bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin D binding protein correlate with estrogen increase after administration of human chorionic gonadotropin but do not affect ovulation, embryo, or pregnancy outcomes
Authors: Chen Huijun , Yao Jianghui , Hu Liang , Liu Yvonne , Hocher Johann-Georg , Zhang Xiaoli , Hasan Ahmed A. , Lin Ge , Gong Fei , Hocher Berthold 
Published: May 2024

BackgroundVitamin D binding protein (DBP) might increase substantially after ovarian stimulation and hence could be associated with IVF/ICSI outcomes because it determines the fraction of free bioavailable 25(OH) vitamin D. In this study, we aim to determine whether DBP is associated with E2 level after ovarian stimulation and IVF/ICSI outcomes.DesignPost-hoc analysis of a prospective observational cohort.SettingSingle-center study.Participants2569 women receiving embryo transfer.InterventionNone.Main outcome measuresThe main outcomes were oocyte and embryo quality as well as pregnancy outcomes.ResultsDBP concentration correlates with E2 on hCG day (=day of inducing ovulation with hCG; correlation coefficient r = 0.118, P&lt;0.001) and E2 x-fold change to baseline level (r = 0.108, P&lt;0.001). DBP is also positively correlated with total 25(OH)D (r = 0.689, R2 = 0.475, P&lt;0.001) and inversely with free 25(OH)D (r=-0.424, R2=0.179, P&lt;0.001), meaning that E2-stimulated DBP synthesis results in a decrease of free 25(OH)D during ovarian stimulation. However, such alteration does not affect IVF/ICSI outcomes when considering confounding factors, such as the number and quality of oocytes nor embryo quality as well as pregnancy outcomes.ConclusionDBP concentration correlates with the degree of E2 increase after ovarian stimulation. DBP is also positively correlated with total 25(OH)D and inversely with free 25(OH)D, suggesting that the proportion of free 25(OH)D decreases during ovarian stimulation caused by E2-stimulated DBP synthesis. However, such alteration does not affect clinical IVF/ICSI outcomes.
Genetically predicted asthma and the risk of abnormal spermatozoa
Authors: Li Zhichao , Teng Zhihai , Han Zhenwei , Zhang Yanping , Wang Yaxuan 
Published: May 2024

BackgroundSeveral previous animal and human studies have found a strong association between asthma and spermatozoa quality, but whether these associations are causal or due to bias remains to be elucidated.MethodsWe performed a two-sample Mendelian randomization (MR) analysis to assess the causal effect of genetically predicted asthma on the risk of abnormal spermatozoa. Asthma, childhood-onset asthma (COA), and adult-onset asthma (AOA) (sample sizes ranging from 327,670 to 408,442) were included as the exposures. Genetic information for abnormal spermatozoa was obtained from a genome-wide association study (GWAS) comprising 209,921 participants. In univariable MR (UVMR) analysis, the inverse variance weighted (IVW) method was conducted as the primary method, with the MR Egger and weighted median used as supplementary methods for causal inference. Sensitivity analyses, including the Cochran Q test, Egger intercept test, MR-PRESSO, and leave-one-out analysis, were performed to verify the robustness of the MR results. Multivariable MR (MVMR) was conducted to evaluate the direct causal effects of asthma on abnormal spermatozoa risk.ResultsUVMR detected causal associations between genetically predicted asthma and an increased risk of abnormal spermatozoa (OR: 1.270, 95% CI: 1.045–1.545, p = 0.017). Moreover, we found that AOA (OR: 1.46, 95% CI: 1.051, 2.018, p = 0.024) has positive causal effects on the risk of abnormal spermatozoa rather than COA (p = 0.558). Sensitivity analysis found little evidence of bias in the current study (p &gt; 0.05). MVMR further confirmed that asthma directly affected the risk of abnormal spermatozoa.ConclusionOur MR study suggested that genetically predicted asthma could be associated with an increased risk of abnormal spermatozoa, and similar results were obtained in AOA. Further studies are warranted to explain the underlying mechanisms of this association and may provide new avenues for prevention and treatment.
Exosomal ROR1 in peritoneal fluid identifies peritoneal disseminated PDAC and is associated with poor survival
Authors: Mittelstädt Anke , Anthuber Anna , David Paul , Podolska Malgorzata , Bénard Alan , Brunner Maximilian , Krautz Christian , Jacobsen Anne , Denz Axel , Weber Klaus , Merkel Susanne , Hackner Danilo , Buniatov Timur , Roßdeutsch Lotta , Klösch Bettina , Swierzy Izabella , Hansen Frederik J. , Strobel Deike , Zopf Yurdagül , Baur Jan-Ole , Van Deun Jan , Immanuel Geppert Carol , Gießl Andreas , Lettmaier Sebastian , Semrau Sabine , Grützmann Robert , Kouhestani Dina , Weber Georg F. 
Published: May 2024

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and peritoneal dissemination is one major cause for this poor prognosis. Exosomes have emerged as promising biomarkers for gastrointestinal cancers and can be found in all kinds of bodily fluids, also in peritoneal fluid (PF). This is a unique sample due to its closeness to gastrointestinal malignancies. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) has been identified as a potential biomarker in human cancers and represents a promising target for an immunotherapy approach, which could be considered for future treatment strategies. Here we prospectively analyzed the exosomal surface protein ROR1 (exo-ROR1) in PF in localized PDAC patients (PER-) on the one hand and peritoneal disseminated tumor stages (PER+) on the other hand followed by the correlation of exo-ROR1 with clinical-pathological parameters.MethodsExosomes were isolated from PF and plasma samples of non-cancerous (NC) (n = 15), chronic pancreatitis (CP) (n = 4), localized PDAC (PER-) (n = 18) and peritoneal disseminated PDAC (PER+) (n = 9) patients and the surface protein ROR1 was detected via FACS analysis. Additionally, soluble ROR1 in PF was analyzed. ROR1 expression in tissue was investigated using western blots (WB), qPCR, and immunohistochemistry (IHC). Exosome isolation was proven by Nano Tracking Analysis (NTA), WB, Transmission electron microscopy (TEM), and BCA protein assay. The results were correlated with clinical data and survival analysis was performed.ResultsPDAC (PER+) patients have the highest exo-ROR1 values in PF and can be discriminated from NC (p &lt;0.0001), PDAC (PER-) (p &lt;0.0001), and CP (p = 0.0112). PDAC (PER-) can be discriminated from NC (p = 0.0003). In plasma, exo-ROR1 is not able to distinguish between the groups. While there is no expression of ROR1 in the exocrine pancreatic tissue, PDAC and peritoneal metastasis show expression of ROR1. High exo-ROR1 expression in PF is associated with lower overall survival (p = 0.0482).ConclusionWith exo-ROR1 in PF we found a promising diagnostic and prognostic biomarker possibly discriminating between NC, PDAC (PER-) and PDAC (PER+) and might shed light on future diagnostic and therapeutic concepts in PDAC.
Exosomes derived from miR-146a-overexpressing fibroblast-like synoviocytes in cartilage degradation and macrophage M1 polarization: a novel protective agent for osteoarthritis?
Authors: Wang Huan , Zhang Yue , Zhang Chengfei , Zhao Yan , Shu Jun , Tang Xuezhang 
Published: May 2024

IntroductionPathological changes in the articular cartilage (AC) and synovium are major manifestations of osteoarthritis (OA) and are strongly associated with pain and functional limitations. Exosome-derived microRNAs (miRNAs) are crucial regulatory factors in intercellular communication and can influence the progression of OA by participating in the degradation of chondrocytes and the phenotypic transformation in the polarization of synovial macrophages. However, the specific relationships and pathways of action of exosomal miRNAs in the pathological progression of OA in both cartilage and synovium remain unclear.MethodsThis study evaluates the effects of fibroblast-like synoviocyte (FLS)-derived exosomes (FLS-Exos), influenced by miR-146a, on AC degradation and synovial macrophage polarization. We investigated the targeted relationship between miR-146a and TRAF6, both in vivo and in vitro, along with the involvement of the NF-κB signaling pathway.ResultsThe expression of miR-146a in the synovial exosomes of OA rats was significantly higher than in healthy rats. In vitro, the upregulation of miR-146a reduced chondrocyte apoptosis, whereas its downregulation had the opposite effect. In vivo, exosomes derived from miR-146a-overexpressing FLSs (miR-146a-FLS-Exos) reduced AC injury and chondrocyte apoptosis in OA. Furthermore, synovial proliferation was reduced, and the polarization of synovial macrophages shifted from M1 to M2. Mechanistically, the expression of TRAF6 was inhibited by targeting miR-146a, thereby modulating the Toll-like receptor 4/TRAF6/NF-κB pathway in the innate immune response.DiscussionThese findings suggest that miR-146a, mediated through FLS-Exos, may alleviate OA progression by modulating cartilage degradation and macrophage polarization, implicating the NF-κB pathway in the innate immune response. These insights highlight the therapeutic potential of miR-146a as a protective agent in OA, underscoring the importance of exosomal miRNAs in the pathogenesis and potential treatment of the disease.
CAP2 contributes to Parkinson’s disease diagnosed by neutrophil extracellular trap-related immune activity
Authors: Li Xiaohe , Luo Meiling , Xu Hangrui , Jia Lei , Liang Yanan , Xu Qianxi , Wang Yonghui 
Published: May 2024

IntroductionNeutrophil extracellular traps (NETs) constitute a crucial element of the immune system, and dysfunction in immune responses is implicated in the susceptibility and progression of Parkinson's disease (PD). Nevertheless, the mechanism connecting PD and NETs remains unclear. This study aims to uncover potential NETs-related immune biomarkers and elucidate their role in PD pathogenesis.MethodsThrough differential gene analysis of PD and NETs in GSE7621 datasets, we identified two PD subtypes and explored potential biological pathways. Subsequently, using ClusterWGCNA, we pinpointed pertinent genes and developed clinical diagnostic models. We then optimized the chosen model and evaluated its association with immune infiltration. Validation was conducted using the GSE20163 dataset. Screening the single-cell dataset GSE132758 revealed cell populations associated with the identified gene. ResultsOur findings identified XGB as the optimal diagnostic model, with CAP2 identified as a pivotal gene. The risk model effectively predicted overall diagnosis rates, demonstrating a robust correlation between infiltrating immune cells and genes related to the XGB model. DiscussionIn conclusions, we identified PD subtypes and diagnostic genes associated with NETs, highlighting CAP2 as a pivotal gene. These findings have significant implications for understanding potential molecular mechanisms and treatments for PD.
Real-world outcomes of chemotherapy plus immune checkpoint inhibitors versus chemotherapy alone in advanced, unresectable, and recurrent intrahepatic cholangiocarcinoma
Authors: Madzikatire Tinotenda Blessing , Heng Shan , Gu HongYi , Shan YunFeng , Lin EnHua , Banda Joshua , Debora Asta , Madziva Brandon Anotida , Bowa Mutale Jaeste , Mudhuri Munyaradzi Godfrey , Bwalya Canol 
Published: May 2024

BackgroundThere are limited treatment options available to improve the prognosis of patients with advanced or metastatic cholangiocarcinoma particularly intrahepatic cholangiocarcinoma (iCCA). This study aimed to evaluate the efficacy and safety of combining chemotherapy plus anti-PD-1/L1 drugs compared to chemotherapy alone in advanced, unresectable, and recurrent intrahepatic cholangiocarcinoma patients.MethodsPatients with advanced, unresectable, or recurrent iCCA who received chemotherapy combined with PD-1/PD-L1 inhibitors or chemotherapy alone were retrospectively screened and analyzed. The primary outcomes were overall survival (OS) and progression-free survival (PFS). The secondary outcomes were overall response rate (ORR), disease control rate (DCR), and safety.Results81 eligible patients were included in the study (chemotherapy plus anti-PD-1/L1 group n=51, and chemotherapy-alone group n=30). The median OS was 11 months for the chemotherapy plus anti-PD-1/L1 group, significantly longer than the 8 months in the chemotherapy-alone group, with a hazard ratio (HR) of 0.53 (95% CI 0.30–0.94, P = 0.008). The median PFS of 7 months in the chemotherapy plus anti-PD-1/L1 group was significantly longer than the 4 months in the chemotherapy-alone group, with HR of 0.48 (95% CI 0.27–0.87); P = 0.002). Similarly, the combined therapy group showed a higher ORR (29.4%) and DCR (78.4%) compared to 13.3% and 73.3% in the chemotherapy-alone group, respectively. More grade 3–4 treatment-related adverse effects were recorded in the chemotherapy plus anti-PD-1/L1 group (66.7%) compared to the chemotherapy-alone group (23.3%), however, they were manageable and tolerable.ConclusionChemotherapy plus anti-PD-1/L1 represents a more effective and tolerable treatment option for advanced, unresectable, and recurrent iCCA patients compared to chemotherapy alone.
Genetically predicted N-methylhydroxyproline levels mediate the association between naive CD8+ T cells and allergic rhinitis: a mediation Mendelian randomization study
Authors: Chen Zhengjie , Suo Ying , Du Xintao , Zhao Xiaoyun 
Published: May 2024

BackgroundAllergic rhinitis (AR), a prevalent chronic inflammatory condition triggered by immunoglobulin E (IgE), involves pivotal roles of immune and metabolic factors in its onset and progression. However, the intricacies and uncertainties in clinical research render current investigations into their interplay somewhat inadequate.ObjectiveTo elucidate the causal relationships between immune cells, metabolites, and AR, we conducted a mediation Mendelian randomization (MR) analysis.MethodsLeveraging comprehensive publicly accessible summary-level data from genome-wide association studies (GWAS), this study employed the two-sample MR research method to investigate causal relationships among 731 immune cell phenotypes, 1400 metabolite levels, and AR. Additionally, employing the mediation MR approach, the study analyzed potential mediated effect of metabolites in the relationships between immune cells and AR. Various sensitivity analysis methods were systematically employed to ensure the robustness of the results.ResultsFollowing false discovery rate (FDR) correction, we identified three immune cell phenotypes as protective factors for AR: Naive CD8br %CD8br (odds ratio (OR): 0.978, 95% CI = 0.966–0.990, P = 4.5×10–4), CD3 on CD39+ activated Treg (OR: 0.947, 95% CI = 0.923–0.972, P = 3×10–5), HVEM on CD45RA- CD4+ (OR: 0.967, 95% CI = 0.948–0.986, P = 4×10–5). Additionally, three metabolite levels were identified as risk factors for AR: N-methylhydroxyproline levels (OR: 1.219, 95% CI = 1.104–1.346, P = 9×10–5), N-acetylneuraminate levels (OR: 1.133, 95% CI = 1.061–1.211, P = 1.7×10–4), 1-stearoyl-2-arachidonoyl-gpc (18:0/20:4) levels (OR: 1.058, 95% CI = 1.029–1.087, P = 5×10–5). Mediation MR analysis indicated a causal relationship between Naive CD8br %CD8br and N-methylhydroxyproline levels, acting as a protective factor (OR: 0.971, 95% CI = 0.950–0.992, P = 8.31×10–3). The mediated effect was -0.00574, accounting for 26.1% of the total effect, with a direct effect of -0.01626. Naive CD8+ T cells exert a protective effect on AR by reducing N-methylhydroxyproline levels.ConclusionOur study, delving into genetic information, has substantiated the intricate connection between immune cell phenotypes and metabolite levels with AR. This reveals a potential pathway to prevent the onset of AR, providing guiding directions for future clinical investigations.
Tidal zone effects on the diet composition of leaf-eating crabs in natural mangrove communities: a stable isotope analysis
Authors: Lu Xiaoyan , Gu Xuan , Zhang Lin , Zhang Jinhan , Wang Wenqing , Wang Mao 
Published: May 2024

BackgroundIn natural mangrove communities, mangrove species are often distributed zonally. Leaf-eating crabs are one of the most abundant and iconic arboreal brachyurans in mangrove forests, but variation in the composition of crab diets in different mangrove tidal zones is unknown.MethodsTo determine the contributions of mangrove leaves and other organic carbon (C) sources to leaf-eating crab diets, dual stable C and nitrogen (N) isotope signatures (δ13C and 1δ5N) were used in a Bayesian stable isotope mixing model. We conducted experiments at various tidal levels in the Dongzhaigang Bay National Natural Reserve in China. We analyzed δ13C and δ15N of leaf-eating crabs, mangrove leaves, sediment organic matter (SOM), and animal tissues (prey).ResultsThe food composition of the dominant crab species, Parasesarma continentale, exhibited significant differences among the four tidal zones. From the margin to the high tide zone, the main food source shifted from predominantly mangrove leaves and SOM to primarily SOM and animal tissues. We observed a significant negative relationship between the C/N ratios of mangrove leaves and the proportion of leaves consumed by leaf-eating crabs. Additionally, as the tidal level increased, the C/N ratio of mangrove leaves also increased, whereas the proportion of leaves consumed by crabs decreased.ConclusionLeaf-eating crab diets vary significantly across tidal zones, highlighting the importance of considering tidal zone differentiation when studying consumer diets in mangrove ecosystems.
A nomogram for predicting survival in patients with gastrointestinal stromal tumor: a study based on the surveillance, epidemiology, and end results database
Authors: Li Xiaxi , You Lijuan , Liu Qinghua , He Wenhua , Cui Xiaobing , Gong Wei 
Published: May 2024

PurposeThe objective of this investigation was to construct and validate a nomogram for prognosticating cancer-specific survival (CSS) in patients afflicted with gastrointestinal stromal tumor (GIST) at 3-, 5-, and 8-years post-diagnosis.MethodsData pertaining to patients diagnosed with GIST were acquired from the Surveillance, Epidemiology, and End Results (SEER) database. Through random selection, a training cohort (70%) and a validation cohort (30%) were established from the patient population. Employing a backward stepwise Cox regression model, independent prognostic factors were identified. Subsequently, these factors were incorporated into the nomogram to forecast CSS rates at 3-, 5-, and 8-years following diagnosis. The nomogram’s performance was assessed using indicators such as the consistency index (C-index), the area under the time-dependent receiver operating characteristic curve (AUC), the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), calibration curves, and decision-curve analysis (DCA).ResultsThis investigation encompassed a cohort of 3,062 GIST patients. By analyzing the Cox regression model within the training cohort, nine prognostic factors were identified: age, sex, race, marital status, AJCC (American Joint Committee on Cancer) stage, surgical status, chemotherapy status, radiation status, and income status. The nomogram was subsequently developed and subjected to both internal and external validation. The nomogram exhibited favorable discrimination abilities, as evidenced by notably high C-indices and AUC values. Calibration curves confirmed the nomogram’s reliability. Moreover, the nomogram outperformed the AJCC model, as demonstrated by enhanced NRI and IDI values. The DCA curves validated the clinical utility of the nomogram.ConclusionThe present study has successfully constructed and validated the initial nomogram for predicting prognosis in GIST patients. The nomogram’s performance and practicality suggest its potential utility in clinical settings. Nevertheless, further external validation is warranted.
Diagnosis of hemidiaphragm paralysis: refine ultrasound criteria
Authors: Boussuges Alain , Fourdrain Alex , Leone Marc , Brioude Geoffrey , Menard Amelie , Zieleskiewicz Laurent , Delliaux Stephane , Gouitaa Marion , Dutau Hervé , Brégeon Fabienne 
Published: May 2024

BackgroundUltrasound has demonstrated its interest in the analysis of diaphragm function in patients with respiratory failure. The criteria used to diagnose hemidiaphragm paralysis are not well defined.MethodsThe aim of this observational retrospective study was to describe the ultrasound findings in 103 patients with diaphragm paralysis, previously diagnosed by conventional methods after various circumstances such as trauma or surgery. The ultrasound study included the recording of excursions of both diaphragmatic domes and the measurement of inspiratory thickening.ResultsOn paralyzed hemidiaphragm, thickening was less than 20% in all patients during deep inspiration. Thinning was recorded in 53% of cases. In some cases, the recording of the thickening could be difficult. The study of motion during voluntary sniffing reported a paradoxical excursion in all but one patient. During quiet breathing, an absence of movement or a paradoxical displacement was observed. During deep inspiration, a paradoxical motion at the beginning of inspiration followed by a reestablishment of movement in the cranio-caudal direction was seen in 82% of cases. In some patients, there was a lack of movement followed, after an average delay of 0.4 s, by a cranio-caudal excursion. Finally, in 4 patients no displacement was recorded. Evidence of hyperactivity (increased inspiratory thickening and excursion) of contralateral non-paralyzed hemidiaphragm was observed.ConclusionTo accurately detect hemidiaphragm paralysis, it would be interesting to combine the ultrasound study of diaphragm excursion and thickening. The different profiles reported by our study must be known to avoid misinterpretation.
Irisin alleviated the reproductive endocrinal disorders of PCOS mice accompanied by changes in gut microbiota and metabolomic characteristics
Authors: Yang Meina , Deng Hongxia , Zhou Siyu , Lu Danhua , Shen Xiaoyang , Huang Lu , Chen Yan , Xu Liangzhi 
Published: May 2024

IntroductionFolliculogenesis and oligo/anovulation are common pathophysiological characteristics in polycystic ovary syndrome (PCOS) patients, and it is also accompanied by gut microbiota dysbiosis. It is known that physical activity has beneficial effects on improving metabolism and promoting ovulation and menstrual cycle disorder in PCOS patients, and it can also modulate the gastrointestinal microbiota in human beings. However, the mechanism remains vague. Irisin, a novel myokine, plays a positive role in the mediating effects of physical activity.MethodsMice were randomly divided into the control group, PCOS group and PCOS+irisin group. PCOS model was induced by dehydroepiandrosterone (DHEA) and high-fat diet (HFD). The PCOS+irisin group was given irisin 400μg/kg intraperitoneal injection every other day for 21 days. The serum sex hormones were measured by radioimmunoassay. Hematoxylin and Eosin (H&amp;E) Staining and immunohistochemistry (IHC) were conducted on ovarian tissue. The feces microbiota and metabolomic characteristics were collected by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC–MS).ResultsIn this study, we demonstrated that irisin supplementation alleviated reproductive endocrine disorders of PCOS mice, including estrous cycle disturbance, ovarian polycystic degeneration, and hyperandrogenemia. Irisin also improved the PCOS follicles dysplasia and ovulation disorders, while it had no significant effect on the quality of oocytes. Moreover, irisin could mitigate the decreased bacteria of Odoribacter and the increased bacteria of Eisenbergiella and Dubosiella in PCOS mice model. Moreover, irisin could alleviate the increased fecal metabolites: Methallenestril and PS (22:5(4Z,7Z,10Z,13Z,16Z)/ LTE4).ConclusionThese results suggest that irisin may alleviate the status of PCOS mice model by modulating androgen-induced gut microbiota dysbiosis and fecal metabolites. Hence, our study provided evidence that irisin may be considered as a promising strategy for the treatment of PCOS.