bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geographical inequality in service utilization for primary aldosteronism screening: spatial epidemiological study in Southern Thailand
Authors: Suntornlohanakul Onnicha , Sakarin Suporn , Kietsiriroje Noppadol , Sriplung Hutcha 
Published: April 2022

Abstract
Background
Primary aldosteronism (PA), the most common cause of secondary hypertension is considered as a “major public health issue” due to higher risk of cardiovascular complications compared to blood-pressure-match hypertension and increase in prevalence around the world. In Thailand, though PA screening is provided under the universal health coverage, the service can be offered only at some centers. Hence, the service availability affects an accessibility of health care in patients. Our study aimed to evaluate the service utilization in PA screening and diagnosis in terms of geographical inequality in health resources in Southern Thailand.

Methods
Data of 688 patients who underwent PA screening from 2011 to 2017 were obtained from the electronic database of Songklanagarind Hospital, a super-tertiary center in this region. The patients’ residence in the province, district and subdistrict were transformed to a 6-digit numbers corresponding to the global one (GADM©). The areas with PA screening and diagnosis were visualized by disease mapping procedures. A general log linear model was used to identify the factors affecting patient’s service accessibility.

Results
From the geographic distribution, patients living in or near the area of the super-tertiary center (Songkhla) had high probability of receiving PA screening. The analysis of factors contributing to PA screening by multivariate log-linear model demonstrated that the distance from the super-tertiary center was a predictive factor for screening while the presence of endocrinologists and cultural differences were not. The chance of patients living in Songkhla, living less than 200 km, and more than 200 km from Songkhla to receive PA screening was 100, 82, and 66%, respectively. The crude incidence rate of PA in Southern Thailand was 1.66/106 person-years. The provinces located adjacent to the Andaman Sea had the highest incidences of PA (3.62-5.17 patients/106 person-years).

Conclusions
There is still geographical inequality and the strategy to decrease the barrier should be resolved. The policymaker should develop a transfer system of blood tests for PA investigation from the local hospital to reduce the burden such as transportation costs in patients who live far away from the super-tertiary hospital. In addition, PA screening should be implemented in hypertension care plan.
Exploring genetic association of insomnia with allergic disease and asthma: a bidirectional Mendelian randomization study
Authors: Li Rong , Chen Yiting , Zhao Anda , Huang Lili , Long Zichong , Kang Wenhui , Yin Yong , Tong Shilu , Guo Yongmei , Li Shenghui 
Published: April 2022

Abstract
Background
Insomnia is highly prevalent among patients with allergic disease and asthma; however, few studies have investigated their causal relationship. We aim to explore the causal association between insomnia and allergic disease/asthma by performing bidirectional Mendelian randomization (MR) study.

Methods
Instrumental variables were constructed using single nucleotide polymorphisms (SNPs). Summary statistics for insomnia, allergic disease, and asthma were obtained from four large-scale genome-wide association studies (GWAS) of European ancestry. The pleiotropy analysis was applied by using the MR-Egger intercept test and the MR pleiotropy residual sum and outlier (MR-PRESSO) test. MR analyses were conducted by using inverse variance weighted (IVW), weighted median, and MR-Egger method.

Results
Based on the multiplicative random effects IVW method, the MR analysis showed that genetically predicted insomnia was causally associated with an increased risk of allergic disease [odds ratio (OR) = 1.054, 95% confidence interval (CI) = 1.031–1.078, P = 3.817 × 10–06], asthma (OR = 1.043, 95% CI = 1.010–1.077, P = 9.811 × 10–03), moderate-severe asthma (OR = 1.168, 95% CI = 1.069–1.277, P = 6.234 × 10–04), and adult-onset asthma (OR = 1.086, 95% CI = 1.037–1.138, P = 4.922 × 10–04). In bidirectional analyses, we did not find evidence supporting the reverse causality relations.

Conclusions
Our MR study suggested that genetically predicted insomnia was the risk factor for allergic disease and asthma. Improving sleep quality could be one of the cornerstones in the prevention of allergic disease and asthma.
Regulation of heterologous subtilin production in Bacillus subtilis W168
Authors: Zhang Qian , Kobras Carolin M. , Gebhard Susanne , Mascher Thorsten , Wolf Diana 
Published: April 2022

Abstract
Background
Subtilin is a peptide antibiotic (lantibiotic) natively produced by Bacillus subtilis ATCC6633. It is encoded in a gene cluster spaBTCSIFEGRK (spa-locus) consisting of four transcriptional units: spaS (subtilin pre-peptide), spaBTC (modification and export), spaIFEG (immunity) and spaRK (regulation). Despite the pioneer understanding on subtilin biosynthesis, a robust platform to facilitate subtilin research and improve subtilin production is still a poorly explored spot.

Results
In this work, the intact spa-locus was successfully integrated into the chromosome of Bacillus subtilis W168, which is the by far best-characterized Gram-positive model organism with powerful genetics and many advantages in industrial use. Through systematic analysis of spa-promoter activities in B. subtilis W168 wild type and mutant strains, our work demonstrates that subtilin is basally expressed in B. subtilis W168, and the transition state regulator AbrB strongly represses subtilin biosynthesis in a growth phase-dependent manner. The deletion of AbrB remarkably enhanced subtilin gene expression, resulting in comparable yield of bioactive subtilin production as for B. subtilis ATCC6633. However, while in B. subtilis ATCC6633 AbrB regulates subtilin gene expression via SigH, which in turn activates spaRK, AbrB of B. subtilis W168 controls subtilin gene expression in SigH-independent manner, except for the regulation of spaBTC. Furthermore, the work shows that subtilin biosynthesis in B. subtilis W168 is regulated by the two-component regulatory system SpaRK and strictly relies on subtilin itself as inducer to fulfill the autoregulatory circuit. In addition, by incorporating the subtilin-producing system (spa-locus) and subtilin-reporting system (PpsdA-lux) together, we developed “online” reporter strains to efficiently monitor the dynamics of subtilin biosynthesis.

Conclusions
Within this study, the model organism B. subtilis W168 was successfully established as a novel platform for subtilin biosynthesis and the underlying regulatory mechanism was comprehensively characterized. This work will not only facilitate genetic (engineering) studies on subtilin, but also pave the way for its industrial production. More broadly, this work will shed new light on the heterologous production of other lantibiotics.
Antifungal application of biosynthesized selenium nanoparticles with pomegranate peels and nanochitosan as edible coatings for citrus green mold protection
Authors: Salem Mohamed F. , Abd-Elraoof Wessam A. , Tayel Ahmed A. , Alzuaibr Fahad M. , Abonama Osama M. 
Published: April 2022

Abstract
Background
Citrus production and trading are seriously affected by fungal decays worldwide; the green mold infection by Penicillium digitatum could be the most disastrous. The substitutions of chemical and synthetic fungicides with effectual natural alternatives are global demands; plant extract from pomegranates peels (PPE), biosynthesized selenium nanoparticles with PPE (PPE/SeNPs) and chitosan nanoparticles (NCT) were suggested as efficacious fungicidal agents/nanocomposites to control P. digitatum strains.

Method
PPE from Punica granatum was extracted and employed directly for synthesizing SeNPs, whereas NCT was produced using ionic gelation method of chitosan extracted from white prawn (Fenneropenaeus indicus) shells. The physiochemical, biochemical and structural characterization of generated molecules were conducted using infra-red spectroscopy, particles’ size (Ps) and charge assessment and electron microscopes imaging. Antifungal potentialities were investigated in vitro and in infected fruits with P. digitatum by applying NCT nanocomposites-based edible coating.

Results
The synthesis of PPE-synthesized SeNPs and NCT was successfully achieved, the molecular bonding in synthesized agents/composites were proved with infrared spectroscopy to have both biochemical and physical interactions. The nanoparticles had 82.72, 9.41 and 85.17 nm mean diameters for NCT, PPE/SeNPs and NCT/PPE/SeNPs nanocomposites, respectively. The nanoparticles had homogenous spherical shapes and good distribution attributes. The entire agents/nanocomposites exhibited potent fungicidal potentialities toward P. digitatum isolates; NCT/PPE/SeNPs nanocomposite was the most forceful and significantly exceeded the fungicidal action of standard fungicide. The direct treatment of fungal mycelia with NCT/PPE/SeNPs nanocomposite led to remarkable lysis and deformations of P. digitatum hyphae within 12 h of treatment. The coating of infected orange with NCT-based edible coatings reduced the green mold infection signs by 91.7, 95.4 and 100%, for NCT, NCT/PPE and NCT/PPE/SeNPs based coating solutions, respectively.

Conclusions
NCT, PPE-synthesized SeNPs, and their innovative nanocomposites NCT/PPE/SeNPs are convincingly recommended for formulating effectual antifungal and edible coatings to eliminate postharvest fungal pathogen, both with protection from their invasion or with destructing their existing infections.

Graphical Abstract
The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα
Authors: Miao Yumeng , Zhang Changliu , Yang Ling , Zeng Xi , Hu Yuxiao , Xue Xinru , Dai Yue , Wei Zhifeng 
Published: April 2022

Abstract
Background
Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. This study aimed to solve this problem in view of cellular metabolism.

Methods
Three recognized PPARγ agonists (synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin) were used as the tools to activate PPARγ. The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout.

Results
Rosiglitazone, 15d-PGJ2 and morin all increased the frequency of CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells, boosted the transcription of Foxp3, IL-10, CTLA4 and TIGIT, and facilitated the function of Treg cells. They significantly promoted FAO in differentiating Treg cells by up-regulating the levels of CD36 and CPT1 but not other enzymes involved in FAO such as ACADL, ACADM, HADHA or HADHB, and siCD36 or siCPT1 dampened PPARγ agonists-promoted Treg responses. Moreover, PPARγ agonists enhanced UDP-GlcNAc biosynthesis and subsequent N-linked glycosylation, but did not affect the expressions of N-glycan branching enzymes Mgat1, 2, 4 and 5. Notably, the enzyme activity of phosphofructokinase (PFK) was inhibited by PPARγ agonists and the effect was limited by siCD36 or siCPT1, implying PFK to be a link between PPARγ agonists-promoted FAO and UDP-GlcNAc biosynthesis aside from acetyl-CoA. Furthermore, PPARγ agonists facilitated the cell surface abundance of TβRII and IL-2Rα via N-linked glycosylation, thereby activating TGF-β/Smads and IL-2/STAT5 signaling, and the connection between N-linked glycosylation and Treg responses was revealed by tunicamycin. However, the increased surface abundance of CD36 was demonstrated to be mainly owing to PPARγ agonists-up-regulated overall expression. Finally, PPARγ antagonist GW9662 or CRISPR/Cas9-mediated knockout of PPARγ constrained the effects of rosiglitazone, 15d-PGJ2 and morin, confirming the exact role of PPARγ.

Conclusions
The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα, which is beneficial for inflammatory and autoimmune diseases.

Graphical abstract
TRIM3 facilitates estrogen signaling and modulates breast cancer cell progression
Authors: Zhuang Ting , Wang Beibei , Tan Xiaojing , Wu Le , Li Xin , Li Zhongbo , Cai Yuqing , Fan Rongrong , Yang Xiao , Zhang Chenmiao , Xia Yan , Niu Zhiguo , Liu Bingtian , Cao Qi , Ding Yinlu , Zhou Zhipeng , Huang Qingsong , Yang Huijie 
Published: April 2022

Abstract
Background
Breast cancer is the most common cancer in women worldwide. More than 70% of breast cancers are estrogen receptor (ER) alpha positive. Compared with ER alpha-negative breast cancer, which is more aggressive and has a shorter survival time, ER alpha-positive breast cancer could benefit from endocrine therapy. Selective estrogen receptor modulators, such as tamoxifen, are widely used in endocrine therapy. Approximately half of ER alpha-positive breast cancer patients will eventually develop endocrine resistance, making it a major clinical challenge in therapy. Thus, decoding the throughput of estrogen signaling, including the control of ER alpha expression and stability, is critical for the improvement of breast cancer therapeutics.

Methods
TRIM3 and ER alpha protein expression levels were measured by western blotting, while the mRNA levels of ER alpha target genes were measured by RT–PCR. A CCK-8 assay was used to measure cell viability. RNA sequencing data were analyzed by Ingenuity Pathway Analysis. Identification of ER alpha signaling activity was accomplished with luciferase assays, RT–PCR and western blotting. Protein stability assays and ubiquitin assays were used to detect ER alpha protein degradation. Ubiquitin-based immunoprecipitation assays were used to detect the specific ubiquitination modification on the ER alpha protein.

Results
In our current study, we found that TRIM3, an E3 ligase, can promote ER alpha signaling activity and breast cancer progression. TRIM3 depletion inhibits breast cancer cell proliferation and migration, while unbiased RNA sequencing data indicated that TRIM3 is required for the activity of estrogen signaling on the -genome-wide scale. The immunoprecipitation assays indicated that TRIM3 associates with ER alpha and promotes its stability, possibly by inducing K63-linked polyubiquitination of ER alpha. In conclusion, our data implicate a nongenomic mechanism by which TRIM3 stabilizes the ER alpha protein to control ER alpha target gene expression linked to breast cancer progression.

Conclusion
Our study provides a novel posttranslational mechanism in estrogen signaling. Modulation of TRIM3 expression or function could be an interesting approach for breast cancer treatment.

Graphical abstract
Extracorporeal membrane oxygenation for severe COVID-19-associated acute respiratory distress syndrome in Poland: a multicenter cohort study
Authors: Trejnowska Ewa , Drobiński Dominik , Knapik Piotr , Wajda-Pokrontka Marta , Szułdrzyński Konstanty , Staromłyński Jakub , Nowak Wojciech , Urlik Maciej , Ochman Marek , Goździk Waldemar , Serednicki Wojciech , Śmiechowicz Jakub , Brączkowski Jakub , Bąkowski Wojciech , Kwinta Anna , Zembala Michał O. , Suwalski Piotr 
Published: April 2022

Abstract
Background
In Poland, the clinical characteristics and outcomes of patients with COVID-19 requiring extracorporeal membrane oxygenation (ECMO) remain unknown. This study aimed to answer these unknowns by analyzing data collected from high-volume ECMO centers willing to participate in this project.

Methods
This retrospective, multicenter cohort study was completed between March 1, 2020, and May 31, 2021 (15 months). Data from all patients treated with ECMO for COVID-19 were analyzed. Pre-ECMO laboratory and treatment data were compared between non-survivors and survivors. Independent predictors for death in the intensive care unit (ICU) were identified.

Results
There were 171 patients admitted to participating centers requiring ECMO for refractory hypoxemia due to COVID-19 during the defined time period. A total of 158 patients (mean age: 46.3 ± 9.8 years) were analyzed, and 13 patients were still requiring ECMO at the end of the observation period. Most patients (88%) were treated after October 1, 2020, 77.8% were transferred to ECMO centers from another facility, and 31% were transferred on extracorporeal life support. The mean duration of ECMO therapy was 18.0 ± 13.5 days. The crude ICU mortality rate was 74.1%. In the group of 41 survivors, 37 patients were successfully weaned from ECMO support and four patients underwent a successful lung transplant. In-hospital death was independently associated with pre-ECMO lactate level (OR 2.10 per 1 mmol/L, p = 0.017) and BMI (OR 1.47 per 5 kg/m2, p = 0.050).

Conclusions
The ICU mortality rate among patients requiring ECMO for COVID-19 in Poland was high. In-hospital death was independently associated with increased pre-ECMO lactate levels and BMI.
Women’s decision-making capacity and its association with comprehensive knowledge of HIV/AIDS in 23 sub-Saharan African countries
Authors: Zegeye Betregiorgis , Anyiam Felix Emeka , Ahinkorah Bright Opoku , Ameyaw Edward Kwabena , Budu Eugene , Seidu Abdul-Aziz , Yaya Sanni 
Published: April 2022

Abstract
Background
Globally, Human Immunodeficiency Virus (HIV) that causes Acquired Immunodeficiency Syndrome (AIDS) remains a public health problem with a higher burden in sub-Saharan African countries. Though the coverage is low in sub-Saharan Africa (SSA), comprehensive knowledge about HIV is vital for preventing and controlling the transmission of the virus. Women’s decision-making power is significantly linked with the knowledge and use of healthcare services. However, there is no available evidence on women’s decision-making capacity and comprehensive knowledge of HIV. Therefore, this study investigated the association between women’s decision-making capacity within households and comprehensive knowledge of HIV/AIDS in SSA.

Methods
We derived data from the 2010 to 2020 Demographic and Health Surveys of 23 sub-Saharan African countries for the analysis. Using Stata version 14, both bivariate logistic regression and multivariate multilevel logistic regression analyses were used to examine the association between women’s decision-making capacity and comprehensive knowledge of HIV/AIDS at p ≤ 0.05. Results were reported using adjusted odds ratios (aOR) with their respective 95% confidence interval (CI).

Results
The pooled results show that comprehensive HIV/AIDS knowledge among married women in the studied countries was 35.5%, from 18.3% in Chad to 77.1% in Rwanda. Regarding sub-regional distribution, comprehensive knowledge of HIV/AIDS in Southern Africa was 73.2%, followed by East Africa (52.4%), West Africa (43.6%), and Central Africa (35.5%). The study showed higher odds of comprehensive knowledge of HIV/AIDS among married women who had decision making power (yes-aOR = 1.20, 95% CI; 1.16–1.25) compared to those who had no decision-making power. Age, women and partner’s level of education, place of residence, exposure to media, HIV testing status, community socio-economic status, parity, religion, and distance to health facilities also had significant association with comprehensive HIV/AIDS knowledge.

Conclusions
Comprehensive knowledge of HIV/AIDS in SSA is low but varies per country. Married women with decision-making capacity were more likely to have comprehensive knowledge of HIV compared to those with no decision-making capacity. Therefore, comprehensive knowledge of HIV/AIDS can be increased through enhancing women’s decision-making capacities, strengthening employment opportunities, socioeconomic capacities and creating awareness through media. Moreover, improving access to health care facilities working closely with religious leaders, can be considered to increase coverage of comprehensive knowledge of HIV among married women in SSA.
Addressing child undernutrition in Tanzania with the ASTUTE program
Authors: Beckstead E , Mulokozi G , Jensen M , Smith J , Baldauf M , Dearden K. A. , Linehan M. , Torres S. , Glenn J. , West J. H. , Hall P. C. , Crookston B. T. 
Published: April 2022

Abstract
Background
Optimal infant and young child feeding practices (IYCFP) reduce childhood stunting and are associated with additional health benefits. In Tanzania, IYCFP are far from optimal where 32% of children under the age of 5 years are stunted. The purpose of this study was to examine whether behavior change communication focused on reducing child undernutrition was associated with improved IYCFP in Tanzania.

Methods
A cross-sectional survey was administered to approximately 10,000 households with children under the age of 2 at baseline and endline. Bivariate analyses and logistic regression was used to examine the relationship between exposure to behavior change communication and timely initiation of breastfeeding, exclusive breastfeeding, continued breastfeeding at one year, timely complementary feeding (CF), minimum meal frequency (MMF), minimum dietary diversity (MDD), and minimum acceptable diet (MAD).

Results
Mothers who heard a radio spot about IYCFP were more likely than mothers who had not heard a radio spot about IYCFP to begin complementary foods at six months. Their children were also more likely to achieve MMF, MDD, and MAD with odds ratios of 2.227 (p = 0.0061), 1.222 (p = 0.0454), 1.618 (p =  < .0001), and 1.511 (p = 0.0002), respectively. Mothers who saw a TV spot about IYCFP were more likely to have greater odds of knowing when to begin complementary feeding, feeding their child a minimally diverse diet (4 food groups or more), and serving a minimum acceptable diet with odds ratios of 1.335 (p = 0.0081),
1.360 (p = 0.0003), and 1.268 (p = 0.0156), respectively.

Conclusion
Exposure to behavior change communication in Tanzania was generally associated with some increased knowledge of optimal IYCFP as well as practicing IYCF behaviors. Behavior change communication planners and implementers may want to consider conducting similar campaigns as an important component of behavior change to reduce undernutrition and poor health outcomes in developing settings.