bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short-Term Oral Quercetin Supplementation Improves Post-exercise Insulin Sensitivity, Antioxidant Capacity and Enhances Subsequent Cycling Time to Exhaustion in Healthy Adults: A Pilot Study
Authors: Tsao Jung-Piao , Bernard Jeffrey R. , Hsu Hsiu-Chen , Hsu Chin-Lin , Liao Su-Fen , Cheng I-Shiung 
Published: April 2022

AimQuercetin has been reported to have antioxidant and anti-inflammatory properties on health promotion in human studies. The main purpose of this study was to investigate the effect of short-term oral quercetin supplementation on post-exercise whole-body energy metabolism. This study also aimed to determine the effects of supplementation on oxygen stress, inflammation, muscle damage, and high-intensity cycling exercise performance.MethodTwelve healthy participants, physically active students, were recruited to perform a randomized, single-blind crossover study. All subjects completed 7-days of quercetin (quercetin:1,000 mg per day for 7-days) and placebo supplementation in a randomized order. Supplement/placebo was combined with exercise consisting of 70% V̇O2max cycling for 60-min, followed by 3-h of recovery, then a subsequent single bout of cycling exercise with 75% V̇O2max to exhaustion. Time to exhaustion, indicators of muscle damage, as well as blood and gaseous parameters relating to energy metabolism, oxidative stress, inflammatory response, respectively, were determined.ResultsThe results showed that 7-day quercetin supplementation significantly attenuated the post-exercise glucose-induced insulin response, increased total antioxidant capacity (TAC) and superoxidase dismutase (SOD) activities, and mitigated malondialdehyde (MDA) levels during the recovery period (p &lt; 0.05). While subsequent 75% V̇O2max cycling performance was significantly improved after quercetin treatment and accompanied by lower responses of interleukin 6 and creatine kinase at 24-h. However, it’s noted that there were no significant responses in glucose, respiratory exchange rate, tumor necrosis factor-α (TNF-α), myoglobin, and high sensitivity C-reactive protein between quercetin and placebo trials.ConclusionOur findings concluded that 7-day oral quercetin supplementation enhances high-intensity cycling time to exhaustion, which may be due in part to the increase in whole-body insulin-stimulated glucose uptake and attenuation of exercise-induced oxygen stress and pro-inflammation. Therefore, quercetin may be considered an effective ergogenic aid for enhancing high-intensity cycling performance among young adults.
Sequential CAR T-Cell Therapy After Autologous Stem Cell Transplantation for the Treatment of Relapsed/Refractory Intravascular Large B-Cell Lymphoma With Central Nervous System Involvement: A Case Report
Authors: Liu Wanying , Li Chunrui , Cao Yang , Wang Na , Huang Liang , Shang Zhen , Wang Jue , Huang Lifang , Xu Jinhuan , Xiao Min , Zhang Yicheng , Zhou Jianfeng , Chen Liting , Xiao Yi 
Published: April 2022

BackgroundIntravascular large B-cell lymphoma (IVLBCL) is a rare, aggressive, large B-cell non-Hodgkin’s lymphoma. The prognosis of IVLBCL in patients with central nervous system recurrence after first-line chemotherapy treatment is extremely poor. Among immunotherapies, chimeric antigen receptor (CAR) T-cell immunotherapy has been recently found to be a highly effective treatment for B-cell lymphoma, especially for relapsed or refractory diffuse large B-cell lymphoma. However, no guidelines are available that provide a clear consensus regarding the management of patients with relapsed/refractory IVLBCL. Here, we report, for the first time, the use of autologous hematopoietic stem cell transplantation (ASCT) and CAR T-cell therapy in a patient with relapsed/refractory IVLBCL.Case PresentationA 42‐year‐old woman was diagnosed with IVLBCL based on liver biopsy and developed central nervous system (CNS) progression. The patient received ASCT combined with murine monoclonal anti-CD19 and anti-CD22 CAR T-cell therapy. She achieved complete remission for 22 months so far with negative minimal residual disease and continues to be followed up.ConclusionASCT combined with CAR T-cell therapy was the best choice for treatment of relapsed/refractory IVLBCL, as it allowed the achievement of a lasting complete remission.
Afatinib for the Treatment of Non-Small Cell Lung Cancer Harboring Uncommon EGFR Mutations: An Updated Database of 1023 Cases Brief Report
Authors: Yang James Chih-Hsin , Schuler Martin , Popat Sanjay , Miura Satoru , Park Keunchil , Passaro Antonio , De Marinis Filippo , Solca Flavio , Märten Angela , Kim Edward S. 
Published: April 2022

IntroductionPreviously, we developed a database of 693 patients with NSCLC and uncommon EGFR mutations treated with afatinib. Here, we provide an update of &gt;1000 patients, with more data on specific mutations.MethodsPatients were identified from a prospective database developed by Boehringer Ingelheim and via literature review. Mutations were categorized as T790M-positive, exon 20 insertions, major uncommon (G719X, L861Q, S768I) and ‘others’. Patients with compound mutations (≥2 EGFR mutations) were analyzed separately. Key endpoints were time to treatment failure (TTF) and objective response rate (ORR).ResultsOf 1023 patients included, 587 patients were EGFR TKI-naïve and 425 were EGFR TKI-pretreated. The distribution of mutation categories was: major uncommon (41.4%); exon 20 insertions (22.3%); T790M (20.3%); and ‘others’ (15.9%); 38.6% had compound mutations. Overall, median TTF (TKI naïve/pretreated) was 10.7 and 4.5 months. ORR was 49.8% and 26.8%, respectively. In TKI-naïve patients, afatinib demonstrated activity against major uncommon mutations (median TTF: 12.6 months; ORR: 59.0%), ‘other’ mutations (median TTF: 10.7 months; ORR: 63.9%) including strong activity against E709X (11.4 months; 84.6%) and L747X (14.7 months; 80.0%), and compound mutations (11.5 months; 63.9%). Although sample sizes were small, notable activity was observed against specific exon 20 insertions at residues A763, M766, N771, and V769, and against osimertinib resistance mutations (G724S, L718X, C797S).ConclusionAfatinib should be considered as a first-line treatment option for NSCLC patients with major uncommon, compound, ‘other’ (including E709X and L747X) and some specific exon 20 insertion mutations. Moderate activity was seen against osimertinib resistance EGFR mutations.
Human Epidermal Growth Factor Receptor 2 Overexpression and Amplification in Patients With Colorectal Cancer: A Large-Scale Retrospective Study in Chinese Population
Authors: Ni Shujuan , Wang Xin , Chang Jinjia , Sun Hui , Weng Weiwei , Wang Xu , Tan Cong , Zhang Meng , Wang Lei , Huang Zhaohui , Huang Dan , Xu Midie , Sheng Weiqi 
Published: April 2022

BackgroundCumulative evidence in colorectal cancer (CRC) suggests that patients with human epidermal growth factor receptor 2 (HER2) overexpression or amplification can benefit from anti-HER2 therapy. The purpose of our study was to evaluate HER2 status and its correlation with clinicopathological characteristics and survival according to currently utilized HER2 diagnostic criteria in a large cohort of Chinese CRC patients.MethodsHER2 protein expression was tested by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded (FFPE) samples from 4,836 CRC patients in our institution. Breast cancer (BC) and gastroesophageal adenocarcinoma (GEA) criteria, as well as the HERACLES criteria, were used for the determination of HER2 status. Dual-color silver-enhanced in situ hybridization (DSISH) was performed in all IHC 2+~3+ cases determined by BC/GEA criteria.ResultsThe HER2 expression rate of IHC (1+~3+) was 7.01% (339/4,836) and 6.02% (291/4,836) in CRCs based on the BC/GEA criteria and the HERACLES criteria, respectively, while combined DSISH results in the HER2 amplification/overexpression ratio of 3.39% (164/4,836) in our cohort. HER2 expression detected by IHC was positively correlated with the female gender, whereas the HER2 overexpression/amplification showed no correlation with any clinicopathological parameter. In addition, no significant correlation was found between HER2 statuses and either disease-free survival or overall survival regardless of the evaluation criterion used. However, patients with HER2 1+ CRC showed a tendency of having the shortest overall survival as compared with any other group of patients according to the HERACLES criteria, and this trend has always existed in the rectal location, T3 stage, and TNM stage II, medium differentiation, and perineural invasion stratified group. Furthermore, the HER2 protein expression was significantly negatively correlated with RAS/BRAF mutations according to the HERACLES criteria.ConclusionTo our knowledge, this is the largest study of HER2 status in Asian patients with CRC. Our findings suggest that the current most commonly used HERACLES criteria might be too strict for patients with CRC. Future studies are needed to explore the most suitable criteria for screening CRC patients who could benefit from anti-HER2 therapy as much as possible.
Association Between Diabetes Risk Reduction Diet and Lung Cancer Risk in 98,159 Participants: Results From a Prospective Study
Authors: Zhang Yin , Zhong Guochao , Zhu Min , Chen Ling , Wan Huajing , Luo Fengming 
Published: April 2022

PurposeTo evaluate the association between diabetes risk reduction diet (DRRD) score and the risk of lung cancer in a large population.MethodsData of participants in this study were collected from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated in the Cox proportional hazards regression model for the association of DRRD score and lung cancer incidence in all included participants. Prespecified subgroup analyses were performed to evaluate whether the observed association was modified by age, sex, BMI, race/ethnicity, family history of lung cancer, smoking status and history of diabetes.ResultsA total of 98,159 participants were included in this study. The mean (SD) age of the study participants cohort at baseline was 65.5 (5.73) years old. The mean (SD) follow-up time was 8.83 (1.96) years. The mean (SD) score of DRRD was 26.82 (5.19), and ranged from 20.47 (2.3) to 33.65 (2.42) from the lowest quartile to the highest quartile of the DRRD score, inferring the possibility of highest through the lowest risk of type 2 diabetes. The calculated HRs showed there was a trend that higher quartile indicated lower risk of lung cancer after adjusted for covariates (HRQ4vsQ1: 0.85; 95% CI:0.73,0.98; p for trend =0.036). The inverse trend between higher DRRD score and the risk of squamous cell carcinoma was more evident (HRQ4vsQ1: 0.50; 95% CI:0.34,0.73; p for trend =0.002). The inverse association between DRRD score and the incidence of lung cancer was more pronounced in participants who had a clear family history of lung cancer (p for interaction=0.016).ConclusionA protective association between DRRD score and risk of lung cancer is obtained. People are encouraged to adhere to higher DRRD score in their daily diet. Further studies should be conducted to confirm the result and explore the mechanism.
Development and Validation of a Prognostic Model for Post-Operative Recurrence of Pituitary Adenomas
Authors: Lu Liang , Wan Xueyan , Xu Yu , Chen Juan , Shu Kai , Lei Ting 
Published: April 2022

BackgroundWe aimed to assess clinical factors associated with tumor recurrence and build a nomogram based on identified risk factors to predict postoperative recurrence in patients with pituitary adenomas (PAs) who underwent gross-total resection (GTR).MethodsA total of 829 patients with PAs who achieved GTR at Tongji Hospital between January 2013 and December 2018 were included in this retrospective study. The median follow-up time was 66.7 months (range: 15.6–106.3 months). Patients were randomly divided into training (n = 553) or validation (n = 276) cohorts. A range of clinical characteristics, radiological findings, and laboratory data were collected. Uni- and multivariate Cox regression analyses were applied to determine the potential risk factors for PA recurrence. A nomogram model was built from the identified factors to predict recurrence. Concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) were used to determine the predictive accuracy of the nomogram. Decision curve analysis (DCA) was performed to evaluate the clinical efficacy of the nomogram.ResultsPseudocapsule-based extracapsular resection (ER), cavernous sinus invasion (CSI), and tumor size were included in the nomogram. C-indices of the nomogram were 0.776 (95% confidence interval [CI]: 0.747–0.806) and 0.714 (95% CI: 0.681–0.747) for the training and validation cohorts, respectively. The area under the curve (AUC) of the nomogram was 0.770, 0.774, and 0.818 for 4-, 6-, 8-year progression-free survival (PFS) probabilities in the training cohort, respectively, and 0.739, 0.715 and 0.740 for 4-, 6-, 8-year PFS probabilities in the validation cohort, respectively. Calibration curves were well-fitted in both training and validation cohorts. DCA revealed that the nomogram model improved the prediction of PFS in both cohorts.ConclusionsPseudocapsule-based ER, CSI, and tumor size were identified as independent predictors of PA recurrence. In the present study, we developed a novel and valid nomogram with potential utility as a tool for predicting postoperative PA recurrence. The use of the nonogram model can facilitate the tailoring of counseling to meet the individual needs of patients.
Noninvasive Pediatric Liver Fibrosis Measurement: Two-Dimensional Shear Wave Elastography Compared With Transient Elastography
Authors: Tran Léa Chantal , Ley Delphine , Bourdon Gurvan , Coopman Stéphanie , Lerisson Héloïse , Tillaux Céline , Béhal Hélène , Gottrand Frédéric , Aumar Madeleine 
Published: April 2022

ObjectivesAlthough transient elastography (TE) is the primary noninvasive method for assessing liver fibrosis, its use remains to be validated in children. This study aims to evaluate the agreement between two-dimensional ultrasound shear wave elastography (2D-SWE) and TE to assess pediatric liver stiffness method.MethodsDuring the 18-month study, we prospectively included 101 consecutive children (median age: 8.5 years, range: 1 month to 17 years) who required TE for medical reasons, and in whom 2D-SWE measurement was performed within a 3-month follow-up during a routine ultrasound. Liver elasticity values were classified according to the Metavir score using published pediatric norms for TE and according to the manufacturer's reference values for 2D-SWE. The Spearman's correlation coefficient was used to assess the relationship between the elasticity measured by the two techniques. Concordance was described by the Bland–Altman method.ResultsA strong correlation (rho = 0.70, p &lt; 0.001) was found between 2D-SWE and TE for the elasticity measures. The strength of correlation was higher among patients older than 6 years (rho = 0.79, p &lt; 0.001). Concordance between liver fibrosis stages assessed by these techniques was moderate [weighted kappa = 0.46, (95% CI: 0.35–0.57)]. When considering stages over F2, 2D-SWE diagnostic performances showed a sensitivity of 85% (95% CI: 74–92) and a specificity of 57% (95% CI: 42–70) compared with TE.ConclusionMeasurements of the liver stiffness using 2D-SWE and TE are strongly correlated. The moderate concordance between these techniques for assessing the liver fibrosis stage provides evidence against alternating between these methods during follow-up of patients with the chronic liver diseases.
Prevalence and Risk Factors for Rapid Eye Movement-Related Obstructive Sleep Apnea in Children
Authors: Chamnanpet Surisa , Tovichien Prakarn , Tanphaichitr Archwin , Chotinaiwattarakul Wattanachai 
Published: April 2022

ObjectivesDifferent pathophysiological mechanisms and the distribution of respiratory events among rapid eye movement (REM) and non-rapid eye movement (NREM) sleep modulate the effect of obstructive sleep apnea (OSA). We aimed to study the prevalence and risk factors for REM-related OSA in children.Study DesignRetrospective, cross-sectional study.MethodsWe recruited 366 children with OSA confirmed by polysomnography (PSG) over a 5-year period. REM-related OSA is defined by an obstructive apnea-hypopnea index (OAHI) in the REM sleep ≥2× than during NREM sleep.ResultsThe prevalence of REM-related OSA in children was 50.3%. Children with REM-related OSA were more likely to be female (P = 0.042), and had lower prevalence of adenotonsillar hypertrophy (P = 0.043) compared with children with other OSA subtypes. Children with REM-related OSA slept longer in the supine position (P = 0.003), had shorter duration of NREM1 sleep (P = 0.018), lower nadir SpO2 (P = 0.005), and a higher oxygen desaturation index 3% (ODI3%) (P = 0.014), and lower arousal index (P = 0.034) compared with other OSA subtypes. Female gender and supine sleep was the independent risk factors for REM-related OSA.ConclusionThe prevalence of REM-related OSA was 50.3%. OAHIREM should be considered as an important parameter in future clinical research studies done in children with OSA.
Effects of Early Motor Interventions on Gross Motor and Locomotor Development for Infants at-Risk of Motor Delay: A Systematic Review
Authors: Dumuids-Vernet Marie-Victorine , Provasi Joëlle , Anderson David Ian , Barbu-Roth Marianne 
Published: April 2022

AimTo systematically examine the effect of early motor interventions on motor and locomotor development in infants &lt;1 year of age with motor developmental disability or at risk of motor delay.MethodsPertinent literature from January 2000 to September 2021 was identified by searching the PubMed, Embase, Cochrane, Pedro and Web of Science databases. Selection criteria included interventions starting before 12 months corrected age. Methodological quality was assessed with AACPDM criteria, Mallen score and Cochrane risk of bias methodology. Evaluation procedure was performed using PRISMA protocol (PICO approach) and AMSTAR-2. This review was preregistered in PROSPERO (CRD42021286445).ResultsTen articles met the inclusion criteria; seven had moderate to strong methodological quality. The interventions included treadmill training (n = 3), crawling training (n = 1), “tummy time” (n = 1), physical therapy with neonatal developmental program (n = 1) or Bobath approach (n = 1), treadmill training combined with active leg movements (n = 2) or Bobath physiotherapy (n = 1). The three key characteristics of effective interventions that emerged from the review were: (1) the infants' disability or risk of delay was well-defined; (2) the protocol was standardized and easy to replicate; (3) infants were required to make active movements.ConclusionThere is an urgent need for additional high-quality studies on the effects of early motor interventions on the gross motor and locomotor development of infants with a range of disabilities or risks for delay. Suggestions for future research are outlined.
Di’ao Xinxuekang Capsule Improves the Anti-Atherosclerotic Effect of Atorvastatin by Downregulating the SREBP2/PCSK9 Signalling Pathway
Authors: Liang Jiyi , Li Wei , Liu Honglin , Li Xiaofen , Yuan Chuqiao , Zou Wenjun , Qu Liping 
Published: April 2022

Statins are the first choice for lowering low-density lipoprotein cholesterol (LDL-C) and preventing atherosclerotic cardiovascular disease (ASCVD). However, statins can also upregulate proprotein convertase subtilisin/kexin type 9 (PCSK9), which in turn might limits the cholesterol-lowering effect of statins through the degradation of LDL receptors (LDLR). Di’ao Xinxuekang (DXXK) capsule, as a well-known traditional Chinese herbal medicine for the prevention and treatment of coronary heart disease, can alleviate lipid disorders and ameliorate atherosclerosis in atherosclerosis model mice and downregulate the expression of PCSK9. In this study, we further explored whether DXXK has a synergistic effect with atorvastatin (ATO) and its underlying molecular mechanism. The results showed that both ATO monotherapy (1.3 mg/kg) and ATO combined with DXXK therapy significantly lowered serum lipid levels and reduced the formation of atherosclerotic plaques and the liver lipid accumulation. Moreover, compared with ATO monotherapy, the addition of DXXK (160 mg/kg) to the combination therapy further lowered LDL-C by 15.55% and further reduced the atherosclerotic plaque area by 25.98%. In addition, the expression of SREBP2, PCSK9 and IDOL showed a significant increase in the model group, and the expression of LDLR was significantly reduced; however, there were no significant differences between the ATO (1.3 mg/kg) and the model groups. When ATO was combined with DXXK, the expression of LDLR was significantly increased and was higher than that of the model group and the expression of SREBP2 and PCSK9 in the liver was also significantly inhibited. Moreover, it can be seen that the expression of SREBP2 and PCSK9 in the combination treatment group was significantly lower than that in the ATO monotherapy group (1.3 mg/kg). Besides, the expression of IDOL mRNA in each treatment group was not significantly different from that of the model group. Our study suggests that DXXK might have a synergistic effect on the LDL-C lowering and antiatherosclerosis effects of ATO through the SREBP2/PCSK9 pathway. This indicates that a combination of DXXK and ATO may be a new treatment for atherosclerosis.
Effect of Combined Mycophenolate and Rapamycin Treatment on Kidney Fibrosis in Murine Lupus Nephritis
Authors: Zhang Chenzhu , Tam Tsz Wai , Chau Mel KM , García Córdoba Cristina Alexandra , Yung Susan , Chan Tak Mao 
Published: April 2022

Background: A significant proportion of lupus nephritis patients develop chronic kidney disease (CKD) and progressive kidney fibrosis, for which there is no specific treatment. We previously reported that mycophenolate or rapamycin monotherapy showed comparable efficacy in suppressing kidney fibrosis in a murine model of lupus nephritis through their direct action on mesangial cells. We extended our study to investigate the effect of combined mycophenolate and rapamycin treatment (MR) on kidney fibrosis in NZBWF1/J mice.Methods: Female NZBWF1/J mice with active nephritis were randomized to receive vehicle or treatment with mycophenolate (50 mg/kg/day) and rapamycin (1.5 mg/kg/day) (MR) for up to 12 weeks, and the effect of treatment on clinical parameters, kidney histology, and fibrotic processes was investigated.Results: Progression of nephritis in untreated mice was accompanied by mesangial proliferation, glomerulosclerosis, tubular atrophy, protein cast formation, increased mTOR and ERK phosphorylation, and induction of TGF-β1, IL-6, α-smooth muscle actin, fibronectin, and collagen expression. Combined MR treatment prolonged survival, improved kidney function, decreased anti-dsDNA antibody level, and ameliorated histopathological changes. The effect of combined MR treatment on kidney histology and function was comparable to that of mycophenolate or rapamycin monotherapy. In vitro studies in human mesangial cells showed that exogenous TGF-β1 and IL-6 both induced mTOR and ERK phosphorylation and downstream fibrotic processes. Both mycophenolic acid and rapamycin inhibited inflammatory and fibrotic processes induced by TGF-β1 or IL-6 by downregulating mTOR and ERK phosphorylation.Conclusions: Our findings indicate that combined mycophenolate and rapamycin, at reduced dose, improves kidney fibrosis in murine lupus nephritis through their distinct effect on mTOR and ERK signaling in mesangial cells.