bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Inflammation and Insulin Resistance Related Indicator to Predict the Survival of Patients With Cancer
Authors: Ruan Guo-Tian , Xie Hai-Lun , Zhang He-Yang , Liu Chen-An , Ge Yi-Zhong , Zhang Qi , Wang Zi-Wen , Zhang Xi , Tang Meng , Song Meng-Meng , Zhang Xiao-Wei , Yang Ming , Chen Yong-Bing , Yu Kai-Ying , Deng Li , Gong Yi-Zhen , Hu Wen , Wang Kun-Hua , Cong Ming-Hua , Shi Han-Ping 
Published: June 2022

BackgroundSystemic inflammation and insulin resistance (IR) are closely related in patients with cancer. However, there is no relevant indicator that combines inflammation and IR to predict patient prognosis. Therefore, this study aimed to develop and validate a novel inflammation- and IR-related marker in patients with cancer.MethodsThe total cohort of this study included 5221 patients with cancer, and the training and validation cohorts were randomized in a 7:3 ratio. C-reactive protein (CRP) and fasting triglyceride glucose (TyG) were used to reflect patients’ inflammation and IR status, respectively. The CRP-TyG index (CTI) was composed of CRP and TyG. The concordance (C)-index, receiver operator characteristic (ROC) curve, and calibration curve reflected the prognostic predictive power of CTI. Univariate and multivariate survival analyses predicted the prognostic value of CTI in patients with cancer.ResultsThe C-indices of CTI in patients with cancer were 0.636, 0.617, and 0.631 in the total, training, and validation cohorts, respectively. The 1-, 3-, and 5-year ROC and calibration curves showed that CTI had a good predictive ability of survival in patients with cancer. Meanwhile, patients with high CTI had a worse prognosis compared to patients with low CTI (total cohort: hazard ratio [HR] = 1.46, 95% confidence interval [95% CI] = 1.33–1.59; training cohort: HR = 1.36, 95% CI = 1.22–1.52; validation cohort: HR = 1.73, 95% CI = 1.47–2.04].ConclusionThe CTI is a useful prognostic indicator of poor prognosis and a promising tool for treatment strategy decision-making in patients with cancer.
Clinical Implications of Necroptosis Genes Expression for Cancer Immunity and Prognosis: A Pan-Cancer Analysis
Authors: Li Xin-yu , Su Li-xin , Chen Wen-Xue , Liu Hui , Zhang Lu-yu , Shen Yu-Chen , You Jian-Xiong , Wang Jing-Bing , Zhang Liming , Wang Deming , Wen Ming-Zhe , Wang Zhenfeng , Shao Yu-hao , Chen De-Hu , Yang Xi-tao 
Published: June 2022

BackgroundNecroptosis, a form of programmed cell death, is increasingly being investigated for its controversial role in tumorigenesis and progression. Necroptosis suppresses tumor formation and tumor development by killing tumor cells; however, the necrotic cells also promote tumor formation and tumor development via the immunosuppressive effect of necroptosis and inflammatory response caused by cytokine release. Thus, the exact mechanism of necroptosis in pan-cancer remains unknown.MethodsThe data of 11,057 cancer samples were downloaded from the TCGA database, along with clinical information, tumor mutation burden, and microsatellite instability information of the corresponding patients. We used the TCGA data in a pan-cancer analysis to identify differences in mRNA level as well as single nucleotide variants, copy number variants, methylation profiles, and genomic signatures of miRNA-mRNA interactions. Two drug datasets (from GDSC, CTRP) were used to evaluate drug sensitivity and resistance against necroptosis genes.ResultsNecroptosis genes were aberrantly expressed in various cancers. The frequency of necroptosis gene mutations was highest in lung squamous cell carcinoma. Furthermore, the correlation between necroptosis gene expression in the tumor microenvironment and immune cell infiltration varied for different cancers. High necroptosis gene expression was found to correlate with NK, Tfh, Th1, CD8_T, and DC cells. These can therefore be used as biomarkers to predict prognosis. By matching gene targets with drugs, we identified potential candidate drugs.ConclusionOur study showed the genomic alterations and clinical features of necroptosis genes in 33 cancers. This may help clarify the link between necroptosis and tumorigenesis. Our findings may also provide new approaches for the clinical treatment of cancer.
Human Platelet Lysate as Alternative of Fetal Bovine Serum for Enhanced Human In Vitro Bone Resorption and Remodeling
Authors: de Wildt Bregje W. M. , Ito Keita , Hofmann Sandra 
Published: June 2022

IntroductionTo study human physiological and pathological bone remodeling while addressing the principle of replacement, reduction and refinement of animal experiments (3Rs), human in vitro bone remodeling models are being developed. Despite increasing safety-, scientific-, and ethical concerns, fetal bovine serum (FBS), a nutritional medium supplement, is still routinely used in these models. To comply with the 3Rs and to improve the reproducibility of such in vitro models, xenogeneic-free medium supplements should be investigated. Human platelet lysate (hPL) might be a good alternative as it has been shown to accelerate osteogenic differentiation of mesenchymal stromal cells (MSCs) and improve subsequent mineralization. However, for a human in vitro bone model, hPL should also be able to adequately support osteoclastic differentiation and subsequent bone resorption. In addition, optimizing co-culture medium conditions in mono-cultures might lead to unequal stimulation of co-cultured cells.MethodsWe compared supplementation with 10% FBS vs. 10%, 5%, and 2.5% hPL for osteoclast formation and resorption by human monocytes (MCs) in mono-culture and in co-culture with (osteogenically stimulated) human MSCs.Results and DiscussionSupplementation of hPL can lead to a less donor-dependent and more homogeneous osteoclastic differentiation of MCs when compared to supplementation with 10% FBS. In co-cultures, osteoclastic differentiation and resorption in the 10% FBS group was almost completely inhibited by MSCs, while the supplementation with hPL still allowed for resorption, mostly at low concentrations. The addition of hPL to osteogenically stimulated MSC mono- and MC-MSC co-cultures resulted in osteogenic differentiation and bone-like matrix formation, mostly at high concentrations.ConclusionWe conclude that hPL could support both osteoclastic differentiation of human MCs and osteogenic differentiation of human MSCs in mono- and in co-culture, and that this can be balanced by the hPL concentration. Thus, the use of hPL could limit the need for FBS, which is currently commonly accepted for in vitro bone remodeling models.
Comprehensive Pneumonitis Profile of Thoracic Radiotherapy Followed by Immune Checkpoint Inhibitor and Risk Factors for Radiation Recall Pneumonitis in Lung Cancer
Authors: Lu Xiaotong , Wang Jianyang , Zhang Tao , Zhou Zongmei , Deng Lei , Wang Xin , Wang Wenqing , Liu Wenyang , Tang Wei , Wang Zhijie , Wang Jie , Jiang Wei , Bi Nan , Wang Luhua 
Published: June 2022

PurposeWhilst survival benefits of thoracic radiotherapy (TRT) followed by immune checkpoint inhibitor (ICI) have been reported in patients with lung cancer, the potential high risk of treatment-related pneumonitis remains a concern. Asians may be more sensitive to lung toxicity than other races. This retrospective study intended to provide a comprehensive pneumonitis profile of TRT followed by ICI and investigate the risk factors from a Chinese cohort of lung cancer.Methods and MaterialsFrom January 2016 to July 2021, 196 patients with lung cancer who received TRT prior to ICI were retrospectively analyzed. Treatment-related pneumonitis, including checkpoint inhibitor pneumonitis (CIP), radiation pneumonitis (RP), and radiation recall pneumonitis (RRP), were recorded and graded through medical records and chest computed tomography. Characteristics predictive of pneumonitis were assessed using logistic regression models, and the receiver operating characteristic analyses were performed to identify optimal cut points for quantitative variables.ResultsWith a median follow-up of 18 months, a total of 108 patients (55.1%) developed treatment-related pneumonitis during ICI therapy, with an incidence of 25.5% for grade 2 or higher (G2+) and 4.1% for G3+. The overall rates of CIP, RP and RRP were 8.2% (n=16), 46.9% (n=92) and 7.1% (n=14), respectively. With a total mortality rate of 1.5%, vast majority of the patients recovered from pneumonitis or remained stable. No patients died of RRP. Half of the patients with G2+ RP who withheld ICI therapy restarted ICI safely after resolution of RP. The history of chronic pulmonary diseases (P=0.05), mean lung dose (MLD, P=0.038), percent volume of lung receiving ≥5 Gy (V5, P=0.012) and percent volume of lung receiving ≥20 Gy (V20, P=0.030) predicted the occurrence of RRP in univariate analyses. Interval between TRT and ICI less than 3 months was an independent predictor for G2+ treatment-related pneumonitis in a multivariate model (Odds ratio OR=2.787, P=0.004).ConclusionsTreatment-related pneumonitis, especially RRP, is acceptable and manageable in the setting of TRT followed by ICI in this Asian population. Dosimetric parameters MLD, V5 and V20 may improve the predictions of RRP in clinical practice.
EZH2 Promotes T Follicular Helper Cell Differentiation Through Enhancing STAT3 Phosphorylation in Patients With Primary Sjögren’s Syndrome
Authors: He Chengmei , Yang Yanlei , Chen Zhilei , Liu Suying , Lyu Taibiao , Zeng Liuting , Wang Li , Li Yongzhe , Wang Mu , Chen Hua , Zhang Fengchun 
Published: June 2022

ObjectivesEnhancer of zeste homolog 2 (EZH2) is an epigenetic regulator that plays an essential role in immune system development and autoimmune diseases. This study aimed to characterize the role of EZH2 in the pathogenesis of primary Sjögren’s syndrome (pSS).MethodsWe analyzed EZH2 expression in two transcriptomic datasets of peripheral blood mononuclear cells (PBMCs) from pSS patients and healthy controls. We measured EZH2 expression in CD4+ T cells, CD8+ T cells, and CD19+ B cells from pSS patients and healthy controls and correlated EZH2 expression with clinical parameters. We also examined the activation, proliferation, and T-cell differentiation of CD4+ T cells using the EZH2 inhibitor GSK126, EZH2 siRNA, and EZH2-expressing vector. We further examined the STAT3 signaling pathway after EZH2 inhibition and detected Tfh differentiation in EZH2-overexpressed CD4+ T cells with STAT3 knocked down.ResultsEZH2 was upregulated in GSE164885 and GSE48378. EZH2 expression was higher in pSS CD4+ and CD8+ T cells, and EZH2 expression in circulating pSS CD4+ T cells was positively correlated with IgG, IgA, ESR, RF, and the circulating Tfh population. EZH2 inhibition and silencing EZH2 suppressed activation, proliferation, and Tfh differentiation. Furthermore, overexpressing EZH2 promoted activation, proliferation, and Tfh differentiation in CD4+ T cells. EZH2 inhibition attenuated STAT3 phosphorylation in CD4+ T cells. STAT3 knockdown abrogated EZH2-promoted Tfh differentiation.ConclusionsEZH2 expression was abnormally elevated in pSS CD4+ T cells, which facilitated Tfh differentiation of CD4+ T cells by enhancing STAT3 phosphorylation. EZH2 promotes Tfh differentiation and might be implicated in pSS pathogenesis.
A Dual-Polarized Frequency-Selective Rasorber With a Switchable Wide Passband Based on Characteristic Mode Analysis
Authors: Wang He , Kong Xiangkun , Zhang Xinyu 
Published: June 2022

This study proposes a dual-polarized frequency-selective rasorber (FSR) with a switchable wide passband. The FSR is made up of two layers: the first is a lossy frequency-selective surface (FSS), which is made up of meander lines and lumped resistors that absorb energy. The position of the lumped resistors can be determined via characteristic mode analysis. Another layer is a lossless FSS with PIN diodes for the reconfigurable function. The lossless FSS is made up of three layers for a wide passband. When PIN diodes are turned off, the absorption bands in the lower band vary from 2.73 to 3.76GHz, while the upper band ranges from 6.07 to 7.94 GHz. Meanwhile, the reflect band with a value greater than −3 dB spans the frequency range from 4.21 to 5.88 GHz. When the PIN diodes are turned on, the passband with insertion loss less than −1 dB extends from 3.82 to 5.3 GHz. At the same time, the absorption band ranges from 5.9 to 7 GHz. Due to the nonlinearity of PIN diodes, there is a certain difference between the simulated and the measured results. Also, we analyzed the influence of the inductance value of PIN diodes on the whole structure.
A Novel Non-Invasive Approach Based on Serum Ceruloplasmin for Identifying Non-Alcoholic Steatohepatitis Patients in the Non-Diabetic Population
Authors: Wang Qingling , Zhou Da , Wang Mingjie , Zhu Mingyu , Chen Peizhan , Li Hu , Lu Meng , Zhang Xinxin , Shen Xizhong , Liu Taotao , Chen Li 
Published: June 2022

Background and AimFew non-invasive models were established to identify patients with non-alcoholic steatohepatitis (NASH). Liver biopsy remains the gold standard in the clinic. Decreased serum ceruloplasmin (CP) is reported in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to develop a non-invasive model incorporating CP for identifying NASH from NAFLD without type 2 diabetes mellitus (T2DM).MethodsA total of 138 biopsy-proven patients with NAFLD without T2DM were enrolled. The CP ratio was calculated for standardization as the CP value divided by the lower limit of normal. The clinical, anthropometric, biochemical, and histological parameters were compared between the low and high CP ratio groups divided by the median value. Multivariate logistic regression analysis was performed to develop a model for identifying NASH in patients with NAFLD.ResultsThe medians of the high (n = 69) and low (n = 69) CP ratio groups were 1.43 (1.28–1.61) and 1.03 (0.94–1.12), respectively. A comparison of the two groups showed that the severity of steatosis, hepatocellular ballooning, inflammation activity, fibrosis, and liver iron deposition decreased along with the CP ratio (p &lt; 0.05). The median CP ratio of patients with NASH was significantly lower than those with NAFL [1.15 (1.01–1.41) vs. 1.33 (1.24–1.54), p = 0.001]. A novel model which consists of the CP ratio, BMI, and aspartate aminotransferase (AST) was developed. The AUCs of the model in discriminating NASH from NAFLD was 0.796 (0.694–0.899) and 0.849 (0.713–0.984) in the training and validation groups, and 0.836 (0.659–1.000), 0.833 (0.705–0.962), and 0.821 (0.612–1.000) in patients with normal serum alanine aminotransferase, AST, and both levels, respectively.ConclusionsDecreased CP ratio is associated with more severe histological activity, a diagnosis of NASH, and hepatic iron deposition among patients with NAFLD without T2DM. The CP ratio model could be served as a non-invasive approach to identifying patients with NASH, which might reduce the need for liver biopsy.
N6-Methyladenosine Methylomic Landscape of Ureteral Deficiency in Reflux Uropathy and Obstructive Uropathy
Authors: Shi Hua , Xiang Tianchao , Feng Jiayan , Yang Xue , Li Yaqi , Fang Ye , Xu Linan , Qi Qi , Shen Jian , Tang Liangfeng , Shen Qian , Wang Xiang , Xu Hong , Rao Jia 
Published: June 2022

BackgroundCongenital anomalies of the kidneys and urinary tracts (CAKUT) represent the most prevalent cause for renal failure in children. The RNA epigenetic modification N6-methyladenosine (m6A) methylation modulates gene expression and function post-transcriptionally, which has recently been revealed to be critical in organ development. However, it is uncertain whether m6A methylation plays a role in the pathogenesis of CAKUT. Thus, we aimed to explore the pattern of m6A methylation in CAKUT.MethodsUsing m6A-mRNA epitranscriptomic microarray, we investigated the m6A methylomic landscape in the ureter tissue of children with obstructive megaureter (M group) and primary vesicoureteral reflux (V group).ResultsA total of 228 mRNAs engaged in multiple function-relevant signaling pathways were substantially differential methylated between the “V” and “M” groups. Additionally, 215 RNA-binding proteins that recognize differentially methylated regions were predicted based on public databases. The M group showed significantly higher mRNA levels of m6A readers/writers (YTHDF1, YTHDF2, YTHDC1, YTHDC2 and WTAP) and significantly lower mRNA levels of m6A eraser (FTO) according to real-time PCR. To further investigate the differentially methylated genes, m6A methylome and transcriptome data were integrated to identified 298 hypermethylated mRNAs with differential expressions (265 upregulation and 33 downregulation) and 489 hypomethylated mRNAs with differential expressions (431 upregulation and 58 downregulation) in the M/V comparison.ConclusionThe current results highlight the pathogenesis of m6A methylation in obstructive and reflux uropathy.
Telemedicine for Stroke: Quantifying the Long-Term National Costs and Health Benefits
Authors: Gao Lan , Tan Elise , Kim Joosup , Bladin Christopher F. , Dewey Helen M. , Bagot Kathleen L. , Cadilhac Dominique A. , Moodie Marj 
Published: June 2022

ObjectiveFew countries have established national programs to maximize access and reduce operational overheads. We aimed to use patient-level data up to 12 months to model the potential long-term costs and health benefits attributable to implementing such a program for Australia.MethodsA Markov model was created for Australia with an inception population of 10,000 people with stroke presenting to non–urban or suburban hospitals without stroke medical specialists that could receive stroke telemedicine under a national program. Seven Markov states represented the seven modified Rankin Scale (mRS) scores (0 no disability to 6 dead) plus an absorbing state for all other causes of death. The literature informed inputs for the model; for the telemedicine program (including program costs and effectiveness) and patients, these were extrapolated from the Victorian Stroke Telemedicine (VST) program with the initial status of patients being their health state at day 365 as determined by their mRS score. Costs (2018 Australian dollars, healthcare, non–medical, and nursing home) and benefits were reported for both the societal and healthcare perspectives for up to a 25 years (lifetime) time horizon.ResultsWe assumed 4,997 to 12,578 ischemic strokes would arrive within 4.5 h of symptom onset at regional hospitals in 2018. The average per person lifetime costs were $126,461 and $127,987 from a societal perspective or $76,680 and $75,901 from a healthcare system perspective and benefits were 4.43 quality-adjusted life years (QALYs) and 3.98 QALYs gained, respectively, for the stroke telemedicine program and practice without such program. The stroke telemedicine program was associated with a cost saving of $1,526 (from the societal perspective) or an additional $779 (from the healthcare system perspective) and an additional 0.45 QALY gained per patient over the lifetime. The incremental costs of the stroke telemedicine program ($2,959) and management poststroke ($813) were offset by cost savings from rehospitalization (–$552), nursing home care (–$2178), and non–medical resource use (–$128).ConclusionThe findings from this long-term model provide evidence to support ongoing funding for stroke telemedicine services in Australia. Our estimates are conservative since other benefits of the service outside the use of intravenous thrombolysis were not included.
Changes in Volume of Subregions Within Basal Ganglia in Obsessive–Compulsive Disorder: A Study With Atlas-Based and VBM Methods
Authors: Chen Jiaxiang , Tian Chong , Zhang Qun , Xiang Hui , Wang Rongpin , Hu Xiaofei , Zeng Xianchun 
Published: June 2022

BackgroundThe role of basal ganglia in the pathogenesis of obsessive–compulsive disorder (OCD) remains unclear. The studies on volume changes of basal ganglia in OCD commonly use the VBM method; however, the Atlas-based method used in such research has not been reported. Atlas-based method has a lower false positive rate compared with VBM method, thus having advantages partly.ObjectivesThe current study aimed to detect the volume changes of subregions within basal ganglia in OCD using Atlas-based method to further delineate the precise neural circuitry of OCD. What is more, we explored the influence of software used in Atlas-based method on the volumetric analysis of basal ganglia and compared the results of Atlas-based method and regularly used VBM method.MethodsWe analyzed the brain structure images of 37 patients with OCD and 41 healthy controls (HCs) using the VBM method, Atlas-based method based on SPM software, or Freesurfer software to find the areas with significant volumetric variation between the two groups, and calculated the effects size of these areas.ResultsVBM analysis revealed a significantly increased volume of bilateral lenticular nucleus in patients compared to HCs. In contrast, Atlas-based method based on Freesurfer revealed significantly increased volume of left globus pallidus in patients, and the largest effect size of volumetric variation was revealed by Freesurfer analysis.ConclusionsThis study showed that the volume of bilateral lenticular nucleus significantly increased in patients compared to HCs, especially left globus pallidus, which was in accordance with the previous findings. In addition, Freesurfer is better than SPM and a good choice for Atlas-based volumetric analysis of basal ganglia.
Acute Water Supplementation Improved the Body Composition of Young Female Adults After Water Restriction of 12 h in Baoding, China: A Randomized Controlled Trial (RCT)
Authors: Zhang Jianfen , Zhang Na , Du Songming , Liu Shufang , Ma Guansheng 
Published: June 2022

Insufficient intake of water may influence the balance of water in the human body. In this study, we explore the impacts of water supplementation on body composition indices among young adults after 12 h of water restriction, with the aim to determine the optimum volume of water for improving body water composition. A randomized controlled trial study was conducted among 64 young men and women in Baoding, China. After fasting overnight for 12 h, anthropometric measurements and urine and blood samples were collected as a baseline test at 8:00 a.m. of Day 2. Body composition was determined by measuring the ECW (extracellular water), ICW (intracellular water), and TBW (total body water) through bioelectrical impedance analysis (BIA). The participants were randomly divided into four groups, including water supplementation (WS) groups 1, 2, and 3, with 500, 200, and 100 mL of water, respectively, and a no water supplementation (NW) group. After 90 min, they were reassessed in a rehydration test (at 10:00 a.m. of Day 2). Repeated measurement ANOVA was used to assess the impact of water supplementation on body composition. Comparing the baseline and rehydration tests, interactions between time and volume were not significant among the men (all p &gt; 0.05). Among women, a significant interaction was only found in ECW (p = 0.043), with TBW tending toward being significant (p = 0.055). Comparing the baseline and rehydration tests, the ECW in WS group 1, WS group 3, and the NW group all decreased (p = 0.028, p = 0.001, and p = 0.029), with reductions of 0.1, 0.3, and 0.2 kg, respectively; however, no significant decrease was observed in WS group 2 (p = 0.329). Furthermore, comparing the WS groups with the NW group in the rehydration test, the differences were not significant (p = 1.000, p = 1.000, and p = 0.288, respectively). Between men and women within groups, all of the body composition indices differed significantly, both at baseline and rehydration tests (all p &lt; 0.05). Water supplementation led to changes in the distribution of the water content in young female adults in this study—but not men—after 12 h of water restriction, with no decrease in ECW. Finally, we found that 200 mL was the minimum volume capable of improving the water content distribution in participants in this study.Trial Registration[www.chictr.org.cn], identifier [ChiCTR-IOR-17011568].