bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higher exposure to childhood adversity associates with lower adult flourishing
Authors: Wang Lin , Yu Zhiyuan , Chen Wenyi , Zhang Juan , Bettencourt Amie F. 
Published: March 2022

Abstract
Background
Adverse childhood experiences (ACEs) are prevalent and associated with negative health and social outcomes. However, our understanding of how patterns of ACEs exposure relate to positive outcomes in adulthood remains limited. This study aims to identify patterns of ACEs and examine associations with flourishing in a sample of Chinese young adults.

Methods
This cross-sectional study was conducted from August to November 2020. Young adults, ages 18–35, enrolled in undergraduate or graduate programs at universities in Mainland China were recruited through convenience and snowball sampling to participate in a survey. The exposure to ACEs was measured by the twelve-item Chinese version of the ACE-International Questionnaire. Additional measures included six domains of flourishing assessed using the Chinese version of the Flourishing Measure, and demographic covariates (i.e., gender, age, year in university, marital status). Descriptive statistical analysis and latent class analysis (LCA) were performed using SPSS 27 and Mplus 8.5.

Results
Participants included 9468 young adults (mean age = 20.1 years). Majority of participants were female (75.3%), undergraduate students (96.4%), and single (79.8%). Approximately 56% of participants reported at least one ACE; 7.0% reported four or more ACEs. Emotional neglect (33.2%), household violence (20.6%), and parental separation/divorce (13.9%) were the most frequently reported ACEs. LCA identified three ACEs classes: multiple maltreatment and household violence (4.7%), emotional neglect and household violence (16.2%), and low ACEs (79.1%). Individuals in the low ACEs class had the highest level of flourishing whereas individuals in multiple maltreatment and household violence had the lowest level of flourishing in all six domains. There were no significant differences in flourishing between the multiple maltreatment and household violence and the emotional neglect and household violence classes except in the physical and mental health (means = 6.17 vs 6.51, p = 0.02) and the financial and material stability domains (means = 5.25 vs 5.66, p = 0.04).

Conclusions
Patterns of multiple ACEs exposures were associated with lower levels of flourishing. Our findings have implications for efforts to prevent ACEs exposure through monitoring and promoting family well-being and routine screening to identify those with ACEs exposure to prevent negative social and health sequelae.
An educational intervention using the health belief model for improvement of oral health behavior in grade-schoolers: a randomized controlled trial
Authors: Sanaeinasab Hormoz , Saffari Mohsen , Taghavi Hassan , Karimi Zarchi Aliakbar , Rahmati Fatemeh , Al Zaben Faten , Koenig Harold G. 
Published: March 2022

Abstract
Background
Oral health problems especially dental caries are common in school children, and education programs may help to prevent these conditions. The aim of current study was to examine the effects of an educational program based on a Health Belief Model (HBM) to improve oral health behaviors of elementary school children.

Methods
A total of 112 children ages 6–12 years old accompanied by one of their parents were randomly assigned to intervention/test and control groups. In the intervention group, five consecutive weekly educational sessions based on the HBM were provided, while the control group received only routine education delivered by the dental clinic. The Decayed, Missing, and Filled Teeth (DMFT) score, papillary bleeding index, and responses to the HBM questionnaire were assessed in the intervention and control groups at baseline and three-month follow-up after the intervention was completed. Within-group and between-group differences were examined using the Student’s t-test and analysis of covariance.

Results
All HBM domains were improved at follow-up in the intervention group compared to the control group (p < 0.001). The largest change was in perceived susceptibility, whereas the smallest changes were in perceived severity and perceived benefits. The papillary bleeding index demonstrated a significant change from baseline to follow-up in the intervention group (reduction of 0.7, 95% CI = − 0.9 to − 0.5). All components of the DMFT score except missing teeth also improved in the intervention group compared to controls. However, no significant difference was found in total DMFT score between intervention and control groups.

Conclusion
An education program based on HBM may be more effective than current methods used to educate children and their parents on optimal oral health behaviors. Administration of interventions of this type along with other school-based programs to prevent dental caries may be helpful in grade-school children.
Domestic violence against married women during the COVID-19 pandemic in Egypt
Authors: Abu-Elenin Mira M. , Elshora Ahmed A. , Sadaka Mohamed Saad , Abdeldaim Doaa E. 
Published: March 2022

Abstract
Background
In face of the COVID-19 pandemic, many countries including Egypt implemented stay indoor rules. These regulations slowed the propagation of the coronavirus, meanwhile they contributed to increase mental health issues, particularly the risk of experiencing intimate partner violence (IPV). That might lead to adverse health and social outcomes on the abused women and the children. This study aimed to examine the effect of the COVID-19 pandemic on the incidence of intimate partner violence against married women in Egypt.

Methods
A cross-sectional study enrolled 2068 married women through an electronic survey link. An anonymous self-administered questionnaire was used. It included demographic data and assessed the frequency of exposure to various forms of spousal violence before and after the COVID-19 pandemic.

Results
The mean age of respondents was 33.8 ± 6.3 years. The commonest types of violent behaviors that have been increased significantly after the COVID-19 pandemic were: twisting arms/pulling the hair (pre 32.8%, post 75%), leaving the house without informing or giving the wife money (pre 12.2%, post 30.3%), restricting interaction with her family members (pre 26.1, post 40.4%), treating her as a servant (pre 28.7%, post 36.7%) and insulting her in front of others (pre 22.9%, post 30.8%).The associated determinants for higher violence rate were; low women education, young age at marriage, low educational and job rank of husband, husband’s tobacco use and reduced family income (p < 0.05).

Conclusions
The overall prevalence of economic and some types of physical and emotionally abusive behaviors have been increased after the emergence of COVID-19 pandemic. Special intervention should be designed to address this issue in collaboration with public health organizations.
Analysis of the genotype–phenotype correlation of MYO15A variants in Chinese non-syndromic hearing loss patients
Authors: Fu Ying , Huang Shasha , Gao Xue , Han Mingyu , Wang Guojian , Kang Dongyang , Yuan Yongyi , Dai Pu 
Published: March 2022

Abstract
Background
Mutations in the MYO15A gene are a widely recognized cause of autosomal recessive non-syndromic sensorineural hearing loss (NSHL) globally. Here, we examined the role and the genotype–phenotype correlation of MYO15A variants in a cohort of Chinese NSHL cases.

Methods
Eighty-one cases with evidenced MYO15A variants from the 2263 Chinese NSHL cases, who underwent next-generation sequencing (NGS), were enrolled in the study. We investigated the association of MYO15A variants with the severity, progression and age of onset of hearing loss, as well as compared it to the previous reports in different nationalities. The cases were divided into groups according to the number of truncating variants: 2 truncating, 1 truncating and 1 non-truncating, 2 non-truncating variants, and compared the severity of HL among the groups.

Results
MYO15A accounted for 3.58% (81/2263) of all NSHL cases. We analyzed 81 MYO15A-related NSHL cases, 73 of whom were with congenital bilateral, symmetric or severe-to-profound hearing loss (HL), however, 2 of them had a postlingual, asymmetric, mild or moderate HL. There were 102 variants identified in all MYO15A structural domains, 76.47% (78/102) of whom were novel. The most common types of detected variants were missense (44/102, 43.14%), followed by frameshift (27/102, 26.47%), nonsense (14/102, 13.72%), splice site (10/102, 9.80%), in frame (4/102, 3.92%), non-coding (2/102, 1.96%) and synonymous (1/102, 0.98%). The most recurrent variant c.10245_10247delCTC was detected in 12 cases. We observed that the MYO15A variants, located in its N-terminal, motor and FERM domains, led to partial deafness with better residual hearing at low frequencies. There were 34 cases with biallelic truncating variants, 37 cases with monoallelic truncating variants, and 13 cases with biallelic non-truncating variants. The biallelic non-truncating variants group had the least number of cases (12/81), and most of them (10/12) were with profound NSHL.

Conclusions
MYO15A is a major gene responsible for NSHL in China. Cases with MYO15A variants mostly showed early-onset, symmetric, severe-to-profound hearing loss. This study is by far the largest focused on the evaluation of the genotype–phenotype correlations among the variants in the MYO15A gene and its implication in the outcome of NSHL. The biallelic non-truncating MYO15A variants commonly caused profound HL, and the cases with one or two truncating MYO15A variants tended to increase the risk of HL. Nevertheless, further investigations are needed to clarify the causes for the variable severities and progression rates of hearing loss and the detected MYO15A variants in these cases.
Lipidomic analysis identifies age-disease-related changes and potential new biomarkers in brain-derived extracellular vesicles from metachromatic leukodystrophy mice
Authors: Pergande Melissa R. , Kang Christina , George Diann , Sutter Pearl A. , Crocker Stephen J. , Cologna Stephanie M. , Givogri Maria I. 
Published: March 2022

Abstract
Background
Recent findings show that extracellular vesicle constituents can exert short- and long-range biological effects on neighboring cells in the brain, opening an exciting avenue for investigation in the field of neurodegenerative diseases. Although it is well documented that extracellular vesicles contain many lipids and are enriched in sphingomyelin, cholesterol, phosphatidylserines and phosphatidylinositols, no reports have addressed the lipidomic profile of brain derived EVs in the context of Metachromatic Leukodystrophy, a lysosomal storage disease with established metabolic alterations in sulfatides.

Methods
In this study, we isolated and characterized the lipid content of brain-derived EVs using the arylsulfatase A knockout mouse as a model of the human condition.

Results
Our results suggest that biogenesis of brain-derived EVs is a tightly regulated process in terms of size and protein concentration during postnatal life. Our lipidomic analysis demonstrated that sulfatides and their precursors (ceramides) as well as other lipids including fatty acids are altered in an age-dependent manner in EVs isolated from the brain of the knockout mouse.

Conclusions
In addition to the possible involvement of EVs in the pathology of Metachromatic Leukodystrophy, our study underlines that measuring lipid signatures in EVs may be useful as biomarkers of disease, with potential application to other genetic lipidoses.
Establishment of a finite element model and stress analysis of intra-articular impacted fragments in posterior malleolar fractures
Authors: Xie Wenyong , Lu Hao , Zhan Sizheng , Liu Yijun , Quan Yuan , Xu Hailin , Fu Zhongguo , Zhang Dianying 
Published: March 2022

Abstract
Background
Intra-articular impacted fragments (IAIFs) are considered articular surface fragments resulting from impact and compressive forces. The malreduction of IAIFs in posterior malleolar fractures has been associated with talar subluxation and long-term post-traumatic arthritis. In this study, we establish IAIF defect finite element models of different sizes in posterior malleolar fractures and explored how IAIF defects predict the onset of post-traumatic arthritis.

Methods
A reliable three-dimensional finite element model of the normal ankle was established. Finite element models with different sizes of IAIF defects were created to calculate ankle joint contact stress. The finite element data were recorded and analyzed.

Results
There was a linear relationship between the size of the IAIF defect and MCS with IAIF defects in the posterolateral region. The result of Pearson linear correlation analysis was r = 0.963, P = 0.009. The regression equation was MCS = 0.087*AI + 2.951 (AI, area of IAIF) by simple linear regression analysis. When the IAIF defect was in the posteromedial region, there was also a linear relationship between the size of the IAIF defect and MCS. The result of Pearson linear correlation analysis was r = 908, P = 0.033. The regression equation was MCS = 0.065*AI + 1.841. The MCS was increased mainly in the border of the IAIF defect.

Conclusions
A small IAIF defect in the posterior malleolus will result in a high MCS, and the MCS in the posterolateral region is larger than the MCS in the posteromedial region when the size of the IAIF defect is the same. We obtain the regression equation of MCS and area of IAIF defect. This indicates that patients are more prone to post-trauma arthritis when the size of IAIF defects is more than 17.8 mm2 in the posterolateral region and more than 40.9 mm2 in the posteromedial region.
Trial registration Retrospectively registered.
Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer’s disease
Authors: Visser Pieter Jelle , Reus Lianne M. , Gobom Johan , Jansen Iris , Dicks Ellen , van der Lee Sven J. , Tsolaki Magda , Verhey Frans R. J. , Popp Julius , Martinez-Lage Pablo , Vandenberghe Rik , Lleó Alberto , Molinuevo José Luís , Engelborghs Sebastiaan , Freund-Levi Yvonne , Froelich Lutz , Sleegers Kristel , Dobricic Valerija , Lovestone Simon , Streffer Johannes , Vos Stephanie J. B. , Bos Isabelle ,   ADNI, Smit August B. , Blennow Kaj , Scheltens Philip , Teunissen Charlotte E. , Bertram Lars , Zetterberg Henrik , Tijms Betty M. , Smit August B. , Blennow Kaj , Scheltens Philip , Teunissen Charlotte E. , Bertram Lars , Zetterberg Henrik , Tijms Betty M. 
Published: March 2022

Abstract
Background
Increased total tau (t-tau) in cerebrospinal fluid (CSF) is a key characteristic of Alzheimer’s disease (AD) and is considered to result from neurodegeneration. T-tau levels, however, can be increased in very early disease stages, when neurodegeneration is limited, and can be normal in advanced disease stages. This suggests that t-tau levels may be driven by other mechanisms as well. Because tau pathophysiology is emerging as treatment target for AD, we aimed to clarify molecular processes associated with CSF t-tau levels.

Methods
We performed a proteomic, genomic, and imaging study in 1380 individuals with AD, in the preclinical, prodromal, and mild dementia stage, and 380 controls from the Alzheimer’s Disease Neuroimaging Initiative and EMIF-AD Multimodality Biomarker Discovery study.

Results
We found that, relative to controls, AD individuals with increased t-tau had increased CSF concentrations of over 400 proteins enriched for neuronal plasticity processes. In contrast, AD individuals with normal t-tau had decreased levels of these plasticity proteins and showed increased concentrations of proteins indicative of blood–brain barrier and blood-CSF barrier dysfunction, relative to controls. The distinct proteomic profiles were already present in the preclinical AD stage and persisted in prodromal and dementia stages implying that they reflect disease traits rather than disease states. Dysregulated plasticity proteins were associated with SUZ12 and REST signaling, suggesting aberrant gene repression. GWAS analyses contrasting AD individuals with and without increased t-tau highlighted several genes involved in the regulation of gene expression. Targeted analyses of SNP rs9877502 in GMNC, associated with t-tau levels previously, correlated in individuals with AD with CSF concentrations of 591 plasticity associated proteins. The number of APOE-e4 alleles, however, was not associated with the concentration of plasticity related proteins.

Conclusions
CSF t-tau levels in AD are associated with altered levels of proteins involved in neuronal plasticity and blood–brain and blood-CSF barrier dysfunction. Future trials may need to stratify on CSF t-tau status, as AD individuals with increased t-tau and normal t-tau are likely to respond differently to treatment, given their opposite CSF proteomic profiles.
Psychogenic fever and postural tachycardia syndrome among school-aged children and adolescents with fever of unknown origin
Authors: Ishizaki Yuko , Yanagimoto Yoshitoki , Fujii Yuri , Yamamoto Mana , Kaneko Kazunari 
Published: March 2022

Abstract
Background
Although fever is a common symptom in pediatric practice, its origin is often unknown in pediatric patients. Psychogenic fever is a stress-related, psychosomatic disease observed especially in young women. This study aimed to estimate the prevalence of psychogenic fever in pediatric patients with fever of unknown origin by surveying the medical records of school-aged children and adolescents.

Methods
The study subjects included 47 patients aged 6–15 years who visited the Department of Pediatrics in Kansai Medical University Medical Center between January 2006 and December 2020 with fever of unknown origin. Data on age, sex, final estimated diagnosis, and comorbid psychosocial issues were collected from the medical records.

Results
The study was composed of 47 patients, including 22 male and 25 female patients (male/female ratio, 1:1.36). The mean age was 10.1 (standard deviation, 2.4) years for boys and 11.6 (standard deviation, 2.7) years for girls (p = .047). The final estimated diagnoses were psychogenic fever, physical disorder, infection of unknown origin, and miscellaneous in 18, 12, 12, and 5 patients, respectively. The most common comorbidity in these pediatric patients with psychogenic fever was postural tachycardia syndrome.

Conclusion
Psychogenic fever was a common cause of fever of unknown origin in pediatric patients, and postural tachycardia was prevalent among children with psychogenic fever. Enhanced sympathetic response to stress might play an important role in both psychogenic fever and postural tachycardia.
Immune cell atlas of cholangiocarcinomas reveals distinct tumor microenvironments and associated prognoses
Authors: Xia Tao , Li Keyu , Niu Nan , Shao Yingkuan , Ding Ding , Thomas Dwayne L. , Jing Hao , Fujiwara Kenji , Hu Haijie , Osipov Arsen , Yuan Chunhui , Wolfgang Christopher L. , Thompson Elizabeth D. , Anders Robert A. , He Jin , Mou Yiping , Murphy Adrian G. , Zheng Lei 
Published: March 2022

Abstract
Background
Immunotherapy has demonstrated a limited clinical efficacy in approximately 5% of cholangiocarcinoma. The main challenges for an effective immunotherapy response in cholangiocarcinoma arise from the tumor microenvironment, which is poorly understood.

Methods
For a comprehensive analysis of the tumor microenvironment in cholangiocarcinoma, we performed multiplex immunohistochemistry with two 15-marker immune panels and Nanostring assays for a comprehensive analysis of 104 surgically resected cholangiocarcinomas including intrahepatic, hilar, and distal cholangiocarcinoma. We also validated some key findings with a batch integration analysis of published single cell RNA sequencing data.

Results
This study found that natural killer cells occupy the largest immune cell compartment in cholangiocarcinoma. Granzyme-B+CD8+ effector T cells are significantly associated with better overall survival in both intrahepatic and distal cholangiocarcinoma. Above 85% of intrahepatic cholangiocarcinomas with higher density of PD-1−EOMES−CD8+ effector T cells are associated with long-term survival. However, only the density of PD-1−EOMES−CD8+ T cells in the tumor areas, but not in the peripheries of the tumors, is prognostic. In all three cholangiocarcinoma subtypes, T regulator cells are significantly associated with a poor prognosis; however, M1 and M2 tumor-associated macrophages or PD-L1+ tumor-associated macrophage demonstrate different prognostic values. Combining PD-L1+ M1 or M2, PD-L1− M1 or M2 tumor-associated macrophages, and T regulator cells to subgroup intrahepatic and distal cholangiocarcinoma, the prognosis is significantly better distinguished. Moreover, PD-L1− M2 tumor-associated macrophages is associated with a good prognosis in intrahepatic and distal cholangiocarcinoma, suggesting this subtype of M2 tumor-associated macrophages may be antitumoral. Interestingly, lower densities of various types of immunosuppressive cells are associated with decreased infiltration of effector T cells in distal and hilar cholangiocarcinoma, but not in intrahepatic cholangiocarcinoma. In intrahepatic cholangiocarcinoma, PD-L1+ tumor-associated macrophages exert their immunosuppressive function likely through promoting T cell exhaustion.

Conclusions
This study suggests that the densities of Granzyme-B+CD8+ effector T cells and non-exhausted PD-1−EOMES−CD8+ T cells and the PD-L1 status in the tumor-associated macrophages are prognostic makers in cholangiocarcinomas. The study also supports targeting PD-L1+ tumor-associated macrophages as the immunotherapy for cholangiocarcinoma.
Reduction in pediatric growth hormone deficiency and increase in central precocious puberty diagnoses during COVID 19 pandemics
Authors: Peinkhofer Martina , Bossini Benedetta , Penco Arturo , Giangreco Manuela , Pellegrin Maria Chiara , Vidonis Viviana , Vittori Giada , Grassi Nicoletta , Faleschini Elena , Barbi Egidio , Tornese Gianluca 
Published: March 2022

Abstract
Background
While several studies have been published so far on the effect of COVID-19 pandemic on health care for non-COVID-19 diseases, to date no study evaluated the impact of the COVID-19 pandemic on the entire field of pediatric endocrinology. This study aimed to evaluate differences in pediatric endocrine stimulation tests after the advent of COVID-19 pandemics.

Methods
Retrospective study with data collection for pediatric endocrine stimulation tests performed in 2019 and 2020 in a tertiary center.

Results
Overall, 251 tests were performed on 190 patients in 2020, compared to 278 tests on 206 patients in 2019 (− 10% tests; − 8% children evaluated). A significant reduction was found in tests to diagnose growth hormone deficiency (GHD) (− 35%), while LHRH tests increased (+ 22%). A reduction of 30% in GHD diagnosis was observed. Central precocious puberty (CPP) diagnosis increased by 38% compared to 2019, mainly in females.

Conclusion
This study found a significant reduction of tests investigating GHD during COVID-19 pandemics. It also showed a clinically meaningful increase in cases of CPP in girls. These results suggest the need for families and pediatricians to monitor children’s growth during isolation and enlighten new perspectives towards conditions associated with lockdown restrictions as increased screen time, social isolation, and children’s anxiety as possible triggers of CPP.