bluuebunny/crossref_metadata_2025_split huggingface dataset:
A combined transcriptomics and proteomics approach reveals S100A4 as a potential biomarker for Graves’ orbitopathy
Authors: Chng Chiaw-Ling , Lai Oi Fah , Seah Lay-Leng , Yong Kai-Ling , Chung Yvonne Hsi-Wei , Goh Rochelle , Lim Che Kang 
Published: September 2024

BackgroundThere are no reliable biomarkers to identify Graves’ disease patients who will develop severe Graves’ orbitopathy (GO). We hypothesize that integrating various omics platforms can enhance our understanding of disease mechanisms and uncover potential biomarkers. This study aimed to (1) elucidate the differential gene expression profile of orbital fibroblasts in GO during early adipogenesis to better understand disease mechanisms and (2) compare tear protein profiles from our earlier study and the transcriptome profiles of orbital fibroblasts (OFs) to identify possible biomarkers of the disease.MethodsOFs were grown from orbital adipose tissue obtained from nine GO patients (three for discovery and six for validation experiments). Total RNA was extracted from OFs on day 0 as the baseline for each sample and from differentiated OFs on days 4 and 8. Protein–protein interaction (PPI) analysis and functional enrichment analysis were also carried out. The differentially expressed genes (DEGs) from the RNA sequencing experiments were then compared to the full tear proteome profile from the author’s previous study, which examined the tear protein changes of GO patients based on fold change &gt; 1.6 or &lt; −1.6. FDR &lt; 0.05 was applied within all datasets. Further validation of S100 calcium-binding protein A4 (S100A4) downregulation in GO was performed via quantitative real-time PCR (qPCR).ResultsThe whole transcriptomic analysis revealed 9 upregulated genes and 15 downregulated genes in common between the discovery and validation experiments. From the PPI network analysis, an interaction network containing six identified DEGs (ALDH2, MAP2K6, MT2A, SOCS3, S100A4, and THBD) was observed. The functional enrichment network analysis identified a set of genes related to oxysterol production. S100A4 was found to be consistently downregulated in both our transcriptome studies and the full-tear proteome profile from the author’s previous study.ConclusionOur study identified several DEGs and potential gene pathways in GO patients, which concurred with the results of other studies. Tear S100A4 may serve as a biomarker for the propensity to develop thyroid eye disease (TED) in patients with autoimmune thyroid disease (AITD) before clinical manifestation and should be confirmed in future studies.
Genetic characterization of cashmere goat (Capra hircus) populations in Mongolia
Authors: Baldan Sergelen , Sölkner Johann , Gebre Kahsa Tadel , Mészáros Gábor , Crooijmans Richard , Periasamy Kathiravan , Pichler Rudolf , Manaljav Bayarjargal , Baatar Narantuya , Purevdorj Myagmarsuren 
Published: September 2024

ObjectiveCharacterization studies of the phenotypic and genetic diversity of Mongolian goats are limited, despite several goat breeds being registered in the country. This study aimed to evaluate the phenotypic and genetic diversity of 14 cashmere goat populations in Mongolia, consisting largely of identified goat breeds.MethodsBody weight, cashmere quality, and coat color were the phenotypic traits considered in this study. A linear model was used to fit body weight and cashmere traits, and least squares means (LSMs) were estimated for the region and location classes. Genetic diversity and structure were assessed using a goat 50K SNP array.ResultsThe studied populations exhibited greater phenotypic diversity at the regional level. A very small overall differentiation index (Fst: 0.017) was revealed by Wright’s Fst and a very small overall inbreeding index (FROH1:0.019) was revealed based on runs of homozygosity. Genetic clustering of populations by principal components showed large variances for the two goat populations of the Russian admixture (Gobi Gurvan Saikhan and Uuliin Bor), and smaller but differentiated clusters for the remaining populations. Similar results were observed in the admixture analysis, which identified populations with the highest (Govi Gurvan Saikhan and Uuliin Bor) and lowest (Tsagaan Ovoo Khar) exotic admixtures. A genomewide association study (GWAS) of body weight and cashmere traits identified a few significant variants on chromosomes 2, 4, 5, 9, and 15, with the strongest variant for cashmere yield on chromosome 4. The GWAS on coat color yielded nine significant variants, with the strongest variants located on chromosomes 6, 13, and 18 and potential associations with KIT, ASIP, and MC1R genes. These signals were also found in other studies on coat color and patterns in goats.ConclusionMongolian cashmere goats showed relatively low genetic differentiation and low inbreeding levels, possibly caused by the traditional pastoral livestock management system and the practice of trading breeding bucks across provinces, along with a recent increase in the goat population. Further investigation of cashmere traits using larger samples and alternative methods may help identify the genes or genomic regions underlying cashmere quality in goats.
FCGR2/3 polymorphisms are associated with susceptibility to Kawasaki disease but do not predict intravenous immunoglobulin resistance and coronary artery aneurysms
Authors: Uittenbogaard Paula , Netea Stejara A. , Tanck Michael W. T. , Geissler Judy , Buda Piotr , Kowalczyk-Domagała Monika , Okarska-Napierała Magdalena , van Stijn Diana , Tacke Carline E. ,   US Kawasaki Disease Genetics Consortium, Burgner David P. , Shimizu Chisato , Burns Jane C. , Kuipers Irene M. , Kuijpers Taco W. , Nagelkerke Sietse Q. 
Published: September 2024

IntroductionKawasaki disease (KD) is a pediatric vasculitis that can result in coronary artery aneurysm (CAA) formation, which is a dangerous complication. Treatment with intravenous immunoglobulin (IVIg) significantly decreases the risk of CAA, possibly through competitive binding to Fc-gamma receptors (FcγRs), which reduces the binding of pathological immune complexes. However, ~20% of children have recrudescence of fever and have an increased risk of CAA. Therefore, we aimed to identify genetic markers at the FCGR2/3 locus associated with susceptibility to KD, IVIg resistance, or CAA.Materials and methodsWe investigated the association of single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs) at the FCGR2/3 locus with KD susceptibility, IVIg resistance, and CAA risk using a family-based test (KD susceptibility) and case–control analyses (IVIg resistance and CAA risk) in different cohorts, adding up to a total of 1,167 KD cases. We performed a meta-analysis on IVIg resistance and CAA risk including all cohorts supplemented by previous studies identified through a systematic search.ResultsFCGR2A-p.166His was confirmed to be strongly associated with KD susceptibility (Z = 3.17, p = 0.0015). In case–control analyses, all of the investigated genetic variations at the FCGR2/3 locus were generally not associated with IVIg resistance or with CAA risk, apart from a possible association in a Polish cohort for the FCGR3B-NA2 haplotype (OR = 2.15, 95% CI = 1.15–4.01, p = 0.02). Meta-analyses of all available cohorts revealed no significant associations of the FCGR2/3 locus with IVIg resistance or CAA risk.DiscussionFCGR2/3 polymorphisms are associated with susceptibility to KD but not with IVIg resistance and CAA formation. Currently known genetic variations at the FCGR2/3 locus are not useful in prediction models for IVIg resistance or CAA risk.
Obstetrical and perinatal outcomes of women with preeclampsia at Woldia Comprehensive Specialized Hospital, Northeast Ethiopia
Authors: Kumsa Henok , Mergiyaw Desalew 
Published: September 2024

BackgroundPreeclampsia is a multisystem disorder that affects pregnant women. Preeclampsia and its complications are the leading causes of maternal and perinatal morbidity and mortality in developing countries. Studies conducted in Ethiopia have primarily concentrated on preeclampsia’s trends and prevalence rather than its obstetrical and perinatal consequences. Thus, this study aimed to determine the risk of adverse obstetric and perinatal outcomes among women with preeclampsia at Woldia Comprehensive Specialized Hospital, Northeast Ethiopia.MethodsA retrospective cohort study was conducted among 140 preeclamptic women and 280 normotensive women who gave birth at Woldia Comprehensive Specialized Hospital between 30 December 2020 and 29 December 2022. Maternal records were retrieved using data-extraction tools. The data were entered into EpiData version 4.6.0.6 and analyzed using SPSS version 26. Binary and multivariable logistic regression models were used to test the associations between independent and outcome variables. The adjusted odds ratio (OR) with a 95% confidence interval (CI) and p-values &lt;0.05 were used to measure the strength of the association and declare the level of statistical significance.ResultsThe odds of at least one adverse obstetric outcome among preeclamptic women were 2.25 times higher than those among normotensive women [AOR: 2.25, 95% CI: (1.06, 4.77)]. In addition, babies born to preeclamptic women were at a higher risk of perinatal death [AOR: 2.90, 95% CI: (1.10, 8.17)], low birth weight [AOR: 3.11, 95% CI: (1.43, 6.7)], birth asphyxia [AOR: 2.53, 95% CI: (1.15, 5.5)], and preterm birth [AOR: 2.21, 95% CI: (1.02, 4.8)] than babies born to normotensive women.ConclusionMore adverse obstetric and perinatal outcomes were observed in women with preeclampsia than those in normotensive women. This study highlights the significantly elevated level of at least one adverse obstetric outcome associated with preeclampsia, low hemoglobin level, and rural residents. Moreover, perinatal death, low birth weight, asphyxia, and preterm birth were significantly associated with preeclampsia.
Comparative effectiveness of combined biologic agents versus standard therapies in the treatment of plaque psoriasis: a retrospective analysis
Authors: Wu Bo , Chen Qian , Cao Rong , Zhu Lei , Zhu Hongyan 
Published: September 2024

IntroductionPlaque psoriasis is a persistent skin disorder that necessitates efficient management. This study investigates the therapeutic effectiveness and timeline for skin lesion resolution in plaque psoriasis patients treated with combined biologic agents compared to standard therapies.MethodsConducted retrospectively between March 2020 and March 2023, the study included 162 patients with moderate to severe plaque psoriasis. Participants were divided into two groups: the Control Group, which received standard treatments, and the Combined Biologic Agent Group, which received additional biologic therapy with secukinumab. Participants in the Control Group received standard treatments, while those in the Combined Biologic Agent Group received standard treatments plus secukinumab.ResultsThe results showed that the Combined Biologic Agent Group experienced a significantly faster onset of therapeutic effects, with an average time of 3.04 ± 2.25 days compared to 6.12 ± 2.06 days in the Control Group. Additionally, skin lesion resolution occurred more rapidly in the biologic agent group (7.04 ± 2.13 days) than in the control group (14.56 ± 4.73 days). By week 24, the Psoriasis Area and Severity Index (PASI) scores demonstrated a more substantial reduction in the biologic agent group, decreasing from 26.98 ± 11.28 to 2.48 ± 3.01, whereas the control group showed a reduction from 25.82 ± 10.47 to 10.40 ± 7.63. The overall effectiveness rate was higher in the biologic agent group, with no cases of ineffectiveness, compared to a 20.99% ineffectiveness rate in the control group. Furthermore, there was no recurrence of the disease in the biologic agent group, while the control group experienced an 11.11% recurrence rate. Both groups had a similar incidence of adverse reactions, indicating that the addition of biologic agents does not significantly increase the risk of adverse events.DiscussionThese findings suggest that combined biologic agent therapy offers a more effective and faster treatment option for plaque psoriasis without compromising safety. However, larger-scale clinical trials are necessary to validate these results and establish the long-term benefits and safety of this treatment approach in diverse patient populations.
Solubilization and enhanced degradation of benzene phenolic derivatives—Bisphenol A/Triclosan using a biosurfactant producing white rot fungus Hypocrea lixii S5 with plant growth promoting traits
Authors: Chaturvedi Mridula , Kaur Navpreet , Rahman Pattanathu K. S. M. , Sharma Shashi 
Published: September 2024

IntroductionEndocrine disrupting chemicals (EDCs) as benzene phenolic derivatives being hydrophobic partition to organic matter in sludge/soil sediments and show slow degradation rate owing to poor bioavailability to microbes.MethodsIn the present study, the potential of a versatile white rot fungal isolate S5 identified as Hypocrea lixii was monitored to degrade bisphenol A (BPA)/triclosan (TCS) under shake flask conditions with concomitant production of lipopeptide biosurfactant (BS) and plant growth promotion.ResultsSufficient growth of WRF for 5 days before supplementation of 50 ppm EDC (BPA/TCS) in set B showed an increase in degradation rates by 23% and 29% with corresponding increase in secretion of lignin-modifying enzymes compared to set A wherein almost 84% and 97% inhibition in fungal growth was observed when BPA/TCS were added at time of fungal inoculation. Further in set B, EDC concentration stimulated expression of laccase and lignin peroxidase (Lip) with 24.44 U/L of laccase and 281.69 U/L of Lip in 100 ppm BPA and 344 U/L Lip in 50 ppm TCS supplemented medium compared to their respective controls (without EDC). Biodegradation was also found to be correlated with lowering of surface tension from 57.02 mN/m (uninoculated control) to 44.16 mN/m in case of BPA and 38.49 mN/m in TCS, indicative of biosurfactant (BS) production. FTIR, GC-MS, and LC-ESI/MSMS confirmed the presence of surfactin lipopeptide isoforms. The WRF also displayed positive plant growth promoting traits as production of ammonia, indole acetic acid, siderophores, Zn solubilization, and 1-1-aminocyclopropane-1-carboxylate (ACC) deaminase activity, reflecting its soil restoration ability.DiscussionThe combined traits of biosurfactant production, EDC degradation and plant growth promotion displayed by WRF will help in emulsifying the hydrophobic pollutants favoring their fast degradation along with restoration of contaminated soil in natural conditions.
Co-expression of endoglucanase and cellobiohydrolase from yak rumen in lactic acid bacteria and its preliminary application in whole-plant corn silage fermentation
Authors: Wan Xuerui , SunKang Yongjie , Chen Yijun , Zhang Zhao , Gou Huitian , Xue Yu , Wang Chuan , Wei Yaqin , Yang Yuze 
Published: September 2024

IntroductionEndoglucanase (EG) and cellobiohydrolase (CBH) which produced by microorganisms, have been widely used in industrial applications.MethodsIn order to construct recombinant bacteria that produce high activity EG and CBH, in this study, eg (endoglucanase) and cbh (cellobiohydrolase) were cloned from the rumen microbial genome of yak and subsequently expressed independently and co-expressed within Lactococcus lactis NZ9000 (L. lactis NZ9000).ResultsThe recombinant strains L. lactis NZ9000/pMG36e-usp45-cbh (L. lactis-cbh), L. lactis NZ9000/pMG36e-usp45-eg (L. lactis-eg), and L. lactis NZ9000/pMG36e-usp45-eg-usp45-cbh (L. lactis-eg-cbh) were successfully constructed and demonstrated the ability to secrete EG, CBH, and EG-CBH. The sodium carboxymethyl cellulose activity of the recombinant enzyme EG was the highest, and the regenerated amorphous cellulose (RAC) was the specific substrate of the recombinant enzyme CBH, and EG-CBH. The optimum reaction temperature of the recombinant enzyme CBH was 60°C, while the recombinant enzymes EG and EG-CBH were tolerant to higher temperatures (80°C). The optimum reaction pH of EG, CBH, and EG-CBH was 6.0. Mn2+, Fe2+, Cu2+, and Co2+ could promote the activity of CBH. Similarly, Fe2+, Ba2+, and higher concentrations of Ca2+, Cu2+, and Co2+ could promote the activity of EG-CBH. The addition of engineered strains to whole-plant corn silage improved the nutritional quality of the feed, with the lowest pH, acid detergent fiber (ADF), and neutral detergent fiber (NDF) contents observed in silage from the L. lactis-eg group (p &lt; 0.05), and the lowest ammonia nitrogen (NH3-N), and highest lactic acid (LA) and crude protein (CP) contents in silage from the L. lactis-eg + L. lactis-cbh group (p &lt; 0.05), while the silage quality in the L. lactis-cbh group was not satisfactory. DiscussionConsequently, the recombinant strains L. lactis-cbh, L. lactis-eg, and L. lactis-eg-cbh were successfully constructed, which could successfully expressed EG, CBH, and EG-CBH. L. lactis-eg promoted silage fermentation by degrading cellulose to produce sugar, enabling the secretory expression of EG, CBH, and EG-CBH for potential industrial applications in cellulose degradation.
Genomic surveillance reveals low-level circulation of two subtypes of genogroup C coxsackievirus A10 in Nanchang, Jiangxi Province, China, 2015–2023
Authors: He Fenglan , Zhu Chunlong , Wu Xuan , Yi Liu , Lin Ziqi , Wen Weijie , Zhu Chunhui , Tu Junling , Qian Ke , Li Qingxiang , Ma Guangqiang , Li Hui , Wang Fang , Zhou Xianfeng 
Published: September 2024

IntroductionIn recent years, coxsackievirus (CV) A10 has been associated with increasing sporadic hand, foot, and mouth disease (HFMD) cases and outbreaks globally. In addition to mild symptoms such as pharyngitis and herpangina, CVA10-related complications or even fatality can occur. Currently, systematic phylogenetic studies of CVA10 are limited.MethodsIn this study, we first explored the epidemiological and genetic characteristics of CVA10 in Nanchang, an inland southeastern city of China, based on the HFMD surveillance network from 2015-2023.ResultsAmong 3429 enterovirus-positive cases, 110 (3.04%) were associated with CVA10, with a male-to-female ratio of 1.62. The median age of the CVA10 patients was 2.3 years (interquartile range, IQR 1.0-4.0), with 94.55% (104/110) of the patients aged less than 5 years. Phylogenetic analyses using the full-length VP1, 5’UTR, P1, P2, P3 sequences and near full-length genomes indicated that CVA10 strains (n = 57) isolated in Nanchang belonged to genogroup C; two strains identified in 2017 belonged to C1 subtypes clustered with strains from Vietnam, Madagascar, France and Spain; and the others belonged to C2 subtypes interdigitating with CVA10 isolates from mainland China, the United States and Australia. Through extensive analysis, we identified a rare F168Y mutation in epitope 4 of VP1 in a Madagascar strain of genogroup F and a Chinese strain of genogroup C. Based on Bayesian evolutionary analyses, the average nucleotide substitution rate for the VP1 gene of CV10 strains was 3.07×10–3 substitutions/site/year. The most recent common ancestor (tMRCA) of genogroup C was dated 1990.84, and the tMRCA of CVA10 strains from Nanchang was dated approximately 2003.16, similar to strains circulating in other regions of China, suggesting that the viruses were likely introduced and cryptically circulated in China before the establishment of the HFMD surveillance network. Recombination analysis indicated intertypic recombination of the Nanchang strain with the genogroup G strain in the 3D region.DiscussionGiven the shifting dominance of viral genotypes and frequent recombination events, the existing surveillance system needs to be regulated to enhance genomic surveillance efforts on a more diverse spectrum of genotypes in the future.
Disruptive and complementary effects of depression symptoms on spontaneous brain activity in the subcortical vascular mild cognitive impairment
Authors: Hu Liyu , Chen Jianxiang , Li Xinbei , Zhang Haoran , Zhang Jinhuan , Lu Yingqi , Lian Jie , Yu Haibo , Yang Nan , Wang Jianjun , Lyu Hanqing , Xu Jinping 
Published: September 2024

BackgroundAlthough depression symptoms are commonly reported in patients with subcortical vascular mild cognitive impairment (svMCI), their impact on brain functions remains largely unknown, with diagnoses mainly dependent on behavioral assessments.MethodsIn this study, we analyzed resting-state fMRI data from a cohort of 34 svMCI patients, comprising 18 patients with depression symptoms (svMCI+D) and 16 patients without (svMCI-D), along with 34 normal controls (NC). The study used the fraction of the amplitude of low-frequency fluctuations (fALFF), resting-state functional connectivity, correlation analyses, and support vector machine (SVM) techniques.ResultsThe fALFF of the right cerebellum (CERE.R) differed among the svMCI+D, svMCI-D, and NC groups. Specifically, the regional mean fALFF of CERE. R was lower in svMCI-D patients compared to NC but higher in svMCI+D patients compared to svMCI-D patients. Moreover, the adjusted fALFF of CERE. R showed a significant correlation with Montreal Cognitive Assessment (MOCA) scores in svMCI-D patients. The fALFF of the right orbital part of the superior frontal gyrus was significantly correlated with Hamilton Depression Scale scores in svMCI+D patients, whereas the fALFF of the right postcingulate cortex (PCC.R) showed a significant correlation with MOCA scores in svMCI-D patients. Furthermore, RSFC between PCC. R and right precuneus, as well as between CERE. R and the right lingual gyrus (LING.R), was significantly reduced in svMCI-D patients compared to NC. In regional analyses, the adjusted RSFC between PCC. R and PreCUN. R, as well as between CERE. R and LING. R, was decreased in svMCI-D patients compared to NC but increased in svMCI+D patients compared to svMCI-D. Further SVM analyses achieved good performances, with an area under the curve (AUC) of 0.82 for classifying svMCI+D, svMCI-D, and NC; 0.96 for classifying svMCI+D and svMCI-D; 0.82 for classifying svMCI+D and NC; and 0.92 for classifying svMCI-D and NC.ConclusionThe study revealed disruptive effects of cognitive impairment, along with both disruptive and complementary effects of depression symptoms on spontaneous brain activity in svMCI. Moreover, these findings suggest that the identified features might serve as potential biomarkers for distinguishing between svMCI+D, svMCI-D, and NC, thereby guiding clinical treatments such as transcranial magnetic stimulation for svMCI.