bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of basic drug exposure in milk using a lactation model algorithm integrated within a physiologically based pharmacokinetic model
Authors: Pansari Amita , Faisal Muhammad , Jamei Masoud , Abduljalil Khaled 
Published: October 2022

AbstractMedication use during breastfeeding can be a matter of concern due to unintended infant exposure to drugs through breast milk. The available information relating to the safety of most medications is limited and may vary. More precise information is needed regarding the safety to the newborn or infants of the medications taken by the mother during breastfeeding. Physiologically based Pharmacokinetic Model (PBPK) approaches can be utilized to predict the drug exposure in the milk of breastfeeding women and can act as a supporting tool in the risk assessment of feeding infants. This study aims to assess the predictive performance of an integrated ‘log transformed phase‐distribution’ lactation model within a PBPK platform. The model utilizes the physicochemical properties of four basic drugs, namely tramadol, venlafaxine, fluoxetine, and paroxetine, and analyses the milk compositions to predict the milk‐to‐plasma (M/P) ratio. The M/P prediction model was incorporated within the Simcyp Simulator V20 to predict the milk exposure and to estimate the likely infant dose for these drugs. The PBPK models adequately predicted the maternal plasma exposure, M/P ratio, and the infant daily dose to within two‐fold of the clinically observed values for all four compounds. Integration of the lactation model within PBPK models facilitates the prediction of drug exposure in breast milk. The developed model can inform the design of lactation studies and assist with the neonatal risk assessment after maternal exposure to such environmental chemicals or basic drugs which diffuse passively into the milk.
Asymmetric inheritance of cytoophidia could contribute to determine cell fate and plasticity
Authors: Darekar Suhas , Laín Sonia 
Published: October 2022

AbstractTwo enzymes involved in the synthesis of pyrimidine and purine nucleotides, CTP synthase (CTPS) and IMP dehydrogenase (IMPDH), can assemble into a single or very few large filaments called rods and rings (RR) or cytoophidia. Most recently, asymmetric cytoplasmic distribution of organelles during cell division has been described as a decisive event in hematopoietic stem cell fate. We propose that cytoophidia, which could be considered as membrane‐less organelles, may also be distributed asymmetrically during mammalian cell division as previously described for Schizosaccharomyces pombe. Furthermore, because each type of nucleotide intervenes in distinct processes (e.g., membrane synthesis, glycosylation, and G protein‐signaling), alterations in the rate of synthesis of specific nucleotide types could influence cell differentiation in multiple ways. Therefore, we hypothesize that whether a daughter cell inherits or not CTPS or IMPDH filaments determines its fate and that this asymmetric inheritance, together with the dynamic nature of these structures enables plasticity in a cell population.
Is online self‐regulatory training effective in weight control? A pilot experiment on adolescence obesity during coronavirus‐19 lockdown
Authors: Rezaei Niyasar Asiyeh , Moradi Alireza , Radman Narges , Sadeghi Meysam , Mahmoudi Maryam 
Published: October 2022

AbstractObjectiveStudies have shown that obesity is associated with decreased executive function. Impaired executive functions lead to poor self‐regulation, which in turn may result in persistence of unhealthy behaviors, including eating behaviors, throughout life. Increasing self‐regulation in childhood and adolescence has positive effects on creating healthy behaviors such as reducing unnecessary eating and changing unhealthy eating habits. The main purpose of this study is to evaluate an intervention package based on cognitive self‐regulation training in changing eating behaviors and reducing obesity in children and adolescents.MethodsFifty‐six students with obesity aged 12–16 years participated in the study in three groups (cognitive self‐regulation training [CSRT], diet, and control). The CSRT group received twenty 30‐min online training sessions with a diet over 10 weeks. The diet group received only a diet with no other intervention, and the control group did not receive any intervention.ResultsThe results of our 2 × 3 repeated‐measures ANOVA showed that the CSRT group had a mean BMI decrease of 2.21 (kg/m2) after ten weeks, and 3.24 (kg/m2) at the follow‐up time. The diet group had a BMI decrease of 0.49 (kg/m2) at the ten weeks. In addition, the results showed that the CSRT had a significant reduction in eating behaviors such as external eating and emotional eating. However, the other two groups showed no changes in eating behaviors.ConclusionsOur results show that online cognitive self‐regulation training has been effective in weight loss and eating behaviors. This study shows promising evidence for the efficacy of the online CSRT‐training as a weight stabilization intervention in children with obesity.
Corticotropin‐releasing factor is involved in acute stress‐induced analgesia and antipruritus
Authors: Wang Xiao‐Dong , Bai Hao‐Miao , Li Xiao‐Lan , Zhang Lin‐Fang , Li Fei , Bai Yang , Wu Zhen‐Yu , Liu Shang‐Qing , Li Hui 
Published: October 2022

AbstractBackgroundUnder the condition of stress, the hypothalamic–pituitary–adrenal axis (HPA axis) is activated and causes the secretion of corticotropin‐releasing factor (CRF). Previous studies have demonstrated that CRF is involved in the regulation of pain and itch. Thus, it remains worthy to explore whether the desensitization of pain and itch under high‐intensity acute stress (such as high fear and tension) is related to the sharp increase of CRF.MethodsForced swimming was used to simulate acute stress. ELISA and pharmacological methods were conducted to observe the effects of forced swimming on acute pain or itch and the relationship between blood CRF content and itch or pain behavior. Intracerebroventricular (ICV) administration of CRF was conducted to examine the effects of CRF on acute pain or itch. Intrathecal administration of CRF receptor agonist or antagonist was conducted to examine the receptor mechanisms of the regulatory role of CRF in pain and itch.ResultsELISA experiment showed that the serum CRF in mice reached its peak within 5–10 min after acute stress (forced swimming). Behavioral data showed that the scratching behavior induced by itch agents decreased after acute swimming, while the mechanical pain threshold increased significantly. The inhibitory effect of acute stress on pain and itch is mediated by CRF receptor2 (CRFR2). Then, ICV injection of CRF was used to simulate the massive release of CRF under acute stress, and we observed that the scratching behavior induced by histamine or chloroquine was significantly inhibited after ICV injection of CRF. The above effects of CRF are mainly mediated by CRFR2. These results suggest that 5–10 min after acute stress, a large amount of CRF is released into the blood from the hypothalamus, which significantly inhibits acute pain and itch by acting on CRFR2. ICV injection of CRF can replicate the antipruritus effects of acute stress.ConclusionsThe present study investigated the mechanism of acute stress‐induced analgesia and antipruritus and provided theoretical support for the treatment of pain and itch.
N‐acetyltransferase 10 promotes colon cancer progression by inhibiting ferroptosis through N4‐acetylation and stabilization of ferroptosis suppressor protein 1 (FSP1) mRNA
Authors: Zheng Xiao , Wang Qi , Zhou You , Zhang Dachuan , Geng Yiting , Hu Wenwei , Wu Changping , Shi Yufang , Jiang Jingting 
Published: October 2022

AbstractBackgroundN‐acetyltransferase 10 (NAT10) is the only enzyme known to mediate the N4‐acetylcytidine (ac4C) modification of mRNA and is crucial for mRNA stability and translation efficiency. However, its role in cancer development and prognosis has not yet been explored. This study aimed to examine the possible role of NAT10 in colon cancer.MethodsThe expression levels of NAT10 were evaluated by immunohistochemical analyses with a colon cancer tissue microarray, and its prognostic value in patients was further analyzed. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blotting were performed to analyze NAT10 expression in harvested colon cancer tissues and cell lines. Stable NAT10‐knockdown and NAT10‐overexpressing colon cancer cell lines were constructed using lentivirus. The biological functions of NAT10 in colon cancer cell lines were analyzed in vitro by Cell Counting Kit‐8 (CCK‐8), wound healing, Transwell, cell cycle, and ferroptosis assays. Xenograft models were used to analyze the effect of NAT10 on the tumorigenesis and metastasis of colon cancer cells in vivo. Dot blotting, acetylated RNA immunoprecipitation‐qPCR, and RNA stability analyses were performed to explore the mechanism by which NAT10 functions in colon cancer progression.ResultsNAT10 was upregulated in colon cancer tissues and various colon cancer cell lines. This increased NAT10 expression was associated with shorter patient survival. Knockdown of NAT10 in two colon cancer cell lines (HT‐29 and LoVo) impaired the proliferation, migration, invasion, tumor formation and metastasis of these cells, whereas overexpression of NAT10 promoted these abilities. Further analysis revealed that NAT10 exerted a strong effect on the mRNA stability and expression of ferroptosis suppressor protein 1 (FSP1) in HT‐29 and LoVo cells. In these cells, FSP1 mRNA was found to be modified by ac4C acetylation, and this epigenetic modification was associated with the inhibition of ferroptosis.ConclusionsOur study revealed that NAT10 plays a critical role in colon cancer development by affecting FSP1 mRNA stability and ferroptosis, suggesting that NAT10 could be a novel prognostic and therapeutic target in colon cancer.
Current updates of CRISPR/Cas9‐mediated genome editing and targeting within tumor cells: an innovative strategy of cancer management
Authors: Allemailem Khaled S. , Alsahli Mohammed A , Almatroudi Ahmad , Alrumaihi Faris , Alkhaleefah Fahd Khaleefah , Rahmani Arshad Husain , Khan Amjad Ali 
Published: October 2022

AbstractClustered regularly interspaced short palindromic repeats‐associated protein (CRISPR/Cas9), an adaptive microbial immune system, has been exploited as a robust, accurate, efficient and programmable method for genome targeting and editing. This innovative and revolutionary technique can play a significant role in animal modeling, in vivo genome therapy, engineered cell therapy, cancer diagnosis and treatment. The CRISPR/Cas9 endonuclease system targets a specific genomic locus by single guide RNA (sgRNA), forming a heteroduplex with target DNA. The Streptococcus pyogenes Cas9/sgRNA:DNA complex reveals a bilobed architecture with target recognition and nuclease lobes. CRISPR/Cas9 assembly can be hijacked, and its nanoformulation can be engineered as a delivery system for different clinical utilizations. However, the efficient and safe delivery of the CRISPR/Cas9 system to target tissues and cancer cells is very challenging, limiting its clinical utilization. Viral delivery strategies of this system may have many advantages, but disadvantages such as immune system stimulation, tumor promotion risk and small insertion size outweigh these advantages. Thus, there is a desperate need to develop an efficient non‐viral physical delivery system based on simple nanoformulations. The delivery strategies of CRISPR/Cas9 by a nanoparticle‐based system have shown tremendous potential, such as easy and large‐scale production, combination therapy, large insertion size and efficient in vivo applications. This review aims to provide in‐depth updates on Streptococcus pyogenic CRISPR/Cas9 structure and its mechanistic understanding. In addition, the advances in its nanoformulation‐based delivery systems, including lipid‐based, polymeric structures and rigid NPs coupled to special ligands such as aptamers, TAT peptides and cell‐penetrating peptides, are discussed. Furthermore, the clinical applications in different cancers, clinical trials and future prospects of CRISPR/Cas9 delivery and genome targeting are also discussed.
SDCBP‐AS1 destabilizes β‐catenin by regulating ubiquitination and SUMOylation of hnRNP K to suppress gastric tumorigenicity and metastasis
Authors: Han Jing , Nie Menglin , Chen Cong , Cheng Xiaojing , Guo Ting , Huangfu Longtao , Li Xiaomei , Du Hong , Xing Xiaofang , Ji Jiafu 
Published: October 2022

AbstractBackgroundGastric cancer (GC) is among the most malignant tumors, yet the pathogenesis is not fully understood, especially the lack of detailed information about the mechanisms underlying long non‐coding RNA (lncRNA)‐mediated post‐translational modifications. Here, the molecular mechanisms and clinical significance of the novel lncRNA syndecan‐binding protein 2‐antisense RNA 1 (SDCBP2‐AS1) in the tumorigenesis and progression of GC were investigated.MethodsThe expression levels of SDCBP2‐AS1 in 132 pairs of GC and adjacent normal tissues were compared, and the biological functions were assessed in vitro and in vivo. RNA pull‐down and immunoprecipitation assays were conducted to clarify the interactions of SDCBP2‐AS1 and heterogeneous nuclear ribonucleoprotein (hnRNP) K. RNA‐sequencing, immunoprecipitation, immunofluorescence, and luciferase analyses were performed to investigate the functions of SDCBP2‐AS1.ResultsSDCBP2‐AS1 was significantly downregulated in GC tissues and predictive of poor patient prognosis. Silencing of SDCBP2‐AS1 promoted the proliferation and migration of GC cells both in vitro and in vivo. Mechanically, SDCBP2‐AS1 physically bound to hnRNP K to repress SUMOylation of hnRNP K and facilitated ubiquitination of hnRNP K and β‐catenin, thereby promoting the degradation of β‐catenin in the cytoplasm. Silencing of SDCBP2‐AS1 caused SUMOylation of hnRNP K and stabilized β‐catenin activity, which altered transcription of downstream genes, resulting in tumorigenesis and metastasis of GC. Moreover, the knockdown of hnRNP K partially abrogated the effects of SDCBP2‐AS1.ConclusionsSDCBP2‐AS1 interacts with hnRNP K to suppress tumorigenesis and metastasis of GC and regulates post‐transcriptional modifications of hnRNP K to destabilize β‐catenin. These findings suggest SDCBP2‐AS1 as a potential target for the treatment of GC.
A comparison of men and women referred to provincial correctional mental health services in Ontario, Canada
Authors: Ray Ipsita , Fulham Lindsay , Simpson Alexander I. , Vogel Tobias , Gerritsen Cory , Patel Kiran , Jones Roland M. 
Published: October 2022

AbstractBackgroundWomen comprise around 15% of admissions to provincial correctional institutions in Canada. Women in custody are known to have a high prevalence of mental health concerns, but little is known about how those referred to mental health services compare with referred men at a similar stage of imprisonment.AimsOur aim was to describe and compare clinical, social and demographic characteristics of a complete cohort of custodially remanded men and women who were referred to mental health services while under custodial remand in two correctional institutions.MethodsWe carried out retrospective analysis of data obtained from 4040 men and 1734 provincially detained women referred to mental health services in two correctional centres holding mainly pre‐trial prisoners and serving a large mixed urban‐rural catchment area in Toronto, Canada over a nearly five‐year period. Men and women were first screened using the Brief Jail Mental Health Screen. Those who screened positive were assessed using the Jail Screening Assessment Tool the Brief Psychopathology Rating Scale—Expanded (BPRS‐E) and the Clinical Global Impression—Corrections (CGI‐C).ResultsThere were many similarities between men and women, but also some important differences. Women were more socioeconomically disadvantaged than men. More women than men reported having children, yet fewer reported having any form of employment or social supports, although men were more likely to report unstable housing. In addition, women were significantly more likely to have mood and anxiety problems and to be self‐harming, but did not differ from men in current psychotic symptoms. We also found differences in patterns of substance use, with a higher proportion of women using heroin and methamphetamines but fewer women having accessed addiction services.ConclusionsOur findings have implications for clinicians and service planners. They underscore the value of systematic screening for identifying need. More specifically, they suggest need for increased availability of addiction services for women as well as ensuring support for those women who have dependent‐age children. Improvement in supports for entry into employment is particularly needed for women, while men are particularly likely to need access to stable housing.
Hemangioma of the umbilical cord: A case report on a rare entity
Authors: Ben Thayer Maissa , Helal Imen , Khanchel Fatma , Mbarki Chaouki , Bettaieb Hajer , Ben Brahim Ehsen , Jouini Raja , Chadli Debbiche Aschraf 
Published: October 2022

AbstractSeveral hundred cases of placental hemangiomas have been reported in the literature. However, the umbilical cord is extremely uncommon as a site of occurrence. We present a case of postnatal discovery of giant hemangioma of the umbilical cord (HUM) in a Coronavirus Disease 2019 (COVID 19) positive mother. To our knowledge, this is the first reported case of HUM synchronous to a maternal infection with COVID 19. We aim, through this case and a review of the literature, to study the clinicopathological characteristics of this singular entity. Our patient, a 37‐year‐old woman, presented to the Department Of Obstetrics And Gynecology for respiratory distress and loss of fetal movements. Ultrasound examination concluded to intrauterine fetal desmise. After stabilization of the patient, a cesarean section was performed. A macerated fetus was extracted. Placenta showed a giant mass attached to the cord. It was submitted for pathological examination. Gross examination showed that the umbilical cord was inserted eccentrically with a fusiform dilation. Near its placental end, three cohesive solid angiomatous nodules were noted. Microscopic examination revealed lobules of dilated blood‐filled capillaries set in a myxoid stroma. The diagnosis of HUM have been established. HUM arise from endothelial cells of the umbilical vessels. Their etiology, physio‐pathology and pathways of tumorigenesis are not yet well defined. Further studies are needed to explore the pathways of tumorigenesis and to determin the implication of COVID‐19 in HUM.
Modelling temperature dynamics of the SAGD process in an oil reservoir by the discovery of parametric partial differential equations
Authors: Raviprakash Kiran , Ganesh Ajay , Huang Biao , Prasad Vinay 
Published: October 2022

AbstractMany chemical and industrial processes are complex, and the dynamics of such processes cannot be explained using a partial differential equation (PDE) or a system of PDEs with constant coefficients. Parametric PDEs, that is, PDEs with their coefficients varying across time or space, are utilized for this purpose. The non‐availability of data at all spatial locations and partially available process knowledge add to the complexity of modelling such processes. This paper proposes a framework to discover parametric PDEs using data‐driven and hybrid modelling approaches with the temperature dynamics of steam‐assisted gravity drainage (SAGD) process in an oil reservoir as the system under study. We utilize an ensemble of 200 realizations of the temperature dynamics generated using the variogram for the PDE discovery. Permeability, which is one of the oil reservoir's petrophysical properties, is used to develop the hybrid models. We infer that utilizing partial process knowledge aids in improving the model's accuracy.
Transient multiphase CO2 release from high‐pressure tanks: Influence of phase changes, viscous heating, and Joule–Thomson effect
Authors: Fiore Piergiuseppe , Coppola Michela , Meninno Paola , Sannino Maddalena , De Marco Giuseppe , Sacco Serafino , Caravella Alessio 
Published: October 2022

AbstractIn this study, CO2 free expansion from high‐pressure tanks is studied in a transient state while considering the influence of different phenomena—that is, viscous heating, phase transition (solid/liquid/vapour phase), and the Joule–Thomson effect—in an initially supersonic flow. This investigation is performed using computational fluid dynamics (CFD) techniques, comparing the obtained results with some experimental data of the literature with a maximum discrepancy of around 8.5%. In particular, for the first time from the literature, it is observed that, according to the velocity evolution at the outlet, the discharge process is conveniently divided into three here‐defined stages: (1) shocking flow, where pressure abruptly decreases with time and flow becomes supersonic, this leading to the condensation of part of CO2; (2) transition flow, characterized by a sort of constant pressure time trend; and (3) flashing flow, where pressure decreases less abruptly following an asymptotic pattern up to the atmospheric one and flow becomes subsonic. Furthermore, non‐equilibrium condensation occurring in the tank, tube, and outlet is observed, finding that the minimum temperature reached by the fluid is around 235 K (−38°C). As well, the non‐equilibrium condensation is taken into account in order to give an indication of the amount of liquid CO2 leaving the outlet in the form of high‐speed jet, which can be a serious danger for personnel and surrounding installations. Moreover, we observe an important effect of viscous heating in the early‐stage expansion for a relatively short time range, within which the temperature in the tube experiences an abrupt increase of around 210 K (from 170 to 380 K). The same effect in the external room creates a convection flow, pushing CO2 towards the top. The results of the present work can be used for health, safety, and environment (HSE) management purposes and for a more precise process design related to CO2 storage and sequestration.
Optimizing the extraction of cobalt ions under response surface methodology and without organic solutions
Authors: Sobhi Amjad Razieh , Asadollahzadeh Mehdi , Torkaman Rezvan , Torab‐Mostaedi Meisam 
Published: October 2022

AbstractIn this study, response surface methodology was used to evaluate the extraction of cobalt ions using an aqueous two‐phase system (ATPS). This method is environmentally benign and low‐risk because water has replaced the poisonous and dangerous organic solvents in this extraction procedure. For the first time, a central composite design was employed to examine the effect of various factors on the extraction of cobalt ions. The findings of the experimental design revealed that the concentration and volume of cobalt ions had a considerable impact on the extraction percentage in the ATPS system. In contrast, the concentration of ammonium sulphate and pH had only a minor effect. The value of the correlation coefficient (R2 = 0.9565) clearly shows the agreement between the mathematical model and the experimental results. The maximum extraction percentage was attained in optimum conditions (50% polyethylene glycol concentration, 3.75 M salt concentration, 0.5 ml cobalt volume, and pH 4).