bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uganda chicken genetic resources: II. genetic diversity and population demographic history inferred from mitochondrial DNA D-loop sequences
Authors: Yussif Illyass , Kugonza Donald Rugira , Masembe Charles 
Published: March 2024

The genetic diversity of indigenous chickens, which comprise over 80% of the chicken resources in Uganda, is largely not well-characterized for their genetic contribution. This study assessed the genetic diversity and population structure of the indigenous chicken population in Uganda to serve as an essential component for improvement and conservation strategies. A set of 344 mitochondrial DNA (mtDNA) D-loop sequences among 12 Ugandan chicken populations was evaluated. Twenty-eight polymorphic sites, accounting for 4.26% of the total analyzed loci of 658 bp, defined 32 haplotypes. The haplotype diversity (Hd) was 0.437, with a nucleotide diversity (π) of 0.0169, while the average number of nucleotide differences (k) was 0.576, indicating a population that is moderately genetically diverse. Analysis of molecular variance found 98.39% (ρ &lt; 0.01) of the total sequence variation among the chicken haplotypes within populations, 1.08% (ρ &lt; 0.05) among populations, and 0.75% (ρ &gt; 0.05) among populations within regions. This revealed subtle genetic differentiation among the populations, which appeared to be influenced by population fragmentation, probably due to neutral mutation, random genetic drift, and/or balancing selection. All the haplotypes showed affinity exclusively to the haplogroup-E mtDNA phylogeny, with haplotype UGA01 signaling an ancestral haplotype in Uganda. Neutrality tests Tajima’s D (−2.320) and Fu’s Fs (−51.369), augmented with mismatch distribution to measure signatures of recent historical demographic events, supported a population expansion across the chicken populations. The results show one matrilineal ancestry of Ugandan chickens from a lineage widespread throughout the world that began in the Indian subcontinent. The lack of phylogeographic signals is consistent with recent expansion events with extensive within-country genetic intermixing among haplotypes. Thus, the findings in this study hold the potential to guide conservation strategies and breeding programs in Uganda, given that higher genetic diversity comes from within the chicken population.
Mendelian randomization study shows no causal relationship between psychiatric disorders and glaucoma in European and East Asian populations
Authors: Zhang Yan , Fu Longhui , Feng Fang , Liu Bo , Lei Ying , Kang Qianyan 
Published: March 2024

Background: Glaucoma is a leading cause of blindness strongly associated with psychiatric disorders, but the causal association between glaucoma and psychiatric disorders remains uncertain because of the susceptibility of observational studies to confounding and reverse causation. This study aims to explore the potential causal association between glaucoma and three highly related psychiatric disorders (Depression, Insomnia, and Schizophrenia) in the European and East Asian populations using a two-sample Mendelian randomization analysis.Methods: Instrumental variables (IVs) of depression, insomnia, and schizophrenia in the European population were obtained after strict filtering. Summary-level data for glaucoma and glaucoma subtypes (primary open-angle glaucoma and primary closed-angle glaucoma) were obtained as outcomes. The inverse variance weighting (IVW) method was used as the primary method. Additionally, the causal effect was evaluated in the East Asian population using the same methods to validate analysis results. The robustness of these results was confirmed using heterogeneity, pleiotropy, and Steiger directionality test.Results: The primary MR results indicated that genetically driven psychiatric disorders were not causally associated with glaucoma (Depression: odds ratio (OR): 1.15, 95% confidence interval (CI): 0.93–1.42, p = 0.20; Insomnia: OR: 1.14, 95% CI: 0.63–2.05, p = 0.66; Schizophrenia: OR: 1.00, 95% CI: 0.93–1.08, p = 0.95), either with the risk of glaucoma subtypes in the European population. Meanwhile, results in the East Asian population were consistent with the results among the European population (Depression: OR = 1.38, CI 0.75–2.53, p = 0.30; Insomnia: OR = 0.99, CI 0.83–1.18, p = 0.93; Schizophrenia: OR = 1.06, CI 0.94–1.20, p = 0.34) with similar causal estimates in direction. Consistency was obtained by corroborating with other supporting methods. Besides, the robustness of the results was proved and the directionality test confirmed our estimation of potential causal direction (p &lt; 0.001).Conclusion: This study found a non-causal association between psychiatric disorders and the risk of glaucoma in the European and East Asian populations, which contradicts many existing observational reports, indicating that increased psychiatric disorders in glaucoma patients were more likely modifiable rather not inheritable.
Searching for gene-gene interactions through variance quantitative trait loci of 29 continuous Taiwan Biobank phenotypes
Authors: Lin Wan-Yu 
Published: March 2024

Introduction: After the era of genome-wide association studies (GWAS), thousands of genetic variants have been identified to exhibit main effects on human phenotypes. The next critical issue would be to explore the interplay between genes, the so-called “gene-gene interactions” (GxG) or epistasis. An exhaustive search for all single-nucleotide polymorphism (SNP) pairs is not recommended because this will induce a harsh penalty of multiple testing. Limiting the search of epistasis on SNPs reported by previous GWAS may miss essential interactions between SNPs without significant marginal effects. Moreover, most methods are computationally intensive and can be challenging to implement genome-wide.Methods: I here searched for GxG through variance quantitative trait loci (vQTLs) of 29 continuous Taiwan Biobank (TWB) phenotypes. A discovery cohort of 86,536 and a replication cohort of 25,460 TWB individuals were analyzed, respectively.Results: A total of 18 nearly independent vQTLs with linkage disequilibrium measure r2 &lt; 0.01 were identified and replicated from nine phenotypes. 15 significant GxG were found with p-values &lt;1.1E-5 (in the discovery cohort) and false discovery rates &lt;2% (in the replication cohort). Among these 15 GxG, 11 were detected for blood traits including red blood cells, hemoglobin, and hematocrit; 2 for total bilirubin; 1 for fasting glucose; and 1 for total cholesterol (TCHO). All GxG were observed for gene pairs on the same chromosome, except for the APOA5 (chromosome 11)—TOMM40 (chromosome 19) interaction for TCHO.Discussion: This study provided a computationally feasible way to search for GxG genome-wide and applied this approach to 29 phenotypes.
In a novel autoimmune and high-pressure glaucoma model a complex immune response is induced
Authors: Reinehr Sabrina , Wulf Julien , Theile Janine , Schulte Kim K. , Peters Marcus , Fuchshofer Rudolf , Dick H. Burkhard , Joachim Stephanie C. 
Published: March 2024

BackgroundThe neurodegenerative processes leading to glaucoma are complex. In addition to elevated intraocular pressure (IOP), an involvement of immunological mechanisms is most likely. In the new multifactorial glaucoma model, a combination of high IOP and optic nerve antigen (ONA) immunization leads to an enhanced loss of retinal ganglion cells accompanied by a higher number of microglia/macrophages in the inner retina. Here, we aimed to evaluate the immune response in this new model, especially the complement activation and the number of T-cells, for the first time. Further, the microglia/macrophage response was examined in more detail.MethodsSix-week-old wildtype (WT+ONA) and βB1-connective tissue growth factor high-pressure mice (CTGF+ONA) were immunized with 1 mg ONA. A wildtype control (WT) and a CTGF group (CTGF) received NaCl instead. Six weeks after immunization, retinae from all four groups were processed for immunohistology, RT-qPCR, and flow cytometry, while serum was used for microarray analyses.ResultsWe noticed elevated numbers of C1q+ cells (classical complement pathway) in CTGF and CTGF+ONA retinae as well as an upregulation of C1qa, C1qb, and C1qc mRNA levels in these groups. While the complement C3 was only increased in CTGF and CTGF+ONA retinae, enhanced numbers of the terminal membrane attack complex were noted in all three glaucoma groups. Flow cytometry and RT-qPCR analyses revealed an enhancement of different microglia/macrophages markers, including CD11b, especially in CTGF and CTGF+ONA retinae. Interestingly, increased retinal mRNA as well as serum levels of the tumor necrosis factor α were found throughout the different glaucoma groups. Lastly, more T-cells could be observed in the ganglion cell layer of the new CTGF+ONA model.ConclusionThese results emphasize an involvement of the complement system, microglia/macrophages, and T-cells in glaucomatous disease. Moreover, in the new multifactorial glaucoma model, increased IOP in combination with autoimmune processes seem to enforce an additional T-cell response, leading to a more persistent pathology. Hence, this new model mimics the pathomechanisms occurring in human glaucoma more accurately and could therefore be a helpful tool to find new therapeutic approaches for patients in the future.
Optimization of surface roughness in milling of EN 24 steel with WC-Coated inserts using response surface methodology: analysis using surface integrity microstructural characterizations
Authors: Patil Shashwath , Sathish Thanikodi , Rao P. S. , Prabhudev M. S. , Vijayan V. , Rajkumar S. , Sharma Shubham , Kumar Abhinav , Abbas Mohamed , Makki Emad 
Published: March 2024

Introduction: Among alloys of medium-carbon and high-strength steel, EN 24 steel is characterised by its nickel-chromium-molybdenum composition. EN 24 steel is highly suitable for application in heavy-duty projects due to its notable resilience to damage, especially when exposed to low temperatures. With the objective of minimising surface irregularities, this research endeavours to enhance the milling process of EN 24 steel by employing coated tungsten carbide (WC) tool inserts.Methods: Feed rate, cutting speed, depth of cut, and cutting fluid are all crucial process factors in the experimental investigation. Four distinct levels are applied to each factor. The research utilises the Design of Experiments (DOE)-based Central Composite Design of Response Surface Methodology. To predict output parameters, mathematical models are developed utilising analysis of variance (ANOVA) for optimisation purposes.Results and discussions: Through the utilisation of multi-objective optimisation, the optimal combination for tungsten carbide inserts was determined, which provided surface irregularities of 0.301 µm. Cutting speed (CS) of 149.507 m/min, feed rate (FR) of 340.27 mm/min, depth of cut (DOC) of 0.599 mm, and cutting fluid (CF) of 12.50 L/min are the optimal parameters. The surface morphologies of the machined workpiece at particular parameter values can be discerned through scanning electron microscope (SEM) analysis, yielding significant insights. The optimal parameters that have been identified provide practical recommendations for improving the milling method of EN 24 steel when tungsten carbide inserts are utilised. Understanding the milling process in its entirety is facilitated by SEM analysis of surface morphologies and microstructures under particular cutting conditions. The morphology and surface irregularities of the machined workpiece are evaluated using profilometry, which provides additional insight into surface integrity. The discourse investigates the potential applications and implications of the results, as well as suggests directions for further study concerning the enhancement of milling processes for similar steel alloys.
Association between gut microbiota and menstrual disorders: a two-sample Mendelian randomization study
Authors: Yao Yufan , Hu Haoran , Chen Longhao , Zheng Hong 
Published: March 2024

BackgroundEvidence from observational studies and clinical trials suggests that the gut microbiota is associated with gynecological diseases. However, the causal relationship between gut microbiota and menstrual disorders remains to be determined.MethodsWe obtained summary data of gut microbiota from the global consortium MiBio-Gen’s genome-wide association study (GWAS) dataset and data on menstrual disorders from the IEU Open GWAS project. MR-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode were used to examine the causal association between gut microbiota and menstrual disorders. Thorough sensitivity studies were performed to confirm the data’s horizontal pleiotropy, heterogeneity, and robustness.ResultsThrough MR analysis of 119 kinds of gut microbiota and 4 kinds of clinical phenotypes, it was discovered that 23 different kinds of gut microbiota were loosely connected to menstrual disorders. After FDR correction, the results showed that only Escherichia/Shigella (p = 0.00032, PFDR = 0.0382, OR = 1.004, 95%CI = 1.002–1.006) is related to menstrual disorders.ConclusionAccording to our MR Analysis, there are indications of a causal relationship between menstrual disorders and gut microbiota. This finding could lead to new discoveries into the mechanisms behind menstrual disorders and clinical research involving the microbiota.
From acidophilic to ornithogenic: microbial community dynamics in moss banks altered by gentoo penguins
Authors: Prekrasna-Kviatkovska Yevheniia , Parnikoza Ivan , Yerkhova Anna , Stelmakh Olesia , Pavlovska Mariia , Dzyndra Marta , Yarovyi Oleksandr , Dykyi Evgen 
Published: March 2024

IntroductionThe study explores the indirect impact of climate change driven by gentoo’s penguin colonization pressure on the microbial communities of moss banks formed by Tall moss turf subformation in central maritime Antarctica.MethodsMicrobial communities and chemical composition of the differently affected moss banks (Unaffected, Impacted and Desolated) located on Galindez Island and Сape Tuxen on the mainland of Kyiv Peninsula were analyzed.ResultsThe native microbiota of the moss banks’ peat was analyzed for the first time, revealing a predominant presence of Acidobacteria (32.2 ± 14.4%), followed by Actinobacteria (15.1 ± 4.0%) and Alphaproteobacteria (9.7 ± 4.1%). Penguin colonization and subsequent desolation of moss banks resulted in an increase in peat pH (from 4.7 ± 0.05 to 7.2 ± 0.6) and elevated concentrations of soluble nitrogen (from 1.8 ± 0.4 to 46.9 ± 2.1 DIN, mg/kg) and soluble phosphorus compounds (from 3.6 ± 2.6 to 20.0 ± 1.8 DIP, mg/kg). The contrasting composition of peat and penguin feces led to the elimination of the initial peat microbiota, with an increase in Betaproteobacteria (from 1.3 ± 0.8% to 30.5 ± 23%) and Bacteroidota (from 5.5 ± 3.7% to 19.0 ± 3.7%) proportional to the intensity of penguins’ impact, accompanied by a decrease in community diversity. Microbial taxa associated with birds’ guts, such as Gottschalkia and Tissierella, emerged in Impacted and Desolated moss banks, along with bacteria likely benefiting from eutrophication. The changes in the functional capacity of the penguin-affected peat microbial communities were also detected. The nitrogen-cycling genes that regulate the conversion of urea into ammonia, nitrite oxide, and nitrate oxide (ureC, amoA, nirS, nosZ, nxrB) had elevated copy numbers in the affected peat. Desolated peat samples exhibit the highest nitrogen-cycle gene numbers, significantly differing from Unaffected peat (p &lt; 0.05).DiscussionThe expansion of gentoo penguins induced by climate change led to the replacement of acidophilic microbiomes associated with moss banks, shaping a new microbial community influenced by penguin guano’s chemical and microbial composition.
Risk factors for intracerebral hemorrhage in small-vessel disease and non-small-vessel disease etiologies—an observational proof-of-concept study
Authors: Arndt Philipp , Chahem Christian , Luchtmann Michael , Kuschel Jan-Niklas , Behme Daniel , Pfister Malte , Neumann Jens , Görtler Michael , Dörner Marc , Pawlitzki Marc , Jansen Robin , Meuth Sven G. , Vielhaber Stefan , Henneicke Solveig , Schreiber Stefanie 
Published: March 2024

BackgroundSporadic cerebral small-vessel disease (CSVD), i.e., hypertensive arteriopathy (HA) and cerebral amyloid angiopathy (CAA), is the main cause of spontaneous intracerebral hemorrhage (ICH). Nevertheless, a substantial portion of ICH cases arises from non-CSVD etiologies, such as trauma, vascular malformations, and brain tumors. While studies compared HA- and CAA-related ICH, non-CSVD etiologies were excluded from these comparisons and are consequently underexamined with regard to additional factors contributing to increased bleeding risk beyond their main pathology.MethodsAs a proof of concept, we conducted a retrospective observational study in 922 patients to compare HA, CAA, and non-CSVD-related ICH with regard to factors that are known to contribute to spontaneous ICH onset. Medical records (available for n = 861) were screened for demographics, antithrombotic medication, and vascular risk profile, and CSVD pathology was rated on magnetic resonance imaging (MRI) in a subgroup of 185 patients. The severity of CSVD was assessed with a sum score ranging from 0 to 6, where a score of ≥2 was defined as advanced pathology.ResultsIn 922 patients with ICH (median age of 71 years), HA and CAA caused the majority of cases (n = 670, 73%); non-CSVD etiologies made up the remaining quarter (n = 252, 27%). Individuals with HA- and CAA-related ICH exhibited a higher prevalence of predisposing factors than those with non-CSVD etiologies. This includes advanced age (median age: 71 vs. 75 vs. 63 years, p &lt; 0.001), antithrombotic medication usage (33 vs. 37 vs. 19%, p &lt; 0.001), prevalence of vascular risk factors (70 vs. 67 vs. 50%, p &lt; 0.001), and advanced CSVD pathology on MRI (80 vs. 89 vs. 51%, p &gt; 0.001). However, in particular, half of non-CSVD ICH patients were either aged over 60 years, presented with vascular risk factors, or had advanced CSVD on MRI.ConclusionRisk factors for spontaneous ICH are less common in non-CSVD ICH etiologies than in HA- and CAA-related ICH, but are still frequent. Future studies should incorporate these factors, in addition to the main pathology, to stratify an individual’s risk of bleeding.
Neurophysiological indices for split phenomena: correlation with age and sex and potential implications in amyotrophic lateral sclerosis
Authors: Zoccolella Stefano , Milella Giammarco , Giugno Alessia , Devitofrancesco Vito , Damato Rosaria , Tamburrino Ludovica , Misceo Salvatore , Filardi Marco , Logroscino Giancarlo 
Published: March 2024

BackgroundSplit phenomena (SP) are characterized by patterns of differential muscle wasting and atrophy, which are highly prevalent in amyotrophic lateral sclerosis (ALS) patients. Several neurophysiological indicators, including the split-hand index (SHI), split-leg index (SLI), and split-elbow index (SEI), have been proposed to assess SP. Nevertheless, their cutoff values and the impact of age and sex on these measures remain unclear.MethodsWe prospectively collected neurophysiological data from 300 healthy adult subjects. The following indices were measured from compound muscle action potentials (CMAPs): SHI [abductor pollicis brevis (APBcmap) x first dorsal interosseous (FDI)cmap/adductor digiti minimi (ADMcmap)], SEI (BICEPScmap/TRICEPScmap), SLI (extensor digit brevis (EDB)cmap/abductor Hallucis (AH)cmap), and the neurophysiological ratios APBcmap /ADMcmap and FDIcmap/ADMcmap. Multiple linear regression analysis was used to investigate the association between age, sex, CMAPs, and neurophysiological indicators.ResultsThe median SHI was 10.4, with a median APBcmap/ADMcmap ratio of 0.9 and a median FDIcmap/ADMcmap ratio of 1.2. The median SEI was 1.6 (IQR:1.1–2.4) and the median SLI was 0.7 (IQR:0.5–1.0). Negative associations were observed between age, most of the CMAPs, and all the neurophysiological indices, except for SLI. The male subjects exhibited significantly higher CMAP values for the first dorsal interosseous (FDI), biceps, and SHI compared to the female participants.ConclusionOur findings highlight the importance of age- and sex-adjusted normative data for SP indices, which could enhance their diagnostic accuracy and clinical utility in patients with ALS. The SL index appears to be the most reliable indicator, as it showed no significant association with age or sex.
Integrative effects of transcutaneous auricular vagus nerve stimulation on esophageal motility and pharyngeal symptoms via vagal mechanisms in patients with laryngopharyngeal reflux disease
Authors: Huang Yizhou , Liu Jie , Lv Chaolan , Sun Chenyu , Meng Muzi , Lowe Scott , Yu Yue 
Published: March 2024

Background and aimLaryngopharyngeal reflux disease (LPRD) is primarily characterized by discomfort in the pharynx and has limited treatment options. This research aimed to assess the efficacy of transcutaneous auricular vagus nerve stimulation (tVNS) in patients with LPRD and delve into the potential underlying mechanisms.MethodsA total of 44 participants, diagnosed with LPRD were divided into two groups randomly. Twice-daily stimulation was delivered for 2 weeks for patients in experimental group, with stimulation ranging from 1.0 mA to 1.5 mA (n = 22), while the control group underwent sham tVNS (n = 22) with the same stimulation parameters and different anatomical location. The severity of symptoms and levels of anxiety and depression were monitored using questionnaires. High-resolution esophageal manometry data were collected, and the patients’ autonomic function was assessed through heart rate variability analysis.ResultsThere was a positive correlation between reflux symptom index (RSI) scores and low frequency/high frequency (LF/HF) ratio (r = 0.619; p &lt; 0.001), Hamilton anxiety scale (HAMA) scores (r = 0.623; p &lt; 0.001), and Hamilton depression scale (HAMD) scores (r = 0.593; p &lt; 0.001). Compared to the pre-tVNS phase, RSI (p &lt; 0.001), HAMA (p &lt; 0.001), and HAMD (p &lt; 0.001) scores were significantly reduced after 2 weeks of treatment. Additionally, the resting pressure of the upper esophageal sphincter (UESP; p &lt; 0.05) and lower esophageal sphincter (LESP; p &lt; 0.05) showed significant enhancement. Notably, tVNS led to an increase in root mean square of successive differences (RMSSD; p &lt; 0.05) and high frequency (HF; p &lt; 0.05) within heart rate variability compared to the pre-treatment baseline. Compared to the control group, RSI (p &lt; 0.001), HAMA (p &lt; 0.001), and HAMD (p &lt; 0.001) scores in tVNS group were significantly lower at the end of treatment. Similarly, the resting pressure of UESP (p &lt; 0.05) and LESP (p &lt; 0.05) in tVNS group were significantly higher than that of control group. Notably, RMSSD (p &lt; 0.05) and HF (p &lt; 0.05) in tVNS group were significantly higher than that of control group.ConclusionThis study demonstrated that tVNS as a therapeutic approach is effective in alleviating LPRD symptoms. Furthermore, it suggests that improvements in esophageal motility could be associated with vagus nerve-dependent mechanisms.