bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and validation of critical genes with prognostic value in gastric cancer
Authors: Dong Ningxin , Ma Xiaolong , Shen Jing , Zheng Yunlu , Li Guiyuan , Zheng Shaoqiang , Huang Xiaoyi 
Published: December 2022

Background: Gastric cancer (GC) is a digestive system tumor with high morbidity and mortality rates. Molecular targeted therapies, including those targeting human epidermal factor receptor 2 (HER2), have proven to be effective in clinical treatment. However, better identification and description of tumor-promoting genes in GC is still necessary for antitumor therapy.Methods: Gene expression and clinical data of GC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Last absolute shrinkage and selection operator (LASSO) Cox regression were applied to build a prognostic model, the Prognosis Score. Functional enrichment and single-sample gene set enrichment analysis (ssGSEA) were used to explore potential mechanisms. Western blotting, RNA interference, cell migration, and wound healing assays were used to detect the expression and function of myosin light chain 9 (MYL9) in GC.Results: A four-gene prognostic model was constructed and GC patients from TCGA and meta-GEO cohorts were stratified into high-prognosis score groups or low-prognosis score groups. GC patients in the high-prognosis score group had significantly poorer overall survival (OS) than those in the low-prognosis score groups. The GC prognostic model was formulated as PrognosisScore = (0.06 × expression of BGN) - (0.008 × expression of ATP4A) + (0.12 × expression of MYL9) - (0.01 × expression of ALDH3A1). The prognosis score was identified as an independent predictor of OS. High expression of MYL9, the highest weighted gene in the prognosis score, was correlated with worse clinical outcomes. Functional analysis revealed that MYL9 is mainly associated with the biological function of epithelial-mesenchymal transition (EMT). Knockdown of MYL9 expression inhibits migration of GC cells in vitro.Conclusion: We found that PrognosisScore is potential reliable prognostic marker and verified that MYL9 promotes the migration and metastasis of GC cells.
E-mental health implementation in inpatient care: Exploring its potential and future challenges
Authors: Van Assche Eva , Bonroy Bert , Mertens Marc , Van den Broeck Lore , Desie Kimberly , Bolinski Felix , Amarti Khadicha , Kleiboer Annet , Riper Heleen , Van Daele Tom 
Published: December 2022

BackgroundThere is a great evidence base today for the effectiveness of e-mental health, or the use of technology in mental healthcare. However, large-scale implementation in mental healthcare organisations is lacking, especially in inpatient specialized mental healthcare settings.AimThe current study aimed to gain insights into the factors that promote or hinder the implementation of e-mental health applications on organisational, professional and patient levels in Belgium.MethodsFour Belgian psychiatric hospitals and psychiatric departments of general hospitals invited their professionals and patients to use Moodbuster, which is a modular web-based platform with a connected smartphone application for monitoring. The platform was used in addition to treatment as usual for three to four months. The professionals and patients completed pre- and post-implementation questionnaires on their reasons to participate or to decline participation and experiences with the Moodbuster platform.ResultsMain reasons for the organisations to participate in the implementation study were a general interest in e-mental health and seeing it is a helpful add-on to regular treatment. The actual use of Moodbuster by professionals and patients proved to be challenging with only 10 professionals and 24 patients participating. Implementation was hindered by technical difficulties and inpatient care specific factors such as lack of structural facilities to use e-mental health and patient-specific factors. Professionals saw value in using e-mental health applications for bridging the transition from inpatient to outpatient care. Twenty-two professionals and 31 patients completed the questionnaire on reasons not to participate. For the patients, lack of motivation because of too severe depressive symptoms was the most important reason not to participate. For professionals, it was lack of time and high workload.ConclusionsThe current implementation study reveals several important barriers to overcome in order to successfully implement e-mental health in inpatient psychiatric care.
Effect of Codonopsis Radix and Polygonati Rhizoma on the regulation of the IRS1/PI3K/AKT signaling pathway in type 2 diabetic mice
Authors: Mao Yong-po , Song Yi-ming , Pan Sheng-wang , Li Ning , Wang Wen-xiang , Feng Bin-bin , Zhang Jian-hai 
Published: December 2022

ObjectiveCodonopsis Radix and Polygonati Rhizoma (CRPR) has a good hypoglycemic effect. The aims of the present study were to investigate the effect of CRPR on high-fat/high-sugar diet (HFHSD)- and streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) mice as well as to investigate the involved mechanism.MethodsA T2DM mouse model was generated by combining HFHSD and STZ. After the model was established, normal and model groups received the same volume of normal saline intragastrically, and the negative control group was treated with metformin (200 mg/kg·BW). The low, medium, and high CRPR groups received four consecutive weeks of oral gavage with CRPR doses of 2.5, 5, and 10 g/kg·BW, respectively, during the course of the study. Body weight and fasting blood glucose (FBG) were measured on a weekly basis. Enzyme-linked immunosorbent assay (ELISAs) were used to evaluate the serum and liver samples. Hematoxylin and eosin (H&amp;E) staining was utilized to observe the pathological status of the liver and pancreas. Western blot (WB) analysis was performed to evaluate the protein expression levels of PI3K, p-PI3K, AKT, and p-AKT.ResultsCompared to model mice, each treatment group had significantly elevated levels of FBG, total cholesterol (TC), and triacylglycerol (TG) (P&lt;0.01 and P&lt;0.05, respectively). The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly reduced in the treatment groups compared to the model group (P&lt;0.01). Compared to the model group, fasting insulin (FINS) levels were elevated in all groups of CRPR (P&lt;0.05), and there were significantly higher levels of high-density lipoprotein cholesterol (HDL-C) in both the low-dose and high-dose CRPR groups (P&lt;0.05). H&amp;E staining indicated that CRPR treatment reduced organ enlargement, improved liver lipid accumulation, and repaired islet injury in T2DM mice. Moreover, WB analysis demonstrated that all CRPR groups significantly upregulated the protein expression of IRS1, p-GSK3β, PI3K, p-Akt and p-FOXO1(P&lt;0.05) as well as significantly downregulated p-IRS1 and FOXO1 protein expression (P&lt;0.05).ConclusionThe present study demonstrated that CRPR effectively improves the metabolic disturbance of lipids, repairs damaged liver tissues, repairs damaged pancreatic tissues, and reduces insulin resistance (IR) in T2DM mice. The mechanism of action may be associated with upregulation of the IRS1/PI3K/AKT signaling pathway and inhibition of IRS1 phosphorylation.
The extrafollicular response is sufficient to drive initiation of autoimmunity and early disease hallmarks of lupus
Authors: Voss Lasse F. , Howarth Amanda J. , Wittenborn Thomas R. , Hummelgaard Sandra , Juul-Madsen Kristian , Kastberg Kristian S. , Pedersen Mathias K. , Jensen Lisbeth , Papanastasiou Anastasios D. , Vorup-Jensen Thomas , Weyer Kathrin , Degn Søren E. 
Published: December 2022

IntroductionMany autoimmune diseases are characterized by germinal center (GC)-derived, affinity-matured, class-switched autoantibodies, and strategies to block GC formation and progression are currently being explored clinically. However, extrafollicular responses can also play a role. The aim of this study was to investigate the contribution of the extrafollicular pathway to autoimmune disease development.MethodsWe blocked the GC pathway by knocking out the transcription factor Bcl-6 in GC B cells, leaving the extrafollicular pathway intact. We tested the impact of this intervention in two murine models of systemic lupus erythematosus (SLE): a pharmacological model based on chronic epicutaneous application of the Toll-like receptor (TLR)-7 agonist Resiquimod (R848), and 564Igi autoreactive B cell receptor knock-in mice. The B cell intrinsic effects were further investigatedin vitroand in autoreactive mixed bone marrow chimeras.ResultsGC block failed to curb autoimmune progression in the R848 model based on anti-dsDNA and plasma cell output, superoligomeric DNA complexes, and immune complex deposition in glomeruli. The 564Igi model confirmed this based on anti-dsDNA and plasma cell output.In vitro, loss of Bcl-6 prevented GC B cell expansion and accelerated plasma cell differentiation. In a competitive scenarioin vivo, B cells harboring the genetic GC block contributed disproportionately to the plasma cell output.DiscussionWe identified the extrafollicular pathway as a key contributor to autoimmune progression. We propose that therapeutic targeting of low quality and poorly controlled extrafollicular responses could be a desirable strategy to curb autoreactivity, as it would leave intact the more stringently controlled and high-quality GC responses providing durable protection against infection.
Impact of hepatic steatosis on treatment response of autoimmune hepatitis: A retrospective multicentre analysis
Authors: Liu Peiyan , Li Mingkai , Zhao Lili , Yu Hongsheng , Zhao Chang , Chen Jianning , Shi Ruifang , Zhou Li , Zhou Qi , Wu Bin , Li Jia 
Published: December 2022

BackgroundThere is a paucity of data on whether steatosis impacts autoimmune hepatitis (AIH) treatment response. We aimed to evaluate the influence of baseline steatosis on the biochemical response, fibrosis progression, and adverse longterm outcomes of AIH.MethodsSteatosis was diagnosed by a controlled attenuation parameter (CAP) ≥ 248 dB / m. Only patients who underwent immunosuppressive therapy with available liver histological material at diagnosis and qualified CAP within seven days of the liver biopsy were included. Univariate and multivariate analyses were subsequently conducted.ResultsThe multicentre and retrospective cohort enrolled 222 subjects (88.3% female, median age 54 years, median follow-up 48 months) in the final analysis, and 56 (25.2%) patients had hepatic steatosis. Diabetes, hypertension, and significant fibrosis at baseline were more common in the steatosis group than in the no steatosis group. After adjusting for confounding factors, hepatic steatosis was an independent predictor of insufficient biochemical response (OR: 8.07) and identified as an independent predictor of long-term adverse outcomes (HR: 4.07). By subgroup multivariate analysis (different degrees of steatosis, fibrosis, and prednisone dose), hepatic steatosis independently showed a relatively stable correlation with treatment response. Furthermore, in contrast to those without steatosis, a significant increase in liver stiffness (LS) was observed in patients with steatosis (4.1%/year vs. -16%/year, P &lt; 0.001).ConclusionsConcomitant hepatic steatosis was significantly associated with poor response to treatment in AIH patients. Routine CAP measurements are therefore essential to guide the management of AIH.
Duration biased distribution of clinical and immunological phenotypes in active SLE
Authors: Yan Qingran , Liu Bei , Yang Minjie , Li Qianqian , Wang Jieying , Li Ting , Lu Liangjing 
Published: December 2022

IntroductionThis study is aimed to map the clinical and immunological features of active lupus patients with different disease duration.MethodsFor clinical phenotype analysis, we enriched eligible medical records with active SLE (SLEDAI-2k≥8) from the Renji Lupus registry, a single-center database of hospitalized SLE patients with standard care, which covered national-wide patients. Patients with repeated hospitalization records in this enrichment were analyzed longitudinally as validation for the cross-sectional study above.ResultsWe enriched a total of 1313 eligible records on active SLE (SLEDAI-2k≥8) for cross-sectional analysis. Stratified into four groups by a 5-year interval of disease duration, these active SLE patients showed a significantly shifting clinical phenotype along with the duration (ascending nephritis, pulmonary hypertension and descending fever, cutaneous symptoms, arthritis, and neuropsychiatric manifestations), especially in stratifications with disease onset age ≤ 45 years old. A longitudinal analysis of 55 patients with repeated hospitalizations for active lupus showed a similar trend. In the cross-sectional study of 222 records with full information on serology and lymphocyte subsets, peripheral B cell proportion, anti-dsDNA antibody, and serum IgG/IgM negatively correlated with duration, while CD8+ T cell proportion was positively correlated (P values, 0.029-4.8×10-17), which were supported by the sensitivity analysis in patient subgroups according to disease onset age and recent treatment. Multivariate linear regression identified duration as the only significant associator with both B cell and CD8+ T cell proportion (P values, 8.9×10-8 and 7.6×10-5, respectively). These duration biased immune phenotypes were highly consistent with the longitudinal observation in 14 patients with repeated hospitalizations.ConclusionsBoth clinical and immunological features of active SLE are significantly duration biased distributed, which merits further investigations in the evolution of SLE pathogenesis.
T cell repertoire profiling in allografts and native tissues in recipients with COVID–19 after solid organ transplantation: Insight into T cell–mediated allograft protection from viral infection
Authors: Fu Jianing , Rust Dylan , Fang Zhou , Jiao Wenyu , Lagana Stephen , Batal Ibrahim , Chen Bryan , Merl Sarah , Jones Rebecca , Sykes Megan , Weiner Joshua 
Published: December 2022

IntroductionThe effects of the SARS-CoV-2 virus on the body, and why the effects are more severe in certain patients, remain incompletely understood. One population of special interest is transplant recipients because of their immunosuppressed state. Understanding the pathophysiology of graft dysfunction in transplant patients with the COVID-19 viral syndrome is important for prognosticating the risk to the graft as well as understanding how best to prevent and, if necessary, treat graft injury in these patients.MethodsWe analyzed multiple types of solid organ transplant recipients (liver, kidney, heart or lung) at our institution who died from SARS-CoV-2 and underwent autopsy (n = 6) or whose grafts were biopsied during active SARS-CoV-2 infection (n = 8). Their serum inflammatory markers were examined together with the histological appearance, viral load, and TCR repertoire of their graft tissue and, for autopsy patients, several native tissues.ResultsHistology and clinical lab results revealed a systemic inflammatory pattern that included elevated inflammatory markers and diffuse tissue damage regardless of graft rejection. Virus was detected throughout all tissues, although most abundant in lungs. The TCR repertoire was broadly similar throughout the tissues of each individual, with greater sharing of dominant clones associated with more rapid disease course. There was no difference in viral load or clonal distribution of overall, COVID-associated, or putative SARS-CoV-2-specific TCRs between allograft and native tissue. We further demonstrated that SARSCoV-2-specific TCR sequences in transplant patients lack a donor HLArestricted pattern, regardless of distribution in allograft or native tissues,suggesting that recognition of viral antigens on infiltrating recipient cells can effectively trigger host T cell anti-viral responses in both the host and graft.DiscussionOur findings suggest a systemic immune response to the SARS-CoV-2 virus in solid organ transplant patients that is not associated with rejection and consistent with a largely destructive effect of recipient HLA-restricted T cell clones that affects donor and native organs similarly.
Pan-cancer analysis of FBXW family with potential implications in prognosis and immune infiltration
Authors: Huang Tingting , OuYang XIaoxiao , Li Jiwei , Shi Bingbing , Shan Zhengda , Shi Zhiyuan , Yang Zhangru 
Published: December 2022

BackgroundThe F-box and WD repeat domain containing (FBXW) family of SCF E3 complexes has 10 members that are responsible for ubiquitination and degradation of substrate proteins involved in cell cycle regulation and tumorigenesis. Among them, FBXW1 (also called b-TrCP1/BTRC) and FBXW7 are the central proteins in this category. However, there is still a lack of elaborate exploration of the contribution of FBXW family members, especially FBXW1 and FBXW7, in various tumor types.MethodsIn this present study, we preliminarily analyzed the genetic structure characteristics of the FBXW family, and systematically investigated their expression patterns and clinical correlations based on the TCGA pan-cancer data. Survival analysis of FBXWs was also conducted through the Kaplan-Meier method. In addition, we assessed their immune infiltration level through immune-related algorithms like Timer and xCell.ResultsThere were obvious genetic heterogeneity and different clinical traits in FBXW family members. Moreover, we found that FBXW family genes may be useful in predicting prognosis and therapeutic efficacy using survival analysis. In addition, the immune infiltration of FBXW family was also clearly illustrated in this study. The results showed these genes were closely involved in immune components such as immune score, immune subtypes, tumor-infiltrating lymphocytes and immune checkpoints. Notedly, FBXW1 as an oncogene and FBXW7 as a tumor suppressor gene also show opposite relationships on immune cells.ConclusionOur results provided valuable strategies to guide the therapeutic orientation concerning the role of FBXW family genes in cancer.
Methylation changes induced by a glycodendropeptide immunotherapy and associated to tolerance in mice
Authors: Núñez Rafael , Rodríguez María J. , Lebrón-Martín Clara , Martín-Astorga María del Carmen , Palomares Francisca , Ramos-Soriano Javier , Rojo Javier , Torres María J. , Cañas José Antonio , Mayorga Cristobalina 
Published: December 2022

IntroductionAllergen-specific immunotherapy (AIT) is applied as treatment to rise tolerance in patients with food allergies. Although AIT is thoroughly used, the underlying epigenetic events related to tolerant induction are still unknown. Thus, we aim to investigate epigenetic changes that could be related to tolerance in dendritic cells (DCs) from anaphylactic mice to lipid transfer proteins, Pru p 3, in the context of a sublingual immunotherapy (SLIT) with a glycodendropeptide (D1ManPrup3) that has demonstrated tolerant or desensitization responses depending on the treatment dose.MethodsChanges in DNA methylation in CpG context were determined comparing Sensitized (Antigen-only) animals and two groups receiving SLIT with the D1ManPrup3 nanostructure (D1ManPrup3-SLIT): Tolerant (2nM D1ManPrup3) and Desensitized (5nM D1ManPrup3), against anaphylactic animals. DNA from lymph nodes-DCs were isolated and then, Whole Genome Bisulphite Sequencing was performed to analyze methylation.ResultsMost differentially methylated regions were found on the area of influence of gene promoters (DMPRs). Compared to the Anaphylactic group, the highest value was found in Desensitized mice (n = 7,713 DMPRs), followed by Tolerant (n = 4,091 DMPRs) and Sensitized (n = 3,931 DMPRs) mice. Moreover, many of these epigenetic changes were found in genes involved in immune and tolerance responses (Il1b, Il12b, Il1a, Ifng, and Tnf) as shown by functional enrichment (DCs regulation, B cell-mediated immunity, and effector mechanisms).DiscussionIn conclusion, different doses of D1ManPrup3-SLIT induce different DNA methylation changes, which are reflected in the induction of distinct responses, tolerance, or desensitization.
Risk for excessive anticoagulation during hemodialysis is associated with type of vascular access and bedside coagulation testing: Results of a cross-sectional study
Authors: De Troyer Marijke , Wissing Karl Martin , De Clerck Dieter , Cambier Marie-Laure , Robberechts Tom , Tonnelier Annelies , François Karlien 
Published: December 2022

BackgroundRecommendations and practice patterns for heparin dosing during hemodialysis show substantial heterogeneity and are scantly supported by evidence. This study assessed the variability in unfractionated heparin (UFH) dosing during hemodialysis and its clinical and biological anticoagulatory effects, and identified explanatory factors of heparin dosing.MethodsCross-sectional study assessing UFH dosing, coagulation tests – activated partial thromboplastin time (aPTT) and activated clotting time (ACT) before dialysis start, 1 h after start and at treatment end (4 h) – and measurement of residual blood compartment volume of used dialyzers.Results101 patients, 58% male, with a median dialysis vintage of 33 (6–71) months received hemodialysis using a total UFH dose of 9,306 ± 4,079 (range 3,000–23,050) IU/session. Use of a dialysis catheter (n = 56, 55%) was associated with a 1.4 times higher UFH dose (p &lt; 0.001) irrespective of prior access function. aPTT increased significantly more than ACT both 1 h and 4 h after dialysis start, independent of the dialysis access used. 53% of patients with catheter access and ACT ratio &lt; 1.5, 1 h after dialysis start had simultaneous aPTT ratios &gt; 2.5. Similar findings were present at 1 h for patients with AVF/AVG and at dialysis end for catheter use. No clinically significant clotting of the extracorporeal circuit was noted during the studied sessions. Dialyzer’s blood compartment volume was reduced with a median of 9% (6–20%) without significant effect of UFH dose, aPTT or ACT measurements and vascular access type.ConclusionUFH dose adaptations based on ACT measurements frequently result in excessive anticoagulation according to aPTT results. Higher doses of UFH are used in patients with hemodialysis catheters without evidence that this reduces dialyzer clotting.
Psychometric evaluation of a national exam for clinical undergraduates
Authors: Han Yuting , Jiang Zhehan , Ouyang Jinying , Xu Lingling , Cai Ting 
Published: December 2022

BackgroundAs a high-stake national-level examination administrated before students’ clerkship in China, the Standardized Competence Test for Clinical Medicine Undergraduates (SCTCMU) has received much attention from the relevant educational departments and society at large. Investigating SCTCMU’s validity and reliability is critical to the national healthcare profession education.Materials and methodsRaw responses from SCTCMU, answered by 44,332 examines of 4th-year undergraduate medical students on 300 multiple-choice items, were used to evaluate the quality of the exam via psychometric methods based on item response theory (IRT). The core assumptions and model-data fit of IRT models were evaluated, as well as the item properties and information functions.ResultsThe IRT models were fitted to the observed assessment data, where all the required assumptions were met. The IRT analysis showed that most items had acceptable psychometric properties, and the passing score was located close to the lowest measurement error computed from the model outcomes.ConclusionThe proposed modern psychometric method provides a practical and informative approach to calibrating and analyzing medical education assessments. This work showcases a realistic depiction of the IRT analysis process and therefore facilitates the work of applied researchers wanting to conduct, interpret, and report IRT analyses on medical assessments.