bluuebunny/crossref_metadata_2025_split huggingface dataset:
Educational inequality in multimorbidity: causality and causal pathways. A mendelian randomisation study in UK Biobank
Authors: North Teri-Louise , Harrison Sean , Bishop Deborah C , Wootton Robyn E , Carter Alice R , Richardson Tom G , Payne Rupert A , Salisbury Chris , Howe Laura D 
Published: August 2023

Abstract
Background
Multimorbidity, typically defined as having two or more long-term health conditions, is associated with reduced wellbeing and life expectancy. Understanding the determinants of multimorbidity, including whether they are causal, may help with the design and prioritisation of prevention interventions. This study seeks to assess the causality of education, BMI, smoking and alcohol as determinants of multimorbidity, and the degree to which BMI, smoking and alcohol mediate differences in multimorbidity by level of education.

Methods
Participants were 181,214 females and 155,677 males, mean ages 56.7 and 57.1 years respectively, from UK Biobank. We used a Mendelian randomization design; an approach that uses genetic variants as instrumental variables to interrogate causality.

Results
The prevalence of multimorbidity was 55.1%. Mendelian randomization suggests that lower education, higher BMI and higher levels of smoking causally increase the risk of multimorbidity. For example, one standard deviation (equivalent to 5.1 years) increase in genetically-predicted years of education decreases the risk of multimorbidity by 9.0% (95% CI: 6.5 to 11.4%). A 5 kg/m2 increase in genetically-predicted BMI increases the risk of multimorbidity by 9.2% (95% CI: 8.1 to 10.3%) and a one SD higher lifetime smoking index increases the risk of multimorbidity by 6.8% (95% CI: 3.3 to 10.4%). Evidence for a causal effect of genetically-predicted alcohol consumption on multimorbidity was less strong; an increase of 5 units of alcohol per week increases the risk of multimorbidity by 1.3% (95% CI: 0.2 to 2.5%). The proportions of the association between education and multimorbidity explained by BMI and smoking are 20.4% and 17.6% respectively. Collectively, BMI and smoking account for 31.8% of the educational inequality in multimorbidity.

Conclusions
Education, BMI, smoking and alcohol consumption are intervenable causal risk factors for multimorbidity. Furthermore, BMI and lifetime smoking make a considerable contribution to the generation of educational inequalities in multimorbidity. Public health interventions that improve population-wide levels of these risk factors are likely to reduce multimorbidity and inequalities in its occurrence.
Factors influencing mobility in community-dwelling older adults during the early COVID-19 pandemic: a cross-sectional study
Authors: Kim Hyori , Kim Juah , Ha Jiyeon 
Published: August 2023

Abstract
Background
In older adults, mobility is important for maintaining their independence and quality of life, and it influences their physical, cognitive, and social health. This study aimed to identify the physical and psychosocial factors that affected the mobility of community-dwelling older adults, aged 65 years or older, who were socially isolated during the coronavirus disease 2019 (COVID-19) pandemic due to stay-at-home policies.

Methods
The participants in this study were 214 community-dwelling older adults in Korea, and a cross-sectional survey was conducted from December 2020 to January 2021. Variables included participants’ general characteristics, mobility, sitting time, depression, social support, and cognitive function.

Results
Multiple linear regression analysis showed that the factors influencing older adults’ mobility during the COVID-19 pandemic were depression (β=-0.29, p < .001), age (65–74 years old) (β = 0.19, p = .002), a lower level of education (β=-0.17, p = .006), two or more comorbidities (β=-0.18, p = .001), sitting time (β=-0.17, p = .004), and the ability to drive a vehicle (β = 0.14, p = .017).

Conclusions
Home healthcare interventions are needed to limit psychosocial issues and improve mobility for older adults who had limited mobility during the COVID-19 pandemic.
RETRACTED ARTICLE: Association of milk consumption with the incidence of cholelithiasis disease in the US adult population
Authors: Jia Feng , Ma Yu , Liu Yahui 
Published: August 2023

Abstract
Background
Cholelithiasis is a common digestive system disease that imposes major burden on patients and society. Investigating the relationship between dietary factors and cholelithiasis risk can provide a basis for disease prevention. Previous studies on milk intake and cholelithiasis incidence have been limited.Therefore, the aim of our study was to assess the association between milk consumption and the incidence of cholelithiasis in males and females.

Methods
We selected 14,722 adults (≥ 18 years old) from National Center for Health Statistics (NHANSE) 2017–2020, and collected general characteristics of patients in the database, such as age, gender, race and body mass index (BMI), as well as dietary information (milk consumption). The occurrence of cholelithiasis was used as the outcome event, and the group was divided into cholelithiasis and non-cholelithiasis groups according to the outcome event. We used logistic regression models in generalized linear model (GLM) functions, controlling for demographic, lifestyle, and dietary factors, to estimate the association between milk intake and the incidence of cholelithiasis in males and females.

Results
A total of 14,722 adults were included. In the present study, the overall weighted prevalence of cholelithiasis was 10.96%, with 15.18% and 6.48% prevalence in females and males, respectively. Compared to infrequent milk intake, frequent milk intake (once a week or more) in females was associated with reduced cholelithiasis risk (OR 0.74, 95% CI 0.61–0.90). Daily milk intake in males was also related to lower cholelithiasis risk (OR 0.69–0.82). As adjusted variables increased in the models, predictive performance was improved (AUC 0.711 in females, 0.730 in males).

Conclusions
Appropriate milk intake may correlate with decreased cholelithiasis risk. Our study provides a basis for dietary interventions against gallstones, but prospective studies are needed to verify the results.
Evaluation of the use of methylprednisolone and dexamethasone in asthma critically ill patients with COVID-19: a multicenter cohort study
Authors: Al Sulaiman Khalid , Aljuhani Ohoud , Korayem Ghazwa B. , Altebainawi Ali , Alharbi Reham , Assadoon Maha , Vishwakarma Ramesh , Ismail Nadia H. , Alshehri Asma A. , Al Mutairi Faisal E. , AlFaifi Mashael , Alharthi Abdullah F. , Alenazi Abeer A. , Alalawi Mai , Al Zumai Omar , Al Haji Hussain , Al Dughaish Sarah T. , Alawaji Abdulrahman S. , Alhaidal Haifa A. , Al Ghamdi Ghassan 
Published: August 2023

Abstract
Background
Previous studies have shown mortality benefits with corticosteroids in Coronavirus disease-19 (COVID-19). However, there is inconsistency regarding the use of methylprednisolone over dexamethasone in COVID-19, and this has not been extensively evaluated in patients with a history of asthma. This study aims to investigate and compare the effectiveness and safety of methylprednisolone and dexamethasone in critically ill patients with asthma and COVID-19.

Methods
The primary endpoint was the in-hospital mortality. Other endpoints include 30-day mortality, respiratory failure requiring mechanical ventilation (MV), acute kidney injury (AKI), acute liver injury, length of stay (LOS), ventilator-free days (VFDs), and hospital-acquired infections. Propensity score (PS) matching, and regression analyses were used.

Results
A total of one hundred-five patients were included. Thirty patients received methylprednisolone, whereas seventy-five patients received dexamethasone. After PS matching (1:1 ratio), patients who received methylprednisolone had higher but insignificant in-hospital mortality in both crude and logistic regression analysis, [(35.0% vs. 18.2%, P = 0.22) and (OR 2.31; CI: 0.56 – 9.59; P = 0.25), respectively]. There were no statistically significant differences in the 30-day mortality, respiratory failure requiring MV, AKI, acute liver injury, ICU LOS, hospital LOS, and hospital-acquired infections.

Conclusions
Methylprednisolone in COVID-19 patients with asthma may lead to increased in-hospital mortality and shorter VFDs compared to dexamethasone; however, it failed to reach statistical significance. Therefore, it is necessary to interpret these data cautiously, and further large-scale randomized clinical trials are needed to establish more conclusive evidence and support these conclusions.
NHS-POx-loaded patch versus fibrin sealant patch in a porcine robotic liver bleeding model
Authors: D’Hondt Mathieu , Roozen Edwin A. , Nuytens Frederiek , Bender Johan , Mottrie Alexandre , Bauwens Kevin , Head Stuart J. 
Published: August 2023

Abstract
Background
The management of bleeding is paramount to any surgical procedure. With the increased use of less invasive laparoscopic and robotic methods, achieving hemostasis can be challenging since the surgeons cannot manually apply hemostatic agents directly onto bleeding tissue. In this study, we assessed the use of a pliable hemostatic sealant patch comprising fibrous gelatin carrier impregnated with poly(2-oxazoline) (NHS-POx) for hemostasis in robotic liver resection in a porcine bleeding model.

Methods
The NHS-POx-loaded patch (GATT-Patch), was first evaluated in a Feasibility Study to treat surgical bleeding in 10 lesions, followed by a Comparative Study in which the NHS-POx patch was compared to a standard-of-care fibrin sealant patch (TachoSil), in 36 lesions (superficial, resection, or deep injuries mimicking metastasectomies). For each lesion type, the NHS-POx and fibrin sealant patches were used in an alternating fashion with 18 lesions treated with NHS-POx and 18 with the fibrin patch. Animal preparation and surgical procedures were consistent across studies. The primary outcome was time to hemostasis (TTH) within 3 min for the Feasibility Study and within 5 min for the Comparative Study.

Results
In the Feasibility Study, 8 of the 10 NHS-POx-treated lesions achieved hemostasis at 30 s and 3 min. In the Comparative Study, all 18 NHS-POx patch-treated lesions and 9 of the 18 fibrin sealant patch-treated lesions achieved hemostasis at 5 min. Median TTH with NHS-POx vs fibrin sealant patch was 30 vs 300 s (P < 0.001).

Conclusions
In this animal study, hemostasis during robotic liver surgery was achieved faster and more often with the NHS-POx loaded vs fibrin sealant patch.
Clinical features and surgical selection in colitis-associated colorectal cancer with ulcerative colitis
Authors: Kuwahara Ryuichi , Ikeuchi Hiroki , Kusunoki Kurando , Minagawa Tomohiro , Horio Yuki , Kimura Kei , Kataoka Kozo , Beppu Naohito , Ikeda Masataka , Uchino Motoi 
Published: August 2023

Abstract
Purpose
The aim of this study was to compare the clinical characteristics of ulcerative colitis (UC) patients who underwent surgery for cancer/dysplasia with those who underwent surgery for refractory disease and to discuss the preoperative preparation for successful hand-sewn IPAA.

Methods
Patients who underwent surgery for UC between January 2014 and December 2021 at Hyogo Medical University were included in the study. A total of 443 UC surgical cases were included in the study, which comprised 188 cancer/dysplasia patients and 255 refractory patients. Clinical records were compared retrospectively.

Results
The proportion of surgical UC cases with cancer/dysplasia has been on the rise, accounting for approximately 40% in recent years. The duration of disease (months) was 186 (2–590) in the cancer/dysplasia group and 48 (1–580) in the refractory group (p = 0.02). UC severity (mild/moderate/severe) was 119/69/0 in the cancer/dysplasia group and 18/157/80 in the refractory group (p < 0.01). The four nutrition factors of weight (55.2 (32.7–99.6) kg: 49.9 (20.3–85.2) kg), body mass index (21.0 (13.9–32.5) kg/m2: 18.3 (11.4–34.1)kg/m2), serum albumin level (4.3 (2.7–5.0)g/dl: 3.4 (1.4–5.2)g/dl) and prognostic nutrition index (49.2 (33.2–61.2): 40.9 (17.4–61.1)) were significantly higher in the cancer/dysplasia group (p < 0.01). The degree of obesity was also significantly higher in the cancer/dysplasia group (p < 0.01).

Conclusion
UC patients with cancer/dysplasia were more likely than refractory patients to have mild inflammation; they also had a longer duration of UC disease and better nutritional status.
Inflammatory parameters and color alterations of dental bleaching in patients wearing fixed orthodontic appliance: a randomized clinical trial
Authors: Barbosa Edson Gustavo Pereira , Lima Suellen Nogueira Linares , de Araújo Gurgel Júlio , Fernandes Elizabeth Soares , Neto Sebastião Marinho Pinheiro , de Jesus Tavarez Rudys Rodolfo , da Silva Karine Letícia , Loguercio Alessandro D. , Pinzan-Vercelino Célia Regina Maio 
Published: August 2023

Abstract
Background
Many orthodontic patients request dental bleaching during orthodontic treatment to achieve a faster aesthetic resolution, however, no attention has been paid to the inflammatory processes that can occur when both therapies are indicated together. So, this clinical trial evaluated the inflammatory parameters and color alterations associated with dental bleaching in patients wearing a fixed orthodontic appliance.

Methods
Thirty individuals aged between 18 and 40 years were equally and randomly allocated into three groups: FOA (fixed orthodontic appliance), BLE (dental bleaching), and FOA + BLE (fixed orthodontic appliance + dental bleaching). The orthodontic appliances and the bleaching procedures were performed in the maxillary premolars and molars. For dental bleaching a 35% hydrogen peroxide was used. The gingival crevicular fluid (GCF) and nitric oxide (NO-) levels were evaluated at different time-points. Color evaluation was performed using an Easyshade spectrophotometer at baseline (FOA, FOA + BLE, BLE), one month after (FOA + BLE) and 21 days after appliance removing (FOA + BLE and FOA groups), in each tooth bleached. The ANOVA and Tukey’s tests, with a significance level of 5%, were used for statistical analysis.

Results
The GCF volume in the FOA + BLE and FOA groups significantly increased at the time points evaluated (p < 0.001); however, this did not occur in the BLE group (p > 0.05). On the other hand, NO- levels significantly decreased during dental bleaching with or without fixed orthodontic appliances (FOA + BLE and BLE groups; p < 0.05), while no significant changes were observed in the FOA group (p > 0.05). Significant changes in color were observed in the FOA + BLE and BLE groups compared to in the FOA group (p < 0.01). However, the presence of fixed orthodontic appliance (FOA + BLE) negatively affected the bleaching efficacy compared to BLE group (p < 0.01).

Conclusions
Dental bleaching did not increase the inflammatory parameters in patients wearing fixed orthodontic appliance. However, in the presence of orthodontic appliances, the bleaching efficacy was lower than that of bleaching teeth without orthodontic appliances.

Trial registration
RBR-3sqsh8 (first trial registration: 09/07/2018).
Differential functions of RhoGDIβ in malignant transformation and progression of urothelial cell following N-butyl-N-(4-hydmoxybutyl) nitrosamine exposure
Authors: Hua Xiaohui , Zou Ronghao , Bai Xiaoyue , Yang Yuyao , Lu Juan , Huang Chuanshu 
Published: August 2023

Abstract
Background
Functional role of Rho GDP-dissociation inhibitor beta (RhoGDIβ) in tumor biology appears to be contradictory across various studies. Thus, the exploration of the molecular mechanisms underlying the differential functions of this protein in urinary bladder carcinogenesis is highly significant in the field. Here, RhoGDIβ expression patterns, biological functions, and mechanisms leading to transformation and progression of human urothelial cells (UROtsa cells) were evaluated following varying lengths of exposure to the bladder carcinogen N-butyl-N-(4-hydmoxybutyl) nitrosamine (BBN).

Results
It was seen that compared to expression in vehicle-treated control cells, RhoGDIβ protein expression was downregulated after 2-month of BBN exposure, but upregulated after 6-month of exposure. Assessments of cell function showed that RhoGDIβ inhibited UROtsa cell growth in cells with BBN for 2-month exposure, whereas it promoted the invasion of cells treated with BBN for 6 months. Mechanistic studies revealed that 2-month of BBN exposure markedly attenuated DNMT3a abundance, and this led to reduced miR-219a promoter methylation, increased miR-219a binding to the RhoGDIβ mRNA 3’UTR, and reduced RhoGDIβ protein translation. While after 6-mo of BBN treatment, the cells showed increased PP2A/JNK/C-Jun axis phosphorylation and this in turn mediated overall RhoGDIβ mRNA transcription and protein expression as well as invasion.

Conclusions
These findings indicate that RhoGDIβ is likely to inhibit the transformation of human urothelial cells during the early phase of BBN exposure, whereas it promotes invasion of the transformed/progressed urothelial cells in the late stage of BBN exposure. The studies also suggest that RhoGDIβ may be a useful biomarker for evaluating the progression of human bladder cancers.
Global impact and cost-effectiveness of one-dose versus two-dose human papillomavirus vaccination schedules: a comparative modelling analysis
Authors: Prem Kiesha , Choi Yoon Hong , Bénard Élodie , Burger Emily A. , Hadley Liza , Laprise Jean-François , Regan Mary Caroline , Drolet Mélanie , Sy Stephen , Abbas Kaja , Portnoy Allison , Kim Jane J. , Brisson Marc , Jit Mark 
Published: August 2023

Abstract
Background
To eliminate cervical cancer as a public health problem, the World Health Organization had recommended routine vaccination of adolescent girls with two doses of the human papillomavirus (HPV) vaccine before sexual initiation. However, many countries have yet to implement HPV vaccination because of financial or logistical barriers to delivering two doses outside the infant immunisation programme.

Methods
Using three independent HPV transmission models, we estimated the long-term health benefits and cost-effectiveness of one-dose versus two-dose HPV vaccination, in 188 countries, under scenarios in which one dose of the vaccine gives either a shorter duration of full protection (20 or 30 years) or lifelong protection but lower vaccine efficacy (e.g. 80%) compared to two doses. We simulated routine vaccination with the 9-valent HPV vaccine in 10-year-old girls at 80% coverage for the years 2021–2120, with a 1-year catch-up campaign up to age 14 at 80% coverage in the first year of the programme.

Results
Over the years 2021–2120, one-dose vaccination at 80% coverage was projected to avert 115.2 million (range of medians: 85.1–130.4) and 146.8 million (114.1–161.6) cervical cancers assuming one dose of the vaccine confers 20 and 30 years of protection, respectively. Should one dose of the vaccine provide lifelong protection at 80% vaccine efficacy, 147.8 million (140.6–169.7) cervical cancer cases could be prevented. If protection wanes after 20 years, 65 to 889 additional girls would need to be vaccinated with the second dose to prevent one cervical cancer, depending on the epidemiological profiles of the country. Across all income groups, the threshold cost for the second dose was low: from 1.59 (0.14–3.82) USD in low-income countries to 44.83 (3.75–85.64) USD in high-income countries, assuming one dose confers 30-year protection.

Conclusions
Results were consistent across the three independent models and suggest that one-dose vaccination has similar health benefits to a two-dose programme while simplifying vaccine delivery, reducing costs, and alleviating vaccine supply constraints. The second dose may become cost-effective if there is a shorter duration of protection from one dose, cheaper vaccine and vaccination delivery strategies, and high burden of cervical cancer.
The recurrent WASF1 nonsense variant identified in two unaffected Chinese families with neurodevelopmental disorder: case report and review of the literatures
Authors: Tang Xiang , Liu Guoqing , Lin Li , Xiao Nong , Chen Yuxia 
Published: August 2023

Abstract
Background
Neurodevelopmental disorder with absent language and variable seizures (NEDALVS, # 618707) are characterized by delayed speech and motor development, ocular abnormalities, and seizures. NEDAVLS is an autosomal dominant disorder caused by de novo mutations in the wasp protein family member 1 (WASF1) gene.

Case presentation
We identified a de novo nonsense variant c.1516 C > T (p.Arg506*) of WASF1 gene (NM_003931.3) in two pediatric female patients with delayed motor and language development.

Conclusion
This case demonstrates the effective role of WES in the diagnosis of NEDALVS. To the best of our knowledge, this variant has not been reported in the Chinese population. This contributes to our further understanding of the disease and to research related to the genetic and clinical heterogeneity, the treatment and prognosis of the disease.
A comparative study of in vitro air–liquid interface culture models of the human airway epithelium evaluating cellular heterogeneity and gene expression at single cell resolution
Authors: Prescott Rachel A. , Pankow Alec P. , de Vries Maren , Crosse Keaton M. , Patel Roosheel S. , Alu Mark , Loomis Cynthia , Torres Victor , Koralov Sergei , Ivanova Ellie , Dittmann Meike , Rosenberg Brad R. 
Published: August 2023

Abstract
Background
The airway epithelium is composed of diverse cell types with specialized functions that mediate homeostasis and protect against respiratory pathogens. Human airway epithelial (HAE) cultures at air–liquid interface are a physiologically relevant in vitro model of this heterogeneous tissue and have enabled numerous studies of airway disease. HAE cultures are classically derived from primary epithelial cells, the relatively limited passage capacity of which can limit experimental methods and study designs. BCi-NS1.1, a previously described and widely used basal cell line engineered to express hTERT, exhibits extended passage lifespan while retaining the capacity for differentiation to HAE. However, gene expression and innate immune function in BCi-NS1.1-derived versus primary-derived HAE cultures have not been fully characterized.

Methods
BCi-NS1.1-derived HAE cultures (n = 3 independent differentiations) and primary-derived HAE cultures (n = 3 distinct donors) were characterized by immunofluorescence and single cell RNA-Seq (scRNA-Seq). Innate immune functions were evaluated in response to interferon stimulation and to infection with viral and bacterial respiratory pathogens.

Results
We confirm at high resolution that BCi-NS1.1- and primary-derived HAE cultures are largely similar in morphology, cell type composition, and overall gene expression patterns. While we observed cell-type specific expression differences of several interferon stimulated genes in BCi-NS1.1-derived HAE cultures, we did not observe significant differences in susceptibility to infection with influenza A virus and Staphylococcus aureus.

Conclusions
Taken together, our results further support BCi-NS1.1-derived HAE cultures as a valuable tool for the study of airway infectious disease.