bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic causal relationship between immune diseases and migraine: a Mendelian randomization study
Authors: Li Guanglu , Duan Shaojie ,   International Headache Genetics Consortium (IHGC), Zheng Tao , Zhu Tiantian , Qu Baoquan , Liu Lei , Liu Zunjing 
Published: April 2024

BackgroundMigraine has an increased prevalence in several immune disorders, but genetic cause-effect relationships remain unclear. Mendelian randomization (MR) was used in this study to explore whether immune diseases are causally associated with migraine and its subtypes.MethodsWe conducted a two-sample bidirectional multivariate Mendelian randomization study. Single-nucleotide polymorphisms (SNP) for six immune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1D), allergic rhinitis (AR), asthma and psoriasis, were used as genetic instrumental variables. Summary statistics for migraine were obtained from 3 databases: the International Headache Genetics Consortium (IHGC), UK Biobank, and FinnGen study. MR analyses were performed per outcome database for each exposure and subsequently meta-analyzed. Reverse MR analysis was performed to determine whether migraine were risk factors for immune diseases. In addition, we conducted a genetic correlation to identify shared genetic variants for these two associations.ResultsNo significant causal relationship was found between immune diseases and migraine and its subtypes. These results were robust with a series of sensitivity analyses. Using the linkage disequilibrium score regression method (LDSC), we detected no genetic correlation between migraine and immune diseases.ConclusionThe evidence from our study does not support a causal relationship between immune diseases and migraine. The mechanisms underlying the frequent comorbidity of migraine and several immune diseases need to be further elucidated.
Analysis of gene expression dynamics and differential expression in viral infections using generalized linear models and quasi-likelihood methods
Authors: Rezapour Mostafa , Walker Stephen J. , Ornelles David A. , McNutt Patrick M. , Atala Anthony , Gurcan Metin Nafi 
Published: April 2024

IntroductionOur study undertakes a detailed exploration of gene expression dynamics within human lung organ tissue equivalents (OTEs) in response to Influenza A virus (IAV), Human metapneumovirus (MPV), and Parainfluenza virus type 3 (PIV3) infections. Through the analysis of RNA-Seq data from 19,671 genes, we aim to identify differentially expressed genes under various infection conditions, elucidating the complexities of virus-host interactions.MethodsWe employ Generalized Linear Models (GLMs) with Quasi-Likelihood (QL) F-tests (GLMQL) and introduce the novel Magnitude-Altitude Score (MAS) and Relaxed Magnitude-Altitude Score (RMAS) algorithms to navigate the intricate landscape of RNA-Seq data. This approach facilitates the precise identification of potential biomarkers, highlighting the host’s reliance on innate immune mechanisms. Our comprehensive methodological framework includes RNA extraction, library preparation, sequencing, and Gene Ontology (GO) enrichment analysis to interpret the biological significance of our findings.ResultsThe differential expression analysis unveils significant changes in gene expression triggered by IAV, MPV, and PIV3 infections. The MAS and RMAS algorithms enable focused identification of biomarkers, revealing a consistent activation of interferon-stimulated genes (e.g., IFIT1, IFIT2, IFIT3, OAS1) across all viruses. Our GO analysis provides deep insights into the host’s defense mechanisms and viral strategies exploiting host cellular functions. Notably, changes in cellular structures, such as cilium assembly and mitochondrial ribosome assembly, indicate a strategic shift in cellular priorities. The precision of our methodology is validated by a 92% mean accuracy in classifying respiratory virus infections using multinomial logistic regression, demonstrating the superior efficacy of our approach over traditional methods.DiscussionThis study highlights the intricate interplay between viral infections and host gene expression, underscoring the need for targeted therapeutic interventions. The stability and reliability of the MAS/RMAS ranking method, even under stringent statistical corrections, and the critical importance of adequate sample size for biomarker reliability are significant findings. Our comprehensive analysis not only advances our understanding of the host’s response to viral infections but also sets a new benchmark for the identification of biomarkers, paving the way for the development of effective diagnostic and therapeutic strategies.
Multidimensional features of sporadic Creutzfeldt-Jakob disease in the elderly: a case report and systematic review
Authors: Liao Jiangfeng , Hu Wenming , Chen Shiheng , Huang Chunyu , Dong Senwei , Chen Wanjin , Chen Xiaochun , Chen Longfei 
Published: April 2024

BackgroundAs a rare neurodegenerative disease, sporadic Creutzfeldt-Jakob disease (sCJD) is poorly understood in the elderly populace. This study aims to enunciate the multidimensional features of sCJD in this group.MethodsA case of probable sCJD was reported in a 90-year-old Chinese man with initial dizziness. Then, available English literature of the elderly sCJD cases (aged 80 years and over) was reviewed and analyzed. Patients (15 cases) were subdivided and compared geographically.ResultsIn the elderly sCJD cohort, the onset age was 84.9 ± 4.5 years and the median disease duration was 6.8 months, with respiratory infection/failure as the commonest death cause. Various clinical symptoms were identified, with cognitive disorder (86.7%) as the commonest typical symptom and speech impairment (66.7%) as the most atypical one. Restricted hyperintensities were reported in 60.0% cases on DWI, periodic sharp wave complexes in 73.3% cases on electroencephalogram, and cerebral hypoperfusion/hypometabolism in 26.7% cases on molecular imaging. The sensitive cerebrospinal fluid biomarkers were total tau (83.3%), 14-3-3 protein (75.0%), and PrP RT-QuIC (75.0%). Neuropathological profiles in the cerebral cortex revealed vacuolar spongiosis, neuronal loss, gliosis, and aging-related markers, with synaptic deposit as the commonest PrP pattern (60.0%). The polymorphic PRNP analysis at codon 129 was M/M (90.9%), with MM1 and MM2C as the primary molecular phenotypes. Latency to first clinic visit, hyperintense signals on DWI, and disease duration were significantly different between the patient subgroups.ConclusionThe characteristics of sCJD are multidimensional in the elderly, deepening our understanding of the disease and facilitating an earlier recognition and better care for this group.
Protective effect of oxytocin on vincristine-induced gastrointestinal dysmotility in mice
Authors: Li Shuang , Shi Yao , Zhu Jianchun , Li Jingxin , Wang Shuanglian , Liu Chuanyong 
Published: April 2024

Aims: Vincristine (VCR), an antineoplastic drug, induces peripheral neuropathy characterized by nerve damage, limiting its use and reducing the quality of life of patients. VCR causes myenteric neuron damage, inhibits gastrointestinal motility, and results in constipation or paralytic ileus in patients. Oxytocin (OT) is an endogenous neuropeptide produced by the enteric nerve system, which regulates gastrointestinal motility and exerts neuroprotective effects. This study aimed to investigate whether OT can improve VCR-induced gastrointestinal dysmotility and evaluate the underlying mechanism.Methods: Mice were injected either with saline or VCR (0.1 mg/kg/d, i. p.) for 14 days, and OT (0.1 mg/kg/d, i.p.) was applied 1 h before each VCR injection. Gastrointestinal transit and the contractile activity of the isolated colonic segments were assessed. The concentration of OT in plasma was measured using ELISA. Immunofluorescence staining was performed to analyze myenteric neurons and reactive oxygen species (ROS) levels. Furthermore, the indicators of oxidative stress were detected. The protein expressions of Nrf2, ERK1/2, P-ERK1/2, p38, and P-p38 in the colon were tested using Western blot.Results: VCR reduced gastrointestinal transit and the responses of isolated colonic segments to electrical field stimulation and decreased the amount of neurons. Furthermore, VCR reduced neuronal nitric oxide synthase and choline acetyltransferase immunopositive neurons in the colonic myenteric nerve plexus. VCR increased the concentration of OT in plasma. Exogenous OT pretreatment ameliorated the inhibition of gastrointestinal motility and the injury of myenteric neurons caused by VCR. OT pretreatment also prevented the decrease of superoxide dismutase activity, glutathione content, total antioxidative capacity, and Nrf2 expression, the increase of ROS levels, and the phosphorylation of ERK1/2 and p38 MAPK following VCR treatment.Conclusion: Our results suggest that OT pretreatment can protect enteric neurons from VCR-induced injury by inhibiting oxidative stress and MAPK pathways (ERK1/2, p38). This may be the underlying mechanism by which it alleviates gastrointestinal dysmotility.
Clinical efficacy and safety analysis of aumolertinib in real-world treatment of EGFR-mutated advanced non-small-cell lung cancer
Authors: Zhang Xiaojuan , Zhang Mina , Du Xinyang , Zhang Guowei , Niu Yuanyuan , Wei Chunhua , Guo Lanwei , Shi Chao , Liu Hangfan , Wang Huijuan 
Published: April 2024

Background: This study aims to determine the efficacy and safety profile of aumolertinib in the real-word treatment setting for advanced non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations.Methods: We retrospectively analyzed the clinical data of 173 EGFR-mutated advanced NSCLC patients who received aumolertinib treatment at Henan Cancer Hospital from April 2020 to December 2022. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan–Meier survival curves, while a Cox regression model was used for multifactorial analysis and prognostic factor assessment.Results: Among patients administered first-line aumolertinib (n = 77), the objective remission rate (ORR) of 77.92% was observed, along with a disease control rate (DCR) of 100%. The median progression-free survival (mPFS) was 24.97 months, which did not reach the median overall survival (mOS). The patients treated with aumolertinib after progression on prior EGFR-tyrosine kinase inhibitor (TKI) therapy (n = 96) exhibited an ORR of 46.88%, a DCR of 89.58%, an mPFS of 15.17 months, and an mOS of 21.27 months. First-line treatment multivariate Cox regression analysis demonstrated a statistically significant impact of elevated creatine kinase on PFS (p = 0.016) and a similar significant influence of co-mutation on OS (p = 0.034). Furthermore, subsequent-line treatment multivariate Cox regression analysis showed a statistically significant impact of elevated creatine kinase on median PFS (p = 0.026) and a significant effect on the number of metastatic organs (p = 0.017), co-mutation (p = 0.035), and elevated creatine kinase (p = 0.014) on median OS.Conclusion: Aumolertinib has shown clinical significance and can safely be used in the real-world setting for patients with EGFR mutation-positive NSCLC.
A study on the impact of systematic desensitization training on competitive anxiety among Latin dance athletes
Authors: Chen Jie , Zhou Duoqi , Gong Dan , Wu Shunli , Chen Weikai 
Published: April 2024

ObjectiveIn the domain of competitive events, Latin dance athletes have always suffered competitive anxiety, which is a prevalent and prevailing psychological facet, in pre-, intra-, and post-competitive engagements. Usually, the implementation of systematic desensitization training is an efficacious approach to reduce competitive anxiety levels in routine sports to fortify psychological resilience of athletes (like swimming, volleyball, and basketball). This study focuses on the effect of systematic desensitization training on competition anxiety in the training of Latin dancers to establish good mental ability and promote the competitive ability of athletes.MethodologyThe “Sports Competition Anxiety Test Questionnaire” was used to evaluate and classify the competitive anxiety levels of 150 Latin dance athletes. Then, the top 48 participants were selected (24 in the intervention cohort and 24 in the non-intervention cohort) as the study participants after stratifying anxiety score levels from the highest to the lowest. The intervention group was treated with an 8-week psychological intervention by employing systematic desensitization training techniques (encompassing imagery desensitization and in vivo desensitization). The anxiety levels of the subjects were quantified by employing the “Sport Competition Trait Anxiety Inventory” (CCTAI-C) and the “Competitive State Anxiety Inventory” (CSAI-2) to scrutinize the efficacy of systematic desensitization training in regulating competitive anxiety levels among Latin dance athletes.ResultsAfter applying systematic desensitization training, the intervention group displayed a notable reduction in sport cognitive trait anxiety. Specifically, there was a decrease of 29.37% in social evaluation anxiety, 20.31% in competition preparation anxiety, 16.98% in performance anxiety, 25.16% in failure anxiety, 34.47% in opponent’s ability anxiety, and 25.16% in injury anxiety. Moreover, for competitive state anxiety, cognitive state anxiety and somatic state anxiety decreased by 39.19 and 21.43%. The state self-confidence increased by 14.42%.ConclusionThe result indicated that systematic desensitization training not only mitigates anxiety but also positively intervenes in sports-related anxiety. Moreover, systematic desensitization training can significantly diminish competitive anxiety among Latin dance athletes to bolster confidence during competitions. Integrating desensitization training into the regular regimen of Latin dance practice has the potential to fortify dancers’ psychological resilience against anxiety.
Conduct problems, hyperactivity, and screen time among community youth: can mindfulness help? an exploratory study
Authors: Kim Soyeon , Munten Stephanie , Kolla Nathan J. , Konkolÿ Thege Barna 
Published: April 2024

BackgroundThe influence of mindfulness-based intervention (MBI) programs on behavioural problems among community youth is largely understudied. While technology continues to evolve and the prevalence of screen-based activities is rising, limited studies have accounted for screen time when examining the efficacy of an MBI. Accordingly, this study investigated the impact of MBI on conduct problems and hyperactivity among community youth, accounting for sociodemographic characteristics and four types of screen time.MethodLinear regression models were used to investigate 1) the association between four types of screen time and behavioural problems (i.e., conduct problems and hyperactivity) and 2) the efficacy of online mindfulness programs in reducing behavioural problems among community youth. The data were collected at baseline, intervention completion and 1-month follow-up (Spring 2021 to Spring 2022) in Ontario, Canada (n=117, mean age=16.82, male=22%, non-White=21%).ResultsThe average score for conduct problems was within the normal range, while the average score for hyperactivity was considered borderline at baseline. Accounting for other types of screen time, time spent playing video games was significantly associated with increased conduct problems (β= 1.75, p=.03), albeit rendering non-significant after correcting for multiple comparisons. The online mindfulness program was significantly associated with reduced hyperactivity, controlling for baseline mental health, age, sex and screen time.ConclusionThe current findings suggest a 12-week online mindfulness program may play a positive role in reducing hyperactivity even when accounting for screen time. Our findings advocate the evidence base on the efficacy of MBI in managing hyperactivity.
Mucosal affairs: glycosylation and expression changes of gill goblet cells and mucins in a fish–polyopisthocotylidan interaction
Authors: Riera-Ferrer Enrique , Del Pozo Raquel , Muñoz-Berruezo Uxue , Palenzuela Oswaldo , Sitjà-Bobadilla Ariadna , Estensoro Itziar , Piazzon M. Carla 
Published: April 2024

IntroductionSecreted mucins are highly O-glycosylated glycoproteins produced by goblet cells in mucosal epithelia. They constitute the protective viscous gel layer overlying the epithelia and are involved in pathogen recognition, adhesion and expulsion. The gill polyopisthocotylidan ectoparasite Sparicotyle chrysophrii, feeds on gilthead seabream (Sparus aurata) blood eliciting severe anemia.MethodsControl unexposed and recipient (R) gill samples of gilthead seabream experimentally infected with S. chrysophrii were obtained at six consecutive times (0, 11, 20, 32, 41, and 61 days post-exposure (dpe)). In histological samples, goblet cell numbers and their intensity of lectin labelling was registered. Expression of nine mucin genes (muc2, muc2a, muc2b, muc5a/c, muc4, muc13, muc18, muc19, imuc) and three regulatory factors involved in goblet cell differentiation (hes1, elf3, agr2) was studied by qPCR. In addition, differential expression of glycosyltransferases and glycosidases was analyzed in silico from previously obtained RNAseq datasets of S. chrysophrii-infected gilthead seabream gills with two different infection intensities.Results and DiscussionIncreased goblet cell differentiation (up-regulated elf3 and agr2) leading to neutral goblet cell hyperplasia on gill lamellae of R fish gills was found from 32 dpe on, when adult parasite stages were first detected. At this time point, acute increased expression of both secreted (muc2a, muc2b, muc5a/c) and membrane-bound mucins (imuc, muc4, muc18) occurred in R gills. Mucins did not acidify during the course of infection, but their glycosylation pattern varied towards more complex glycoconjugates with sialylated, fucosylated and branched structures, according to lectin labelling and the shift of glycosyltransferase expression patterns. Gilthead seabream gill mucosal response against S. chrysophrii involved neutral mucus hypersecretion, which could contribute to worm expulsion and facilitate gas exchange to counterbalance parasite-induced hypoxia. Stress induced by the sparicotylosis condition seems to lead to changes in glycosylation characteristic of more structurally complex mucins.
Knowledge, attitudes, and practices on antimicrobial use and antimicrobial resistance among poultry practitioner veterinarians
Authors: Shahi Manoj Kumar , Jeamsripong Saharuetai 
Published: April 2024

BackgroundAntimicrobial resistance (AMR) poses a serious global threat to human and animal health. In the context of antimicrobial usage (AMU) in livestock production, veterinarians are key stakeholders. However, there is a lack of comprehensive situational analysis regarding the current Knowledge, Attitudes, and Practices (KAP) among veterinarians concerning AMU and AMR in poultry production in Nepal.MethodsThe primary objective of this study was to evaluate the situation of AMU and KAP regarding AMU and AMR of among poultry practitioner veterinarians in Nepal. A total of 327 respondents from 56 districts across seven provinces participated. Demographic information and AMU situation were collected and analyzed using descriptive statistics, and factors affecting KAP on AMU and AMR were performed using logistic regression analysis.ResultsNearly half of veterinarians (49.2%) were from Bagmati, followed by Lumbini (16.5%) and Gandaki (8.9%) provinces. Most of the respondents (85.0%) identified themselves as male with a mean age of 31.9 ± 7.8 years, with a range of 24–74 years. A large proportion of veterinarians held a master’s degree (43.8%). Regarding reasons for AMR, 51.1% of them attributed it to the irrational use of antimicrobials. Other identified reasons for AMR, including over-the-counter sales (27.8%), low-dose administration (12.3%), and low-quality antimicrobials (6.7%). Based on antibiotic prescription rates, most veterinarians (50.8%) prescribed antimicrobials at a rate of 20–40%, while 25.9% prescribed at a rate of less than 20.0 and 18.9% at a rate of 40–60%. Approximately 89.0% of veterinarians agreed that vaccination could reduce the use of antimicrobials in poultry, and 75.6% preferred narrow-spectrum antimicrobials than broad-spectrum antimicrobials. A combination of broad-spectrum antimicrobials such as colistin with amoxicillin, gentamicin, tylosin, and tetracycline was commonly used in poultry production.DiscussionIn logistic regression analysis, it was observed that veterinarians aged 45–60 years demonstrated significantly higher levels of knowledge concerning AMU and AMR (p = 0.02) compared to those in the 24–30 age group. This study indicates that the need for robust regulatory mechanisms in veterinary drug administration and increased awareness among veterinarians to address the AMR issue livestock production.
Effect of Brosimum alicastrum Foliage on Intake, Kinetics of Fermentation and Passage and Microbial N Supply in Sheep Fed Megathyrsus maximus Hay
Authors: Valdivia-Salgado Vicente , Flores-Santiago Ever del Jesús , Ramírez-Avilés Luis , Segura-Correa José Candelario , Calzada-Marín Jesús Miguel , Ku-Vera Juan Carlos 
Published: April 2024

An experiment was carried out to assess the effect of the incorporation of sun-dried foliage of Brosimum alicastrum into rations based on hay of Megathyrsus maximus on intake, rumen fermentation, kinetics of passage, microbial nitrogen supply to the small intestine, apparent digestibility in Pelibuey hair sheep. Four rations were randomly allotted to four rumen-cannulated lambs (BW = 37.4 ± 4.9 kg) using a 4 × 4 Latin square design to assess the effect of increasing levels (0, 15, 30 and 45% DM basis) of foliage of Brosimum alicastrum on a basal ration of M. maximus. Organic matter intake and water consumption increased linearly (p < 0.01) with increasing levels of B. alicastrum in the ration. The rate and potential extent of rumen fermentation of OM and CP of B. alicastrum were 10.6%/h and 86.6% and 11.4%/h and 95.2%, respectively, but no effect (p > 0.05) was found on the potential rumen degradation of DM (40.2%) or on the rate of degradation of DM (0.033%/h) of M. maximus, although a positive effect was found in the rumen degradation rate of NDF (p < 0.05). VFA and ammonia concentration in the rumen and the rate of passage of solids and liquids through the rumen (k1) increased linearly (p < 0.01) with increasing levels of B. alicastrum. Rumen pH was not affected by the incorporation of B. alicastrum (p > 0.05). Microbial nitrogen supply to the small intestine (p < 0.001), apparent digestibility of dry matter (p < 0.01) and NDF (p < 0.05) of the rations were also significantly increased as a result of the incorporation of B. alicastrum foliage. Results from this experiment suggest that the foliage of Brosimum alicastrum can be readily incorporated at around 30% of the ration of dry matter in hair sheep with beneficial effects on feed intake, rate of passage and microbial N supply to the lower tract.