bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Validation of an 8-Gene Signature to Improve Survival Prediction of Colorectal Cancer
Authors: Zhou Leqi , Yu Yue , Wen Rongbo , Zheng Kuo , Jiang Siyuan , Zhu Xiaoming , Sui Jinke , Gong Haifeng , Lou Zheng , Hao Liqiang , Yu Guanyu , Zhang Wei 
Published: May 2022

BackgroundMost prognostic signatures for colorectal cancer (CRC) are developed to predict overall survival (OS). Gene signatures predicting recurrence-free survival (RFS) are rarely reported, and postoperative recurrence results in a poor outcome. Thus, we aim to construct a robust, individualized gene signature that can predict both OS and RFS of CRC patients.MethodsPrognostic genes that were significantly associated with both OS and RFS in GSE39582 and TCGA cohorts were screened via univariate Cox regression analysis and Venn diagram. These genes were then submitted to least absolute shrinkage and selection operator (LASSO) regression analysis and followed by multivariate Cox regression analysis to obtain an optimal gene signature. Kaplan–Meier (K–M), calibration curves and receiver operating characteristic (ROC) curves were used to evaluate the predictive performance of this signature. A nomogram integrating prognostic factors was constructed to predict 1-, 3-, and 5-year survival probabilities. Function annotation and pathway enrichment analyses were used to elucidate the biological implications of this model.ResultsA total of 186 genes significantly associated with both OS and RFS were identified. Based on these genes, LASSO and multivariate Cox regression analyses determined an 8-gene signature that contained ATOH1, CACNB1, CEBPA, EPPHB2, HIST1H2BJ, INHBB, LYPD6, and ZBED3. Signature high-risk cases had worse OS in the GSE39582 training cohort (hazard ratio [HR] = 1.54, 95% confidence interval [CI] = 1.42 to 1.67) and the TCGA validation cohort (HR = 1.39, 95% CI = 1.24 to 1.56) and worse RFS in both cohorts (GSE39582: HR = 1.49, 95% CI = 1.35 to 1.64; TCGA: HR = 1.39, 95% CI = 1.25 to 1.56). The area under the curves (AUCs) of this model in the training and validation cohorts were all around 0.7, which were higher or no less than several previous models, suggesting that this signature could improve OS and RFS prediction of CRC patients. The risk score was related to multiple oncological pathways. CACNB1, HIST1H2BJ, and INHBB were significantly upregulated in CRC tissues.ConclusionA credible OS and RFS prediction signature with multi-cohort and cross-platform compatibility was constructed in CRC. This signature might facilitate personalized treatment and improve the survival of CRC patients.
3,5,3′-Triiodothyronine–Loaded Liposomes Inhibit Hepatocarcinogenesis Via Inflammation-Associated Macrophages
Authors: Sun Gangqi , Hou Xiaojuan , Zhang Luyao , Zhang Hengyan , Shao Changchun , Li Fengwei , Zong Chen , Li Rong , Shi Junxia , Yang Xue , Zhang Li 
Published: May 2022

BackgroundHepatocellular carcinoma (HCC) is inflammation-related cancer. Persistent inflammatory injury of the liver is an important factor mediating the occurrence and development of liver cancer. Hepatic macrophages play an important role in the inflammatory microenvironment, which mediates tumor immune escape, tumor growth, and metastasis. Previous studies have suggested that L-3,5,3-triiodothyronine (T3) can regulate inflammation; however, its use is associated with serious cardiac side effects, and its role in hepatocarcinogenesis remains unclear. In this study, we aimed to develop an effective T3 delivery system with reduced cardiac toxicity and to explore its effects on HCC occurrence.MethodsT3 liposomes (T3-lipo) were prepared using the thin-film hydration method, and their characteristics, including particle size, polydispersity index, zeta potential, encapsulation efficiency, drug loading, drug release, and stability, were evaluated in vitro. We assessed the effect of T3-lipo on hepatocarcinogenesis in diethylnitrosamine (DEN)–induced primary HCC in rats and examined the biodistribution of T3 and T3-lipo by high-performance liquid chromatography–mass spectrometry. Furthermore, we explored the potential molecular mechanism of T3-lipo in hepatocarcinogenesis by immunohistochemistry and immunofluorescence analyses, Bio-Plex assays, real-time polymerase chain reaction analysis, and Western blotting assays.ResultsCompared with T3, T3-lipo had an enhanced inhibitory effect on hepatocarcinogenesis and reduced cardiac side effects in DEN-induced primary HCC in rats. Mechanistically, T3-lipo were absorbed by hepatic macrophages and regulated the secretion of inflammatory cytokines in macrophages by inhibiting inflammatory signaling pathways.ConclusionsT3-lipo may suppress hepatocarcinogenesis by regulating the inflammatory microenvironment in the liver and reduce the cardiac side effects meanwhile.
Gender Differences in Medication Adverse Effects Experienced by People Living With Chronic Pain
Authors: Nguena Nguefack Hermine Lore , Gabrielle Pagé M. , Guénette Line , Blais Lucie , Diallo Mamadou , Godbout-Parent Marimée , Angarita-Fonseca Adriana , Lacasse Anaïs 
Published: May 2022

ObjectivesUnderstanding gender differences in chronic pain (CP) outcome research is essential to optimal treatment delivery. This study explored the associations between gender identity, gender roles, and the number of non-life-threatening pain medication adverse effects reported as severe by people living with CP.MethodsThe analyses were conducted using the COPE Cohort, a dataset generated through a web-based recruitment of adults with CP. Participants were asked how they identified themselves (women, men, unknown, unspecified) and gender roles were measured using the Bem Sex-Role Inventory (subgroups were formed applying the median split method). Pain medication adverse effects were assessed using a standardized checklist (none/mild/moderate/severe). A zero-inflated Poisson model was used to assess gender identity, gender roles and their interaction as potential predictors of the number of pain medication adverse effects.ResultsA total of 1,343 participants reported using pain medications. Adjusting for potential confounders, both gender identity (men vs. women: ß = −0.32, p = 0.0024) and gender roles (androgynous vs. undifferentiated: ß = 0.26, p = 0.0030) were associated with the number of pain medication adverse effects reported as severe, and they interacted with each other. The stratified analysis by gender roles showed that women reported a greater number of severe adverse effects than men among those classified as masculine and androgynous.DiscussionAlthough we are unable to confirm whether the associations can be explained by differences in the experience or in the reporting of effects, gender identity and gender roles should both be explored when studying pain medication adverse effects.
The Airway Microbiome and Metabolome in Preterm Infants: Potential Biomarkers of Bronchopulmonary Dysplasia
Authors: Xu Qi , Yu Jialin , Liu Dong , Tan Qi , He Yu 
Published: May 2022

ObjectivesWe investigated the genomic and metabolic characteristics of the airway microbiome in mild, moderate, severe, and non-bronchopulmonary dysplasia (BPD) preterm infants and explored possible mechanisms underlying BPD.MethodsTwenty-eight preterm infants with gestational age ≤34 weeks and intubated within 24 h after birth were enrolled. According to the severity of BPD, the patients were divided into mild, moderate and severe BPD groups, and the non-BPD group was the control group. Tracheal aspirates (TA) were obtained at intubation and on day 7 after birth. The bacterium in the aspirates were sequenced by 16S rRNA, and the metabolomics of the aspirates were identified by high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-Q-TOF/MS). The correlation between the differential metabolite and differential bacteria was investigated using Pearson’s correlation coefficient corrected for gestational age and birth weight and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases.ResultsThere were significant differences in the diversity and composition of airway microbiome and metabolome between severe, moderate and mild BPD and non-BPD premature infants. At birth (day 1), the difference was more pronounced than at day 7. The diversity of airway microbial community decreased, the abundance of Stenotrophomonas increased, and the increased level of sn-glycerol 3-phosphoethanolamine was positively correlated with the severity of BPD. There was a significant positive correlation between the abundance of Stenotrophomonas and the level of sn-glycerol 3-phosphoethanolamine.ConclusionDecreased diversity of the airway microbiome, increased abundance of Stenotrophomonas, and increased level of sn-glycerol 3-phosphoethanolamine may have potential as biomarkers for BPD. The occurrence and severity of BPD are closely related to Stenotrophomonas, which may influence the composition of the lower airway microbiome through its metabolite sn-glycerol 3-phosphoethanolamine, and may be the triggering factor of the disease. The causal relationship needs further study.
Hemostatic Evaluation With Viscoelastic Coagulation Monitor: A Nicu Experience
Authors: Amelio Giacomo Simeone , Raffaeli Genny , Amodeo Ilaria , Gulden Silvia , Cortesi Valeria , Manzoni Francesca , Pesenti Nicola , Ghirardello Stefano , Mosca Fabio , Cavallaro Giacomo 
Published: May 2022

BackgroundViscoelastic coagulation tests provide valuable information in neonatal intensive care units (NICUs), but the lack of reference intervals still limits their decision-making power according to gestational age. The aim of the present study is to evaluate the hemostasis of a cohort of full-term (FT) and late-preterm (LP) infants using the viscoelastic coagulation monitor (VCM®) system, a new portable device that uses untreated whole blood.MethodsAn observational study was performed to identify non-coagulopathic FT and LP infants admitted to III° level NICU (January 2020 to December 2021) with a VCM test in the first 72 h of life.ResultsForty-five patients were enrolled, 26 FT and 19 LP. No statistical differences in hemostatic parameters were observed between FT and LP nor between stable and unstable neonates. Clotting time (CT) was positive correlated with PT (p = 0.032), not with aPTT (p = 0.185). From linear regression, platelet resulted associated with: clot formation time (CTF, p = 0.003), alpha angle (Alpha, p = 0.010), amplitude at 10 (A10, p = 0.001), amplitude at 20 min (A20, p &lt; 0.001), maximum clot firmness (MCF, p &lt; 0.001); and fibrinogen was associated with: A10 (p = 0.008), A20 (p = 0.015) and MCF (p = 0.024). Compared to the adult reference population, neonates showed shorter CT (mean (SD): 5.3 (1.4) vs. 7.0 (0.9) min, p &lt; 0.001), CFT (2.4 (0.7) vs. 2.8 (0.6) minutes, p &lt; 0.001) and higher Alpha (60.8 (6.3) vs. 55 (5)°, p &lt; 0.001). In addition, the neonatal cohort showed an early transient difference in amplitude and fibrinolysis, as follows: A10 (28.0 (5.0) vs. 26 (4) VCM units, p =0.004), A20 (34.8 (5.0) vs. 33 (4) VCM units, p =0.012), and LI30 (99.8 (0.5) vs. 99 (1)%, p &lt;0.001).ConclusionsThe viscoelastic profile of FT and LP infants assessed with VCM showed a hemostatic competence characterized by accelerated coagulation and clot formation time, in line with other viscoelastic techniques. VCM system provides promising applications in the NICU setting.
Pharmacokinetic Characteristics of Siponimod in Healthy Volunteers and Patients With Multiple Sclerosis: Analyses of Published Clinical Trials
Authors: Chaoyang Chen , Xiu Dong , Ran Wei , Lingyun Ma , Simiao Zhao , Ruoming Li , Enyao Zhang , Ying Zhou , Yimin Cui , Zhenming Liu 
Published: May 2022

Objectives: This study aimed to investigate the pharmacokinetic characteristics of siponimod in healthy volunteers and patients with MS based on aggregated data from published clinical trials, and to explore the factors influencing siponimod exposure.Methods: A total of 476 siponimod plasma concentrations aggregated from 28 dosage groups (corresponding to 294 healthy volunteers and 207 patients with MS) were collected from published clinical trials. Population pharmacokinetic (PPK) analysis was performed using a nonlinear, mixed-effect modeling approach. The pharmacokinetic properties of siponimod in healthy volunteers and patients with MS were compared, and the influence of covariates on siponimod exposure was evaluated using both PPK analysis and noncompartmental analysis (NCA).Results: A one-compartment model with first-order absorption and elimination adequately described siponimod pharmacokinetics. The typical population parameter estimates of clearance (CL/F), apparent volume of distribution (V/F), and absorption rate constant (ka) were 3.17 L/h, 112.70 L, and 0.38 h−1, respectively. An 11.85% lower siponimod clearance was estimated for patients with MS relative to healthy volunteers. Subgroup analyses using NCA assessments revealed that siponimod presented an accumulation index of approximately 2 after multiple administration. Compared with nonobese participants, obese participants had a relatively lower dose-corrected area under the concentration-time curve (AUC0-∞/D) (0.31 vs. 0.42 h/L) and V/F (120.95 vs. 133.75 L), and a relatively higher CL/F (3.25 vs. 3.21 L/h). Participants with CYP2C9*2/*3, *1/*3, and *3/*3 genotypes experienced an increased (1.3- and 3.4-fold, respectively) AUC0-∞/D and a decreased (0.7- and 0.3-fold, respectively) CL/F compared with those in participants with the CYP2C9*1/*1, *1*2, and *2*2 genotypes. Fluconazole combination led to a decrease in CL/F (approximately 0.5 times) and an increase in AUC0-∞/D (approximately 1.3 times).Conclusion: Siponimod pharmacokinetic properties in healthy volunteers and patients with MS were explored using complementary model-based meta-analysis (MBMA) and NCA approaches. A slightly lower siponimod clearance was observed in patients with MS than in healthy volunteers. The dosage regimen, body mass index, CYP2C9 genetic polymorphism and fluconazole combination may had influences on siponimod pharmacokinetics. Such model paves the road to more population-based analyses in different patient populations with MS to quantify the effect of any influencing factors on siponimod pharmacokinetics.
Seasonality of Children’s Height and Weight and Their Contribution to Accelerated Summer Weight Gain
Authors: Moreno Jennette P. , Musaad Salma , Dadabhoy Hafza , Baranowski Tom , Crowley Stephanie J. , Thompson Debbe , Chen Tzuan A. , Johnston Craig A. 
Published: May 2022

Background: While children have been shown to have increased BMI during the summer compared to the school year, it is not known if this may be due to seasonal variations in height or weight separately.Methods: Trained nurses measured heights (cm) and weights (kg) in a cohort of Kindergarteners (n = 7648) twice per year from the beginning of kindergarten through 5th grade. Variation in height and weight by season (school year vs. summer) was examined using separate mixed-effects models. Season, sex, and BMI trajectory group were tested as fixed effects. Random effects included repeated measurements of time, students nested within a school, intercept, and slope for growth over time. Similar models using BMIz as the outcome examined the interaction of height or weight with season.Results: The rate of height gain was greater during the school year (∼Sept to April) compared to summer (∼April to Sept) (β = -0.05, SE = 0.013, p &lt; 0.0001). The rate of weight gain did not differ seasonally. Height gain was more strongly associated with increased BMIz during summer compared to the school year (β =.02, SE = 0.005, p &lt;0 .0001), mainly among children who remained healthy weight throughout elementary school (β = 0.014, SE = 0.003, p &lt; 0.0001) and those who transitioned to a healthier weight status (β = 0.026, SE = 0.008, p = 0.004). We found a similar seasonal effect for the association between weight with BMIz among children who maintained a healthy weight status (β = 0.014, SE = 0.014, p &lt; 0.0001).Conclusion: This study indicates seasonality in children’s height gain, gaining height at a faster rate during the school year compared to the summer, while weight gain remained relatively more consistent throughout the year. Seasonality in height and weight gain had the greatest impact on BMIz among children with a healthy weight status. Future research with more frequent measurements is needed to better understand the seasonal regulation of children’s growth and weight gain.
Antidiabetic and Antihyperlipidemic Effects of Methanolic Extract of Leaves of Spondias mombin in Streptozotocin-Induced Diabetic Rats
Authors: Gobinath Ramachawolran , Parasuraman Subramani , Sreeramanan Subramaniam , Enugutti Balaji , Chinni Suresh V. 
Published: May 2022

Objective:Spondias mombin is a plant that reported to have anticonvulsant, antimicrobial, antioxidant, antiulcer, antiasthmatic, and wound healing activities. Diabetes dyslipidemic effect of Spondias mombin leaves is not clear. Hence, current study planned to evaluate the antidiabetic and antihyperlipidemic effects of methanolic extract of leaves of Spondias mombin (MESM) in streptozotocin (STZ) induced diabetic rats.Methods: Phytochemicals were determined by standard method and antioxidant activity was determined by DPPH free radical scavenging and FRAP assay. Diabetes was induced by injecting a single dose of STZ (55 mg/kg) into female sprague dawley rats. After 3 days of induction of diabetes, the diabetic animals were treated for 28 days with MESM (125, 250, and 500 mg/kg) and glibenclamide (20 mg/kg) orally. The body weight of rats and blood glucose levels were monitored at regular intervals during the experiment. At the end of study, blood sample was collected from all the animals and subjected to biochemical, lipid profile, and they were sacrificed and their organs such as pancreas, liver and kidney were used for histopathological analysis.Results: Quantitative analysis of MESM showed the presence of anthraquinone, tannins, saponins, steroid, phenols, flavonoids, alkaloids, and reducing sugars. Reduction in body weight and elevated blood glucose were observed in diabetic rats. Treatment with MESM in a concentration of 125, 250, and 500 mg/kg significantly reversed the elevated levels of blood glucose, reduced aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, urea, creatinine, total serum cholesterol (TC), serum triglyceride (TG), low-density lipoprotein (LDL), Very low-density lipoprotein (VLDL), and increased plasma insulin, total protein, albumin, globulin, A/G ratio, and high-density lipoprotein (HDL).Conclusion: MESM exhibited a significant antidiabetic and antihyperlipidemic activities against STZ-induced diabetes in rats.
Unexpected Cardiovascular Oscillations at 0.1 Hz During Slow Speech Guided Breathing (OM Chanting) at 0.05 Hz
Authors: Hotho Gerard , von Bonin Dietrich , Krüerke Daniel , Wolf Ursula , Cysarz Dirk 
Published: May 2022

Slow breathing at 0.1 Hz (i.e., 6 cycles per minute, cpm) leads to strong cardiovascular oscillations. However, the impact of breathing below 6 cpm is rarely addressed. We investigated the influence of OM chanting, an ancient Indian mantra, with approx. 3 respiratory cpm (0.05 Hz) on the synchronisation of heart period (RR), respiration (RESP) and systolic blood pressure (SBP). Nine healthy, trained speech practitioners chanted three sequences of five subsequent OM with 2 min pauses in between. Each single OM chanting consisted of taking a deep breath and a long “OM” during expiration and lasted approx. 20 s. ECG, respiration and blood pressure were recorded continuously, of which the RR tachogram, RESP and SBP were derived. Synchronisation between the signals was computed using the phase difference between two signals. During OM chanting synchronisation among the oscillations of RR, SBP and RESP was significantly increased compared to rest. Furthermore, OM chanting at breathing frequencies between 0.046 and 0.057 Hz resulted in 0.1 Hz oscillations in RR and SBP. In conclusion, OM chanting strongly synchronized cardiorespiratory and blood pressure oscillations. Unexpected oscillations at 0.1 Hz in SBP and RR appear at breathing frequencies of approx. 0.05 Hz. Such frequency doubling may originate from an interaction of breathing frequency with endogenous Mayer waves.
Occurrence of Relative Bradycardia and Relative Tachycardia in Individuals Diagnosed With COVID-19
Authors: Natarajan Aravind , Su Hao-Wei , Heneghan Conor 
Published: May 2022

The COVID-19 disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become one of the worst global pandemics of the century. Wearable devices are well suited for continuously measuring heart rate. Here we show that the Resting Heart Rate is modified for several weeks following a COVID-19 infection. The Resting Heart Rate shows 3 phases: 1) elevated during symptom onset, with average peak increases relative to the baseline of 1.8% (3.4%) for females (males), 2) decrease thereafter, reaching a minimum on average ≈13 days after symptom onset, and 3) subsequent increase, reaching a second peak on average ≈28 days from symptom onset, before falling back to the baseline ≈112 days from symptom onset. All estimates vary with disease severity1.
Morpho-Physiological and Proteomic Response of Bt-Cotton and Non-Bt Cotton to Drought Stress
Authors: Nagamalla Swetha Sudha , Alaparthi Malini Devi , Mellacheruvu Sunitha , Gundeti Ravindar , Earrawandla Jana Priya Sony , Sagurthi Someswar Rao 
Published: May 2022

Graphical AbstractSchematic diagram showing the differential responses of NCS BG II BT and Non BT varities to drought stress. NCS BG II BT variety showed better drought tolerance compared with Non BT plant variety.