bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges and opportunities in vascularized composite allotransplantation of joints: a systematic literature review
Authors: Zhang Lei , Hoyos Isabel Arenas , Zubler Cédric , Rieben Robert , Constantinescu Mihai , Olariu Radu 
Published: May 2023

BackgroundJoint allotransplantation (JA) within the field of vascularized composite allotransplantation (VCA) holds great potential for functional and non-prosthetic reconstruction of severely damaged joints. However, clinical use of JA remains limited due to the immune rejection associated with all forms of allotransplantation. In this study, we aim to provide a comprehensive overview of the current state of JA through a systematic review of clinical, animal, and immunological studies on this topic.MethodsWe conducted a systematic literature review in accordance with the PRISMA guidelines to identify relevant articles in PubMed, Cochrane Library, and Web of Science databases. The results were analyzed, and potential future prospects were discussed in detail.ResultsOur review included 14 articles describing relevant developments in JA. Currently, most JA-related research is being performed in small animal models, demonstrating graft survival and functional restoration with short-term immunosuppression. In human patients, only six knee allotransplantations have been performed to date, with all grafts ultimately failing and a maximum graft survival of 56 months.ConclusionResearch on joint allotransplantation has been limited over the last 20 years due to the rarity of clinical applications, the complex nature of surgical procedures, and uncertain outcomes stemming from immune rejection. However, the key to overcoming these challenges lies in extending graft survival and minimizing immunosuppressive side effects. With the emergence of new immunosuppressive strategies, the feasibility and clinical potential of vascularized joint allotransplantation warrants further investigation.
Delayed and limited administration of the JAKinib tofacitinib mitigates chronic DSS-induced colitis
Authors: Seal Rishav , Schwab Lara S. U. , Chiarolla Cristina M. , Hundhausen Nadine , Klose Georg Heinrich , Reu-Hofer Simone , Rosenwald Andreas , Wiest Johannes , Berberich-Siebelt Friederike 
Published: May 2023

In inflammatory bowel disease, dysregulated T cells express pro-inflammatory cytokines. Using a chronic azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis model resembling ulcerative colitis, we evaluated whether and when treatment with the Janus kinase (JAK) inhibitor tofacitinib could be curative. Comparing the treatment with two and three cycles of tofacitinib medication in drinking water – intermittently with DSS induction – revealed that two cycles were not only sufficient but also superior over the 3-x regimen. The two cycles of the 2-x protocol paralleled the second and third cycles of the longer protocol. T cells were less able to express interferon gamma (IFN-γ) and the serum levels of IFN-γ, interleukin (IL)-2, IL-6, IL-17, and tumor necrosis factor (TNF) were significantly reduced in sera, while those of IL-10 and IL-22 increased under the 2-x protocol. Likewise, the frequency and effector phenotype of regulatory T cells (Tregs) increased. This was accompanied by normal weight gain, controlled clinical scores, and restored stool consistency. The general and histologic appearance of the colons revealed healing and tissue intactness. Importantly, two phases of tofacitinib medication completely prevented AOM-incited pseudopolyps and the hyper-proliferation of epithelia, which was in contrast to the 3-x regimen. This implies that the initial IBD-induced cytokine expression is not necessarily harmful as long as inflammatory signaling can later be suppressed and that time-restricted treatment allows for anti-inflammatory and tissue-healing cytokine activities.
Integrative bioinformatics and validation studies reveal KDM6B and its associated molecules as crucial modulators in Idiopathic Pulmonary Fibrosis
Authors: Chen Anning , Sun Zhun , Sun Donglin , Huang Meiying , Fang Hongwei , Zhang Jinyuan , Qian Guojun 
Published: May 2023

BackgroundIdiopathic Pulmonary Fibrosis (IPF) can be described as a debilitating lung disease that is characterized by the complex interactions between various immune cell types and signaling pathways. Chromatin-modifying enzymes are significantly involved in regulating gene expression during immune cell development, yet their role in IPF is not well understood.MethodsIn this study, differential gene expression analysis and chromatin-modifying enzyme-related gene data were conducted to identify hub genes, common pathways, immune cell infiltration, and potential drug targets for IPF. Additionally, a murine model was employed for investigating the expression levels of candidate hub genes and determining the infiltration of different immune cells in IPF.ResultsWe identified 33 differentially expressed genes associated with chromatin-modifying enzymes. Enrichment analyses of these genes demonstrated a strong association with histone lysine demethylation, Sin3-type complexes, and protein demethylase activity. Protein-protein interaction network analysis further highlighted six hub genes, specifically KDM6B, KDM5A, SETD7, SUZ12, HDAC2, and CHD4. Notably, KDM6B expression was significantly increased in the lungs of bleomycin-induced pulmonary fibrosis mice, showing a positive correlation with fibronectin and α-SMA, two essential indicators of pulmonary fibrosis. Moreover, we established a diagnostic model for IPF focusing on KDM6B and we also identified 10 potential therapeutic drugs targeting KDM6B for IPF treatment.ConclusionOur findings suggest that molecules related to chromatin-modifying enzymes, primarily KDM6B, play a critical role in the pathogenesis and progression of IPF.
Performance of spectral flow cytometry and mass cytometry for the study of innate myeloid cell populations
Authors: van der Pan Kyra , Khatri Indu , de Jager Anniek L. , Louis Alesha , Kassem Sara , Naber Brigitta A.E. , de Laat Inge F. , Hameetman Marjolijn , Comans Suzanne E.T. , Orfao Alberto , van Dongen Jacques J.M. , Díez Paula , Teodosio Cristina 
Published: May 2023

IntroductionMonitoring of innate myeloid cells (IMC) is broadly applied in basic and translational research, as well as in diagnostic patient care. Due to their immunophenotypic heterogeneity and biological plasticity, analysis of IMC populations typically requires large panels of markers. Currently, two cytometry-based techniques allow for the simultaneous detection of ≥40 markers: spectral flow cytometry (SFC) and mass cytometry (MC). However, little is known about the comparability of SFC and MC in studying IMC populations.MethodsWe evaluated the performance of two SFC and MC panels, which contained 21 common markers, for the identification and subsetting of blood IMC populations. Based on unsupervised clustering analysis, we systematically identified 24 leukocyte populations, including 21 IMC subsets, regardless of the cytometry technique.ResultsOverall, comparable results were observed between the two technologies regarding the relative distribution of these cell populations and the staining resolution of individual markers (Pearson’s ρ=0.99 and 0.55, respectively). However, minor differences were observed between the two techniques regarding intra-measurement variability (median coefficient of variation of 42.5% vs. 68.0% in SFC and MC, respectively; p&lt;0.0001) and reproducibility, which were most likely due to the significantly longer acquisition times (median 16 min vs. 159 min) and lower recovery rates (median 53.1% vs. 26.8%) associated with SFC vs. MC.DiscussionAltogether, our results show a good correlation between SFC and MC for the identification, enumeration and characterization of IMC in blood, based on large panels (&gt;20) of antibody reagents.
The complement receptor C5aR2 regulates neutrophil activation and function contributing to neutrophil-driven epidermolysis bullosa acquisita
Authors: Seiler Daniel L. , Kähler Katja H. , Kleingarn Marie , Sadik Christian D. , Bieber Katja , Köhl Jörg , Ludwig Ralf J. , Karsten Christian M. 
Published: May 2023

IntroductionThe function of the second receptor for the complement cleavage product C5a, C5aR2, is poorly understood and often neglected in the immunological context. Using mice with a global deficiency of C5aR2, we have previously reported an important role of this receptor in the pathogenesis of the neutrophil-driven autoimmune disease epidermolysis bullosa acquisita (EBA). Based on in vitro analyses, we hypothesized that the absence of C5aR2 specifically on neutrophils is the cause of the observed differences. Here, we report the generation of a new mouse line with a LysM-specific deficiency of C5aR2.MethodsLysM-specific deletion of C5aR2 was achieved by crossing LysMcre mice with tdTomato-C5ar2fl/fl mice in which the tdTomato-C5ar2 gene is flanked by loxP sites. Passive EBA was induced by subcutaneous injection of rabbit anti-mouse collagen type VII IgG. The effects of targeted deletion of C5ar2 on C5a-induced effector functions of neutrophils were examined in in vitro assays.ResultsWe confirm the successful deletion of C5aR2 at both the genetic and protein levels in neutrophils. The mice appeared healthy and the expression of C5aR1 in bone marrow and blood neutrophils was not negatively affected by LysM-specific deletion of C5aR2. Using the antibody transfer mouse model of EBA, we found that the absence of C5aR2 in LysM-positive cells resulted in an overall amelioration of disease progression, similar to what we had previously found in mice with global deficiency of C5aR2. Neutrophils lacking C5aR2 showed decreased activation after C5a stimulation and increased expression of the inhibitory Fcγ receptor FcγRIIb.DiscussionOverall, with the data presented here, we confirm and extend our previous findings and show that C5aR2 in neutrophils regulates their activation and function in response to C5a by potentially affecting the expression of Fcγ receptors and CD11b. Thus, C5aR2 regulates the finely tuned interaction network between immune complexes, Fcγ receptors, CD11b, and C5aR1 that is important for neutrophil recruitment and sustained activation. This underscores the importance of C5aR2 in the pathogenesis of neutrophil-mediated autoimmune diseases.
FAM family gene prediction model reveals heterogeneity, stemness and immune microenvironment of UCEC
Authors: Chi Hao , Gao Xinrui , Xia Zhijia , Yu Wanying , Yin Xisheng , Pan Yifan , Peng Gaoge , Mao Xinrui , Teichmann Alexander Tobias , Zhang Jing , Tran Lisa Jia , Jiang Tianxiao , Liu Yunfei , Yang Guanhu , Wang Qin 
Published: May 2023

Background: Endometrial cancer (UCEC) is a highly heterogeneous gynecologic malignancy that exhibits variable prognostic outcomes and responses to immunotherapy. The Familial sequence similarity (FAM) gene family is known to contribute to the pathogenesis of various malignancies, but the extent of their involvement in UCEC has not been systematically studied. This investigation aimed to develop a robust risk profile based on FAM family genes (FFGs) to predict the prognosis and suitability for immunotherapy in UCEC patients.Methods: Using the TCGA-UCEC cohort from The Cancer Genome Atlas (TCGA) database, we obtained expression profiles of FFGs from 552 UCEC and 35 normal samples, and analyzed the expression patterns and prognostic relevance of 363 FAM family genes. The UCEC samples were randomly divided into training and test sets (1:1), and univariate Cox regression analysis and Lasso Cox regression analysis were conducted to identify the differentially expressed genes (FAM13C, FAM110B, and FAM72A) that were significantly associated with prognosis. A prognostic risk scoring system was constructed based on these three gene characteristics using multivariate Cox proportional risk regression. The clinical potential and immune status of FFGs were analyzed using CiberSort, SSGSEA, and tumor immune dysfunction and rejection (TIDE) algorithms. qRT-PCR and IHC for detecting the expression levels of 3-FFGs.Results: Three FFGs, namely, FAM13C, FAM110B, and FAM72A, were identified as strongly associated with the prognosis of UCEC and effective predictors of UCEC prognosis. Multivariate analysis demonstrated that the developed model was an independent predictor of UCEC, and that patients in the low-risk group had better overall survival than those in the high-risk group. The nomogram constructed from clinical characteristics and risk scores exhibited good prognostic power. Patients in the low-risk group exhibited a higher tumor mutational load (TMB) and were more likely to benefit from immunotherapy.Conclusion: This study successfully developed and validated novel biomarkers based on FFGs for predicting the prognosis and immune status of UCEC patients. The identified FFGs can accurately assess the prognosis of UCEC patients and facilitate the identification of specific subgroups of patients who may benefit from personalized treatment with immunotherapy and chemotherapy.
The effects of proprioceptive weighting changes on posture control in patients with chronic low back pain: a cross-sectional study
Authors: Cheng Xue , Yang Jiajia , Hao Zengming , Li Yan , Fu Ruochen , Zu Yao , Ma Jinjin , Lo Wai Leung Ambrose , Yu Qiuhua , Zhang Guifang , Wang Chuhuai 
Published: May 2023

IntroductionPatients with chronic low back pain (CLBP) exhibit changes in proprioceptive weighting and impaired postural control. This study aimed to investigate proprioceptive weighting changes in patients with CLBP and their influence on posture control.MethodsSixteen patients with CLBP and 16 healthy controls were recruited. All participants completed the joint reposition test sense (JRS) and threshold to detect passive motion test (TTDPM). The absolute errors (AE) of the reposition and perception angles were recorded. Proprioceptive postural control was tested by applying vibrations to the triceps surae or lumbar paravertebral muscles while standing on a stable or unstable force plate. Sway length and sway velocity along the anteroposterior (AP) and mediolateral (ML) directions were assessed. Relative proprioceptive weighting (RPW) was used to evaluate the proprioception reweighting ability. Higher values indicated increased reliance on calf proprioception.ResultsThere was no significant difference in age, gender, and BMI between subjects with and without CLBP. The AE and motion perception angle in the CLBP group were significantly higher than those in the control group (JRS of 15°: 2.50 (2.50) vs. 1.50 (1.42), JRS of 35°: 3.83 (3.75) vs. 1.67 (2.00),pJRS&lt; 0.01; 1.92 (1.18) vs. 0.68 (0.52),pTTDPM&lt; 0.001). The CLBP group demonstrated a significantly higher RPW value than the healthy controls on an unstable surface (0.58 ± 0.21 vs. 0.41 ± 0.26,p&lt; 0.05). Under the condition of triceps surae vibration, the sway length (pstable&lt; 0.05;punstable&lt; 0.001), AP velocity (pstable&lt; 0.01;punstable&lt; 0.001) and ML velocity (punstable&lt; 0.05) had significant group main effects. Moreover, when the triceps surae vibrated under the unstable surface, the differences during vibration and post vibration in sway length and AP velocity between the groups were significantly higher in the CLBP group than in the healthy group (p&lt; 0.05). However, under the condition of lumbar paravertebral muscle vibration, no significant group main effect was observed.ConclusionThe patients with CLBP exhibited impaired dynamic postural control in response to disturbances, potentially linked to changes in proprioceptive weighting.
Effects of low-frequency rTMS combined with antidepressants on depression in patients with post-stroke depression: a systematic review and meta-analysis
Authors: Pan Juanhong , Li Hongpeng , Wang Yongshen , Lu Li , Wang Ying , Zhao Tianyu , Zhang Di , Jin Song 
Published: May 2023

ObjectiveTo evaluate the effect of low-frequency (≤1 Hz) repetitive transcranial magnetic stimulation (low-frequency rTMS) combined with antidepressants on depression and the levels of inflammatory factors IL-6 and TNF-α in patients with post-stroke depression (PSD).DesignPubMed, Embase, Web of Science, Cochrane Library (CBM), China National Knowledge Infrastructure, Technology Periodical Database, and Wanfang Database were searched until October 2022 for randomized controlled trials.ParticipantsPatients with post-stroke depression (PSD) participated in the study.ResultsA total of 16 randomized controlled trials (RCTs) involving 1,463 patients with PSD were included. According to the Physiotherapy Evidence Database (PEDro) quality assessment, three studies received high quality (eight scores) and 13 RCTs received moderate quality (six scores) results. The meta-analysis showed that low-rTMS combined with an antidepressant significantly reduced the Hamilton Depression Scale (HAMD) score and the National Institutes of Health Stroke Scale (NIHSS) score, reduced IL-6 and TNF-α levels, and improved the MMSE score in PSD compared to an antidepressant alone.ConclusionThe results of this meta-analysis evidenced the efficacy and safety of low-rTMS combined with antidepressants in the treatment of depression in PSD patients. The combined therapy could reduce The depression state and the levels of IL-6 and TNF-α, and enhance the cognitive function of patients. In addition, low-rTMS had fewer adverse effects, proving safety. However, there are shortcomings, such as a lack of long-term follow-up, different intervention sites of low-rTMS, and different intervention frequencies (0.5 or 1 Hz). Thus, in the future, RCTs with a larger sample size and longer-term observation are required to verify the efectiveness of low-rTMS combined therapy on PSD. Meantime, a new meta-analysis could be analysized, which intervention sites and frequency are more effective in treating PSD.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42022376845.
Diffusion-weighted MRI of the spinal cord in cervical spondylotic myelopathy after instrumented fusion
Authors: Koch Kevin M. , Nencka Andrew S. , Klein Andrew , Wang Marjorie , Kurpad Shekar , Vedantam Aditya , Budde Matthew 
Published: May 2023

IntroductionThis study investigated tissue diffusion properties within the spinal cord of individuals treated for cervical spondylotic myelopathy (CSM) using post-decompression stabilization hardware. While previous research has indicated the potential of diffusion-weighted MRI (DW-MRI) markers of CSM, the metallic implants often used to stabilize the decompressed spine hamper conventional DW-MRI.MethodsUtilizing recent developments in DW-MRI metal-artifact suppression technologies, imaging data was acquired from 38 CSM study participants who had undergone instrumented fusion, as well as asymptomatic (non-instrumented) control participants. Apparent diffusion coefficients were determined in axial slice sections and split into four categories: a) instrumented levels, b) non-instrumented CSM levels, c) adjacent-segment (to instrumentation) CSM levels, and d) non-instrumented control levels. Multi-linear regression models accounting for age, sex, and body mass index were used to investigate ADC measures within each category. Furthermore, the cord diffusivity within CSM subjects was correlated with symptom scores and the duration since fusion procedures.ResultsADC measures of the spinal cord in CSM subjects were globally reduced relative to control subjects (p = 0.005). In addition, instrumented levels within the CSM subjects showed reduced diffusivity relative to controls (p = 0.003), while ADC within non-instrumented CSM levels did not statistically deviate from control levels (p = 0.107).DiscussionMulti-spectral DW-MRI technology can be effectively employed to evaluate cord diffusivity near fusion hardware in subjects who have undergone surgery for CSM. Leveraging this advanced technology, this study had identified significant reductions in cord diffusivity, relative to control subjects, in CSM patients treated with conventional metallic fusion instrumentation.
Clinical, radiological, therapeutic and prognostic differences between MOG-seropositive and MOG-seronegative pediatric acute disseminated encephalomyelitis patients: a retrospective cohort study
Authors: Dong Xueshan , Jiang Yan , Yuan Ping , Fan Xiao , Ma Jiannan , Wu Peng , Jiang Li , Li Xiujuan 
Published: May 2023

ObjectiveThis study aimed to compare the clinical, radiological, therapeutic, and prognostic differences between pediatric patients showing acute disseminated encephalomyelitis (ADEM) with and without myelin oligodendrocyte glycoprotein (MOG) antibodies.MethodsWe retrospectively collected all available data of children diagnosed with ADEM and tested for serum MOG antibodies at the Children's Hospital of Chongqing Medical University from January 2017 to May 2021.ResultsA total of 62 patients were included in our cohort, of which 35 were MOG-seropositive and 27 were MOG-seronegative. MOG-seropositive ADEM children presented with significantly lower rates of seizures (P = 0.038) and cranial nerve (III–XII) palsy (P = 0.003). Isolated leukocytosis in the blood was more common in ADEM children with MOG antibodies (P &lt; 0.001). The two groups showed no significant differences in the distributions and extent of the MRI lesions as well as the appearance of typical/atypical magnetic resonance imaging (MRI) features. MOG-seropositive children were more likely to relapse (P = 0.017) despite having slower oral prednisolone tapering after acute treatments (P = 0.028). In scoring performed on the basis of two neurological function scoring systems, MOG-seropositive children showed milder neurological disability status at onset (P = 0.017 and 0.025, respectively) but showed no difference during follow-up.ConclusionIn summary, the differences in the clinical manifestations and auxiliary examination findings for MOG-seropositive and MOG-seronegative ADEM children lacked significance and specificity, making early identification difficult. MOG-seropositive children were more likely to relapse and showed slower steroid tapering. Moreover, MOG-seronegative children tended to have more severe neurological impairments at onset with no difference during follow-up.