bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emerging small-molecule antiviral agents in long COVID prevention
Authors: He Xiaomeng , Zhang Xiang , Zhong Wu 
Published: October 2024

Long COVID, or Post-Acute Sequelae of COVID-19 (PASC), was characterized by persistent symptoms such as fatigue, shortness of breath, and cognitive impairments. These symptoms, emerging one to 2 months post-infection and persisting for several months, cannot be attributed to other diagnoses. The pathophysiology of long COVID remained elusive; however, emerging studies suggested multiple potential mechanisms, including the reactivation of Epstein-Barr virus, persistent SARS-CoV-2 reservoirs, neuroinflammation, and vascular damage, which may contribute to its development. Long COVID affected multiple organ systems, including respiratory, circulatory, and nervous systems, leading to a range of functional impairments. Additionally, it showed a profound impact on mental health, manifesting as anxiety and depression, which significantly degraded the quality of life. The absence of definitive treatments underscored the importance of prevention. Recent evidence indicated that early antiviral intervention—particularly with small-molecule drugs such as Metformin, Ensitrelvir, Molnupiravir, and Nirmatrelvir—may effectively reduce the incidence of long COVID. This underscored the promising role of small-molecule compounds in mitigating long-term COVID-19 consequences, offering a novel preventive strategy against long COVID and its extensive impacts on patients.
Combining mathematical modeling, in vitro data and clinical target expression to support bispecific antibody binding affinity selection: a case example with FAP-4-1BBL
Authors: Sanchez Javier , Claus Christina , McIntyre Christine , Tanos Tamara , Boehnke Axel , Friberg Lena E. , Jönsson Siv , Frances Nicolas 
Published: October 2024

The majority of bispecific costimulatory antibodies in cancer immunotherapy are capable of exerting tumor-specific T-cell activation by simultaneously engaging both tumor-associated targets and costimulatory receptors expressed by T cells. The amount of trimeric complex formed when the bispecific antibody is bound simultaneously to the T cell receptor and the tumor-associated target follows a bell-shaped curve with increasing bispecific antibody exposure/dose. The shape of the curve is determined by the binding affinities of the bispecific antibody to its two targets and target expression. Here, using the case example of FAP-4-1BBL, a fibroblast activation protein alpha (FAP)-directed 4-1BB (CD137) costimulator, the impact of FAP-binding affinity on trimeric complex formation and pharmacology was explored using mathematical modeling and simulation. We quantified (1) the minimum number of target receptors per cell required to achieve pharmacological effect, (2) the expected coverage of the patient population for 19 different solid tumor indications, and (3) the range of pharmacologically active exposures as a function of FAP-binding affinity. A 10-fold increase in FAP-binding affinity (from a dissociation constant [KD] of 0.7 nM–0.07 nM) was predicted to reduce the number of FAP receptors needed to achieve 90% of the maximum pharmacological effect from 13,400 to 4,000. Also, the number of patients with colon cancer that would achieve 90% of the maximum effect would increase from 6% to 39%. In this work, a workflow to select binding affinities for bispecific antibodies that integrates preclinical in vitro data, mathematical modeling and simulation, and knowledge on target expression in the patient population, is provided. The early implementation of this approach can increase the probability of success with cancer immunotherapy in clinical development.
Advances in VNS efficiency and mechanisms of action on cognitive functions
Authors: Wang Wendi , Li Rui , Li Chuangtao , Liang Qimin , Gao Xiaolin 
Published: October 2024

ObjectiveThis systematic review aims to comprehensively analyze the efficacy and underlying mechanisms of vagus nerve stimulation (VNS) in enhancing cognitive functions and its therapeutic potential for various cognitive impairments. The review focuses on the impact of VNS on emotional processing, executive functions, learning, memory, and its clinical applications in conditions such as epilepsy, depression, Alzheimer’s disease, and other neurological disorders.MethodsA systematic search of electronic databases (PubMed, Scopus, Web of Science) was conducted using the keywords “vagus nerve stimulation,” “cognitive enhancement,” “emotional processing,” “executive function,” “learning and memory,” “epilepsy,” “depression,” “Alzheimer’s disease,” “neurological disorders,” “attention-deficit/hyperactivity disorder,” “sleep disorders,” and “long COVID.” The inclusion criteria encompassed controlled trials, longitudinal studies, and meta-analyses published in English between 2000 and July 2024.ResultsA comprehensive review of 100 articles highlighted the cognitive effects of Vagus Nerve Stimulation (VNS). Studies show that VNS, especially through transcutaneous auricular VNS (taVNS), enhances emotional recognition, particularly for facial expressions, and improves selective attention under high cognitive demands. Additionally, VNS enhances learning and memory, including associative memory and spatial working memory tasks. In clinical applications, VNS exhibits promising benefits for improving cognitive functions in treatment-resistant epilepsy, depression, and Alzheimer’s disease.ConclusionVNS represents a promising therapeutic approach for enhancing cognitive function across diverse patient populations. The reviewed evidence highlights its efficacy in modulating cognitive domains in healthy individuals and improving cognition in neurological conditions. However, the comparative effectiveness of different VNS modalities and the differential effects of online versus offline VNS on cognitive psychology require further investigation. Future research should focus on optimizing VNS protocols and elucidating specific cognitive domains that benefit most from VNS interventions. This ongoing exploration is essential for maximizing the therapeutic potential of VNS in clinical practice.
Identification and expression profiling of neuropeptides and neuropeptide receptor genes in a natural enemy, Coccinella septempunctata
Authors: Han ShunDa , Chen JunJie , Liu ZhaoHan , Zhang MaoSen , Guo PengHui , Liu XiaoXiao , Wang LongRui , Shen ZhongJian , Zhang LiSheng 
Published: October 2024

IntroductionNeuropeptides and their receptors constitute diverse and abundant signal molecules in insects, primarily synthesized and released primarily from neurosecretory cells within the central nervous system Neuropeptides act as neurohormones and euromodulators, regulating insect behavior, lifecycle, and physiology by binding to receptors on cell surface. As a typical natural predator of agricultural pests, the lady beetle, Coccinella septempunctata, has been commercially mass-cultured and widely employed in pest management. Insect diapause is a physiological and ecological adaptative strategy acquired in adverse environments. In biological control programs, knowledge about diapause regulation in natural enemy insects provides important insight for improving long-term storage, transportation, and field adoption of these biological control agents. However, little is known about the function of neuropeptides and their receptors in controlling reproductive diapause of C. septempunctata. It is unclear which neuropeptides affect diapause of C. septempunctata.MethodsIn this study, RNA-seq technology and bioinformatics were utilized to investigate genes encoding neuropeptides and their receptors in female adults of C. septempunctata. Quantitative real-time PCR (qRT-PCR) analysis was employed to examine gene expression across different development/diapause stages.ResultsA total of 17 neuropeptide precursor genes and 9 neuropeptide receptor genes were identified, implicated in regulating various behaviors such as feeding, reproduction, and diapause. Prediction of partial mature neuropeptides from precursor sequences was also performed using available information about these peptides from other species, conserved domains and motifs. During diapause induction, the mRNA abundance of AKH was notably higher on the 10th day compared to non-diapause females, but decreased by the 20th day. In contrast, GPHA showed lower expression levels on the 5th day of diapause induction compared to non-diapause females, but increased significantly by the 15th and 20th days. NPF was higher expressed in head and midgut while DH showed higher expression in the fat body and midgut. Additionally, NPF expression remained consistently lower throughout all stages of diapause induction compared to non-diapause conditions in females.DiscussionThis study represents the first sequencing, identification, and expression analysis of neuropeptides and neuropeptide receptor genes in C. septempunctata. Our results could provide a foundational framework for further investigations into the presence, functions, and potential targets of neuropeptides and their receptors, particularly in devising novel strategies for diapause regulation in C. septempunctata.
Expectations concerning cancer treatment: perspectives of medical oncologists and patients on advanced, unresectable lung carcinoma
Authors: Cruz-Castellanos Patricia , Jiménez-Fonseca Paula , Galán-Moral Rocío , Piera-Molons Nuria , Gustems Marina , Calderon Caterina 
Published: October 2024

IntroductionThis study seeks to compare expectations regarding systemic cancer treatment for advanced lung cancer from the perspectives of both patient and medical oncologist.MethodsA cross-sectional study involving 17 medical oncologists from 13 Spanish hospitals between 2021 and 2022. Patients with advanced, unresectable lung cancer were recruited prior to initiating systemic cancer treatment. Both patients and oncologists completed the NEOetic-EIT and the STAR.ResultsSeventeen medical oncologists specializing in lung cancer participated, with a mean age of 36.2 years (range 28–56); 65% were female. The study included 298 patients with advanced, unresectable lung cancer, predominantly non-small cell type (72%), and most at stage IV (77%). Most patients were retired or unemployed (71%), and married or partnered (77%). Treatment approaches varied, with 44% based on biomarkers. Oncologists had greater expectations of positive outcomes for participants with better baseline prognosis, such as ECOG 0, newly diagnosed, locally advanced, unresectable non-small cell lung cancer, and those receiving biomarker-based treatments. In contrast, patients’ treatment expectations did not vary based on sociodemographic or clinical factors. Generally, patients had high expectations of cure, in contrast to oncologists’ lower expectations, though both anticipated similar quality-of-life improvements. Patients anticipated more side effects than oncologists. Among oncologists, expectations varied by gender and decreased with age and experience, with no differences detected among patients based on gender, age, or doctor-patient relationship.ConclusionThis study reveals the complex expectations of patients and oncologists in advanced lung cancer treatment. It underscores the need for effective communication in oncology to align patient expectations with clinical realities.
“… give me a lawyer, dawg”: recognizing youthful pleas for advice and support
Authors: Wilford Miko M. , Frazier Annabelle 
Published: October 2024

(1) Youth are particularly vulnerable to making suboptimal legal decisions due to added challenges in comprehension, as well as their ongoing neurological development.(2) This fact is especially problematic in our system of pleas, which frequently expects defendants to determine the outcome of their own cases (by accepting or rejecting plea offers).(3) To better ensure that guilty pleas entered by youthful defendants are indeed knowing, intelligent, and voluntary, legal counsel should be mandatory during any and all juvenile criminal proceedings.(4) Further, an additional “translator” (similar to a guardian ad litem), who has specialized training in developmental psychology, should be present to effectively counsel and support youth defendants who might otherwise fail to comprehend the advice of their attorneys (and other court actors).
Dissecting implicit food-related behaviors in Binge Eating Disorder and obesity: insights from a mobile approach-avoidance framework
Authors: Collantoni Enrico , Meregalli Valentina , Granziol Umberto , Di Vincenzo Angelo , Rossato Marco , Giovannini Serena , Capobianco Elisa , Zech Hilmar , Vettor Roberto , Favaro Angela 
Published: October 2024

IntroductionBulimic episodes experienced by patients with Binge Eating Disorder (BED) might be sustained by an enhanced behavioral propensity to approach food stimuli.MethodsTo test this hypothesis, automatic approach avoidance tendencies toward high-calorie foods (HCF), low-calorie foods (LCF), and neutral objects were assessed in a group of 23 patients with BED, and their performance was compared to the one of 17 patients with obesity without BED and a group of 32 normal weight participants. All participants performed a mobile approach-avoidance task in which they were required to approach and avoid different stimuli by respectively pulling their phone toward themselves or pushing it away. Reaction times were analyzed.ResultsResults showed a significant three-way interaction between group, type of movement and stimulus. Post-hoc analyses revealed that all the groups displayed an approach bias toward HCF. Patients with BED and healthy controls also displayed an approach bias toward LCF, a bias that was absent in obese individuals without BED. Moreover, patients with BED were faster in approaching food stimuli, both HCF and LCF, compared to healthy controls.DiscussionThese behavioral tendencies are quite consistent with the real-life attitudes of both BED patients and patients with obesity and might contribute to the maintenance of unhealthy eating habits such as binging in patients with BED and high-calorie diets in patients with obesity.
A method and approach for evaluating coparenting events during couples group interventions
Authors: McHale James P. , Irace Karina , Cowan Philip , Cowan Carolyn Pape , Odgaard Eric 
Published: October 2024

IntroductionWhen interventionists stimulate productive father-mother dialogues around coparenting, there are numerous potential benefits for families. Families stand to benefit from more positive involvement of fathers with both coparents and children, key contributors to healthy child developmental outcomes. In this report, we introduce a new strategy and rating system for helping practitioners and supervisors assess the nature and quality of coparenting-related dialogues and conversations in the context of couples group interventions.MethodThe system derives from analysis of 24 relationship-enhancement groups, 13 enrolling English-speaking couples and 11 enrolling Spanish-speaking couples, all parents of young children. All groups were co-led by a male-female team explicitly trained to focus on marital and parenting themes and supervised to address couples issues - not coparenting issues explicitly. All co-leaders spoke the native language of group participants. We documented how frequently coparenting events occurred, and how the nature and quality of events varied within and across groups.ResultsOverall, in both English- and Spanish-speaking groups expressly assembled to focus on marital and parenting issues, coparenting events occurred relatively infrequently. At the same time, both mothers and fathers appeared motivated to raise and discuss issues associated with their coparenting, and extended discussions about coparenting issues broached by the parents blossomed in approximately 37% of all instances. Process-oriented (rather than didactic) co-leader responses appeared especially helpful in scaffolding prolonged coparenting discussions.DiscussionWe propose that use of the system as a training, supervision and self-assessment tool can help clinicians become more consciously aware of how well their interventions succeed in promoting and scaffolding coparenting conversations during group interactions.
Cultural adaptation and preliminary validation of the Flexibility Scale for Spain
Authors: Rodríguez-Armendariz Ekaine , Petrolini Valentina , Martín-González Isabel , Juncal-Ruiz Maria , Vicente Agustín 
Published: October 2024

BackgroundIndividuals exhibit varying degrees of flexibility depending on different characteristics, conditions, and diagnoses. The Flexibility Scale is a comprehensive informant-report measure used to assess multiple aspects of flexibility in autistic and non-autistic children and youth, with an emphasis on cognitive aspects. This tool has not been adapted nor validated for use in Spain.MethodsIn this paper we aim to provide a culturally adapted and validated version of the Flexibility Scale for Spain. We detail the procedure followed by our research team to obtain a cultural adaptation of the scale for Spain, including forward and back translations, cognitive interviews, feedback from experts, and preliminary validation. Our participants in the validation process were 75 autistic and 39 typically developing children and adolescents between the ages of 6 and 17.ResultsWe reached a culturally adapted and preliminary validated version of the Flexibility Scale for Spain (Escala de Flexibilidad).ConclusionsWe make the scale available to researchers and practitioners working in Spain. This contributes to laying the groundwork for further testing and adaptations in Spanish-speaking countries and communities worldwide.
Effectiveness of a peer-to-peer, self-management intervention for young people with depression and anxiety in Denmark: an observational study and a propensity score-matched comparison
Authors: Andersen Susan , Thygesen Lau Caspar , Jensen Marie Pil , Lauridsen Sigurd , Folker Anna Paldam , Nielsen Maj Britt Dahl 
Published: October 2024

ObjectiveThis study investigated the effectiveness of a 7-weeks peer-to-peer program for young people aged 15 to 25 years with depression or anxiety symptoms in Denmark.MethodsA total of 483 participants (72% women) participated in the program and the evaluation. The participants completed questionnaires at baseline, postintervention, and at 5-month follow-up to assess changes in depression symptoms (using Beck’s Depression Inventory-II), anxiety symptoms (using Spielbergers State–Trait Anxiety Inventory for Adults) and self-efficacy in controlling or managing the illness (using the personal control subscale from the Illness Perception Questionnaire-Revised). Analyses were done using repeated measures mixed linear regression models. Moreover, a register-based matched comparison group was derived as a comparison to assess changes in being in education and employment at 8-month follow-up.ResultsWithin the intervention group, both depression and anxiety scores declined across the 5-month follow-up compared to baseline (b = −9.6, 95% CI: −11.2, −8.1 for depression symptoms). The self-efficacy score increased from baseline to post-intervention (b = 1.4, 95% CI: 1.0, 1.8) and this level was maintained at follow-up. More than half of the participants were in education at baseline while 24% received social transfer payments. Compared with matched comparison group, a lower proportion of the intervention group remaining in education (71% vs. 80%). Among participants who were employed at baseline, a higher proportion of the intervention group were enrolled in education (27% vs. 19%) and were unemployed (14% vs. 4%) compared to the matched comparison group.ConclusionThis study supports the effectiveness of a peer-to-peer intervention for depression and anxiety symptoms, and self-efficacy in symptom control. However, mixed effects on education and employment were observed, indicating a negative impact on education among those initially enrolled and a higher proportion of employed participants starting education.
The ABCs of mental health at the university: a multi-level intervention design for promoting mental well-being
Authors: Nielsen Line , Bermejo-Martins Elena , Nelausen Malene Kubstrup , Madsen Cecilie Schacht , Riva Elena , Koushede Vibeke Jenny , Meilstrup Charlotte Bjerre 
Published: October 2024

BackgroundThere is an escalating concern for the mental health of university students being recognized as a high-risk group for psychological distress. Despite research emphasizing the need to integrate mental well-being into higher education, existing interventions primarily focus on challenges and support services, leaving a gap in practical insights for promoting mental well-being at the university as a whole.ObjectivesThis paper aims to cover the theoretical and methodological foundations for the design and development of a complex multi-level intervention called the ABCs of mental health at the university (ABC-uni).MethodsFollowing the MRC framework for complex interventions, the design and development of a novel complex intervention is described (Phase I). Using the socio-ecological model and incorporating principles from health promotion charters, capacity building, organizational change models, and the principles of the ABCs of mental health a program theory for mental health promotion at the university is proposed. Following this theoretical foundation a logic model outlines the ABC-uni intervention components at structural, community, and individual levels. The components include staff training, campaign materials, a photovoice project, integration of mental well-being literacy into introductory programs, a credit-bearing course, and an online module. Preferably, most of these components are developed and carried out collaboratively with students at the university. As proposed in the logic model expected outcomes encompass heightened awareness, supportive environments, commitment, and accountability, aiming to enhance mental well-being across the entire university. The design and development of the intervention components occur at a Danish public university.DiscussionThis section addresses the strengths and limitations of the design of the ABC-uni intervention. Future research will cover the feasibility phase of each components of the ABC-uni intervention (phase II). The conceptual framework and program theory outlining mental health promotion at the university, along with the detailed description of the intervention components, provides valuable insights for fostering mental well-being in the university community.