bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dinaciclib as an effective pan-cyclin dependent kinase inhibitor in platinum resistant ovarian cancer
Authors: Howard David , James David , Garcia-Parra Jezabel , Pan-Castillo Belen , Worthington Jenny , Williams Nicole , Coombes Zoe , Rees Sophie Colleen , Lutchman-Singh Kerryn , Francis Lewis W. , Rees Paul , Margarit Lavinia , Conlan R. Steven , Gonzalez Deyarina 
Published: November 2022

BackgroundOvarian cancer (OC) is amongst the most lethal of common cancers in women. Lacking in specific symptoms in the early stages, OC is predominantly diagnosed late when the disease has undergone metastatic spread and chemotherapy is relied on to prolong life. Platinum-based therapies are preferred and although many tumors respond initially, the emergence of platinum-resistance occurs in the majority of cases after which prognosis is very poor. Upregulation of DNA damage pathways is a common feature of platinum resistance in OC with cyclin dependent kinases (CDKs) serving as key regulators of this process and suggesting that CDK inhibitors (CDKis) could be effective tools in the treatment of platinum resistant and refractory OC.AimThe aim of this study was to evaluate the efficacy of CDKis in platinum resistant OC models and serve as a predictor of potential clinical utility.MethodsThe efficacy of CDKi, dinaciclib, was determined in wildtype and platinum resistant cell line pairs representing different OC subtypes. In addition, dinaciclib was evaluated in primary cells isolated from platinum-sensitive and platinum-refractory tumors to increase the clinical relevance of the study.Results and conclusionsDinaciclib proved highly efficacious in OC cell lines and primary cells, which were over a thousand-fold more sensitive to the CDKi than to cisplatin. Furthermore, cisplatin resistance in these cells did not influence sensitivity to dinaciclib and the two drugs combined additively in both platinum-sensitive and platinum-resistant OC cells suggesting a potential role for pan-CDKis (CDKis targeting multiple CDKs), such as dinaciclib, in the treatment of advanced and platinum-resistant OC.
Pharmacogenetics-based population pharmacokinetic analysis and dose optimization of valproic acid in Chinese southern children with epilepsy: Effect of ABCB1 gene polymorphism
Authors: Shen Xianhuan , Chen Xinyi , Lu Jieluan , Chen Qing , Li Wenzhou , Zhu Jiahao , He Yaodong , Guo Huijuan , Xu Chenshu , Fan Xiaomei 
Published: November 2022

Objective: The aim of this study was to establish a population pharmacokinetic (PPK) model of valproic acid (VPA) in pediatric patients with epilepsy in southern China, and provide guidance for individualized medication of VPA therapy.Methods: A total of 376 VPA steady-state trough concentrations were collected from 103 epileptic pediatric patients. The PPK parameter values for VPA were calculated by using the nonlinear mixed-effects modeling (NONMEM) method, and a one-compartment model with first-order absorption and elimination processes was applied. Covariates included demographic information, concomitant medications and selected gene polymorphisms. Goodness-of-fit (GOF), bootstrap analysis, and visual predictive check (VPC) were used for model evaluation. In addition, we used Monte Carlo simulations to propose dose recommendations for different subgroup patients.Results: A significant effect of the patient age and ABCB1 genotypes was observed on the VPA oral clearance (CL/F) in the final PPK model. Compared with patients with the ABCB1 rs3789243 AA genotype, CL/F in patients with GG and AG genotypes was increased by 8% and reduced by 4.7%, respectively. The GOF plots indicated the satisfactory predictive performance of the final model, and the evaluation by bootstrap and VPC showed that a stable model had been developed. A table of individualized dosing regimens involving age and ABCB1 genotype was constructed based on the final PPK model.Conclusion: This study quantitatively investigated the effects of patient age and ABCB1 rs3789243 variants on the pharmacokinetic variability of VPA. The PPK models could be beneficial to individual dose optimization in epileptic children on VPA therapy.
Assessment of the effectiveness and efficiency of the West Africa medicines regulatory harmonization initiative by the member countries
Authors: Owusu-Asante Mercy , Darko Delese Mimi , Walker Stuart , Salek Sam 
Published: November 2022

Background: The West Africa Health Organization launched the West Africa Medicines Regulatory Harmonization Project (WA-MRH) in 2017 with the overarching objective to improve the availability of high-quality, safe and effective medicines and vaccines by the 15 countries in the Economic Community of West African States region. Although this project has made significant progress towards the realisation of its goals, challenges still remain. The aims of this study were to evaluate the effectiveness and efficiency of the WA-MRH, examine what challenges are being encountered and identify strategies that would strengthen the process for realising the initiative’s goals.Methods: The Process Effectiveness and Efficiency Rating (PEER) questionnaire was used to collect data from assessors representing the seven active NMRAs in the joint assessment procedure that identified the benefits, challenges and recommendations for improving the performance of the WA-MRH project.Results: The benefits of the joint assessment procedure include time savings to manufacturers resulting from submitting one dossier and the same response package to multiple countries resulting in access to the multiple African markets within the same timeframe. Additionally, some of the NMRAs have been able to strengthen their technical capacity as a result of this initiative. Key challenges to the project include the lack of a robust information technology system that would enable dossier tracking and constraints in human resources needed to support dossier submissions and the assessment process.Conclusion: This study identified the strengths of the WA-MRH initiative as well as strategies for improvement and achievement of its objectives. The centralised submission of a dossier and its tracking is key to the regulatory assessment process. This research has demonstrated that amongst other considerations, a robust information technology system, coupled with the necessary human resource capacity would greatly enhance the effectiveness and efficiency of the WA-MRH initiative.
Monsoon intensification in East Asia triggered the evolution of its flora
Authors: Ye Jun-Wei , Tian Bin , Li De-Zhu 
Published: November 2022

IntroductionEast Asia (EA), which falls within the region of the Asian monsoon that is composed of the East Asia monsoon (EAM) and the Indian monsoon (IM), is known for its high species diversity and endemism. This has been attributed to extreme physiographical heterogeneity in conjunction with climate and sea-level changes during the Pleistocene, this hypothesis has been widely proven by phylogeographic studies. Recently, dated phylogenies have indicated that the origins (stem age) of the flora occurred after the Oligocene–Miocene boundary and are related to the establishment of the EAM.MethodsHence, this study further examined whether the strengthening of the monsoons triggered floral evolution via a meta-analysis of the tempo-spatial pattern of evolutionary radiation dates (crown ages) of 101 endemic seed plant genera.ResultsTaxonomic diversification began during the late Eocene, whereas the accumulated number of diversifications did not significantly accelerate until the late Miocene. The distribution of the weighted mean and the average divergence times in the EAM, IM, or transitional regions all fall within the mid-late Miocene. Fossils of the Tertiary relict genera are mostly and widely distributed outside EA and only half of the earliest fossils in the EA region are not older than Miocene, while their divergence times are mostly after the late Miocene. The pattern of divergence time of monotypic and polytypic taxa suggest the climatic changes after the late Pliocene exert more influence on monotypic taxa.DiscussionThe two key stages of floral evolution coincide with the intensifications of the EAM and IM, especially the summer monsoon which brings a humid climate. An integrated review of previous studies concerning flora, genus, and species levels further supports our suggestion that monsoon intensification in EA triggered the evolution of its flora.
Effects of chilling on the photosynthetic performance of the CAM orchid Phalaenopsis
Authors: Daems Stijn , Ceusters Nathalie , Valcke Roland , Ceusters Johan 
Published: November 2022

IntroductionCrassulacean acid metabolism (CAM) is one of the three main metabolic adaptations for CO2 fixation found in plants. A striking feature for these plants is nocturnal carbon fixation and diurnal decarboxylation of malic acid to feed Rubisco with CO2 behind closed stomata, thereby saving considerable amounts of water. Compared to the effects of high temperatures, drought, and light, much less information is available about the effects of chilling temperatures on CAM plants. In addition a lot of CAM ornamentals are grown in heated greenhouses, urging for a deeper understanding about the physiological responses to chilling in order to increase sustainability in the horticultural sector.MethodsThe present study focuses on the impact of chilling temperatures (10°C) for 3 weeks on the photosynthetic performance of the obligate CAM orchid Phalaenopsis ‘Edessa’. Detailed assessments of the light reactions were performed by analyzing chlorophyll a fluorescence induction (OJIP) parameters and the carbon fixation reactions by measuring diel leaf gas exchange and diel metabolite patterns.Results and DiscussionResults showed that chilling already affected the light reactions after 24h. Whilst the potential efficiency of photosystem II (PSII) (Fv/Fm) was not yet influenced, a massive decrease in the performance index (PIabs) was noticed. This decrease did not depict an overall downregulation of PSII related energy fluxes since energy absorption and dissipation remained uninfluenced whilst the trapped energy and reduction flux were upregulated. This might point to the presence of short-term adaptation mechanisms to chilling stress. However, in the longer term the electron transport chain from PSII to PSI was affected, impacting both ATP and NADPH provision. To avoid over-excitation and photodamage plants showed a massive increase in thermal dissipation. These considerations are also in line with carbon fixation data showing initial signs of cold adaptation by achieving comparable Rubisco activity compared to unstressed plants but increasing daytime stomatal opening in order to capture a higher proportion of CO2 during daytime. However, in accordance with the light reactions data, Rubisco activity declined and stomatal conductance and CO2 uptake diminished to near zero levels after 3 weeks, indicating that plants were not successful in cold acclimation on the longer term.
The influence of social constraints on the quality of life of hematopoietic stem cell transplantation survivors: The chain mediating effect of illness perceptions and the fear of cancer recurrence
Authors: Shen Zhiying , Shi Shuangjiao , Li Chengyuan , Ruan Chunhong 
Published: November 2022

ObjectiveThis cross-sectional correlational study aims to explore the relationship between social constraints and the quality of life of hematopoietic stem cell transplantation (HCT) survivors. Additionally, we also seek to demonstrate the chain mediating effect of illness perceptions and the fear of cancer recurrence on this relationship.MethodsConvenience sampling was employed in this study. A total of 232 HCT survivors were interviewed using the Social Constraints Scale, the Brief Illness Perception Questionnaire, the Fear of Cancer Recurrence Inventory (Short Form) and the Functional Assessment of Cancer Therapy–Bone Marrow Transplant. IBM SPSS 24.0 were used for data analyses, and PROCESS macro (Model 6) was used to examine the hypothesized chain mediation model.ResultsA positive relationship between social constraints and quality of life verified the mediating effect of illness perceptions and the fear of cancer recurrence on this relationship. Social constraints affect the quality of life of HCT survivors via three pathways: the mediating role of illness perceptions, the mediating role of fear of cancer recurrence and the chain mediating effect of both factors.ConclusionThe chain mediating effect of illness perceptions and the fear of cancer recurrence on quality of life indicates that these two variables have important practical significance with respect to improving HCT survivors’ physical and mental health. The study thus serves as a reference for health workers to improve HCT survivors’ quality of life in the future.
How do compulsory citizenship behaviors affect moral disengagement in organizations? Significance of anger toward the organization during the COVID-19 pandemic
Authors: Yildiz Bora , Yildiz Harun , Ozbilgin Mustafa 
Published: November 2022

BackgroundWith the COVID-19 pandemic, healthcare professionals, especially nurses, are confronted with an intensified workload. The literature on compulsory citizenship behaviors and their consequences is still far from explaining the cognitive and emotional mechanisms that underlie this relationship.MethodsDrawing on the resource depletion theory, we unpack the mechanism by which compulsory citizenship behaviors influence moral disengagement with the mediation effects of anger toward the organization. We are reporting a cross-sectional survey of nurses (n = 294) in private and public hospitals in Istanbul, Turkey. The data analysis involved structural equation modeling and Bayesian mediation.ResultsThe study revealed that compulsory citizenship behaviors positively influenced anger toward the organization and moral disengagement. Further, anger toward the organization mediates the link between compulsory citizenship behaviors and moral disengagement. Likewise, the Bayesian mediation analysis indicated that the proportion mediated (PM), which ensures a prediction of the extent to which the pathway explains the total effect through the mediation effect, was 33.74%.ConclusionThe findings show that exposure to compulsory citizenship behaviors lead to negative emotional (anger toward to organization) and cognitive (moral disengagement) consequences in nurses.Practical implicationsHospital managers should not force nurses to display discretionary work tasks outside their job descriptions. Providing an organizational milieu where voluntarily extra-role behaviors are encouraged may help reduce nurses’ moral disengagement and, in turn, ease their anger toward the organization.
Preliminary validation of a brief PROM assessing psychological distress in patients with malignant mesothelioma: The mesothelioma psychological distress tool—Patients
Authors: Guglielmucci Fanny , Bonafede Michela , Azzolina Danila , Marinaccio Alessandro , Franzoi Isabella Giulia , Migliore Enrica , Mensi Carolina , Chellini Elisabetta , Romeo Elisa , Grosso Federica , Granieri Antonella 
Published: November 2022

ObjectivePsychological suffering in malignant mesothelioma (MM) differs from that in other cancers because of its occupational etiology, and we aimed to develop specific patient-reported outcome measures to assess it.MethodsWe used a multi-method prospective observational multicentric study (N = 149), and a preliminary questionnaire validation was performed through a Bayesian approach.ResultsItem analysis showed a good internal consistency and reliability (Cronbach alpha = 0.79 [95% CI = 0.74–0.93]. Twenty of the 41 initial items were selected as posterior 95% highest density interval factor loading standardized effect size fell outside of the region of practical equivalence. Bayesian exploratory factor analysis showed a two-factor structure: (1) Trauma-related reactions (TR, 13 items) and (2) Claim for justice (CJ, 7 items), confirmed by the Bayesian confirmatory factor analysis. Latent factors were poorly correlated (Posterior median: 0.13; 95% CI = −0.079 to 0.323). The 90% root mean square error of approximation posterior median was 0.04 [90% CI = 0.03–0.58]; the 90% chi-square posterior median was 242 [90% CI = 209–287].ConclusionPsychological suffering in MM patients implies negative cognitive, emotional, and somatic reactions related to the traumatic impact of the disease and the need to obtain justice through economic compensation. Our findings provide preliminary evidence that the Mesothelioma Psychological Distress Tool-Patients could be a promising and reliable instrument to assess MM patients’ psychological distress.
Impact of the COVID-19 pandemic and the Russia-Ukraine war on stress and anxiety in students: A systematic review
Authors: Limone Pierpaolo , Toto Giusi Antonia , Messina Giovanni 
Published: November 2022

BackgroundThe outbreak of the COVID-19 pandemic at the end of 2019 and the Russian-Ukrainian war in February 2022 created restrictions and uncertainties that affected the general population’s mental health. One of the affected groups was students. This systematic review summarizes the current literature on the prevalence, outcomes, and interventions for stress and anxiety among university, college, graduate, or postsecondary populations.MethodsA systematic literature search was performed on PubMed, Web of Science, Scopus, Embase, Cochrane Library, CINAHL, PsychInfo, and ProQuest, following PRISMA guidelines. Specific inclusion and exclusion criteria were applied, and screening was performed to identify the definitive studies.ResultsThe prevalence of anxiety was relatively high, ranging from 88.9 to 13.63%, and the prevalence of stress ranged from 56 to 28.14%. The predictors of stress and anxiety included young age, gender being female, STEM course, loneliness, low academic level in school, urban lockdown, confinement, having a preexisting disease, having relatives or friends infected with COVID-19, and proximity to a COVID-19 zone. The predictors of stress included gender being female, living with family, living in a household with many people, being confined rather than having the freedom to relocate, proximity to confirmed cases of COVID-19, lack of access to materials on COVID-19, preexisting mental disorders, and lack of knowledge on the preventable nature of COVID-19. The sources of anxiety among the university students identified in the study included academics, postponement of graduation, cancelation or disruption of planned events, inability to achieve goals, and finances. In addition, the students used trauma-focused, forward-focused, task-oriented, emotion-oriented, and avoidance-oriented coping strategies.ConclusionThe included studies showed that stress and anxiety increased during the pandemic and the war, with gender and uncertainty playing a critical role. The studies provide insights into the widespread use of problem-focused and task-focused coping strategies despite their impact on increasing stress and anxiety.
Biochemical, hematologic, and skeletal features associated with underweight, overweight, and eating disorders in young Korean women: A population-based study
Authors: An Zhen , Kim Kyung-Hee , Kim Mirihae , Kim Youl-Ri 
Published: November 2022

BackgroundExtreme weight conditions in young women are associated with adverse health outcomes. Closely linked with extreme weight status, eating disorders (EDs) are associated with several medical complications and high mortality rates.ObjectiveThe study aimed to investigate the biochemical, hematologic, and skeletal features of young Korean women with underweight (UW) and overweight/obesity (OW) conditions, and patients with anorexia nervosa (AN) and bulimia nervosa (BN) compared to women with normal-weight (NW).MethodA total of 808 women (mean age 22.3 ± 3.4 years) were recruited for the study, including 144 with UW status [body mass index (BMI) &lt; 18.5 kg/m2], 364 with NW, 137 with OW or obesity (27 with obesity; BMI ≥ 25 kg/m2), 63 patients with anorexia nervosa (AN), and 100 with bulimia nervosa (BN). We measured blood pressure and performed biochemical, hematologic and bone mineral density (BMD) evaluations at the lumbar and femoral neck.ResultsBlood pressure and triiodothyronine levels were found to be lower in both ED groups and higher in the OW group, but no difference in the UW group, compared to the NW group. The aminotransferases and total cholesterol levels were higher in the ED and OW groups, compared to the NW group. Blood cell counts were decreased in the AN group, while increased in the OW group, compared to the NW group. Blood urea nitrogen was elevated in both ED groups. The UW and AN groups had lower BMD, whereas the OW group had higher BMD, compared to the NW group.ConclusionOur findings suggested that both ED groups were associated with decreases in the resting energy expenditure. OW status was associated with a risk of metabolic syndrome, and UW status with lower BMD in young women. Overall, the medical parameters in Korean patients with ED were similar to the patterns reported in Western samples in previous studies, with few exceptions such as potassium level in BN.
Holding on or letting go? Patient experiences of control, context, and care in oral esketamine treatment for treatment-resistant depression: A qualitative study
Authors: Breeksema Joost J. , Niemeijer Alistair , Kuin Bouwe , Veraart Jolien , Kamphuis Jeanine , Schimmel Nina , van den Brink Wim , Vermetten Eric , Schoevers Robert 
Published: November 2022

BackgroundKetamine and its enantiomer esketamine represent promising new treatments for treatment-resistant depression (TRD). Esketamine induces acute, transient psychoactive effects. How patients perceive esketamine treatment, and which conditions facilitate optimal outcomes, remains poorly understood. Understanding patient perspectives on these phenomena is important to identify unmet needs, which can be used to improve (es)ketamine treatments.AimsTo explore the perspectives of TRD patients participating in “off label” oral esketamine treatment.Materials and methodsIn-depth interviews were conducted with 17 patients (11 women) after a six-week, twice-weekly esketamine treatment program, and subsequently after six months of at-home use. Interviews explored participants’ perspectives, expectations, and experiences with esketamine treatment. Audio interviews were transcribed verbatim and analysed following an Interpretative Phenomenological Analysis (IPA) framework.ResultsKey themes included overwhelming experiences; inadequate preparation; letting go of control; mood states influencing session experiences; presence and emotional support, and supportive settings. Patients’ attempts to let go and give into vs. attempts to maintain control over occasionally overwhelming experiences was a central theme. Multiple factors influenced patients’ ability to give into the experience and appeared to impact their mood and anxiety about future sessions, including level of preparation and education, physical and emotional support, and setting during the session.ConclusionBetter preparation beforehand, an optimized treatment setting, and emotional and psychological support during (es)ketamine sessions can help patients to “let go” and may lead to better quality of care and outcomes. Recommendations to improve quality of patient care in (es)ketamine treatment are provided, including suggestions for the training of nurses and other support staff.