bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short- and long-term agreement and reproducibility of 48-hours intraocular pressure measurements in glaucoma patients
Authors: Zimmermann Marion , Giers Bert C. , Beck Anna , Bell Katharina , Zimmermann Herwig , Hechtner Marlene , Hoffmann Esther M. , Pfeiffer Norbert , Lorenz Katrin 
Published: June 2021

Abstract
Background
Glaucomatous eyes often show strong intraocular pressure (IOP) fluctuations and individual measurements at different time points are necessary for personalized therapy. To survey IOP variations 48-hours diurnal and nocturnal IOP measurements were performed on two consecutive days. Aims of this study were to investigate the short-term repeatability of 48-hours measurements within one patient’s IOP profile and long-term repeatability between two separate IOP profiles of the same patient.

Methods
A retrospective cohort study was performed evaluating data of 90 glaucoma patients in a German university medical center between 2006 and 2013. All patients underwent two separate diurnal IOP profiles of 48 h. IOP was measured at 8 am, 2 pm, 6 pm, 9 pm using Goldmann applanation tonometry and at 12 midnight using Perkins tonometry in supine position on two consecutive days. Intraclass correlation coefficients (ICC) were calculated to evaluate agreement for the same time points (each time point agreement) and for consecutive measurements within the IOP profiles (between time point agreement). ICC ≤ 0.4 was defined as poor agreement, 0.4–0.75 as moderate and ≥ 0.75 as excellent. Differences between time points were investigated by Bland Altman plots.

Results
Each time point measurements of profile 1 showed moderate to excellent agreement (ICCs 0.62–0.93). There was a moderate to excellent agreement for measurements between time points of profile 1 (ICCs day one 0.57–0.86, day two 0.71–0.90). Profile 2 was performed at a median interval of 12.0 months (quartiles 11.0 to 21.0). Each time point agreements within profile 2 showed ICCs from 0.23 to 0.81. It showed moderate to excellent agreement for changes between time points (ICCs 0.53–0.94). Day two demonstrated ICCs from 0.74 to 0.88. Long term IOP repeatability (over both pressure profiles) showed moderate to good agreement (ICCs 0.39–0.67).

Conclusions
Short and long-term agreement of IOP measurements evaluated by diurnal IOP profiles is moderate to good. Due to mostly moderate agreements, which we believe represent IOP fluctuations, we conclude that it is necessary to perform 48-hours IOP profiles to gain a better overview of the individual IOP fluctuations.
Examining the impact of the early stages of the COVID-19 pandemic period on youth cannabis use: adjusted annual changes between the pre-COVID and initial COVID-lockdown waves of the COMPASS study
Authors: Leatherdale Scott T. , Bélanger Richard E. , Gansaonré Rabi Joël , Patte Karen A. , deGroh Margaret , Jiang Ying , Haddad Slim 
Published: June 2021

AbstractBackgroundGiven the high rates of cannabis use among Canadian youth and that adolescence is a critical period for cannabis use trajectories, the purpose of this paper was to examine the effect of the early stages of the COVID-19 pandemic period on youth cannabis use in the context of a natural experiment.We used 3-year linked data from the COMPASS study, including 7653 Canadian (Quebec, Ontario) adolescents from which 1937 completed all 3 survey waves (pre-COVID-19 [2018, 2019] and online [2020] during the early pandemic period [May–July 2020]). Structural equation modeling (SEM) and double difference (DD) models were used to estimate pre-COVID-19 to initial COVID-19 pandemic period change (2019–2020) in cannabis use (monthly, weekly, daily) compared to 2018 to 2019 change to adjust for age-related effects. Models were adjusted for age of entry into the cohort and sociodemographic characteristics.ResultsIn the SEM and DD models, monthly, weekly, and daily cannabis use increased across all waves; however, the expected increases from the pre-COVID-19 wave (2019) to the initial COVID-19 period wave (2020) were lesser relative to the changes seen across the 2018 to 2019 waves. The cross-sectional data from May to July 2020 identified that the majority of youth who use cannabis did not report increased cannabis use due to COVID-19 or using cannabis to cope with COVID-19.ConclusionDuring the early stages of the COVID-19 pandemic period, there does not appear to be a detrimental effect on youth cannabis use, when adjusted for age-related changes. Further prospective research is needed to explore the impact of the ongoing pandemic response on youth cannabis use onset and progression.
Reliability and validity of simplified Chinese version of the Italian spine youth quality of life questionnaire in adolescents with idiopathic scoliosis
Authors: Liu Shanshan , Liang Junyang , Xu Nanfang , Mai Shuo , Wang Qi , Zeng Lin , Du Chaojun , Du Yaoxu , Zeng Yan , Yu Miao , Liu Zhongjun 
Published: June 2021

Abstract
Background
The Italian Spine Youth Quality of Life (ISYQOL) questionnaire is used to evaluate health-related quality of life in adolescents with Idiopathic Scoliosis. The study aimed to undertake the process of cultural adaptation of the ISYQOL questionnaire into Simplified Chinese.

Methods
Translate from Italian into Simplified Chinese. It involved 138 adolescents whose Cobb angle ranged between 20 and 40 degrees, 50 wearing the brace and 88 not wearing the brace. Statistical analysis calculated the reliability, floor effects, and ceiling effects of the ISYQOL. After that, construct validity was measured by analyzing the ISYQOL relationship Scoliosis Research Society-22 patient Questionnaire (SRS-22).

Results
There were no floor or ceiling effects in the ISYQOL questionnaire. Cronbach’s alpha coefficient evaluated for Internal consistency was 0.75 in the no-treated group and 0.88 in the brace-treated group. Intraclass correlation coefficients assessed with the use of the test-retest method were 0.72 in the no-treated group and 0.80 in the brace-treated group. A strong relationship exists between the ISYQOL measure and SRS-22 scores (rho = 0.62; p < 0.01), reflecting the high validity of the questionnaires. Both ISYQOL and SRS-22 scores showed no statistical difference between groups wearing and not wearing the brace (p > 0.05).

Conclusions
Trans-cultural validation in Chinses language showed the reliability and validity of the ISYQOL.
Relugolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, in women with endometriosis-associated pain: phase 2 safety and efficacy 24-week results
Authors: Osuga Yutaka , Seki Yoshifumi , Tanimoto Masataka , Kusumoto Takeru , Kudou Kentarou , Terakawa Naoki 
Published: June 2021

Abstract
Background
Relugolix is a once-daily, oral, nonpeptide, gonadotropin-releasing hormone receptor antagonist. The aim of this study was to evaluate safety of relugolix over 24 weeks in women with endometriosis-associated pain.

Methods
This phase 2, randomized, open-label, parallel-group extension study was conducted in 101 clinics in Japan. Patients (premenopausal females ≥ 20 years) who completed the preceding 12-week relugolix phase 2 study continued to receive relugolix (10 mg, 20 mg, or 40 mg), placebo, or leuprorelin (3.75 mg) for an additional 12 weeks. Relugolix was administered orally once daily, and leuprorelin subcutaneously once every 4 weeks. The primary outcome was safety, including bone mineral density (BMD) and treatment-emergent adverse events (TEAEs). Secondary endpoints included visual analog scale (VAS) scores for endometriosis-associated pain. Analysis sets were defined as all patients who were administered the study drug.

Results
Of 487 randomized patients in the preceding study, 397 enrolled in this extension study and continued to receive placebo (n = 77), relugolix 10 mg (n = 84), relugolix 20 mg (n = 78), relugolix 40 mg (n = 89), or leuprorelin (n = 69). Baseline characteristics were similar between extension study patients and patients in the preceding study. Frequency of TEAEs including metrorrhagia, menorrhagia, and hot flush was similar in the relugolix 40-mg and leuprorelin groups. Mean (SD) change in BMD from baseline at Week 24 was − 0.2 (1.99)% for placebo;  − 1.6 (2.34)%,  − 2.6 (2.94)%, and  − 4.9 (2.91)% for the relugolix 10-mg, 20-mg, and 40-mg groups, respectively; and − 4.4 (2.16)% for leuprorelin. Mean ± SD change from baseline in mean VAS score (mm) for pelvic pain at end of treatment was − 3.2 ± 12.16 for placebo; − 6.8 ± 10.56, − 9.0 ± 11.84, and − 11.9 ± 11.26 for the relugolix 10-mg, 20-mg, and 40-mg groups, respectively; and − 12.7 ± 12.57 for leuprorelin. Estradiol levels decreased with increasing relugolix dose and remained below postmenopausal levels throughout the 24-week relugolix 40-mg treatment period.

Conclusions
Treatment with relugolix for 24 weeks was generally well tolerated and demonstrated similar pain reduction to leuprorelin in women with endometriosis. The dose-dependent loss in BMD observed with relugolix treatment was expected due to an induced hypoestrogenic state. Relugolix demonstrated a similar benefit/risk profile to injectable therapy in this phase 2 study.
Trial registration NCT01452685 (ClinicalTrials.gov, registered 17/10/2011).
Mealtime caregiving approaches and behavioral symptoms in persons living with dementia: a longitudinal, observational study
Authors: Lee Ji Yeon , Lee Kyung Hee , McConnell Eleanor S. 
Published: June 2021

Abstract
Background
Behavioral symptoms during mealtime can prohibit persons living with dementia from obtaining sufficient nutrition. However, little research has examined the relationship between behavioral symptoms and caregiving approaches. This study examines this relationship and further explores which specific caregiver behaviors were related to behavioral symptoms among persons living with dementia.

Methods
A secondary data analysis was performed using 86 mealtime videos from a longitudinal, observational study. The videos were repeatedly taken at months 0, 3, and 6 with 30 persons living with dementia in one of four long-term care facilities. Video coding was performed using coding schemes modified from the Cohen-Mansfield Agitation Inventory for behavioral symptoms and the Person-/Task-Centered Behavior Inventory for caregiving approaches. Coding schemes for behavioral symptoms consisted of four categories: total duration, aggressive behavior, physically nonaggressive behavior, and verbally agitated behavior. Caregiving approaches consisted of ten-verbal/seven-nonverbal person-centered behavior codes, four-verbal/four-nonverbal task-centered behavior codes, and no-verbal/no-nonverbal interaction codes. A mixed-effect model was conducted using variables such as demographics, medical information, cognitive status, depression, function, and caregiving approaches as fixed effects, participant as a random effect, and four categories of behavioral symptoms as dependent variables.

Results
The total duration of the Cohen-Mansfield Agitation Inventory was associated with no verbal response (β = 9.09) and task-centered verbal behavior (β = 8.43), specifically verbal controlling (β = 7.87). Physically nonaggressive behavior was associated with no verbal response (β = 9.36). Verbally agitated behavior was associated with task-centered nonverbal behavior (β = 51.29), and specifically inappropriate touch (β = 59.05).

Conclusions
Mealtime is indispensable to dementia care for ensuring adequate nutrition and promoting personhood. Our findings revealed caregivers’ task-centered behaviors and no interaction were related to behavioral symptoms of persons living with dementia. When caregivers encounter behavioral symptoms during mealtime, it is recommended to avoid no response and task-centered behaviors, especially verbal controlling and inappropriate touch, and to promote person-centered behaviors.
Visceral adipose tissue imparts peripheral macrophage influx into the hypothalamus
Authors: Chen Kuan-Hui Ethan , Lainez Nancy M. , Nair Meera G. , Coss Djurdjica 
Published: June 2021

Abstract
Background
Obesity is characterized by a systemic inflammation and hypothalamic neuroinflammation. Systemic inflammation is caused by macrophages that infiltrate obese adipose tissues. We previously demonstrated that high-fat diet (HFD)-fed male mice exhibited peripheral macrophage infiltration into the hypothalamus, in addition to activation of resident microglia. Since this infiltration contributes to neuroinflammation and neuronal impairment, herein we characterize the phenotype and origin of these hypothalamic macrophages in HFD mice.

Methods
C57BL/6J mice were fed HFD (60% kcal from fat) or control diet with matching sucrose levels, for 12–16 weeks. Males and females were analyzed separately to determine sex-specific responses to HFD. Differences in hypothalamic gene expression in HFD-fed male and female mice, compared to their lean controls, in two different areas of the hypothalamus, were determined using the NanoString neuroinflammation panel. Phenotypic changes in macrophages that infiltrated the hypothalamus in HFD-fed mice were determined by analyzing cell surface markers using flow cytometry and compared to changes in macrophages from the adipose tissue and peritoneal cavity. Adipose tissue transplantation was performed to determine the source of hypothalamic macrophages.

Results
We determined that hypothalamic gene expression profiles demonstrate sex-specific and region-specific diet-induced changes. Sex-specific changes included larger changes in males, while region-specific changes included larger changes in the area surrounding the median eminence. Several genes were identified that may provide partial protection to female mice. We also identified diet-induced changes in macrophage migration into the hypothalamus, adipose tissue, and peritoneal cavity, specifically in males. Further, we determined that hypothalamus-infiltrating macrophages express pro-inflammatory markers and markers of metabolically activated macrophages that were identical to markers of adipose tissue macrophages in HFD-fed mice. Employing adipose tissue transplant, we demonstrate that hypothalamic macrophages can originate from the visceral adipose tissue.

Conclusion
HFD-fed males experience higher neuroinflammation than females, likely because they accumulate more visceral fat, which provides a source of pro-inflammatory macrophages that migrate to other tissues, including the hypothalamus. Our findings may explain the male bias for neuroinflammation and the metabolic syndrome. Together, our results demonstrate a new connection between the adipose tissue and the hypothalamus in obesity that contributes to neuroinflammation and hypothalamic pathologies.
Managing borders during public health emergencies of international concern: a proposed typology of cross-border health measures
Authors: Lee Kelley , Grépin Karen A. , Worsnop Catherine , Marion Summer , Piper Julianne , Song Mingqi 
Published: June 2021

Abstract
Background
The near universal adoption of cross-border health measures during the COVID-19 pandemic worldwide has prompted significant debate about their effectiveness and compliance with international law. The number of measures used, and the range of measures applied, have far exceeded previous public health emergencies of international concern. However, efforts to advance research, policy and practice to support their effective use has been hindered by a lack of clear and consistent definition.

Results
Based on a review of existing datasets for cross-border health measures, such as the Oxford Coronavirus Government Response Tracker and World Health Organization Public Health and Social Measures, along with analysis of secondary and grey literature, we propose six categories to define measures more clearly and consistently – policy goal, type of movement (travel and trade), adopted by public or private sector, level of jurisdiction applied, stage of journey, and degree of restrictiveness. These categories are then brought together into a proposed typology that can support research with generalizable findings and comparative analyses across jurisdictions. Addressing the current gaps in evidence about travel measures, including how different jurisdictions apply such measures with varying effects, in turn, enhances the potential for evidence-informed decision-making based on fuller understanding of policy trade-offs and externalities. Finally, through the adoption of standardized terminology and creation of an agreed evidentiary base recognized across jurisdictions, the typology can support efforts to strengthen coordinated global responses to outbreaks and inform future efforts to revise the WHO International Health Regulations (2005).

Conclusions
The widespread use of cross-border health measures during the COVID-19 pandemic has prompted significant reflection on available evidence, previous practice and existing legal frameworks. The typology put forth in this paper aims to provide a starting point for strengthening research, policy and practice.
Cornuside I promoted osteogenic differentiation of bone mesenchymal stem cells through PI3K/Akt signaling pathway
Authors: Gao Feng , Xia Sheng-Li , Wang Xiu-Hui , Zhou Xiao-Xiao , Wang Jun 
Published: June 2021

Abstract
Background
Osteoporosis is a common disease closely associated with aging. In this study, we aimed to investigate the role of Cornuside I in promoting osteogenic differentiation of bone mesenchymal stem cells (BMSCs) and the potential mechanism.

Methods
BMSCs were isolated and treated with different concentrations of Cornuside I (0, 10, 30, 60 μM). Cell proliferation was analyzed by Cell Counting Kit-8 (CCK-8) assay. RNA sequencing was performed on the isolated BMSCs with control and Cornuside I treatment. Differentially expressed genes were obtained by the R software. Alkaline phosphatase (ALP) staining and Alizarin Red Staining (ARS) were performed to assess the osteogenic capacity of the NEO. qRT-PCR and western blot were used to detect the expression of osteoblast markers.

Results
Cornuside I treatment significantly improved BMSC proliferation. The optimal dose of Cornuside I was 30 μM (P < 0.05). Cornuside I dose dependently increased the ALP activity and calcium deposition than control group (P < 0.05). A total of 704 differentially expressed genes were identified between Cornuside I and normal BMSCs. Cornuside I significantly increased the PI3K and Akt expression. Moreover, the promotion effects of Cornuside I on osteogenic differentiation of BMSCs were partially blocked by PI3K/Akt inhibitor, LY294002.

Conclusion
Cornuside I plays a positive role in promoting osteogenic differentiation of BMSCs, which was related with activation of PI3K/Akt signaling pathway.
Lateral entry pins and Slongo’s external fixation: which method is more ideal for older children with supracondylar humeral fractures?
Authors: He Man , Wang Qian , Zhao Jingxin , Jin Yu , Wang Yu 
Published: June 2021

Abstract
Objective
The standard surgical treatment for supracondylar humeral fractures in children is closed reduction and percutaneous pinning. Given the need for greater fixation strength and higher risk of joint stiffness for children older than 8 years, external fixation is often performed for treating supracondylar humeral fractures in older children. The aim of this study was to compare the efficacy of lateral entry pins and Slongo’s external fixation for treating supracondylar humeral fractures in older children.

Methods
Children older than 8 years who underwent surgery for supracondylar humeral fractures at our hospital for surgery from January 2016 to December 2020 are to be retrospectively assessed. One group (n = 36) underwent internal fixation and percutaneous pinning with three lateral Kirschner wires, and the other group (n = 32) underwent Slongo’s external fixator surgery. The demographic data, operation duration, number of fluoroscopies, and fracture healing time were compared between both groups. The elbow joint function was evaluated 6 months after the surgery on the basis of fracture healing time, lifting angle, elbow joint range of motion (ROM), and Flynn score. The incidence of postoperative complications was also recorded.

Results
There was no significant difference between the two patient groups in terms of the demographic parameters. Compared to external fixation surgery, Kirschner wire surgery required shorter duration and fewer fluoroscopies (P < 0.05). Nevertheless, the fracture healing time was significantly less (P < 0.05), and the elbow ROM and Flynn scores were higher in the external fixator group compared to the Kirschner wire fixation group (P < 0.05). There was one case of secondary fracture displacement in the Kirschner wire group and one of pin tract infection in the external fixator group. No other iatrogenic injuries or complications were observed.

Conclusion
Maybe Slongo’s external fixator is a suitable alternative treatment option for supracondylar humeral fractures in children older than 8 years since it can achieve better fixation strength and early restoration of elbow joint movement with a lower risk of joint stiffness.
GxEsum: a novel approach to estimate the phenotypic variance explained by genome-wide GxE interaction based on GWAS summary statistics for biobank-scale data
Authors: Shin Jisu , Lee Sang Hong 
Published: June 2021

AbstractGenetic variation in response to the environment, that is, genotype-by-environment interaction (GxE), is fundamental in the biology of complex traits and diseases. However, existing methods are computationally demanding and infeasible to handle biobank-scale data. Here, we introduce GxEsum, a method for estimating the phenotypic variance explained by genome-wide GxE based on GWAS summary statistics. Through comprehensive simulations and analysis of UK Biobank with 288,837 individuals, we show that GxEsum can handle a large-scale biobank dataset with controlled type I error rates and unbiased GxE estimates, and its computational efficiency can be hundreds of times higher than existing GxE methods.