bluuebunny/crossref_metadata_2025_split huggingface dataset:
A newly defined basement membrane-related gene signature for the prognosis of clear-cell renal cell carcinoma
Authors: Zhou Tao , Chen Weikang , Wu Zhigang , Cai Jian , Zhou Chaofeng 
Published: September 2022

Background: Basement membranes (BMs) are associated with cell polarity, differentiation, migration, and survival. Previous studies have shown that BMs play a key role in the progression of cancer, and thus could serve as potential targets for inhibiting the development of cancer. However, the association between basement membrane-related genes (BMRGs) and clear cell renal cell carcinoma (ccRCC) remains unclear. To address that gap, we constructed a novel risk signature utilizing BMRGs to explore the relationship between ccRCC and BMs.Methods: We gathered transcriptome and clinical data from The Cancer Genome Atlas (TCGA) and randomly separated the data into training and test sets to look for new potential biomarkers and create a predictive signature of BMRGs for ccRCC. We applied univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses to establish the model. The risk signature was further verified and evaluated through principal component analysis (PCA), the Kaplan-Meier technique, and time-dependent receiver operating characteristics (ROC). A nomogram was constructed to predict the overall survival (OS). The possible biological pathways were investigated through functional enrichment analysis. In this study, we also determined tumor mutation burden (TMB) and performed immunological analysis and immunotherapeutic drug analysis between the high- and low-risk groups.Results: We identified 33 differentially expressed genes and constructed a risk model of eight BMRGs, including COL4A4, FREM1, CSPG4, COL4A5, ITGB6, ADAMTS14, MMP17, and THBS4. The PCA analysis showed that the signature could distinguish the high- and low-risk groups well. The K-M and ROC analysis demonstrated that the model could predict the prognosis well from the areas under the curves (AUCs), which was 0.731. Moreover, the nomogram showed good predictability. Univariate and multivariate Cox regression analysis validated that the model results supported the hypothesis that BMRGs were independent risk factors for ccRCC. Furthermore, immune cell infiltration, immunological checkpoints, TMB, and the half-inhibitory concentration varied considerably between high- and low-risk groups.Conclusion: Employing eight BMRGs to construct a risk model as a prognostic indicator of ccRCC could provide us with a potential progression trajectory as well as predictions of therapeutic response.
Long-term prognostic value of inflammatory biomarkers for patients with acute heart failure: Construction of an inflammatory prognostic scoring system
Authors: Zhu Xu , Cheang Iokfai , Xu Fang , Gao Rongrong , Liao Shengen , Yao Wenming , Zhou Yanli , Zhang Haifeng , Li Xinli 
Published: September 2022

ObjectiveSystemic inflammation is associated with a poor prognosis in acute heart failure (AHF). This study was to assess the long-term prognostic value of combining the accessible inflammatory markers in relation to all-cause mortality in patients with AHF.MethodsConsecutive patients with AHF who were hospitalized between March 2012 and April 2016 at the Department of Cardiology of the First Affiliated Hospital of Nanjing Medical University were enrolled in this prospective study. The LASSO regression model was used to select the most valuable inflammatory biomarkers to develop an inflammatory prognostic scoring (IPS) system. Kaplan-Meier method, multivariate COX regression and time-dependent ROC analysis were used to assess the relationship between inflammatory markers and AHF prognosis. A randomized survival forest model was used to estimate the relative importance of each inflammatory marker in the prognostic risks of AHF.ResultsA total of 538 patients with AHF were included in the analysis (mean age, 61.1 ± 16.0 years; 357 [66.4%] men). During a median follow-up of 34 months, there were 227 all-cause deaths (42.2%). C-reactive protein (CRP), red blood cell distribution width (RDW) and neutrophil-to-lymphocyte ratio (NLR) were incorporated into the IPS system (IPS = 0.301×CRP + 0.263×RDW + 0.091×NLR). A higher IPS meant a significantly worse long-term prognosis in Kaplan-Meier analysis, with 0.301 points as the optimal cut-off value (P log-rank &lt;0.001). IPS remained an independent prognostic factor associated with an increased risk of all-cause mortality among patients with AHF in multivariate Cox regression models with a full adjustment of the other significant covariables. Random forest variable importance and minimal depth analysis further validated that the IPS system was the most predictive for all-cause mortality in patients with AHF.ConclusionsInflammatory biomarkers were associated with the risk of all-cause mortality in patients with AHF, while IPS significantly improved the predictive power of the model and could be used as a practical tool for individualized risk stratification of patients with AHF.
Role of complement C1q/C3-CR3 signaling in brain injury after experimental intracerebral hemorrhage and the effect of minocycline treatment
Authors: Zheng Yonghe , Fan Linfeng , Xia Siqi , Yang Qiguo , Zhang Zhihua , Chen Huaijun , Zeng Hanhai , Fu Xiongjie , Peng Yucong , Xu Chaoran , Yu Kaibo , Liu Fuyi , Cao Shenglong 
Published: September 2022

AimThe complement cascade is activated and may play an important pathophysiologic role in brain injury after experimental intracerebral hemorrhage (ICH). However, the exact mechanism of specific complement components has not been well studied. This study determined the role of complement C1q/C3-CR3 signaling in brain injury after ICH in mice. The effect of minocycline on C1q/C3-CR3 signaling-induced brain damage was also examined.MethodsThere were three parts to the study. First, the natural time course of C1q and CR3 expression was determined within 7 days after ICH. Second, mice had an ICH with CR3 agonists, LA-1 or vehicle. Behavioral score, neuronal cell death, hematoma volume, and oxidative stress response were assessed at 7 days after ICH. Third, the effect of minocycline on C1q/C3-CR3 signaling and brain damage was examined.ResultsThere were increased numbers of C1q-positive and CR3-positive cells after ICH. Almost all perihematomal C1q-positive and CR3-positive cells were microglia/macrophages. CR3 agonist LA-1 aggravated neurological dysfunction, neuronal cell death, and oxidative stress response on day 7 after ICH, as well as enhancing the expression of the CD163/HO-1 pathway and accelerating hematoma resolution. Minocycline treatment exerted neuroprotective effects on brain injury following ICH, partly due to the inhibition of C1q/C3-CR3 signaling, and that could be reversed by LA-1.ConclusionsThe complement C1q/C3-CR3 signaling is upregulated after ICH. The activation of C1q/C3-CR3 signaling by LA-1 aggravates brain injury following ICH. The neuroprotection of minocycline, at least partly, is involved with the repression of the C1q/C3-CR3 signaling pathway.
Frequency of positive antiphospholipid antibodies in pregnant women with SARS-CoV-2 infection and impact on pregnancy outcome: A single-center prospective study on 151 pregnancies
Authors: Gozzoli Giorgia Ingrid , Piovani Elda , Negri Beatrice , Mascherpa Margaret , Orabona Rossana , Zanardini Cristina , Zatti Sonia , Piantoni Silvia , Lazzaroni Maria Grazia , Tomasi Cesare , Prefumo Federico , Sartori Enrico , Franceschini Franco , Tincani Angela , Andreoli Laura 
Published: September 2022

BackgroundAt the beginning of the SARS-CoV-2 pandemic, there was a lack of information about the infection’s impact on pregnancy and capability to induce de novo autoantibodies. It soon became clear that thrombosis was a manifestation of COVID-19, therefore the possible contribution of de novo antiphospholipid antibodies (aPL) raised research interest. We aimed at screening SARS-CoV-2 positive pregnant patients for aPL.MethodsThe study included consecutive pregnant women who were hospitalized in our Obstetric Department between March 2020 and July 2021 for either a symptomatic SARS-CoV-2 infection or for other reasons (obstetric complications, labour, delivery) and found positive at the admission nasopharyngeal swab. All these women underwent the search for aPL by means of Lupus Anticoagulant (LA), IgG/IgM anti-cardiolipin (aCL), IgG/IgM anti-beta2glycoprotein I (aB2GPI). Data about comorbidities, obstetric and neonatal complications were collected.Results151 women were included. Sixteen (11%) were positive for aPL, mostly at low titre. Pneumonia was diagnosed in 20 women (5 with positive aPL) and 5 required ICU admission (2 with positive aPL). Obstetric complications occurred in 10/16 (63%) aPL positive and in 36/135 (27%) negative patients. The occurrence of HELLP syndrome and preeclampsia was significantly associated with positive aPL (p=0,004). One case of maternal thrombosis occurred in an aPL negative woman. aPL positivity was checked after at least 12 weeks in 7/16 women (44%): 3 had become negative; 2 were still positive (1 IgG aB2GPI + IgG aCL; 1 IgM aB2GPI); 1 remained positive for IgG aCL but became negative for aB2GPI; 1 became negative for LA but displayed a new positivity for IgG aCL at high titre.ConclusionsThe frequency of positive aPL in pregnant women with SARS-CoV-2 infection was low in our cohort and similar to the one described in the general obstetric population. aPL mostly presented as single positive, low titre, transient antibodies. The rate of obstetric complications was higher in aPL positive women as compared to negative ones, particularly hypertensive disorders. Causality cannot be excluded; however, other risk factors, including a full-blown picture of COVID-19, may have elicited the pathogenic potential of aPL and contributed themselves to the development of complications.
Marek’s disease virus-specific T cells proliferate, express antiviral cytokines but have impaired degranulation response
Authors: Boodhoo Nitish , Behboudi Shahriar 
Published: September 2022

The major histocompatibility complex (MHC) haplotype is one of the major determinants of genetic resistance and susceptibility of chickens to Marek’s disease (MD) which is caused by an oncogenic herpesvirus; Marek’s disease virus (MDV). To determine differential functional abilities of T cells associated with resistance and susceptibility to MD, we identified immunodominant CD4+TCRvβ1 T cell epitopes within the pp38 antigen of MDV in B19 and B21 MHC haplotype chickens using an ex vivo ELISPOT assay for chicken IFN-gamma. These novel pp38 peptides were used to characterize differential functional abilities of T cells as associated with resistance and susceptibility to MD. The results demonstrated an upregulation of cytokines (IL-2, IL-4, IL-10) and lymphocyte lysis-related genes (perforin and granzyme B) in an antigen specific manner using RT-PCR. In the MD-resistant chickens (B21 MHC haplotype), antigen-specific and non-specific response was highly skewed towards Th2 response as defined by higher levels of IL-4 expression as well as lymphocyte lysis-related genes compared to that in the MD-susceptible chicken line (B19 MHC haplotype). Using CD107a degranulation assay, the results showed that MDV infection impairs cytotoxic function of T cells regardless of their genetic background. Taken together, the data demonstrate an association between type of T cell response to pp38 and resistance to the disease and will shed light on our understanding of immune response to this oncogenic herpesvirus and failure to induce sterile immunity.
A cytokine/PTX3 prognostic index as a predictor of mortality in sepsis
Authors: Davoudian Sadaf , Piovani Daniele , Desai Antonio , Mapelli Sarah N. , Leone Roberto , Sironi Marina , Valentino Sonia , Silva-Gomes Rita , Stravalaci Matteo , Asgari Fatemeh , Madera Alessandra , Piccinini Daniele , Fedeli Carlo , Comina Denise , Bonovas Stefanos , Voza Antonio , Mantovani Alberto , Bottazzi Barbara 
Published: September 2022

BackgroundEarly prognostic stratification of patients with sepsis is a difficult clinical challenge. Aim of this study was to evaluate novel molecules in association with clinical parameters as predictors of 90-days mortality in patients admitted with sepsis at Humanitas Research Hospital.MethodsPlasma samples were collected from 178 patients, diagnosed based on Sepsis-3 criteria, at admission to the Emergency Department and after 5 days of hospitalization. Levels of pentraxin 3 (PTX3), soluble IL-1 type 2 receptor (sIL-1R2), and of a panel of pro- and anti-inflammatory cytokines were measured by ELISA. Cox proportional-hazard models were used to evaluate predictors of 90-days mortality.ResultsCirculating levels of PTX3, sIL-1R2, IL-1β, IL-6, IL-8, IL-10, IL-18, IL-1ra, TNF-α increased significantly in sepsis patients on admission, with the highest levels measured in shock patients, and correlated with SOFA score (PTX3: r=0.44, p&lt;0.0001; sIL-1R2: r=0.35, p&lt;0.0001), as well as with 90-days mortality. After 5 days of hospitalization, PTX3 and cytokines, but not sIL-1R2 levels, decreased significantly, in parallel with a general improvement of clinical parameters. The combination of age, blood urea nitrogen, PTX3, IL-6 and IL-18, defined a prognostic index predicting 90-days mortality in Sepsis-3 patients and showing better apparent discrimination capacity than the SOFA score (AUC=0.863, 95% CI: 0.780−0.945vs.AUC=0.727, 95% CI: 0.613-0.840; p=0.021 respectively).ConclusionThese data suggest that a prognostic index based on selected cytokines, PTX3 and clinical parameters, and hence easily adoptable in clinical practice, performs in predicting 90-days mortality better than SOFA. An independent validation is required.
Serum MUC5AC protein levels are correlated with the development and severity of connective tissue disease-associated pulmonary interstitial lesions
Authors: Weng Lin , Liu Wei , Wang Lingye , Wu Zhichao , Liu Dehao , Lin Yihua , Song Shuli , Yu Ciyuan , Chen Yaqiong , Chen Juan , Ge Shengxiang 
Published: September 2022

BackgroundMucin 5AC (MUC5AC) and mucin 5B (MUC5B) are the major components of airway mucins. The expression levels of MUC5AC and MUC5B are related to connective tissue disease-associated interstitial lung disease (CTD-ILD) in the promoter region of MUC5AC and MUC5B and the relevant bronchoalveolar lavage fluid. However, the serum protein levels of MUC5AC and MUC5B have not been tested in CTD-ILD patients. In this study, we tested the serum levels of MUC5AC and MUC5B proteins in CTD-ILD patients and assessed their relationship with the occurrence and development of ILD.MethodsSerum samples were obtained from 168 CTD and 80 healthy participants from the First Affiliated Hospital of Xiamen University. The serum levels of MUC5AC and MUC5B proteins were measured by enzyme-linked immunosorbent assay.ResultsOf the 168 individuals with CTD, 70 had primary Sjögren’s syndrome (pSS), 64 had systemic sclerosis (SSc), and 34 had polymyositis/dermatomyositis (PM/DM). There were 116 cases with concurrent ILD; ILD scores were 1 (n=23), 2 (n=41), and 3 (n=52). Serum MUC5AC and MUC5B protein levels were considerably higher in CTD-ILD than CTD-only individuals or healthy controls (both p&lt;0.005). Among the CTD subgroups, MUC5AC was higher in individuals with concurrent ILD than in those without ILD (all p&lt;0.05). MUC5AC was positively correlated with ILD severity in all three CTD subgroups (all R&gt;0.47 and all p&lt;0.05). The MUC5B levels varied substantially between SSc and SSc patients with concurrent ILD (p=0.032) and were related to ILD severity only in PM/DM patients (R=0.346 and p=0.045).ConclusionMUC5AC is correlated with the occurrence and development of ILD, while MUC5B is associated with ILD diagnosis and severity in CTD subgroups. Serum MUC5AC levels present a definite diagnostic utility for CTD-ILD and as proxies for its severity.
High-dose vitamin C on sepsis: Protocol of a prospective, multi-centered, double-blinded, randomized, and placebo-controlled superiority study
Authors: Zhao Bing , Li Mengjiao , Sun Wenwu , Li Jian , Liu Leshan , Wang Yihui , Sun Silei , Xu Lili , Qi Xing , Xie Mengqi , Zhou Yuhua , Ni Tongtian , Yao Yi , Chen Peili , Yu Meiling , Jiang Weisong , Ning Ning , Sheng Huiqiu , Chen Erzhen , Wang Ruilan , Tong Chaoyang , Cao Yu , Sun Mingwei , Mao Enqiang 
Published: September 2022

BackgroundSepsis is an inflammatory syndrome with life-threatening organ dysfunction and high mortality. In the recent 10 years, high-dose intravenous injection of vitamin C, the first-line antioxidant of humans, has received highlighted attention in the field of critical care. The study aims to examine the efficacy and safety of high-dose intravenous injection of vitamin C in the treatment of sepsis.Methods and designHere, we are conducting a prospective, multi-centered, double-blinded, randomized, and placebo-controlled superiority study named High-Dose Vitamin C on Sepsis (HDVCOS). A total of 620 participants diagnosed with sepsis in four participating sites across China that satisfy the eligibility criteria will be randomized at a ratio of 1:1 to receive treatment with a high-dose intravenous injection of vitamin C (200 mg/kg/24 h) or placebo (saline) for 4 days. The primary outcome is 28 days of mortality. The secondary outcomes include the incidence of organ failure, Sequential Organ Failure Assessment (SOFA) score change, organ support, the relationship between plasma vitamin C concentration and outcomes, and adverse events.ConclusionThe findings of this study will provide potential evidence for high-dose intravenous injection of vitamin C in the treatment of sepsis.Clinical trial registration[http://www.chictr.org.cn/showprojen.aspx?proj=29851], identifier [ChiCTR1800017633].
Gynecological complications in long-term survivors after allogeneic hematopoietic cell transplantation—a single-center real-life cross-sectional study
Authors: Su Huina , Zhou Xinyu , Zhao Yanli , Lu Yue , Liu DeYan , Zhang Janping , Yang Xin 
Published: September 2022

Background and objectivesHematopoietic stem cell transplantation (HCT) is a treatment for hematopoietic diseases. However, most cured female patients may suffer from premature ovarian insufficiency (POI) after HCT, which is mainly caused by the pre-HCT conditioning regimen. Hence, this study aims to explore the impact of HCT treatment on reproductive and ovarian functions in female survivors.MethodsA total of 55 female participants under the age of 40, who underwent HCT and met the inclusion criteria were enrolled. Data related to blood disease, menstruation, and fertility in the 3 years following HCT were collected.ResultsThe involved patients received transplantation at different age stages, ranging from 8 to 37. All patients, except those with aplastic anemia (AA; 5/55), received a myeloablative conditioning regimen, usually modified total body irradiation/cyclophosphamide (TBI/Cy; 25/55) or modified Busulfan/cyclophosphamide (Bu/Cy; 23/55). Among women (42/55) who menstruated before HCT, 16.67% (7/42) had a spontaneous menstrual relapse and 83.3% (35/42) had amenorrhea after HCT. 72.7% (40/55) could be regarded as having POI. This proportion included 100% (25/25) of women aged 21–40 at the time of HCT, 62.5% (15/24) of those aged 11–20, and 0% (0/6) of those ≤10 years old. Patients with AML were more likely to have POI (95.7%). Patients aged ≤10 years (0%) or 11–20 years (16.7%) at the time of HCT were less likely to have moderate to severe menopause than those 21–40 years old (44%).ConclusionThe prevalence of POI following HCT was high and POI was associated with age, conditioning regimen, and type of blood disease.
Primary diffuse large B-cell lymphoma of orbit: A population-based analysis
Authors: Chen Yu-Qing , Yue Zi-Fan , Chen Sai-Nan , Tong Fei , Yang Wei-Hua , Wei Rui-Li 
Published: September 2022

ObjectivePrimary orbital lymphoma (POL) accounts for an essential part of adult orbital malignancies. Nevertheless, it remains a relatively rare lymphoid malignancy, accounting for &lt;1% of all non-Hodgkin's lymphoma (NHL) cases. Orbital diffuse large B-cell lymphoma (DLBCL) is one of the most prevalent subtypes of POL that confers the worst outcomes. The prognostic determinants of orbital DLBCL remain unknown. Therefore, a retrospective analysis was conducted by investigating the Surveillance, Epidemiology, and End Results (SEER) database for independent predictive factors for the prognosis of orbital DLBCL.Materials and methodsUsing the SEER program, we acquired patient data including demographics, clinical characteristics, and treatment strategies. Our cohort included cases of primary orbital DLBCL diagnosed from 2000 to 2017. We conducted Kaplan-Meier analyses to visualize the overall survival (OS) and cause-specific survival (CSS). The Cox proportional hazard regression models were applied to assess the effects of these prognostic factors on OS and CSS.ResultsThe present cohort included 332 patients with orbital DLBCL. Age was the most impacted variable by orbital DLBCL. Three independent prognostic variables of orbital DLBCL were identified on diagnosis: advanced age, no radiation treatment, and late-stage (Stage IV). Moreover, patients who underwent chemotherapy demonstrated a greater OS when compared with those who did not. In orbital DLBCL, being unmarried was also a poor prognostic factor.ConclusionThe current study is the largest population-based case series of orbital DLBCL. The age at the time of diagnosis, marital status, absence of chemotherapy or radiotherapy, and tumor stage were all found to be correlated with worse prognosis.
FOSL1 promotes tumor growth and invasion in ameloblastoma
Authors: Xiong Gan , Ouyang Shengqi , Xie Nan , Xie Jiaxiang , Wang Wenjin , Yi Chen , Zhang Ming , Xu Xiuyun , Chen Demeng , Wang Cheng 
Published: September 2022

BackgroundFOSL1, a key component of the Activating protein-1 (AP-1) transcriptional complex, plays an important role in cancer cell migration, invasion, and proliferation. However, the impact of FOSL1 in ameloblastoma (AM) has not been clarified. Herein, we aimed to assess the expression of FOSL1 and investigate its functional role in AM.MethodsThe expression of FOSL1 was examined based on an immunohistochemistry analysis of 96 AM samples. Cell proliferation, migration, invasion, and tumorigenesis were assessed using Cell Counting Kit-8 (CCK-8), colony formation, Transwell, and sphere formation assays. RNA sequencing (RNA-seq) was employed to investigate the molecular alterations of AM cells upon FOSL depletion. Microarrays of AMs were downloaded from the Gene Expression Omnibus (GEO) database for bioinformatics analysis. In addition, patient-derived AM organoids were used to evaluate the therapeutic value of the AP-1 inhibitor.ResultsFOSL1 was detected in the nuclei of AMs and upregulated in conventional AMs compared to unicystic AMs and normal oral epithelium. Compared with primary AM, FOSL1 expression was significantly increased in recurrent AM. Genetic knockdown of FOSL1 suppressed the proliferation, migration, invasion, and sphere formation of AMs. Similar results were also observed by pharmacological inhibition of AP-1 activity. Moreover, the AP-1 inhibitor T5224 impeded the growth of organoids derived from AM patients. Mechanistically, our Ingenuity Pathway Analysis (IPA) and gene set enrichment analysis (GSEA) results revealed that depletion of FOSL1 inactivated kinetochore metaphase signaling and the epithelial–mesenchymal transition pathway and then impaired the aggressiveness of AM cells accordingly.ConclusionFOSL1 promotes tumor recurrence and invasive growth in AM by modulating kinetochore metaphase signaling and the epithelial–mesenchymal transition pathway; thus, it represents a promising therapeutic target for AM treatment.