rabbits, and related metabolic pathways of differential metabolites and correlation between candidate biochemical indices and differential metabolites were analyzed. Finally, the candidate biomarkers were verified with human samples using a targeted metabolomics method.

Results
The result of biochemical indices indicated C. sinensis infection would affect the liver function biochemical indices, especially alanine aminotransferase, aspartate transaminase (AST), glutamyl transpeptidase (GGT), total bile acid, high-density lipoprotein, and cholinesterase. The metabonomic results showed that 58, 212, 23, and 21 differential metabolites were identified in different phases of the infection. Multivariate statistical analysis of differential metabolites revealed distinct metabolic signatures during different phases of infection, with most of these signatures being observed at 14 dpi, which mainly influences the amino acid metabolisms. For metabolites and biochemical indices, AST, GGT, hypoxanthine, l-pipecolic acid, and d-glucuronate represented potential noninvasive biomarkers for the diagnosis of C. sinensis (P < 0.05 and AUC > 0.8). Furthermore, GGT and d-glucuronate levels were positively correlated with the infection (r(28) = 0.98, P < 0.0001) and showed excellent diagnostic performance (AUC = 0.972; 95% confidence interval, 0.921 to 1.000).

Conclusions
The present results provide new insights into plasma metabolic changes in rabbits during C. sinensis infection, and the potential biomarker may be used for developing an effective method to diagnose clonorchiasis in the future.

Graphical Abstract