bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety, tolerability, pharmacokinetics, and pharmacodynamics of a soluble guanylate cyclase stimulator, HEC95468, in healthy volunteers: a randomized, double-blinded, placebo-controlled phase 1 trial
Authors: Gui Yu-zhou , Wang Wei , Wu Qing-qing , Ding Qi-chen , Qian Hong-jie , Lu Qiu-bei , Zhang Ying-jun , Zhuang Yu-lei , Deng Li , Zuo Ying-lin , Luo Lin , Jia Jing-ying 
Published: June 2024

Heart failure is the most costly cardiovascular disorder. New treatments are urgently needed. This study aims to evaluate the safety, pharmacokinetics, and pharmacodynamic profile of HEC95468, a soluble guanylate cyclase (sGC) stimulator, in healthy volunteers. Sixty-two, eighteen, and forty-eight participants were enrolled in the single ascending dose (SAD) study, the food effect (FE) study, and the multiple ascending dose (MAD) study, respectively. The study conforms to good clinical practice and the Declaration of Helsinki. Overall, HEC95468 was safe and tolerable; a higher proportion of HEC95468-treated participants reported mild headaches, dizziness, decreased blood pressure, increased heart rate, and gastrointestinal-related treatment-emergent adverse events (TEAEs), similar to the sGC stimulators riociguat and vericiguat. In terms of pharmacokinetic parameters, the maximum observed plasma concentration (Cmax) and the area under the concentration-time curve (AUC0-t) were dose-proportional over the dose range. Moderate accumulation was observed after multiple administrations of HEC95468. Systolic blood pressure (SBP) and diastolic blood pressure decreased, while 3′,5′-cyclic guanosine monophosphate (cGMP) concentration in plasma increased and heart rate was induced. Vasoactive hormones (renin, angiotensin II, and norepinephrine) in plasma were compensatorily elevated after oral administration. These data supported further clinical trials of HEC95468 in the treatment of heart failure and pulmonary arterial hypertension.Systematic Review Registration:http://www.chinadrugtrials.org.cn, identifier CTR20210064.
The efficacy and safety of Xiao-Ban-Xia-Tang in the treatment of chemotherapy-induced nausea and vomiting: A systematic review and meta-analysis
Authors: Li Ling , Jia Shangmei , Yu Chenghao , Shi Shasha , Peng Fu 
Published: June 2024

BackgroundChemotherapy-induced nausea and vomiting (CINV) is one of the most frequent and critical side effects due to chemotherapeutics. In China, Xiao-Ban-Xia-Tang (XBXT) has already been applied extensively to prevent and treat CINV. However, there is limited testimony on the effectiveness and safety of this purpose, and there was no correlative systematic review. The aim of this review was to systematically evaluate the effectiveness and safety of XBXT in preventing and treating CINV.MethodsThe systematic search was conducted in eight databases to acquire randomized controlled trials (RCTs) that appraised the effect of XBXT in treating CINV. The vomiting and nausea relief efficiency, eating efficiency, quality of life, and adverse reactions were explored for efficacy assessment. Bias risk was rated by manipulating the Cochrane risk of bias tool 2.0 (RoB 2). The retrieved investigations were analyzed by utilizing ReviewManager 5.4 and Stata 17.0. The quality of evidence was evaluated adopting the GRADE tool.ResultsA total of 16 clinical RCTs of XBXT in the treatment of CINV were incorporated into the investigation, with a total of 1246 participants. The meta-analysis showed that compared with conventional antiemetic drugs, XBXT and antiemetics improved the vomiting relief efficiency (RR 1.35, 95% confidence interval: 1.25–1.46, p &lt; 0.00001), nausea relief efficiency (N = 367, RR 1.23, 95% CI: 1.09–1.38, p &lt; 0.00001), and quality of life (RR = 1.37, 95% CI: 1.14–1.65, p = 0.0009) and reduced the adverse events (N = 370, RR 0.53, 95% CI: 0.29–0.96, p = 0.04). XBXT and DARAs raised eating efficiency compared with DARAs (N = 208, RR 1.30, 95% CI: 1.07–1.57, p = 0.007). The data existed as statistically significant, and the publication bias was identified as relatively low from the funnel plot and trim and fill analysis. In addition, sensitivity analysis demonstrated robust outcomes. The quality of evidence for each outcome ranged from moderate to high.ConclusionThere is some encouraging evidence that XBXT and antiemetics had better therapeutic effects and safety in treating CINV than antiemetic drugs alone. The quality assessment and low publication bias indicated that the overall criterion was scientific. Better research is required to verify the evidence designed with large-scale RCTs and rigorous methods.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=281046.
In silico approaches for drug repurposing in oncology: a scoping review
Authors: Cavalcante Bruno Raphael Ribeiro , Freitas Raíza Dias , Siquara da Rocha Leonardo de Oliveira , Santos Roberto de Souza Batista Dos , Souza Bruno Solano de Freitas , Ramos Pablo Ivan Pereira , Rocha Gisele Vieira , Gurgel Rocha Clarissa Araújo 
Published: June 2024

Introduction: Cancer refers to a group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body. Due to its complexity, it has been hard to find an ideal medicine to treat all cancer types, although there is an urgent need for it. However, the cost of developing a new drug is high and time-consuming. In this sense, drug repurposing (DR) can hasten drug discovery by giving existing drugs new disease indications. Many computational methods have been applied to achieve DR, but just a few have succeeded. Therefore, this review aims to show in silico DR approaches and the gap between these strategies and their ultimate application in oncology.Methods: The scoping review was conducted according to the Arksey and O’Malley framework and the Joanna Briggs Institute recommendations. Relevant studies were identified through electronic searching of PubMed/MEDLINE, Embase, Scopus, and Web of Science databases, as well as the grey literature. We included peer-reviewed research articles involving in silico strategies applied to drug repurposing in oncology, published between 1 January 2003, and 31 December 2021.Results: We identified 238 studies for inclusion in the review. Most studies revealed that the United States, India, China, South Korea, and Italy are top publishers. Regarding cancer types, breast cancer, lymphomas and leukemias, lung, colorectal, and prostate cancer are the top investigated. Additionally, most studies solely used computational methods, and just a few assessed more complex scientific models. Lastly, molecular modeling, which includes molecular docking and molecular dynamics simulations, was the most frequently used method, followed by signature-, Machine Learning-, and network-based strategies.Discussion: DR is a trending opportunity but still demands extensive testing to ensure its safety and efficacy for the new indications. Finally, implementing DR can be challenging due to various factors, including lack of quality data, patient populations, cost, intellectual property issues, market considerations, and regulatory requirements. Despite all the hurdles, DR remains an exciting strategy for identifying new treatments for numerous diseases, including cancer types, and giving patients faster access to new medications.
Visuospatial perspective-taking of a protagonist during narrative comprehension: the effects of task load and individual differences in visuospatial working memory
Authors: Hosokawa Asako , Kitagami Shinji 
Published: June 2024

IntroductionThis study examined whether visuospatial perspective uses the character perspective during narrative comprehension.MethodParticipants read narrative stimuli depicting the spatial positional relationships between characters and objects and judged whether the objects were on the left or right from the character's perspective. We manipulated whether the spatial positional relationships between characters depicted in the narrative stimuli resulted in a visuospatial perspective. We hypothesized that the high-load perspective-taking condition would indicate longer reaction times compared to the low-load perspective-taking condition, as shifting perspectives between characters in the high-load condition require more time for visuospatial perspective-taking.ResultsAs predicted, the reaction time was longer for high-load perspective-taking than for low-load perspective-taking.DiscussionDuring narrative comprehension, the reaction time for visuospatial perspective-taking must move virtually within the representation from the main character's perspective to that of another character. Visuospatial perspective-taking is involved in narrative comprehension.
Investigating the trajectory of post-COVID impairments: a longitudinal study in Sweden
Authors: Badinlou Farzaneh , Abzhandadze Tamar , Rahimian Fatemeh , Jansson-Fröjmark Markus , Hedman-Lagerlöf Maria , Lundgren Tobias 
Published: June 2024

IntroductionIndividuals recovering from COVID-19 often experience a range of post-recovery symptoms. However, the literature on post-COVID-19 symptoms reveals conflicting results, necessitating a heightened focus on longitudinal studies to comprehend the trajectory of impairments over time. Our study aimed to investigate changes in long-term impairments among individuals infected with COVID-19 and explore potential predictors influencing these changes.MethodsWe conducted a web-survey targeting individuals that had been infected with COVID-19 at four time-points: T0 (baseline), T1 (three months), T2 (six months), and T3 (twelve months). The survey included contextual factors, factors related to body functions and structures, and post-COVID impairments. The longitudinal sample included 213 individuals (with a mean age of 48.92 years). Linear mixed models were employed to analyze changes in post-COVID impairments over time and identify impacting factors.ResultsFindings revealed a general decline in post-COVID impairments over time, with each symptom exhibiting a dynamic pattern of fluctuations. Factors such as initial infection severity, education level, and work status were significantly associated with the levels of impairments.DiscussionThe study emphasizes that post-COVID impairments are not static but exhibit variations over time. Personalized care, especially for vulnerable populations, is crucial. The results underscore the need for long-term monitoring and multidisciplinary treatment approaches. Targeted support and interventions are highlighted for individuals with severe initial infections and those in socioeconomically disadvantaged groups.
Nicotine and fluoxetine alter adolescent dopamine-mediated behaviors via 5-HT1A receptor activation
Authors: Yuan Menglu , Leslie Frances M. 
Published: June 2024

IntroductionAbuse or misuse of tobacco, e-cigarettes, or antidepressants may have serious clinical consequences during adolescence, a sensitive period during brain development when the distinct neurobiology of adolescent serotonin (5-HT) and dopamine (DA) systems create unique behavioral vulnerabilities to drugs of abuse. MethodsUsing a pharmacological approach, we modeled the behavioral and neurochemical effects of subchronic (4-day) nicotine (60µg/kg, i.v.) or fluoxetine (1mg/kg, i.v.) exposure in adolescent and adult male rats. ResultsNicotine and fluoxetine significantly enhance quinpirole-induced locomotor activity and initial cocaine self-administration in adolescents, but not adults. These effects were blocked by serotonin 5-HT1A receptor antagonists, WAY-100,635 (100 µg/kg, i.v.) or S-15535 (300 µg/kg, i.v.). Neurochemical and anatomical autoradiographic analysis of 8-OH-DPAT-stimulated [35S]GTPγS reveal that prior exposure to nicotine and fluoxetine results in both overlapping and distinct effects on regional 5-HT1A receptor activity. Both fluoxetine and nicotine enhance adolescent 5-HT1A receptor activity in the primary motor cortex (M1), whereas fluoxetine alone targets prefrontal cortical neurocircuitry and nicotine alone targets the amygdala. DiscussionGiven their different pharmacological profiles, comparison between WAY-100,635 and S-15535 indicates that postsynaptic 5-HT1A receptors mediate the behavioral effects of prior nicotine and fluoxetine exposure. In addition, within the adolescent M1, maladaptive changes in 5-HT signaling and 5-HT1A activity after nicotine or fluoxetine exposure may potentiate hyper-responsiveness to dopaminergic drugs and prime adolescent vulnerability for future substance abuse.
Re-assessment of schistosomiasis in nine endemic districts with cluster sampling in Sierra Leone
Authors: Kargbo-Labour Ibrahim , Redwood-Sawyerr Victoria , Conteh Abdulai , Chop Elisabeth , Bah Mohamed S. , Koroma Abdulai , Kabia Unidiatu , Klein Luke , Juneja Sugandh , Houck Patricia , Reid Steven , Evans Darin , Weaver Angela M. , Phillips Anna E. , Zhang Yaobi 
Published: June 2024

BackgroundBaseline mapping showed that schistosomiasis was highly/moderately endemic in nine districts in Sierra Leone. Mass drug administration (MDA) with praziquantel started in 2009, and after multiple rounds of treatment, an impact assessment was conducted in 2016 followed by a second re-assessment in 2022 using cluster sampling to provide more granular data for refining chiefdom (sub-district) treatment strategies.MethodsOn average, 20 rural villages were systematically selected per district by probability proportional to population size across the nine districts. Surveys were conducted in schools, and 24 school children aged between 5 and 14 years were randomly selected, with an equal number of boys and girls. One stool sample and one urine sample were collected per child. Two Kato-Katz slides were examined per stool for Schistosoma mansoni infection. Hemastix strips were used as a proxy for S. haematobium infection with urine filtration used for egg counts on hematuria-positive samples.ResultsIn total, 4,736 stool samples and 4,618 urine samples were examined across 200 schools in 125 chiefdoms. Overall, the prevalence of S. mansoni was 16.3% (95% CI: 15.3–17.4%), while the overall prevalence of S. haematobium was 2.0% (95% CI: 1.6–2.4%) by hematuria. The prevalence of heavy infections for S. mansoni and S. haematobium was 1.5% (95% CI: 1.1–1.9%) and 0.02% (95% CI: 0.0–0.14%), respectively. Among 125 chiefdoms surveyed, the overall schistosomiasis prevalence was &lt;10% in 65 chiefdoms, 10–49.9% in 47 chiefdoms, and ≥ 50% in 13 chiefdoms. There was a mixed relationship between schistosomiasis in school children and WASH access in schools.ConclusionSierra Leone has made significant progress in reducing schistosomiasis prevalence across the country after a decade of MDA intervention. However, high prevalence remains in some hotspot chiefdoms. The next steps are for the national program to investigate and address any potential issues such as low coverage or poor knowledge of schistosomiasis risk behaviors and, where appropriate, consider broadening to community-wide treatment in hotspot chiefdoms or communities.
Detection of antibiotic resistant Enterobacterales in commercial raw pet food: a preliminary study
Authors: Fisher Carolyn D. , Call Douglas R. , Omulo Sylvia 
Published: June 2024

IntroductionRaw diets have become popular in companion animal nutrition, but these diets may be contaminated with harmful bacteria because heat processing is not utilized to mitigate pathogens during the production process. We analyzed 24 commercially available frozen raw canine and feline diets for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E).MethodsSamples were incubated in tryptic soy broth augmented with 50 μg/mL ampicillin to enrich for ESBL-E. ESBL-E were isolated using CHROMagar ESBL plates and isolate identification and antibiotic susceptibility testing were confirmed using the VITEK®2 instrument.ResultsESBL-E were isolated from 42% (10/24) of raw diets, with E. coli, Enterobacter cloacae complex and Klebsiella pneumoniae predominating. Most ESBL-E isolates (71%, 32/45) were multidrug-resistant. Direct plating of samples onto tryptic soy agar yielded bacterial counts &gt;6 log10 for 2 samples from two different manufacturers.ConclusionThis preliminary study justifies further investigation into the potential contribution of raw diets to the dissemination of antibiotic resistant bacteria in companion animals and domestic living spaces.
Depressive Symptoms Among Higher Education Students in Germany—A Systematic Review and Meta-Analysis
Authors: Heumann Eileen , Palacio Siebe Ana Valentina , Stock Christiane , Heinrichs Katherina 
Published: June 2024

ObjectivesHigher education students in Germany are vulnerable to depressive symptoms. Despite ample evidence, no comprehensive review has recently been conducted. Thus, our systematic review and meta-analysis aims at describing the extent to which students are affected by depressive symptoms.MethodsWe searched three databases for articles reporting the prevalence rates of depressiveness among students in Germany published between 2002 and 2023. Pooled prevalence rates were calculated using random effects models, both for the overall sample and for subgroups categorized by gender, study setting, assessment instrument, and whether the study was conducted before or during the COVID-19 pandemic.ResultsThe search yielded 992 records. After screening, 60 articles remained for data extraction. About one out of five students (21.1%) exhibits depressive symptoms. Pooled prevalence rates differ between subgroups, with higher rates during the COVID-19 pandemic than before (30.6% versus 18.0%) and with females being more affected than their male counterparts (29.0% versus 23.1%).ConclusionThis review underlines the urgency with which the mental health of students should be addressed at the (higher educational) policy level.Clinical Trial Registration:PROPSPERO, Identifier CRD42022384066.
PENGUATAN IDENTITAS SEKOLAH KATOLIK MELALUI PENERAPAN PROGRAM PASTORAL SEKOLAH DI SMAK ST THOMAS AQUINO MOJOKERTO
Authors: Poto Maria Kumala Mutiara , Permana Natalis Sukma 
Published: June 2024

This research aims to determine the efforts of Catholic schools, especially SMAK St. Thomas Aquino Mojokerto in carring out the process of strengthening the identity of Catholic schools, especially through school pastoral programs. Strengthening the identity of Catholic schools is a means of integrating the values of the Catholic faith. Integrating the values of the Catholic faith can be done through a school pastoral program implemented with the aim of helping students become familiar with the teachings of the Catholic faith and forming good character of the students. In this research the author uses a qualitative approach focusing with a case study method. Research data collection was carried out using observation, interview and documentation techniques. The research data analysis was carried out using a condensation approach.The results of research show that the school pastoral program is a means of strengthening the identity of Catholic schools at SMAK St.Thomas Aquino Mojokerto. Through this school's pastoral program, the Catholic values in the form of faith in God, social values of justice, morality, intellectual values and love have been taught to students at SMAK St. Thomas Aquino Mojokerto aims of strengthening the identity of this Catholic school.
An Investigation of Private School Psychological Counseling and Guidance Teachers’ Views on Immigrant Students
Authors: Şenel Mustafa 
Published: June 2024

Migration continues to emerge as a significant issue in the present day, extending beyond its historical context. This phenomenon not only forms a broad spectrum of impact in social, economic, and cultural realms but also holds notable consequences in the realm of education. Migration, on one hand, has the potential to stimulate cultural interaction, enhancing diversity in knowledge and experience. On the other hand, immigrant individuals may encounter early challenges such as educational inequalities or negative attitudes. This intricate relationship between migration and education contributes to cultural development while simultaneously bringing about areas of societal conflict. Understanding the effects of migration on the younger generation falls within the responsibilities of Psychological Counseling and Guidance (PCG) teachers. These educators aim to support students’ academic, personal, social, and emotional development, particularly addressing the challenges posed by the education of immigrant students in the context of social diversity. Research on understanding the attitudes among school stakeholders towards immigrant students contributes valuable insights to this field. In this context, the study is an original work focusing on the perspectives of PCG teachers concerning the attitudes of other stakeholders in schools with immigrant students in private schools. Conducted using qualitative research methods and the phenomenology design, the study involved 12 PCG teachers working in private schools in Gaziantep, Kilis, and Mersin, which are among Turkey’s cities experiencing significant migration. Data collected through interviews were analyzed using content analysis. The findings revealed that, overall, teachers and students in private schools with immigrant students tended to have a positive attitude, while parents held a negative outlook. A collective evaluation of all data suggests a notably positive perception and attitude toward immigrant students.
Identidad Cultural y Fragmentación Social. Crítica al relativismo identitario
Authors: Lazo López Luis Miguel 
Published: June 2024

Las sociedades contemporáneas vienen enfrentando diversos problemas sociales, uno de estos, oculto, o en todo caso no muy manifiesto, y en consecuencia poco dilucidado, es la identidad cultural, el colectivismo identidario y el multiculturalismo. Específicamente, se trata del daño colateral que trae la identidad cultural a la sociedad actual, este mal, es la fragmentación social. Es así que, en el presente manuscrito se explica la relación causal y malsana que existe entre identidad cultural y fragmentación social. A partir de una fundamentación teórica, se hace una crítica al relativismo identitario. Se revisa a los teóricos más importantes sobre el tema de la identidad cultural, concretamente a los que la critican, a saber; Slavoj Žižek, Jordan Peterson y François Jullien. Por tanto, la tesis conclusiva del estudio es que, la identidad cultural es un problema para la sociedad, porque la fragmenta y divide; porque genera agrietas, fracturas y conflictos sociales. La identidad cultural trae fragmentación social.