bluuebunny/crossref_metadata_2025_split huggingface dataset:
Going deeper with health equity measurement: how much more can surveys reveal about inequalities in health intervention coverage and mortality in Zambia?
Authors: Blanchard Andrea K. , Jacobs Choolwe , Musukuma Mwiche , Chooye Ovost , Sikapande Brivine , Michelo Charles , Boerma Ties , Wehrmeister Fernando C. 
Published: June 2023

Abstract
Background
Although Zambia has achieved notable improvements in reproductive, maternal, newborn and child health (RMNCH), continued efforts to address gaps are essential to reach the Sustainable Development Goals by 2030. Research to better uncover who is being most left behind with poor health outcomes is crucial. This study aimed to understand how much more demographic health surveys can reveal about Zambia’s progress in reducing inequalities in under-five mortality rates and RMNCH intervention coverage.

Methods
Using four nationally-representative Zambia Demographic Health Surveys (2001/2, 2007, 2013/14, 2018), we estimated under-five mortality rates (U5MR) and RMNCH composite coverage indices (CCI) comparing wealth quintiles, urban‐rural residence and provinces. We further used multi-tier measures including wealth deciles and double disaggregation between wealth and region (urban residence, then provinces). These were summarised using slope indices of inequality, weighted mean differences from overall mean, Theil and concentration indices.

Results
Inequalities in RMNCH coverage and under-five mortality narrowed between wealth groups, residence and provinces over time, but in different ways. Comparing measures of inequalities over time, disaggregation with multiple socio-economic and geographic stratifiers was often valuable and provided additional insights compared to conventional measures. Wealth quintiles were sufficient in revealing mortality inequalities compared to deciles, but comparing CCI by deciles provided more nuance by showing that the poorest 10% were left behind by 2018. Examining wealth in only urban areas helped reveal closing gaps in under-five mortality and CCI between the poorest and richest quintiles. Though challenged by lower precision, wealth gaps appeared to close in every province for both mortality and CCI. Still, inequalities remained higher in provinces with worse outcomes.

Conclusions
Multi-tier equity measures provided similarly plausible and precise estimates as conventional measures for most comparisons, except mortality among some wealth deciles, and wealth tertiles by province. This suggests that related research could readily use these multi-tier measures to gain deeper insights on inequality patterns for both health coverage and impact indicators, given sufficient samples. Future household survey analyses using fit-for-purpose equity measures are needed to uncover intersecting inequalities and target efforts towards effective coverage that will leave no woman or child behind in Zambia and beyond.
Pregnancy and neonatal outcomes of monozygotic twins resulting from assisted reproductive technology: a 10-year retrospective study
Authors: Li Yubin , Chang Qiyuan , Mai Qingyun 
Published: June 2023

Abstract
Background
Monozygotic twins (MZTs) are associated with high risks of maternal and fetal complications. Even with the widely used elective single embryo transfer (SET), the risk of MZTs following assisted reproductive technology (ART) treatments remains. However, most studies of MZTs focused on the relevant etiology, with few studies describing pregnancy and neonatal outcomes.

Methods
This retrospective cohort study included 19,081 SET cycles resulting from in-vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), preimplantation genetic testing (PGT) and testicular sperm aspiration (TESA) performed between January 2010 and July 2020 in a single university-based center. A total of 187 MZTs were included in this investigation. The main outcome measures were the incidence, pregnancy and neonatal outcomes of MZTs. Multivariate logistic regression analysis was performed to figure out the risk factors for pregnancy loss.

Results
The overall rate of MZTs from ART treatment in SET cycles was 0.98%. No significant difference was found in the incidence of MZTs among the four groups (p = 0.259). The live birth rate of MZTs in the ICSI group (88.5%) was significantly more favorable than in the IVF, PGT and TESA groups (60.5%, 77.2% and 80%, respectively). IVF resulted in a significantly increased risk of pregnancy loss (39.4%) and early miscarriage (29.5%) in MZT pregnancies compared to ICSI (11.4%, 8.5%), PGT (22.7%, 16.6%) and TESA (20%, 13.3%). The total rate of twin-to-twin transfusion syndrome (TTTS) in MZTs was 2.7% (5/187); however, the TESA group had the highest rate at 20% and was significantly higher than the PGT group (p = 0.005). The four ART groups had no significant effect on the occurrence of congenital abnormalities or other neonatal outcomes in newborns from MZT pregnancies. Multivariate logistic regression analysis revealed that infertility duration, cause of infertility, the total dose of Gn used, history of miscarriages, and the number of miscarriages were not related to the risk of pregnancy loss (p > 0.05).

Conclusions
The rate of MZTs was similar among the four ART groups. The pregnancy loss and the early miscarriage rate of MZTs was increased in IVF patients. Neither the cause of infertility nor the history of miscarriage was correlated with the risk of pregnancy loss. MZTs in the TESA group had a higher risk of TTTS, placental effects influenced by sperm and paternally expressed genes may play a role. However, due to the small total number, studies with larger sample sizes are still needed to validate these result. Pregnancy and neonatal outcomes of MZTs after PGT treatment seem to be reassuring but the duration of the study was short, and long-term follow-up of the children is needed.
LOX-1 mediates inflammatory activation of microglial cells through the p38-MAPK/NF-κB pathways under hypoxic-ischemic conditions
Authors: Aoki Yoshinori , Dai Hongmei , Furuta Fumika , Akamatsu Tomohisa , Oshima Takuya , Takahashi Naoto , Goto Yu-ichi , Oka Akira , Itoh Masayuki 
Published: June 2023

Abstract
Background
Microglial cells play an important role in the immune system in the brain. Activated microglial cells are not only injurious but also neuroprotective. We confirmed marked lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression in microglial cells in pathological lesions in the neonatal hypoxic-ischemic encephalopathy (nHIE) model brain. LOX-1 is known to be an activator of cytokines and chemokines through intracellular pathways. Here, we investigated a novel role of LOX-1 and the molecular mechanism of LOX-1 gene transcription microglial cells under hypoxic and ischemic conditions.

Methods
We isolated primary rat microglial cells from 3-day-old rat brains and confirmed that the isolated cells showed more than 98% Iba-1 positivity with immunocytochemistry. We treated primary rat microglial cells with oxygen glucose deprivation (OGD) as an in vitro model of nHIE. Then, we evaluated the expression levels of LOX-1, cytokines and chemokines in cells treated with or without siRNA and inhibitors compared with those of cells that did not receive OGD-treatment. To confirm transcription factor binding to the OLR-1 gene promoter under the OGD conditions, we performed a luciferase reporter assay and chromatin immunoprecipitation assay. In addition, we analyzed reactive oxygen species and cell viability.

Results
We found that defects in oxygen and nutrition induced LOX-1 expression and led to the production of inflammatory mediators, such as the cytokines IL-1β, IL-6 and TNF-α; the chemokines CCL2, CCL5 and CCL3; and reactive oxygen/nitrogen species. Then, the LOX-1 signal transduction pathway was blocked by inhibitors, LOX-1 siRNA, the p38-MAPK inhibitor SB203580 and the NF-κB inhibitor BAY11-7082 suppressed the production of inflammatory mediators. We found that NF-κB and HIF-1α bind to the promoter region of the OLR-1 gene. Based on the results of the luciferase reporter assay, NF-κB has strong transcriptional activity. Moreover, we demonstrated that LOX-1 in microglial cells was autonomously overexpressed by positive feedback of the intracellular LOX-1 pathway.

Conclusion
The hypoxic/ischemic conditions of microglial cells induced LOX-1 expression and activated the immune system. LOX-1 and its related molecules or chemicals may be major therapeutic candidates.
Increasing access to psychological services within pediatric rheumatology care
Authors: Goldstein-Leever Alana , Bearer Christine , Sivaraman Vidya , Akoghlanian Shoghik , Gallup James , Ardoin Stacy 
Published: June 2023

Abstract
Background
Given the impact of psychological factors on rheumatic disease, pediatric psychologists serve a vital role in promoting quality of life and managing common problems among youth with rheumatic disease. The aim of this project was to increase access to psychological services among youth with rheumatic disease at a children’s hospital.

Methods
A quality improvement (QI) team identified key drivers and interventions aimed to increase access to psychological services for youth with rheumatic disease. Data was collected for a 6-month baseline period and 4-year intervention period. We applied the Plan-Do-Study Act method of QI and the American Society for Quality criteria to adjust the center line and control limits.

Results
There were two statistically significant center line shifts in the number of patients seen by psychology and one statistically significant shift in referrals to psychology over time with applied stepwise interventions. Patients seen by a psychologist increased by 3,173% from a baseline average of 1.8 to 59.9 patients seen per month (p < 0.03). Psychology referrals increased by 48% from a baseline average of 9.85 to 14.58 referrals per month over the intervention period (p < .01).

Conclusions
Youth with rheumatic disease received increased access to mental health treatment when psychological services were imbedded within rheumatology care. Psychology referrals also increased significantly, suggesting that psychology integration within a medical clinic can increase identification of needs. Results suggest that psychology integration into rheumatology care may increase access to mental health treatment and identification of psychological needs in this at-risk population.
Impact of comorbidities on the serological response to COVID-19 vaccination in a Taiwanese cohort
Authors: Huang Chung-Feng , Jang Tyng-Yuan , Wu Ping-Hsun , Kuo Mei-Chuan , Yeh Ming-Lun , Wang Chih-Wen , Liang Po-Cheng , Wei Yu-Ju , Hsu Po-Yao , Huang Ching-I , Hsieh Ming-Yen , Lin Yi-Hung , Hsiao Hui-Hua , Hsu Chin-Mu , Huang Chien-Tzu , Lee Chun-Yuan , Chen Yen-Hsu , Chen Tun-Chieh , Lin Kun-Der , Wang Shuo-Hung , Wang Sheng-Fan , Huang Jee-Fu , Dai Chia-Yen , Chuang Wan-Long , Yu Ming-Lung 
Published: June 2023

Abstract
Background/Aims
Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the best policies to control COVID-19 pandemic. The serological response to COVID-19 vaccination in Taiwanese patients with different comorbidities is elusive.

Methods
Uninfected subjects who received 3 doses of mRNA vaccines (BNT162b2 [Pfizer-BioNTech, BNT] and mRNA-1273 [Moderna]), viral vector-based vaccines (ChAdOx1-S (AZD1222, AZ) or protein subunit vaccines (Medigen COVID-19 vaccine) were prospectively enrolled. The SARS-CoV-2-IgG spike antibody level was determined within three months after the 3rd dose of vaccination. The Charlson Comorbidity Index (CCI) was applied to determine the association between vaccine titers and underlying comorbidities.

Results
A total of 824 subjects were enrolled in the current study. The proportions of CCI scores of 0–1, 2–3 and > 4 were 52.8% (n = 435), 31.3% (n = 258) and 15.9% (n = 131), respectively. The most commonly used vaccination combination was AZ–AZ–Moderna (39.2%), followed by Moderna–Moderna–Moderna (27.8%). The mean vaccination titer was 3.11 log BAU/mL after a median of 48 days after the 3rd dose. Factors associated with potentially effective neutralization capacity (IgG level ≥ 4160 AU/mL) included age ≥ 60 years (odds ratio [OR]/95% confidence interval [CI]: 0.50/0.34–0.72, P < 0.001), female sex (OR/CI: 1.85/1.30–2.63, P = 0.001), Moderna–Moderna-based vaccination (compared to AZ–AZ-based vaccination, OR/CI: 6.49/3.90–10.83, P < 0.001), BNT–BNT-based vaccination (compared to AZ–AZ-based vaccination, OR/CI: 7.91/1.82–34.3, P = 0.006) and a CCI score ≥ 4 (OR/CI: 0.53/0.34–0.82, P = 0.004). There was a decreasing trend in antibody titers with increasing CCI scores (trend P < 0.001). Linear regression analysis revealed that higher CCI scores (β: − 0.083; 95% CI: − 0.094–0.011, P = 0.014) independently correlated with low IgG spike antibody levels.

Conclusions
Subjects with more comorbidities had a poor serological response to 3 doses of COVID-19 vaccination.
Functional mechanism of miR-92b-3p in osteogenic differentiation of fibroblasts in patients with ankylosing spondylitis via the TOB1/BMP/Smad pathway
Authors: Lu Liansong , Sun Shaohua , Li Haojie , Xie Yingzhi 
Published: June 2023

Abstract
Background
Ankylosing spondylitis (AS) is a chronic inflammatory arthritis. Upregulation of microRNA (miR)-92b-3p is associated with enhanced osteoblastic differentiation. The current study sought to investigate the functional mechanism of miR-92b-3p in osteogenic differentiation of AS fibroblasts.

Methods
First, fibroblasts were isolated from AS and non-AS patients and cultured. Next, cell morphology was observed, cell proliferation was assessed and the vimentin expression pattern was determined. Alkaline phosphatase (ALP) activity and levels of osteogenic markers RUNX2, OPN, OSX, and COL I were additionally measured, followed by determination of miR-92b-3p and TOB1 levels. The binding site of miR-92b-3p and TOB1 was predicted, and their target relationship was validated. Lastly, miR-92b-3p inhibitor, si-TOB1, and the BMP/Smad signaling pathway inhibitor LDN193189 were delivered into AS fibroblasts to evaluate the osteogenic differentiation of AS fibroblasts and the activation of the BMP/Smad pathway.

Results
miR-92b-3p was highly expressed in AS fibroblasts. AS fibroblasts showed enhanced osteogenic differentiation and proliferation, while inhibition of miR-92b-3p suppressed osteogenic differentiation and proliferation of AS fibroblasts. miR-92b-3p targeted TOB1, and TOB1 was poorly expressed in AS fibroblasts. The concurrent downregulation of TOB1 and inhibition of miR-92b-3p elevated the levels of RUNX2, OPN, OSX, and COL I and ALP activity and further enhanced the proliferation of AS fibroblasts. The BMP/Smad pathway was activated in AS fibroblasts. Silencing miR-92b-3p could inhibit the activation of the BMP/Smad pathway by upregulating TOB1. Inhibition of the BMP/Smad pathway reduced the number of calcified nodules and hindered the osteogenic differentiation and proliferation of AS fibroblasts.

Conclusion
Our findings highlighted that silencing miR-92b-3p inhibited the osteogenic differentiation and proliferation of AS fibroblasts by upregulation of TOB1 and inhibition of the BMP/Smad pathway.

Graphical abstract
The challenges of classical galactosemia: HRQoL in pediatric and adult patients
Authors: Hermans Merel E. , van Oers Hedy A. , Geurtsen Gert J. , Haverman Lotte , Hollak Carla E. M. , Rubio-Gozalbo M. Estela , Bosch Annet M. 
Published: June 2023

Abstract
Background
Classical galactosemia (CG), an inborn error of galactose metabolism, results in long-term complications including cognitive impairment and movement disorders, despite early diagnosis and dietary treatment. Two decades ago, lower motor-, cognitive- and social health related quality of life (HRQoL) was demonstrated in pediatric and adult patients. Since then, the diet has been relaxed, newborn screening was implemented and new international guidelines resulted in major changes in follow-up. The aim of this study was to assess HRQoL of CG by means of online self- and/or proxy-HRQoL-questionnaires focusing on the main areas of concern of CG (i.e. anxiety, depression, cognition, fatigue, social- and upper extremity function) within the patient-reported outcomes measurement information system (PROMIS®) and generic HRQoL-questionnaires (TAPQOL, TACQOL, TAAQOL).

Results
Data of 61 Dutch patients (aged 1–52 years) were collected and compared to available Dutch or US reference populations. On the PROMIS-questionnaires, children reported more fatigue (P = 0.044), lower function in upper extremities (P = 0.021), more cognitive difficulties (P = 0.055, d = 0.56) and higher anxiety (P = 0.063, d = 0.52) than reference children although the latter findings remained non-significant. Parents of CG patients reported lower quality of peer relationships of their children (P < 0.001). Both children and parents reported lower cognitive functioning (P = 0.005, P = 0.010) on the TACQOL. Adults reported on PROMIS domains lower cognitive functioning (P = 0.030), higher anxiety (P = 0.004) and more fatigue (P = 0.026). Cognitive difficulties were reported on the TAAQOL by adults (P < 0.001), as well as physical-, sleeping and social difficulties.

Conclusions
CG remains to impact the HRQoL of pediatric and adult patients negatively on several domains including cognition, anxiety, motor function and fatigue. A lower social health was mainly reported by parents, and not by patients themselves. The Covid-19 pandemic might have amplified the results on anxiety although higher levels of anxiety fit pre-pandemic findings. The reported fatigue is a new finding in CG. Because the effect of lockdown fatigue could not be eliminated and fatigue is a frequent finding in patients with chronic disorders, future studies are warranted. Clinicians and researchers should be attentive to both pediatric and adult patients, and the age-dependent difficulties they might encounter.
The clinical effects of modified tinnitus relieving sound (MTRS) for chronic tinnitus: protocol for a randomized controlled trial
Authors: Tang Dongmei , Wang Jinghan , Yu Xiaopei , Yu Huiqian 
Published: June 2023

Abstract
Introduction
Chronic subjective tinnitus has become an increasingly serious hazard that affects the health-related quality of life for millions of people. Due to the lack of curative treatment strategies, this study aims to introduce a novel acoustic therapy named the modified tinnitus relieving sound (MTRS) for tinnitus and to evaluate the efficacy of MTRS in comparison with unmodified music (UM) which served as a control.

Methods and analysis
A randomized, double-blinded, controlled, clinical trial will be carried out. Sixty-eight patients with subjective tinnitus will be recruited and randomly allocated into two groups in 1:1 ratio. The primary outcome is Tinnitus Handicapped Inventory (THI); the secondary outcomes are the Hospital Anxiety and Distress Scale (HADS; HADS subscales for Anxiety (HADS-A) and Depression (HADS-D)), Athens Insomnia Scale (AIS), the visual analog scale (VAS) for tinnitus, and tinnitus loudness matched by sensation level (SL). Assessment will be performed at baseline and at 1, 3, 9, and 12 months post-randomization. The sound stimulus will be persistent until 9 months after randomization, and be interdictory in the last three months. Data collected during the intervention process will be analyzed and compared to baseline.

Ethics and dissemination
This trial received ethical approval from the Institutional Review Board (IRB) of Eye & ENT Hospital of Fudan University (No. 2017048). The study results will be disseminated via academic journals and conferences.

Funding
This study is supported by the Shanghai Shenkang Development Program (SHDC12019119), the Excellent Doctors-Excellent Clinical Researchers Program (SYB202008), the Shanghai Rising-Star Program (23QC1401200), the Shanghai Rising Stars of Medical Talent Youth Development Program (2021–99), the National Natural Science Foundation of China (81800912), and the National Natural Science Foundation of Shanghai (21ZR1411800).

Trial registration
ClinicalTrials.gov NCT04026932. Registered on 18 July 2019.
Molecular pathogen screening of louse flies (Diptera: Hippoboscidae) from domestic and wild ruminants in Austria
Authors: Peña-Espinoza Miguel , Em Daniel , Shahi-Barogh Bita , Berer Dominik , Duscher Georg G. , van der Vloedt Lara , Glawischnig Walter , Rehbein Steffen , Harl Josef , Unterköfler Maria S. , Fuehrer Hans-Peter 
Published: June 2023

AbstractBackgroundHippoboscid flies (Diptera: Hippoboscidae), also known as louse flies or keds, are obligate blood-sucking ectoparasites of animals, and accidentally of humans. The potential role of hippoboscids as vectors of human and veterinary pathogens is being increasingly investigated, but the presence and distribution of infectious agents in louse flies is still unknown in parts of Europe. Here, we report the use of molecular genetics to detect and characterize vector-borne pathogens in hippoboscid flies infesting domestic and wild animals in Austria.MethodsLouse flies were collected from naturally infested cattle (n = 25), sheep (n = 3), and red deer (n = 12) across Austria between 2015 and 2019. Individual insects were morphologically identified to species level and subjected to DNA extraction for molecular pathogen screening and barcoding. Genomic DNA from each louse fly was screened forBorreliaspp.,Bartonellaspp., Trypanosomatida, Anaplasmataceae, Filarioidea and Piroplasmida. Obtained sequences of Trypanosomatida andBartonellaspp. were further characterized by phylogenetic and haplotype networking analyses.ResultsA total of 282 hippoboscid flies corresponding to three species were identified:Hippobosca equina(n = 62) collected from cattle,Melophagus ovinus(n = 100) from sheep andLipoptena cervi(n = 120) from red deer (Cervus elaphus). Molecular screening revealed pathogen DNA in 54.3% of hippoboscids, including infections with single (63.39%), two (30.71%) and up to three (5.90%) distinct pathogens in the same individual.BartonellaDNA was detected in 36.9% of the louse flies.Lipoptena cerviwere infected with 10 distinct and previously unreportedBartonellasp. haplotypes, some closely associated with strains of zoonotic potential. DNA of trypanosomatids was identified in 34% of hippoboscids, including the first description ofTrypanosomasp. inH. equina. Anaplasmataceae DNA (Wolbachiaspp.) was detected only inM. ovinus(16%), while < 1% of the louse flies were positive forBorreliaspp. and Filarioidea. All hippoboscids were negative for Piroplasmida.ConclusionsMolecular genetic screening confirmed the presence of several pathogens in hippoboscids infesting domestic and wild ruminants in Austria, including novel pathogen haplotypes of zoonotic potential (e.g.Bartonellaspp.) and the first report ofTrypanosomasp. inH. equina, suggesting a potential role of this louse fly as vector of animal trypanosomatids. Experimental transmission studies and expanded monitoring of hippoboscid flies and hippoboscid-associated pathogens are warranted to clarify the competence of these ectoparasites as vectors of infectious agents in a One-Health context.Graphical Abstract