bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic changes in PSA levels predict prognostic outcomes in prostate cancer patients undergoing androgen -deprivation therapy: A multicenter retrospective analysis
Authors: Hu Mingqiu , Mao Yifeng , Guan Chao , Tang Zhizhong , Bao Zhihang , Li Yingbang , Liang Guowu 
Published: February 2023

BackgroundAndrogen-deprivation therapy (ADT) is used for the treatment of prostate cancer. However, the specific risk factors for the development of castration-resistant disease are still unclear. The present study sought to identify predictors of patient prognostic outcomes through analyses of clinical findings in large numbers of prostate cancer patients following ADT treatment.MethodsData pertaining to 163 prostate cancer patients treated at the Second Affiliated Hospital of Bengbu Medical University and Maoming People’s Hospital from January 1, 2015, to December 30, 2020, were retrospectively analyzed. Dynamic changes in prostate-specific antigen (PSA) levels were regularly assessed, including both time to nadir (TTN) and nadir PSA (nPSA). Univariate and multivariate analyses were performed with Cox risk proportional regression models, while differences in biochemical progression-free survival (bPFS) were compared among groups with Kaplan-Meier curves and log-rank tests.ResultsThe bPFS values over the median 43.5-month follow-up period differed significantly between patients with nPSA levels &lt; 0.2 ng/mL and ≥ 0.2 ng/mL, being 27.6 months and 13.5 months, respectively (log-rank P &lt; 0.001). A significant difference in median bPFS was also observed when comparing patients with a TTN ≥ 9 months (27.8 months) to those with a TTN &lt; 9 months (13.5 months) (log-rank P &lt; 0.001).ConclusionsTTN and nPSA are valuable predictors of prognosis in prostate cancer patients after ADT treatment, with better outcomes evident in patients with nPSA &lt; 0.2 ng/mL and TTN &gt; 9 months.
A phase Ib study of interleukin-2 plus pembrolizumab for patients with advanced melanoma
Authors: Silk Ann W. , Curti Brendan , Bryan Jennifer , Saunders Tracie , Shih Weichung , Kane Michael P. , Hannon Phoebe , Fountain Christopher , Felcher Jessica , Zloza Andrew , Kaufman Howard L. , Mehnert Janice M. , McDermott David F. 
Published: February 2023

IntroductionHigh-dose interleukin-2 (HD IL-2) and pembrolizumab are each approved as single agents by the U.S. F.D.A. for the treatment of metastatic melanoma. There is limited data using the agents concurrently. The objectives of this study were to characterize the safety profile of IL-2 in combination with pembrolizumab in patients with unresectable or metastatic melanoma.MethodsIn this Phase Ib study, patients received pembrolizumab (200 mg IV every 3 weeks) and escalating doses of IL-2 (6,000 or 60,000 or 600,000 IU/kg IV bolus every 8 hours up to 14 doses per cycle) in cohorts of 3 patients. Prior treatment with a PD-1 blocking antibody was allowed. The primary endpoint was the maximum tolerated dose (MTD) of IL-2 when co-administered with pembrolizumab.ResultsTen participants were enrolled, and 9 participants were evaluable for safety and efficacy. The majority of the evaluable participants (8/9) had been treated with PD-1 blocking antibody prior to enrollment. Patients received a median of 42, 22, and 9 doses of IL-2 in the low, intermediate, and high dose cohorts, respectively. Adverse events were more frequent with increasing doses of IL-2. No dose limiting toxicities were observed. The MTD of IL-2 was not reached. One partial response occurred in 9 patients (11%). The responding patient, who had received treatment with an anti-PD-1 prior to study entry, was treated in the HD IL-2 cohort.DiscussionAlthough the sample size was small, HD IL-2 therapy in combination with pembrolizumab appears feasible and tolerable.Clinical trial registrationClinicalTrials.gov, identifier NCT02748564.
Mitochondrial gene expression signature predicts prognosis of pediatric acute myeloid leukemia patients
Authors: Chaudhary Shilpi , Ganguly Shuvadeep , Palanichamy Jayanth Kumar , Singh Archna , Pradhan Dibyabhaba , Bakhshi Radhika , Chopra Anita , Bakhshi Sameer 
Published: February 2023

IntroductionGene expression profile of mitochondrial-related genes is not well deciphered in pediatric acute myeloid leukaemia (AML). We aimed to identify mitochondria-related differentially expressed genes (DEGs) in pediatric AML with their prognostic significance.MethodsChildren with de novo AML were included prospectively between July 2016-December 2019. Transcriptomic profiling was done for a subset of samples, stratified by mtDNA copy number. Top mitochondria-related DEGs were identified and validated by real-time PCR. A prognostic gene signature risk score was formulated using DEGs independently predictive of overall survival (OS) in multivariable analysis. Predictive ability of the risk score was estimated along with external validation in The Tumor Genome Atlas (TCGA) AML dataset.ResultsIn 143 children with AML, twenty mitochondria-related DEGs were selected for validation, of which 16 were found to be significantly dysregulated. Upregulation of SDHC (p&lt;0.001), CLIC1 (p=0.013) and downregulation of SLC25A29 (p&lt;0.001) were independently predictive of inferior OS, and included for developing prognostic risk score. The risk score model was independently predictive of survival over and above ELN risk categorization (Harrell’s c-index: 0.675). High-risk patients (risk score above median) had significantly inferior OS (p&lt;0.001) and event free survival (p&lt;0.001); they were associated with poor-risk cytogenetics (p=0.021), ELN intermediate/poor risk group (p=0.016), absence of RUNX1-RUNX1T1 (p=0.027), and not attaining remission (p=0.016). On external validation, the risk score also predicted OS (p=0.019) in TCGA dataset.DiscussionWe identified and validated mitochondria-related DEGs with prognostic impact in pediatric AML and also developed a novel 3-gene based externally validated gene signature predictive of survival.
Construction and validation of a novel nomogram to predict cancer-specific survival in patients with gastric adenocarcinoma
Authors: Nie Guole , Zhang Honglong , Yan Jun , Xie Danna , Zhang Haijun , Li Xun 
Published: February 2023

Background and aimsAdenocarcinoma is one of the most common pathological types of gastric cancer. The aims of this study were to develop and validate prognostic nomograms that could predict the probability of cancer-specific survival (CSS) for gastric adenocarcinoma (GAC) patients at 1, 3, and 5 years.MethodsIn total, 7747 patients with GAC diagnosed between 2010 and 2015, and 4591 patients diagnosed between 2004 and 2009 from the Surveillance, Epidemiology, and End Results (SEER) database were included in this study. The 7747 patients were used as a prognostic cohort to explore GAC-related prognostic risk factors. Moreover, the 4591 patients were used for external validation. The prognostic cohort was also divided into a training and internal validation sets for construction and internal validation of the nomogram. CSS predictors were screened using least absolute shrinkage and selection operator regression analysis. A prognostic model was built using Cox hazard regression analysis and provided as static and dynamic network-based nomograms.ResultsThe primary site, tumor grade, surgery of the primary site, T stage, N stage, and M stage were determined to be independent prognostic factors for CSS and were subsequently included in construction of the nomogram. CSS was accurately estimated using the nomogram at 1, 3, and 5 years. The areas under the curve (AUCs) for the training group at 1, 3, and 5 years were 0.816, 0.853, and 0.863, respectively. Following internal validation, these values were 0.817, 0.851, and 0.861. Further, the AUC of the nomogram was much greater than that of American Joint Committee on Cancer (AJCC) or SEER staging. Moreover, the anticipated and actual CSS values were in good agreement based on decision curves and time-calibrated plots. Then, patients from the two subgroups were divided into high- and low-risk groups based on this nomogram. The survival rate of high-risk patients was considerably lower than that of low-risk patients, according to Kaplan–Meier (K-M) curves (p&lt;0.0001).ConclusionsA reliable and convenient nomogram in the form of a static nomogram or an online calculator was constructed and validated to assist physicians in quantifying the probability of CSS in GAC patients.
GPX3 expression was down-regulated but positively correlated with poor outcome in human cancers
Authors: Hu Qingyi , Chen Jiaoshun , Yang Wen , Xu Ming , Zhou Jun , Tan Jie , Huang Tao 
Published: February 2023

IntroductionCancer is a crucial public health problem and one of the leading causes of death worldwide. Previous studies have suggested that GPX3 may be involved in cancer metastasis and chemotherapy resistance. However, how GPX3 affects cancer patients’ outcomes and the underlying mechanism remains unclear.MethodsSequencing data and clinical data from TCGA, GTEx, HPA, and CPTAC were used to explore the relationship between GPX3 expression and clinical features. Immunoinfiltration scores were used to assess the relationship between GPX3 and the tumor immune microenvironment. Functional enrichment analysis was used to predict the role of GPX3 in tumors. Gene mutation frequency, methylation level, and histone modification were used to predict the GPX3 expression regulation method. Breast, ovarian, colon, and gastric cancer cells were used to investigate the relationship between GPX3 expression and cancer cell metastasis, proliferation, and chemotherapy sensitivity.ResultsGPX3 is down-regulated in various tumor tissues, and GPX3 expression level can be used as a marker for cancer diagnosis. However, GPX3 expression is associated with higher stage and lymph node metastasis, as well as poorer prognosis. GPX3 is closely related to thyroid function and antioxidant function, and its expression may be regulated by epigenetic inheritance such as methylation modification or histone modification. In vitro experiments, GPX3 expression is associated with cancer cell sensitivity to oxidant and platinum-based chemotherapy and is involved in tumor metastasis in oxidative environments.DiscussionWe explored the relationship between GPX3 and clinical features, immune infiltration characteristics, migration and metastasis, and chemotherapy sensitivities of human cancers. We further investigated the potential genetic and epigenetic regulation of GPX3 in cancer. Our results suggested that GPX3 plays a complicated role in the tumor microenvironment, simultaneously promoting metastasis and chemotherapy resistance in human cancers.
Seroprevalence of Epstein–Barr virus infection in children during the COVID-19 pandemic in Zhejiang, China
Authors: Cai Fengqing , Gao Hui , Ye Qing 
Published: February 2023

AimWe aimed to investigate the seroprevalence of Epstein–Barr virus (EBV) infection in children before and during the COVID-19 pandemic.MethodsAll children admitted to the Children's Hospital Affiliated to Zhejiang University from January 2019 to December 2021 with suspected EBV-associated disease and EBV antibodies were detected by a two-step indirect method of chemiluminescence technology. A total of 44,943 children were enrolled in this study. The seroprevalence of EBV infections was compared from January 2019 to December 2021.ResultsThe total seropositive rate of EBV infections was 61.02% between January 2019 and December 2021, and the seropositive trend decreased year by year. The total number of seropositive EBV infections in 2020 was reduced by 30% compared to that in 2019. In particular, nearly 30% and 50% reductions in the number of acute EBV infections and EBV reactivations or late primary infections from 2019 to 2020 were found, respectively. The number of acute EBV infections in children aged 1–3 years and EBV reactivation or late primary infection in children aged 6–9 years in 2020 sharply dropped by approximately 40% and 64% compared to that in 2019.ConclusionsOur study further demonstrated that the prevention and control measures for COVID-19 in China had a certain effect on containing acute EBV infections and EBV reactivations or late primary infections.
Identification of the molecular determinants of antagonist potency in the allosteric binding pocket of human P2X4
Authors: Pasqualetto Gaia , Zuanon Marika , Brancale Andrea , Young Mark T. 
Published: February 2023

P2X receptors are a family of ATP-gated cation channels comprising seven subtypes in mammals, which play key roles in nerve transmission, pain sensation and inflammation. The P2X4 receptor in particular has attracted significant interest from pharmaceutical companies due to its physiological roles in neuropathic pain and modulation of vascular tone. A number of potent small-molecule P2X4 receptor antagonists have been developed, including the allosteric P2X4 receptor antagonist BX430, which is approximately 30-fold more potent at human P2X4 compared with the rat isoform. A single amino-acid difference between human and rat P2X4 (I312T), located in an allosteric pocket, has previously been identified as critical for BX430 sensitivity, implying that BX430 binds in this pocket. Using a combination of mutagenesis, functional assay in mammalian cells and in silico docking we confirmed these findings. Induced-fit docking, permitting the sidechains of the amino-acids of P2X4 to move, showed that BX430 could access a deeper portion of the allosteric pocket, and that the sidechain of Lys-298 was important for shaping the cavity. We then performed blind docking of 12 additional P2X4 antagonists into the receptor extracellular domain, finding that many of these compounds favored the same pocket as BX430 from their calculated binding energies. Induced-fit docking of these compounds in the allosteric pocket enabled us to show that antagonists with high potency (IC50 ≤ 100 nM) bind deep in the allosteric pocket, disrupting a network of interacting amino acids including Asp-85, Ala-87, Asp-88, and Ala-297, which are vital for transmitting the conformational change following ATP binding to channel gating. Our work confirms the importance of Ile-312 for BX430 sensitivity, demonstrates that the allosteric pocket where BX430 binds is a plausible binding pocket for a series of P2X4 antagonists, and suggests a mode of action for these allosteric antagonists involving disruption of a key structural motif required for the conformational change induced in P2X4 when ATP binds.
Sinusoidal CO2 respiratory challenge for concurrent perfusion and cerebrovascular reactivity MRI
Authors: Vu Chau , Xu Botian , González-Zacarías Clio , Shen Jian , Baas Koen P. A. , Choi Soyoung , Nederveen Aart J. , Wood John C. 
Published: February 2023

Introduction: Deoxygenation-based dynamic susceptibility contrast (dDSC) has previously leveraged respiratory challenges to modulate blood oxygen content as an endogenous source of contrast alternative to gadolinium injection in perfusion-weighted MRI. This work proposed the use of sinusoidal modulation of end-tidal CO2 pressures (SineCO2), which has previously been used to measure cerebrovascular reactivity, to induce susceptibility-weighted gradient-echo signal loss to measure brain perfusion.Methods:SineCO2 was performed in 10 healthy volunteers (age 37 ± 11, 60% female), and tracer kinetics model was applied in the frequency domain to calculate cerebral blood flow, cerebral blood volume, mean transit time, and temporal delay. These perfusion estimates were compared against reference techniques, including gadolinium-based DSC, arterial spin labeling, and phase contrast.Results: Our results showed regional agreement between SineCO2 and the clinical comparators. SineCO2 was able to generate robust CVR maps in conjunction to baseline perfusion estimates.Discussion: Overall, this work demonstrated feasibility of using sinusoidal CO2 respiratory paradigm to simultaneously acquire both cerebral perfusion and cerebrovascular reactivity maps in one imaging sequence.
Altered dynamics of mitochondria and reactive oxygen species in the erythrocytes of migrating red-headed buntings
Authors: Bhardwaj Nitin , Kumar Anit , Gupta Neelu Jain 
Published: February 2023

Background: Blood antioxidants provide propensity to mitigate reactive oxygen species (ROS) apart from other oxidative challenges during a high-energy state of migration in night migratory songbirds. The study investigated the modulation of erythrocytes, mitochondrial abundance, hematocrit changes, and relative expression of fat transport-related genes during migration in red-headed buntings (Emberiza bruniceps). We hypothesized an increase in antioxidants along with the mitigation of mitochondria-related reactive oxygen species elevation and consequential apoptosis occurring during migration.Methods: Male red-headed buntings (n = 6) were placed under short days (8 h of light and 16 h of dark, 8L:16D)/long days (14L:10D) and photo induced to simulated non-migratory, nMig; pre-migratory, pMig; and migratory, Mig, states. Erythrocyte shape, reactive oxygen species production, mitochondrial membrane potential (MMP), reticulocyte proportion, and apoptosis were analyzed using flow cytometry and relative expression of fat metabolizing and antioxidant genes was measured by using qPCR.Results: There was a significant increase in hematocrit, erythrocyte area, and mitochondrial membrane potential. Reactive oxygen species and apoptotic erythrocyte proportion declined in the Mig state. The changes in antioxidant genes (SOD1 and NOS2), fatty acid translocase (CD36), and metabolic (FABP3, DGAT2, GOT2, and ATGL) genes showed a significant increment during the Mig state.Conclusion: These results suggested that adaptive changes occur in mitochondrial behavior and apoptosis of erythrocytes. The transition in erythrocytes, antioxidant genes, and fatty acid metabolism gene expressions suggested differences in regulatory strategies at the cellular/transcriptional level during different states of simulated migration in birds.
The role of climate, vegetation, and soil factors on carbon fluxes in Chinese drylands
Authors: Liu Zhaogang , Chen Zhi , Yu Guirui , Zhang Weikang , Zhang Tianyou , Han Lang 
Published: February 2023

Drylands dominate the trend and variability of the land carbon (C) sink. A better understanding of the implications of climate-induced changes in the drylands for C sink-source dynamics is urgently needed. The effect of climate on ecosystem C fluxes (gross primary productivity (GPP), ecosystem respiration (ER), and net ecosystem productivity (NEP)) in drylands has been extensively explored, but the roles of other concurrently changing factors, such as vegetation conditions and nutrient availability, remain unclear. We used eddy-covariance C-flux measurements from 45 ecosystems with concurrent information on climate (mean annual temperature (MAT) and mean annual precipitation (MAP)), soil (soil moisture (SM) and soil total nitrogen content (soil N)), and vegetation (leaf area index (LAI) and leaf nitrogen content (LNC)) factors to assess their roles in C fluxes. The results showed that the drylands in China were weak C sinks. GPP and ER were positively correlated with MAP, while they were negatively correlated with MAT. NEP first decreased and then increased with increasing MAT and MAP, and 6.6 °C and 207 mm were the boundaries for the NEP response to MAT and MAP, respectively. SM, soil N, LAI, and MAP were the main factors affecting GPP and ER. However, SM and LNC had the most important influence on NEP. Compared with climate and vegetation factors, soil factors (SM and soil N) had a greater impact on C fluxes in the drylands. Climate factors mainly affected C fluxes by regulating vegetation and soil factors. To accurately estimate the global C balance and predict the response of ecosystems to environmental change, it is necessary to fully consider the discrepant effects of climate, vegetation, and soil factors on C fluxes, as well as the cascade relationships between different factors.
Family functioning and mobile phone addiction in university students: Mediating effect of loneliness and moderating effect of capacity to be alone
Authors: Li Guan-Ru , Sun Jian , Ye Jia-Nuo , Hou Xiao-Hui , Xiang Ming-Qiang 
Published: February 2023

BackgroundWith the increasing popularity of smartphones, mobile phone addiction in university students has attracted widespread societal attention. Previous studies showed that family functioning and mobile phone addiction are related. However, the potential mechanisms involved in this relationship are unknown. This study examined the mediating effect of loneliness and the moderating effect of capacity to be alone on the relationship between family functioning and mobile phone addiction.MethodsA total of 1,580 university students were recruited. A cross-sectional study design and online questionnaire survey were employed to measure demographic variables, family functioning, loneliness, capacity to be alone, and mobile phone addiction in university students.ResultsFamily functioning is a significantly negative predictor of mobile phone addiction in university students, and loneliness has a mediating effect on the relationship between family functioning and mobile phone addiction. The capacity to be alone has moderating effects on the relationship between family functioning and loneliness and between family functioning and mobile phone addiction, and these correlation is stronger in university students with a low capacity to be alone.ConclusionThe moderated mediation model in this study improves understanding of the correlation between family functioning and mobile phone addiction in university students. Education professionals and parents should pay particular attention to family functioning in mobile phone addiction, particularly university students with low capacity to be alone.