bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and adherence of bictegravir/emtricitabine/tenofovir alafenamide for HIV post-exposure prophylaxis among adults in Guiyang China: a prospective cohort study
Authors: Gan Lin , Xie Xiaoxin , Fu Yanhua , Yang Xiaoyan , Ma Shujing , Kong Linghong , Song Chunli , Song Yebing , Ren Tingting , Long Hai
Published: June 2024

Background

The effectiveness of post-exposure prophylaxis (PEP) depends on participants adherence, making it crucial to assess and compare regimen options to enhance human immunodeficiency virus (HIV) prophylaxis strategies. However, no prospective study in China has shown that the completion rate and adherence of single-tablet regimens in HIV PEP are higher than those of multi-tablet preparations. Therefore, this study aimed to assess the completion rate and adherence of two HIV PEP regimens.

Methods

In this single-center, prospective, open-label cohort study, we included 179 participants from May 2022 to March 2023 and analyzed the differences in the 28-day medication completion rate, adherence, safety, tolerance, and effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir disoproxil fumarate, emtricitabine, and dolutegravir (TDF/FTC + DTG).

Results

The PEP completion rate and adherence were higher in the BIC/FTC/TAF group than in the TDF/FTC + DTG group (completion rate: 97.8% vs. 82.6%, P = 0.009; adherence: 99.6 ± 2.82% vs. 90.2 ± 25.29%, P = 0.003). The incidence of adverse reactions in the BIC/FTC/TAF and TDF/FTC + DTG groups was 15.2% and 10.3% (P = 0.33), respectively. In the TDF/FTC + DTG group, one participant stopped PEP owing to adverse reactions (1.1%). No other participants stopped PEP due to adverse events.

Conclusions

BIC/FTC/TAF and TDF/FTC + DTG have good safety and tolerance as PEP regimens. BIC/FTC/TAF has a higher completion rate and increased adherence, thus, is recommended as a PEP regimen. These findings emphasize the importance of regimen choice in optimizing PEP outcomes.

Trial registration

The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200059994(2022-05-14), https://www.chictr.org.cn/bin/project/edit?pid=167391).
Optimal ICSI timing on immature oocytes for low prognosis patients under the POSEIDON classification
Authors: Shi Cheng , Wang Ping , Liang Rong , Fu Min , Duan Sheng Nan , Shen Huan , Yang Mei , Chen Xi
Published: June 2024

Background

The optimal timing of performing ICSI on immature oocytes for POSEIDON patients is still unknown to get better early embryonic development outcomes. The purpose of this study was to implore the most appropriate time to carry out ICSI on in vitro maturation GV and MI oocytes for POSEIDON patients.

Methods

Two hundred thirty-nine immature oocytes from 163 POSEIDON patients were prospectively performed ICSI at different timings: P-ICSI (ICSI was performed on in vitro matured oocytes 4–6 h after the first polar body extrusion, N = 81), R-ICSI (ICSI was performed on in vitro matured oocytes less than 4 h after the first polar body extrusion, N = 80), and E-ICSI (ICSI was performed on in vitro matured oocytes the next day after oocytes retrieval, N = 78). Fertilization and embryonic development outcomes were collected and statistically analyzed. Mitochondria distribution of cytoplasm of in vitro matured oocytes with different time cultures after the first polar body (PB1) extrusion was stained.

Results

Compared to the E-ICSI group, more day 3 embryos from P-ICSI became blastocysts after sequential culture though without statistical significance (OR = 3.71, 95% CI: 0.94—14.63, P = 0.061). Compared to the E-ICSI group, more embryos from both P-ICSI and R-ICSI groups were clinically used with statistical significance (OR = 5.67, 95% CI: 2.24—14.35, P = 0.000 for P-ICSI embryos; OR = 3.23, 95% CI: 1.23—8.45, P = 0.017 for R-ICSI embryos). Compared to the E-ICSI group, transferred embryos from P-ICSI and R-ICSI had a higher implantation rate though without statistical significance (35.3% for P-ICSI embryos; 9.1% or R-ICSI embryos and 0% for E-ICSI embryos, P = 0.050). Among the three group, there were most healthy babies delivered from the P-ICSI group (5, 1 and 0 for P-ICSI, R-ICSI and E-ICSI respectively). The mitochondria in the cytoplasm of in vitro matured oocytes with a less than 4 h and 4–6 h culture after PB1 extrusion presented semiperipheral and diffused distribution patterns, respectively.

Conclusions

Our results revealed P-ICSI (ICSI was performed on in vitro matured oocytes 4–6 h after the first polar body extrusion) provided the most efficient method to utilize the immaturation oocytes basing on embryos utilization and live birth outcome for low prognosis patients under the POSEIDON classification. The mitochondria distribution of the in vitro matured oocytes’ cytoplasm from P-ICSI varied that from R-ICSI.
The receipt of health information on neonatal dangers signs during the immediate postpartum period and its determinants in Ethiopia: a multilevel mixed-effects logistic regression analysis of the 2016 Ethiopian demographic health survey report
Authors: Habte Aklilu , Tamene Aiggan , Sewalem Zablon Wale
Published: June 2024

Background

Identification of neonatal danger signs and immediate access to health care are two global efforts aimed at enhancing newborn and child survival by preventing 75% of neonatal deaths. Despite various small-scale studies on women’s awareness of neonatal danger signs in Ethiopia, little is known about the level of receiving health information on those danger signs during the immediate postpartum period at the national level. Hence, this study aimed at assessing the level, and its determinants of the service uptake in Ethiopia.

Methods

The data for this study was taken from the Ethiopian Demographic and Health Survey (EDHS), which took place from January to June 2016 and covered all administrative regions of Ethiopia. A weighted sample of 7,589.8 women was analyzed using STATA version 16. To account for data clustering, a multivariable multilevel mixed-effect logistic regression analysis was employed to determine the effects of each predictor on the outcome variable. Adjusted odds ratio with its corresponding 95% confidence interval was used to declare the statistical significance of the explanatory variables.

Results

The receipt of health information on neonatal danger signs during the immediate postpartum period was 10.70% [95% CI:10.01, 11.40]. Variables namely living in Metropolitans [AOR = 2.06; 95%CI: 1.48, 2.88] and Large central [AOR = 1.83; 95%CI: 1.38, 2.42] regions, being in the highest wealth quintile [AOR = 1.87; 95% CI: 1.23, 2.84], being nulliparous [AOR = 0.27; 95% CI: 0.08, 0.87] and primiparous[AOR = 0.61;95% CI: 0.46, 0.79], getting adequate antenatal visits [AOR = 2.42; 95% CI: 1.75, 3.33], institutional delivery [AOR = 5.91; 95% CI: 4.66, 7.53], and receipt of postnatal visits [AOR = 3.52; 95% CI: 2.84, 4.38] were identified as significant determinants of receiving health information on newborn danger signs.

Conclusion

The findings revealed that unacceptably low uptake of health information on newborn danger signs during the immediate postpartum period in Ethiopia. A concerted effort is needed from all stakeholders in the health sector to enhance the uptake of maternal health services (antenatal care, skilled delivery service, and postnatal care). Healthcare providers should pay special attention to nulliparous and primiparous women during and after delivery, and the government should also focus on women of peripheral regions, who make up a large portion of the low coverage.
The significance and prognostic value of multifocal papillary thyroid carcinoma in children and adolescents
Authors: Sun Yuxiao , Liu Yihao , Li Hongqiang , Tang Yifeng , Liu Weihao , Zhang Yifei , Yin Detao
Published: June 2024

Introduction

The prognostic value of multifocality in paediatric papillary thyroid carcinoma (PTC) patients remains a subject of debate. This study aimed to explore the clinical significance and prognostic value of multifocality in children and adolescents with PTC.

Methods

This study retrospectively analysed the clinicopathological characteristics and postoperative follow-up data of 338 PTC patients aged ≤ 20 years from May 2012 to July 2022. The clinical and pathological characteristics of 205 patients with unifocal lesions and 133 patients with multifocal lesions were compared. A logistic regression model evaluated the relationship between multifocal lesions and disease recurrence/persistence in children and adolescents with PTC. Based on the median follow-up time of children with multifocal PTC, 114 patients with multifocal PTC older than 20 years were added, and the clinicopathological characteristics were compared between the 133. paediatric/adolescent patients and 114 adult patients with multifocal PTC.

Results

Among the paediatric and adolescent patients, over a median follow-up time of 49 months, 133 had multifocal disease and 205 had unifocal disease. Multifocal PTC patients exhibited stronger invasiveness in the form of extrathyroidal extension, tumour diameter, lymph node metastasis, and distant metastasis. Multifocality (OR 2.68; p = 0.017), lateral lymph node metastasis (OR 2.85; p = 0.036), and distant metastasis (OR 4.28; p = 0.010) were identified as independent predictive factors for the recurrence/persistence of disease. Comparing the paediatric/adolescent vs. adult multifocal patients, the former demonstrated greater tumour invasiveness. Lateral lymph node metastasis (OR 6.36; P = 0.012) and distant metastasis (OR 3.70; P = 0.027) were independent predictive factors for recurrence/persistence of disease in multifocal patients, while age was not (OR 0.95; P = 0.455).

Conclusion

Tumour multifocality independently predicts persistent/recurrent disease in paediatric and adolescent PTC patients.
Retrospective ACEs predict complex PTSD symptoms in a large sample of Chinese young adults longitudinally: the moderating role of self-compassion
Authors: Ren Yizhen , Yang Shuhan , Peng Yu , Liu Aiyi , Zhu Zibin
Published: June 2024

This longitudinal study in Mainland China (2021–2022) explored the impact of adverse childhood experiences (ACEs) on complex posttraumatic stress disorder (CPTSD) symptoms, with a focus on the role of self-compassion. Among 18,933 surveyed university students, 21.2% reported experiencing at least one ACE. Results revealed a clear relationship between ACEs and CPTSD symptoms. Furthermore, self-compassion, particularly the dimensions of self-judgment and isolation, moderated the association between retrospective ACEs and posttraumatic stress disorder (PTSD) and disturbance in self-organization (DSO) symptoms. These findings highlight the enduring impact of ACEs on CPTSD symptoms and emphasize the importance of early identification and targeted interventions, especially addressing self-judgment and isolation, to mitigate CPTSD risk among young Chinese adults.
Prevalence rate of primary osteoporosis in China: a meta-analysis
Authors: Lyu Fang Fei , Ramoo Vimala , Chui Ping Lei , Ng Chong Guan , Zhang Yuanyuan
Published: June 2024

Background

Primary osteoporosis (POP) is recognized as a “silent disease” and often ignored. This meta-analysis aimed to determine the prevalence of POP in the Chinese population over the past 20 years to raise awareness of the disease’s epidemiology, which is hoped to help prevent and treat the condition better.

Methods

Eight English and three Chinese language databases were searched systematically from January 2002 to December 2023. Relevant data were analysed using Stata 16.0. Meta-regression and subgroup analyses were performed to explore causes of heterogeneity. A funnel plot was further drawn in combination with Egger and Begg tests to determine publication bias.

Results

A total of 45 studies (241,813 participants) were included. The meta-analysis revealed that the overall prevalence of POP in the Chinese population was 18.2% (95% CI: 14.7–21.7%), showing a positive correlation with age. Specifically, prevalence rates were 23.4% (18.3–28.5%) in women and 11.5% (9.1–13.9%) in men. A notable increase was observed within the span of 20 years (16.9% before 2010 and 20.3% in 2011–2020). Notably, regional variations were observed, with southern China reporting a lower prevalence of 16.4% compared to 20.2% in northern China. Meta-regression suggested that sample size significantly influenced the estimation of point prevalence (P = 0.037).

Conclusions

Over the past two decades, there has been an increase in the prevalence of POP within the Chinese population. The growing prevalence of older individuals and women further highlights the urgency for tailored disease prevention and control measures.
Risk factors for maternal near-miss in an undeveloped province in south-central China, 2012–2022
Authors: Zhou Xu , Fang Junqun , Wu Yinglan , Gao Jie , Chen Xiaoying , Wang Aihua , Shu Chuqiang
Published: June 2024

Objective

To explore the risk factors for maternal near-miss (MNM) using the WHO near-miss approach.

Methods

Data were obtained from the Maternal Near-Miss Surveillance System in Hunan Province, China, 2012–2022. Multivariate logistic regression analysis (method: Forward, Wald, α = 0.05) and adjusted odds ratios (aORs) were used to identify risk factors for MNM.

Results

Our study included 780,359 women with 731,185 live births, a total of 2461 (0.32%) MNMs, 777,846 (99.68%) non-MNMs, and 52 (0.006%) maternal deaths were identified. The MNM ratio was 3.37‰ (95%CI: 3.23–3.50). Coagulation/hematological dysfunction was the most common cause of MNM (75.66%). Results of multivariate logistic regression analysis showed risk factors for MNM: maternal age > = 30 years old (aOR > 1, P < 0.05), unmarried women (aOR = 2.21, 95%CI: 1.71–2.85), number of pregnancies > = 2 (aOR > 1, P < 0.05), nulliparity (aOR = 1.51, 95%CI: 1.32–1.72) or parity > = 3 (aOR = 1.95, 95%CI: 1.50–2.55), prenatal examinations < 5 times (aOR = 1.13, 95%CI: 1.01–1.27), and number of cesarean sections was 1 (aOR = 1.83, 95%CI: 1.64–2.04) or > = 2 (aOR = 2.48, 95%CI: 1.99–3.09).

Conclusion

The MNM ratio was relatively low in Hunan Province. Advanced maternal age, unmarried status, a high number of pregnancies, nulliparity or high parity, a low number of prenatal examinations, and cesarean sections were risk factors for MNM. Our study is essential for improving the quality of maternal health care and preventing MNM.
Non-pharmaceutical interventions in containing COVID-19 pandemic after the roll-out of coronavirus vaccines: a systematic review
Authors: He Xiaona , Chen Huiting , Zhu Xinyu , Gao Wei
Published: June 2024

Background

Non-pharmaceutical interventions (NPIs) have been widely utilised to control the COVID-19 pandemic. However, it is unclear what the optimal strategies are for implementing NPIs in the context of coronavirus vaccines. This study aims to systematically identify, describe, and evaluate existing ecological studies on the real-world impact of NPIs in containing COVID-19 pandemic following the roll-out of coronavirus vaccines.

Methods

We conducted a comprehensive search of relevant studies from January 1, 2021, to June 4, 2023 in PubMed, Embase, Web of science and MedRxiv. Two authors independently assessed the eligibility of the studies and extracted the data. A risk of bias assessment tool, derived from a bibliometric review of ecological studies, was applied to evaluate the study design, statistical methodology, and the quality of reporting. Data were collected, synthesised and analysed using qualitative and quantitative methods. The results were presented using summary tables and figures, including information on the target countries and regions of the studies, types of NPIs, and the quality of evidence.

Results

The review included a total of 17 studies that examined the real-world impact of NPIs in containing the COVID-19 pandemic after the vaccine roll-out. These studies used five composite indicators that combined multiple NPIs, and examined 14 individual NPIs. The studies had an average quality assessment score of 13 (range: 10–16), indicating moderately high quality. NPIs had a larger impact than vaccination in mitigating the spread of COVID-19 during the early stage of the vaccination implementation and in the context of the Omicron variant. Testing policies, workplace closures, and restrictions on gatherings were the most effective NPIs in containing the COVID-19 pandemic, following the roll-out of vaccines. The impact of NPIs varied across different time frames, countries and regions.

Conclusion

NPIs had a larger contribution to the control of the pandemic as compared to vaccination during the early stage of vaccine implementation and in the context of the omicron variant. The impact of NPIs in containing the COVID-19 pandemic exhibited variability in diverse contexts. Policy- and decision-makers need to focus on the impact of different NPIs in diverse contexts. Further research is needed to understand the policy mechanisms and address potential future challenges.
Epidemiology of alcohol use disorder in the general population of Togo and Benin: the ALCOTRANS study
Authors: Gellé Thibaut , Paquet Aude , Wenkourama Damega , Girard Murielle , Lacroix Aurélie , Togan Roméo Mèdéssè , Degboe Zinsou Selom , Boni Richard Biaou , Sacca Hélène Robin , Boumediene Farid , Houinato Dismand , Dassa Simliwa Kolou , Ekouevi Didier K. , Preux Pierre- Marie , Nubukpo Philippe
Published: June 2024

Introduction

Access to data concerning mental health, particularly alcohol use disorders (AUD), in sub-Saharan Africa is very limited. This study aimed to estimate AUD prevalence and identify the associated factors in Togo and Benin.

Methods

A cross-sectional study was conducted between April and May 2022, targeting individuals aged 18 years and above in the Yoto commune of Togo and the Lalo commune of Benin. Subjects were recruited using a multi-stage random sampling technique. AUD diagnoses were made using the MINI adapted to DSM-5 criteria. Our study collected sociodemographic information, data on psychiatric comorbidities, stigmatization, and assessed cravings, using a series of scales. The association between AUD and various factors was analyzed using multivariable logistic regression.

Results

In Togo, 55 of the 445 people investigated had AUD (12.4%; [95% CI: 9.5-15.7%]). Among them, 39 (70.9%) had severe AUD and the main associated comorbidities were suicidal risk (36.4%), and major depressive disorder (16.4%). Associated factors with AUD were male gender (aOR: 11.3; [95% CI: 4.8–26.7]), a higher Hamilton Depression Rating Scale (HDRS) score (aOR: 1.2; [95% CI: 1.1–1.3]) and a lower Stigma score measured by the Explanatory Model Interview Catalogue (EMIC) (aOR: 0.9; [95% CI: 0.8–0.9). The stigma scores reflect perceived societal stigma towards individuals with AUD. In Benin, 38 of the 435 people investigated had AUD (8.7%; [95% CI: 6.4–11.7]), and the main associated comorbidities were suicidal risk (18.4%), tobacco use disorder (13.2%) and major depressive episode (16.4%). Associated factors with AUD were male gender (aOR: 6.4; [95% CI: 2.4–17.0]), major depressive disorder (aOR: 21.0; [95% CI: 1.5-289.8]), suicidal risk (aOR: 3.7; [95% CI: 1.2–11.3]), a lower Frontal Assessment Battery (FAB) score (aOR:0.8; [95% CI: 0.8–0.9]) and a lower perceived stigma score (by EMIC )(aOR: 0.9; [95% CI: 0.8–0.9]).

Conclusion

In these communes of Togo and Benin, AUD prevalence is notably high. A deeper understanding of the disease and its local determinants, paired with effective prevention campaigns, could mitigate its impact on both countries.
Association between lactate dehydrogenase and ventilator-associated pneumonia risk: an analysis of the MIMIC database 2001–2019
Authors: Qian Xiangfeng , Sheng Yi , Jiang Yinsheng , Xu Yongan
Published: June 2024

Background

Serum lactate dehydrogenase (LDH) is a nonspecific inflammatory biomarker and has been reported to be associated with pneumonia prognosis. This study aimed to evaluate the relationship between LDH levels and ventilator-associated pneumonia (VAP) risk in intensive care unit (ICU) patients.

Methods

This retrospective cohort study used data from the Multiparameter Intelligent Monitoring in Intensive Care database from 2001 to 2019. ICU patients aged ≥ 18 years and receiving mechanical ventilation were included. LDH levels were analyzed as continuous and categorical variables (< 210, 210–279, 279–390, > 390 IU/L), respectively. Restricted cubic spline (RCS) curves and quartiles were used to categorize LDH levels. Logistic regression and linear regression were utilized to assess the relationship of LDH levels with VAP risk and duration of mechanical ventilation, respectively.

Results

A total of 9,164 patients were enrolled, of which 646 (7.05%) patients developed VAP. High levels of LDH increased the risk of VAP [odds ratio (OR) = 1.15, 95% confidence interval (CI): 1.06–1.24] and LDH levels were positively correlated with the duration of mechanical ventilation [β = 4.49, 95%CI: (3.42, 5.56)]. Moreover, patients with LDH levels of 279–390 IU/L (OR = 1.38, 95%CI: 1.08–1.76) and > 390 IU/L (OR = 1.50, 95%CI: 1.18–1.90) had a higher risk of VAP than patients with LDH levels < 210 IU/L. Patients with LDH levels of 279–390 IU/L [β = 3.84, 95%CI: (0.86, 6.82)] and > 390 IU/L [β = 11.22, 95%CI: (8.21, 14.22)] (vs. <210 IU/L) had a longer duration of mechanical ventilation.

Conclusion

Elevated serum LDH levels were related to a higher risk of VAP and longer duration of mechanical ventilation and may be useful for monitoring VAP risk.
Salvia miltiorrhiza bunge extracts: a promising source for anti-atopic dermatitis activity
Authors: Ryu Da Hye , Cho Jwa Yeong , Yu Hyung-Seok , Kim Jin-Woo , Kim Jin-Chul , Son Yang-Ju , Nho Chu Won , Hamayun Muhammad , Kim Ho-Youn
Published: June 2024

Background

Atopic dermatitis (AD) is a chronic inflammatory condition characterized by the accumulation of reactive oxygen species and the expression of inflammatory factors. Regarding its anti-atopic activity, numerous traditional medicinal materials and secondary metabolic products play pivotal roles in modulating the associated mechanisms.

Methods

This study aimed to utilize Salvia miltiorrhiza Bunge (SMB) as an anti-AD source. In-vitro activity assessments and qualitative and quantitative analyses using UPLC-TQ-MS/MS and HPLC-DAD were conducted in two cultivars (‘Dasan’ and ‘Kosan’). Statistical analysis indicated that the profiles of their secondary metabolites contribute significantly to their pharmacological properties. Consequently, bio-guided fractionation was undertaken to figure out the distinct roles of the secondary metabolites present in SMB.

Results

Comparative study of two cultivars indicated that ‘Dasan’, having higher salvianolic acid A and B, exhibited stronger antioxidant and anti-inflammatory activities. Meanwhile, ‘Kosan’, containing higher tanshinones, showed higher alleviating activities on anti-AD related genes in mRNA levels. Additionally, performed bio-guided fractionation re-confirmed that the hydrophilic compounds of SMB can prevent AD by inhibiting accumulation of ROS and suppressing inflammatory factors and the lipophilic components can directly inhibit AD.

Conclusions

SMB was revealed as a good source for anti-AD activity. Several bioactive compounds were identified from the UPLC-TQ-MS/MS and different compounds content was linked to biological activities. Characterization of these compounds may be helpful to understand differential role of secondary metabolites from SMB on alleviation of AD.
Multi-stage optimization strategy based on contextual analysis to create M-health components for case management model in breast cancer transitional care: the CMBM study as an example
Authors: Chengang Hong , Liping Wang , Shujin Wang , Chen Chen , Jiayue Yang , Jingjing Lu , Shujie Hua , Jieming Wu , Liyan Yao , Ni Zeng , Jinhui Chu , Jiaqi Sun
Published: June 2024

Background

None of the early M-Health applications are designed for case management care services. This study aims to describe the process of developing a M-health component for the case management model in breast cancer transitional care and to highlight methods for solving the common obstacles faced during the application of M-health nursing service.

Methods

We followed a four-step process: (a) Forming a cross-functional interdisciplinary development team containing two sub-teams, one for content development and the other for software development. (b) Applying self-management theory as the theoretical framework to develop the M-health application, using contextual analysis to gain a comprehensive understanding of the case management needs of oncology nursing specialists and the supportive care needs of out-of-hospital breast cancer patients. We validated the preliminary concepts of the framework and functionality of the M-health application through multiple interdisciplinary team discussions. (c) Adopting a multi-stage optimization strategy consisting of three progressive stages: screening, refining, and confirmation to develop and continually improve the WeChat mini-programs. (d) Following the user-centered principle throughout the development process and involving oncology nursing specialists and breast cancer patients at every stage.

Results

Through a continuous, iterative development process and rigorous testing, we have developed patient-end and nurse-end program for breast cancer case management. The patient-end program contains four functional modules: “Information”, “Interaction”, “Management”, and “My”, while the nurse-end program includes three functional modules: “Consultation”, “Management”, and “My”. The patient-end program scored 78.75 on the System Usability Scale and showed a 100% task passing rate, indicating that the programs were easy to use.

Conclusions

Based on the contextual analysis, multi-stage optimization strategy, and interdisciplinary team work, a WeChat mini-program has been developed tailored to the requirements of the nurses and patients. This approach leverages the expertise of professionals from multiple disciplines to create effective and evidence-based solutions that can improve patient outcomes and quality of care.
Two novel TMEM67 variations in a Chinese family with recurrent pregnancy loss: a case report
Authors: Pang Jialun , Kong Fanjuan , Tang Wanglan , Xi Hui , Ma Na , Sheng Xiaoqi , Peng Ying , Liu Zhiyu
Published: June 2024

Background

Recurrent pregnancy loss (RPL) is a common pregnancy complication that brings great pain to pregnant women and their families. Genetic factors are an important cause reason of RPL. However, clinical research on monogenic diseases with recurrent miscarriage is insufficient.

Case presentation

Here we reported a Chinese family with RPL and genetic analysis of the abortion and parents. A paternally inherited heterozygous missense variant c.1415T > G (p.V472G) and a maternally inherited heterozygous nonsense variant c.2314del (p.M772*) in TMEM67 gene were identified by trio-exome sequencing. c.2314del (p.M772*) generated a premature stop codon and truncated protein, was classified as “pathogenic”. c.1415T > G (p.V472G) located in extra-cellular region, was classified as “likely pathogenic”. Biallelic variants in TMEM67 gene cause lethal Meckel syndrome 3, consistent with the proband’s prenatal phenotype.

Conclusion

The current study of the Chinese family expands the pathogenic variant spectrum of TMEM67 and emphasizes the necessity of exome sequencing in RPL condition.
Systemic antibiotics for Pseudomonas aeruginosa infection in outpatients with non-hospitalised exacerbations of pre-existing lung diseases: a randomised clinical trial
Authors: Eklöf Josefin , Alispahic Imane Achir , Armbruster Karin , Lapperre Therese Sophie , Browatzki Andrea , Overgaard Rikke Holmen , Harboe Zitta Barrella , Janner Julie , Moberg Mia , Ulrik Charlotte Suppli , Andreassen Helle Frost , Weinreich Ulla Møller , Kjærgaard Jakob Lyngby , Villadsen Jenny , Fenlev Camilla Sund , Jensen Torben Tranborg , Christensen Christina Wellendorph , Bangsborg Jette , Ostergaard Christian , Ghathian Khaled Saoud Ali , Jordan Alexander , Klausen Tobias Wirenfeldt , Nielsen Thyge Lynghøj , Wilcke Torgny , Seersholm Niels , Sivapalan Pradeesh , Jensen Jens-Ulrik Stæhr
Published: June 2024

Background

The effect of dual systemic antibiotic therapy against Pseudomonas aeruginosa in patients with pre-existing lung disease is unknown. To assess whether dual systemic antibiotics against P. aeruginosa in outpatients with COPD, non-cystic fibrosis (non-CF) bronchiectasis, or asthma can improve outcomes.

Methods

Multicenter, randomised, open-label trial conducted at seven respiratory outpatient clinics in Denmark. Outpatients with COPD, non-CF bronchiectasis, or asthma with a current P. aeruginosa-positive lower respiratory tract culture (clinical routine samples obtained based on symptoms of exacerbation not requiring hospitalisation), regardless of prior P. aeruginosa-status, no current need for hospitalisation, and at least two moderate or one hospitalisation-requiring exacerbation within the last year were eligible. Patients were assigned 1:1 to 14 days of dual systemic anti-pseudomonal antibiotics or no antibiotic treatment. Primary outcome was time to prednisolone or antibiotic-requiring exacerbation or death from day 20 to day 365.

Results

The trial was stopped prematurely based in lack of recruitment during the COVID-19 pandemic, this decision was endorsed by the Data and Safety Monitoring Board. Forty-nine outpatients were included in the study. There was a reduction in risk of the primary outcome in the antibiotic group compared to the control group (HR 0.51 (95%CI 0.27–0.96), p = 0.037). The incidence of admissions with exacerbation within one year was 1.1 (95%CI 0.6–1.7) in the dual antibiotic group vs. 2.9 (95%CI 1.3–4.5) in the control group, p = 0.037.

Conclusions

Use of dual systemic antibiotics for 14 days against P. aeruginosa in outpatients with chronic lung diseases and no judged need for hospitalisation, improved clinical outcomes markedly. The main limitation was the premature closure of the trial.

Trial Registration

ClinicalTrials.gov, NCT03262142, registration date 2017–08-25.
LLIN Evaluation in Uganda Project (LLINEUP): modelling the impact of COVID-19-related disruptions on delivery of long-lasting insecticidal nets on malaria indicators in Uganda
Authors: Okiring Jaffer , Gonahasa Samuel , Maiteki-Sebuguzi Catherine , Katureebe Agaba , Bagala Irene , Mutungi Peter , Kigozi Simon P. , Namuganga Jane F. , Nankabirwa Joaniter I. , Kamya Moses R. , Donnelly Martin J. , Churcher Thomas S. , Staedke Sarah G. , Sherrard-Smith Ellie
Published: June 2024

Background

Disruptions in malaria control due to COVID-19 mitigation measures were predicted to increase malaria morbidity and mortality in Africa substantially. In Uganda, long-lasting insecticidal nets (LLINs) are distributed nationwide every 3–4 years, but the 2020–2021 campaign was altered because of COVID-19 restrictions so that the timing of delivery of new nets was different from the original plans made by the National Malaria Control Programme.

Methods

A transmission dynamics modelling exercise was conducted to explore how the altered delivery of LLINs in 2020–2021 impacted malaria burden in Uganda. Data were available on the planned LLIN distribution schedule for 2020–2021, and the actual delivery. The transmission model was used to simulate 100 health sub-districts, and parameterized to match understanding of local mosquito bionomics, net use estimates, and seasonal patterns based on data collected in 2017–2019 during a cluster-randomized trial (LLINEUP). Two scenarios were compared; simulated LLIN distributions matching the actual delivery schedule, and a comparable scenario simulating LLIN distributions as originally planned. Model parameters were otherwise matched between simulations.

Results

Approximately 70% of the study population received LLINs later than scheduled in 2020–2021, although some areas received LLINs earlier than planned. The model indicates that malaria incidence in 2020 was substantially higher in areas that received LLINs late. In some areas, early distribution of LLINs appeared less effective than the original distribution schedule, possibly due to attrition of LLINs prior to transmission peaks, and waning LLIN efficacy after distribution. On average, the model simulations predicted broadly similar overall mean malaria incidence in 2021 and 2022. After accounting for differences in cluster population size and LLIN distribution dates, no substantial increase in malaria burden was detected.

Conclusions

The model results suggest that the disruptions in the 2020–2021 LLIN distribution campaign in Uganda did not substantially increase malaria burden in the study areas.
Association of longitudinal pet ownership with wheezing in 3-year-old children using the distributed lag model: the Japan Environment and Children’s Study
Authors: Shirato Kota , Oba Koji , Matsuyama Yutaka , Hagiwara Yasuhiro ,   The Japan Environment and Children’s Study (JECS) Group
Published: June 2024

Background

Time-varying exposures like pet ownership pose challenges for identifying critical windows due to multicollinearity when modeled simultaneously. The Distributed Lag Model (DLM) estimates critical windows for time-varying exposures, which are mainly continuous variables. However, applying complex functions such as high-order splines and nonlinear functions within DLMs may not be suitable for situations with limited time points or binary exposure, such as in questionnaire surveys.

Objectives

(1) We examined the estimation performance of a simple DLM with fractional polynomial function for time-varying binary exposures through simulation experiments. (2) We evaluated the impact of pet ownership on childhood wheezing onset and estimate critical windows.

Methods

(1) We compared logistic regression including time-varying exposure in separate models, in one model simultaneously, and using DLM. For evaluation, we employed bias, empirical standard error (EmpSE), and mean squared error (MSE). (2) The Japan Environment and Children's Study (JECS) is a prospective birth cohort study of approximately 100,000 parent-child pairs, registered across Japan from 2011 to 2014. We applied DLM to the JECS data up to age 3. The estimated odds ratios (OR) were considered to be within critical windows when they were significant at the 5% level.

Results

(1) DLM and the separate model exhibited lower bias compared to the simultaneously model. Additionally, both DLM and the simultaneously model demonstrated lower EmpSEs than the separate model. In all scenarios, DLM had lower MSEs than the other methods. Specifically, where critical windows is clearly present and exposure correlation is high, DLM showed MSEs about 1/2 to 1/200 of those of other models. (2) Application of DLM to the JECS data showed that, unlike other models, a significant exposure effect was observed only between the ages of 0 and 6 months. During that periods, the highest ORs were 1.07 (95% confidence interval, 1.01 to 1.14) , observed between the ages of 2 and 5 months.

Conclusions

(1) A simple DLM improves the accuracy of exposure effect and critical windows estimation. (2) 0–6 months may be the critical windows for the effect of pet ownership on the wheezing onset at 3 years.
Recent advances in the use of extracellular vesicles from adipose-derived stem cells for regenerative medical therapeutics
Authors: Yang Song , Sun Yiran , Yan Chenchen
Published: June 2024

Adipose-derived stem cells (ADSCs) are a subset of mesenchymal stem cells (MSCs) isolated from adipose tissue. They possess remarkable properties, including multipotency, self-renewal, and easy clinical availability. ADSCs are also capable of promoting tissue regeneration through the secretion of various cytokines, factors, and extracellular vesicles (EVs). ADSC-derived EVs (ADSC-EVs) act as intercellular signaling mediators that encapsulate a range of biomolecules. These EVs have been found to mediate the therapeutic activities of donor cells by promoting the proliferation and migration of effector cells, facilitating angiogenesis, modulating immunity, and performing other specific functions in different tissues. Compared to the donor cells themselves, ADSC-EVs offer advantages such as fewer safety concerns and more convenient transportation and storage for clinical application. As a result, these EVs have received significant attention as cell-free therapeutic agents with potential future application in regenerative medicine. In this review, we focus on recent research progress regarding regenerative medical use of ADSC-EVs across various medical conditions, including wound healing, chronic limb ischemia, angiogenesis, myocardial infarction, diabetic nephropathy, fat graft survival, bone regeneration, cartilage regeneration, tendinopathy and tendon healing, peripheral nerve regeneration, and acute lung injury, among others. We also discuss the underlying mechanisms responsible for inducing these therapeutic effects. We believe that deciphering the biological properties, therapeutic effects, and underlying mechanisms associated with ADSC-EVs will provide a foundation for developing a novel therapeutic approach in regenerative medicine.

Graphical Abstract
Role of mesenchymal stem cell-derived exosomes in the regeneration of different tissues
Authors: Huang Defa , Shen Haibin , Xie Fangfang , Hu Die , Jin Qing , Hu Yuexin , Zhong Tianyu
Published: June 2024

Exosomes are nanovesicles with multiple components used in several applications. Mesenchymal stem cells (MSCs) are well known for their great potential in clinical applications. MSC-derived exosomes (MSC-Exos) have been shown to mediate tissue regeneration in various diseases, including neurological, autoimmune, and inflammatory diseases, cancer, ischemic heart disease, lung injury, and liver fibrosis. They can modulate the immune response by interacting with immune effector cells in the presence of anti-inflammatory compounds and are involved in intercellular communication through various types of cargo. This review summarizes the MSC-Exos-mediated tissue regeneration in various diseases, including neurological, cardiovascular, liver, kidney, articular cartilage, and oral tissue applications. In addition, we discuss the challenges and prospects of MSC-Exos in tissue regeneration.
Hypoxia and re-oxygenation effects on human cardiomyocytes cultured on polycaprolactone and polyurethane nanofibrous mats
Authors: Iwoń Zuzanna , Krogulec Ewelina , Kierlańczyk Aleksandra , Wojasiński Michał , Jastrzębska Elżbieta
Published: June 2024

Heart diseases are caused mainly by chronic oxygen insufficiency (hypoxia), leading to damage and apoptosis of cardiomyocytes. Research into the regeneration of a damaged human heart is limited due to the lack of cellular models that mimic damaged cardiac tissue. Based on the literature, nanofibrous mats affect the cardiomyocyte morphology and stimulate the growth and differentiation of cells cultured on them; therefore, nanofibrous materials can support the production of in vitro models that faithfully mimic the 3D structure of human cardiac tissue. Nanofibrous mats were used as scaffolds for adult primary human cardiomyocytes (HCM) and immature human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). This work focuses on understanding the effects of hypoxia and re-oxygenation on human cardiac cells cultured on polymer nanofibrous mats made of poly(ε-caprolactone) (PCL) and polyurethane (PU). The expression of selected genes and proteins in cardiomyocytes during hypoxia and re-oxygenation were evaluated. In addition, the type of cell death was analyzed. To the best of our knowledge, there are no studies on the effects of hypoxia on cardiomyocyte cells cultured on nanofibrous mats. The present study aimed to use nanofiber mats as scaffolds that structurally could mimic cardiac extracellular matrix. Understanding the impact of 3D structural properties in vitro cardiac models on different human cardiomyocytes is crucial for advancing cardiac tissue engineering and regenerative medicine. Observing how 3D scaffolds affect cardiomyocyte function under hypoxic conditions is necessary to understand the functioning of the entire human heart.
NSUN2/YBX1 promotes the progression of breast cancer by enhancing HGH1 mRNA stability through m5C methylation
Authors: Zhang Xuran , An Ke , Ge Xin , Sun Yuanyuan , Wei Jingyao , Ren Weihong , Wang Han , Wang Yueqin , Du Yue , He Lulu , Li Ouwen , Zhou Shaoxuan , Shi Yong , Ren Tong , Yang Yun-gui , Kan Quancheng , Tian Xin
Published: June 2024

Background

RNA m5C methylation has been extensively implicated in the occurrence and development of tumors. As the main methyltransferase, NSUN2 plays a crucial regulatory role across diverse tumor types. However, the precise impact of NSUN2-mediated m5C modification on breast cancer (BC) remains unclear. Our study aims to elucidate the molecular mechanism underlying how NSUN2 regulates the target gene HGH1 (also known as FAM203) through m5C modification, thereby promoting BC progression. Additionally, this study targets at preliminarily clarifying the biological roles of NSUN2 and HGH1 in BC.

Methods

Tumor and adjacent tissues from 5 BC patients were collected, and the m5C modification target HGH1 in BC was screened through RNA sequencing (RNA-seq) and single-base resolution m5C methylation sequencing (RNA-BisSeq). Methylation RNA immunoprecipitation-qPCR (MeRIP-qPCR) and RNA-binding protein immunoprecipitation-qPCR (RIP-qPCR) confirmed that the methylation molecules NSUN2 and YBX1 specifically recognized and bound to HGH1 through m5C modification. In addition, proteomics, co-immunoprecipitation (co-IP), and Ribosome sequencing (Ribo-Seq) were used to explore the biological role of HGH1 in BC.

Results

As the main m5C methylation molecule, NSUN2 is abnormally overexpressed in BC and increases the overall level of RNA m5C. Knocking down NSUN2 can inhibit BC progression in vitro or in vivo. Combined RNA-seq and RNA-BisSeq analysis identified HGH1 as a potential target of abnormal m5C modifications. We clarified the mechanism by which NSUN2 regulates HGH1 expression through m5C modification, a process that involves interactions with the YBX1 protein, which collectively impacts mRNA stability and protein synthesis. Furthermore, this study is the first to reveal the binding interaction between HGH1 and the translation elongation factor EEF2, providing a comprehensive understanding of its ability to regulate transcript translation efficiency and protein synthesis in BC cells.

Conclusions

This study preliminarily clarifies the regulatory role of the NSUN2-YBX1-m5C-HGH1 axis from post-transcriptional modification to protein translation, revealing the key role of abnormal RNA m5C modification in BC and suggesting that HGH1 may be a new epigenetic biomarker and potential therapeutic target for BC.
DNA methylation patterns of transcription factor binding regions characterize their functional and evolutionary contexts
Authors: Rimoldi Martina , Wang Ning , Zhang Jilin , Villar Diego , Odom Duncan T. , Taipale Jussi , Flicek Paul , Roller Maša
Published: June 2024

Background

DNA methylation is an important epigenetic modification which has numerous roles in modulating genome function. Its levels are spatially correlated across the genome, typically high in repressed regions but low in transcription factor (TF) binding sites and active regulatory regions. However, the mechanisms establishing genome-wide and TF binding site methylation patterns are still unclear.

Results

Here we use a comparative approach to investigate the association of DNA methylation to TF binding evolution in mammals. Specifically, we experimentally profile DNA methylation and combine this with published occupancy profiles of five distinct TFs (CTCF, CEBPA, HNF4A, ONECUT1, FOXA1) in the liver of five mammalian species (human, macaque, mouse, rat, dog). TF binding sites are lowly methylated, but they often also have intermediate methylation levels. Furthermore, biding sites are influenced by the methylation status of CpGs in their wider binding regions even when CpGs are absent from the core binding motif. Employing a classification and clustering approach, we extract distinct and species-conserved patterns of DNA methylation levels at TF binding regions. CEBPA, HNF4A, ONECUT1, and FOXA1 share the same methylation patterns, while CTCF's differ. These patterns characterize alternative functions and chromatin landscapes of TF-bound regions. Leveraging our phylogenetic framework, we find DNA methylation gain upon evolutionary loss of TF occupancy, indicating coordinated evolution. Furthermore, each methylation pattern has its own evolutionary trajectory reflecting its genomic contexts.

Conclusions

Our epigenomic analyses indicate a role for DNA methylation in TF binding changes across species including that specific DNA methylation profiles characterize TF binding and are associated with their regulatory activity, chromatin contexts, and evolutionary trajectories.
The impact of inactivity during the COVID-19 pandemic on the physical performance of high school athletes
Authors: Asan Selim , Ulupınar Süleyman , Özbay Serhat , Namlı Sevinç , Gençoğlu Cebrail , Canyurt Ferhat , Çingöz Yunus Emre , Özkara Abdullah Bora
Published: June 2024

Background/Objective

This study was conducted during the 2019–2020 academic year to evaluate the impact of participation in school sports on students’ Body Mass Index (BMI) and Assessing Levels of Physical Activity (ALPHA) test scores. Interrupted by the COVID-19 pandemic, which led to a suspension of in-person education, the study resumed in September 2021, refocusing on the effects of pandemic-induced inactivity on the physical fitness levels of the same cohort.

Methods

The study included twenty-nine male high school students (age: 17,24 ± 0,73 years), divided into thirteen athletes (participating in sports such as football, basketball, and track) and sixteen non-athletic counterparts. They underwent reassessment using the ALPHA test battery, evaluating cardiorespiratory, musculoskeletal, and motor skills fitness. Data were analyzed using independent and paired samples t-tests and a two-way repeated measures ANOVA to assess changes over time and between groups. Discriminant function analysis evaluated the ALPHA test’s ability to classify students based on their athletic status pre- and post-pandemic.

Results

Initially, athlete students exhibited significantly better BMI, 20 m shuttle run, and 4 × 10 m speed run scores compared to their non-athlete peers. After the pandemic, only the 20 m shuttle run scores remained significantly higher for athletes, with diminished distinctions in other fitness areas. The classification accuracy of the ALPHA test battery decreased from 89.7 to 75.9% post-pandemic.

Conclusion

The enforced sedentary lifestyle due to the COVID-19 pandemic adversely affected all students, particularly diminishing health-related fitness parameters such as body composition, cardiorespiratory and musculoskeletal strength, and motor skills. Students previously engaged in regular physical activity, notably school athletes, experienced significant fitness declines. This highlights the urgent need for targeted interventions to encourage active lifestyles among youth in the post-pandemic phase, aiming to avert long-term adverse health outcomes.
On the fractional perturbed neutral integro-differential systems via deformable derivatives: an existence study
Authors: Sreedharan R. , Balachandar S. Raja , Udhayakumar R. , Etemad Sina , Avcı İbrahim , Rezapour Shahram
Published: June 2024

In this paper, we provide some appropriate conditions for the existence of solutions for a perturbed fractional neutral integro-differential system under the deformable derivative in a Banach space. Using the Banach contraction principle and Krasnoselskii’s fixed point theorem, we establish some new existence theorems. Moreover, we provide two numerical examples to demonstrate the applicability of the theoretical results