bluuebunny/crossref_metadata_2025_split huggingface dataset:
p53: A Regulator of Ferroptosis Induced by Galectin-1 Derived Peptide 3 in MH7A Cells
Authors: Hu Junzheng , Zhang Rui , Chang Qing , Ji Mingliang , Zhang Haixiang , Geng Rui , Li Chao , Wang Zhen 
Published: July 2022

Backgrounds: Rheumatoid arthritis synovial fibroblasts (RASFs) are the primary cells responsible for destruction of marginal cartilage in rheumatoid arthritis (RA). G1dP3, a bioactive peptide derived from galectin-1 domain, possesses potent anti-inflammatory and anti-proliferation properties in RASFs. This study aimed to determine the effects of G1dP3 ferroptosis induction in RASFs and to further clarify the possible mechanisms.Methods: TNF-α was used to establish a RA model in MH7A cells. Cell Counting Kit-8 assays were employed to detect MH7A cell viability with different treatments. The occurrence of ferroptosis was examined by Lipid ROS assay, cellular labile iron pool measurement, reduced glutathione/oxidized glutathione activity, Gpx4 expression and transmission electron microscopy (TEM) morphology observation. Lentiviral-mediated siRNA interference was used to determine the downstream pathway.Results: G1dP3 markedly suppressed MH7A cell viability induced by TNF-α. G1dP3-treated MH7A cells presented the morphological features of ferroptosis. Moreover, G1dP3 triggered ferroptosis in MH7A cells by promoting the accumulation of lipid peroxides as well as iron deposition. Inhibition of ferroptosis alleviated G1dP3-mediated suppression of MH7A cell viability. Furthermore, G1dP3 increased p53 expression, which in turn transcriptionally suppressed SLC7A11, a key component of system Xc− essential for ferroptosis. Knockdown of p53 abrogated the ferroptotic effects of G1dP3 on MH7A cells.Conclusion: Our findings reveal that the bioactive peptide G1dP3 promotes RASFs ferroptosis cell death via a p53/SLC7A11 axis-dependent mechanism, suggesting its potential role in the treatment of RA.
The Outcome of Induction Therapy for EBV-Related Hemophagocytic Lymphohistiocytosis: A Model for Risk Stratification
Authors: Cui Tingting , Wang Jingshi , Wang Zhao 
Published: July 2022

BackgroundEpstein–Barr virus (EBV)–related hemophagocytic lymphohistiocytosis (HLH) is an abnormal inflammation caused by EBV infection, which has high mortality during induction therapy.ObjectivesThis study is aimed to build a model to predict the risk of death during induction therapy.MethodsThe patients with EBV-HLH admitted from January 2015 to December 2018 were retrospectively reviewed. The primary outcome was death during induction therapy. The interval from receiving therapy to death or the end of induction therapy was the observing time. The patients admitted from January 2015 to December 2017 were assigned to the primary group, and the patients admitted from January to December 2018 were assigned to the validation group.ResultsWe included 234 patients with EBV-HLH, of whom 65 (27.4%) died during induction therapy. The middle observing time was 25 days. On the basis of the primary group, the multivariate Cox analysis demonstrated age &gt;18 years, blood urea nitrogen, procalcitonin &gt;2 µg/L, serum CD25, and EBV-DNA in peripheral blood mononuclear cell as the risk factors of death during induction therapy. We developed a nomogram integrating the above factors with high predictive accuracy (c-statistic, 0.86) and stratified all patients into the high-risk and the low-risk groups. On the basis of the validation group, the high-risk patients had a higher risk of death (hazard ratio, 4.93; P = 0.012). In the subgroup analysis based on patients receiving etoposide-based strategy, the mortality in high-risk and low-risk patients was 43.9 and 3.1 per 100 person-weeks, respectively.ConclusionWe developed a nomogram for risk stratification of patients with EBV-HLH receiving induction therapy.
Clinical Evaluation of Autologous and Allogeneic Stem Cell Therapy for Intrauterine Adhesions: A Systematic Review and Meta-Analysis
Authors: Chen Jia-ming , Huang Qiao-yi , Chen Wei-hong , Lin Shu , Shi Qi-yang 
Published: July 2022

ObjectiveIntrauterine adhesions (IUAs) are a major cause of female infertility. Stem cells can be used to restore endometrial function owing to their regenerative abilities. We compared the safety and efficacy of autologous and allogeneic stem cell treatments in patients with recurrent IUA after conventional therapy based on a systematic review of the related literature.MethodsThe PubMed, Embase, and Cochrane databases were systematically searched. All analysis were performed using Review Manager 5.4. We compared improvements in endometrial thickness, pregnancy rates, menstruation, and side effects after autologous and allogeneic stem cell therapy. The study was registered with PROSPERO, CRD 42022322870.ResultsOur search returned 154 reports, 10 of which met the inclusion criteria, representing 116 patients. Of these, 44 patients in two studies were treated with allogeneic stem cells and 72 patients in eight studies were treated with autologous stem cells. Improvements in endometrial thickness and pregnancy rates after intrauterine device treatment were compared between the autologous and allogeneic stem cell groups. Endometrial thickness increased more after autologous stem cell IUA treatment (mean difference, 1.68; 95% confidence interval [CI]: 1.30–2.07; P &lt; 0.00001), and the pregnancy rate was also improved (relative risk, 1.55; 95% CI: 1.19–2.02, P &lt; 0. 001). No obvious and serious adverse reactions were observed during stem cell therapy in either group.ConclusionsThis meta-analysis and systematic review of the results of randomized trials of autologous and allogeneic stem cell treatments for IUA suggests that autologous stem cells have a better effect in improving the endometrium thickness and pregnancy rate.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022322870.
Cross-Talk of Multiple Types of RNA Modification Regulators Uncovers the Tumor Microenvironment and Immune Infiltrates in Soft Tissue Sarcoma
Authors: Qi Lin , Zhang Wenchao , Ren Xiaolei , Xu Ruiling , Yang Zhimin , Chen Ruiqi , Tu Chao , Li Zhihong 
Published: July 2022

BackgroundSoft-tissue sarcoma (STS) represents a rare and diverse cohort of solid tumors, and encompasses over 100 various histologic and molecular subtypes. In recent years, RNA modifications including m6A, m5C, m1A, and m7G have been demonstrated to regulate immune response and tumorigenesis. Nevertheless, the cross-talk among these RNA modification regulators and related effects upon the tumor microenvironment (TME), immune infiltrates, and immunotherapy in STS remain poorly understood.MethodsIn this study, we comprehensively investigated transcriptional and genetic alterations of 32 RNA modification regulators in STS patients from The Cancer Genome Atlas (TCGA) cohort and validated them in the Gene Expression Omnibus (GEO) cohort. Single-cell transcriptomes were introduced to identify regulators within specific cell types, with own sequencing data and RT-qPCR conducted for biological validation. Distinct regulator clusters and regulator gene subtypes were identified by using unsupervised consensus clustering analysis. We further built the regulator score model based on the prognostic regulator-related differentially expressed genes (DEGs), which could be used to quantitatively assess the risk for individual STS patients. The clinical and biological characteristics of different regulator score groups were further examined.ResultsA total of 455 patients with STS were included in this analysis. The network of 32 RNA modification regulators demonstrated significant correlations within multiple different RNA modification types. Distinct regulator clusters and regulator gene subtypes were characterized by markedly different prognoses and TME landscapes. The low regulator score group in the TCGA-SARC cohort was characterized by poor prognosis. The robustness of the scoring model was further confirmed by the external validation in GSE30929 and GSE17674. The regulator score was negatively correlated with CD4+ T cell, Th2 cell, and Treg cell recruitment and most immunotherapy-predicted pathways, and was also associated with immunotherapy efficacy.ConclusionsOverall, our study is the first to demonstrate the cross-talk of RNA modification regulators and the potential roles in TME and immune infiltrates in STS. The individualized assessment based on the regulator score model could facilitate and optimize personalized treatment.
Comparison of Rapid Cytokine Immunoassays for Functional Immune Phenotyping
Authors: Bonavia Anthony S. , Samuelsen Abigail , Chroneos Zissis C. , Halstead Eric Scott 
Published: July 2022

BackgroundCell-based functional immune-assays may allow for risk stratification of patients with complex, heterogeneous immune disorders such as sepsis. Given the heterogeneity of patient responses and the uncertain immune pathogenesis of sepsis, these assays must first be defined and calibrated in the healthy population.ObjectiveOur objective was to compare the internal consistency and practicality of two immune assays that may provide data on surrogate markers of the innate and adaptive immune response. We hypothesized that a rapid turnaround, microfluidic-based immune assay (ELLA) would be comparable to a dual-color, enzyme-linked immunospot (ELISpot) assay in identifying tumor necrosis factor (TNF) and interferon (IFN)γ production following ex vivo whole blood stimulation.DesignThis was a prospective, observational cohort analysis. Whole blood samples from ten healthy, immune-competent volunteers were stimulated for either 4 hours or 18 hours with lipopolysaccharide, anti-CD3/anti-CD28 antibodies, or phorbol 12-myristate 13-acetate with ionomycin to interrogate innate and adaptive immune responses, respectively.Measurements and Main ResultsELLA analysis produced more precise measurement of TNF and IFNγ concentrations as compared with ELISpot, as well as a four- to five-log10 dynamic range for TNF and IFNγ concentrations, as compared with a two-log10 dynamic range with ELISpot. Unsupervised clustering accurately predicted the ex vivo immune stimulant used for 90% of samples analyzed via ELLA, as compared with 72% of samples analyzed via ELISpot.ConclusionsWe describe, for the first time, a rapid and precise assay for functional interrogation of the innate and adaptive arms of the immune system in healthy volunteers. The advantages of the ELLA microfluidic platform may represent a step forward in generating a point-of-care test with clinical utility, for identifying deranged immune phenotypes in septic patients.
Interleukin 10 Polymorphisms as Risk Factors for Progression to Chagas Disease Cardiomyopathy: A Case-Control Study and Meta-Analysis
Authors: Grijalva Alicia , Gallo Vaulet Lucia , Agüero Roberto Nicolas , Toledano Analia , Risso Marikena Guadalupe , Quarroz Braghini Juan , Sosa David , Ruybal Paula , Repetto Silvia , Alba Soto Catalina Dirney 
Published: July 2022

BackgroundChagas disease is a lifelong infection caused by the protozoa Trypanosoma cruzi endemic in Latin-America and emergent worldwide. Decades after primary infection, 20-30% of infected people develop chronic Chagas cardiomyopathy (CCC) while the others remain asymptomatic. CCC pathogenesis is complex but associated with sustained pro-inflammatory response leading to tissue damage. Hence, levels of IL-10 could have a determinant role in CCC etiology. Studies with Latin-American populations have addressed the association of genetic variants of IL-10 and the risk of developing CCC with inconsistent results. We carried out a case control study to explore the association between IL-10-1082G&gt;A (rs18008969), -819C&gt;T (rs1800871), -592A&gt;C (rs1800872) polymorphisms and CCC in a population attending a hospital in Buenos Aires Argentina. Next, a systematic review of the literature and a meta-analysis were conducted combining present and previous studies to further study this association.MethodsOur case control study included 122 individuals with chronic T. cruzi infection including 64 patients with any degree of CCC and 58 asymptomatic individuals. Genotyping of IL-10 -1082G&gt;A, -819C&gt;T, -592A&gt;C polymorphisms was performed by capillary sequencing of the region spanning the three polymorphic sites and univariate and multivariate statistical analysis was undertaken. Databases in English, Spanish and Portuguese language were searched for papers related to these polymorphisms and Chagas disease up to December 2021. A metanalysis of the selected literature and our study was performed based on the random effect model.ResultsIn our cohort, we found a significant association between TT genotype of -819 rs1800871 and AA genotype of -592 rs1800872 with CCC under the codominant (OR=5.00; 95%CI=1.12-23.87 P=0,04) and the recessive models (OR=5.37; 95%CI=1.12-25.68; P=0,03). Of the genotypes conformed by the three polymorphic positions, the homozygous genotype ATA was significantly associated with increased risk of CCC. The results of the meta-analysis of 754 cases and 385 controls showed that the TT genotype of -819C&gt;T was associated with increased CCC risk according to the dominant model (OR=1.13; 95% CI=1.02–1.25; P=0,03).ConclusionThe genotype TT at -819 rs1800871 contributes to the genetic susceptibility to CCC making this polymorphism a suitable candidate to be included in a panel of predictive biomarkers of disease progression.
Predictive Risk Factors at Admission and a “Burning Point” During Hospitalization Serve as Sequential Alerts for Critical Illness in Patients With COVID-19
Authors: Yin Zhengrong , Zhou Mei , Xu Juanjuan , Wang Kai , Hao Xingjie , Tan Xueyun , Li Hui , Wang Fen , Dai Chengguqiu , Ma Guanzhou , Wang Zhihui , Duan Limin , Jin Yang 
Published: July 2022

BackgroundWe intended to establish a novel critical illness prediction system combining baseline risk factors with dynamic laboratory tests for patients with coronavirus disease 2019 (COVID-19).MethodsWe evaluated patients with COVID-19 admitted to Wuhan West Union Hospital between 12 January and 25 February 2020. The data of patients were collected, and the illness severity was assessed.ResultsAmong 1,150 enrolled patients, 296 (25.7%) patients developed into critical illness. A baseline nomogram model consists of seven variables including age [odds ratio (OR), 1.028; 95% confidence interval (CI), 1.004–1.052], sequential organ failure assessment (SOFA) score (OR, 4.367; 95% CI, 3.230–5.903), neutrophil-to-lymphocyte ratio (NLR; OR, 1.094; 95% CI, 1.024–1.168), D-dimer (OR, 1.476; 95% CI, 1.107–1.968), lactate dehydrogenase (LDH; OR, 1.004; 95% CI, 1.001–1.006), international normalised ratio (INR; OR, 1.027; 95% CI, 0.999–1.055), and pneumonia area interpreted from computed tomography (CT) images (medium vs. small [OR, 4.358; 95% CI, 2.188–8.678], and large vs. small [OR, 9.567; 95% CI, 3.982–22.986]) were established to predict the risk for critical illness at admission. The differentiating power of this nomogram scoring system was perfect with an area under the curve (AUC) of 0.960 (95% CI, 0.941–0.972) in the training set and an AUC of 0.958 (95% CI, 0.936–0.980) in the testing set. In addition, a linear mixed model (LMM) based on dynamic change of seven variables consisting of SOFA score (value, 2; increase per day [I/d], +0.49), NLR (value, 10.61; I/d, +2.07), C-reactive protein (CRP; value, 46.9 mg/L; I/d, +4.95), glucose (value, 7.83 mmol/L; I/d, +0.2), D-dimer (value, 6.08 μg/L; I/d, +0.28), LDH (value, 461 U/L; I/d, +13.95), and blood urea nitrogen (BUN value, 6.51 mmol/L; I/d, +0.55) were established to assist in predicting occurrence time of critical illness onset during hospitalization.ConclusionThe two-checkpoint system could assist in accurately and dynamically predicting critical illness and timely adjusting the treatment regimen for patients with COVID-19.
A Convolutional Neural Network Model for Detecting Sellar Floor Destruction of Pituitary Adenoma on Magnetic Resonance Imaging Scans
Authors: Feng Tianshun , Fang Yi , Pei Zhijie , Li Ziqi , Chen Hongjie , Hou Pengwei , Wei Liangfeng , Wang Renzhi , Wang Shousen 
Published: July 2022

ObjectiveConvolutional neural network (CNN) is designed for image classification and recognition with a multi-layer neural network. This study aimed to accurately assess sellar floor invasion (SFI) of pituitary adenoma (PA) using CNN.MethodsA total of 1413 coronal and sagittal magnetic resonance images were collected from 695 patients with PAs. The enrolled images were divided into the invasive group (n = 530) and the non-invasive group (n = 883) according to the surgical observation of SFI. Before model training, 100 images were randomly selected for the external testing set. The remaining 1313 cases were randomly divided into the training and validation sets at a ratio of 80:20 for model training. Finally, the testing set was imported to evaluate the model performance.ResultsA CNN model with a 10-layer structure (6-layer convolution and 4-layer fully connected neural network) was constructed. After 1000 epoch of training, the model achieved high accuracy in identifying SFI (97.0 and 94.6% in the training and testing sets, respectively). The testing set presented excellent performance, with a model prediction accuracy of 96%, a sensitivity of 0.964, a specificity of 0.958, and an area under the receptor operator curve (AUC-ROC) value of 0.98. Four images in the testing set were misdiagnosed. Three images were misread with SFI (one with conchal type sphenoid sinus), and one image with a relatively intact sellar floor was not identified with SFI.ConclusionThis study highlights the potential of the CNN model for the efficient assessment of PA invasion.
Brain Amyloid Index as a Probable Marker Bridging Between Subjective Memory Complaint and Objective Cognitive Performance
Authors: Choe Young Min , Suh Guk-Hee , Lee Boung Chul , Choi Ihn-Geun , Lee Jun Ho , Kim Hyun Soo , Hwang Jaeuk , Kim Jee Wook 
Published: July 2022

BackgroundThe association between types of subjective memory complaint (SMC), poor objective cognitive performance, and brain Aβ deposition have been poorly understood. We investigated the association between types of SMC and objective global cognitive performance, then assessed whether this association is mediated by the brain amyloid prediction index (API).MethodsIn total, 173 non-demented older adults [63 cognitively normal (CN) and 110 mild cognitive impairment (MCI)] underwent comprehensive clinical assessments. Objective global cognitive performance and brain amyloid index were measured using the total score (TS) of the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery and API, respectively. In total, four items of SMC from the subjective memory complaints questionnaire (SMCQ) (SMCQ1: a feeling of memory problem; SMCQ2: the feeling of worse memory than 10 years ago; SMCQ3: the feeling of worse memory than others of similar age; or SMCQ4: the feeling of difficulty in everyday life) in global memory function were assessed.ResultsIn non-demented and participants with MCI, SMCQ3-positive and SMCQ4-positive groups were associated with decreased TS. In participants with MCI, the SMCQ3-positive group was associated with increased API, and API was associated with decreased TS, but the SMCQ4-positive group did not. In addition, the association between the SMCQ3-positive group and poor TS disappeared when API was controlled as a covariate, indicating that API has a mediation effect.ConclusionThe present findings suggest that SMC, a feeling of worse memory performance than others in a similar age group, in the older adults without dementia is associated with poor objective cognitive performanceviaincreased brain amyloid index.
The Antidepressant Effect of Deoiled Sunflower Seeds on Chronic Unpredictable Mild Stress in Mice Through Regulation of Microbiota–Gut–Brain Axis
Authors: Lu Xiaomeng , Qi Ce , Zheng Jie , Sun Mei , Jin Long , Sun Jin 
Published: July 2022

ObjectivesSunflower seeds provide tryptophan-rich proteins with the potential to protect against depression. Tryptophan is a precursor of serotonin and a substrate for the production of indole derivatives by gut microbiota. This study aimed to investigate the association between the depression-alleviating effects of deoiled and dechlorogenic sunflower seeds (DSFS) and regulation of gut microbiota.Materials and MethodsMale C57BL/6J mice were fed a diet comprising a source of soy protein (normal and model control), DSFS or whey protein concentrate (positive control) for 7 weeks, and chronic stress-induced depression was induced.ResultsFeeding the DSFS diet prevented depression-like behaviors, intestinal barrier damage, elevated plasma corticosterone, and reduced hippocampal serotonin levels in mice. Meanwhile, Feeding the DSFS diet significantly altered the gut microbiota structure, characterized by elevated relative abundances ofIleibacterium valens,Ruminococcus flavefaciens,Clostridium scindens, andOlsenella massiliensis, which were inversely associated with depressive behaviors and markers of mucosal barrier damage. DSFS also altered the gut metabolite profile, prevented depression-induced gutL-tryptophan depletion, and upregulated its metabolite indoleacetaldehyde.ConclusionFeeding the DSFS diet prevented depression in mice by remodeling the gut microbiota and bacterial tryptophan metabolism.
Real-World Effectiveness of Palbociclib Plus Letrozole vs Letrozole Alone for Metastatic Breast Cancer With Lung or Liver Metastases: Flatiron Database Analysis
Authors: Brufsky Adam , Liu Xianchen , Li Benjamin , McRoy Lynn , Layman Rachel M. 
Published: July 2022

BackgroundCyclin-dependent kinase 4/6 inhibitors are a standard treatment for patients with hormone receptor−positive (HR+)/human epidermal growth factor receptor 2−negative (HER2−) metastatic breast cancer (MBC). However, real-world data on effectiveness in patients with liver or lung metastatic disease is limited. This study compared outcomes of palbociclib plus letrozole versus letrozole alone in patients with HR+/HER2− MBC with lung or liver metastasis treated in routine clinical practice in the United States.MethodsThis retrospective analysis used Flatiron Health’s database of electronic health records. Women with HR+/HER2− MBC and liver or lung metastasis received first-line palbociclib plus letrozole or letrozole alone between February 2015 and February 2019. Real-world progression-free survival (rwPFS) was defined as time from start of treatment to death or disease progression. Stabilized inverse probability treatment weighting (sIPTW) was used to balance baseline demographic and clinical characteristics between palbociclib plus letrozole versus letrozole cohorts. Cox proportional-hazards models were used to estimate the effectiveness of palbociclib plus letrozole versus letrozole alone in rwPFS and overall survival (OS).ResultsThe study included 353 patients with lung metastasis, 123 with liver metastasis, and 75 with both. After sIPTW, palbociclib plus letrozole versus letrozole alone was significantlly associated with prolonged rwPFS (hazard ratio (HR), 0.56) and OS (HR, 0.58) (both p&lt;0.001) in all patients. Palbociclib plus letrozole compared with letrozole alone demonstrated a median rwPFS of 16.5 versus 10.5 months, respectively (adjusted HR, 0.52; P&lt;0.001), a median OS of not reached versus 40.3 months (adjusted HR, 0.60; P&lt;0.01) in patients with lung metastasis, and median OS of 30.1 versus 16.8 months (adjusted HR, 0.56; P&lt;0.03 in patients with liver metastasis. In patients with liver metastasis, palbociclib plus letrozole had a median rwPFS of 10.7 months versus 8.0 months in the letrozole alone cohort (adjusted HR, 0.70; P=0.12).ConclusionsIn this real-world population, palbociclib in combination with letrozole is associated with improved outcomes compared with letrozole alone for patients with HR+/HER2− MBC and liver or lung metastasis in the first-line setting. The findings support first-line palbociclib in combination with an aromatase inhibitor as standard of care for HR+/HER2− MBC regardless of visceral disease.Clinical Trial RegistrationNCT04176354.