bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of short birth interval among married multiparous women in Chinaksen district, eastern Ethiopia: a case-control study
Authors: Aleye Bekry , Usso Ahmedin Aliyi , Mengistie Bezatu , Dessie Yadeta , Adem Hassen Abdi , Alemu Addisu , Yuya Mohammed , Mohammed Aminu 
Published: January 2024

BackgroundThe short birth interval is a common public health issue that affects women's and children's health in sub-Saharan Africa. Despite a higher burden of short birth intervals reported in Ethiopia, there is limited evidence to indicate the primary risk factors, particularly in rural eastern Ethiopia. Therefore, this study assessed the determinants of the short birth interval among married multiparous women in Chinaksen district, Eastern Ethiopia.MethodsA community-based case-control study was conducted among randomly selected 210 cases and 210 controls from April 01 to June 30, 2019. The total sample size (219 cases and 219 controls) were calculated using Epi-Info software version 7.2. Data were entered using EpiData version 3.1 and analyzed using SPSS version 27, and multivariable logistic regression analyses conducted to identify the determinants of short birth intervals. Adjusted odds ratio (AOR) with a 95% confidence interval (CI) was used to report the strength of association and statistical significance declared at p-value &lt; 0.05.ResultsThe women in the young age group (AOR = 2.33, 95% CI: 1.03, 5.26), missed their antenatal care visits (AOR = 2.23, 95% CI: 1.18, 4.21), failed to utilize postpartum contraceptives (AOR = 5.98, 95% CI: 3.62, 9.89), did not attend postnatal care visit (AOR = 1.86, 95% CI: 1.13, 3.05), nonexclusive breastfed (AOR = 4.05, 95% CI: 2.18, 7.52), short and medium period of breastfeeding (AOR = 4.00, 95% CI: 1.34, 12.10) and (AOR = 3.56, 95% CI: 1.62, 7.82), respectively and female sex of preceding child (AOR = 1.92, 95% CI: 1.18, 3.12) were the important risk factors of short birth interval.ConclusionsWomen's age, antenatal care visits, postnatal care attendance, utilization of postpartum contraceptives, exclusive breastfeeding practice, duration of breastfeeding, and sex of the preceding child were the primary predictors of short birth intervals. Improving the utilization of maternal healthcare services in health facilities would be imperative to prevent and reduce short birth intervals, and its negative consequences.
DNases improve effectiveness of antibiotic treatment in murine polymicrobial sepsis
Authors: Willemsen Jan-Fritjof , Wenskus Julia , Lenz Moritz , Rhode Holger , Trochimiuk Madgalena , Appl Birgit , Pagarol-Raluy Laia , Börnigen Daniela , Bang Corinna , Reinshagen Konrad , Herrmann Martin , Elrod Julia , Boettcher Michael 
Published: January 2024

IntroductionNeutrophil extracellular traps (NETs) have various beneficial and detrimental effects in the body. It has been reported that some bacteria may evade the immune system when entangled in NETs. Thus, the aim of the current study was to evaluate the effects of a combined DNase and antibiotic therapy in a murine model of abdominal sepsis.MethodsC57BL/6 mice underwent a cecum-ligation-and-puncture procedure. We used wild-type and knockout mice with the same genetic background (PAD4-KO and DNase1-KO). Mice were treated with (I) antibiotics (Metronidazol/Cefuroxime), (II) DNAse1, or (III) with the combination of both; mock-treated mice served as controls. We employed a streak plate procedure and 16s-RNA analysis to evaluate bacterial translocation and quantified NETs formation by ELISA and immune fluorescence. Western blot and proteomics analysis were used to determine inflammation.ResultsA total of n=73 mice were used. Mice that were genetically unable to produce extended NETs or were treated with DNases displayed superior survival and bacterial clearance and reduced inflammation. DNase1 treatment significantly improved clearance of Gram-negative bacteria and survival rates. Importantly, the combination of DNase1 and antibiotics reduced tissue damage, neutrophil activation, and NETs formation in the affected intestinal tissue.ConclusionThe combination of antibiotics with DNase1 ameliorates abdominal sepsis. Gram-negative bacteria are cleared better when NETs are cleaved by DNase1. Future studies on antibiotic therapy should be combined with anti-NETs therapies.
HOXA3 functions as the on-off switch to regulate the development of hESC-derived third pharyngeal pouch endoderm through EPHB2-mediated Wnt pathway
Authors: Fu Yingjie , Zhang Xueyan , Wu Haibin , Zhang Pingping , Liu Shoupei , Guo Tingting , Shan Huanhuan , Liang Yan , Chen Honglin , Xie Jinghe , Duan Yuyou 
Published: January 2024

ObjectivesNormal commitment of the endoderm of the third pharyngeal pouch (3PP) is essential for the development and differentiation of the thymus. The aim of this study was to investigate the role of transcription factor HOXA3 in the development and differentiation of 3PP endoderm (3PPE) from human embryonic stem cells (hESCs).MethodsThe 3PPE was differentiated from hESC-derived definitive endoderm (DE) by mimicking developmental queues with Activin A, WNT3A, retinoic acid and BMP4. The function of 3PPE was assessed by further differentiating into functional thymic epithelial cells (TECs). The effect of HOXA3 inhibition on cells of 3PPE was subsequently investigated.ResultsA highly efficient approach for differentiating 3PPE cells was developed and these cells expressed 3PPE related genes HOXA3, SIX1, PAX9 as well as EpCAM. 3PPE cells had a strong potential to develop into TECs which expressed both cortical TEC markers K8 and CD205, and medullary TEC markers K5 and AIRE, and also promoted the development and maturation of T cells. More importantly, transcription factor HOXA3 not only regulated the differentiation of 3PPE, but also had a crucial role for the proliferation and migration of 3PPE cells. Our further investigation revealed that HOXA3 controlled the commitment and function of 3PPE through the regulation of Wnt signaling pathway by activating EPHB2.ConclusionOur results demonstrated that HOXA3 functioned as the on-off switch to regulate the development of hESC-derived 3PPE through EPHB2-mediated Wnt pathway, and our findings will provide new insights into studying the development of 3PP and thymic organ in vitro and in vivo.
Targeting STAT3 in tumor-associated antigen-presenting cells as a strategy for kidney and bladder cancer immunotherapy
Authors: Alcantara Marice B. , Tang Wilson S. , Wang Dongfang , Kaniowski Damian , Kang Elaine , Dizman Nazli , Chehrazi-Raffle Alexander , Meza Luis , Zengin Zeynep , Hall Jeremy , Hsu JoAnn , Egelston Colt , Moreira Dayson , Horsager Alan , Pal Sumanta K. , Kortylewski Marcin 
Published: January 2024

IntroductionImmune checkpoint blockade (ICB) improved clinical outcomes in renal and bladder cancer patients, but the response rates remain limited especially in metastatic disease. While STAT3 transcription factor is well-known master regulator of tumor immune evasion, little is known about the role of STAT3 in the resistance of renal or bladder cancers to immunotherapy.MethodsTo better understand immune alterations associated with ICB resistance, we assessed blood biomarkers in renal cancer patients classified as responders or non-responders to first line nivolumab/ipilimumab immunotherapy.ResultsWe observed that non-responders showed elevated levels of proinflammatory mediators, such as IL-1RA, IL-6, IL-8 and to lesser extent IL-10, which are associated with STAT3 activation and tumor immunosuppression. In addition, we found STAT3 activation primarily in circulating myeloid immune cells such as tolerogenic MDSCs. To assess whether STAT3 inhibition within these cell subsets can promote antitumor immune responses and/or enhance sensitivity to ICB in vivo, we used an original antisense oligonucleotide (ASO) strategy for myeloid-cell selective STAT3 knockdown (CpG-STAT3ASO). Our results in syngeneic models of renal and bladder cancers in mice demonstrated potent antitumor activity of CpG-STAT3ASO alone in contrast to PD1 blockade alone in both models. The CpG-STAT3ASO/anti-PD1 combination improved therapeutic efficacy especially against bladder tumors. Therapeutic efficacy correlated with activation of dendritic cells (DCs) and M1 macrophages in the tumor microenvironment, reduced percentages of regulatory T cells (Tregs) and the expansion of CD8 T cells in both tumor models.Discussion/ConclusionOur study underscores the potential of using myeloid-cell targeted CpG-STAT3 inhibitors for genitourinary cancer therapy to disrupt tolerogenic signaling, restore immune cell activity and sensitivity to immune checkpoint inhibitors and/or T cell-based immunotherapies.
A zinc metabolism-related gene signature for predicting prognosis and characteristics of breast cancer
Authors: Hong Jinghui , Li Mengxin , Chen Yichang , Du Ye , Song Dong 
Published: January 2024

BackgroundBreast cancer is one of the most serious and prevalent malignancies. Zinc is commonly known to play a crucial role in the development and progression of breast cancer; however, the detailed mechanisms underlying this role are not well understood. This study aimed to develop a zinc metabolism-related gene (ZMRG) signature based on a multi-database study to predict patient prognosis and investigate the relationship between drug therapy response and immune enrichment.MethodsData for breast cancer samples from The Cancer Genome Atlas and Gene Expression Omnibus databases were screened for zinc metabolism-related genes using the Molecular Signature Database. Cox and Least Absolute Shrinkage and Selection Operator regressions were performed to construct a ZMRG signature. To assess the predictive performance of the gene signature, Kaplan–Meier analysis and receiver operating characteristic curves were used. Additionally, we utilised single-sample gene set enrichment analysis, the Tumour Immune Estimation Resource, the Genomics of Drug Sensitivity in Cancer database, and the Cancer Therapeutics Response Portal to investigate the association between the tumour microenvironment and drug sensitivity. Quantitative PCR was used to assess the expression of each gene in the signature in breast cancer cell lines and patient samples.ResultsFive ZMRGs were identified (ATP7B, BGLAP, P2RX4, SLC39A11, and TH) and a risk profile was constructed for each. Two risk groups, high- and low-risk, were identified in this way, and the high-risk score subgroups were found to have worse prognosis. This risk profile was validated using the GSE42568 dataset. Tumour microenvironment and drug sensitivity analyses showed that the expression of these five ZMRGs was significantly associated with immune response. The high-risk group showed substantial immune cell infiltration and enrichment of immune pathways, and patients were more sensitive to drugs commonly used in breast cancer.ConclusionThe ZMRG signature represents a new prognostic predictor for patients with breast cancer, and may also provide new insights into individualised treatment of breast cancer.
J-shaped association of dietary catechins intake with the prevalence of osteoarthritis and moderating effect of physical activity: an American population-based cohort study
Authors: Fu Yuesong , Li Lu , Gao Jing , Wang Fazheng , Zhou Zihan , Zhang Yiwei 
Published: January 2024

BackgroundCatechins are a class of natural compounds with a variety of health benefits, The relationship between catechins and the prevalence of osteoarthritis (OA) is unknown. This study investigated the associations between daily intake of catechins and the prevalence of OA among American adults and assessed the moderating effect of physical activity (PA).MethodsThis study included 10,039 participants from the National Health and Nutrition Examination Survey (2007–2010,2017-2018). The logistic regression, weighted quantile sum (WQS) regression, and restricted cubic spline (RCS) regression models were conducted to explore the associations between daily intake of catechins and the prevalence of OA. Moreover, interaction tests were performed to assess the moderating effect of PA.ResultsAfter multivariable adjustment, the weighted multivariable logistic regression and RCS regression analyses revealed significant J-shaped non-linear correlations between intakes of epigallocatechin and epigallocatechin 3-gallate had significant associations with the prevalence of OA among in U.S. adults. WQS regression analysis showed that excessive epigallocatechin intake was the most significant risk factor for OA among all subtypes of catechins. In the interaction assay, PA showed a significant moderating effect in the relationship between epigallocatechin intake and OA prevalence.ConclusionsThe intake of gallocatechin and gallocatechin 3-gallate had a significant negative correlation with the prevalence of OA and the dose-response relationship was J-shaped.PA below 150 MET-min/week and the threshold intakes of 32.70mg/d for epigallocatechin and 76.24mg/d for epigallocatechin 3-gallate might be the targets for interventions to reduce the risk of developing OA.
PRMT5 regulates epigenetic changes in suppressive Th1-like iTregs in response to IL-12 treatment
Authors: Jadon Nidhi , Shanthalingam Sudarvili , Tew Gregory N. , Minter Lisa M. 
Published: January 2024

BackgroundInduced regulatory T cells (iTregs) are a heterogeneous population of immunosuppressive T cells with therapeutic potential. Treg cells show a range of plasticity and can acquire T effector-like capacities, as is the case for T helper 1 (Th1)-like iTregs. Thus, it is important to distinguish between functional plasticity and lineage instability. Aplastic anemia (AA) is an autoimmune disorder characterized by immune-mediated destruction of hematopoietic stem and progenitor cells in the bone marrow (BM). Th1-like 1 iTregs can be potent suppressors of aberrant Th1-mediated immune responses such as those that drive AA disease progression. Here we investigated the function of the epigenetic enzyme, protein arginine methyltransferase 5 (PRMT5), its regulation of the iTreg-destabilizing deacetylase, sirtuin 1 (Sirt1) in suppressive Th1-like iTregs, and the potential for administering Th1-like iTregs as a cell-based therapy for AA.MethodsWe generated Th1-like iTregs by culturing iTregs with IL-12, then assessed their suppressive capacity, expression of iTreg suppression markers, and enzymatic activity of PRMT5 using histone symmetric arginine di-methylation (H3R2me2s) as a read out. We used ChIP sequencing on Th1 cells, iTregs, and Th1-like iTregs to identify H3R2me2s-bound genes unique to Th1-like iTregs, then validated targets using CHiP-qPCR. We knocked down PRMT5 to validate its contribution to Th1-like iTreg lineage commitment. Finally we tested the therapeutic potential of Th1-like iTregs using a Th1-mediated mouse model of AA.ResultsExposing iTregs to the Th1 cytokine, interleukin-12 (IL-12), during early events of differentiation conveyed increased suppressive function. We observed increased PRMT5 enzymatic activity, as measured by H3R2me2s, in Th1-like iTregs, which was downregulated in iTregs. Using ChIP-sequencing we discovered that H3R2me2s is abundantly bound to the Sirt1 promoter region in Th1-like iTregs to negatively regulate its expression. Furthermore, administering Th1-like iTregs to AA mice provided a survival benefit.ConclusionsKnocking down PRMT5 in Th1-like iTregs concomitantly reduced their suppressive capacity, supporting the notion that PRMT5 is important for the superior suppressive capacity and stability of Th1-like iTregs. Conclusively, therapeutic administration of Th1-like iTregs in a mouse model of AA significantly extended their survival and they may have therapeutic potential.
Systemic inflammation response index is a useful indicator in distinguishing MOGAD from AQP4-IgG-positive NMOSD
Authors: Wang Lei , Xia Ruihong , Li Xiangliang , Shan Jingli , Wang Shengjun 
Published: January 2024

ObjectiveTo identify reliable immune-inflammation indicators for distinguishing myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) from anti–aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSD). To assess these indicators’ predictive significance in MOGAD recurrence.MethodsThis study included 25 MOGAD patients, 60 AQP4-IgG-positive NMOSD patients, and 60 healthy controls (HCs). Age and gender were matched among these three groups. Participant clinical and imaging findings, expanded disability status scale (EDSS) scores, cerebrospinal fluid (CSF) information, and blood cell counts were documented. Subsequently, immune-inflammation indicators were calculated and compared among the MOGAD, AQP4-IgG-positive NMOSD, and HC groups. Furthermore, we employed ROC curve analysis to assess the predictive performance of each indicator and binary logistic regression analysis to assess potential risk factors.ResultsIn MOGAD patients, systemic inflammation response index (SIRI), CSF white cell count (WCC), and CSF immunoglobulin A (IgA) levels were significantly higher than in AQP4-IgG-positive NMOSD patients (p = 0.038, p = 0.039, p = 0.021, respectively). The ROC curves showed that SIRI had a sensitivity of 0.68 and a specificity of 0.7 for distinguishing MOGAD from AQP4-IgG-positive NMOSD, with an AUC of 0.692 (95% CI: 0.567-0.818, p = 0.0054). Additionally, compared to HCs, both MOGAD and AQP4-IgG-positive NMOSD patients had higher neutrophils, neutrophil-to-lymphocyte ratio (NLR), SIRI, and systemic immune-inflammation index (SII). Eight (32%) of the 25 MOGAD patients had recurrence within 12 months. We found that the monocyte-to-lymphocyte ratio (MLR, AUC = 0.805, 95% CI = 0.616–0.994, cut-off value = 0.200, sensitivity = 0.750, specificity = 0.882) was an effective predictor of MOGAD recurrence. Binary logistic regression analysis showed that MLR below 0.200 at first admission was the only risk factor for recurrence (p = 0.005, odds ratio =22.5, 95% CI: 2.552–198.376).ConclusionElevated SIRI aids in distinguishing MOGAD from AQP4-IgG-positive NMOSD; lower MLR levels may be linked to the risk of MOGAD recurrence.
Diffusion tensor imaging and plasma immunological biomarker panel in a rat traumatic brain injury (TBI) model and in human clinical TBI
Authors: To Xuan Vinh , Mohamed Abdalla Z. , Cumming Paul , Nasrallah Fatima A. 
Published: January 2024

IntroductionNeuroinflammatory reactions play a significant role in the pathology and long-term consequences of traumatic brain injury (TBI) and may mediate salutogenic processes that white matter integrity. This study aimed to investigate the relationship between inflammatory markers and white matter integrity following TBI in both a rat TBI model and clinical TBI cases. MethodsIn the rat model, blood samples were collected following a controlled cortical impact (CCI) to assess a panel of inflammatory markers; MR-based diffusion tensor imaging (DTI) was employed to evaluate white matter integrity 60 days post-injury. 15 clinical TBI patients were similarly assessed for a panel of inflammatory markers and DTI post-intensive care unit discharge. Blood samples from healthy controls were used for comparison of the inflammatory markers. ResultsTime-dependent elevations in immunological markers were observed in TBI rats, with a correlation to preserved fractional anisotropy (FA) in white matter. Specifically, TBI-induced increased plasma levels of IL-1β, IL-6, G-CSF, CCL3, CCL5, and TNF-α were associated with higher white matter integrity, as measured by FA. Clinical cases had similar findings: elevated inflammatory markers (relative to controls) were associated with preservation of FA in vulnerable white matter regions. DiscussionInflammatory markers in post-TBI plasma samples are ambivalent with respect to prediction of favourable outcome versus a progression to more pervasive pathology and morbidity.
Lysophosphatidylcholine acyltransferase level predicts the severity and prognosis of patients with community-acquired pneumonia: a prospective multicenter study
Authors: Chen Li , Xue Jianbo , Zhao Lili , He Yukun , Fu Shining , Ma Xinqian , Yu Wenyi , Tang Yanfen , Wang Yu , Gao Zhancheng 
Published: January 2024

BackgroundIdentifying the diagnosis as well as prognosis for patients presented with community-acquired pneumonia (CAP) remains challenging. We aimed to identify the role of lysophosphatidylcholine acyl-transferase (LPCAT) for CAP along with assessing this protein’s effectiveness as a biomarker for severity of disease and mortality.MethodsProspective multicenter research study was carried out among hospitalized patients. A total of 299 CAP patients (including 97 severe CAP patients [SCAP]) and 20 healthy controls (HC) were included. A quantitative enzyme-linked immunosorbent test kit was employed for detecting the LPCAT level in plasma. We developed a deep-learning-based binary classification (SCAP or non-severe CAP [NSCAP]) model to process LPCAT levels and other laboratory test results.ResultsThe level of LPCAT in patients with SCAP and death outcome was significantly higher than that in other patients. LPCAT showed the highest predictive value for SCAP. LPCAT was able to predict 30-day mortality among CAP patients, combining LPCAT values with PSI scores or CURB-65 further enhance mortality prediction accuracy.ConclusionThe on admission level of LPCAT found significantly raised among SCAP patients and strongly predicted SCAP patients but with no correlation to etiology. Combining the LPCAT value with CURB-65 or PSI improved the 30-day mortality forecast significantly.Trial registrationNCT03093220 Registered on March 28th, 2017.
Anxiety disorders and adhesive capsulitis: a bidirectional Mendelian randomization study
Authors: Ouyang Yi , Dai Miaomiao 
Published: January 2024

BackgroundPrevious epidemiological investigations and related research efforts consistently have outlined an observable association between anxiety disorders and adhesive capsulitis (AC). However, the intricate nature of the causal connection between these entities has yet to be fully clarified. Therefore, this investigative study aims to thoroughly examine and delineate the causal interrelationship between anxiety disorders and AC using a bidirectional, two-sample Mendelian randomization (MR) approach.MethodsTo pursue this inquiry, datasets related to anxiety disorders and AC were meticulously obtained from a publicly accessible genomewide association study. Instrumental variables, in the form of single nucleotide polymorphisms, were subsequently identified, undergoing a rigorous screening process that included intensity adjustment and the amelioration of linkage disequilibrium. The primary analytical tool for scrutinizing causal ramifications was the inverse variance weighting (IVW) methodology, complemented by supplementary analytical techniques such as weighted median, MR-Egger, simple mode, and weighted mode. Additionally, evaluations of heterogeneity and pleiotropy were meticulously conducted. Heterogeneity was assessed using Cochran’s Q-test in conjunction with the IVW and MR-Egger methods, while pleiotropy was appraised through the MR-Egger intercept and MR-PRESSO analysis methods. A leave-one-out analysis was undertaken to enhance the reliability of our findings. Finally, AC was utilized to infer reverse causality concerning the risk of anxiety disorders.ResultsThe random effects IVW analysis results yielded statistical significance (P = 9.362 × 10-6), demonstrating a causal link between anxiety disorders and elevated susceptibility to AC, reflected in an odds ratio of 1.267 (95% confidence interval: 1.141–1.407). Conversely, the inverse MR analysis predominantly produced null findings. Furthermore, sensitivity analyses underscored the robustness of our conclusions.ConclusionIn summary, our meticulously conducted study unequivocally supports the presence of a causal connection between anxiety disorders and an increased propensity for AC. Unfortunately, the reverse MR analysis failed to provide compelling evidence indicative of a reciprocal genetic causative relationship between AC and anxiety disorders.