bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revisiting roles of mast cells and neural cells in keloid: exploring their connection to disease activity
Authors: Yeo Eunhye , Shim Joonho , Oh Se Jin , Choi YoungHwan , Noh Hyungrye , Kim Heeyeon , Park Ji-Hye , Lee Kyeong-Tae , Kim Seok-Hyung , Lee Dongyoun , Lee Jong Hee 
Published: March 2024

BackgroundMast cells (MCs) and neural cells (NCs) are important in a keloid microenvironment. They might contribute to fibrosis and pain sensation within the keloid. However, their involvement in pathological excessive scarring has not been adequately explored.ObjectivesTo elucidate roles of MCs and NCs in keloid pathogenesis and their correlation with disease activity.MethodsKeloid samples from chest and back regions were analyzed. Single-cell RNA sequencing (scRNA-seq) was conducted for six active keloids (AK) samples, four inactive keloids (IK) samples, and three mature scar (MS) samples from patients with keloids.ResultsThe scRNA-seq analysis demonstrated notable enrichment of MCs, lymphocytes, and macrophages in AKs, which exhibited continuous growth at the excision site when compared to IK and MS samples (P = 0.042). Expression levels of marker genes associated with activated and degranulated MCs, including FCER1G, BTK, and GATA2, were specifically elevated in keloid lesions. Notably, MCs within AK lesions exhibited elevated expression of genes such as NTRK1, S1PR1, and S1PR2 associated with neuropeptide receptors. Neural progenitor cell and non-myelinating Schwann cell (nmSC) genes were highly expressed in keloids, whereas myelinating Schwann cell (mSC) genes were specific to MS samples.ConclusionsscRNA-seq analyses of AK, IK, and MS samples unveiled substantial microenvironmental heterogeneity. Such heterogeneity might be linked to disease activity. These findings suggest the potential contribution of MCs and NCs to keloid pathogenesis. Histopathological and molecular features observed in AK and IK samples provide valuable insights into the mechanisms underlying pain and pruritus in keloid lesions.
Expression of immune related genes and possible regulatory mechanisms in different stages of non-alcoholic fatty liver disease
Authors: He Risheng , Guan Canghai , Zhao Xudong , Yu Liang , Cui Yunfu 
Published: March 2024

BackgroundNon-alcoholic fatty liver disease (NAFLD), which includes simple steatosis (SS) and non-alcoholic steatohepatitis (NASH), is a significant contributor to liver disease on a global scale. The change of immunity-related genes (IRGs) expression level leads to different immune infiltrations. However, the expression of IRGs and possible regulatory mechanisms involved in NAFLD remain unclear. The objective of our research is to investigate crucial genes linked to the development of NAFLD and the transition from SS to NASH.MethodsDataset GSE89632, which includes healthy controls, SS patients, and NASH patients, was obtained using the GEO database. To examine the correlation between sets of genes and clinical characteristics, we employed weighted gene co-expression network analysis (WGCNA) and differential expression analysis. Hub genes were extracted using a network of protein-protein interactions (PPI) and three different machine learning algorithms. To validate the findings, another dataset that is publicly accessible and mice that were subjected to a high-fat diet (HFD) or MCD diet were utilized. Furthermore, the ESTIMATE algorithm and ssGSEA were employed to investigate the immune landscape in the normal versus SS group and SS versus NASH group, additionally, the relationship between immune infiltration and the expression of hub genes was also examined.ResultsA total of 28 immune related key genes were selected. Most of these genes expressed reverse patterns in the initial and progressive stages of NAFLD. GO and KEGG analyses showed that they were focused on the cytokine related pathways and immune cell activation and chemotaxis. After screening by various algorithms, we obtained two hub genes, including JUN and CCL20. Validation of these findings was confirmed by analyzing gene expression patterns in both the validation dataset and the mouse model. Ultimately, two hub genes were discovered to have a significant correlation with the infiltration of immune cells.ConclusionWe proposed that there were dynamic changes in the expression levels of IRGs in different stages of NAFLD disease, which led to different immune landscapes in SS and NASH. The findings of our research could serve as a guide for the accurate management of various phases of NAFLD.
Neoadjuvant therapy with chemotherapy and immune checkpoint inhibitor for laryngeal function preservation in locally advanced hypopharyngeal cancer
Authors: Wu San-Gang , Wang Run-Jie , Zhou Yi , Luo Xian-Yang 
Published: March 2024

PurposeTo evaluate the efficacy and laryngeal function preservation of neoadjuvant treatment with chemotherapy and immune checkpoint inhibitor for locally advanced hypopharyngeal cancer (LAHPC).MethodsWe retrospectively collected LAHPC patients who were diagnosed between February 2022 and June 2023. The patients received a combination of chemotherapy and immune checkpoint inhibitors as the neoadjuvant therapy. The response to treatment, laryngeal function preservation rate, and short-term survival were assessed.ResultsA total of 20 patients were included. Of these patients, 17 (85.0%) had stage IVA-B disease. Ten (50%) and four (20%) patients achieved pathological complete response (PCR) and major pathological response (MPR) to the primary tumor, respectively. In addition, 6 patients had incomplete pathological response (IPR). In the neck, 19 patients had node-positive disease before treatment, and only 5 patients (26.4%) had PCR to regional lymph nodes. Pathologically positive lymph nodes were still observed in 14 (73.6%) patients. Significant downgrading on narrow-band imaging assessment in primary tumors was associated with a higher probability of PCR or MPR than those with IPR (92.9% vs. 33.3%, P=0.014). The overall rate of laryngeal preservation was 95.0%. No severe perioperative complications or perioperative death were found. All patients completed the recommended postoperative radiotherapy/chemoradiotherapy. The median follow-up period was 12.1 months. The 1-year progression-free survival and overall survival were 94.1% and 92.9%, respectively. During the follow-up period, all 19 patients who underwent laryngeal preservation surgery had their laryngeal function preserved.ConclusionThe addition of an immune checkpoint inhibitor to neoadjuvant chemotherapy effectively preserves laryngeal function without increasing complications related to surgery and postoperative radiotherapy in LAHPC.
Multiple environmental antigens may trigger autoimmunity in psoriasis through T-cell receptor polyspecificity
Authors: Ishimoto Tatsushi , Arakawa Yukiyasu , Vural Secil , Stöhr Julia , Vollmer Sigrid , Galinski Adrian , Siewert Katherina , Rühl Geraldine , Poluektov Yuri , Delcommenne Marc , Horvath Orsolya , He Mengwen , Summer Burkhard , Pohl Ralf , Alharbi Rehab , Dornmair Klaus , Arakawa Akiko , Prinz Jörg C. 
Published: March 2024

IntroductionPsoriasis is a T-cell mediated autoimmune skin disease. HLA-C*06:02 is the main psoriasis-specific risk gene. Using a Vα3S1/Vβ13S1 T-cell receptor (TCR) from a lesional psoriatic CD8+ T-cell clone we had discovered that, as an underlying pathomechanism, HLA-C*06:02 mediates an autoimmune response against melanocytes in psoriasis, and we had identified an epitope from ADAMTS-like protein 5 (ADAMTSL5) as a melanocyte autoantigen. The conditions activating the psoriatic autoimmune response in genetically predisposed individuals throughout life remain incompletely understood. Here, we aimed to identify environmental antigens that might trigger autoimmunity in psoriasis because of TCR polyspecificity.MethodsWe screened databases with the peptide recognition motif of the Vα3S1/Vβ13S1 TCR for environmental proteins containing peptides activating this TCR. We investigated the immunogenicity of these peptides for psoriasis patients and healthy controls by lymphocyte stimulation experiments and peptide-loaded HLA-C*06:02 tetramers.ResultsWe identified peptides from wheat, Saccharomyces cerevisiae, microbiota, tobacco, and pathogens that activated both the Vα3S1/Vβ13S1 TCR and CD8+ T cells from psoriasis patients. Using fluorescent HLA-C*06:02 tetramers loaded with ADAMTSL5 or wheat peptides, we find that the same CD8+ T cells may recognize both autoantigen and environmental antigens. A wheat-free diet could alleviate psoriasis in several patients.DiscussionOur results show that due to TCR polyspecificity, several environmental antigens corresponding to previously suspected psoriasis risk conditions converge in the reactivity of a pathogenic psoriatic TCR and might thus be able to stimulate the psoriatic autoimmune response against melanocytes. Avoiding the corresponding environmental risk factors could contribute to the management of psoriasis.
Shengu granules ameliorate ovariectomy-induced osteoporosis by the gut-bone-immune axis
Authors: Chen Xiao cong , Li Wei ju , Zeng Jia ying , Dong Yun peng , Qiu Jian ming , Zhang Bing , Wang Dong yang , Liu Jun , Lyu Zhao hui 
Published: March 2024

IntroductionPostmenopausal osteoporosis (PMOP) is a common chronic disease, and the loss of bone density and bone strength after menopause are its main symptoms. Effective treatments for PMOP are still uncertain, but Chinese medicine has some advantages in slowing down bone loss. Shengu granules are often used clinically to treat PMOP. It has been shown to be an effective prescription for the treatment of PMOP, and there is evidence that gut flora may play an important role. However, whether Shengu granules attenuate PMOP by modulating gut flora and related mechanisms remains unclear.MethodsIn this study, we mainly examined the bone strength of the femur, the structure of the intestinal microbiota, SCFAs in the feces and the level of FOXP3 cells in the colon. To further learn about the inflammation response, the condition of the mucosa and the level of cytokines in the serum also included in the testing. In addition, to get the information of the protein expression, the protein expression of OPG and RANKL in the femur and the protein expression of ZO-1 and Occludin in the colon were taken into account.ResultsThe osteoporosis was significantly improved in the SG group compared with the OVX group, and the diversity of intestinal flora, the secretion level of SCFAs and the expression level of FOXP3 were significantly increased compared with the OVX group. In terms of inflammatory indicators, the intestinal inflammation scores of the SG group was significantly lower than those in the OVX group. Additionally, the serum expression levels of IL-10 and TGF-β in the SG group were significantly increased compared with the OVX group, and the expression levels of IL-17 and TNF-α were significantly decreased compared with the OVX group. In terms of protein expression, the expression levels of ZO-1, Occluding and OPG were significantly increased in the SG group compared with the OVX group, and the expression level of RANKL was significantly decreased compared with the OVX group.DiscussionShengu granules treatment can improve the imbalance of intestinal flora, increase the secretion of SCFAs and the expression of FOXP3, which reduces the inflammatory response and repairs the intestinal barrier, as well as regulates the expression of OPG/RANKL signaling axis. Overall, Shengu granules ameliorate ovariectomy-induced osteoporosis by the gut-bone-immune axis.
Effects of dietary chlorogenic acid on cecal microbiota and metabolites in broilers during lipopolysaccharide-induced immune stress
Authors: Hu Xiaodi , Zhen Wenrui , Bai Dongying , Zhong Jiale , Zhang Ruilin , Zhang Haojie , Zhang Yi , Ito Koichi , Zhang Bingkun , Ma Yanbo 
Published: March 2024

AimsThe aim of this study was to investigate the effects of chlorogenic acid (CGA) on the intestinal microorganisms and metabolites in broilers during lipopolysaccharide (LPS)-induced immune stress.MethodsA total of 312 one-day-old Arbor Acres (AA) broilers were randomly allocated to four groups with six replicates per group and 13 broilers per replicate: (1) MS group (injected with saline and fed the basal diet); (2) ML group (injected with 0.5 mg LPS/kg and fed the basal diet); (3) MA group (injected with 0.5 mg LPS/kg and fed the basal diet supplemented with 1,000 mg/kg CGA); and (4) MB group (injected with saline and fed the basal diet supplemented with 1,000 mg/kg CGA).ResultsThe results showed that the abundance of beneficial bacteria such as Bacteroidetes in the MB group was significantly higher than that in MS group, while the abundance of pathogenic bacteria such as Streptococcaceae was significantly decreased in the MB group. The addition of CGA significantly inhibited the increase of the abundance of harmful bacteria such as Streptococcaceae, Proteobacteria and Pseudomonas caused by LPS stress. The population of butyric acid-producing bacteria such as Lachnospiraceae and Coprococcus and beneficial bacteria such as Coriobacteriaceae in the MA group increased significantly. Non-targeted metabonomic analysis showed that LPS stress significantly upregulated the 12-keto-tetrahydroleukotriene B4, riboflavin and mannitol. Indole-3-acetate, xanthurenic acid, L-formylkynurenine, pyrrole-2-carboxylic acid and L-glutamic acid were significantly down-regulated, indicating that LPS activated inflammation and oxidation in broilers, resulting in intestinal barrier damage. The addition of CGA to the diet of LPS-stimulated broilers significantly decreased 12-keto-tetrahydro-leukotriene B4 and leukotriene F4 in arachidonic acid metabolism and riboflavin and mannitol in ABC transporters, and significantly increased N-acetyl-L-glutamate 5-semialdehyde in the biosynthesis of amino acids and arginine, The presence of pyrrole-2-carboxylic acid in D-amino acid metabolism and the cecal metabolites, indolelactic acid, xanthurenic acid and L-kynurenine, indicated that CGA could reduce the inflammatory response induced by immune stress, enhance intestinal barrier function, and boost antioxidant capacity.ConclusionWe conclude that CGA can have a beneficial effect on broilers by positively altering the balance of intestinal microorganisms and their metabolites to inhibit intestinal inflammation and barrier damage caused by immune stress.
Exploring the application and challenges of fNIRS technology in early detection of Parkinson’s disease
Authors: Hui Pengsheng , Jiang Yu , Wang Jie , Wang Congxiao , Li Yingqi , Fang Boyan , Wang Hujun , Wang Yingpeng , Qie Shuyan 
Published: March 2024

BackgroundParkinson’s disease (PD) is a prevalent neurodegenerative disorder that significantly benefits from early diagnosis for effective disease management and intervention. Despite advancements in medical technology, there remains a critical gap in the early and non-invasive detection of PD. Current diagnostic methods are often invasive, expensive, or late in identifying the disease, leading to missed opportunities for early intervention.ObjectiveThe goal of this study is to explore the efficiency and accuracy of combining fNIRS technology with machine learning algorithms in diagnosing early-stage PD patients and to evaluate the feasibility of this approach in clinical practice.MethodsUsing an ETG-4000 type near-infrared brain function imaging instrument, data was collected from 120 PD patients and 60 healthy controls. This cross-sectional study employed a multi-channel mode to monitor cerebral blood oxygen changes. The collected data were processed using a general linear model and β values were extracted. Subsequently, four types of machine learning models were developed for analysis: Support vector machine (SVM), K-nearest neighbors (K-NN), random forest (RF), and logistic regression (LR). Additionally, SHapley Additive exPlanations (SHAP) technology was applied to enhance model interpretability.ResultsThe SVM model demonstrated higher accuracy in differentiating between PD patients and control group (accuracy of 85%, f1 score of 0.85, and an area under the ROC curve of 0.95). SHAP analysis identified the four most contributory channels (CH) as CH01, CH04, CH05, and CH08.ConclusionThe model based on the SVM algorithm exhibited good diagnostic performance in the early detection of PD patients. Future early diagnosis of PD should focus on the Frontopolar Cortex (FPC) region.
The effect of argatroban on early neurological deterioration and outcomes in minor ischemic stroke: preliminary findings
Authors: Jin Xuehong , Li Xia , Zhang Hong , Yao Xiaohan , Gu Yongquan , Pei Shaofang , Hu Lan 
Published: March 2024

BackgroundMinor ischemic stroke (MIS) is associated with early neurological deterioration (END) and poor prognosis. Here, we investigated whether argatroban administration can mitigate MIS-associated END and improve functional outcomes by monitoring activated partial thrombin time (APTT).MethodsData were collected for patients with MIS admitted to our hospital from January 2019 to December 2022. Patients were divided into a dual antiplatelet therapy (DAPT) group (aspirin + clopidogrel) and an argatroban group (aspirin + argatroban). Those in the latter group who achieved a target APTT of 1.5–3-fold that of baseline and &lt;100 s at 2 h after argatroban infusion were included in the argatroban subgroup. The primary outcome was the END rate of the DAPT group versus that of the argatroban group or the argatroban subgroup. Secondary outcomes included the proportion of patients with modified Rankin Scale (mRS) 0–2 at 7 and 90 days. In addition, baseline date were compared between patients with and without END in the argatroban group.Results363 patients were included in the DAPT group and 270 in the argatroban group. There were no significant differences in any above outcome between them. 207 pairs were included in the DAPT group and the argatroban subgroup after 1:1 propensity score matching (PSM). Significant differences were observed in the proportion of END (OR, 2.337; 95% CI, 1.200–4.550, p = 0.011) and mRS 0–2 at 7 days (OR, 0.624; 95% CI, 0.415–0.939, p = 0.023), but not in mRS 0–2 at 90 days or the hemorrhagic events between the two groups. In the argatroban group, univariate analysis showed that the rate of diabetes (OR, 2.316; 95% CI, 1.107–4.482, p = 0.023), initial random blood glucose (OR, 1.235; 95% CI, 1.070–1.425, p = 0.004), drinking history (OR, 0.445; 95% CI, 0.210–0.940, p = 0.031) or those reaching the target APTT (OR, 0.418; 95% CI, 0.184–0.949, p = 0.033) was significantly different among patients with and without END. However, there were no statistical differences in these parameters between them following multivariate analysis.ConclusionIn patients with MIS, argatroban administration and reaching the target APTT can reduce the incidence of END and improve short-term functional prognosis.
Transcutaneous auricular vagus nerve stimulation with task-oriented training improves upper extremity function in patients with subacute stroke: a randomized clinical trial
Authors: Wang Meng-Huan , Wang Yi-Xiu , Xie Min , Chen Li-Yan , He Meng-Fei , Lin Feng , Jiang Zhong-Li 
Published: March 2024

BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising brain stimulation modality in poststroke upper extremity rehabilitation. Although several studies have examined the safety and reliability of taVNS, the mechanisms underlying motor recovery in stroke patients remain unclear.ObjectivesThis study aimed to investigate the effects of taVNS paired with task-oriented training (TOT) on upper extremity function in patients with subacute stroke and explore the potential underlying mechanisms.MethodsIn this double-blinded, randomized, controlled pilot trial, 40 patients with subacute stroke were randomly assigned to two groups: the VNS group (VG), receiving taVNS during TOT, and the Sham group (SG), receiving sham taVNS during TOT. The intervention was delivered 5 days per week for 4 weeks. Upper extremity function was measured using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), the Action Research Arm Test (ARAT). Activities of daily living were measured by the modified Barthel Index (MBI). Motor-evoked potentials (MEPs) were measured to evaluate cortical excitability. Assessments were administered at baseline and post-intervention. Additionally, the immediate effect of taVNS was detected using functional near-infrared spectroscopy (fNIRS) and heart rate variability (HRV) before intervention.ResultsThe VG showed significant improvements in upper extremity function (FMA-UE, ARAT) and activities of daily living (MBI) compared to the SG at post-intervention. Furthermore, the VG demonstrated a higher rate of elicited ipsilesional MEPs and a shorter latency of MEPs in the contralesional M1. In the VG, improvements in FMA-UE were significantly associated with reduced latency of contralesional MEPs. Additionally, fNIRS revealed increased activation in the contralesional prefrontal cortex and ipsilesional sensorimotor cortex in the VG in contrast to the SG. However, no significant between-group differences were found in HRV.ConclusionThe combination of taVNS with TOT effectively improves upper extremity function in patients with subacute stroke, potentially through modulating the bilateral cortex excitability to facilitate task-specific functional recovery.
Frontline pembrolizumab monotherapy for metastatic non-small cell lung cancer with PD-L1 expression ≥50%: real-world outcomes in a US community oncology setting
Authors: Gadgeel Shirish M. , Rai Pragya , Annavarapu Srinivas , Alam Sartaj , Goldschmidt Jerome H. , West Howard (Jack) , Santorelli Melissa , Martins Renata Eiras 
Published: March 2024

BackgroundThis study investigated real-world time on treatment (rwToT) and overall survival (OS) for patients with metastatic non-small cell lung cancer (mNSCLC) who initiated first-line (1L) pembrolizumab monotherapy. We also explored discontinuation reasons and subsequent treatments, stratified by number of cycles among those who completed ≥17 cycles of 1L pembrolizumab.MethodsPatients with mNSCLC without actionable genetic aberrations, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 and unknown, and PD-L1 TPS ≥ 50% starting 1L pembrolizumab monotherapy between 24-Oct-2016 and 31-Dec-2018 within The US Oncology Network were identified retrospectively and evaluated using structured data, with a data cutoff of 30-Sep-2021. Patient characteristics and disposition were summarized using descriptive statistics. OS and rwToT were evaluated using Kaplan-Meier method for all ECOG PS and PS 0-1. A subgroup of patients who completed ≥17 cycles were evaluated using supplemental chart review data to discern reasons for discontinuation.ResultsOf the 505 patients with mNSCLC with PD-L1 TPS ≥50%, 61% had ECOG PS 0-1, 23% had ECOG PS 2, and 65% had nonsquamous histology. Median rwToT and OS of pembrolizumab were 7.0 (95% CI, 6.0–8.4) months and 24.5 (95% CI, 20.1–29.3) months, respectively. In the subgroup with ECOG PS 0-1, they were 7.6 months (95% CI, 6.2-9.2) and 28.8 months (95% CI, 22.4-37.5), respectively. Of the 103 patients who completed ≥17 cycles, 57 (55.3%) patients received 17 – 34 cycles and 46 (44.7%) patients received ≥35 cycles. Approximately 7.7% of the study population received pembrolizumab beyond 35 cycles. Most common reasons for discontinuation were disease progression (38.6%) and toxicity (19.3%) among patients who received 17-34 cycles of pembrolizumab, and disease progression (13.0%) and completion of therapy (10.9%) among patients who received ≥35 cycles.ConclusionConsistent with findings from KEYNOTE-024 and other real-world studies, this study demonstrates the long-term effectiveness of pembrolizumab monotherapy as 1L treatment for mNSCLC with PD-L1 TPS ≥50%. Among patients who completed ≥17 cycles, nearly half completed ≥35 cycles. Disease progression and toxicity were the most common reasons for discontinuation among patients who received 17-34 cycles of pembrolizumab. Reasons for discontinuation beyond 35 cycles need further exploration.