Use of parvovirus B19-like particles in self-illuminated photodynamic therapy for solid tumors.

Bioluminescence resonance energy transfer photodynamic therapy, which uses light generated by bioluminescent proteins to activate photosensitizers and produce reactive oxygen species without the need for external irradiation, has shown promising results in cancer models. However, the characterization of delivery systems that can incorporate the components of this therapy for preferential delivery to the tumor remains necessary. In this work, we have characterized parvovirus B19-like particles (B19V-VLPs) as a platform for a photosensitizer and a bioluminescent protein. By chemical and biorthogonal conjugation, we conjugated rose Bengal photosensitizer and firefly luciferase to B19V-VLPs and a protein for added specificity. The results showed that B19V-VLPs can withstand decoration with all three components without affecting its structure or stability. The conjugated luciferase showed activity and was able to activate rose Bengal to produce singlet oxygen without the need for external light. The photodynamic reaction generated by the functionalized VLPs-B19 can decrease the viability of tumor cells in vitro and affect tumor growth and metastasis in the 4 T1 model. Treatment with functionalized VLPs-B19 also increased the percentage of CD4 and CD8 cell populations in the spleen and in inguinal lymph nodes compared to vehicle-treated mice. Our results support B19V-VLPs as a delivery platform for bioluminescent photodynamic therapy components to solid tumors.

Incorporation of patient-reported outcomes in early-phase clinical trials for childhood and adolescent cancer.

INTRODUCTION: The assessment of quality of life (QoL) should be one of the main objectives in paediatric clinical trials. Even though researchers, regulators and advocates support the use of patient-reported outcomes (PROs), this has not been fully implemented. The aim of this study is to assess the measurement of QoL and the usage of PROs, palatability assessments and medication diaries in early-phase clinical trials for childhood and adolescent cancer. METHODS: Early-phase clinical trials for children and adolescents with cancer opened between 2005 and 2022 at the Royal Marsden Hospital (London, UK) and Vall d'Hebron University Hospital (Barcelona, Spain) were interrogated for trial characteristics and the use of QoL questionnaires, PROs, palatability assessments and medication diaries. RESULTS: Overall, 72 clinical trials were analysed: 12 (16.7%) evaluated QoL and eight (11.1%) evaluated PROs. Palatability was tested in 21/40 (52.5%) trials of oral drugs and 23/72 (31.9%) incorporated medication diaries. No studies mentioned patient involvement in the trial protocol. Use of PROs increased from one of 36 (2.8%) to seven of 36 (19.4%) between the first period (2005-2016) and the second period (2017-2022) (p = .02). Implementation of medication diaries increased from seven of 36 (19.4%) to 16/36 (44.4%) in each period, respectively (p = .02). CONCLUSION: Only a minor proportion of the international/multicentric early-phase trials evaluated included QoL/PROs and medication diaries or palatability questionnaires to help assess these, although this trend seems to be increasing over recent years. Greater implementation of QoL/PROs has the potential to improve the patient's wellbeing and facilitate symptom control, to enhance patient/parent involvement in future trial designs and to provide information for drug prioritisation.

Increase of pertussis cases in the Vallès region, Catalonia, Spain, September 2023 to April 2024.

We describe a pertussis outbreak in the Vallès region of Catalonia, from September 2023 to April 2024. Incidence was high in children aged 10-14 years compared with previous outbreaks. Limited impact in newborns could be explained by the high vaccination coverage during pregnancy and at 11 months of age in 2022, at 85% and 94.1 %, respectively. A third booster vaccine dose during preadolescence should be considered and vaccination coverage in pregnant women be improved to control future outbreaks.

Ultrasound Cut-Off Values for Rectus Femoris for Detecting Sarcopenia in Patients with Nutritional Risk.

BACKGROUND: A nationwide, prospective, multicenter, cohort study (the Disease-Related caloric-protein malnutrition EChOgraphy (DRECO) study) was designed to assess the usefulness of ultrasound of the rectus femoris for detecting sarcopenia in hospitalized patients at risk of malnutrition and to define cut-off values of ultrasound measures. METHODS: Patients at risk of malnutrition according to the Malnutrition Universal Screening Tool (MUST) underwent handgrip dynamometry, bioelectrical impedance analysis (BIA), a Timed Up and Go (TUG) test, and rectus femoris ultrasound studies. European Working Group on Sarcopenia in Older People (EWGSOP2) criteria were used to define categories of sarcopenia (at risk, probable, confirmed, severe). Receiver operating characteristic (ROC) and area under the curve (AUC) analyses were used to determine the optimal diagnostic sensitivity, specificity, and predictive values of cut-off points of the ultrasound measures for the detection of risk of sarcopenia and probable, confirmed, and severe sarcopenia. RESULTS: A total of 1000 subjects were included and 991 of them (58.9% men, mean age 58.5 years) were evaluated. Risk of sarcopenia was detected in 9.6% patients, probable sarcopenia in 14%, confirmed sarcopenia in 9.7%, and severe sarcopenia in 3.9%, with significant differences in the distribution of groups between men and women (p < 0.0001). The cross-sectional area (CSA) of the rectus femoris showed a significantly positive correlation with body cell mass of BIA and handgrip strength, and a significant negative correlation with TUG. Cut-off values were similar within each category of sarcopenia, ranging between 2.40 cm2 and 3.66 cm2 for CSA, 32.57 mm and 40.21 mm for the X-axis, and 7.85 mm and 10.4 mm for the Y-axis. In general, these cut-off values showed high sensitivities, particularly for the categories of confirmed and severe sarcopenia, with male patients also showing better sensitivities than women. CONCLUSIONS: Sarcopenia in hospitalized patients at risk of malnutrition was high. Cut-off values for the better sensitivities and specificities of ultrasound measures of the rectus femoris are established. The use of ultrasound of the rectus femoris could be used for the prediction of sarcopenia and be useful to integrate nutritional study into real clinical practice.

Predictive Biophysical Neural Network Modeling of a Compendium of in vivo Transcription Factor DNA Binding Profiles for Escherichia coli.

The DNA binding of most Escherichia coli Transcription Factors (TFs) has not been comprehensively mapped, and few have models that can quantitatively predict binding affinity. We report the global mapping of in vivo DNA binding for 139 E. coli TFs using ChIP-Seq. We used these data to train BoltzNet, a novel neural network that predicts TF binding energy from DNA sequence. BoltzNet mirrors a quantitative biophysical model and provides directly interpretable predictions genome-wide at nucleotide resolution. We used BoltzNet to quantitatively design novel binding sites, which we validated with biophysical experiments on purified protein. We have generated models for 125 TFs that provide insight into global features of TF binding, including clustering of sites, the role of accessory bases, the relevance of weak sites, and the background affinity of the genome. Our paper provides new paradigms for studying TF-DNA binding and for the development of biophysically motivated neural networks.

Posttraumatic Scrotal Reconstruction with a Pedicled "Extended" Superficial Circumflex Iliac Artery Perforator Flap: A Case Report.

The superficial circumflex iliac artery (SCIA) perforator (SCIP) flap has been used for scrotal reconstruction after Fournier's gangrene, skin cancer, or infections. However, there are few publications with regard to penoscrotal reconstruction after a traumatic injury with this flap. In this article, we propose a new SCIP flap variation, the "extended" or "direct" SCIP flap, to effectively reconstruct a wide scrotal defect after a traumatic injury. The "extended" SCIP flap is designed medial and cranial to the anterosuperior iliac spine (ASIS) using the superficial branch of the SCIA as the main pedicle.

Corrigendum: Neutrophil to lymphocyte ratio and principal component analysis offer prognostic advantage for dogs with mammary tumors.

[This corrects the article DOI: 10.3389/fvets.2023.1187271.].

Female authorship positions in health economic evaluations: a cross-sectional analysis.

OBJECTIVE: To investigate the gender of the authors who publish articles of health economic evaluations in medicine and healthcare journals. METHOD: We evaluated a random sample of economic evaluations indexed in MEDLINE during 2019. Gender of the first, last and corresponding author was determined by review of the author's first name. Data were summarized as frequency and percentage for categorical items and median and interquartile range (IQR) for continuous items. We also calculated the index of authors per paper. RESULTS: We included 200 studies with 1365 authors (median of 6 authors per paper; IQR: 4-9). Gender identification was possible for all authors in the study sample: 802 (59%) were men and 563 (41%) were women. The number of female first, last, and corresponding authors respectively were 78 (39%), 68 (34%), and 80 (40%) for health economic evaluations. DISCUSSION: Female scientists were underrepresented as co-authors and in prominent authorship positions in health economic evaluations. This study serves as a call to action for the scientific community to actively work towards equity and inclusion.

Fearlessness as an Underlying Mechanism Leading to Conduct Problems: Testing the INTERFEAR Model in a Community Sample in Spain.

Conduct problems (CP) in childhood and adolescence have a significant impact on the individual, family, and community. To improve treatment for CP, there is a need to improve the understanding of the developmental pathways leading to CP in boys and girls. Prior research has linked the child's fearlessness and callous-unemotional (CU) traits, as well as experiences of parental warmth and punitive parenting, to CP. However, few studies have tested the interplay of these factors in contributing to future CP development. The present study aimed to test the InterFear model, which suggests that fearlessness in early childhood leads to CP through an indirect pathway involving low positive parenting, high negative/punitive parenting, and callous-unemotional (CU) traits. The sample included 2467 Spanish children (48.1% girls; Mage = 4.25; SD = 0.91), followed up across a five-year period. Besides a direct association between fearlessness in early childhood and future CP, the results found an indirect pathway whereby fearlessness reduces positive parenting and increases punitive parenting, which contributes to the development of CU traits and sets the stage for CP in later childhood. The specific indirect effect from fearlessness to CP via CU traits accounted for most of the variance, suggesting the existence of a temperamental pathway independent of parental variables. Further, two additional indirect pathways, exclusive of fearlessness, were identified, which started with low parental warmth and positive parenting, leading to CP via CU traits. These findings support the InterFear model, demonstrating multiple pathways to CP with the involvement of fearlessness, parenting practices, and CU traits. This model might play a pivotal role in the development of targeted prevention and intervention strategies for CP.

Differences in the temporal trends of childhood overweight and obesity in Spain in the 2011-2019 period by sex, age and socioeconomic level: results of the ALADINO study.

INTRODUCTION: Childhood excess weight is a growing public health problem. The aim of this study was to assess temporal trends in the prevalence of overweight, obesity and central obesity in schoolchildren aged 6-9 years in Spain between 2011 and 2019 based on demographic and socioeconomic characteristics. METHODOLOGY: The analysis included data from the 2011, 2015 and 2019 rounds of the cross-sectional observational and descriptive ALADINO study in schoolchildren of both sexes aged 6-9 years. We conducted a descriptive analysis of the trends in the prevalence of overweight and obesity (defined according to the criteria of the World Health Organization and the International Obesity Task Force) and of central obesity, in addition to associated demographic and socioeconomic variables. RESULTS: Between 2011 and 2019, the prevalence of overweight (WHO criteria) decreased in boys aged 6, 7 and 8 years (by -5.4%, -5.7% and -5.3%, respectively) and boys whose parents had a higher educational attainment (by -5.3%). In relation to the socioeconomic level, overweight in boys declined at all income levels. However, between 2011 and 2019, both the prevalence of overweight in girls and the prevalence of obesity (applying the WHO and IOTF criteria) and the prevalence of central obesity in both sexes remained stable. CONCLUSIONS: The prevalence of overweight and the prevalence of obesity in schoolchildren aged 6-9 years in Spain remain high. Between 2011 and 2019, the prevalence of overweight in children aged 6-8 years and in children whose parents had university degrees decreased, whereas obesity in boys, overweight and obesity in girls and central obesity in both sexes remained stable.

The NDV-MLS as an Immunotherapeutic Strategy for Breast Cancer: Proof of Concept in Female Companion Dogs with Spontaneous Mammary Cancer.

The absence of tumor-infiltrating lymphocytes negatively impacts the response to chemotherapy and prognosis in all subtypes of breast cancer. Therapies that stimulate a proinflammatory environment may help improve the response to standard treatments and also to immunotherapies such as checkpoint inhibitors. Newcastle disease virus (NDV) shows oncolytic activity, as well as immune modulating potential, in the treatment of breast cancer in vitro and in vivo; however, its potential to enhance tumor-infiltrating immune cells in breast cancer has yet to be evaluated. Since spontaneous canine mammary tumors represent a translational model of human breast cancer, we conducted this proof-of-concept study, which could provide a rationale for further investigating NDV-MLS as immunotherapy for mammary cancer. Six female companion dogs with spontaneous mammary cancer received a single intravenous and intratumoral injection of oncolytic NDV-MLS. Immune cell infiltrates were evaluated by histology and immunohistochemistry in the stromal, intratumoral, and peritumoral compartments on day 6 after viral administration. Increasing numbers of immune cells were documented post-viral treatment, mainly in the peritumoral compartment, where plasma cells and CD3+ and CD3-/CD79- lymphocytes predominated. Viral administration was well tolerated, with no significant adverse events. These findings support additional research on the use of NDV-MLS immunotherapy for mammary cancer.

Emotion Recognition Deficits in Children and Adolescents with Psychopathic Traits: A Systematic Review.

Children and adolescents with psychopathic traits show deficits in emotion recognition, but there is no consensus as to the extent of their generalizability or about the variables that may be moderating the process. The present Systematic Review brings together the existing scientific corpus on the subject and attempts to answer these questions through an exhaustive review of the existing literature according to PRISMA 2020 statement. Results confirmed the existence of pervasive deficits in emotion recognition and, more specifically, on distress emotions (e.g., fear), a deficit that transcends all modalities of emotion presentation and all emotional stimuli used. Moreover, they supported the key role of attention to relevant areas that provide emotional cues (e.g., eye-region) and point out differences according to the presence of disruptive behavior and based on the psychopathy dimension examined. This evidence could advance the current knowledge on developmental models of psychopathic traits. Yet, homogenization of the conditions of research in this area should be prioritized to be able to draw more robust and generalizable conclusions.

The importance of a healthy lifestyle despite chronic pain: Prospective cohort with 11-year register follow-up.

The purpose of the study was to investigate to which extent a healthy lifestyle in female healthcare workers with chronic pain contributes to reducing the risk of disability pension. We conducted a prospective cohort study with an 11-year registry follow-up. Overall, 2386 Danish female healthcare workers with chronic pain completed a questionnaire about work and lifestyle (leisure-time physical activity, smoking, and body mass index (BMI)). Data on disability benefit payments were obtained from the Danish Register for Evaluation of Marginalization. Two models (minimally and fully adjusted for different potential confounders) were tested using the Cox proportional hazards model. During the follow-up period, 17.9% of the healthcare workers obtained disability pension. Low levels of leisure time physical activity (reference: moderate level) increased the risk of disability pension in the minimally (Hazard Ratio: 1.38 (95% CI: 1.14-1.69)) and fully adjusted models (Hazard Ratio: 1.27 (95% CI: 1.04-1.56)). Being highly physically active, as opposed to being moderately active, did not confer additional protection. Additionally, a positive association was observed between smoking and disability pension in the minimally adjusted model (Hazard Ratio: 1.27 (95% CI: 1.05-1.54)). BMI was not an influential factor. In female healthcare workers with chronic pain, at least moderate levels of physical activity is a protective factor for disability pension. Effective promotion strategies should be designed for both workplace and non-workplace settings.

In Search of Conceptual Clarity About the Structure of Psychopathic Traits in Children: A Network-Based Proposal.

Psychopathic traits in childhood have been revealed as potential identifiers of risk, being predictive of later forms of behavioral maladjustment. Yet, it is still under debate how psychopathic traits in children should be best conceptualized and which are the core dimensions for construct definition and prediction. The present study aims to examine the structure of psychopathic traits in childhood, and its predictive value, by using a combination of traditional factor analysis and more recent network-based methods. Data on psychopathic traits, as measured by the Child Problematic Traits Inventory (CPTI), were collected in a large sample of children (n = 2454; 48.2% girls), aged 3 to 6 at the onset of the study (Mage = 4.26; SD = 0.91), who were followed-up one and two years later using parent- and teacher-reports. Results showed that psychopathic traits measured via CPTI are best conceptualized as five latent factors encompassing grandiosity, deceitfulness, callousness, impulsivity and need of stimulation, a result that converged across informants and time. Callousness and grandiosity emerged as central traits using network analysis of parent-reports, while deceitfulness was most central using teacher-reports. Finally, callousness, impulsivity and deceitfulness emerged as the best predictors of concurrent, prospective and stable conduct problems. These results provide a refined structure of psychopathic traits in children that better accounts for the core elements of the construct. Additional theoretical and practical implications will be discussed in terms of assessment, diagnostic classification and tailored prevention/intervention.

The Prognostic Usefulness of Multiple Specifiers for Subtyping Conduct Problems in Early Childhood.

OBJECTIVE: To better describe and treat children with conduct problems (CP), grandiose-manipulative and daring-impulsive traits are proposed for subtyping CP, instead of using only a callous-unemotional specifier. However, the acclaimed benefits of having multiple specifiers for CP remain largely untested and therefore highly speculative. To fill this gap, this study tested longitudinal relations between these 3 specifiers and developmental outcomes in childhood and adolescence, independent of early childhood CP. METHOD: Longitudinal data from 2 community studies were used. Teacher ratings were used to measure CP and the specifiers in 3- to 5-year-olds from Sweden (n = 2,064) and Spain (n = 2,055). Developmental outcomes were assessed by multiple informants (ie, teachers, parents, and children) 1 to 8 years later. RESULTS: Early childhood CP were predictive of all outcomes. Callous-unemotional traits predicted low levels of social competence and prosocial behavior, independent of CP (and age, sex, and socioeconomic status). Grandiose-manipulative and daring-impulsive traits were predictive of aggression and violent delinquency, respectively, independent of CP, but also of higher levels of prosocial behavior or social competence. CONCLUSION: The 3 specifiers are predictive of different outcomes, independent of CP, which is thought to form the basis for developing specifiers for CP. Findings tentatively challenge the centrality of callous-unemotional traits for subtyping CP, but it is premature to conclude that grandiose-manipulative and daring-impulsive specifiers are needed in future revisions of DSM and ICD. Efforts to systematically evaluate the utility of these specifiers should be welcomed to inform ongoing debates on this matter.

Considerations for future modification of The Association for the Study of Reproductive Biology embryo grading system incorporating time-lapse observations.

The Association for the Study of Reproductive Biology (ASEBIR) Interest Group in Embryology (in Spanish 'Grupo de Interés de Embriología') reviewed key morphokinetic parameters to assess the contribution of time-lapse technology (TLT) to the ASEBIR grading system. Embryo grading based on morphological characteristics is the most widely used method in human assisted reproduction laboratories. The introduction and implementation of TLT has provided a large amount of information that can be used as a complementary tool for morphological embryo evaluation and selection. As part of IVF treatments, embryologists grade embryos to decide which embryos to transfer or freeze. At the present, the embryo grading system developed by ASEBIR does not consider dynamic events observed through TLT. Laboratories that are using TLT consider those parameters as complementary data for embryo selection. The aim of this review was to evaluate review time-specific morphological changes during embryo development that are not included in the ASEBIR scoring system, and to consider them as candidates to add to the scoring system.

Transparency, openness, and reproducible research practices are frequently underused in health economic evaluations.

OBJECTIVES: To investigate the extent to which articles of economic evaluations of healthcare interventions indexed in MEDLINE incorporate research practices that promote transparency, openness, and reproducibility. STUDY DESIGN AND SETTING: We evaluated a random sample of health economic evaluations indexed in MEDLINE during 2019. We included articles written in English reporting an incremental cost-effectiveness ratio in terms of costs per life years gained, quality-adjusted life years, and/or disability-adjusted life years. Reproducible research practices, openness, and transparency in each article were extracted in duplicate. We explored whether reproducible research practices were associated with self-report use of a guideline. RESULTS: We included 200 studies published in 147 journals. Almost half were published as open access articles (n = 93; 47%). Most studies (n = 150; 75%) were model-based economic evaluations. In 109 (55%) studies, authors self-reported use a guideline (e.g., for study conduct or reporting). Few studies (n = 31; 16%) reported working from a protocol. In 112 (56%) studies, authors reported the data needed to recreate the incremental cost-effectiveness ratio for the base case analysis. This percentage was higher in studies using a guideline than studies not using a guideline (72/109 [66%] with guideline vs. 40/91 [44%] without guideline; risk ratio 1.50, 95% confidence interval 1.15-1.97). Only 10 (5%) studies mentioned access to raw data and analytic code for reanalyses. CONCLUSION: Transparency, openness, and reproducible research practices are frequently underused in health economic evaluations. This study provides baseline data to compare future progress in the field.

Proposed Specifiers for Conduct Disorder (PSCD) self-report: Factor structure and validation in a community sample of Belgian youth.

The current study examined the psychometric properties of the Proposed Specifiers for Conduct Disorder (PSCD) in a sample of school-attending adolescent Belgian youth (N = 599; M age = 16.51 years, SD = 1.27). Given the recent interest in the PSCD-Short Version (PSCD-SV), this study focused on the 13-item variant of the PSCD. Study findings showed that the PSCD-SV had a hierarchical four-factor structure including the components of grandiose-manipulative (GM), callous-unemotional (CU), daring-impulsive (DI), and conduct disorder (CD). These interrelated factors were found to be internally consistent. The study also showed that the PSCD-SV total score was positively and significantly related to an alternate measure of psychopathy. Further, the study revealed the PSCD-SV was meaningfully related to the five-factor personality domains (i.e., extraversion, conscientiousness, agreeableness) as well as peer functioning and prosocial behavior. Bivariate correlations demonstrated that the dimensions differed in their associations with external correlates (e.g., peer functioning). Regression analyses showed that the GM, CU, and CD components of the PSCD-SV were uniquely associated to externalizing difficulties, whereas only the GM and CU components of the PSCD-SV were associated with low prosocial behaviors. These findings shed light on the conceptual and developmental models for the consideration of psychopathy and conduct problems. The use of the broader psychopathy condition as well as its underpinning dimensions may have important implications for assessment, treatment, and diagnostic manuals. The implications of the current study are further discussed.

Advances in robotic lung transplantation: development and validation of a new surgical technique in animal models.

The objective of this study was to describe a novel minimally invasive robotic video-assisted approach for lung transplantation, utilizing a minimally invasive technique with a subxiphoid incision, in an animal experimentation model. Two left robotic-assisted single lung transplants were performed in sheep using a robotic surgical system. A subxiphoid incision was made, and robotic ports were inserted into the thoracic cavity for dissection and anastomoses of the bronchus, artery, and pulmonary veins. The integrity of anastomoses was evaluated, and procedural details were recorded. Both animals survived the procedure, with a mean duration of 255 min and a mean console time of 201 min. Anastomoses were performed without complications, and the closed-chest approach with a subxiphoid incision proved successful in preventing gas leakage. The novel approach demonstrated improved exposure and workflow compared to existing techniques. The minimally invasive robotic video-assisted approach for lung transplantation utilizing a closed-chest technique with a subxiphoid incision appears safe and feasible in an animal experimentation model. Further studies in the clinical setting are warranted to establish its feasibility and safety in human lung transplantation. This approach has the potential to offer benefits over the traditional Clamshell incision in lung transplantation procedures.

Adverse childhood experiences and residential care environment: The mediating role of trauma-related symptoms and psychological maladjustment in adolescents.

BACKGROUND: Research has consistently found poorer outcomes in adolescents who have been exposed to early interpersonal adversities, especially those in out-of-home placements. The presence of mental health problems also contributes to the perception of a more negative group climate and peer interactions through cascading effects. OBJECTIVE: To analyze the sequential relationships between exposure to adverse childhood experiences (ACEs), trauma-related symptoms, psychological maladjustment, and the perception of group climate and peer interactions. In addition, the study analyzes the mediating role of trauma-related symptoms and psychological maladjustment. PARTICIPANTS AND SETTING: The sample comprised 161 adolescents in out-of-home care (46.6 % males, 49.7 % females, 3.7 % non-binary), aged 12-18 (M = 15.22, SD = 1.59) from 24 residential facilities in Spain. METHODS: This study is part of the VRINEP project. Group care workers reported about ACEs and trauma-related symptoms through online questionnaires, whereas adolescents self-reported about psychological maladjustment, group climate, and peer interactions. RESULTS: Differential associations between ACEs with trauma-related symptoms and internalizing problems were found. The relationship between certain ACEs and externalizing problems was fully mediated by trauma-related symptoms. Likewise, psychological maladjustment was related to a more negative perception of the group climate and peer interactions. Although trauma-related symptoms were not directly associated with the perception of the residential environment, they were indirectly associated with peer relational aggression through externalizing problems. CONCLUSIONS: Mental health has a significant impact on the perception of the group climate and peer interactions among adolescents in residential care who have been exposed to ACEs.