bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weight gain from early to middle adulthood increases the risk of incident asthma later in life in the United States: a retrospective cohort study
Authors: Wang Tao , Zhou Yunping , Kong Nan , Zhang Jianzhong , Cheng Guo , Zheng Yuxin 
Published: May 2021

Abstract
Background
Data describing the effects of weight change across adulthood on asthma are important for the prevention of asthma. This study aimed to investigate the association between weight change from early to middle adulthood and risk of incident asthma.

Methods
Using data from the National Health and Nutrition Examination Survey (NHANES), we performed a nationally retrospective cohort study of the U.S. general population. A total of 20,771 people aged 40–74 years with recalled weight at young and middle adulthood were included in the cohort. Four weight change groups were categorized: stable non-obesity, non-obesity to obesity, obesity to non-obesity, and stable obesity. Hazard ratios (HRs) and 95% confidence intervals (CIs) relating weight change to incident asthma over 10 years of follow-up were calculated using Cox models adjusting for covariates.

Results
Compared with the stable non-obesity group, the HRs of incident asthma were 1.63 (95% CI = 1.29 to 2.07, P < 0.001) for the non-obesity to obesity group, 1.41 (95% CI = 0.97 to 2.05, P = 0.075) for stable obesity group, and 1.21 (95% CI = 0.41 to 3.62, P = 0.730) for the obesity to non-obesity group. In addition, participants who gained more than 20 kg from young to middle adulthood had a HR of 1.53 (95% CI = 1.15 to 2.03, P = 0.004), compared with those whose weight remained stable (weight change within 2.5 kg).

Conclusions
Weight gain from early to middle adulthood was associated with higher risk of incident asthma as compared to those who maintained normal weight. Thus, maintaining normal weight throughout adulthood might be important for the primary prevention of adult-onset asthma.
Associations of continuous glucose monitoring-assessed glucose variability with intima-media thickness and ultrasonic tissue characteristics of the carotid arteries: a cross-sectional analysis in patients with type 2 diabetes
Authors: Taya Naohiro , Katakami Naoto , Mita Tomoya , Okada Yosuke , Wakasugi Satomi , Yoshii Hidenori , Shiraiwa Toshihiko , Otsuka Akihito , Umayahara Yutaka , Ryomoto Kayoko , Hatazaki Masahiro , Yasuda Tetsuyuki , Yamamoto Tsunehiko , Gosho Masahiko , Shimomura Iichiro , Watada Hirotaka 
Published: May 2021

Abstract
Background
The association between glucose variability and the progression of atherosclerosis is not completely understood. We aimed to evaluate the associations of glucose variability with the progression of atherosclerosis in the early stages.

Methods
We conducted a cross-sectional analysis to investigate the associations of glucose variability, assessed by continuous glucose monitoring, with intima-media thickness (IMT) and gray-scale median (GSM) of the carotid arteries, which are different indicators for the progression of atherosclerosis. We used baseline data from a hospital-based multicenter prospective observational cohort study among Japanese patients with type 2 diabetes without a history of cardiovascular diseases aged between 30 and 80 years. Continuous glucose monitoring was performed by Freestyle Libre Pro, and glucose levels obtained every 15 min for a maximum of eight days were used to calculate the metrics of glucose variability. IMT and GSM were evaluated by ultrasonography, and the former indicates thickening of intima-media complex in the carotid artery wall, while the latter indicates tissue characteristics.

Results
Among 600 study participants (age: 64.9 ± 9.2 (mean ± SD) years; 63.2%: men; HbA1c: 7.0 ± 0.8%), participants with a larger intra- and inter-day glucose variability had a lower GSM and most of these associations were statistically significant. No trend based on glucose variability was shown regarding IMT. Standard deviation of glucose (regression coefficient, β = − 5.822; 95% CI − 8.875 to − 2.768, P < 0.001), glucose coefficient of variation (β = − 0.418; − 0.685 to − 0.151, P = 0.002), mean amplitude of glycemic excursion (β = − 1.689; − 2.567 to − 0.811, P < 0.001), mean of daily differences (β = − 6.500; − 9.758 to − 3.241, P < 0.001), and interquartile range (β = − 4.289; − 6.964 to − 1.614, P = 0.002) had a statistically significant association with mean-GSM after adjustment for conventional cardiovascular risk factors, including HbA1c. No metrics of glucose variability had a statistically significant association with IMT.

Conclusions
Continuous glucose monitoring-assessed glucose variability was associated with the tissue characteristics of the carotid artery wall in type 2 diabetes patients without cardiovascular diseases.
Effects of pemafibrate on glucose metabolism markers and liver function tests in patients with hypertriglyceridemia: a pooled analysis of six phase 2 and phase 3 randomized double‐blind placebo‐controlled clinical trials
Authors: Yokote Koutaro , Yamashita Shizuya , Arai Hidenori , Araki Eiichi , Matsushita Mitsunori , Nojima Toshiaki , Suganami Hideki , Ishibashi Shun 
Published: May 2021

AbstractBackgroundIncreased risk of cardiovascular events is associated not only with dyslipidemias, but also with abnormalities in glucose metabolism and liver function. This study uses pooled analysis to explore the in-depth effects of pemafibrate, a selective peroxisome proliferator-activated receptor α modulator (SPPARMα) already known to decrease elevated triglycerides, on glucose metabolism and liver function in patients with hypertriglyceridemia.MethodsWe performed a post-hoc analysis of six phase 2 and phase 3 Japanese randomized double-blind placebo-controlled trials that examined the effects of daily pemafibrate 0.1 mg, 0.2 mg, and 0.4 mg on glucose metabolism markers and liver function tests (LFTs). Primary endpoints were changes in glucose metabolism markers and LFTs from baseline after 12 weeks of pemafibrate treatment. All adverse events and adverse drug reactions were recorded as safety endpoints.ResultsThe study population was 1253 patients randomized to placebo (n = 298) or pemafibrate 0.1 mg/day (n = 127), 0.2 mg/day (n = 584), or 0.4 mg/day (n = 244). Participant mean age was 54.3 years, 65.4 % had BMI ≥ 25 kg/m2, 35.8 % had type 2 diabetes, and 42.6 % had fatty liver. Fasting glucose, fasting insulin, and HOMA-IR decreased significantly in all pemafibrate groups compared to placebo. The greatest decrease was for pemafibrate 0.4 mg/day: least square (LS) mean change from baseline in fasting glucose − 0.25 mmol/L; fasting insulin − 3.31 µU/mL; HOMA-IR − 1.28. ALT, γ-GT, ALP, and total bilirubin decreased significantly at all pemafibrate doses vs. placebo, with the greatest decrease in the pemafibrate 0.4 mg/day group: LS mean change from baseline in ALT − 7.6 U/L; γ-GT − 37.3 U/L; ALP − 84.7 U/L; and total bilirubin − 2.27 µmol/L. Changes in HbA1c and AST did not differ significantly from placebo in any pemafibrate groups in the overall study population. The decreases from baseline in LFTs and glucose metabolism markers except for HbA1c were notable among patients with higher baseline values. FGF21 increased significantly in all pemafibrate groups compared to placebo, with the greatest increase in the pemafibrate 0.4 mg/day group. Adverse event rates were similar in all groups including placebo.ConclusionsIn patients with hypertriglyceridemia, pemafibrate can improve glucose metabolism and liver function, and increase FGF21, without increasing adverse event risk.
Immune response induced by oral administration with a Saccharomyces cerevisiae-based SARS-CoV-2 vaccine in mice
Authors: Gao Tong , Ren Yi , Li Shuangqin , Lu Xin , Lei Han 
Published: May 2021

Abstract
Background
The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need to develop safe and effective vaccines with a top priority. Multiple vaccine candidates are under development, and several vaccines are currently available. Efforts need to be undertaken to counter the threat of the global COVID-19 pandemic.

Results
We generated a Saccharomyces cerevisiae (S. cerevisiae)-based SARS-CoV-2 vaccine, EBY100/pYD1-RBD, in which the full-length receptor binding domain (RBD) of the spike protein of SARS-CoV-2 was expressed on the surface of yeast. Mice vaccinated orally with unadjuvanted EBY100/pYD1-RBD could produce significant humoral and mucosal responses as well as robust cellular immune responses. Notably, EBY100/pYD1-RBD elicited a mixed Th1/Th2-type cellular immune response with a Th1-biased immune response in a mouse model.

Conclusions
Our findings highlight the importance of the RBD as a key target to design and develop vaccines against SARS-CoV-2 and provide evidence of oral administration of a S. cerevisiae-based SARS-CoV-2 vaccine eliciting significant immune responses. Most importantly, the S. cerevisiae surface display system can serve as a universal technology platform and be applied to develop other oral viral or bacterial vaccines.
Pentraxin 3 is a diagnostic and prognostic marker for ovarian epithelial cancer patients based on comprehensive bioinformatics and experiments
Authors: Chang Xiaoying , Li Dan , Liu Chang , Zhang Zhe , Wang Tao 
Published: May 2021

AbstractBackgroundOvarian epithelial cancer is one of the leading malignant tumors in gynecology and lacks effective diagnostic and prognostic markers. Our study aims to screen and verify ovarian epithelial cancer biomarkers.MethodsGSE18520 and GSE26712 were downloaded from the GEO database. The “limma” and “WGCNA” packages were used to explore hub genes. The Kaplan–Meier Plotter database was used for survival analysis of the hub genes. Immunohistochemical analysis was used to identify the expression level of Pentraxin 3 in ovarian epithelial cancer samples.ResultsIn this study, we integrated and analyzed two datasets, GSE18520 and GSE26712, and a total of 238 differentially expressed genes (DEGs) were screened out. Enrichment analysis showed that these DEGs were related to collagen-containing extracellular matrix and other pathways. Further application of WGCNA (weighted gene coexpression network analysis) identified 15 gene modules, with the purple module showing the highest correlation with ovarian epithelial cancer. Twenty-five genes were shared between the purple module and DEGs, 13 genes were related to the prognosis of ovarian epithelial cancer patients, and the PTX3 gene had the highest hazardous risk (HR) value. We performed immunohistochemical analyses on the 255 Pentraxin-3 (PTX3)-based clinical samples. PTX3 was found to be overexpressed in ovarian epithelial cancer and related to the degree of differentiation. The Cox proportional hazard model indicates that high PTX3 expression is an independent risk factor for the prognosis of ovarian epithelial cancer patients.ConclusionsIn conclusion, through WGCNA and a series of comprehensive bioinformatics analyses, PTX3 was first identified as a novel diagnostic and prognostic biomarker for ovarian epithelial cancer.
Sugar-sweetened beverage consumption and bone health: a systematic review and meta-analysis
Authors: Ahn Hyejin , Park Yoo Kyoung 
Published: May 2021

Abstract
Background
Current evidence demonstrate that sugar-sweetened beverages (SSBs) and bone health are related; however, there has been only a few reviews on the link between SSBs and bone health. A systematic review and meta-analysis was performed to investigate the association between SSBs consumption and bone health in chidren and adults.

Methods
Relevant studies of SSBs and bone health published up to 15 March 2021 were searched using PubMed, the Web of Science, Cochrane Library, and a reference search. A random-effects meta-analysis was conducted to estimate the standardized mean difference (SMD). Subgroup analyses were performed to identify whether effects were modified by age, sex, measured skeletal sites, type of SSBs, and SSBs intake questionnaire.

Results
Twenty-six publications including 124,691 participants were selected on the review. The results from this meta-analysis showed a significant inverse association between SSBs intake and bone mineral density (BMD) in adults (ES: -0.66, 95% CI: − 1.01, − 0.31, n = 4312). Eighteen of the 20 studies included in the qualitative-only review in children and adults supported the findings from the meta-analysis. When subgroup analysis was performed according to skeletal site, a large effect was found on whole body BMD (ES: -0.97, 95% CI: − 1.54, − 0.40). There was a moderate effect on BMD in females (ES: -0.50, 95% CI: − 0.87, − 0.13). There was a moderate or large effect on BMD in individuals aged under 50 years (under 30 years: ES: -0.57, 95% CI: − 0.97, − 0.17; 30 to 50 years: ES: -1.33, 95% CI: − 1.72, − 0.93). High consumption of carbonated beverages had a moderate effect on BMD (ES: -0.73, 95% CI: − 1.12, − 0.35).

Conclusion
The meta-analysis showed that SSBs consumption such as carbonated beverages were inversely related to BMD in adults. Qualitative review supported the results of meta-analysis.

Trial registration
This review was registered in the PROSPERO database under identifier CRD42020164428.
Research on developing environmental ethics in pharmacists’ activities
Authors: Toma Alexandra , Crişan Ofelia 
Published: May 2021

Abstract
Background
Authors of various backgrounds are preoccupied with the meaning of environmental ethics, which refers to specific values, norms, attitudes, and practices with respect to all beings and elements of nature. Many international organizations have adopted important documents proclaiming the ethical obligation to protect the environment in all professional activities. At the national level, professional associations should include and develop this obligation in their codes of conduct. This study aimed to analyze and compare elements of environmental protection included in codes of conduct for pharmacists, to find ways to integrate environmental ethics into their activities.

Methods
Seven codes of conduct for pharmacists were analyzed using the comparative method and methods of legal interpretation. Based on acknowledged values and principles of environmental ethics, a framework model for developing environmental protection in pharmacists’ activities was created via an iterative process of reflection and discussion.

Results
Explicit provisions for environmental ethics were found in codes in force in three countries and in a Romanian project. These provisions refer, in general, to an ethical duty of environmental protection in pharmacists’ activities. Regarding the other codes, the study could only interpret stipulations of public health ethics to deduce an ethical environmental obligation. Considering the need for developing such provisions, an ethical framework was proposed as a model for professional associations of pharmacists.

Conclusions
The studied codes demonstrate a preoccupation of the professional associations with environmental protection in pharmacists’ activities, with different degrees of interest in developing environmental ethics. To this end, the codes of conduct for pharmacists should include environmental values, principles, and ethics guidelines. Those guidelines should indicate the ethical attitude in relation to the environment for each activity. Further research is needed to stimulate, shape, and develop an environmental ethical behavior in pharmacists’ practice.
Development of the gait outcomes assessment list for lower-limb differences (GOAL-LD) questionnaire: a child and parent reported outcome measure
Authors: Dermott Jennifer A. , Wright F. Virginia , Salbach Nancy M. , Narayanan Unni G. 
Published: May 2021

AbstractBackgroundTo develop a priority-based patient/parent reported outcome measure for children with lower-limb differences (LD) by adapting the Gait Outcomes Assessment List (GOAL) questionnaire.MethodsGuided by a conceptual framework of patient priorities, the GOAL questionnaire was iteratively modified and its sensibility evaluated by field-testing it on children with LD, and their parents. Cognitive interviews were conducted with a subgroup of these children, and an e-survey administered to a multidisciplinary group of health care professionals with expertise in paediatric LD. Findings were integrated to create the final version of the GOAL-LD.ResultsTwenty-five children (9–18 years), 20 parents, and 31 healthcare professionals evaluated the content and sensibility of the GOAL, with an emphasis on the relevance and importance of the items to patients’ health related quality of life (HRQL). This resulted in the retention of 26 of the original 50 items, elimination of 12, modification of 12, and addition of seven new items. The new 45-item GOAL-LD questionnaire was shown to be sensible, and its content deemed important.ConclusionsThe GOAL-LD questionnaire has a high level of face and content validity, and sensibility. It comprehensively captures the HRQL goals and outcomes that matter to children with LD and their parents. Following further psychometric evaluation, the GOAL-LD may serve as a much needed patient and parent reported outcome measure for this population.
Meta-analysis of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for locally advanced rectal cancer
Authors: Lin Huaqin , Wang Lei , Zhong Xiaohong , Zhang Xueqing , Shao Lingdong , Wu Junxin 
Published: May 2021

Abstract
Background and purpose
With the advent of more intensive chemotherapy regimens, neoadjuvant chemoradiotherapy (NACRT) for patients with locally advanced rectal cancer (LARC) has always been questioned due to its inevitable radiation toxicity. Hence, we conducted a meta-analysis to compare the clinical efficacy of neoadjuvant chemotherapy (NAC) and NACRT.

Materials and methods
Eligible studies were searched using PubMed, MEDLINE, Embase, the Cochrane Library, and Web of Science up to 31 July 2020, comparing the clinical efficacy of NAC versus NACRT for LARC. Short- and long-term outcomes were determined using the odds ratio (OR) with 95% confidence interval (CI).

Results
Six studies with 12,812 patients were eligible for this meta-analysis, including 677 patients in the NAC group and 12,135 patients in the NACRT group. There were no significant differences between the two groups in terms of pathological complete response rate (OR=0.62, 95%CI=0.27~1.41), N down-staging rate (OR=1.20, 95%CI=0.25~5.79), R0 resection rate (OR=1.24, 95%CI=0.78~1.98), and local relapse rate (OR=1.12, 95%CI=0.58~2.14). The pooled OR for the total response rate and T down-staging were in favor of NACRT (OR=0.41, 95%CI=0.22~0.76 versus OR=0.67 95%CI=0.52~0.87). However, the pooled OR for the sphincter preservation rate favored NAC compared with NACRT (OR=1.87, 95%CI=1.24~2.81). Moreover, NAC was found to be superior to NACRT in terms of distant metastasis (14.3% vs. 20.4%), but the difference was not significant (OR=0.84, 95%CI=0.31~2.27).

Conclusion
We concluded that NAC was superior to NACRT in terms of the sphincter preservation rate, and non-inferior to NACRT in terms of pCR, N down-staging, R0 resection, local relapse, and distant metastasis. However, the conclusion warrants further validation.
Construct validity and reliability of the physical activity parenting questionnaire for children (PAP-C)
Authors: Laukkanen Arto , Aunola Kaisa , Korhonen Elisa , Barnett Lisa M. , Sääkslahti Arja 
Published: May 2021

Abstract
Background
Children’s perception of parenting is hypothesised to significantly affect their physical activity (PA). This study aimed to examine construct validity, factorial invariance and reliability of a new tool: Physical Activity Parenting questionnaire for Children (PAP-C).

Methods
PAP-C comprised 22 items hypothesised to cover 3 theory-guided factors of physical activity parenting (PAP)—namely, structure for activity, autonomy support and involvement. Construct validity and internal consistency of PAP-C were tested using confirmatory factor analysis (CFA) and composite reliability in a sample of Finnish first, second- and third graders (n = 456; mean age 8.77 ± 0.84 years, girls 51.1%). Factorial invariance of PAP-C across grade levels was investigated using sequential multigroup CFA. Intra-class correlation (ICC) coefficients of the sum factors were calculated in a sample of children who completed a 4-week PAP-C retest (n = 450; mean age 8.83 ± 0.87 years, girls 48.0%).

Results
A first-order 3-factor model of the structure for activity, autonomy support and involvement, with 20 items (two items removed), showed an acceptable fit. The model demonstrated configural, metric, and scalar invariance across grade levels. Composite reliabilities indicated moderate-to-good internal consistency (from .74 to .87) for the factors. ICCs (from .494 to .750, p < .001) showed moderate to excellent test–retest stability for all grade levels.

Conclusions
PAP-C can be considered to be a promising tool for investigating 7–10-year-old children’s perceptions of PAP.
Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa
Authors: Farinre Omotayo , Gounder Kamini , Reddy Tarylee , Tongo Marcel , Hare Jonathan , Chaplin Beth , Gilmour Jill , Kanki Phyllis , Mann Jaclyn K. , Ndung’u Thumbi 
Published: May 2021

Abstract
Background
The HIV-1 epidemic in sub-Saharan Africa is heterogeneous with diverse unevenly distributed subtypes and regional differences in prevalence. Subtype-specific differences in disease progression rate and transmission efficiency have been reported, but the underlying biological mechanisms have not been fully characterized. Here, we tested the hypothesis that the subtypes prevalent in the East Africa, where adult prevalence rate is higher, have lower viral replication capacity (VRC) than their West African counterparts where adult prevalence rates are lower.

Results
Gag-protease sequencing was performed on 213 and 160 antiretroviral-naïve chronically infected participants from West and East Africa respectively and bioinformatic tools were used to infer subtypes and recombination patterns. VRC of patient-derived gag-protease chimeric viruses from West (n = 178) and East (n = 114) Africa were determined using a green fluorescent protein reporter-based cell assay. Subtype and regional differences in VRC and amino acid variants impacting VRC were identified by statistical methods. CRF02_AG (65%, n = 139), other recombinants (14%, n = 30) and pure subtypes (21%, n = 44) were identified in West Africa. Subtypes A1 (64%, n = 103), D (22%, n = 35), or recombinants (14%, n = 22) were identified in East Africa. Viruses from West Africa had significantly higher VRC compared to those from East Africa (p < 0.0001), with subtype-specific differences found among strains within West and East Africa (p < 0.0001). Recombination patterns showed a preference for subtypes D, G or J rather than subtype A in the p6 region of gag, with evidence that subtype-specific differences in this region impact VRC. Furthermore, the Gag A83V polymorphism was associated with reduced VRC in CRF02_AG. HLA-A*23:01 (p = 0.0014) and HLA-C*07:01 (p = 0.002) were associated with lower VRC in subtype A infected individuals from East Africa.

Conclusions
Although prevalent viruses from West Africa displayed higher VRC than those from East Africa consistent with the hypothesis that lower VRC is associated with higher population prevalence, the predominant CRF02_AG strain in West Africa displayed higher VRC than other prevalent strains suggesting that VRC alone does not explain population prevalence. The study identified viral and host genetic determinants of virus replication capacity for HIV-1 CRF02_AG and subtype A respectively, which may have relevance for vaccine strategies.