bluuebunny/crossref_metadata_2025_split huggingface dataset:
Degradation of specific glycosaminoglycans improves transfection efficiency and vector production in transient lentiviral vector manufacturing processes
Authors: Williams-Fegredo Thomas , Davies Lee , Knevelman Carol , Mitrophanous Kyriacos , Miskin James , Rafiq Qasim A. 
Published: June 2024

Both cell surface and soluble extracellular glycosaminoglycans have been shown to interfere with the exogenous nucleic acid delivery efficiency of non-viral gene delivery, including lipoplex and polyplex-mediated transfection. Most gene therapy viral vectors used commercially and in clinical trials are currently manufactured using transient transfection-based bioprocesses. The growing demand for viral vector products, coupled with a global shortage in production capability, requires improved transfection technologies and processes to maximise process efficiency and productivity. Soluble extracellular glycosaminoglycans were found to accumulate in the conditioned cell culture medium of suspension adapted HEK293T cell cultures, compromising transfection performance and lentiviral vector production. The enzymatic degradation of specific, chondroitin sulphate-based, glycosaminoglycans with chondroitinase ABC was found to significantly enhance transfection performance. Additionally, we report significant improvements in functional lentiviral vector titre when cultivating cells at higher cell densities than those utilised in a control lentiviral vector bioprocess; an improvement that was further enhanced when cultures were supplemented with chondroitinase ABC prior to transfection. A 71.2% increase in functional lentiviral vector titre was calculated when doubling the cell density prior to transfection compared to the existing process and treatment of the high-density cell cultures with 0.1 U/mL chondroitinase ABC resulted in a further 18.6% increase in titre, presenting a method that can effectively enhance transfection performance.
Effects of ankylosing spondylitis on cardiovascular disease: aMendelian randomization study
Authors: Xiao Lu , Lin Shudian , Zhan Feng 
Published: June 2024

ObjectiveAccumulating evidence suggests that patients with ankylosing spondylitis (AS) have an elevated risk for cardiovascular disease (CVD) and cardiovascular death, however, whether AS has causal effects on the risk of CVD is unclear.Two-sample Mendelian randomization (MR) was utilizedto examine the probable causal link between them.MethodsSummary statistics from publicly released genome-wide association studies (GWAS) was used to perform MR analyses. Genetically predicted AS was selected as the exposure variable from published GWAS meta-analyses. CVD was adopted as the outcome variable. The inverse variant weighted method was employed to obtain the casual estimates. The robustness of the results was also examined by evaluating the pleiotropy and heterogeneity of single-nucleotide polymorphisms.ResultsAccording to MR analyses, genetic susceptibility to AS was associated with a high risk of heart failure and ischemic stroke, while negativelygenetic susceptibility was found between AS and peripheral atherosclerosis. No statistical relationship was found between AS and venous thromboembolism, atrial fibrillation, coronary atherosclerosis, and valvular heart disease. Sensitivity analysis showed no evidence of horizontal pleiotropy or heterogeneity.ConclusionThe present study suggests that AS exerts causal effects on the risk of CVD, including heart failure, ischemic stroke, and peripheral atherosclerosis.
Identification of differentially expressed genes of blood leukocytes for Schizophrenia
Authors: Wang Feifan , Fan Yao , Li Yinghui , Zhou Yuan , Wang Xin , Zhu Mengya , Chen Xuefei , Xue Yong , Shen Chong 
Published: June 2024

BackgroundSchizophrenia (SCZ) is a severe neurodevelopmental disorder with brain dysfunction. This study aimed to use bioinformatic analysis to identify candidate blood biomarkers for SCZ.MethodsThe study collected peripheral blood leukocyte samples of 9 SCZ patients and 20 healthy controls for RNA sequencing analysis. Bioinformatic analyses included differentially expressed genes (DEGs) analysis, pathway enrichment analysis, and weighted gene co-expression network analysis (WGCNA).ResultsThis study identified 1,205 statistically significant DEGs, of which 623 genes were upregulated and 582 genes were downregulated. Functional enrichment analysis showed that DEGs were mainly enriched in cell chemotaxis, cell surface, and serine peptidase activity, as well as involved in Natural killer cell-mediated cytotoxicity. WGCNA identified 16 gene co-expression modules, and five modules were significantly correlated with SCZ (p &lt; 0.05). There were 106 upregulated genes and 90 downregulated genes in the five modules. The top ten genes sorted by the Degree algorithm were RPS28, BRD4, FUS, PABPC1, PCBP1, PCBP2, RPL27A, RPS21, RAG1, and RPL27. RAG1 and the other nine genes belonged to the turquoise and pink module respectively. Pathway enrichment analysis indicated that these 10 genes were mainly involved in processes such as Ribosome, cytoplasmic translation, RNA binding, and protein binding.ConclusionThis study finds that the gene functions in key modules and related enrichment pathways may help to elucidate the molecular pathogenesis of SCZ, and the potential of key genes to become blood biomarkers for SCZ warrants further validation.
Case report: Disitamab vedotin combined with immunotherapy demonstrated excellent efficacy in scrotal Paget’s disease with Her-2 overexpression
Authors: Wang Jia-Ling , Meng Wen-Jun , Hu Nian , Liu Ji-Yan 
Published: June 2024

BackgroundExtramammary Paget’s disease (EMPD) is a rare epithelial malignancy, and approximately 30%–40% of EMPD patients overexpress human epidermal growth factor receptor 2 (Her-2). Currently, there are no established standard treatments for advanced EMPD while anti–Her-2 therapy is recommended for Her-2–positive cases.Case presentationHere, we report a 51-year-old male diagnosed with advanced Her-2–positive EMPD, presenting with numerous lymph node metastases. This patient received disitamab vedotin (an antibody-drug conjugate, targeting Her-2) combined with serplulimab as first-line treatment. After seven cycles of combination therapy, the patient tolerated the treatment well and the lymph node lesions continued to shrink. However, the patient developed immunotherapy-related pneumonia following the eighth treatment. Hormone therapy was administered while all the anti-tumor therapies were halted. After the pneumonia improved, the patient underwent positron emission tomography-computed tomography, revealing a complete response to his tumor. To consolidate the effect, he received another five cycles of disitamab vedotin monotherapy as maintenance therapy, without experiencing any adverse events. To date, the patient has remained in good health without any recurrence 10 months after drug discontinuance.ConclusionDisitamab vedotin combined with immunotherapy demonstrated a long-term clinical benefit in advanced Her-2–positive EMPD. For rare solid tumors with Her-2 overexpression, disitamab vedotin combined with immunotherapy might offer a viable therapeutic choice.
A degranulation assay using Vγ9Vδ2 T cells for the rapid diagnosis of familial hemophagocytic syndromes
Authors: Jorisch-Mühlebach Olivia , Pitts Dina , Tinner Raphaela , Teh Hong Ying , Roelli Conrad , Prader Seraina , Vavassori Stefano , Pachlopnik Schmid Jana 
Published: June 2024

IntroductionHemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune disorder characterized by uncontrolled lymphocyte and macrophage activation and a subsequent cytokine storm. The timely initiation of immunosuppressive treatment is crucial for survival.MethodsHere, we harnessed Vγ9Vδ2 T cell degranulation to develop a novel functional assay for the diagnosis of HLH. We compared the novel assay with the conventional natural killer (NK) cell stimulation method in terms of efficiency, specificity, and reliability. Our analysis involved 213 samples from 182 individuals, including 23 samples from 12 patients with degranulation deficiency (10 individuals with UNC13D deficiency, 1 with STXBP2 deficiency, and 1 with RAB27A deficiency).ResultsWhile both tests exhibited 100% sensitivity, the Vγ9Vδ2 T cell degranulation assay showed a superior specificity of 86.2% (n=70) compared to the NK cell degranulation assay, which achieved 78.9% specificity (n=213). The Vγ9Vδ2 T cell degranulation assay offered simpler technical requirements and reduced labor intensity, leading to decreased susceptibility to errors with faster processing times.DiscussionThis efficiency stemmed from the sole requirement of dissolving (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) powder, contrasting with the intricate maintenance of K562 cells necessary for the NK cell degranulation assay. With its diminished susceptibility to errors, we anticipate that the assay will require fewer repetitions of analysis, rendering it particularly well-suited for testing infants.ConclusionThe Vγ9Vδ2 T cell degranulation assay is a user-friendly, efficient diagnostic tool for HLH. It offers greater specificity, reliability, and practicality than established methods. We believe that our present findings will facilitate the prompt, accurate diagnosis of HLH and thus enable rapid treatment and better patient outcomes.
Drone-based photogrammetry reveals differences in humpback whale body condition and mass across North Atlantic foraging grounds
Authors: Napoli Chelsi , Hirtle Nathan , Stepanuk Julia , Christiansen Fredrik , Heywood Eleanor I. , Grove Thomas J. , Stoller Alyssa , Dodds Flordespina , Glarou Maria , Rasmussen Marianne H. , Lonati Gina L. , Davies Kimberley T.A. , Videsen Simone , Simon Malene J. , Boye Tenna K. , Zoidis Ann , Todd Sean K. , Thorne Lesley H. 
Published: June 2024

Baleen whales are key consumers in marine ecosystems and can serve as ecosystem sentinels. Body condition, defined as an individual’s energy stores relative to its structural size, can provide a useful proxy for health in baleen whales. As capital breeders, important life history events in baleen whales such as seasonal migrations and reproduction depend on having sufficient energy stores. Spatiotemporal variability of body condition of baleen whales can reflect differences in energy accumulated during the foraging season. Here we assess and compare the body condition and mass of humpback whales (Megaptera novaeangliae) across four different foraging areas from the West Indies distinct population segment in the Northwest Atlantic. Morphometric measurements of humpback whales were obtained using unoccupied aerial systems (UAS, or drones) from the New York Bight, the Gulf of Maine, Iceland, and Greenland. Uncertainty in morphometric estimates was incorporated and propagated using a bootstrapping approach. Measurements were used to estimate body volume and calculate a body condition index (BCI) for each individual whale. Since body mass is a key parameter for understanding animal physiology and bioenergetics, we further compared whale body mass to body size between foraging areas by converting body volume to body mass using estimates of tissue density from tagging studies. BCI showed significant differences between foraging areas with a large effect size (ANCOVA: mean η2 = 0.168; all p&lt; 0.001) when incorporating day of year and year as covariates. Humpback whales in the Gulf of Maine showed significantly higher BCI than those in the New York Bight, Iceland, and Greenland. Standardized Major Axis (SMA) regressions comparing log-log relationships of both body volume and body mass, respectively, to total length reinforced these results. Humpback whales in the Gulf of Maine showed significantly higher elevation in the SMAs than those in the other study regions (p&lt;0.001), implying that humpback whales foraging in the Gulf of Maine accumulated greater energy reserves for a given body size. Estimates of body mass indicate that for a given body length, humpback whales in the Gulf of Maine have an 18% greater body mass than those in the New York Bight, Iceland, or Greenland. Regional differences in prey availability or anthropogenic threats could contribute to the observed patterns in body condition. Our findings highlight the importance of regional environmental factors to the nutritional health of baleen whales.
Mendelian randomization based on genome-wide association studies and expression quantitative trait loci, predicting gene targets for the complexity of osteoarthritis as well as the clinical prognosis of the condition
Authors: Yan Yiqun , He Junyan , Xu Zelin , Wang Chen , Hu Zhongyao , Zhang Chun , Cheng Wendan 
Published: June 2024

BackgroundOsteoarthritis (OA) entails a prevalent chronic ailment, marked by the widespread involvement of entire joints. Prolonged low-grade synovial inflammation serves as the key instigator for a cascade of pathological alterations in the joints.ObjectiveThe study seeks to explore potential therapeutic targets for OA and investigate the associated mechanistic pathways.MethodsSummary-level data for OA were downloaded from the genome-wide association studies (GWAS) database, expression quantitative trait loci (eQTL) data were acquired from the eQTLGen consortium, and synovial chip data for OA were obtained from the GEO database. Following the integration of data and subsequent Mendelian randomization analysis, differential analysis, and weighted gene co-expression network analysis (WGCNA) analysis, core genes that exhibit a significant causal relationship with OA traits were pinpointed. Subsequently, by employing three machine learning algorithms, additional identification of gene targets for the complexity of OA was achieved. Additionally, corresponding ROC curves and nomogram models were established for the assessment of clinical prognosis in patients. Finally, western blotting analysis and ELISA methodology were employed for the initial validation of marker genes and their linked pathways.ResultsTwenty-two core genes with a significant causal relationship to OA traits were obtained. Through the application of distinct machine learning algorithms, MAT2A and RBM6 emerged as diagnostic marker genes. ROC curves and nomogram models were utilized for evaluating both the effectiveness of the two identified marker genes associated with OA in diagnosis. MAT2A governs the synthesis of SAM within synovial cells, thereby thwarting synovial fibrosis induced by the TGF-β1-activated Smad3/4 signaling pathway.ConclusionThe first evidence that MAT2A and RBM6 serve as robust diagnostic for OA is presented in this study. MAT2A, through its involvement in regulating the synthesis of SAM, inhibits the activation of the TGF-β1-induced Smad3/4 signaling pathway, thereby effectively averting the possibility of synovial fibrosis. Concurrently, the development of a prognostic risk model facilitates early OA diagnosis, functional recovery evaluation, and offers direction for further therapy.
Machine vision-based gait scan method for identifying cognitive impairment in older adults
Authors: Qin Yuzhen , Zhang Haowei , Qing Linbo , Liu Qinghua , Jiang Hua , Xu Shen , Liu Yixin , He Xiaohai 
Published: June 2024

ObjectiveEarly identification of cognitive impairment in older adults could reduce the burden of age-related disabilities. Gait parameters are associated with and predictive of cognitive decline. Although a variety of sensors and machine learning analysis methods have been used in cognitive studies, a deep optimized machine vision-based method for analyzing gait to identify cognitive decline is needed.MethodsThis study used a walking footage dataset of 158 adults named West China Hospital Elderly Gait, which was labelled by performance on the Short Portable Mental Status Questionnaire. We proposed a novel recognition network, Deep Optimized GaitPart (DO-GaitPart), based on silhouette and skeleton gait images. Three improvements were applied: short-term temporal template generator (STTG) in the template generation stage to decrease computational cost and minimize loss of temporal information; depth-wise spatial feature extractor (DSFE) to extract both global and local fine-grained spatial features from gait images; and multi-scale temporal aggregation (MTA), a temporal modeling method based on attention mechanism, to improve the distinguishability of gait patterns.ResultsAn ablation test showed that each component of DO-GaitPart was essential. DO-GaitPart excels in backpack walking scene on CASIA-B dataset, outperforming comparison methods, which were GaitSet, GaitPart, MT3D, 3D Local, TransGait, CSTL, GLN, GaitGL and SMPLGait on Gait3D dataset. The proposed machine vision gait feature identification method achieved a receiver operating characteristic/area under the curve (ROCAUC) of 0.876 (0.852–0.900) on the cognitive state classification task.ConclusionThe proposed method performed well identifying cognitive decline from the gait video datasets, making it a prospective prototype tool in cognitive assessment.
The transmission line foreign body detection algorithm based on weighted spatial attention
Authors: Wang Yuanyuan , Tian Haiyang , Yin Tongtong , Song Zhaoyu , Hauwa Abdullahi Suleiman , Zhang Haiyan , Gao Shangbing , Zhou Liguo 
Published: June 2024

IntroductionThe secure operation of electric power transmission lines is essential for the economy and society. However, external factors such as plastic film and kites can cause damage to the lines, potentially leading to power outages. Traditional detection methods are inefficient, and the accuracy of automated systems is limited in complex background environments.MethodsThis paper introduces a Weighted Spatial Attention (WSA) network model to address the low accuracy in identifying extraneous materials within electrical transmission infrastructure due to background texture occlusion. Initially, in the model preprocessing stage, color space conversion, image enhancement, and improved Large Selective Kernel Network (LSKNet) technology are utilized to enhance the model's proficiency in detecting foreign objects in intricate surroundings. Subsequently, in the feature extraction stage, the model adopts the dynamic sparse BiLevel Spatial Attention Module (BSAM) structure proposed in this paper to accurately capture and identify the characteristic information of foreign objects in power lines. In the feature pyramid stage, by replacing the feature pyramid network structure and allocating reasonable weights to the Bidirectional Feature Pyramid Network (BiFPN), the feature fusion results are optimized, ensuring that the semantic information of foreign objects in the power line output by the network is effectively identified and processed.ResultsThe experimental outcomes reveal that the test recognition accuracy of the proposed WSA model on the PL (power line) dataset has improved by three percentage points compared to that of the YOLOv8 model, reaching 97.6%. This enhancement demonstrates the WSA model's superior capability in detecting foreign objects on power lines, even in complex environmental backgrounds.DiscussionThe integration of advanced image preprocessing techniques, the dynamic sparse BSAM structure, and the BiFPN has proven effective in improving detection accuracy and has the potential to transform the approach to monitoring and maintaining power transmission infrastructure.
Age-related alterations in efferent medial olivocochlear-outer hair cell and primary auditory ribbon synapses in CBA/J mice
Authors: Dörje Nele Marie , Shvachiy Liana , Kück Fabian , Outeiro Tiago F. , Strenzke Nicola , Beutner Dirk , Setz Cristian 
Published: June 2024

IntroductionHearing decline stands as the most prevalent single sensory deficit associated with the aging process. Giving compelling evidence suggesting a protective effect associated with the efferent auditory system, the goal of our study was to characterize the age-related changes in the number of efferent medial olivocochlear (MOC) synapses regulating outer hair cell (OHC) activity compared with the number of afferent inner hair cell ribbon synapses in CBA/J mice over their lifespan.MethodsOrgans of Corti of 3-month-old CBA/J mice were compared with mice aged between 10 and 20 months, grouped at 2-month intervals. For each animal, one ear was used to characterize the synapses between the efferent MOC fibers and the outer hair cells (OHCs), while the contralateral ear was used to analyze the ribbon synapses between inner hair cells (IHCs) and type I afferent nerve fibers of spiral ganglion neurons (SGNs). Each cochlea was separated in apical, middle, and basal turns, respectively.ResultsThe first significant age-related decline in afferent IHC-SGN ribbon synapses was observed in the basal cochlear turn at 14 months, the middle turn at 16 months, and the apical turn at 18 months of age. In contrast, efferent MOC-OHC synapses in CBA/J mice exhibited a less pronounced loss due to aging which only became significant in the basal and middle turns of the cochlea by 20 months of age.DiscussionThis study illustrates an age-related reduction on efferent MOC innervation of OHCs in CBA/J mice starting at 20 months of age. Our findings indicate that the morphological decline of efferent MOC-OHC synapses due to aging occurs notably later than the decline observed in afferent IHC-SGN ribbon synapses.
Huangqin Qingre Chubi Capsule inhibits rheumatoid arthritis by regulating intestinal flora and improving intestinal barrier
Authors: Peng Yanhui , Huang Yurong , Li Hui , Li Chen , Wu Yajie , Chen Zhe-Sheng , Wang Xiao , Liao Faxue , Miao Chenggui 
Published: June 2024

BackgroundChanges in intestinal flora and intestinal barrier in patients with preclinical and diagnosed rheumatoid arthritis (RA) suggest that intestinal flora and intestinal barrier play an important role in the induction and persistence of RA. Huangqin Qingre Chubi Capsule (HQC) is a clinically effective herbal formula for the treatment of RA, but its therapeutic mechanism has not been fully clarified.Materials and methodsIn this study, real-time qPCR (RT-qPCR), 16SrRNA sequencing, Western blot (WB), immunofluorescence and other methods were used to investigate whether HQC inhibited RA.ResultsBased on research in collages-induced arthritis (CIA) model in mice, human colon cancer cell line (Caco-2), and fibroblast-like synoviocytes (FLS) from RA patients, we found that intestinal flora was disturbed in CIA model group, intestinal barrier was damaged, and lipolyaccharide (LPS) level was increased, and HQC could regulate intestinal flora and intestinal barrier and reduce LPS translocation into blood. Antibiotic depletion weakened the anti-RA effect of HQC, and HQC fecal microbiota transplantation alleviated RA pathology. In addition, LPS increased the expression of RA pathologic factors MMP3, Fibronectin and inflammatory factors IL-6, TNF-α, IL-1β and IL-8, indicating that elevated peripheral blood level of LPS was related to RA pathology.ConclusionThe dysregulation of intestinal flora and the disruption of intestinal barrier are significant factors in the development of RA. HQC improves RA by regulating intestinal flora, intestinal barrier and inhibiting LPS translocation into blood. The study unveiles RA’s new pathogenesis and laid a scientific groundwork for advancing HQC therapy for RA.