bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between dietary habits and incident thyroid cancer: A prospective cohort study
Authors: Nguyen Linh Thi Dieu , Gunathilake Madhawa , Lee Jeonghee , Kim Jeongseon 
Published: February 2023

BackgroundIn addition to the thyroid cancer (TC) risk from lifestyle and environmental factors such as radiation exposure, some studies have indicated that diet may affect TC development; however, previous findings are inconsistent. The objective of our study was to investigate the association between dietary habits and TC risk in a Korean population.Materials and methodsA total of 13,973 participants were selected after excluding ineligible subjects from the Cancer Screenee Cohort at National Cancer Center in Korea from October 2007 to December 2021. Participants were followed until May 2022 to identify incident TC cases. Information on dietary habits and general characteristics was collected using a self-report questionnaire administered at enrollment without keeping track of changes in eating habits during the follow-up period. A Cox proportional hazards model was used to determine the hazard ratio (HR) and 95% confidence interval (CI) of TC risk for each dietary factor.ResultsA total of 138 incident TC cases were identified during the median follow-up period of 7.6 years. Of the 12 dietary habits evaluated, only two habits showed significant associations with TC. A significantly decreased TC risk was found among participants who consumed milk and/or dairy products 5 or more days a week [adjusted HR (aHR), 0.58; 95% CI, 0.39–0.85]. Notably, a stronger protective effect of dairy consumption was observed in participants aged ≥ 50 years (aHR, 0.44; 95% CI, 0.26–0.75), in women (aHR, 0.53; 95% CI, 0.35–0.81), and in non-smokers (aHR, 0.60; 95% CI, 0.39–0.92). There was a reduced risk of TC in participants with meal durations longer than 10 min (aHR, 0.58; 95% CI, 0.41–0.83). However, this association was limited to individuals aged ≥ 50 years (aHR, 0.49; 95% CI, 0.31–0.79), women (aHR, 0.61; 95% CI, 0.41–0.90), and non-smokers (aHR, 0.62; 95% CI, 0.41–0.92).ConclusionOur findings suggest that consuming milk and/or dairy products 5 or more days a week and having a meal duration longer than 10 min could be protective factors against TC, especially in individuals aged ≥ 50 years, women and non-smokers. Further prospective studies are needed to investigate the association of dietary intake with specific types of TC.
Unveiling the therapeutic potential of cabozantinib-loaded poly D,L-lactic-co-glycolic acid and polysarcosine nanoparticles in inducing apoptosis and cytotoxicity in human HepG2 hepatocellular carcinoma cell lines and in vivo anti-tumor activity in SCID female mice
Authors: Bhattacharya Sankha , Parihar Vipan Kumar , Prajapati Bhupendra G. 
Published: February 2023

IntroductionThe study aimed to develop a nano-based drug delivery system for the treatment of hepatocellular carcinoma (HCC), a type of liver cancer that accounts for 90% of all liver malignancies. The study focused on the use of cabozantinib (CNB), a potent multikinase inhibitor that targets the VEGF receptor 2, as the chemotherapeutic drug. We developed CNB-loaded nanoparticles made from Poly D, L-lactic-co-glycolic acid, and Polysarcosine (CNB-PLGA-PSar-NPs) for use in human HepG2 cell lines.MethodsBy O/W solvent evaporation method, the polymeric nanoparticles were prepared. The various techniques, such as photon correlation spectroscopy, scanning electron microscopy, and transmission electron microscopy were used, to determine the formulation's particle size, zeta potential, and morphology. SYBR Green/ROX qPCR Master Mix and RT-PCR equipment used to measure liver cancer cell line and tissue mRNA expression and MTT assay to test HepG2 cell cytotoxicity. Cell cycle arrest analysis, annexin V assay, and ZE5 Cell Analyzer apoptosis assay were also performed.ResultsThe results of the study showed that the particle diameters were 192.0 ± 3.67 nm with 0.128 PDI and -24.18 ± 3.34 mV zeta potential. The antiproliferative and proapoptotic effects of CNB-PLGA-PSar-NPs were evaluated using MTT and flow cytometry (FCM). The IC50 value of CNB-PLGA-PSar-NPs was 45.67 µg/mL, 34.73 µg/mL, and 21.56 µg/mL for 24, 48, and 72 h, respectively. The study also found that 11.20% and 36.77% of CNB-PLGA-PSar-NPs-treated cells were apoptotic at 60 µg/mL and 80 µg/mL, respectively, suggesting that the nanoparticles were effective in inducing apoptosis in the cancer cells. It can also conclude that, CNB-PLGA-PSar-NPs inhibit human HepG2 hepatocellular carcinoma cells and kill them by upregulating the tumour suppressor genes MT1F, MT1X, and downregulating MTTP, APOA4. Further in vivo antitumor activity was well reported in SCID female mice.DiscussionOverall, this study suggests that the CNB-PLGA-PSar-NPs are a promising drug delivery system for the treatment of HCC, and further research is needed to investigate their potential in clinical treatment.
Lamivudine 24-month-long prophylaxis is a safe and efficient choice for the prevention of hepatitis B virus reactivation in HBsAg-negative/HBcAb-positive patients with advanced DLBCL undergoing upfront R-CHOP-21
Authors: Giordano Claudia , Picardi Marco , Pugliese Novella , Vincenzi Annamaria , Abagnale Davide Pio , De Fazio Laura , Giannattasio Maria Luisa , Fatigati Carmina , Ciriello Mauro , Salemme Alessia , Muccioli Casadei Giada , Vigliar Elena , Mascolo Massimo , Troncone Giancarlo , Pane Fabrizio 
Published: February 2023

IntroductionOccult hepatitis B infection (OBI) is a condition where replication-competent hepatitis B virus-DNA (HBV-DNA) is present in the liver, with or without HBV-DNA in the blood [&lt;200 international units (IU)/ml or absent] in HB surface antigen (HBsAg)-negative/HB core antibody (HBcAb)-positive individuals. In patients with advanced stage diffuse large B-cell lymphoma (DLBCL) undergoing 6 cycles of R-CHOP-21+2 additional R, OBI reactivation is a frequent and severe complication. There is no consensus among recent guidelines on whether a pre-emptive approach or primary antiviral prophylaxis is the best solution in this setting of patients. In addition, questions still unresolved are the type of prophylactic drug against HBV and adequate prophylaxis duration.MethodsIn this case-cohort study, we compared a prospective series of 31 HBsAg−/HBcAb+ patients with newly diagnosed high-risk DLBCL receiving lamivudine (LAM) prophylaxis 1 week before R-CHOP-21+2R until 18 months after (24-month LAM series) versus 96 HBsAg−/HBcAb+ patients (from January 2005 to December 2011) undergoing a pre-emptive approach (pre-emptive cohort) and versus 60 HBsAg−/HBcAb+ patients, from January 2012 to December 2017, receiving LAM prophylaxis [1 week before immunochemotherapy (ICHT) start until 6 months after] (12-month LAM cohort). Efficacy analysis focused primarily on ICHT disruption and secondarily on OBI reactivation and/or acute hepatitis.ResultsIn the 24-month LAM series and in the 12-month LAM cohort, there were no episodes of ICHT disruption versus 7% in the pre-emptive cohort (P = 0.05). OBI reactivation did not occur in any of the 31 patients in the 24-month LAM series versus 7 out of 60 patients (10%) in the 12-month LAM cohort or 12 out of 96 (12%) patients in the pre-emptive cohort (P = 0.04, by χ2 test). No patients in the 24-month LAM series developed acute hepatitis compared with three in the 12-month LAM cohort and six in the pre-emptive cohort.DiscussionThis is the first study collecting data regarding a consistent and homogeneous large sample of 187 HBsAg−/HBcAb+ patients undergoing standard R-CHOP-21 for aggressive lymphoma. In our study, 24-month-long prophylaxis with LAM appears to be the most effective approach with a null risk of OBI reactivation, hepatitis flare-up, and ICHT disruption.
Predicting complications in pediatric Crohn's disease patients followed in CEDATA-GPGE registry
Authors: Klamt Juliane , de Laffolie Jan , Wirthgen Elisa , Stricker Sebastian , Däbritz Jan ,   the CEDATA-GPGE study group
Published: February 2023

BackgroundComplications of Crohn's disease (CD) often impair patients' quality of life. It is necessary to predict and prevent these complications (surgery, stricturing [B2]/penetrating [B3] disease behavior, perianal disease, growth retardation and hospitalization). Our study investigated previously suggested and additional predictors by analyzing data of the CEDATA-GPGE registry.MethodsPediatric patients (&lt; 18 years) diagnosed with CD with follow up data in the registry were included in the study. Potential risk factors for the selected complications were evaluated by performing Kaplan-Meier survival curves and cox regression models.ResultsFor the complication surgery, the potential risk factors older age, B3 disease, severe perianal disease and initial therapy with corticosteroids at the time of diagnosis were identified. Older age, initial therapy with corticosteroids, low weight-for-age, anemia and emesis predict B2 disease. Low weight-for-age and severe perianal disease were risk factors for B3 disease. Low weight-for-age, growth retardation, older age, nutritional therapy, and extraintestinal manifestations (EIM) of the skin were identified as risk factors for growth retardation during the disease course. High disease activity and treatment with biologicals were predictors for hospitalization. As risk factors for perianal disease, the factors male sex, corticosteroids, B3 disease, a positive family history and EIM of liver and skin were identified.ConclusionWe confirmed previously suggested predictors of CD course and identified new ones in one of the largest registries of pediatric CD patients. This may help to better stratify patients’ according to their individual risk profile and choose appropriate treatment strategies.
Platelet and ferritin as early predictive factors for the development of macrophage activation syndrome in children with Kawasaki disease: A retrospective case-control study
Authors: Zhang Hua-yong , Xiao Min , Zhou Dan , Yan Fan , Zhang Yong 
Published: February 2023

ObjectiveTo investigate the early predictive factors for Kawasaki disease complicated with macrophage activation syndrome (KD-MAS)MethodsWe performed a retrospective case-control study in children with KD from August 2017 to August 2022, involving 28 cases with KD-MAS and 112 cases not developing KD-MAS. Based on the univariate analysis, binary logistic regression was used to identify the early predictive factors for KD-MAS development, and the receiver operating characteristic curve (ROC) analysis was carried out to obtain the optimal cut-off value.ResultsTwo predictive factors were associated with the development of KD-MAS, which were PLT (OR = 1.013, 95%CI, 1.001–1.026), and serum ferritin (OR = 0.991, 95%CI, 0.982–0.999). The cut-off value of PLT was 110 × 109/L, and the cut-off value of serum ferritin was 548.4 ng/ml.ConclusionChildren with KD who had a PLT count under 110 × 109/L, and a serum ferritin level over 548.4 ng/ml are more likely to develop KD-MAS.
Effects of a mobile health nutrition intervention on dietary intake in children who have autism spectrum disorder
Authors: Kral Tanja V. E. , O’Malley Lauren , Johnson Kelsey , Benvenuti Teresa , Chittams Jesse , Quinn Ryan J. , Thomas J. Graham , Pinto-Martin Jennifer A. , Levy Susan E. , Kuschner Emily S. 
Published: February 2023

BackgroundChildren who have Autism Spectrum Disorder (ASD) show preferences for processed foods, such as salty and sugary snacks (SSS) and sugar-sweetened beverages (SSB), while healthier foods, such as fruits and vegetables (FV), are consumed less. Innovative tools are needed that can efficiently disseminate evidence-based interventions and engage autistic children to improve their diet.AimThe aim of this 3-month randomized trial was to test the initial efficacy of a mobile health (mHealth) nutrition intervention on changing consumption of targeted healthy (FV) and less healthy foods/beverages (SSS, SSB) in children who have ASD, ages 6–10, who were picky eaters.MethodsThirty-eight parent-child dyads were randomly assigned to either an intervention (technology) group or a wait list control (education) group. The intervention included behavioral skills training, a high level of personalization for dietary goals, and involved parents as “agents of change.” Parents in the education group received general nutrition education and the dietary goals but did not receive skills training. Children's intake was assessed at baseline and at 3 months using 24-hour dietary recalls.ResultsWhile there were no significant group-by-time interactions (P &gt; 0.25) for any of the primary outcomes, we found a significant main effect of time for FV intake (P = 0.04) indicating that both groups consumed more FV at 3 months (2.58 ± 0.30 servings/day) than at baseline (2.17 ± 0.28 servings/day; P = 0.03). Children in the intervention group who consumed few FV at baseline and showed high engagement with the technology increased their FV intake by 1.5 servings/day (P &lt; 0.01). Children's taste/smell sensitivity significantly predicted their FV intake (P = 0.0446); for each unit of lower taste/smell sensitivity (indicating greater sensory processing abnormalities), FV intake increased by 0.13 ± 0.1 servings/day.DiscussionThis mHealth intervention did not yield significant between-group differences for changing consumption of targeted foods/beverages. Only children who consumed few FV at baseline and highly engaged with the technology increased their FV intake at 3 months. Future research should test additional strategies to expand the intervention's impact on a wider range of foods while also reaching a broader group of children who have ASD. This trial was registered at clinicaltrials.gov as NCT03424811.Clinical Trial Registration: This study was registered at clinicaltrials.gov as NCT03424811.
Association of newer definitions of bronchopulmonary dysplasia with pulmonary hypertension and long-term outcomes
Authors: Hwang Jae Kyoon , Shin Seung Han , Kim Ee-Kyung , Kim Seh Hyun , Kim Han-Suk 
Published: February 2023

BackgroundThe definition of bronchopulmonary dysplasia (BPD) has been evolved recently from definition by the National Institute of Child Health and Human Development in 2001 (NICHD 2001) to the definition reported in 2018 (NICHD 2018) and that proposed by Jensen et al. in 2019 (NICHD 2019). The definition was developed based on the evolution of non-invasive respiratory support and to achieve better prediction of later outcomes. Our objective was to evaluate the association between different definitions of BPD and occurrence of pulmonary hypertension (PHN) and long term outcomes.MethodsThis retrospective study enrolled preterm infants born at &lt; 32 weeks of gestation between 2014 and 2018. The association between re-hospitalization owing to a respiratory illness until a corrected age (CA) of 24 months, neurodevelopmental impairment (NDI) at a CA of 18–24 months, and PHN at a postmenstrual age (PMA) of 36 weeks was evaluated, with the severity of BPD defined based on these three definitions.ResultsAmong 354 infants, the gestational age and birth weight were the lowest in severe BPD based on the NICHD 2019 definition. In total, 14.1% of the study population experienced NDI and 19.0% were re-hospitalized owing to a respiratory illness. At a PMA of 36 weeks, PHN was identified in 9.2% of infants with any BPD. Multiple logistic regression analysis showed that the adjusted odds ratio (OR) for re-hospitalization was the highest for Grade 3 BPD of the NICHD 2019 criteria (5.72, 95% confidence interval [CI]: 1.37–23.92), while the adjusted OR of Grade 3 BPD was 4.96 (95% CI: 1.73–14.23) in the NICHD 2018 definition. Moreover, no association of the severity of BPD was found in the NICHD 2001 definition. The adjusted ORs for NDI (12.09, 95% CI: 2.52–58.05) and PHN (40.37, 95% CI: 5.15–316.34) were also the highest for Grade 3 of the NICHD 2019 criteria.ConclusionBased on recently suggested criteria by the NICHD in 2019, BPD severity is associated with long-term outcomes and PHN at a PMA of 36 weeks in preterm infants.
In vitro metabolic characterization of the SARS-CoV-2 papain-like protease inhibitors GRL0617 and HY-17542
Authors: Cho Hyunki , Kim Young Jun , Chae Jung-Woo , Meyer Markus R. , Kim Sang Kyum , Ryu Chang Seon 
Published: February 2023

The SARS-CoV-2 pandemic requires a new therapeutic target for viral infection, and papain-like protease (Plpro) has been suggested as a druggable target. This in-vitro study was conducted to examine the drug metabolism of the GRL0617 and HY-17542, Plpro inhibitors. Metabolism of these inhibitors was studied to predict the pharmacokinetics in human liver microsomes. The hepatic cytochrome P450 (CYP) isoforms responsible for their metabolism were identified using recombinant enzymes. The drug–drug interaction potential mediated by cytochrome P450 inhibition was estimated. In human liver microsomes, the Plpro inhibitors had phase I and phase I + II metabolism with half-lives of 26.35 and 29.53 min, respectively. Hydroxylation (M1) and desaturation (-H2, M3) of the para-amino toluene side chain were the predominant reactions mediated with CYP3A4 and CYP3A5. CYP2D6 is responsible for the hydroxylation of the naphthalene side ring. GRL0617 inhibits major drug-metabolizing enzymes, including CYP2C9 and CYP3A4. HY-17542 is structural analog of GRL0617 and it is metabolized to GRL0617 through non-cytochrome P450 reactions in human liver microsomes without NADPH. Like GRL0617 and HY-17542 undergoes additional hepatic metabolism. The in-vitro hepatic metabolism of the Plpro inhibitors featured short half-lives; preclinical metabolism studies are needed to determine therapeutic doses for these inhibitors.
Association between statin use and the risk of gout in patients with hyperlipidemia: A population-based cohort study
Authors: Lin Guan-Ling , Lin Hsiu-Chen , Lin Hsiu-Li , Keller Joseph Jordan , Wang Li-Hsuan 
Published: February 2023

Objective: To investigate the association between statin use and risk of gout in patients with hyperlipidemia.Methods: In this population-based retrospective cohort study, patients ≥20 years and diagnosed as having incident hyperlipidemia between 2001 and 2012 were identified from the 2000 Longitudinal Generation Tracking Database in Taiwan. Regular statin users (incident statin use, having 2 times and ≥90 days of prescription for the first year) and two active comparators [irregular statin use and other lipid-lowering agent (OLLA) use] were compared; the patients were followed up until the end of 2017. Propensity score matching was applied to balance potential confounders. Time-to-event outcomes of gout and dose- and duration-related associations were estimated using marginal Cox proportional hazard models.Results: Regular statin use non-significantly reduced gout risk compared with irregular statin use (aHR, 0.95; 95% CI, 0.90–1.01) and OLLA use (aHR, 0.94; 95% CI, 0.84–1.04). However, a protective effect was noted for a cumulative defined daily dose (cDDD) of &gt;720 (aHR, 0.57; 95% CI, 0.47–0.69 compared with irregular statin use and aHR, 0.48; 95% CI, 0.34–0.67 compared with OLLA use) or a therapy duration of &gt;3 years (aHR, 0.76; 95% CI, 0.64–0.90 compared with irregular statin use and aHR, 0.50; 95% CI, 0.37–0.68 compared with OLLA use). Dose- and duration-dependent associations were consistent in the 5-year sensitivity analyses.Conclusion: Although statin use was not associated with a reduction in gout risk, the protective benefit was observed in those receiving higher cumulative doses or with a longer therapy duration.
Inhibitory effect of Selaginella doederleinii hieron on human cytochrome P450
Authors: Lin Fei , Lin Xinhua , Wang Xuewen , Mei Guanghui , Chen Bing , Yao Hong , Huang Lingyi 
Published: February 2023

Introduction:Selaginella doederleinii Hieron is a traditional Chinese herbal medicine, the ethyl acetate extract from Selaginella doederleinii (SDEA) showed favorable anticancer potentials. However, the effect of SDEA on human cytochrome P450 enzymes (CYP450) remains unclear. To predict the herb-drug interaction (HDI) and lay the groundwork for further clinical trials, the inhibitory effect of SDEA and its four constituents (Amentoflavone, Palmatine, Apigenin, Delicaflavone) on seven CYP450 isoforms were investigated by using the established CYP450 cocktail assay based on LC-MS/MS.Methods: Appropriate substrates for seven tested CYP450 isoforms were selected to establish a reliable cocktail CYP450 assay based on LC-MS/MS. The contents of four constituents (Amentoflavone, Palmatine, Apigenin, Delicaflavone) in SDEA were determined as well. Then, the validated CYP450 cocktail assay was applied to test the inhibitory potential of SDEA and four constituents on CYP450 isoforms.Results: SDEA showed strong inhibitory effect on CYP2C9 and CYP2C8 (IC50 ≈ 1 μg/ml), moderate inhibitory effect against CYP2C19, CYP2E1 and CYP3A (IC50 &lt; 10 μg/ml). Among the four constituents, Amentoflavone had the highest content in the extract (13.65%) and strongest inhibitory effect (IC50 &lt; 5 μM), especially for CYP2C9, CYP2C8 and CYP3A. Amentoflavone also showed time-dependent inhibition on CYP2C19 and CYP2D6. Apigenin and Palmatine both showed concentration-dependent inhibition. Apigenin inhibited CYP1A2, CYP2C8, CYP2C9, CYP2E1 and CYP3A. Palmatine inhibited CYP3A and had a weak inhibitory effect on CYP2E1. As for Delicaflavone, which has the potential to develop as an anti-cancer agent, showed no obvious inhibitory effect on CYP450 enzymes.Conclusion: Amentoflavone may be one of the main reasons for the inhibition of SDEA on CYP450 enzymes, the potential HDI should be considered when SDEA or Amentoflavone were used with other clinical drugs. On the contrast, Delicaflavone is more suitable to develop as a drug for clinical use, considering the low level of CYP450 metabolic inhibition.