bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of Dexamethasone in Children and Adolescents with Obesity
Authors: Wen Jiali , McCann Sean , Balevic Stephen J. , Muller William J. , Hornik Chi D. , Autmizguine Julie , Anderson Sarah G. , Payne Elizabeth H. , Turdalieva Sitora , Gonzalez Daniel ,   the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
Published: August 2024

AbstractDexamethasone is a synthetic glucocorticoid approved for treating disorders of various organ systems in both adult and pediatric populations. Currently, approved pediatric dosing recommendations are weight‐based, but it is unknown whether differences in dexamethasone drug disposition and exposure exist for children with obesity. This study aimed to develop a population pharmacokinetic (PopPK) model for dexamethasone with data collected from children with obesity. Dexamethasone was given as either IV or oral/enteral administration, and a salt factor correction was used for dexamethasone sodium phosphate injection. A PopPK analysis using dexamethasone plasma concentration versus time was performed using the software NONMEM. A virtual population of 1000 children with obesity across three age groups was generated for dosing simulations. Data from 59 study participants with 82 PK plasma samples were used in the PopPK analysis. A one‐compartment model with first‐order absorption and the inclusion of total body weight as a covariate characterized the data. No other covariates were included in the PopPK model. Single and multiple IV dose(s) of 0.5 and 1 mg/kg every 8 h resulted in 68% or more of virtual children with obesity attaining simulated exposures that were within exposure ranges previously reported in adult studies. In conclusion, this was the first study to characterize dexamethasone's PopPK in children with obesity. Simulation results suggest that virtual children with obesity receiving oral doses of 0.5 and 1 mg/kg had generally comparable dexamethasone exposures as adult estimates. Additional studies are needed to characterize the dexamethasone's target exposure in children.
Driving Efficiency: Leveraging Model‐Informed Approaches in 505(b)(2) Regulatory Actions
Authors: Sharma Vishnu Dutt , Bhattaram Venkatesh Atul , Krudys Kevin , Li Zhihua , Marathe Anshu , Mehrotra Nitin , Wang Xiaofeng , Liu Jiang , Stier Ethan , Florian Jeffry , Madabushi Raj , Zhu Hao 
Published: August 2024

AbstractIntroduced by the Hatch‐Waxman Amendments of 1984, 505(b)(2) applications permit the US Food and Drug Administration to rely, for approval of a new drug application, on information from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference. This pathway is designed to circumvent the unnecessary duplication of studies already conducted on a previously approved drug. It can lead to a considerably more efficient and expedited route to approval compared to a traditional development path. Model‐informed drug development refers to the utilization of a diverse array of quantitative models in drug development to streamline the decision‐making process. In this approach, diverse quantitative models that integrate knowledge of physiology, disease processes, and drug pharmacology are employed to address drug development challenges and guide regulatory decisions. Integration of these model‐informed approaches into 505(b)(2) regulatory submissions and decision‐making can further expedite the approval of new drugs. This article discusses some applications of model‐informed approaches that were used to support 505(b)(2) drug development and regulatory actions. Specifically, various quantitative models such as population pharmacokinetic and exposure‐response models have been employed to provide evidence of effectiveness, guide dosing in subgroups such as subjects with hepatic or renal impairment, and inform policies. These case study examples collectively underscore the significance of model‐informed approaches in drug development and regulatory decisions associated with 505(b)(2) submissions.
Presence of abnormal otoliths in hallucinogenic fish and their comparison with normal otoliths using light and scanning electron digital imaging
Authors: Yedier Serdar , Daban İsmail Burak , Şen Yusuf , Bostancı Derya 
Published: August 2024

AbstractThe otolith organs located in the inner ear of the fish are responsible for vital activities such as balance and hearing. Abnormalities in these organs can adversely affect the vital activities of the fish species. The main purpose of the study is to analyze the abnormalities in the otoliths of Sarpa salpa, known as the hallucinogenic fish. For that, 372 individuals of S. salpa are collected from the North Aegean Sea. As a result of the abnormality analyses in S. salpa otoliths, anomalies were detected such as various prominence structures on the surface of the otolith caused by accumulation and a more transparent appearance due to the different crystal structures in some parts of the otolith. These abnormalities were found in the left and/or right otoliths of male and female individuals in different total lengths. The percentage of individuals with abnormal otoliths of S. salpa is calculated as 52.42%. It was determined that there are statistical differences between the left and right otolith measurements of male and female individuals with abnormal and normal otoliths(p < 0.05). There is no relationship between the percentage of individuals showing abnormality and total length and sex. The current study presents for the first time abnormal otolith information on left and right otoliths in male and female S. salpa. It is thought that abnormalities in hallucinogenic fish otoliths could be related to genetic predisposition as well as stress due to nutritional preference, pollutants, and environmental factors.Research Highlights
The presence of abnormalities in the otoliths of Sarpa salpa, a hallucinogenic fish, was revealed for the first time.
Abnormalities in the otoliths of S. salpa were identified, such as the presence of various prominence structures on the otolith's surface, loss of parts as well as a more transparent appearance in the outlines or surface of the otolith.
Normal and abnormal otoliths of female and male hallucinogenic fish from different size groups were examined using light and scanning electron microscopy.
Abnormality detected in the otoliths of hallucinogenic fish is not related to the gender and size of the fish.
Epidemiology and viral loads of respiratory syncytial virus in hospitalized children prior to and during COVID‐19 pandemic in Hangzhou, China
Authors: Chen Yunying , Zhao Xinfeng , Ye Cuiying , Zhou Jun , Wang Jie , Ye Xianfei 
Published: August 2024

AbstractNon‐pharmaceutical interventions (NPIs) implemented to control SARS‐CoV‐2 have significantly influenced the activity of respiratory pathogens. This study investigated epidemiological changes among hospitalized patients with respiratory syncytial virus (RSV) before (2017–2019) and during (2020–2022) the COVID‐19 pandemic in Hangzhou, China. We also examined viral load distribution across demographic and temporal variables. Nasopharyngeal swabs were collected and RSV loads were quantified using reverse transcriptase polymerase chain reaction (RT‐qPCR). RSV epidemic characteristics, seasonal dynamics, and viral load distributions were compared between pre‐ and pandemic years. General linear models were employed to assess associations between viral loads and age. Among 19 742 cases, 1576 and 2092 tested positive during the pre‐ and pandemic years, respectively. From February to July 2020, the implementation of NPIs led to the cessation of RSV circulation. However, after these measures were relaxed, RSV cases resurged over two consecutive seasons during the pandemic, notably affecting older children compared to those in the pre‐pandemic years (1.00 years, IQR: 0.50–2.00 vs. 0.58 years, IQR: 0.27–1.00, p < 0.001). Specifically, in 2021–2022, an off‐season resurgence of RSV began earlier (mid‐June), lasted longer (40 weeks), and involved more positive cases (1238 cases) than both 2020–2021 and pre‐pandemic years. Viral load distribution demonstrated a clear age‐related relationship in both pre‐ and pandemic years, with younger children consistently showing higher viral loads, independently of gender and season (all p‐values for trends <0.001). These findings highlight the impact of NPIs on RSV epidemiology and underscore the need to prioritize RSV infection prevention in younger children from the perspective of viral load.
Antithrombotic management in atrial fibrillation patients following percutaneous coronary intervention: A clinical review
Authors: Saito Yuichi , Kobayashi Yoshio 
Published: August 2024

AbstractPatients with atrial fibrillation (AF) often develop acute coronary syndrome and undergo percutaneous coronary intervention (PCI), and vice versa. Acute coronary syndrome and PCI mandate the use of dual antiplatelet therapy, while oral anticoagulation is recommended in patients with AF to mitigate thromboembolic risks. Clinical evidence concerning antithrombotic treatment in patients with AF and PCI has been accumulated, but when combined, the therapeutic strategy becomes complex. Although triple therapy, a combination of oral anticoagulation with dual antiplatelet therapy, has been used for patients with AF undergoing PCI as an initial antithrombotic strategy, less intensive regimens may be associated with a lower rate of bleeding without an increased risk in thrombotic events. This narrative review article summarizes currently available evidence of antithrombotic therapy in patients with AF undergoing PCI.
Outcomes of pediatric endoscopic ultrasound‐guided celiac plexus block: A single center pilot study
Authors: Joseph Michael , Liu Edwin , Mark Jacob A. 
Published: August 2024

AbstractCeliac plexus blocks (CPBs) using endoscopic ultrasound (EUS) guidance provide significant pain relief in adults with chronic pancreatitis. We present on EUS‐guided CPB for pediatric patients with abdominal pain from chronic pancreatitis or severe functional dyspepsia necessitating clinically assisted nutrition and hydration. Patients who underwent EUS‐CPB were included and followed prospectively at 2‐, 4‐, and 8‐weeks postprocedure about pain, enteral tolerance, and school/activity attendance. Thirteen patients underwent EUS‐guided CPB with a total of 21 procedures. In the pancreatitis cohort, mean pain relief was 11.7 weeks for those who responded. In the functional dyspepsia cohort, mean improvement (in either pain or enteral tolerance) was 4.8 weeks. Symptom improvement varied between the two cohorts. Acute recurrent/chronic pancreatitis patients demonstrated more sustained relief than the functional dyspepsia cohort. This study adds to the limited data investigating the utility of EUS‐CPB as part of a multimodal treatment plan in pediatrics.
Long‐term stability of extra virgin olive oil: effects of filtration and refrigeration storage on the Kolovi variety
Authors: Lazarou Konstantina , Tsagkaris Aristeidis S. , Drakopoulou Sofia , Kyriakopoulos Antony M. , Martakos Ioannis , Pentogenis Michalis , Glyniadaki Maria , Kritikou Evangelia , Koupa Anastasia , Kostakis Marios , Proestos Charalampos , Dasenaki Marilena , Maragou Niki , Thomaidis Nikolaos 
Published: August 2024

AbstractBackgroundThe composition of extra virgin olive oil (EVOO) defines its sensory, nutritional, and human health benefits, and distinguishes it as a key component of the Mediterranean diet. Nevertheless, EVOO constituents are susceptible to degradation during processing and storage, which reduces the olive oil's quality and limits its shelf life. The present study investigated the effect of molecular filtration before storage and the effect of cool storage at 4 °C on the stability of ‘Kolovi’ EVOO, a variety originating from the Greek island of Lesvos, over a 24 month period.ResultsStoring EVOO at 4 °C positively affected free acidity, peroxide value, K268, fruity qualities, and concentrations of hydroxytyrosol, tyrosol, ligstroside aglycone, lutein, and squalene, in comparison with the control sample stored at room temperature, particularly after 1 year. Molecular filtration significantly affected the ratio of unsaturated fatty acids to saturated fatty acids (UFAs/SFAs). Optimal preservation of parameters such as acidity value and lutein content was achieved by combining molecular filtration with refrigeration.ConclusionsThe present study recommends storing EVOO in the refrigerator for up to 18 months. Based on the regulatory limits of the quality characteristics of acidity, peroxide value, K232 value and fruity sensory attributes, the shelf‐life of the protected geographical indication (PGI) ‘Kolovi’ EVOO can reach 2 years under cool storage (4 °C) and with molecular filtration before storage. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Investigating the impact of climate variables on the organic honey yield in Turkey using XGBoost machine learning
Authors: Sahin Demirel Ayca Nur 
Published: August 2024

AbstractBACKGROUNDThe Turkish organic honey industry, a major player in the global market, faces challenges due to climate fluctuations. Understanding the influence of climate factors on honey production is vital for sustainable farming and economic stability.METHODThis study uses a machine learning approach with the XGBoost algorithm to analyze temperature, wind, humidity, precipitation and surface pressure over a 20‐year period from 2004 to 2023.RESULTSThe results show that these factors significantly impact organic honey production, with temperature, wind, humidity, precipitation and surface pressure having effects of 41.20%, 26.50%, 12.47%, 11.42% and 8.41%, respectively. Sensitivity analysis reveals the model's sensitivity to even minor fluctuations in these variables.CONCLUSIONThe results of this research underscore the necessity of integrating climate change mitigation and adaptation measures into agricultural policies and beekeeping practices. This study showcases the practical application of machine learning in deciphering the intricate relationship between climate change and the production of crops, emphasizing the importance of data‐driven decision‐making to guarantee long‐term sustainability and financial stability in the sector. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
(+)‐Catechins Play a Protective Role in Diabetic Kidney Disease by Alleviating EMT through Multiple Pathways
Authors: Ni Ying , Zhu Dina , Chen Chao , Wang Fan , Miu Yanyan , Zhang Wensheng 
Published: August 2024

ScopeDiabetic nephropathy (DN), a complication of diabetes mellitus, is becoming a significant global health concern, with no complete cure currently available. Tea is regarded as an essential component of a balanced diet and contains (+)‐Catechin (CE), which exert a range of pharmacological effects. Consequently, CE may be a potential treatment for DN. The objective of this study is to examine the protective effects and underlying mechanisms of CE on DN, with a particular focus on the epithelial‐mesenchymal transition (EMT) process, which plays a pivotal role in regulating DN.Methods and resultsIn this study db/db mice are treated with catechins. The results demonstrate that CE reduces obesity and hyperglycemia, improves renal dysfunction and morphological changes in diabetic mice, and inhibits the development of DN through the RAGE/NF‐κB signaling pathway. Among them differentially expressed messenger RNA (mRNA) results, those related to EMT, including Cav1, grem2, macrod2, and kap, are identified. To further validate the results, the same experiments are performed on HK‐2 cells.ConclusionsThe research results offer novel perspectives by emphasizing the anti‐inflammatory properties of CE and their potential role in mitigating DN through the regulation of EMT‐related genes such as RAGE, Cav1, grem2, macrod2, and kap.
Optimizing solar photovoltaic and biomass integration for electric vehicle charging stations in metropolitan cities: A hybrid approach
Authors: Udaiyakumar S. , Kannayeram G. , Hariharan V. S. , Saravanan R. 
Published: August 2024

AbstractThis paper proposes a hybrid strategy for designing and optimizing a hybrid solar photovoltaic (PV) and biomass‐based electric vehicle charging station (EVCS) in metropolitan cities. The proposed strategy is the joint execution of the dung beetle optimizer (DBO) and Finite Basis Physics‐Informed Neural Networks Technique. It is hence called the DBO‐FBPINNs approach. The proposed strategy aims are to minimize initial cost and operating cost, net present cost, and levelized cost of energy. The design phase involves the energy storage systems, integration of solar PV panels, and biomass generators to warranty a reliable and continuous power supply for the EV charging infrastructure. Feasibility analysis encompasses various technical, economic, and environmental aspects. The converter's control signal is optimized via the DBO method. The FBPINNs model is used to forecast the optimal control parameters of the converter. By then, the proposed DBO‐FBPINNs method is implemented in the MATLAB platform and evaluated their performance with various present strategy's like deep neural network (DNN), fuzzy neural network (FNN), and recurrent neural network (RNN). When compared to other current technologies, the proposed strategy exhibits a low cost of $1.2.
Prenatal Diagnosis of Myhre Syndrome in Two Cases: Further Delineation of the Cardiac and External Phenotype
Authors: Jury Jeanne , Joubert Madeleine , Le Vaillant Claudine , Ghesh Leïla , Séguéla Pierre‐Emmanuel , Bruel Ange‐Line , Cogné Benjamin , Nizon Mathilde 
Published: August 2024

ABSTRACTMyhre syndrome is a rare genetic disease caused by recurrent gain‐of‐function variants in SMAD4 (Ile500Thr, Ile500Val, Arg496Cys, and Ile500Met) characterized by postnatal short stature with pseudo‐muscular build, joint stiffness, variable intellectual disability, hearing loss, and a distinctive pattern of dysmorphic facial features. The course can be severe in some cases, with life‐threatening cardiac and pulmonary complications caused by connective tissue involvement. These progressive features over time make early clinical diagnosis difficult but possible by astute clinicians who evaluate young children with autism or short stature and unusual appearance. Only two cases of Myhre syndrome diagnosed during the prenatal period have been reported. Here, we present a detailed description of two unrelated fetuses with Myhre syndrome, each molecularly confirmed by genome or exome sequencing, who underwent fetal examination after termination of pregnancy. One had severe intrauterine growth retardation associated with crossed fused renal ectopia, and the other one had pulmonary atresia with ventricular septal defect (a form of tetralogy of Fallot). Both had mild dysmorphic features with a wide nasofrontal angle. Our results and a systematic prenatal literature review add insight into the early natural history of Myhre syndrome and highlight the contribution of prenatal next‐generation sequencing in prenatal diagnosis and the importance of fetal autopsy in Myhre syndrome.
A Personalized Dose‐Finding Algorithm Based on Adaptive Gaussian Process Regression
Authors: Park Yeonhee , Chang Won 
Published: August 2024

ABSTRACTDose‐finding studies play a crucial role in drug development by identifying the optimal dose(s) for later studies while considering tolerability. This not only saves time and effort in proceeding with Phase III trials but also improves efficacy. In an era of precision medicine, it is not ideal to assume patient homogeneity in dose‐finding studies as patients may respond differently to the drug. To address this, we propose a personalized dose‐finding algorithm that assigns patients to individualized optimal biological doses. Our design follows a two‐stage approach. Initially, patients are enrolled under broad eligibility criteria. Based on the Stage 1 data, we fit a regression model of toxicity and efficacy outcomes on dose and biomarkers to characterize treatment‐sensitive patients. In the second stage, we restrict the trial population to sensitive patients, apply a personalized dose allocation algorithm, and choose the recommended dose at the end of the trial. Simulation study shows that the proposed design reliably enriches the trial population, minimizes the number of failures, and yields superior operating characteristics compared to several existing dose‐finding designs in terms of both the percentage of correct selection and the number of patients treated at target dose(s).
Ginsenoside Re inhibits non‐small cell lung cancer progression by suppressing macrophage M2 polarization induced by AMPKα1/STING positive feedback loop
Authors: Tang Xiaoyu , Zhu Man , Zhu Zeren , Tang Wenjun , Zhang Hongmei , Chen Yanbin , Liu Feng , Zhang Yanmin 
Published: August 2024

AbstractTumor‐associated macrophages (TAMs) in non‐small cell lung cancer (NSCLC) promote tumor cell metastasis by interacting with cancer cells. Ginsenoside Re is capable of modulating the host immune system and exerts anticancer effects through multiple pathways. Both AMPK and STING are involved in the regulation of MΦ polarization, thereby affecting tumor progression. However, whether there is a regulatory relationship between them and its effect on MΦ polarization and tumor progression is unclear. The aim of this study was to provide mechanistic evidence that ginsenoside Re modulates MΦ phenotype through inhibition of the AMPKα1/STING positive feedback loop and thus exerts an antimetastatic effect in NSCLC immunotherapy. Cell culture models and conditioned media (CM) systems were constructed, and the treated MΦ were analyzed by database analysis, RT‐PCR, Western blotting, flow cytometry, and immunofluorescence to determine the regulatory relationship between AMPK and STING and the effects of ginsenoside Re on MΦ polarization and tumor cells migration. The effects of ginsenoside Re (10, 20 mg/kg/day) on TAMs phenotype as well as tumor progression in mice were assessed by HE staining, immunohistochemical staining, and Western blotting. In this study, AMPKα1/STING positive feedback loop in NSCLC TAMs induced M2 type polarization, which in turn promoted NSCLC cell migration. In addition, ginsenoside Re was discovered to inhibit M2‐like MΦ polarization, thereby inhibiting NSCLC cell migration. Mechanistically, Re was able to inhibit the formation of the AMPKα1/STING positive feedback loop, thereby inhibiting its induction of M2‐like MΦ and consequently inhibiting the epithelial‐mesenchymal transition (EMT) process of NSCLC cells. Furthermore, in mouse models, Re was found to suppress LLC tumor growth and colonization by inhibiting M2‐type polarization of TAMs. Our finding indicates that ginsenoside Re can effectively modulate MΦ polarization and thus play an important role in antimetastatic immunotherapy of NSCLC.