bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative Analysis of Biomarkers Through Machine Learning Identifies Stemness Features in Colorectal Cancer
Authors: Wei Ran , Quan Jichuan , Li Shuofeng , Liu Hengchang , Guan Xu , Jiang Zheng , Wang Xishan 
Published: September 2021

Background: Cancer stem cells (CSCs), which are characterized by self-renewal and plasticity, are highly correlated with tumor metastasis and drug resistance. To fully understand the role of CSCs in colorectal cancer (CRC), we evaluated the stemness traits and prognostic value of stemness-related genes in CRC.Methods: In this study, the data from 616 CRC patients from The Cancer Genome Atlas (TCGA) were assessed and subtyped based on the mRNA expression-based stemness index (mRNAsi). The correlations of cancer stemness with the immune microenvironment, tumor mutational burden (TMB), and N6-methyladenosine (m6A) RNA methylation regulators were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify the crucial stemness-related genes and modules. Furthermore, a prognostic expression signature was constructed using the Lasso-penalized Cox regression analysis. The signature was validated via multiplex immunofluorescence staining of tissue samples in an independent cohort of 48 CRC patients.Results: This study suggests that high-mRNAsi scores are associated with poor overall survival in stage IV CRC patients. Moreover, the levels of TMB and m6A RNA methylation regulators were positively correlated with mRNAsi scores, and low-mRNAsi scores were characterized by increased immune activity in CRC. The analysis identified 34 key genes as candidate prognosis biomarkers. Finally, a three-gene prognostic signature (PARPBP, KNSTRN, and KIF2C) was explored together with specific clinical features to construct a nomogram, which was successfully validated in an external cohort.Conclusion: There is a unique correlation between CSCs and the prognosis of CRC patients, and the novel biomarkers related to cell stemness could accurately predict the clinical outcomes of these patients.
Role of Chemical Structure of Support in Enhancing the Catalytic Activity of a Single Atom Catalyst Toward NRR: A Computational Study
Authors: Senthamaraikannan Thillai Govindaraja , Kaliaperumal Selvaraj , Krishnamurty Sailaja 
Published: September 2021

Using the periodic density functional theory–based methodology, we propose a potential catalytic system for dinitrogen activation, viz., single metal atoms (Mo, Fe, and V) supported on graphene-based sheets. Graphene-based sheets show an excellent potential toward the anchoring of single atoms on them (Mo, Fe, and V) with adsorption energies ranging between 1.048 and 10.893 eV. Factors such as defects and BN doping are noted to enhance the adsorption energies of single metal atoms on the support. The adsorption of a dinitrogen molecule on metal atom–anchored graphene-based supports is seen to be highly favorable, ranging between 0.620 and 2.278 eV. The adsorption is driven through a direct hybridization between the d orbitals of the metal atom (Mo, Fe, and V) on the support and the p orbital of the molecular nitrogen. Noticeably, BN-doped graphene supporting a single metal atom (Mo, Fe, and V) activates the N2 molecule with a red shift in the N–N stretching frequency (1,597 cm−1 as compared to 2,330 cm−1 in the free N2 molecule). This red shift is corroborated by an increase in the N–N bond length (1.23 Å from 1.09 Å) and charge transfer to an N2 molecule from the catalyst.
Preparation of Sepiolite Nanofibers Supported Zero Valent Iron Composite Material for Catalytic Removal of Tetracycline in Aqueous Solution
Authors: Han Xiaoyu , Zhang Hong , Zhang Caihong , Zhao Yan , Zhang Na , Liang Jinsheng 
Published: September 2021

The heavy use of antibiotics in medicine, stock farming and agriculture production has led to their gradual accumulation in environmental media, which poses a serious threat to ecological environment and human safety. As an efficient and promising catalyst for the degradation of antibiotics, nanoscale zero valent iron (nZVI) has attracted increasing attention in recent years. In this study, sepiolite nanofiber supported zero valent iron (nZVI/SEP) composite was prepared via a facile and environmentally friendly method. The nZVI particles (with size of 20–60 nm) were dispersed evenly on the surface of sepiolite nanofibers, and the catalytic performance for the removal of tetracycline hydrochloride (TC-HCl) in aqueous system was investigated. The effect of nZVI loading amount, catalyst dosage, H2O2 concentration and pH on the removal efficiency of TC-HCl were studied. It was revealed that the sepiolite supporter effectively inhibited the agglomeration of nZVI particles and increased the contact area between contaminant and the active sites, resulting in the higher catalytic performance than pure nZVI material. The TC-HCl removal efficiency of nZVI/SEP composite was up to 92.67% when TC-HCl concentration of 20 mg/L, catalyst dosage of 1.0 g/L, H2O2 concentration of 1.0 mM, pH value of 7. Therefore, the nZVI/SEP composites possess high catalytic activity for TC-HCl removal and have great application prospects in antibiotic wastewater treatment.
Computed Tomography-Based Assessment of Transvalvular Pressure Gradient in Aortic Stenosis
Authors: Franke Benedikt , Brüning Jan , Yevtushenko Pavlo , Dreger Henryk , Brand Anna , Juri Benjamin , Unbehaun Axel , Kempfert Jörg , Sündermann Simon , Lembcke Alexander , Solowjowa Natalia , Kelle Sebastian , Falk Volkmar , Kuehne Titus , Goubergrits Leonid , Schafstedde Marie 
Published: September 2021

Background: In patients with aortic stenosis, computed tomography (CT) provides important information about cardiovascular anatomy for treatment planning but is limited in determining relevant hemodynamic parameters such as the transvalvular pressure gradient (TPG).Purpose: In the present study, we aimed to validate a reduced-order model method for assessing TPG in aortic stenosis using CT data.Methods: TPGCT was calculated using a reduced-order model requiring the patient-specific peak-systolic aortic flow rate (Q) and the aortic valve area (AVA). AVA was determined by segmentation of the aortic valve leaflets, whereas Q was quantified based on volumetric assessment of the left ventricle. For validation, invasively measured TPGcatheter was calculated from pressure measurements in the left ventricle and the ascending aorta. Altogether, 84 data sets of patients with aortic stenosis were used to compare TPGCT against TPGcatheter.Results: TPGcatheter and TPGCT were 50.6 ± 28.0 and 48.0 ± 26 mmHg, respectively (p = 0.56). A Bland–Altman analysis revealed good agreement between both methods with a mean difference in TPG of 2.6 mmHg and a standard deviation of 19.3 mmHg. Both methods showed good correlation with r = 0.72 (p &lt; 0.001).Conclusions: The presented CT-based method allows assessment of TPG in patients with aortic stenosis, extending the current capabilities of cardiac CT for diagnosis and treatment planning.
Off-Label Underdosing or Overdosing of Non-vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation: A Meta-Analysis
Authors: Wu Xiaojuan , Hu Linyan , Liu Jinjin , Gu Qiuping 
Published: September 2021

Background: Several studies have investigated the role of off-label non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF). We aimed to compare the effectiveness and safety outcomes between off-label underdose or overdose vs. on-label dose of NOACs in AF patients.Methods: The PubMed database was systematically searched until August 2021. Observational cohorts were included if they compared the outcomes of off-label underdose or overdose with on-label dose of NOACs in AF patients. The risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a fixed-effects model (I2 ≤ 50%) or a random-effects model (I2 &gt; 50%).Results: A total of 15 observational studies were included. Compared with on-label dose of NOACs, off-label underdose of NOACs was associated with increased risks of stroke or systemic embolism (RR = 1.09, 95% CI 1.02–1.16), and all-cause death (RR = 1.29, 95% CI 1.10–1.52) but not ischemic stroke (RR = 1.34, 95% CI 0.76–2.36), myocardial infarction (RR = 1.08, 95% CI 0.92–1.28), major bleeding (RR = 0.97, 95% CI 0.89–1.05), intracranial hemorrhage (RR = 1.12, 95% CI 0.90–1.40), and gastrointestinal bleeding (RR = 0.96, 95% CI 0.85–1.07), whereas off-label overdose of NOACs was associated with increased risks of SSE (RR = 1.20, 95% CI 1.05–1.36), all-cause death (RR = 1.22, 95% CI 1.06–1.39), and major bleeding (RR = 1.33, 95% CI 1.16–1.52) but not gastrointestinal bleeding (RR = 1.18, 95% CI 0.99–1.42) and myocardial infarction (RR = 0.98, 95% CI 0.75–1.30).Conclusion: Compared with on-label dose of NOACs, off-label underdose was associated with increased risks of stroke or systemic embolism and all-cause death, whereas off-label overdose of NOACs was associated with increased risks of stroke or systemic embolism, all-cause death, and major bleeding.
Association Between Neonatal Thyroid Function and Anogenital Distance from Birth to 48 Months of Age
Authors: Luan Min , Liang Hong , Fang Guanghong , Wang Ziliang , Su Xiujuan , Chen Aimin , Miao Maohua , Yuan Wei 
Published: September 2021

BackgroundEvidence from animal studies has indicated that neonatal thyroid function is vital for the reproductive development. Anogenital distance (AGD), a sensitive biomarker of the fetal hormonal milieu, can be used to predict adult reproductive disorders. However, few human studies have examined the association between neonatal thyroid function and AGD. We aimed to explore their associations in a birth cohort study.MethodsConcentrations of thyroid stimulating hormone (TSH) and thyroid hormones (THs), including total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), and free thyroxine (FT4) were measured in cord plasma in the Shanghai-Minhang Birth Cohort. The offspring AGD (AGDAP [anus–penis] and AGDAS [anus–scrotum] for boys and AGDAC [anus–clitoris] and AGDAF [anus–fourchette] for girls), body weight and anogenital index (AGI = AGD/weight [mm/kg]) were obtained at each follow-up visit. In total, 344 children (194 boys and 150 girls) with cord plasma concentrations of THs and TSH and at least one AGD measurement at birth and at 6, 12, and 48 months of age were included. Multiple linear regression and generalized estimating equation (GEE) models were used to examine the associations of cord plasma concentrations of THs and TSH with AGI.ResultsMultiple linear regression models showed inverse associations of TT4, FT3, and FT4 with female AGI, although statistical significance was only reached at birth, 6 and 48 months of age. These associations were also found in GEE models: higher TT4 and FT4 concentrations were associated with lower AGIAC (TT4: β = -0.27, 95% CI: -0.50, -0.03 for middle vs. lowest tertile; FT4: β = -0.38, 95% CI: -0.61, -0.16 for middle and β = -0.30, 95% CI: -0.55, -0.04 for highest vs. lowest tertile). Besides, girls with the highest tertile of FT3 concentrations had lower AGIAF than those with the lowest tertile (the highest vs. lowest tertile: β = -0.22, 95% CI: -0.36, -0.08). Positive associations between TSH and AGI at birth and at 12 months of age were observed in boys.ConclusionsThis study provides further evidence on the effects of neonatal thyroid function on reproductive development at an early life stage.
Egg Cannibalism Varies With Sex, Reproductive Status, and Egg and Nymph Ages in Arma custos (Hemiptera: Asopinae)
Authors: Wu Shaolong , Zeng Weiai , Deng Wan , Li Mi , Hu Wei , Cai Hailin , Li Youzhi , Xie Pengfei , Tan Lin , Zhou Zhicheng 
Published: September 2021

Background: Egg cannibalism is common in nature. In China, Arma custos (Hemiptera: Asopinae) has been widely used as a natural enemy to control agricultural and forestry pests. A previous study showed that adult A. custos devour their eggs. However, no research has investigated the interaction between A. custos cannibalism and egg development. Clarifying the mechanisms involved in egg cannibalism by A. custos improves our understanding of the evolutionary relationships to enable more efficient mass rearing and biological control systems.Results: Virgin females showed a lower egg cannibalism inclination than gravid females. Both virgin and mated females showed a higher egg cannibalism inclination than virgin and mated males. The first and second instar nymphs did not devour eggs. The third, fourth, and fifth instar nymphs devoured eggs. Younger eggs were more readily eaten than older eggs. Neither A. custos nymphs nor female adults consumed all the available eggs, allowing an emergence ratio of &gt;70%.Conclusion:Arma custos females exhibit a higher tendency for egg cannibalism than males. Egg cannibalism varies not only with the developmental stage of the eggs and nymphs but also with sex and reproductive status of A. custos females. These findings help us to better understand the evolutionary relationships in egg cannibalism by A. custos and contribute to the efficient mass rearing and realization of A. custos in biological control systems.
Presence of Anti-Thyroid Antibodies Correlate to Worse Outcome of Anti-NMDAR Encephalitis
Authors: Chen Zhongyun , Zhang Yan , Cui Lili , Huang Huijin , Chen Weibi , Su Yingying 
Published: September 2021

ObjectiveTo investigate the characteristics and prognosis of anti-NMDAR encephalitis with the prevalence of anti-thyroid antibodies (ATAbs).MethodsThe clinical data of anti-NMDAR encephalitis patients admitted to Xuanwu Hospital from January 2012 to August 2018 was prospectively analyzed, and the patients were followed up for 24 months.ResultsA total of 120 patients were enrolled, of which 34.2% (41/120) were positive for ATAbs. The antibodies were more frequent in patients with severe disease compared to the non-severe group (51.4% vs. 25.6%, P=0.008). In addition, prevalence of ATAbs correlated with a higher incidence of disturbed consciousness, autonomic dysfunction, central hypoventilation and mechanical ventilation. The ATAbs-positive patients were also more likely to receive intravenous gamma immunoglobulin and immunosuppressor compared to the ATAbs-negative cases (P=0.006; P=0.035). Although the presence of ATAbs was associated with longer hospital stays and worse prognosis at 6 months (P=0.006; P=0.038), it had no impact on long-term patient prognosis. Positive status of anti-thyroglobulin antibody was an independent risk factor for worse prognosis at 6 months [odds ratio (OR)= 3.907, 95% CI: 1.178-12.958, P=0.026].ConclusionATAbs are prevalent in patients with anti-NMDAR encephalitis, especially in severe cases, and correlate with poor prognosis and impaired short-term neurological recovery.
A Multi-Institutional Randomized Controlled Trial to Investigate Whether Zoledronate Prevents Bone Loss After Discontinuation of Denosumab: The Study Protocol of Denosumab Sequential Therapy (DST) Trial
Authors: Lee Chia-Che , Wang Chen-Yu , Hung Chih-Chien , Huang Chuan-Ching , Li Chung-Yi , Chen Hsuan-Yu , Chang Yun-Liang , Tseng Wo-Jan , Wang Ting-Ming , Yang Rong-Sen , Wong Tze-Hong , Fu Shau-Huai 
Published: September 2021

Background: Though denosumab is an effective treatment for osteoporosis, the rebound effect after discontinuation has drawn investigators' attention. It includes a dramatic loss of gained bone mineral density (BMD) and an increased risk of vertebral fractures. This prospective multi-institutional randomized controlled trial aims to investigate whether zoledronate prevents loss of BMD after discontinuation of denosumab. The trial was registered as Denosumab Sequential Therapy (DST) trial in March 2019 at clinicaltrials.gov, with the identifier NCT03868033.Methods: The study is conducted at National Taiwan University Hospital and its branches. Patients who have continuously received denosumab treatment for two or more years are surveyed for eligibility. Baseline characteristics and questionnaires of life quality are recorded after recruitment. BMD, circulating levels of bone turnover markers (BTMs), including serum N-terminal propeptide of type 1 collagen (P1NP) and C-terminal telopeptide (CTX), are checked before the stratified randomization to 4 groups. Biological sex and the T-scores are used to create 4 strata. The participants in group 1 adhere to regular denosumab therapy for another 2 years. All the other patients receive on-time zoledronate treatment in the first year. The participants in group 2, 3, and 4 have on-time denosumab, on-time zoledronate and drug holiday in the second year, respectively. BMDs are checked annually. Pre-scheduled checkpoints of BTMs are also arranged. For patient safety, rescue treatment with another injection of zoledronate will be applied to the patients on drug holiday if the CTX levels raise above the pre-specified threshold, 0.573 ng/mL for women and 0.584 ng/mL for men. The primary outcomes are the percentage changes of BMDs in lumbar spine, total hip and femoral neck. The secondary outcomes include the changes of serum level of the BTMs, new osteoporotic fractures, extra zoledronate injections needed in group 4 and the differences of quality of life.Discussion: We aim to provide evidence whether zoledronate prevents bone loss after denosumab cessation. To our knowledge, the study has the largest sample size. No other randomized controlled study included all the three different treatment strategies and a positive control. It is also the first associated randomized controlled trial outside Europe.
Sex Differences in Adverse Reactions to an Inactivated SARS-CoV-2 Vaccine Among Medical Staff in China
Authors: Zhu Jian-Sheng , Zhang Mei-Xian , Chien Ching-Wen , Yang Wei-Ying , Shi Gui-Feng , Qiu Shulin , Tung Tao-Hsin , Chen Hai-Xiao 
Published: September 2021

Objective: We investigated whether there were sex differences in adverse reactions to an inactivated SARS-CoV-2 vaccine among medical staff in China.Methods: From 24 February to 7 March 2021 an online cross-sectional survey was conducted with a self-administered COVID-19 vaccine questionnaire among medical staff in Taizhou, China. In total, 1397 interviewees (1,107 women and 290 men) participated in the survey.Results: In our study, 178 (16.1%) women and 23 (7.9%) men reported adverse reactions following their first vaccination, and 169 (15.3%) women and 35 (12.1%) men reported adverse reactions following their second vaccination. After adjusting for confounding factors, adverse reactions to other vaccines, worry about adverse reactions, knowledge of the inactivated vaccine being used in the hospital, taking the vaccine for one's family proactively and receiving an influenza vaccination were significantly related to adverse reactions to both injections in women. In contrast, in men, concerns about adverse reactions independently increased the risk of adverse reactions following either vaccination, and a history of adverse reactions to other vaccines also increased the risk of adverse reactions to both injections.Conclusions: Sex differences in the frequency of reported adverse reactions to an inactivated SARS-CoV-2 vaccine and potential factors were demonstrated in a sample of medical staff.
Age-Adjusted Endothelial Activation and Stress Index for Coronavirus Disease 2019 at Admission Is a Reliable Predictor for 28-Day Mortality in Hospitalized Patients With Coronavirus Disease 2019
Authors: Pérez-García Felipe , Bailén Rebeca , Torres-Macho Juan , Fernández-Rodríguez Amanda , Jiménez-Sousa Maria Ángeles , Jiménez Eva , Pérez-Butragueño Mario , Cuadros-González Juan , Cadiñanos Julen , García-García Irene , Jiménez-González María , Ryan Pablo , Resino Salvador 
Published: September 2021

Background: Endothelial Activation and Stress Index (EASIX) predict death in patients undergoing allogeneic hematopoietic stem cell transplantation who develop endothelial complications. Because coronavirus disease 2019 (COVID-19) patients also have coagulopathy and endotheliitis, we aimed to assess whether EASIX predicts death within 28 days in hospitalized COVID-19 patients.Methods: We performed a retrospective study on COVID-19 patients from two different cohorts [derivation (n = 1,200 patients) and validation (n = 1,830 patients)]. The endpoint was death within 28 days. The main factors were EASIX [(lactate dehydrogenase * creatinine)/thrombocytes] and aEASIX-COVID (EASIX * age), which were log2-transformed for analysis.Results: Log2-EASIX and log2-aEASIX-COVID were independently associated with an increased risk of death in both cohorts (p &lt; 0.001). Log2-aEASIX-COVID showed a good predictive performance for 28-day mortality both in the derivation cohort (area under the receiver-operating characteristic = 0.827) and in the validation cohort (area under the receiver-operating characteristic = 0.820), with better predictive performance than log2-EASIX (p &lt; 0.001). For log2 aEASIX-COVID, patients with low/moderate risk (&lt;6) had a 28-day mortality probability of 5.3% [95% confidence interval (95% CI) = 4–6.5%], high (6–7) of 17.2% (95% CI = 14.7–19.6%), and very high (&gt;7) of 47.6% (95% CI = 44.2–50.9%). The cutoff of log2 aEASIX-COVID = 6 showed a positive predictive value of 31.7% and negative predictive value of 94.7%, and log2 aEASIX-COVID = 7 showed a positive predictive value of 47.6% and negative predictive value of 89.8%.Conclusion: Both EASIX and aEASIX-COVID were associated with death within 28 days in hospitalized COVID-19 patients. However, aEASIX-COVID had significantly better predictive performance than EASIX, particularly for discarding death. Thus, aEASIX-COVID could be a reliable predictor of death that could help to manage COVID-19 patients.