bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization of hybrid virulence plasmids in ST11-KL64 KPC-2-producing multidrug-resistant hypervirulent Klebsiella pneumoniae from China
Authors: Zhang Fushan , Li Leyuan , Zhao Yuxin , Dong Huiyue , Zhao Buhui , Zhao Xiaoyu , Xia Ziwei , Chi Leizi , Wang Yan , Li Ruichao , Qin Shangshang , Fu Xiangjing 
Published: March 2024

IntroductionCarbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKP) strains combining virulence and multidrug resistance (MDR) features pose a great public health concern. The aim of this study is to explore the evolutionary characteristics of virulence in CR-HvKP by investigating the genetic features of resistance and virulence hybrid plasmids.MethodsThe resistance and virulence phenotypes were determined by using antimicrobial susceptibility testing and the mouse bacteremia infection model, respectively. Plasmid profiles were investigated by S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting, conjugation assay, and whole genome sequencing (WGS). Bioinformatics tools were used to uncover the genetic features of the resistance and virulence hybrid plasmids.ResultsTwo ST11-KL64 CRKP clinical isolates (KP18-3-8 and KP18-2079), which exhibited enhanced virulence compared with the classic CRKP, were detected positive for blaKPC−2 and rmpA2. The virulence level of the hypermucoviscous strain KP18-3-8 was higher than that of KP18-2079. S1-PFGE, Southern hybridization and WGS analysis identified two novel hybrid virulence plasmids in KP18-3-8 (pKP1838-KPC-vir, 228,158 bp) and KP18-2079 (pKP1838-KPC-vir, 182,326 bp), respectively. The IncHI1B/repB-type plasmid pKP1838-KPC-vir co-harboring blaKPC−2 and virulence genes (rmpA2, iucABCD and iutA) but lacking type IV secretion system could transfer into non-hypervirulent ST11 K. pneumoniae with the assistance of a helper plasmid in conjugation. The IncFII/IncR-type virulence plasmid pKP18-2079-vir may have been generated as a result of recombination between a typical pLVPK-like virulence plasmid and an MDR plasmid.ConclusionOur studies further highlight co-evolution of the virulence and resistance plasmids in ST11-CRKP isolates. Close surveillance of such hybrid virulence plasmids in clinical K. pneumoniae should be performed.
Construction of cellulose-degrading microbial consortium and evaluation of their ability to degrade spent mushroom substrate
Authors: Long Junqiao , Wang Xueli , Qiu Shuyi , Zhou Wei , Zhou Shaoqi , Shen Kaiwei , Xie Lili , Ma Xiao , Zhang Xuyi 
Published: March 2024

IntroductionSpent mushroom substrate (SMS) is a solid waste in agricultural production that contains abundant lignocellulosic fibers. The indiscriminate disposal of SMS will lead to significant resource waste and pollution of the surrounding environment.The isolation and screening of microorganisms with high cellulase degradation capacity is the key to improving SMS utilization.MethodsThe cellulose-degrading microbial consortiums were constructed through antagonism and enzyme activity test. The effect of microbial consortiums on lignocellulose degradation was systematically evaluated by SMS liquid fermentation experiments.ResultsIn this study, four strains of cellulose-degrading bacteria were screened, and F16, F, and F7 were identified as B. amyloliquefaciens, PX1 identified as B. velezensis. At the same time, two groups of cellulose efficient degrading microbial consortiums (PX1 + F7 and F16 + F) were successfully constructed. When SMS was used as the sole carbon source, their carboxymethyl cellulase (CMCase) activities were 225.16 and 156.63 U/mL, respectively, and the filter paper enzyme (FPase) activities were 1.91 and 1.64 U/mL, respectively. PX1 + F7 had the highest degradation rate of hemicellulose and lignin, reaching 52.96% and 52.13%, respectively, and the degradation rate of F16 + F was as high as 56.30%. Field emission scanning electron microscopy (FESEM) analysis showed that the surface microstructure of SMS changed significantly after microbial consortiums treatment, and the change of absorption peak in Fourier transform infrared spectroscopy (FTIR) and the increase of crystallinity in X-ray diffraction (XRD) confirmed that the microbial consortiums had an actual degradation effect on SMS. The results showed that PX1 + F7 and F16 + F could effectively secrete cellulase and degrade cellulose, which had practical significance for the degradation of SMS.DiscussionIn this study, the constructed PX1 + F7 and F16 + F strains can effectively secrete cellulase and degrade cellulose, which holds practical significance in the degradation of SMS. The results can provide technical support for treating high-cellulose solid waste and for the comprehensive utilization of biomass resources.
Correlational patterns of neuronal activation and epigenetic marks in the basolateral amygdala and piriform cortex following olfactory threat conditioning and extinction in rats
Authors: Qin Tian , Xia Yue , Nazari Negar , Sepahvand Tayebeh , Yuan Qi 
Published: March 2024

IntroductionCumulative evidence suggests that sensory cortices interact with the basolateral amygdala (BLA) defense circuitry to mediate threat conditioning, memory retrieval, and extinction learning. The olfactory piriform cortex (PC) has been posited as a critical site for olfactory associative memory. Recently, we have shown that N-methyl-D-aspartate receptor (NMDAR)-dependent plasticity in the PC critically underpins olfactory threat extinction. Aging-associated impairment of olfactory threat extinction is related to the hypofunction of NMDARs in the PC.MethodsIn this study, we investigated activation of neuronal cFos and epigenetic marks in the BLA and PC using immunohistochemistry, following olfactory threat conditioning and extinction learning in rats.ResultsWe found highly correlated cFos activation between the posterior PC (pPC) and BLA. cFos was correlated with the degree of behavioral freezing in the pPC in both adult and aged rats, and in the BLA only in adult rats. Markers of DNA methylation 5 mC and histone acetylation H3K9/K14ac, H3K27ac, and H4ac exhibited distinct training-, region-, and age-dependent patterns of activation. Strong correlations of epigenetic marks between the BLA and pPC in adult rats were found to be a general feature. Conversely, aged rats only exhibited correlations of H3 acetylations between the two structures. Histone acetylation varied as a function of aging, revealed by a reduction of H3K9/K14ac and an increase of H4ac in aged brains at basal condition and following threat conditioning.DiscussionThese findings underscore the coordinated role of PC and BLA in olfactory associative memory storage and extinction, with implications for understanding aging related cognitive decline.
Development of celiac-safe foods: prevention of transglutaminase 2 (TG2) deamidation of gluten in healthy non-celiac volunteers
Authors: Engström Niklas , Böhn Lena , Josefsson Axel , Störsrud Stine , Scheers Nathalie 
Published: March 2024

In celiac disease, intestinal transglutaminase (TG2) produces immunogenic peptides by deamidation of gluten proteins. These products drive the celiac immune response. We have previously identified an interaction between gliadin and a food additive, E304i, which prevents gliadin processing (both deamidation and transamidation) by TG2, in vitro. In this study, we investigated if E304i could prevent TG2 processing of gluten in flours and if the effect was evident after simulated gastrointestinal digestion. We also confirmed the outcome in vivo in a human cross-over intervention study in healthy non-celiac participants. TG2 transamidation experiments (in vitro) of digested wheat and rye flours supplemented with E304i at 30 mg/g indicated full prevention of TG2 processing. In the intervention study, participant serum levels of deamidated gliadin peptides (dGDPs) increased after the intake of reference wheat rolls (80 g per day for a week; 41% ± 4% compared to washout), while the intake of the intervention E304i/zinc sulfate wheat rolls generated a modest response (80 g per day for a week; 8 ± 10% of control). The difference between the groups (32.8 ± 15.6%) was significant (p = 0.00003, n = 9), confirming that E304i /zinc addition to wheat rolls prevented TG2 deamidation of gluten. In conclusion, this study shows that E304i /zinc addition to wheat rolls prevents TG2 deamidation of gluten in non-celiac participants.Clinical trial registrationclinicaltrials.gov, identifier (NCT06005376).
A systematic review and narrative synthesis of prevalence rates, risk and protective factors for suicidal behavior in international students
Authors: Veresova Maria , Lamblin Michelle , Robinson Jo , McKay Samuel 
Published: March 2024

International students are a crucial group for suicide prevention efforts. However, no comprehensive review of the prevalence, risk or protective factors for international student suicide has been conducted, complicating prevention efforts. The current systematic review addresses this issue by identifying the prevalence, risk, and protective factors for suicidal thoughts and behavior in international students enrolled in tertiary institutions. We searched CINAHL, EMBASE, ERIC, Medline, and PsycInfo from inception to November 2023, and 24 papers met the study inclusion criteria. Nineteen studies reported on the prevalence or intensity of suicidal ideation, six reported on the prevalence of suicide attempts, and seven on the prevalence of self-harm. No studies provided data on completed suicides. Studies indicated that international students experienced similar or lower levels of suicidal ideation and self-harm, but more frequent suicide attempts than domestic students. A narrative synthesis of risk and protective factors yielded mixed results, although social isolation, comorbid mental health conditions, and experiences of racism or discrimination were commonly linked to suicidal thoughts and behaviors. The mixed evidence quality, numerous measurement issues, and low number of studies in the literature point to a need for further research on suicide among international students.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022307252.
Acute Stress Disorder among 2022 Ukrainian war refugees: a cross-sectional study
Authors: Kordel Piotr , Rządeczka Marcin , Studenna-Skrukwa Marta , Kwiatkowska-Moskalewicz Katarzyna , Goncharenko Olga , Moskalewicz Marcin 
Published: March 2024

IntroductionFleeing from war can be terrifying and result in Acute Stress Disorder (ASD), a mental health condition that can occur in the first month after a traumatic event. The study aimed to identify the prevalence of ASD among Ukrainian refugees and identify its risk factors to create a profile of the most vulnerable refugees.MethodsThis cross-sectional study of 637 Ukrainian war-displaced persons and refugees in 2022 used the Acute Stress Disorder Scale.ResultsThe prevalence of ASD among participants was high (93.5%). Several factors increasing the risk of developing ASD in the sample were identified, e.g., witnessing Russian attacks (OR 2.92, 95% CI 1.26–6.78), insufficient financial resources (OR 3.56, 95% CI 1.61–7.91), and feeling of loneliness in the host country (OR 3.07, 95% CI 1.58–8.69). Pre-existing depression and the death of a close person, among others, were found to significantly (p &lt; 0.05) exacerbate the ASD symptoms. At the same time, neither age, the distance traveled, time spent on fleeing the country, nor the type of companionship during refuge (escaping alone, with children, pets or the older adults) correlate with the severity of symptoms.ConclusionThe study shows extreme levels of trauma among Ukrainian war refugees and displaced persons. Knowledge regarding ASD vulnerabilities in the present conflict may facilitate prompt and adequate psychological help. Since ASD can be an antecedent of PTSD and several autoimmune disorders, these results may also serve as a predictor of future challenges for Ukrainian society.
Appraisal of universal health insurance and maternal health services utilization: pre- and post-context of the Jaminan Kesehatan Nasional implementation in Indonesia
Authors: Rahmawati Tati , Hsieh Hui-Min 
Published: March 2024

IntroductionThe Indonesian government introduced universal health insurance through the National Social Security System (JKN) in 2014 to enhance overall healthcare. This study compares maternal health care (MHC) service utilization before and after JKN implementation in Indonesia.MethodUsing 2012 and 2017 data from Indonesia Demographic and Health Surveys (DHS), we conducted a two-period cross-sectional design study following the Anderson model. We assessed how the JKN policy and population characteristics influenced healthcare utilization for women aged 15–49 who had given birth in the last 5 years. Multivariable logistic regression models were used to assess the impact of the JKN policy and related factors.ResultIn two waves of Indonesia DHS with 14,782 and 15,021 subjects, this study observed a significant increase in maternal healthcare service utilization post-JKN implementation. Women were more likely to have at least four antenatal care visits (adjusted odds ratio, AOR = 1.17), receive skilled antenatal care (AOR = 1.49), obtain skilled birth assistance (AOR = 1.96), and access facility-based delivery (AOR = 2.45) compared with pre-JKN implementation.ConclusionThis study revealed a significant positive impact of JKN on enhancing MHS utilization. The introduction of universal health insurance coverage likely reduced financial barriers for specific demographics, resulting in increased service utilization. Our study may offer valuable insights for Asian countries with similar demographics and health insurance implementations.
COVID-19 vaccination and the risk of autoimmune diseases: a Mendelian randomization study
Authors: Shan Jiayi , Hu Xiaoyun , Chen Tianzhu , Wang Yuyang , Huang Baoyi , Xin Yijun , Xu Hua 
Published: March 2024

BackgroundIn recent times, reports have emerged suggesting that a variety of autoimmune disorders may arise after the coronavirus disease 2019 (COVID-19) vaccination. However, causality and underlying mechanisms remain unclear.MethodsWe collected summary statistics of COVID-19 vaccination and 31 autoimmune diseases from genome-wide association studies (GWAS) as exposure and outcome, respectively. Random-effects inverse variance weighting (IVW), MR Egger, weighted median, simple mode, and weighted mode were used as analytical methods through Mendelian randomization (MR), and heterogeneity and sensitivity analysis were performed.ResultsWe selected 72 instrumental variables for exposure (p &lt; 5 × 10−6; r2 &lt; 0.001, genetic distance = 10,000 kb), and MR analyses showed that COVID-19 vaccination was causally associated with an increased risk of multiple sclerosis (MS) (IVW, OR: 1.53, 95% CI: 1.065–2.197, p = 0.026) and ulcerative colitis (UC) (IVW, OR: 1.00, 95% CI: 1.000–1.003, p = 0.039). If exposure was refined (p &lt; 5 × 10−8; r2 &lt; 0.001, genetic distance = 10,000 kb), the associations became negative. No causality was found for the remaining outcomes. These results were robust to sensitivity and heterogeneity analyses.ConclusionOur study provided potential evidence for the impact of COVID-19 vaccination on the risk of MS and UC occurrence, but it lacks sufficient robustness, which could provide a new idea for public health policy.
Time-series analysis of the association between air pollution exposure and outpatient visits for dry eye disease: a case study in Zhengzhou, China
Authors: Xia Mengting , Yang Yingrui , Sun Jiali , Huang Ranran , Huang Yonghui , Zhang Mengqi , Yao Xi 
Published: March 2024

BackgroundDry eye disease (DED) is a prevalent ocular surface disease that significantly impacts patients’ quality of life. The association between air pollution and the risk of dry eye disease remains uncertain.MethodsData on outdoor air pollutants, meteorological information, and outpatient visits for DED were collected from July 1, 2014, to December 31, 2019. The relationship between ambient air pollutants and DED outpatient visits was analyzed using a generalized additive model with a Poisson distribution.ResultsAmong the 5,204 DED patients included in the study, 63.76% were female and 36.24% were male. The single-pollutant model revealed a significant association between a 10 μg/m3 increase in concentrations of fine-particulate matter with a median aerometric diameter of less than 10 μm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO) and outpatient visits for DED. Fine-particulate matter with a median aerometric diameter of less than 2.5 μm (PM2.5) showed a significant association with DED outpatient visits in males and the 19–59 years age group. The strongest associations between air pollutants and outpatient visits were observed in male patients and during the cold season.ConclusionThe noteworthy correlation between air pollutants and DED outpatient visits can offer evidence for policy makers and underscore the significance of reinforcing environmental protection.
Operational tolerance research in liver transplantation: a bibliometric analysis using a new web resource
Authors: Esteban-Gil Ángel , Martínez-García Juan José , Vidal-Correoso Daniel , Muñoz-Morales Ana M. , Ramírez Pablo , Pons José Antonio , Baroja-Mazo Alberto 
Published: March 2024

BackgroundOperational tolerance in liver transplantation (OT-LT), defined as the graft survival with normal function in absence of immunosuppression, has been a field of intense research since the 1980s. Thereafter, tens of clinical trials and hundreds of articles have been published, making it challenging for researchers to assimilate all the information, more so outside of their disciplines. The aim of the present study was to analyze the research in OT-LT through a new web tool (https://tolerance.imib.es).MethodsWe have developed a web resource that allowed the identification of the present trends and potential research avenues in OL-LT, an overview biomedical terms that were most often cited, including which journals published the most articles, and an advanced search engine that exploited all the information in these publications.ResultsA total of 734 studies were analyzed until November 2023, with a mean of 15 articles published per year, a total sum of 3,751 impact factor points and a total of 26,542 citations. The analysis of citations allowed us to establish a ranking of the most prolific countries, authors, journals and institutions, in addition to the most influential publications in OT-LT. Likewise, keyword and co-occurrence analyses answered which themes involving OT-LT are the most popular, whereas cooperation analysis showed that principal authors in OT-LT form a network, although the lack of international cooperation, especially with regard to clinical trials, appears to be one of the main challenges.ConclusionDespite its limitations, our web tool will allow both OT-LT expert and novel researchers to be able to draw a comprehensive picture of the past, present and future of OT-LT research.
Enhancement of innate immunity in gingival epithelial cells by vitamin D and HDAC inhibitors
Authors: Figgins Erika L. , Arora Payal , Gao Denny , Porcelli Emily , Ahmed Rabab , Daep Carlo Amorin , Keele Garrett , Ryan Lisa K. , Diamond Gill 
Published: March 2024

IntroductionThe human host defense peptide LL-37 is a component of the innate immune defense mechanisms of the oral cavity against colonization by microbes associated with periodontal disease. We have previously shown that the active form of vitamin D, 1,25(OH)2D3, can induce the expression of LL-37 in gingival epithelial cells (GEC), and prevent the invasion and growth of periopathogenic bacteria in these cells. Further, experimental vitamin D deficiency resulted in increased gingival inflammation and alveolar bone loss. Epidemiological studies have shown associations between vitamin D deficiency and periodontal disease in humans, suggesting application of vitamin D could be a useful therapeutic approach. Further, since we have shown the local activation of vitamin D by enzymes expressed in the GEC, we hypothesized that we could observe this enhancement with the stable, and inexpensive inactive form of vitamin D, which could be further increased with epigenetic regulators.MethodsWe treated 3-dimensional primary cultures of GEC topically with the inactive form of vitamin D, in the presence and absence of selected histone deacetylase (HDAC) inhibitors. LL-37 mRNA levels were quantified by quantitative RT-PCR, and inhibition of invasion of bacteria was measured by fluorescence microscopy.ResultsVitamin D treatment led to an induction of LL-37 mRNA levels, as well as an inhibition of pro-inflammatory cytokine secretion. This effect was further enhanced by HDAC inhibitors, most strongly when the HDAC inhibitor, phenyl butyrate (PBA) was combined with Vitamin D3. This was observed both in solution and in a prototype gel formulation using sodium butyrate. Finally, this combination treatment led to an increase in the antimicrobial activity against infection by Porphyromonas gingivalis and Filifactor alocis, bacteria associated with periodontal lesions, as well as herpes simplex virus, which has also been shown to be associated with periodontal lesions.ConclusionsOur results demonstrate that a combination of inactive vitamin D and sodium butyrate could be developed as a safe treatment for periodontal disease.
Evolution of attack in handball when playing 7 vs. 6 with empty goal between 2020 and 2023: coaches’ perception vs. observational results
Authors: Prudente João Nunes , Cardoso Américo Ramos , Rodrigues Ana José , Mendes João N. , Fernando Catarina , Lopes Helder , Trejo-Silva Alejandro , Sousa Duarte Filipe 
Published: March 2024

IntroductionRecently, several studies on the 7 vs. 6 “empty goal” (EG) in handball have produced different and even contradictory results. The aim of the present study was to investigate the behavior of teams and players in the 7 vs. 6 EG attack in the European (Euro) and World Championships (WCh) between 2020 and 2023 and characterize the coaches’ perceptions.MethodsA mixed-methods approach was used, consisting of the following: (i) an observational methodology and instrument developed and validated to collect observational data on player and team behavior; and (ii) a developed and validated questionnaire to coaches on their perceptions of the 7 vs. 6 game. Observational data were collected during the Euro 2020 and 2022 games (n = 62) and the WCh 2021 and 2023 games (n = 70). A total of 132 games and 391 situations of 7 vs. 6 attacking sequences were observed. In total, 156 coaches participated (146 men), with a mean age 42.33 ± 11.87 years, 19 nationalities, and with 12.77 ± 9.45 years of experience.Results and discussionThe choice of 7 vs. 6 offensive play was mostly made in the second half (&gt;73%). The effectiveness of 7 vs. 6 offensive sequences was higher in the top six teams than in the team's ranked 7th to 12th (Euro 2020 51.6%–50.0%; WCh 2021 52.0%–50.0%; Euro 2022 53.1%–41.7%; WCh 2023 50.0%–43.8%). Some patterns of association were found (p &lt; 0.05 and with values &gt;±1.96): (i) scoring a goal with a breakthrough shot was significantly associated with the effectiveness of the 7 vs. 6 attack (Euro 2020 2.61; WCh 2021 2.87; Euro 2022 2.68; WCh 2023 2.32); (ii) teams in the top six significantly used 7 vs. 6 when they were winning (Euro 2020 2.17; WCh 2021 3.52; Euro 2022 5.88; WCh 2023 2.54); and (iii) teams in the bottom six used it when they were losing by at least four goals (Euro 2020 7.56; Euro 2022 6.64; WCh 2023 4.37) or when they were winning by four goals or more (WCh 2021 2.58). Coaches that agree with the possibility of playing 7 vs. 6 (74.4%), rarely or never do so (55.6%) because it brings little or no advantage (52.6%). The results of the analysis confirmed the perception of the coaches, the low use of 7 vs. 6, the low advantage associated with it, and the influence of the result and the moment of the game on its use.