bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of CTCF loop anchor based on machine learning
Authors: Zhang Xiao , Zhu Wen , Sun Huimin , Ding Yijie , Liu Li 
Published: April 2023

Introduction: Various activities in biological cells are affected by three-dimensional genome structure. The insulators play an important role in the organization of higher-order structure. CTCF is a representative of mammalian insulators, which can produce barriers to prevent the continuous extrusion of chromatin loop. As a multifunctional protein, CTCF has tens of thousands of binding sites in the genome, but only a portion of them can be used as anchors of chromatin loops. It is still unclear how cells select the anchor in the process of chromatin looping.Methods: In this paper, a comparative analysis is performed to investigate the sequence preference and binding strength of anchor and non-anchor CTCF binding sites. Furthermore, a machine learning model based on the CTCF binding intensity and DNA sequence is proposed to predict which CTCF sites can form chromatin loop anchors.Results: The accuracy of the machine learning model that we constructed for predicting the anchor of the chromatin loop mediated by CTCF reached 0.8646. And we find that the formation of loop anchor is mainly influenced by the CTCF binding strength and binding pattern (which can be interpreted as the binding of different zinc fingers).Discussion: In conclusion, our results suggest that The CTCF core motif and it’s flanking sequence may be responsible for the binding specificity. This work contributes to understanding the mechanism of loop anchor selection and provides a reference for the prediction of CTCF-mediated chromatin loops.
Peripheral immune characteristics of hepatitis B virus-related hepatocellular carcinoma
Authors: Sun Ruonan , Li Jiawei , Lin Xianyi , Yang Yidong , Liu Bing , Lan Tianbi , Xiao Shuang , Deng Anyi , Yin Zhinan , Xu Yan , Xiang Zheng , Wu Bin 
Published: April 2023

BackgroundLiver cancer is the sixth most common cancer worldwide and the third leading cause of cancer-related death. As a chronic liver disease, many studies have shown that the immune response plays a key role in the progression of liver cancer. Chronic hepatitis B virus (HBV) infection is one of the high-risk factors for HCC, accounting for 50%–80% of HCC cases worldwide, and little is known about the immune status of HBV associated hepatocellular carcinoma (HBV-HCC), therefore, we aimed to explore the changes in peripheral immunity in patients with HBV-HCC.MethodsIn this study, patients with HBV-HCC (n=26), patients with hepatitis B-related cirrhosis (HBV-LC) (n=31) and healthy volunteers (n=49) were included. The lymphocytes and their subpopulation phenotypes in peripheral blood were characterized. In addition, we explored the effect of viral replication on peripheral immunity in patients with HCC and analyzed the circulating immunophenotypic characteristics at different stages of HCC with flow cytometry.ResultsFirstly, our results showed that the percentages of total αβ T cells in the peripheral blood of HBV-HCC patients was significantly decreased compared to healthy subjects. Secondly, we found that naïve CD4+ T cells in HBV-HCC patients were significantly reduced, terminally differentiated CD8+ T cells, homing memory CD8+ T cells and Th2 cells were increased in peripheral circulation in HBV-HCC patients. Moreover, in the peripheral blood of HBV-HCC patients, expression of TIGIT on CD4+ T cells and PD-1 on the surface of Vδ 1 T cells was increased. In addition, we found that sustained viral replication resulted in up-regulation of TIM3 expression on CD4+ T cells, and TIM3+ γδ T cells increased in peripheral circulation in patients with advanced HBV-HCC.ConclusionOur study showed that circulating lymphocytes in HBV-HCC patients exhibited features of immune exhaustion, especially in HCC patients with persistent viral replication and in patients with intermediate and advanced HBV-HCC, including decreased frequency of T cells and elevated expression of inhibitory receptors including TIGIT and TIM3 on CD4+ T cells and γδ T cells. Meanwhile, our research suggests that the combination of CD3+ T cell and CD8+HLADR+CD38+ T cell may be a potential diagnostic indicator for HBV-HCC. These findings could help us to better understand the immune characteristics of HBV-HCC and explore the immune mechanisms and immunotherapy strategies for HBV-HCC.
Pharmacokinetic characteristics of golidocitinib, a highly selective JAK1 inhibitor, in healthy adult participants
Authors: Chen Kan , Guan Xiaoduo , Yang Zhenfan , Zhou Yue , Liu Ziyi , Deng Xueyuan , Liu Donghong , Hu Pei , Chen Rui 
Published: April 2023

BackgroundGolidocitinib is an orally available, potent and highly selective JAK (Janus kinase)-1 inhibitor of JAK/STAT3 signaling under clinical development for the treatment of cancer and autoimmune diseases. The objectives of the two reported studies were to investigate the pharmacokinetics (PK), safety, and tolerability of golidocitinib in healthy Chinese participants as compared to those healthy Western participants, as well as the food effect exploration.MethodsTwo phase I studies (JACKPOT2 and JACKPOT3) were conducted in USA and China, respectively. In JACKPOT2 study, participants were randomized into placebo or golidocitinib arm in single-ascending dose cohorts (5 - 150 mg) and multiple-ascending dose cohorts (25 - 100 mg, once daily) for 14 days. In the food effect cohort, golidocitinib (50 mg) was administrated shortly after a high-fat meal (fed conditions) as compared to under fasting conditions. In JACKPOT3 study conducted in China, participants were randomized to placebo or golidocitinib arm in single-ascending dose cohorts (25 - 150 mg).ResultsExposure of golidocitinib generally increased in a dose-proportional manner across a dose range of 5 mg to 150 mg (single dose) and 25 mg to 100 mg (once daily). High-fat food did not alter the PK of golidocitinib with statistical significance. Low plasma clearance and extensive volume of distribution characterizes PK of golidoctinib, and long half-life across the dose levels supported once daily dosing. The inter-ethnic difference in primary PK parameters was evaluated. The result suggested slightly higher peak plasma concentrations (Cmax) but comparable area under the plasma concentration-time curve (AUC) was observed in Asian (Chinese) subjects as compared to Caucasian and/or Black subjects, while it was not considered clinically relevant. Golidocitinib was well tolerated without Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher drug-related treatment emergent adverse events (TEAE) reported.ConclusionNo noticeable inter-ethnic difference was observed among Asian, Black, and Caucasian healthy subjects in anticipation of the favorable PK properties of golidocitinib. The effect of food on the bioavailability of golidocitinib was minor following a single oral administration of 50 mg. These data guided to use the same dose and regimen for multinational clinical development.Clinical trial registrationshttps://clinicaltrials.gov/ct2/show/NCT03728023?term=NCT03728023&amp;draw=2&amp;rank=1, identifier (NCT03728023); http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml, identifier (CTR20191011).
Subtype classification based on t cell proliferation-related regulator genes and risk model for predicting outcomes of lung adenocarcinoma
Authors: Yang Qin , Zhu Weiyuan , Gong Han 
Published: April 2023

BackgroundLung adenocarcinoma (LUAD), the major lung cancer histotype, represents 40% lung cancers. Currently, outcomes are remarkably different in LUAD patients with similar AJCC/UICC-TNM features. T cell proliferation-related regulator genes (TPRGs) relate to the proliferation, activity and function of T cells and tumor progression. The values of TPRGs in classifying LUAD patients and predicting outcomes remain unknown.MethodsGene expression profile and corresponding clinical data were downloaded from TCGA and the GEO databases. We systematically analyzed the expression profile characteristics of 35 TPRGs in LUAD patients and investigated the differences in overall survival (OS), biology pathway, immunity and somatic mutation between different TPRGs-related subtypes. Subsequently, we constructed a TPRGs-related risk model in TCGA cohort to quantify risk scores using LASSO cox regression analysis and then validated this risk model in two GEO cohorts. LUAD patients were divided into high- and low-risk subtypes according to the median risk score. We systematically compared the biology pathway, immunity, somatic mutation and drug susceptibility between the two risk subtypes. Finally, we validate biological functions of two TPRGs-encoded proteins (DCLRE1B and HOMER1) in LUAD cells A549.ResultsWe identified different TPRGs-related subtypes (including cluster 1/cluster A and its counterpart cluster 2/cluster B). Compared to the cluster 1/cluster A subtype, cluster 2/cluster B subtype tended to have a prominent survival advantage with an immunosuppressive microenvironment and a higher somatic mutation frequency. Then, we constructed a TPRGs-related 6-gene risk model. The high-risk subtype characterized by higher somatic mutation frequency and lower immunotherapy response had a worse prognosis. This risk model was an independent prognostic factor and showed to be reliable and accurate for LUAD classification. Furthermore, subtypes with different risk scores were significantly associated with drug sensitivity. DCLRE1B and HOMER1 suppressed cell proliferation, migration and invasion in LUAD cells A549, which was in line with their prognostic values.ConclusionWe construed a novel stratification model of LUAD based on TPRGs, which can accurately and reliably predict the prognosis and might be used as a predictive tool for LUAD patients.
Development and assessment of a novel gold immunochromatographic assay for the diagnosis of schistosomiasis japonica
Authors: Mu Yi , McManus Donald P. , Gordon Catherine A. , You Hong , Ross Allen G. , Olveda Remigio M. , Cai Pengfei 
Published: April 2023

BackgroundThe neglected zoonosis, schistosomiasis japonica, remains a major public health problem in the Philippines. The current study aims to develop a novel gold immunochromatographic assay (GICA) and evaluate its performance in the detection of Schistosoma japonicum infection.MethodsA GICA strip incorporating a S. japonicum saposin protein, SjSAP4 was developed. For each GICA strip test, diluted serum sample (50 µl) was loaded and strips were scanned after 10 min to convert the results into images. ImageJ was used to calculate an R value, which was defined as the signal intensity of the test line divided by the signal intensity of the control line within the cassette. After determination of optimal serum dilution and diluent, the GICA assay was evaluated with sera collected from non-endemic controls (n = 20) and individuals living in schistosomiasis-endemic areas of the Philippines (n = 60), including 40 Kato Katz (KK)-positive participants and 20 subjects confirmed as KK-negative and faecal droplet digital PCR assay (F_ddPCR)-negative at a dilution of 1:20. An ELISA assay evaluating IgG levels against SjSAP4 was also performed on the same panel of sera.ResultsPhosphate-buffered saline (PBS) and 0.9% NaCl were determined as optimal dilution buffer for the GICA assay. The strips tested with serial dilutions of a pooled serum sample from KK-positive individuals (n = 3) suggested that a relatively wide range of dilutions (from 1:10 to 1:320) can be applied for the test. Using the non-endemic donors as controls, the GICA strip showed a sensitivity of 95.0% and absolute specificity; while using the KK-negative and F_ddPCR-negative subjects as controls, the immunochromatographic assay had a sensitivity of 85.0% and a specificity of 80.0%. The SjSAP4-incorperated GICA displayed a high concordance with the SjSAP4-ELISA assay.ConclusionsThe developed GICA assay exhibited a similar diagnostic performance with that of the SjSAP4-ELISA assay, yet the former can be performed by local personnel with minimal training with no requirement for specialised equipment. The GICA assay established here represents a rapid, easy-to-use, accurate and field-friendly diagnostic tool for the on-site surveillance/screening of S. japonicum infection.
Development of a new cellular immunological detection method for tuberculosis based on HupB protein induced IL-6 release test
Authors: Yu Xiaoli , Jiang Shengsheng , Li Yang , Zhou Huaiheng , Wei Yutong , Li Xuefang , Zhang Ye , Hu Peng , Wu Haoming , Wang Hualin , Wu Shimin , Zhang Shulin 
Published: April 2023

ObjectiveAs a virulence factor, HupB plays important roles in the survival of MTB after infection and modulates the host immune response. In the current study, we aim to explore a new cellular immunological detection method for tuberculosis infection detection based on HupB protein.MethodsHupB was used to stimulate PBMCs extracted from pulmonary tuberculosis (PTB) patients, and secreted cytokines was examined. Then, we constructed a single center and a multi-center clinical trials to collect PBMCs from PTB patients, nPTB patients, or healthy volunteers to verify our findings.ResultsCytokine’s screening illustrated that IL-6 was the only cytokine released after HupB stimulation. Single-center and multi-center clinical trials showed that HupB stimulation significantly increased the level of IL-6 in the supernatant of PBMCs from PTB patients. Then we compared the specificity and sensitivity of HupB induced IL-6 release assay with ESAT-6 and CFP10 induced interferon γ release assay (IGRA), and found in smear positive PTB patients, the specificity and sensitivity of HupB induced IL-6 release assay was better than IGRA, and in smear negative PTB patients, the sensitivity was better. Combination of both assays provided an improved specificity and sensitivity for tuberculosis diagnosis.ConclusionThis study explored an immunological detection method for tuberculosis infection cells based on HupB protein-induced IL-6 release test, which can be used to enhance the diagnosis diagnostic accuracy of TB.
Effects of traditional Chinese mind–body exercises on older adults with cognitive impairment: A systematic review and meta-analysis
Authors: Yao Ke-ru , Luo Qin , Tang Xi , Wang Zhi-han , Li Lu , Zhao Lu , Zhou Li , Li Ling , Huang Li , Yin Xin-hong 
Published: April 2023

ObjectiveTo determine the effectiveness of traditional Chinese mind–body exercises in improving cognition, memory, and executive function in older adults with cognitive impairment.Data sourcesRelevant English and Chinese language studies published until September 14th, 2022 were retrieved from PubMed, Web of Science, Cochrane Library, Embase, CINAHL, WAN FANG DATA, VIP Information, CNKI, and SinoMed databases.Review methodsRandomized controlled trials assessing traditional Chinese mind–body exercises (Tai Chi, Baduanjin, Qigong, Mind–Body Therapies, and Yijinjing) in older adults with cognitive impairment were included. Two researchers independently identified eligible studies and extracted data. A risk-of-bias assessment was performed using the Cochrane Risk of Bias Tool.ResultsThis study included 15 randomized controlled trials (1,127 participants) from China, Thailand and American. Most studies had a high risk of bias in the blinding of participants and researchers, one study had a high risk of bias in the random sequence generation and two studies had a high risk of bias in the incomplete outcome data. Compared with conventional therapy alone, traditional Chinese mind–body exercises significantly improved global cognitive function (p &lt; 0.00001), and Baduanjin could improve the global cognitive function (p &lt; 0.00001), memory function (p &lt; 0.0001), and executive function (p &lt; 0.0001) outcomes after treatment, and significantly improved some dimensional scores on the auditory verbal learning test after treatment (p = 0.04).ConclusionCompared with conventional therapy, traditional Chinese mind–body exercises (Tai Chi, Baduanjin, and Qigong) significantly improved global cognitive function, and Baduanjin could improve global cognitive function, memory function, and executive function in older adults with cognitive impairment.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/#searchadvanced, CRD42022327563.
Peak width of skeletonized mean diffusivity and cognitive performance in cerebral amyloid angiopathy
Authors: Horn Mitchell J. , Gokcal Elif , Becker J. Alex , Das Alvin S. , Schwab Kristin , Zanon Zotin Maria Clara , Goldstein Joshua N. , Rosand Jonathan , Viswanathan Anand , Polimeni Jonathan R. , Duering Marco , Greenberg Steven M. , Gurol M. Edip 
Published: April 2023

BackgroundCerebral Amyloid Angiopathy (CAA) is a cerebral small vessel disease that can lead to microstructural disruption of white matter (WM), which can be measured by the Peak Width of Skeletonized Mean Diffusivity (PSMD). We hypothesized that PSMD measures would be increased in patients with CAA compared to healthy controls (HC), and increased PSMD is associated with lower cognitive scores in patients with CAA.MethodsEighty-one probable CAA patients without cognitive impairment who were diagnosed with Boston criteria and 23 HCs were included. All subjects underwent an advanced brain MRI with high-resolution diffusion-weighted imaging (DWI). PSMD scores were quantified from a probabilistic skeleton of the WM tracts in the mean diffusivity (MD) image using a combination of fractional anisotropy (FA) and the FSL Tract-Based Spatial Statistics (TBSS) algorithm (www.psmd-marker.com). Within CAA cohort, standardized z-scores of processing speed, executive functioning and memory were obtained.ResultsThe mean of age and sex were similar between CAA patients (69.6 ± 7.3, 59.3% male) and HCs (70.6 ± 8.5, 56.5% male) (p = 0.581 and p = 0.814). PSMD was higher in the CAA group [(4.13 ± 0.94) × 10–4 mm2/s] compared to HCs [(3.28 ± 0.51) × 10–4 mm2/s] (p &lt; 0.001). In a linear regression model corrected for relevant variables, diagnosis of CAA was independently associated with increased PSMD compared to HCs (ß = 0.45, 95% CI 0.13–0.76, p = 0.006). Within CAA cohort, higher PSMD was associated with lower scores in processing speed (p &lt; 0.001), executive functioning (p = 0.004), and memory (0.047). Finally, PSMD outperformed all other MRI markers of CAA by explaining most of the variance in models predicting lower scores in each cognitive domain.DiscussionPeak Width of Skeletonized Mean Diffusivity is increased in CAA, and it is associated with worse cognitive scores supporting the view that disruption of white matter has a significant role in cognitive impairment in CAA. As a robust marker, PSMD can be used in clinical trials or practice.
Real-life data of abiraterone acetate and enzalutamide treatment in post-chemotherapy metastatic castration-resistant prostate cancer in Poland
Authors: Sigorski Dawid , Wilk Michał , Gawlik-Urban Angelika , Sałek-Zań Agata , Kiszka Joanna , Malik Mateusz , Czerko Katarzyna , Kuć Kamil , Szczylik Cezary , Kubiatowski Tomasz , Cybulska-Stopa Bożena , Filipczyk-Cisarż Emilia , Bodnar Lubomir , Skoneczna Iwona 
Published: April 2023

BackgroundAbiraterone acetate (ABI) and Enzalutamide (ENZA) are second-generation hormone drugs that show breakthrough activity in post-chemotherapy, metastatic castration-resistant prostate cancer (mCRPC). The leading oncological and urological guidelines indicate both drugs with the same strong recommendation. There is a lack of randomized trials which compare the efficacy of ABI and ENZA. The current study aimed to compare the effectiveness of the drugs with an analysis of prognostic factors related to those drugs.Patients and methodsThe study included 420 patients with docetaxel (DXL) pretreated mCRPC from seven Polish cancer centers. Patients were treated according to inclusion and exclusion criteria in the Polish national drug program (1000 mg ABI and 10 mg prednisone, n=76.2%; ENZA, 160 mg; n=23.8%). The study retrospectively analyzed the overall survival (OS), time to treatment failure (TTF), PSA 50% decline rate (PSA 50%) and selected clinic-pathological data.ResultsIn the study group, the median OS was 17 months (95% CI: 15.6-18.3). The median OS (26.1 vs. 15.7 mo.; p&lt;0.001), TTF (14.2 vs. 7.6 mo.; p&lt;0.001) and PSA 50% (87.5 vs. 56%; p&lt;0.001) were higher in ENZA than in ABI treatment. Multivariate analysis shows that ENZA treatment and PSA nadir &lt;17.35 ng/mL during or after DXL treatment were related to longer TTF. ENZA treatment, DXL dose ≥750 mg, PSA nadir &lt;17.35 ng/mL during or after DXL treatment was related to longer OS.ConclusionsENZA treatment may be related to more favorable oncological outcomes than ABI treatment in the studied Polish population of patients. A 50% decline in PSA is an indicator of longer TTF and OS. Due to the non-randomized and retrospective nature of the analysis, the current results require prospective validation.
Identification of a prognostic biomarker predicting biochemical recurrence and construction of a novel nomogram for prostate cancer
Authors: Yu Zhaojun , Chao Haichao , Xu Fanghua , Deng Huanhuan , Deng Leihong , Song Zhen , Zeng Tao 
Published: April 2023

BackgroundBiochemical recurrence (BCR) is common in prostate cancer (PCa), but its prediction is based predominantly on clinicopathological characteristics with low accuracy. We intend to identify a potential prognostic biomarker related to the BCR and construct a nomogram for improving the risk stratification of PCa patients.MethodsThe transcriptome and clinical data of PCa patients were obtained from TCGA and GEO databases. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to screen out differentially expressed genes (DEGs) related to the BCR of PCa. Cox regression analysis was further applied to screen out DEGs related to BCR-free survival (BFS). Time-dependent receiver operating curve (ROC) analysis and Kaplan–Meier (K-M) survival analysis were conducted to assess the prognostic value. Then, a prognostic nomogram was established and evaluated. The clinicopathological correlation analysis, GSEA analysis, and immune analysis were used to explore the biological and clinical significance of the biomarker. Finally, the qRT-PCR, western blotting, and immunohistochemistry (IHC) were conducted to validate the expression of the biomarker.ResultsBIRC5 was identified to be the potential prognostic biomarker. The clinical correlation analysis and K-M survival analysis found that the BIRC5 mRNA expression was positively associated with disease progression and negatively associated with the BFS rate. Time-dependent ROC curves verified its accurate prediction performance. The GSEA and immune analysis suggested that the BIRC5 was related to immunity. A nomogram with an accurate prediction for BFS of PCa patients was constructed. qRT-PCR, western blotting, and IHC results validated the expression level of BIRC5 in PCa cells and tissues.ConclusionOur study identified BIRC5 as a potential prognostic biomarker related to BCR of PCa and constructed an efficacy nomogram for predicting BFS to assist clinical decision-making.