bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of pestle needle on Lumbar Disc Herniation: Study Protocol for a Randomized Controlled Trial
Authors: Liu Xuhao , Liao Tiannan , Zhong Lei , Dong Yuanwei , Zhang Di , Shen Yuquan , Fu Ping , Yuan Lei , Yu Yang , Fan Xiaohong
Published: April 2023

Background：Lumbar disc herniation (LDH) is a common and frequent disease in orthopedics. It is caused by degenerative changes of the lumbar spine and compression of the lumbar nerves, with the main clinical manifestation being painful involvement of the lumbar region and the legs，which in severe cases affects the patient's quality of life. The disease is treated in a variety of ways with varying degrees of efficacy, LDH is mainly treated conservatively with oral medication or external therapy of Traditional Chinese medicine (TCM) for mild cases, while surgery is required for severe cases. LDH surgical treatment is effective, but there are still some patients whose symptoms are difficult to improve after surgery and who are not suitable for surgical treatment. Pestle needle therapy is a unique external therapy of TCM method, which is non-invasive, non-painful, not easily infected, easy to operate, and easy for patients to accept. This study aimed to design a randomized controlled trial (RCT) to explore the effectiveness and safety of pestle needle in the treatment of LDH.
Methods：Sixty patients will be enrolled and randomly divided into one of two groups: the pestle needle group and the celecoxib group. The pestle needle group will be treated with pestle needle at Yaoyangguan bazhen, Heche-mingqiang section, BL23, BL25, GB30, BL40, BL57, BL60 for 30 minutes. 5 days is a course of treatment, with an interval of 2 days between courses, a total of 3 courses of treatment. The pestle needle manipulation is performed to the extent that the skin is flushed during the treatment. The celecoxib group participants will take one celecoxib capsule once a day for the duration of the study period. The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) score, Visual Analog Scale（VAS）score and Oswestry Disability Index（ODI）score were used as treatment outcome assessment indicators, while adverse events (AEs) were recorded. Patients were evaluated for efficacy at baseline, at the end of each course of treatment.
Discussion: This study will determine whether pestle needle is more effective and safer than celecoxib in the treatment of patients with LDH.
Trial registration The trial has been registered with the Chinese Clinical Trial Register (ChiCTR) under the Registration March ChiCTR2200057684.
Identification of F7 as a Hub Regulator in Hypertrophic Cardiomyopathy and Potential ceRNA Regulatory Network Based on Weighted Gene Co-expression Network Analysis
Authors: Pei Chong-Zhe , Meng Xinmin , dong yuxin , Sun Dongdong , Wu Xianming , Song Ningning , Zhou Xin , Yang Qing
Published: April 2023

Background. We identified a regulatory competing endogenous RNA (ceRNA) network and a hub gene for hypertrophic cardiomyopathy (HCM).
Methods. We obtained microarray datasets of HCM tissue from NCBI Gene Expression Omnibus (GEO) and identified differentially expressed genes using the R package “limma.” Subsequently, differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs were matched using online databases. We identified relationships between key modules and HCM using weighted gene co-expression network analysis, whereas protein–protein interaction networks were constructed in STRING. To verify hub genes, we performed a gene set enrichment analysis. Real-time quantitative PCR and western blotting were performed to examine hub-gene expression in a mouse model of Ang-II infusion-induced cardiac hypertrophy.
Results. We identified 271 upregulated and 368 downregulated lncRNAs in the GSE68316 dataset, along with 8 upregulated and 13 downregulated miRNAs in the GSE36946 dataset. We constructed a lncRNA–miRNA–mRNA ceRNA network in HCM using 6 downregulated lncRNAs, 1 upregulated miRNA, and 13 downregulated mRNAs. Another lncRNA–miRNA–mRNA ceRNA network in HCM was constructed with 15 upregulated lncRNAs, 1 downregulated miRNA, and 79 upregulated mRNAs. The results of WGCNA showed that black and turquoise modules were significantly related to HCM. Through Gene Ontology (GO) analysis, F7 was identified as a hub gene with network function enriched in neuroactive ligand–receptor interaction, cytokine–cytokine receptor interaction, and actin cytoskeleton regulation.
Conclusions. This study reveals a potential molecular regulatory mechanism that could improve HCM diagnosis and treatment. Furthermore, the hub gene F7 might play an important role in HCM progression and be a valuable biomarker.
Construction of a prognostic nomogram for early-onset colorectal cancer patients ： a population-based study in the SEER database and China
Authors: Chang Zewen , Xiong Huan , Wang Jiaqi , Li Xingyuan , Zhang Hao , Liu Yunxiao , Yuan Ziming , Hu Hanqing , Tang Qingchao
Published: April 2023

Background The prognosis of early-onset colorectal cancer (EOCRC) remains largely constrained by clinical heterogeneity. The aim of this paper was to construct a targeted prognostic nomogram combining multi-indicator to individually predict overall survival (OS) for EOCRC.Methods 6893 patients from the SEER database (SEER training set: n = 3447; SEER validation set: n = 3446) and 271 patients from the Second Affiliated Hospital of Harbin Medical University (External validation set) were included. Independent factors in the multivariate analysis were used to build the nomogram. The performance of nomogram was examined by calibration curves, net reclassification improvement (NRI) index and integrated discrimination improvement (IDI) index, decision curve analyses (DCA) and receiver operating characteristic (ROC) curves.Results Race, marital status, tumor location, histological type, tumor grade, T stage, N stage, M stage, preoperative CEA level, postoperative chemotherapy were identified as independent prognosticators for OS. The calibration curves of the nomogram showed good consistencies between predicted and observed OS. The AUCs, IDI and NRI indicated that the nomogram predicted prognosis with better accuracy than the TNM staging system. DCA also suggested that the proposed nomogram owned more excellent net benefits in guiding clinical decision than TNM staging system.Conclusion The current study conducted a prognostic analysis and built a prognostic nomogram for EOCRC patients, And the nomogram demonstrated superiority over the TNM staging system regrading to prediction capacity for EOCRC patients.
Exploring the Molecular Mechanisms of Asthma Across Multiple Datasets
Authors: Guo Lianshan , Huang Enhao , Wang Tongting , Song Jin , Li Zhengzhao
Published: April 2023

Objective: The aim of this research was to utilize bioinformatics techniques to explore the molecular mechanisms at the gene level that contribute to asthma, with the objective of discovering new treatment strategies and potential targets for addressing the condition.
Methods: The Series Matrix File data files of GSE43696 and GSE67940 were downloaded from the NCBI GEO public database, including expression profile data of 212 patients. Differential gene expression was functionally annotated using clusterProfiler to evaluate relevant functional categories with GO and KEGG. A gene co-expression network was constructed using MEGENA, and feature importance was evaluated by random forest algorithm. Fluorescent quantitative PCR was employed to validate the expression of essential genes, and the variations in KEGG signaling pathways among the groups with high and low expression were examined through GSEA. Asthma targeted therapeutic drugs were predicted using The Connectivity Map. Finally, single-cell sequencing data were annotated and analyzed using the Seurat and celldex packages.
Results: This study screened 267 differentially expressed genes between asthma patients and healthy controls from the GSE43696 dataset and further analyzed them using pathway analysis and multi-scale embedded gene co-expression network analysis, ultimately selecting 12 genes as the candidate gene set for random forest analysis. Based on this, five key genes were selected using random forest algorithm, and their expression was validated in the external dataset GSE67940. The expression of C1orf64 and C7orf26 genes was found to be different between the two groups of patients, and these two genes were found to be associated with immune regulatory factors, chemokines, and cell receptors. The mRNA expression levels of C1orf64 and C7orf26 were consistent with the results of the screening by PCR. Further analysis showed that C1orf64 and C7orf26 were enriched in ABC transporters, cell cycle, cell adhesion molecules, and Notch signaling pathways, and were related to other genes related to asthma. Finally, by classifying the differentially expressed genes using the Connectivity Map, potential clues were provided for finding candidate drugs for asthma treatment.
Conclusion: This study combined bioinformatics methods to identify key genes and pathways for asthma. C1orf64 and C7orf26 genes may be the core genes in the pathogenesis of asthma in asthma patients compared to healthy controls, providing potential targets for asthma treatment. These results also suggest the potential application of drug prediction analysis using CMap and single-cell sequencing analysis in understanding the molecular mechanisms of asthma.
Causal relationship between hypothyroidism and the risk of hearing loss: A bidirectional two-sample Mendelian randomization study
Authors: Zhengxin Zhu , Liu Yuehui
Published: April 2023

Background Hypothyroidism's causal direction and the magnitude of its association with hearing loss is uncertain due to the limitations of observational studies. This study aims to investigate the relationship between hypothyroidism and hearing loss using bidirectional two-sample mendelian randomization (MR).Materials and Methods The genetic variants of 462,933 participants in the hypothyroidism study and 323,978 participants in the hearing loss study were used for bidirectional two-sample MR. Independent genetic variants that were significantly (P < 5×10− 8) associated with each exposure were considered as instruments. To test for sensitivity, Cochran's Q test, the MR-Egger intercept test, and leave-one-out analysis were applied apart from the multiplicative random effects-inverse variance weighted (MRE-IVW) approach used as the main MR analysis.Results The forward MR revealed a significant causal estimate for the genetically predicted hypothyroidism with the high risk of hearing loss [MRE-IVW: odds ratio (OR) = 1.092, P = 0.003]. However, the reverse MR analysis found no significant correlation between genetically predicted hearing loss and hypothyroidism (MRE-IVW: OR = 1.04, P = 0.113). Sensitivity analyses showed that the causal association estimations were stable and reliable.Conclusion In this MR study, we demonstrated hypothyroidism was causally associated with a high risk of hearing loss. However, there was no evidence to support the causality of hearing loss on hypothyroidism.
Body composition of infants at 6 months of age using a 3-compartment model
Authors: Kuriyan Rebecca , Hills Andrew , Murphy-Alford Alexia , Padmanabha Ramya , Nyati Lukhanyo , Byrne Nuala , Kurpad Anura , Norris Shane
Published: April 2023

Background
Two compartment (2C) models of body composition, including Air Displacement Plethysmography (ADP) and Deuterium Dilution (DD), assume constant composition of fat-free mass (FFM), while 3-compartment (3C) model overcomes some of these assumptions; studies are limited in infants.
Objective:
To compare 3C estimates of body composition in 6-mo. old infants from Australia, India and South Africa, including FFM density and hydration, compare with published literature and to evaluate agreement of body composition estimates from ADP and DD.
Methods:
Body volume and water were measured in 176 healthy infants using ADP and DD. 3C-model estimates of fat mass (FM), FFM and its composition were calculated, compared between countries (age and sex adjusted) and with published literature. Agreement between estimates from ADP and DD were compared by Bland-Altman and correlation analyses.
Results:
South African infants had significantly higher % FM (11.5%) and density of FFM compared to Australian infants. Australian infants had significantly higher % FFM (74.7 ± 4.4%) compared to South African infants (71.4 ± 5.0) and higher FFMI (12.7 ± 0.8 kg/m2) compared to South African (12.3 ± 1.2 kg/m2) and Indian infants (11.9 ± 1.0 kg/m2). FFM composition of present study differed significantly from literature. Pooled three country estimates of FM and FFM were comparable between ADP and DD; mean difference of -0.05 (95% CI, -0.64, +0.55) kg and +0.05 (95% CI, -0.55, +0.64) kg.
Conclusion:
3C-model estimates of body composition in infants differed between countries; future studies are needed to confirm these findings and investigate causes for the differences.
An immortal porcine preadipose cell strain for efficient production of cell-cultured fat
Authors: Huang Zan , Cheng Yun-Mou , Hong Peng-Cheng , Zhu Hai-Ning , Qin Jing , Song Ming-Mei , Zhu Weiyun
Published: April 2023

Adding adipose cells to cell-cultured meat can provide a distinctive aroma and juicy texture similar to real meat. However, a significant challenge still exists in obtaining seed cells that can be propagated for long periods, maintain their adipogenic potential, and reduce production costs. In this study, we present a cell strain derived from immortalized porcine preadipocytes that can be subculture for over 40 passages without losing differentiation capacity. This cell strain can be differentiated within 3D bioscaffolds to generate cell-cultured fat using fewer chemicals and less serum. Additionally, it can be expanded and differentiated on microcarriers with upscaled culture to reduce costs and labor. Moreover, it can co-differentiate with muscle precursor cells, producing a marbling pattern. Therefore, our cell strain provides an exceptional model for studying and producing cell-cultured fat.
Second Quantization Approach to Many-Body Dispersion Interactions: Implications for Chemical and Biological Systems
Authors: Tkatchenko Alexandre , Gori Matteo , Kurian Philip
Published: April 2023

The many-body dispersion (MBD) framework is a successful approach for modeling the long- range electronic correlation energy and optical response of systems with thousands of atoms. Inspired by field theory, here we develop a second-quantized MBD formalism (SQ-MBD) that recasts a system of atomic quantum Drude oscillators in a Fock-space representation. SQ-MBD provides: (i) tools for projecting observables (interaction energy, transition multipoles, polarizability tensors) on coarse-grained representations of the atomistic system ranging from single atoms to large structural motifs, (ii) a quantum-information framework to analyze correlations and (non)separability among fragments in a given molecular complex, and (iii) a path toward the applicability of the MBD framework to molecular complexes with millions of atoms. The SQ-MBD approach offers novel insights into quantum fluctuations in molecular systems and enables direct coupling of collective plasmon-like MBD degrees of freedom with arbitrary environments, providing a tractable computational framework to treat dispersion interactions and polarization response in intricate systems.
Integrating Knowledge and Action: Learnings from an implementation program for food security and food sovereignty with First Nations communities in Canada
Authors: Domingo Ashleigh , Yessis Jennifer , Charles Kerry-Ann , Skinner Kelly , Hanning Rhona M.
Published: April 2023

Background: Collaborative approaches to knowledge translation (KT) are important for advancing community-engaged research. However, there is a need for examples of participatory approaches that have effectively supported public health research and program development with First Nations communities. To strengthen KT with communities, we proposed a set of guiding principles for participatory planning and action for local food system change. Principles emerged from a cross-community analysis of Learning Circles: Local Healthy Food to School (LC:LHF2S) a participatory program (2015-2019) for Indigenous food system action. The objective was to identify guiding principles for participatory planning from key learnings and successes on scaling-up the Learning Circle (LC) vertically in Haida Nation, British Columbia (BC) and horizontally in three distinct community contexts: Gitxsan Nation, Hazelton /Upper Skeena, BC; Ministikwan Lake. Application of these principles is discussed in the context of our ongoing partnership with Williams Treaties First Nations to support community planning to enhance food security and sovereignty.
Methods: A cross-community thematic analysis was conducted and guided by an implementation science framework, Foster-Fishman and Watson’s (2012) ABLe Change Framework, to identify key learnings and successes from adapting the LC approach. Information gathered from community interviews (n=52), meeting summaries (n=44) and tracking sheets (n=39) was thematically analyzed to inform development of guiding principles. Community sense making of findings informed applicability in a new community context embarking on food systems work.
Results: Emergent guiding principles for participatory food system planning and action included: (1) Create safe and ethical spaces for dialogue by establishing trust and commitment from the ground up; (2) Understand context for change through community engagement; (3) Foster relationships to strengthen and sustain impact; and (4) Reflect and embrace program flexibility to integrate learnings.
Conclusions: Emergent principles offer guidance to supporting Indigenous community-led research and mobilization of knowledge into action. Principles are intended to support researchers and health system administrators with taking a collaborative approach that fosters relationships and integration of community leadership, knowledge, and action for food system change. Application of principles with implementation frameworks can strengthen KT in Indigenous contexts by incorporating community-protocols and perspectives in support of Indigenous self-determined priorities.
Endotracheal Actinomycosis Combined with Mucormycosis: A Case Report and Literature Review
Authors: Chen Zhujun , Guo Haiqing , Duan Hailing , Zhu Bingjing , Chen Yongfeng , Gong Liang
Published: April 2023

Background: Actinomycosis and mucormycosis are very uncommon in clinical work, a combination of both two infection is much rarer in one host. Actinomycosis of the trachea is a chronic septic disease caused by an actinomycete infection with a very low incidence. It is easily misdiagnosed owing to the difficulty in obtaining microbiological evidence. Likewise, mucormycosis is a rare conditionally pathogenic invasive fungal infection, but with an abrupt start, quick progression, and extremely high mortality. It is frequently observed in individuals with immunosuppression-related disorders. The infection is rare in one host with both of the two above pathogens, and the site of infection involving only the main bronchi is even more uncommon, which is why we report the following case.
Case description: The patient, a 58-year-old lady, has a long history of diabetes and has trouble controlling her blood sugar. A whitish mass in the main bronchus was discovered via fiberoptic bronchoscopy as a result of breathing difficulties. Then, the diagnosis of complex intratracheal actinomycosis with mucor infection was supported by a pathological biopsy. After an active combination treatment with bronchoscopic cryotherapy, Holmium Laser coupled with amphotericin B and penicillin, the patient was successfully discharged.
Conclusions: Clinically, when imaging reveals intratracheal protuberant lesions, further fiberoptic bronchoscopy and an etiological investigation should be carried out as soon as feasible in order to prevent misdiagnosis and missed diagnosis.
Numerical and Physical Modelling of Breast Cancer Based on Image Fusion and Artificial Intelligence
Authors: Dołęga-Kozierowski Bartosz , Kasprzak Piotr , Lis Michał , Szynglarewicz Bartłomiej , Matkowski Rafał , Sawicki Marek , Dymek Mateusz , Szumiejko Adrianna , Carmo Gustavo , Kwiatkowski Artur , Soliński Daniel Grzegorz , Ptak Mariusz
Published: April 2023

Purpose The key problem raised in the paper is the change in the position of the breast tumor due to magnetic resonance imaging examinations in the abdominal position relative to the supine position during the surgical procedure. Changing the position of the patient leads to significant deformation of the breast, which leads to the inability to indicate the location of the neoplastic lesion correctly.Methods This study outlines a methodological process for treating cancer patients. Pre-qualification assessments are conducted for magnetic resonance imaging (MRI), and 3D scans are taken in three positions: supine with arms raised (SU), supine surgical position (SS), and standing (S). MRI and standard ultrasonography (USG) imaging are performed, and breast and cancer tissue are segmented from the MRI images. Finite element analysis is used to simulate tissue behavior in different positions, and an artificial neural network is trained to predict tumor dislocation. Based on the model, a 3D-printed breast with a highlighted tumor is manufactured. This computer-aided analysis is used to create a detailed surgical plan, and lumpectomy surgery is performed in the supine surgical position (SS). In addition, the geometry of the tumor is presented to the medical staff as a 3D-printed element.Results By utilizing a comprehensive range of techniques, including pre-qualification assessment, 3D scanning, MRI and USG imaging, segmentation of breast and cancer tissue, model analysis, image fusion, finite element analysis, artificial neural network training, and additive manufacturing, a detailed surgical plan can be created for performing lumpectomy surgery in the supine surgical position.Conclusion The new approach developed for the pre-operative assessment and surgical planning of breast cancer patients has demonstrated significant potential for improving the accuracy and efficacy of surgical procedures. This procedure may also help the pathomorphological justification. Moreover, transparent 3D-printed breast models can benefit breast cancer operation assistance. The physical and computational models can help surgeons visualize the breast and the tumor more accurately and detailedly, allowing them to plan the surgery with greater precision and accuracy.
Arterial Glyceryl Trinitrate in Acute Ischemic Stroke after Thrombectomy for Neuroprotection (AGAIN)：A Pilot Randomized Controlled Trial
Authors: Cheng Zhe , Gao Jie , Ding Yuchuan , Pang Qi , Rajah Gary B. , Geng Xiaokun
Published: April 2023

Although endovascular therapy demonstrates robust clinical efficacy in acute ischemic stroke (AIS), not all stroke patients benefit from successful reperfusion. This study aimed to evaluate the safety, feasibility, and preliminary efficacy of intra-arterial administration of Glyceryl Trinitrate (GTN) after endovascular recanalization for neuroprotection. This is a prospective randomized controlled study. Eligible patients were randomized to receive 800µg GTN or same volume of normal saline through the catheter after recanalization. The primary outcome was symptomatic intracranial hemorrhage (ICH), while the second outcome included mortality, functional outcome, infarction volume, complications, and blood nitrate index (NOx). A total of 40 patients were enrolled and randomized with no participants being lost to follow-up. There was no significant difference in the proportion of sICH between GTN and control groups. Additionally, no significant difference was observed in mortality or rates of neurological deterioration and other complications. Positive trends in outcome and imaging were noted with functional independence favoring the GTN group (75.0% vs. 65.0%,p = 0.731) at 90 days, as well as reduction in final infarct volume (33.2 vs. 38.9 ml,p = 0.779) for the GTN group. Moreover, the concentration of blood NOXin GTN group was significantly higher than control group at 2 hours after GTN administration (26.2 vs 18.0 µmol/l,p＜0.05). The AGAIN study suggests intra-arterial administration of GTN post endovascular therapy is safe and feasible and GTN successfully raised NOXlevels over controls at 2 hours. A multi-center randomized controlled trial with a larger sample size is warranted to determine GTN neoadjuvant efficacy.
Hematological markers and prostate cancer risk: A Mendelian randomization study
Authors: Zhao Pin , Zhu Zhaowei , Zhang Xuepei Xuepei
Published: April 2023

BackgroundProspective study has indicated an association between hematological markers and the risk of prostate cancer. However, such associations are easily influenced by confounding or reverse causality. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to assess the independent causal effects of hematological markers on the risk of prostate cancer.MethodsWe conducted Mendelian randomization (MR) analyses using publicly available full association studies (GWAS) data, which included 79,148 cases of prostate cancer and 61,106 controls. The analysis revealed that 378 single nucleotide polymorphisms (SNPs) were strongly correlated with mean corpuscular volume, 366 SNPs were tightly linked with mean corpuscular hemoglobin, and 102 SNPs were intricately connected with mean hemoglobin concentration. The primary estimate was obtained using the inverse-variance weighted method, while MR Pleiotropy RESidual Sum and Outlier, MR-Egger, and weighted median methods were utilized to identify heterogeneity and pleiotropy.ResultsIn the meta-analysis of our results, elevated mean corpuscular volume was found to be associated with a decreased risk of prostate cancer (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.90–0.98; P = 0.004). Mean corpuscular hemoglobin (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.91–0.99; P = 0.019) and mean corpuscular hemoglobin concentration (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.81–0.98; P = 0.023) are both associated with a reduced risk of prostate cancer.ConclusionsThis Mendelian randomization study provides evidence supporting the notion that elevated levels of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) may lower the risk of prostate cancer.
The song does not remain the same: daily singing of adult songbirds prevents passive changes in song structure independently of auditory feedback
Authors: Kojima Satoshi , Mizuguchi Daisuke , Sánchez-Valpuesta Miguel , Kim Yunbok , Santos Ednei dos , Kang Hijee , Mori Chihiro , Wada Kazuhiro
Published: April 2023

Many songbirds learned to produce songs through vocal practice in early life and continue to sing these songs daily throughout their lifetime. While it is well-known that adult songbirds sing as part of their mating rituals, the functions of singing behavior outside of reproductive contexts remain unclear. Here, we tested the hypothesis that adult singing outside of reproductive contexts may serve to prevent passive changes in song performance. We found that suppressing daily singing for two weeks altered the acoustic and temporal structure of song, and that the song structure substantially recovered within two weeks of free singing. These reversible song changes were not dependent on auditory feedback or the age of the birds, contrasting with the adult song plasticity that has been reported previously. These results demonstrate that adult song structure is not stable without daily singing in non-reproductive contexts, and suggest that adult songbirds maintain song performance by preventing passive song changes through the physical act of daily singing throughout their life. Such daily singing likely functions as vocal training to maintain the song production system in optimal conditions for song performance in reproductive contexts, similar to how human singers and athletes practice daily to maintain their performance.
25-hydroxycholesterol promotes proliferation and metastasis of lung adenocarcinoma cells by regulating ERβ/TNFRSF17 axis
Authors: Lin Yanliang , He Mengting , Jiang Wenbo , Li Xingkai , Liu Hongjin , Ren Hongsheng
Published: April 2023

Lung adenocarcinoma is the main type of lung cancer in women. Our previous findings have evidenced that 25-hydroxycholesterol (25-HC) promotes migration and invasion of lung adenocarcinoma cells (LAC), during which LXR as a 25-HC receptor plays an important role. Estrogen receptor beta (ERβ) is a receptor of 27-hydroxycholesterol that is structurally analogous to 25-HC, but its role in the functional actions of 25-HC remained largely unknown. In this study, we demonstrated that 25-HC treatment triggered ERβ expression in LAC. Knockdown of ERβ inhibited 25-HC-mediated proliferation, migration and invasion, and reduced 25-HC-induced LAC metastasis in vivo. Further investigation revealed that ERβ knockdown restrained the expression of TNFRSF17 (BCMA). In vivo experiments also confirmed that ERβ knockdown blocked 25-HC-induced TNFRSF17 expression. TNFRSF17 knockdown also restrained 25-HC-induced proliferation, migration and invasion. Bioinformatic analysis showed that the levels of ERβ and TNFRSF17 were elevated in lung adenocarcinoma, and were closely related to tumor stages and nodal metastasis status. These results suggested that 25-HC promoted the proliferation and metastasis of LAC by regulating ERβ/TNFRSF17 axis.
Effects of high-antioxidant activity Lactiplantibacillus plantarum inoculated alfalfa silage on rumen fermentation, antioxidant and immunity status, and mammary gland gene expression in dairy goats
Authors: Zhang Yixin , Usman Samaila , Li Qiang , Li Fuhou , Zhang Xia , Nussio Luiz Gustavo , Guo Xusheng
Published: April 2023

Background During milk synthesis in lactating animals there is a high requirement for energy and oxygen which leads to an increase in the production of reactive oxygen metabolites (ROM), which causes an imbalance between oxidates and antioxidants concentration leading to oxidative stress (OS). In order to prevent OS and other metabolic disorders in dairy goats as well as provide a better understanding of diets’ effects on redox status during the lactation period, this feeding trial was conducted. The trial evaluated the effects of feeding inoculated alfalfa silage with Lactiplantibacillus plantarum strain containing high-antioxidant activity and its effects on rumen fermentation, immune status, and mammary gland gene expression in dairy goats.Methods Twenty-four Guanzhong dairy goats (38.1 ± 1.20 kg) were randomly allocated to two dietary treatments: one diet contain L. plantarum MTD/1 inoculated silage (RSMTD-1) and the other diet contain L. plantarum 24 − 7 with high antioxidant activity inoculated silage (ES24-7).Results Better fermentation quality and antioxidant activity were observed in ES24-7 than in the RSMTD-1 silage. Feed ES24-7 silage as a basal diet increased the total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities in milk, serum, and feces of the lactating goats. The diet with ES24-7 silage also improved casein yield, milk free fatty acid (FFA) content, and vitamin A content in the dairy goats’ milk. Meanwhile, an enhancement of immunoglobulin (Ig)A, IgG, IgM, interleukin (IL)-4, and IL-10 concentrations were observed, with a reduction in IL-1β, IL-2, IL-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α concentrations in the serum of the lactating goats fed ES24-7 dietary treatment. Higher concentrations of total volatile fatty acid (VFA), acetate, and propionate were determined in the rumen fluid of dairy goats fed ES24-7 silage. In addition, the diet of dairy goats containing ES24-7 silage significantly increased the expression of nuclear factor erythroid 2 like 2 (NFE2L2), beta-carotene oxygenase 1 (BCO1), SOD1, SOD2, SOD3, GPX2, CAT, glutathione-disulfide reductase (GSR), and heme oxygenase 1 (HMOX1) genes of the mammary gland, and a reduction of NADPH oxidase 4 (NOX4), TNF, and interferon gamma (IFNG) levels.Conclusions These findings indicated that feeding L. plantarum 24 − 7 inoculated alfalfa silage not only improved rumen fermentation and milk quality of lactating dairy goats, but also enhanced their immunity and antioxidant status by upregulating the levels of several antioxidant- and inflammatory-related genes of the mammary gland.
Encystation stimuli sensing mediated by adenylate cyclase AC2-dependent cAMP signaling in Giardia
Authors: Paredez Alexander , Shih Han-Wei , Alas Germain
Published: April 2023

Protozoan parasites use cAMP signaling to precisely regulate the place and time of developmental differentiation, yet it is unclear how this signaling is initiated. Encystation of the intestinal parasite Giardia lamblia can be activated by multiple stimuli, which we hypothesize result in a common physiological change. We demonstrate that bile alters plasma membrane fluidity by reducing cholesterol-rich lipid microdomains, while alkaline pH enhances bile function. Through depletion of the cAMP producing enzyme Adenylate Cyclase 2 (AC2) and the use of a newly developed Giardia-specific cAMP sensor, we show that AC2 is necessary for encystation stimuli-induced cAMP upregulation and activation of downstream signaling. Conversely, over expression of AC2 or exogenous cAMP were sufficient to initiate encystation. Our findings indicate that encystation stimuli induce membrane reorganization, trigger AC2-dependent cAMP upregulation, and initiate encystation-specific gene expression, thereby advancing our understanding of a critical stage in the life cycle of a globally important parasite.
Safe Use of Hepatitis B Surface Antigen-Positive Grafts in Liver Transplantation: A Nationwide Study Based on the KOTRY Data
Authors: Gang Sujin , Choi YoungRok , Lee Kwang-Woong , Kim Bong-Wan , Kim Dong-Sik , Nah Yang Won , Kim Jong Man , Lee Jae Geun , Ryu Je Ho , Jeong Jaehong , Hong Geun
Published: April 2023

In the era of nucleoside analogs (NA), we investigated liver transplantation (LT) outcomes using hepatitis B surface antigen (HBsAg)-positive(+) grafts and Korean Organ Transplantation Registry (KOTRY) data. The KOTRY database registered 4,265 LTs between April 2014 and January 2020; 20 (0.5%) using HBsAg(+) grafts were identified. HBsAg(+) liver grafts [S(+)] were compared to HBsAg-negative(−) liver grafts (n = 4,100) for LT outcomes. The S(+) group was compared with LTs using HBsAg(−)/hepatitis B core antibody (HBcAb) (+) [C(+), n = 882] and HBsAg(−)/HBcAb(−) [SC(−), n = 3,132] grafts by propensity score matching (PSM) (1:1). Sixteen of 20 HBsAg(+) graft recipients maintained hepatitis B immunoglobulin. Tenofovir is the most commonly used NA. Compared to the HBsAg(II) group, the S(+) group showed no significant differences in patient (P = 0.332) or graft survival (P = 0.152). Age (hazard ratio [HR] = 1.03, P = 0.016), hepatocellular carcinoma (HCC) (HR = 4.61, P < 0.001), the model for end-stage liver disease (MELD) score (HR = 2.82, P = 0.001), ascites (HR = 2.14, P = 0.002), and encephalopathy (HR = 2.53, P < 0.001) were risk factors for patient survival. The graft survival risk factors were HCC (HR = 4.01, P = 0.001), preoperative treatment for HCC (HR = 0.54, P = 0.006), MELD score (HR = 2.14, P = 0.012), ascites (HR = 2.52, P < 0.001), and encephalopathy (HR = 1.99, P < 0.001). PSM between groups S(+) and C(+) and groups S(+) and SC(−) revealed no significant difference in patient survival (P = 0.863 and P = 0.547, respectively) or graft survival (P = 0.576 and P = 0.327, respectively). In hepatitis B virus (HBV)-endemic areas, HBsAg(+) liver grafts can expand the donor pool without compromising outcomes.
Prediction of Autism spectrum disorder from high dimensional data using Machine Learning Techniques
Authors: Pottem Archana , Sirisha G.N.V.G. , Chaitanya R. Krishna
Published: April 2023

Over the past few years due to the changes in the environmental and human lifestyle, several neurodevelopmental disorders are shooting their existence. Autism prevalence percentage is significant when compared to other neurodevelopmental disorders. To diagnose autism spectrum disorder medical experts, need big medical data and lot of time. Early detection of autism at an early age helps in curing the disorder. Machine Learning models are developed to predict Autism in high dimensional datasets. Dimensionality reduction is applied to identify features that effect Autism. Feature subsets are extracted using chi-square test, mutual information and lightgbm. Later the performances of the machine learning algorithms are analysed to find out suitable classifier that predicts the autism spectrum disorder. Using feature selection, the performance of Naïve Bayesian, K Nearest Neighbour has improved. Decision trees classifier performed the best with a performance score of 97.47%.
Comprehensive Analysis of the Expression of the IGF2BPs gene family in Head and Neck Squamous Cell Carcinoma: Association with Prognostic Value and Tumor Immunity
Authors: Tang Hai , Liu Jingpeng , Zhao Jianjiang
Published: April 2023

Background:
Head and neck squamous cell carcinoma (HNSCC) represents a predominant type of malignant cancer found in the head and neck region, characterized by a high incidence and unfavorable prognosis. The IGF2BPs gene family, which belongs to the RNA-binding protein class, has been critically implicated in several cancers, and its involvement in HNSCC necessitates further exploration.
Objective:
To explore the clinical significance and potential biological functions of the IGF2BPs gene family in HNSCC.
Methods:
A bioinformatic methodology was employed to examine the expression profile, diagnostic and prognostic significance, and biological mechanisms of the IGF2BPs gene family in HNSCC, with a particular emphasis on its involvement in the immune function of HNSCC. This was followed by in vitro investigations to unravel the biological roles of the IGF2BPs gene family in HNSCC.
Results:
This investigation has demonstrated that, in contrast with normal control tissue, HNSCC has a substantial elevation in the expression level of the IGF2BPs gene family. Patients with a high level of IGF2BPs gene family expression demonstrated higher prediction accuracy for HNSCC. Furthermore, patients with HNSCC and elevated IGF2BPs gene family expression levels exhibited poor survival outcomes. The IGF2BPs gene family displayed a significant association with a variety of immune infiltrating cells and immune genes in HNSCC. Studies conducted in vitro have confirmed that IGF2BP2 silencing suppressed the migration, proliferation, and invasion of HNSCC cells.
Conclusions:
It has been determined that the IGF2BPs gene family plays a crucial part in the onset and progression of HNSCC, and its association with tumor immunity has been established. The IGF2BPs gene family holds promising potential as a diagnostic and prognostic biomarker for HNSCC.
Robertsonian fusion triggers recombination suppression on sex chromosomes in Coleonyx geckos
Authors: Lisachov Artem , Tishakova Katerina , Romanenko Svetlana , Lisachova Lada , Davletshina Guzel , Prokopov Dmitry , Kratochvíl Lukáš , O`Brien Patricia , Ferguson-Smith Malcolm , Borodin Pavel , Trifonov Vladimir
Published: April 2023

The classical hypothesis proposes that the lack of recombination on sex chromosomes arises due to selection for linkage between a sex-determining locus and sexually antagonistic loci, primarily facilitated by inversions. However, cessation of recombination on sex chromosomes could be attributed also to neutral processes, connected with other chromosome rearrangements or can reflect sex-specific recombination patterns existing already before sex chromosome differentiation. Three Coleonyx gecko species share complex X1X1X2X2/X1X2Y system of sex chromosomes evolved via a fusion of the Y chromosome with an autosome. We analyzed synaptonemal complexes and sequenced the flow-sorted sex chromosomes to investigate the effect of the chromosomal rearrangement on recombination and differentiation of these sex chromosomes. The gecko sex chromosomes evolved from syntenic regions that were also co-opted for sex chromosomes in other reptiles. We showed that male recombination is more prevalent in the proximal regions of gecko chromosomes and is even further drastically reduced around the centromere of the neo-Y chromosome. We highlight that pre-existing recombination patterns and Robertsonian fusions can be responsible for the cessation of recombination on sex chromosomes and that such processes can be largely neutral.
Comparison of widefield swept-source optical coherence tomographic angiography and fluorescein fundus angiography for detection of retinal neovascularization with diabetic retinopathy
Authors: Yang Yanyan , li Fengjiao , Liu Tingting , jiao wanzhen , Zhao Bojun
Published: April 2023

Background: To compare vitreous angiomosaic images (VAMIs), obtained by
widefield swept-source optical coherence tomographic angiography (wfSS-OCTA) and the image of fluorescein fundus angiography (FFA) in the identification of retinal neovascularization (NV) in patients with diabetic retinopathy (DR).
Methods: In this prospective observational study, severe non-proliferative diabetic retinopathy (NPDR) or proliferative DR (PDR) patients were included. All patients underwent FFA and wfSS-OCTA. The number of NVs identified by wfSS-OCTA VAMIs using five fixations 12×12 mm montage scans and the resembling FFA images were compared.
Results: Fifty-three eyes of 29 patients were enrolled. NVs were detected in 25 eyes by using FFA, including 9 NVs of the disc (NVDs) and 72 NVs elsewhere (NVEs), and in 29 eyes by OCTA, including 11 NVDs and 90 NVEs. The detection rate of NV and NVD of OCTA was comparable to that of FFA (p > 0.05), and the level of agreement was excellent (κ = 0.850, κ = 0.754). Using FFA as the gold standard, the sensitivity for detection of NV by OCTA was 100.0%, specificity was 85.7%, the positive-predictive value was 86.2%, and the negative-predictive value was 100.0%. Compared with FFA, OCTA was superior in terms of the number of NVEs identified (p = 0.024). When we excluded images of patients treated with anti-vascular endothelial growth factor (VEGF) intravitreal therapy for < 3 months, OCTA was comparable to FFA in terms of the number of NVEs discovered (p = 0.203), with excellent agreement (intraclass correlation coefficient = 0.941).
Conclusions: WfSS-OCTA is an independent non-invasive alternative to FFA for NV discovery, NVD detection, and individual NVE identification, particularly in patients with PDR who have a history of prior treatment with anti-VEGF.
Systematic mining and functional analysis of factors regulating wheat spike development for breeding selection
Authors: Xiao Jun , Lin Xuelei , Xu Yongxin , Wang Dongzhi , Yang Yiman , Zhang Xiaoyu , Bie Xiao Min , Wang Hongzhe , Jiang Jiafu , Chen Zhongxu , Gui Lixuan , Ding Yiliang , Che Yuqing , Li Aili , Zhang Xueyong , Lu Fei , Zhao Xiang Yu , Zhang Xian Sheng , Fu Xiangdong
Published: April 2023

Spike architecture largely affects grain number embraced, which is an important trait to optimize during wheat breeding process. In this study, we incorporated multi-omic data and investigated the genetic regulation of wheat spike development. We generated transcriptome and epigenome profiles of shoot apex at eight developmental stages and observed that chromatin accessibility and H3K27me3 abundance coordinated with transcriptome alteration for flowering transition. A core transcriptional regulatory network (TRN) that drove the formation of the wheat spike was constructed. Integration of the TRN and genome-wide association analysis (GWAS) led to the identification of 227 transcription factors (TFs) with both known (42) and unknown (185) functions. Multi-layer regulatory module among TaSPL6, TaMADS34 and TaMADS15 identified by TRN was validated experimentally. Of the 85 novel TFs with homozygous mutant lines in TILLING library, 38 showed altered spike architecture or flowering time, including bHLH, MYB, and WRKY. Furthermore, we demonstrated that TaMYB4-A regulates fertile spikelet number likely via regulating hormones homeostasis and signaling, and is downstream of, and repressed by WFZP. The elite allele of TaMYB4-A, with a C-SNP at the WFZP binding site, was selected for balancing spikelet number and fertility during breeding process in China. Collectively, our findings provide high-confidence novel regulators and an efficient strategy for studying the genetic basis of wheat spike development for practical breeding applications.
A Novel CT-Based Radiomics Model for Predicting Response and Prognosis of Chemoradiotherapy in Esophageal Squamous Cell Carcinoma
Authors: Kasai Akinari , Miyoshi Jinsei , Sato Yasushi , Okamoto Koichi , Miyamoto Hiroshi , Kawanaka Takashi , Harada Masafumi , Goto Masakazu , Yoshida Takahiro , Haga Akihiro , Takayama Tetsuji
Published: April 2023

No clinically relevant biomarker has been identified for predicting the response of esophageal squamous cell carcinoma (ESCC) to chemoradiotherapy (CRT). Herein, we established a CT-based radiomics model with artificial intelligence (AI) to predict the response and prognosis of CRT in ESCC. A total of 44 ESCC patients (stage I-IV) were enrolled in this study; training (n = 27) and validation (n = 17) cohorts. First, we extracted a total of 476 radiomics features from three-dimensional CT images of cancer lesions in training cohort, selected 110 features associated with the CRT response by ROC analysis (AUC ≥ 0.7) and identified 12 independent features, excluding correlated features by Pearson’s correlation analysis (r ≥ 0.7). Based on the 12 features, we constructed 5 prediction models of different machine learning algorithms (Random Forest (RF), Ridge Regression, Naive Bayes, Support Vector Machine, and Artificial Neural Network models). Among those, the RF model showed the highest AUC in the training cohort (0.99, p < 0.001) as well as in the validation cohort (0.92, p < 0.001) to predict the CRT response. Additionally, Kaplan-Meyer analysis of the validation cohort and all the patient data revealed that the PFS and OS in the high-prediction score group were significantly longer than those in the low-prediction score group. Univariate and multivariate analyses revealed that the radiomics prediction score could be an independent prognostic biomarker, and moreover significantly superior to serum SCC-Ag, the conventional tumor marker of ESCC. In conclusion, we have developed a novel and robust CT-based radiomics model using AI, which successfully predicts the CRT response as well as the prognosis for ESCC patients with high accuracy, non-invasiveness, and cost-effectiveness.