bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mendelian randomisation identifies priority groups for prophylactic EBV vaccination
Authors: Muckian Marisa D. , Wilson James F. , Taylor Graham S. , Stagg Helen R. , Pirastu Nicola 
Published: February 2023

Abstract
Background
Epstein Barr virus (EBV) infects ~ 95% of the population worldwide and is known to cause adverse health outcomes such as Hodgkin’s, non-Hodgkin’s lymphomas, and multiple sclerosis. There is substantial interest and investment in developing infection-preventing vaccines for EBV. To effectively deploy such vaccines, it is vital that we understand the risk factors for infection. Why particular individuals do not become infected is currently unknown. The current literature, describes complex, often conflicting webs of intersecting factors—sociodemographic, clinical, genetic, environmental-, rendering causality difficult to decipher. We aimed to use Mendelian randomization (MR) to overcome the issues posed by confounding and reverse causality to determine the causal risk factors for the acquisition of EBV.

Methods
We mapped the complex evidence from the literature prior to this study factors associated with EBV serostatus (as a proxy for infection) into a causal diagram to determine putative risk factors for our study. Using data from the UK Biobank of 8422 individuals genomically deemed to be of white British ancestry between the ages of 40 and 69 at recruitment between the years 2006 and 2010, we performed a genome wide association study (GWAS) of EBV serostatus, followed by a Two Sample MR to determine which putative risk factors were causal.

Results
Our GWAS identified two novel loci associated with EBV serostatus. In MR analyses, we confirmed shorter time in education, an increase in number of sexual partners, and a lower age of smoking commencement, to be causal risk factors for EBV serostatus.

Conclusions
Given the current interest and likelihood of a future EBV vaccine, these factors can inform vaccine development and deployment strategies by completing the puzzle of causality. Knowing these risk factors allows identification of those most likely to acquire EBV, giving insight into what age to vaccinate and who to prioritise when a vaccine is introduced.
Small vessel childhood primary angiitis of the central nervous system with positive anti-glial fibrillary acidic protein antibodies: a case report and review of literature
Authors: Datyner E , Adeseye V , Porter K , Dryden I , Sarma A , Vu N , Patrick AE , Paueksakon P 
Published: February 2023

Abstract
Background
Small vessel childhood primary angiitis of the central nervous system (SV-cPACNS) is a rare disease characterized by inflammation within small vessels such as arterioles or capillaries.

Case presentation
We report a case of SV-cPACNS in an 8-year-old boy confirmed by brain biopsy. This patient was also incidentally found to have anti-glial fibrillary acidic protein (GFAP) antibodies in the cerebrospinal fluid (CSF) but had no evidence of antibody-mediated disease on brain biopsy. A literature review highlighted the rarity of SV-cPACNS and found no prior reports of CSF GFAP-associated SV-cPACNS in the pediatric age group.

Conclusion
We present the first case of biopsy proven SV-cPACNS vasculitis associated with an incidental finding of CSF GFAP antibodies. The GFAP antibodies are likely a clinically insignificant bystander in this case and possibly in other diseases with CNS inflammation. Further research is needed to determine the clinical significance of newer CSF autoantibodies such as anti-GFAP before they are used for medical decision-making in pediatrics.
Low impact of regular PCR testing on presence at work site during the COVID-19 pandemic: experiences during an open observational study in Lower Saxony 2020-21
Authors: Seiler Lisa K. , Stolpe Susanne , Stanislawski Nils , Stahl Frank , Witt Martin , Jonczyk Rebecca , Heiden Stefanie , Blume Holger , Kowall Bernd , Blume Cornelia 
Published: February 2023

Abstract
Background
Since social distancing during the COVID-19-pandemic had a profound impact on professional life, this study investigated the effect of PCR testing on on-site work.

Methods
PCR screening, antibody testing, and questionnaires offered to 4,890 working adults in Lower Saxony were accompanied by data collection on demographics, family status, comorbidities, social situation, health-related behavior, and the number of work-related contacts. Relative risks (RR) with 95 % confidence intervals were estimated for the associations between regular PCR testing and other work and health-related variables, respectively, and working on-site. Analyses were stratified by the suitability of work tasks for mobile office.

Results
Between April 2020 and February 2021, 1,643 employees underwent PCR testing. Whether mobile working was possible strongly influenced the work behavior. Persons whose work was suitable for mobile office (mobile workers) had a lower probability of working on-site than persons whose work was not suitable for mobile office (RR = 0.09 (95 % CI: 0.07 – 0.12)). In mobile workers, regular PCR-testing was slightly associated with working on-site (RR = 1.19 (0.66; 2.14)). In those whose working place was unsuitable for mobile office, the corresponding RR was 0.94 (0.80; 1.09). Compared to persons without chronic diseases, chronically ill persons worked less often on-site if their workplace was suitable for mobile office (RR = 0.73 (0.40; 1.33)), but even more often if their workplace was not suitable for mobile office (RR = 1.17 (1.04; 1.33)).

Conclusion
If work was suitable for mobile office, regular PCR-testing did not have a strong effect on presence at the work site.

Trial registration
An ethics vote of the responsible medical association (Lower Saxony, Germany) retrospectively approved the evaluation of the collected subject data in a pseudonymized form in the context of medical studies (No. Bo/30/2020; Bo/31/2020; Bo/32/2020).
Is excessive smartphone use associated with weight status and self-rated health among youth? A smart platform study
Authors: Brodersen Kayla , Hammami Nour , Katapally Tarun Reddy 
Published: February 2023

Abstract
Background
In Canada, it is recommended that youth limit screen time to less than two hours per day, yet, the majority of youth are reportedly spending a significantly higher amount of time in front of a screen. This is particularly concerning given that these recommendations do not take into account smartphone devices, which is the most common screen time technology of choice for the younger generations. This study implements an innovative approach to understanding screen time behavior and aims to investigate the unique relationship between smartphone specific screen time and physical health outcomes.

Methods
This cross-sectional study is part of the Smart Platform, a digital epidemiological and citizen science initiative. 436 youth citizen scientists, aged 13–21 years, provided all data via their own smartphones using a custom-built smartphone application. Participants completed a 124-item baseline questionnaire which included validated self-report surveys adapted to collect data specifically on smartphone use (internet use, gaming, and texting), demographic characteristics, and physical health outcomes such as weight status and self-rated health. Binary regression models determined the relationship between smartphone use and physical health outcomes.

Results
Overall participants reported excessive smartphone use in all categories. 11.4% and 12% of the 436 youth participants reported using their smartphone excessively (greater than 2 h per day) during the week and weekend respectively for gaming and were over 2 times more likely than their peers to fall within an overweight/obese BMI status. Excessive weekend gaming was also associated with self-rated health where participants were over 2 times more likely than their peers to report poor self-rated health.

Conclusions
The results indicate that excessive screen time on smartphones does have complex associations with youth health. Further investigation with more robust study designs is needed to inform smartphone-specific screen time guidelines for youth.
Clinical characteristics of airway impairment assessed by impulse oscillometry in patients with chronic obstructive pulmonary disease: findings from the ECOPD study in China
Authors: Lu Lifei , Peng Jieqi , Wu Fan , Yang Huajing , Zheng Youlan , Deng Zhishan , Zhao Ningning , Dai Cuiqiong , Xiao Shan , Wen Xiang , Xu Jianwu , Wu Xiaohui , Zhou Kunning , Ran Pixin , Zhou Yumin 
Published: February 2023

Abstract
Background
The role of airway impairment assessed by impulse oscillometry (IOS) in patients with chronic obstructive pulmonary disease (COPD) remains unclear. Therefore, this study aimed to analyze the proportion and clinical characteristics of airway impairment assessed by IOS across COPD severities, and explore whether airway impairment is a subtype of COPD.

Methods
This study was based on cross-sectional data from the ECOPD cohort in Guangdong, China. Subjects were consecutively recruited from July 2019 to August 2021. They filled out questionnaires and underwent lung function tests, IOS and computed tomography (CT). COPD was defined as post-bronchodilator forced expiratory volume in one second/forced vital capacity < lower limit of normal (LLN). Meanwhile, airway impairment was defined as IOS parameters > upper limit of normal or < LLN. On the one hand, Poisson regression was employed to analyze the associations between acute exacerbations of COPD (AECOPD) in the previous year and airway impairment. On the other hand, logistic regression was used to assess differences in CT imaging between patients with IOS parameters’ abnormalities and patients with normal IOS parameters.

Results
768 COPD subjects were finally enrolled in the study. The proportion of airway impairment assessed by R5, R20, R5–R20, X5, AX, and Fres was 59.8%, 29.7%, 62.5%, 52.9%, 60.9% and 67.3%, respectively. Airway impairment assessed by IOS parameters (R5, R5–R20, X5, AX, and Fres) in patients with COPD was present across all severities of COPD, particularly in GOLD 3–4 patients. Compared with patients with normal IOS parameters, patients with IOS parameters’ abnormalities had more respiratory symptoms, more severe airway obstruction and imaging structural abnormalities. Patients with IOS parameters’ abnormalities assessed by R5 [risk ratio (RR): 1.58, 95% confidential interval (CI): 1.13–2.19, P = 0.007], R5–R20 [RR: 1.73, 95%CI: 1.22–2.45, P = 0.002], X5 [RR: 2.11, 95%CI: 1.51–2.95, P < 0.001], AX [RR: 2.20, 95%CI: 1.53–3.16, P < 0.001], and Fres [RR: 2.13, 95%CI: 1.44–3.15, P < 0.001] had a higher risk of AECOPD in the previous year than patients with normal IOS parameters.

Conclusions
Airway impairment assessed by IOS may be a subtype of COPD. Future studies are warranted to identify the underlying mechanisms and longitudinal progression of airway impairment.
Lung function and collagen 1a levels are associated with changes in 6 min walk test distance during treatment of TB among HIV-infected adults: a prospective cohort study
Authors: Baik Yeonsoo , Maenetje Pholo , Schramm Diana , Tiemessen Caroline , Ncube Itai , Churchyard Gavin , Wallis Robert , Vangu Mboyo-di-tamba , Kornfeld Hardy , Li Yun , Auld Sara C. , Bisson Gregory P. 
Published: February 2023

Abstract
Background
Patients with tuberculosis (TB) and HIV often present with impairments in lung function and exercise capacity after treatment. We evaluated clinical and immunologic variables associated with a minimum clinically important difference (MCID) in the change in the 6 min walk test distance during the first 24 weeks of antiretroviral (ART) and anti-tubercular therapy.

Methods
Adults initiating ART and anti-TB treatment in the setting of newly-diagnosed HIV and pulmonary TB were enrolled in a prospective cohort study in South Africa. Patients underwent 6 min walk tests and spirometry at weeks 0, 4, 12, and 24 and biomarker level measurements early during treatment, at weeks 0, 4, and 12, when inflammation levels are typically elevated. Biomarkers included matrix metalloproteinases-1 (MMP-1), tissue inhibitor of MMP (TIMP)-1, collagen 1a, IL-6, IL-8, vascular cell adhesion molecule 1 (VCAM-1), C-X-C motif chemokine 10 (CXCL-10), CXCL-11, macrophage colony-stimulating factor (M-CSF), plasminogen activator, vascular endothelial growth factor, and chemokine (C-C) motif-2 (CCL-2). An MCID was derived statistically, and achievement of an MCID was modeled as the outcome using logistic regression model.

Results
Eighty-nine patients walked an average of 393 (± standard deviation = 69) meters at baseline, which increased by an average of 9% (430 ± 70 m) at week 24. The MCID for change in walk distance was estimated as 41 m. Patients experiencing an MCID on treatment had worse lung function, lower 6 min walk test distance, higher levels of proinflammatory biomarkers including TIMP-1 and M-CSF, and lower levels of collagen 1a at baseline. Experiencing an MCID during treatment was associated with increases in forced expiratory volume in 1-s [odds ratio (OR) = 1.17, 95% confidence interval (CI) = 1.05–1.33] and increases in blood collagen 1a levels (OR = 1.31, 95%CI 1.06–1.62).

Conclusions
ART and TB treatment are associated with substantial improvements in 6 min walk test distance over time. Achievement of an MCID in the 6 min walk test in this study was associated with more severe disease at baseline and increases in collagen 1a levels and lung function during therapy.
The efficacy of intra-articular triamcinolone acetonide 10 mg vs. 40 mg in patients with knee osteoarthritis: a non-inferiority, randomized, controlled, double-blind, multicenter study
Authors: Utamawatin Komchan , Phruetthiphat Ong-art , Apinyankul Rit , Chaiamnuay Sumapa 
Published: February 2023

Abstract
Background
Intra-articular (IA) corticosteroid injection is recommended in refractory knee osteoarthritis patients. However, 40-mg of triamcinolone IA every 3 months for 2 years reduces cartilage volume as compared to saline IA.

Objective
To determine the non-inferiority of 10-mg versus 40-mg of triamcinolone acetonide (TA) for treatment of pain in symptomatic knee osteoarthritis at week 12.

Methods
This was a double-blind, randomized, controlled trial conducted in 84 symptomatic knee osteoarthritis patients. The 10-mg or 40-mg of TA were 1:1 randomized and injected to the affected knees. The primary outcome was the 12-week difference from baseline in pain VAS, with a pre-specified lower margin for non-inferiority of 10 mm. The measuring instruments used were: Visual analog scale (VAS: 0–10), modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EuroQol Group 5 Dimensions (EQ5D), Knee Injuries and Osteoarthritis Outcome Score (KOOS) questionnaire, chair standing test and 20-m walking time at baseline, at week 4, and week 12 after randomization. Adverse events were recorded.

Results
Baseline characteristics were similar between two groups. The mean differences of pain VAS (95% confidence interval: CI) between the two groups at baseline and week 12 were 0.8 (-0.8, 2.4) with p of 0.002 for non-inferiority. There were no differences in pain reduction and quality of life improvement between 10-mg and 40-mg groups. The mean differences (95%CI) of WOMAC, KOOS pain, EQ5D and KOOS quality of life between baseline and week 12 were 0.4 (-1.1, 1.9). -8.7 (-21.3, 3.9), 1.3(-7.1, 9.6) and 1.8 (-11.5, 15.0), respectively.
There were significant improvements in pain and quality of life between baseline and week 12 in both groups.

Conclusion
The 10 mg of TA is non-inferior to 40 mg TA in improving pain in patients with symptomatic knee OA. Both 10 mg and 40 mg of TA significantly improved pain and quality of life in patients with symptomatic knee OA.

Trial registration
TCTR, I TCTR20210224002. Retrospectively registered 24 February 2021, http://www.thaiclinicaltrials.org/show/TCTR20210224002
A high Diabetes Risk Reduction Score (DRRS) is associated with a better cardio-metabolic profile among obese individuals
Authors: Siri Goli , Nikrad Negin , Keshavari Sheida , Jamshidi Saideh , Fayyazishishavan Ehsan , Ardekani Abnoos Mokhtari , Farhangi Mahdieh Abbasalizad , Jafarzadeh Faria 
Published: February 2023

AbstractBackgroundDietary indices and scores are valuable predictive markers against chronic diseases. Several previous studies have revealed the beneficial effects of diabetes risk reduction score (DRRS) against diabetes and cancer incidence. However, its association with metabolic abnormalities among obese individuals have not been revealed before. In the current study, we aimed to investigate the association between DRRS and metabolic risk factors among obese individuals.MethodsIn the current cross-sectional study, 342 obese individuals [Body mass index (BMI) ≥ 30 kg/m2] aged 20–50 years were included. Dietary intake was assessed by a validated semi-quantitative food frequency questionnaire (FFQ) of 168 food items and DRRS was calculated. Metabolic syndrome (MetS) was defined based on the guidelines of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III). Enzymatic methods were used to assess serum lipids, glucose, and insulin concentrations. Blood pressure was measured by a sphygmomanometer and body composition with bioelectrical impedance analysis (BIA).ResultsThose with a higher adherence to DRRS had a significantly higher intake of energy, fiber, and lower protein compared with those in the lower quartiles. Moreover, lower intakes of trans fats, meat, sugar sweetened beverages (SSB), and glycemic index (GI) with higher intakes of fruits, cereal fiber, polyunsaturated fatty acids/ saturated fatty acids (PUFA/ SFA) ratio, coffee, and nuts were observed in the highest versus lowest DRRS categories. Lower systolic blood pressure, diastolic blood pressure, triglyceride and, higher high-density lipoprotein values were observed in higher DRRS categories. Logistic regression analysis showed that hypertension was significantly associated with adherence to DRRS among obese individuals, the odds ratio (OR) was 0.686 (95% confidence interval [CI], 0.26–0.84) after adjustment for potential confounders. But the risk of other components of MetS was not significantly associated with higher quartiles of adherence to DRRS. Also, a non-significantly lower prevalence of MetS was observed in the higher quartile of DRRS.ConclusionsAccording to the results of the current study, higher DRRS was associated with lower blood pressure, modified serum lipids, and lower Mets prevalence. Further studies in different populations are warranted for better generalization of the obtained findings.
Significance of computed tomography combined with postural stimulation test in predicting laterality of primary aldosteronism
Authors: Wu Yingxing , Wu Zuxiang , Hu Huan , Rao Jingan , Hu Chenkai , Peng Qiang , Li Ping 
Published: February 2023

Abstract
Backgrounds
Adrenal venous sampling (AVS) represents the gold standard for classifying primary aldosteronism (PA). However, AVS is a technically demanding, expensive and invasive procedure. Computed tomography (CT) scans is recommended as the initial study of classification diagnosis by the current guidelines. In addition, postural stimulation test (PST) has been used to provide additional subtype diagnostic information.

Objective
This work aimed to evaluate the diagnostic utility of the adrenal CT combined with PST in the classification diagnosis of PA.

Methods
We analyzed PA patients who underwent AVS from November 2017 to February 2022 at a single center. Subtype classification of PA was determined by AVS. We analyzed the concordance rate between AVS outcomes, adrenal CT, and PST, and explored the value of adrenal CT combined with PST for predicting laterality of PA.

Results
Total 531 PA patients were included in the present study. The concordance rate between AVS and the adrenal CT was 51.0%(271/531). Receiver operating characteristic (ROC) curve of PST showed that the area under curve (AUC) was 0.604 [95% confidence interval (CI): 0.556, 0.652], the optimal cut-off value was 30%. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+LR), and negative likelihood ratio (−LR) of PST for diagnosis bilateral PA on AVS was 72.8, 46.2%, 0.48, 0.71, 1.35, and 0.59, respectively. The prevalence of unilateral PA on AVS in patients with unilateral lesion on CT and negative PST, unilateral lesion on CT and positive PST, bilateral normal or lesions on CT and negative PST, and bilateral normal or lesions on CT and positive PST was 82.4% (108/131), 59.9% (91/152), 50.7% (37/73), and 44.6% (78/175), respectively. The sensitivity, specificity, PPV, NPV, +LR, and -LR of adrenal CT combined with PST for the diagnosis of unilateral PA were 34.4, 89.4%, 0.82, 0.49, 3.25, and 0.73, respectively.

Conclusions
The combination of CT findings and PST can improve the accuracy of predicting laterality of PA.
Forsythiaside A ameliorates sepsis-induced acute kidney injury via anti-inflammation and antiapoptotic effects by regulating endoplasmic reticulum stress
Authors: Chen Yi , Wei Wei , Fu Jingnan , Zhang Teng , Zhao Jie , Ma Tao 
Published: February 2023

Abstract
Ethnopharmacological relevance
Sepsis is a systemic inflammatory response syndrome caused by an infection in the body, and accompanying acute kidney injury (AKI) is a common complication of sepsis. It is associated with increased mortality and morbidity. Forsythia Fructus, the dried fruit of Forsythia suspensa (Thunb.) Vahl, is a commonly used traditional Chinese medicine.

Aims of the study
This study aimed to elucidate the protective effect of Forsythiaside A (FTA) on sepsis-induced AKI by downregulating inflammatory and apoptotic responses, and exploring its underlying mechanism.

Methods
Septic AKI was induced through intraperitoneal injection of LPS (10 mg/kg) using male C57BL/6 mice and pretreated with FTA or control saline. First, we assessed the degree of renal injury by creatinine, blood urea nitrogen measurement, and HE staining of renal tissue; secondly, the inflammation and apoptosis were measured byELISA, qPCR, and TUNEL immunofluorescence; finally, the mechanism was explored by computer molecular docking and Western blot.

Results
Our data showed that FTA markedly attenuated pathological kidney injuries, alleviated the elevation of serum BUN and Creatinine, suggesting the renal protective effect of FTA. Notably, FTA significantly inhibited the renal expression of proinflammatory cytokine IL-1β, IL-6, and TNF-α both at protein and mRNA levels and attenuated cell apoptosis in the kidney, as measured by caspase-3 immunoblot and TUNEL assay, indicating its anti-Inflammation and antiapoptotic properties. Mechanistically, administration of LPS resulted in robust endoplasmic reticulum (ER) stress responses in the kidney, evidenced by glucose-regulated protein 78(GRP78) upregulation, protein kinase RNA–like endoplasmic reticulum kinase (PERK) activation, eukaryotic initiation factor 2 alpha (elF2α) phosphorylation and C/EBP homologous protein (CHOP) overexpression, which could be significantly blocked by FTA pretreatment. Dynamic simulation and molecular docking were performed to provide further insight.

Conclusions
Collectively, our data suggest that FTA ameliorates sepsis-induced acute kidney injury via its anti-inflammation and antiapoptotic properties by regulating PERK signaling dependent ER stress responses.