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Abstract Background Neutrophil-to-Lymphocyte Ratio (NLR) has been postulated as a useful inflammatory biomarker in the prediction of complications in different pediatric diseases. Our aim is to analyze the predictive value of NLR in the development of complications in burned children, both in the short-term (need for grafting) and in the long-term (need for surgery of the sequelae). Methods A retrospective study was performed on burned patients under 18-years admitted to our Burn Unit between 2015 and 2021. Demographic, clinical and laboratory data at admission were evaluated. Predictive factors for the development of complications after burns (time of evolution, burned total body surface area, and acute phase reactants) were analyzed using sensitivity and specificity analysis (ROC curves). Results A total of 342 patients (198 males, 144 females) were included, with a median age of 27 months (interquartile range 15–83 months). In 97.4% of the cases, burns were primarily caused by thermal injuries (78.4% scald burns). Acute escharectomy and grafting were performed in 85 patients (24.9%), while long-term sequelae were observed in 112 cases (32.7%). NLR was the most sensitive and specific predictor for the need for escharectomy and grafting (Sensitivity 90%, Specificity 88.4%; AUC 0.920), for the development of long-term sequelae (Sensitivity 80.4%, Specificity 83.5%; AUC 0.849) and for the need for surgery of the sequelae (Sensitivity 83.5%, Specificity 80.9%; AUC 0.833). Conclusion NLR may be considered a useful predictor for the development of short- and long-term complications in childhood burns. It may help in the identification of high-risk patients to prevent sequelae.

Abstract Ecosystem services (ES) are benefits people receive from nature. To sustain these benefits, we need to spatially connect communities benefitting from specific ES with landscape features that generate the ES. A variety of process‐based models support ES assessments by estimating the biophysical supply of ES that comes from landscapes. However, less attention has been given to how ES flow from landscapes to beneficiary groups. A ‘serviceshed’ is defined as the spatial area that provides an ecosystem service to beneficiaries at a specific location—thus connecting people to the landscapes and seascapes upon which they depend through ES flows. In this article, we propose a general framework to empirically define serviceshed boundaries. Using publicly available data, we apply this framework to two provisioning and two regulating services (1) agricultural and fishing livelihoods and (2) pollination and coastal flood control, respectively, in Canada. We find that agricultural fields of different types and sizes contribute livelihood value to 85% of the communities in the agricultural landscape, and fishing grounds of different sizes contribute to 24% of the communities in the fishing study area. On average, communities with a lower proportion of agricultural labour are associated with larger fields, whilst larger fishing grounds were associated with communities with a greater percentage of their population in fisheries, showing how different ES can have varied relationships with beneficiary communities. For regulating services, we find 66% of pollinator‐supplying areas are within the serviceshed of farming communities. Natural habitats and agricultural land account for 72% and 28% of this serviceshed area, respectively. Our models suggest also that 26% of saltmarshes are within the serviceshed of flood‐prone communities and most coastal communities in our study area benefit from saltmarshes, especially from those without dykes. We demonstrate how serviceshed mapping, when integrating social and ecological information, can be useful in multiple decision contexts. Servicesheds can help planners and managers better design zoning restrictions, restoration activities to benefit communities, or subsidy programmes to replace the value of ES lost due to climate change or land use development. Read the free Plain Language Summary for this article on the Journal blog.

Esse artigo apresenta um estudo narrativo que objetiva compartilhar as experiências, de uma psicóloga residente, durante a pandemia de COVID-19. Articula relações entre Saúde Coletiva e Psicanálise, trazendo as diretrizes da Política Nacional de Humanização (PNH) e os conceitos da teoria do amadurecimento de Donald Woods Winnicott para pensar um cuidado possível, ou suficientemente bom, no trabalho multiprofissional em saúde, em uma Unidade de Saúde da Família, na região sul do Brasil. Como estratégia metodológica foi utilizada a pesquisa narrativa. Para a produção dos dados foram realizados registros do cotidiano de trabalho em diário de campo, emergindo três temas de análise: valorização do trabalhador, ambiência e acolhimento. O processo de análise esteve ancorado nas articulações entre as diretrizes da PNH e conceitos da psicanálise Winnicottiana. para dar sentido e corpo às discussões. Os dados produzidos apontam que o cuidado suficientemente bom em saúde pública está fortemente atrelado às diretrizes da constituição de espaços receptivos, acolhedores para as demandas que chegam à atenção primária, e ainda, a implementação de estratégias de reconhecimento de valorização do trabalho em saúde. A pesquisa narrativa realizada possibilitou, não só a própria reflexão sobre as práticas de cuidado empregadas em campo, mas também contribuiu para que outros profissionais da atenção básica possam tecer um cuidado suficientemente bom a partir do preconizado nas diretrizes da PNH e das contribuições da psicanálise de D. W. Winnicott.

Abstract How are arbitrary sequences of verbal information retained and manipulated in working memory? Increasing evidence suggests that serial order in verbal WM is spatially coded and that spatial attention is involved in access and retrieval. Based on the idea that brain areas controlling spatial attention are also involved in oculomotor control, we used eye tracking to reveal how the spatial structure of serial order information is accessed in verbal working memory. In two experiments, participants memorized a sequence of auditory words in the correct order. While their eye movements were being measured, they named the memorized items in a self-determined order in Experiment 1 and in a cued order in Experiment 2. We tested the hypothesis that serial order in verbal working memory interacts with the spatial attention system whereby gaze patterns in visual space closely follow attentional shifts in the internal space of working memory. In both experiments, we found that the gaze shifts in visual space correlated with the spatial shifts of attention along the left-to-right one-dimensional mapping of serial order positions in verbal WM. These findings suggest that spatial attention is employed for dynamically searching through verbal WM and that eye movements reflect the spontaneous association of order and space even in the absence of visuospatial input.

Abstract The aging process is marked by a time-dependent deterioration in cellular functions, particularly the immune and neural systems. Understanding the phenotype acquisition of microglia, the sentinel immune cells of the brain, is crucial for understanding the nature of age-related neurological diseases. However, the specific phenotype adopted by microglia during aging remains a subject of debate and is contingent on the chosen experimental model. To address these unresolved questions, we employed a novel and highly controlled approach utilizing long-term cultivated BV-2 microglia, exempted from additional external stimuli. Our findings revealed that aged microglial cells, in comparison to their younger counterparts, acquire a distinct gene expression profile, primarily characterized by alterations in microglial immune response. Indeed, pro-inflammatory stimulated aged and young BV-2 microglia exhibited similar transcriptomic profiles, yet the response intensity to the stimulus was markedly muted in the aged microglia. Functional neurotoxic assays confirmed diminished neuronal death in coculture with aged, activated microglia, underscoring a compromised immune response. Furthermore, a subsequent comparative analysis of aged BV-2 microglia with established transcriptomic microglial datasets from aged mice and humans identified 13 overlapping genes, laying the foundation for identifying core microglial aging signature. Particularly noteworthy were SLC16A3 and P2RY13, which consistently exhibited upregulation and downregulation, respectively, across all datasets. Additionally, four other genes—CAPG, LGALS3BP, NRIP1, and P2RY12—were found to share regulatory patterns in response to both aging and extrinsic activation. An in-depth investigation focused on SLC16A3, encoding the high-affinity lactate transporter MCT4, revealed disruptions in extracellular acidification rate and lactate concentration with age. Microglial purine sensing and motility capacities, regulated by P2RY12/P2RY13, displayed age-related alterations. Remarkably, protein analysis in human brain tissue validated the observed upregulation of MCT4 and downregulation of P2RY12 in aged microglia. In conclusion, our study unveils a distinct phenotype in aged microglia characterized by compromised immune responsiveness. Through the integration of in vitro cultured BV-2 microglia with primary microglia datasets, we identify critical molecular determinants of microglial cellular aging confirmed in human-aged brain tissue. This comprehensive approach offers potential insights for understanding and potentially reprogramming aged microglia, with implications for combating age-related neurological disorders.

Abstract B cells have emerged as central players in the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC). However, although there is clear evidence for their involvement in cancer immunity, scanty data exist on the characterization of B cell phenotypes, bioenergetic profiles and possible interactions with T cells in the context of NSCLC. In this study, using polychromatic flow cytometry, mass cytometry, and spatial transcriptomics we explored the intricate landscape of B cell phenotypes, bioenergetics, and their interaction with T cells in NSCLC. Our analysis revealed that TME contains diverse B cell clusters, including VISTA+ Bregs, with distinct metabolic and functional profiles. Target liquid chromatography-tandem mass spectrometry confirmed the expression of VISTA on B cells. VISTA+ Bregs displayed high metabolic demand and were able to produce different cytokines, including interleukin (IL)-10, transforming growth factor (TGF)-β, IL-6, tumor necrosis factor (TNF), and granulocyte–macrophage colony-stimulating factor (GM-CSF). Spatial analysis showed colocalization of B cells with CD4+/CD8+ T lymphocytes in TME. The computational analysis of intercellular communications that links ligands to target genes, performed by NicheNet, predicted B-T interactions via VISTA-PSGL-1 axis. Colocalization analyses revealed that PSGL-1 T cells and VISTA+ B cells are adjacent in the TME. Notably, tumor infiltrating CD8+ T cells expressing PSGL-1 exhibited enhanced metabolism and cytotoxicity. In NSCLC patients, prediction analysis performed by PENCIL revealed the presence of an association between PSGL-1+CD8+ T cells and VISTA+ Bregs with lung recurrence. Our findings suggest a potential interaction between Bregs and T cells through the VISTA-PSGL-1 axis, that could influence NSCLC recurrence.

Background: Cancer patients who are exposed to sepsis and had previous chemotherapy may have increased severity. Among chemotherapeutic agents, anthracyclines have been associated with cardiac toxicity. Like other chemotherapeutic agents, they may cause endothelial toxicity. The aim of this study was to evaluate the effect of anthracycline treatment on the outcome of cancer patients with sepsis. Methods: Data from cancer patients admitted to intensive care units (ICUs) for sepsis or septic shock were extracted from the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique database (1994–2015). Comparison between patients who received anthracycline and those who did not was performed using a propensity score, including confounding variables (age and underlying diseases). A competing risk adjusted for severity of illness (Sequential Organ Failure Assessment [SOFA] score) was used to analyze the duration of vasopressor requirement. Results: Among 2046 patients, 1070 (52.3%) patients who received anthracycline were compared with 976 (47.7%) who did not. The underlying disease was mostly acute hematological malignancy (49.2%). Sepsis, mostly pneumonia (47.7%), had developed 2 days (interquartile range [IQR]:1–4 days) prior to ICU admission. Most patients (n=1156/1980,58.4%) required vasopressors for 3 days (IQR: 2–6 days). Factors associated with the need for vasopressors were aplasia (hazard ratio [HR]=1.72, 95% confidence interval [CI]: 1.21 to 2.47, P=0.002) and day 1 respiratory SOFA score (HR=7.07, 95% CI: 2.75 to 22.1, P

Abstract A significant challenge in computational chemistry is developing approximations that accelerate ab initio methods while preserving accuracy. Machine learning interatomic potentials (MLIPs) have emerged as a promising solution for constructing atomistic potentials that can be transferred across different molecular and crystalline systems. Most MLIPs are trained only on energies and forces in vacuum, while an improved description of the potential energy surface could be achieved by including the curvature of the potential energy surface. We present Hessian QM9, the first database of equilibrium configurations and numerical Hessian matrices, consisting of 41,645 molecules from the QM9 dataset at the ωB97x/6-31G* level. Molecular Hessians were calculated in vacuum, as well as water, tetrahydrofuran, and toluene using an implicit solvation model. To demonstrate the utility of this dataset, we show that incorporating second derivatives of the potential energy surface into the loss function of a MLIP significantly improves the prediction of vibrational frequencies in all solvent environments, thus making this dataset extremely useful for studying organic molecules in realistic solvent environments for experimental characterization.

Abstract Anhedonia, characterized by diminished motivation and pleasure sensitivity, is increasingly recognized as prevalent among patients with chronic pain. Deep Endometriosis (DE), the most severe endophenotype of the disease, is commonly presented with chronic pelvic pain. This cross-sectional study reports, for the first time, the prevalence of anhedonia in a sample comprised by 212 premenopausal women with suspected DE referred to a tertiary hospital. Our findings show that 27,8% [95% CI 22.1, 26.5] of DE patients experience abnormal hedonic tone. Severity of DE pain-related symptoms significantly correlated with anhedonia, consistent with previous findings. Chronic pelvic pain emerged as a significant predictor of anhedonia (OR 1.5, 95% CI 1.0–1.22, p

Abstract To fully harness mesenchymal-stromal-cells (MSCs)’ benefits during Normothermic Machine Perfusion (NMP), we developed an advanced NMP platform coupled with a MSC-bioreactor and investigated its bio-molecular effects and clinical feasibility using rat and porcine models. The study involved three work packages: 1) Development (n = 5): MSC-bioreactors were subjected to 4 h-liverless perfusion; 2) Rat model (n = 10): livers were perfused for 4 h on the MSC-bioreactor-circuit or with the standard platform; 3) Porcine model (n = 6): livers were perfused using a clinical device integrated with a MSC-bioreactor or in its standard setup. MSCs showed intact stem-core properties after liverless-NMP. Liver NMP induced specific, liver-tailored, changes in MSCs’ secretome. Rat livers exposed to bioreactor-based perfusion produced more bile, released less damage and pro-inflammatory biomarkers, and showed improved mithocondrial function than those subjected to standard NMP. MSC-bioreactor integration into a clinical device resulted in no machine failure and perfusion-related injury. This proof-of-concept study presents a novel MSC-based liver NMP platform that could reduce the deleterious effects of ischemia/reperfusion before transplantation.

Abstract Background Dieting is a common practice around the world. People who wish to lose weight, improve their eating habits, or reach a desired level of health often diet. Rumination, a pattern of repetitive negative thoughts and emotions, is typically found when individuals diet. The current study aimed to identify physical and psychological differences between maladaptive and normative eating behaviors in a sample from Lebanon. Methods A cross-sectional design was adopted for the current study. It occurred between June and July 2022. Four hundred participants aged 18 and above participated. The research team used a snowball sampling method to recruit volunteers from all governorates of Lebanon. Results Beta values were used to compare independent variables in order to infer those that have the strongest effect on the dependent ones. Higher Body Mass Index, and belonging to cluster 3 (restriction of food intake and rumination) and cluster 1 (maladaptive eating behavior and rumination) compared to cluster 2 (normative eating behavior and thought) were significantly related to more dieting. Higher physical activity index and belonging to cluster 3 (restriction of food intake and rumination) and cluster 1 (maladaptive eating behavior and rumination) compared to cluster 2 (normative eating behavior and thought) were significantly related to higher levels of orthorexia nervosa tendencies. Conclusions The current research demonstrated a relationship between Body Mass Index, physical activity, rumination, and maladaptive eating patterns including restriction of food intake, dieting, and orthorexia nervosa. These results can help with identifying physical and psychological factors associated with maladaptive eating patterns, as well as guide interventions within the Lebanese population.

Abstract Background Women in the postpartum period are at greater risk of intimate partner violence (IPV), which may cause physical, sexual, or psychological harm and have a long-lasting negative impact on mother and child. Seeking help in case of IPV in the postpartum period can be difficult. Objective The purpose of this study was to examine service preferences among postpartum women in Germany (non-)affected by IPV. Methods In the cross-sectional study INVITE, postpartum mothers (n = 3,509) were interviewed via telephone. Using the WHO-Violence Against Women Instrument (WHO-VAWI), women were divided into groups: non-affected women and women affected by psychological, physical, and/or sexual IPV. Using analyses of variance, group differences regarding preferred services and modes of service provision were assessed. Examined service domains were psychosocial services (e.g., women´s shelter or self-help groups), medical services (e.g., gynecologist or emergency room), and midwives. Modes of service provision included direct communication (e.g., in person or video conference) and indirect communication (e.g., chat or e-mail). Results People from the women's social environment (e.g., family, friends) and specialized IPV services, such as women's shelters, were the most preferred support. Regarding service categories, women who experienced any type of IPV rated all three service domains less likely to be used than non-affected women. Most preferred provision mode was “in person”. Women affected by physical and/or sexual IPV rated direct modes more negatively than non-affected women. However, there were no differences between (non-)affected women regarding indirect modes, such as e-mails or apps. Discussion The present results indicate that services were rated less likely to be used by postpartum women affected by IPV. Potential barriers which lead to these ratings need to be investigated. Efforts should be made to increase awareness of IPV and the beneficial effects of support.

Using the 2000 Census and 2005–2019 American Community Surveys, we examine the propensity of older adults to live with children. We show that seniors from disadvantaged subgroups are more likely to live in multi- or skip-generational arrangements. Contextual factors associated with more multigenerational living include a less generous safety net and high housing costs. Skip-generational living is associated with high female incarceration rates. Conditional on demographic characteristics and these contextual factors, seniors in multigenerational living arrangements are less likely to be in poverty and those in skip-generational arrangements more likely. Overall, the findings are consistent with the possibility that multigenerational arrangements help families address resource needs, whereas skip-generational arrangements heighten the risk of poverty or reflect crises that do so.

Amyotrophic lateral sclerosis (ALS) is a multisystem neurodegenerative disorder characterized by progressive motor decline. Studies of electroencephalographic (EEG) activity during rest and motor execution have captured network changes in ALS. However, the nature of network-level impairment in the pre-motor activity in ALS remains unclear. Assessing the (dys)function of motor networks engaged prior to motor output is essential for understanding the motor pathophysiology in ALS. We recorded EEG in 22 people with ALS (PwALS) and 16 age-matched healthy controls during rest and isometric pincer-grip tasks. EEG spectral power and coherence were calculated during rest, pre-motor stage, and motor execution. In PwALS, significantly higher event-related spectral perturbations were observed compared to controls over electrodes representing a) contralateral prefrontal and parietal regions in theta band during pre-motor stage, b) contralateral parietal and ipsilateral motor regions in high-beta band during motor execution. Similarly, spectral coherence revealed abnormal EEG connectivity within 1) sensorimotor network during rest in theta band, 2) (pre)motor networks during pre-motor stage in low-alpha and high-beta bands, 3) Fronto-parietal networks during execution in high-beta band. Furthermore, the abnormal EEG connectivity during rest and execution (but not during pre-motor stage) showed significant negative correlation with clinical ALS-functional-rating-scale scores. Combining abnormal EEG connectivity from rest, pre-motor, and execution stages provided more powerful discrimination between patients and controls with a uniquely higher contribution of measures pertaining to the pre-motor stage. The results indicate that pre-motor functional activity reflects a different and unique aspect of network impairment, with potential for inclusion as biomarker candidates in ALS.

Abstract The European Commission’s Strategy for the Rights of Persons with Disabilities 2021–2030 aims to ensure equal opportunities and rights for all individuals, including those with intellectual disabilities. People with intellectual disabilities are often underrepresented in cancer prevention and screening policies, leading to disparities in health outcomes and early mortality. The intersection of intellectual disability, cancer, and depression represents an underexplored area in healthcare research. Individuals with intellectual disability diagnosed with both cancer and depression face compounded challenges impacting their quality of life, proper access to medical care, and treatment outcomes. To address these gaps in the systems globally, a focused effort is indispensable to understand their unique needs and better tailor care strategies for this target group. Therefore, this commentary outlines the challenges in researching individuals with intellectual disabilities who have a dual diagnosis of cancer and depression. Challenges include providing informed consent, ethical researcher–participant relationships, and maintaining confidentiality and autonomy. Strategies for improvement include creating accessible procedures, raising awareness, and involving individuals with intellectual disabilities in research ethics committees.

Abstract Background Fruit quality traits, including taste, flavor, texture, and shelf-life, have emerged as important breeding priorities in blueberry (Vaccinium corymbosum). Organic acids and sugars play crucial roles in the perception of blueberry taste/flavor, where low and high consumer liking are correlated with high organic acids and high sugars, respectively. Blueberry texture and appearance are also critical for shelf-life quality and consumers’ willingness-to-pay. As the genetic mechanisms that determine these fruit quality traits remain largely unknown, in this study, an F1 mapping population was used to perform quantitative trait loci (QTL) mapping for pH, titratable acidity (TA), organic acids, total soluble solids (TSS), sugars, fruit size, and texture at harvest and/or post-storage and weight loss. Results Twenty-eight QTLs were detected for acidity-related parameters (pH, TA, and organic acid content). Six QTLs for pH, TA, and citric acid, two for quinic acid, and two for shikimic acid with major effects were consistently detected across two years on the same genomic regions on chromosomes 3, 4, and 5, respectively. Putative candidate genes for these QTLs were also identified using comparative transcriptomic analysis. No QTL was detected for malic acid content, TSS, or individual sugar content. A total of 146 QTLs with minor effects were identified for texture- and size-related parameters. With a few exceptions, these QTLs were generally inconsistent over years and post-storage, indicating a highly quantitative nature. Conclusions Our findings enhance the understanding of the genetic basis underlying fruit quality traits in blueberry and guide future work to exploit DNA-informed selection strategies in blueberry breeding programs. The major-effect QTLs identified for acidity-related fruit characteristics could be potential targets to develop DNA markers for marker-assisted selection (MAS). On the other hand, genomic selection may be a more suitable approach than MAS when targeting fruit texture, sugars, or size.

Abstract Background TP53 variant classification benefits from the availability of large-scale functional data for missense variants generated using cDNA-based assays. However, absence of comprehensive splicing assay data for TP53 confounds the classification of the subset of predicted missense and synonymous variants that are also predicted to alter splicing. Our study aimed to generate and apply splicing assay data for a prioritised group of 59 TP53 predicted missense or synonymous variants that are also predicted to affect splicing by either SpliceAI or MaxEntScan. Methods We conducted splicing analyses using a minigene construct containing TP53 exons 2 to 9 transfected into human breast cancer SKBR3 cells, and compared results against different splice prediction methods, including correlation with the SpliceAI-10k calculator. We additionally applied the splicing results for TP53 variant classification using an approach consistent with the ClinGen Sequence Variant Interpretation Splicing Subgroup recommendations. Results Aberrant transcript profile consistent with loss of function, and for which a PVS1 (RNA) code would be assigned, was observed for 42 (71%) of prioritised variants, of which aberrant transcript expression was over 50% for 26 variants, and over 80% for 15 variants. Data supported the use of SpliceAI ≥ 0.2 cutoff for predicted splicing impact of TP53 variants. Prediction of aberration types using SpliceAI-10k calculator generally aligned with the corresponding assay results, though maximum SpliceAI score did not accurately predict level of aberrant expression. Application of the observed splicing results was used to reclassify 27/59 (46%) test variants as (likely) pathogenic or (likely) benign. Conclusions In conclusion, this study enhances the integration of splicing predictions and provides splicing assay data for exonic variants to support TP53 germline classification. Graphical abstract

The Galinha dinosaur tracksite (Portugal) was declared a Natural Monument in 1996 and is currently designated as Ourém/Torres Novas Dinosaur Footprints Natural Monument. This tracksite yields a completely new and unique morphology of sauropod tracks from the Middle Jurassic (Bajocian–Bathonian). This new morphotype was named Polyonyx by Santos et al. (2009). However, recently it has been brought to our attention that this ichnotaxon name “Polyonyx” is preoccupied by the porcellanid decapod Polyonyx Stimpson, 1858 (Crustacea: Decapoda: Anomura: Porcellanidae). The priority is given to the latter and to avoid homonymy, the former is issued the new replacement name Galinhapodus igen. nov., creating the new replacement combination name Galinhapodus gomesi.

Abstract Streptococcus pneumoniae and influenza A virus (IAV) are significant agents of pneumonia cases and severe respiratory infections globally. Secondary bacterial infections, particularly by Streptococcus pneumoniae, are common in IAV-infected individuals, leading to critical outcomes. Despite reducing mortality, pneumococcal vaccines have high production costs and are serotype specific. The emergence of new circulating serotypes has led to the search for new prevention strategies that provide a broad spectrum of protection. In this context, vaccination using antigens present in all serotypes, such as Pneumococcal Surface Protein A (PspA), can offer broad coverage regardless of serotype. Employing the reverse genetics technique, our research group developed a recombinant influenza A H1N1 virus that expresses PspA (Flu-PspA), through the replacement of neuraminidase by PspA. This virus was evaluated as a bivalent vaccine against infections caused by influenza A and S. pneumoniae in mice. Initially, we evaluated the Flu-PspA virus’s ability to infect cells and express PspA in vitro, its capacity to multiply in embryonated chicken eggs, and its safety when inoculated in mice. Subsequently, the protective effect against influenza A and Streptococcus pneumoniae lethal challenge infections in mice was assessed using different immunization protocols. Analysis of the production of antibodies against PspA4 protein and influenza, and the binding capacity of anti-PspA4 antibodies/complement deposition to different strains of S. pneumoniae were also evaluated. Our results demonstrate that the Flu-PspA virus vaccine efficiently induces PspA protein expression in vitro, and that it was able to multiply in embryonated chicken eggs even without exogenous neuraminidase. The Flu-PspA-based bivalent vaccine was demonstrated to be safe, stimulated high titers of anti-PspA and anti-influenza antibodies, and protected mice against homosubtypic and heterosubtypic influenza A and S. pneumoniae challenge. Moreover, an efficient binding of antibodies and complement deposition on the surface of pneumococcal strains ascribes the broad-spectrum vaccine response in vivo. In summary, this innovative approach holds promise for developing a dual-protective vaccine against two major respiratory pathogens.

Abstract Background Time to deterioration (TTD) endpoints are often utilized in the analysis of patient-reported outcome (PRO) data in oncology clinical trials but different endpoint definitions and analysis frameworks exist that can impact result interpretation. This review examined the analysis, reporting and heterogeneity of TTD endpoints in the literature, the impact of analysis methods on results, and provides recommendations for future trials. Methods A targeted literature review of articles published between 2017 and 2022 was performed to collate TTD endpoints reported in oncology randomized controlled trials (RCTs). Details of endpoints and results were extracted including; deterioration definition, PRO assessment schedule, methods for handling intercurrent events, statistical analysis methods, main trial results (overall survival and/or progression-free survival) and TTD endpoint results. Results Seventy RCTs were included covering 849 individual TTD endpoints. There were 17 primary cancer types, with lung (26%), breast (11%), and prostate (7%) cancers the most common. Most trials (71%) were for people with advanced cancer. Full definitions of TTD endpoints were often missing. There were no clear trends for a specific TTD definition within cancer types or stages. However, statistical analysis methods were consistent among trials. Conclusion The TTD definition can vary and is ultimately driven by the research question. Points to consider for successfully implementing PRO TTD endpoints in oncology include consideration of the trial setting (e.g., early vs. advanced cancer), expected treatment effect (e.g., improvement vs. worsening), likely adverse event profile (including early vs. delayed) and PRO data collection frequency in order to improve utility of these endpoints.

Abstract Objectives Describe tofacitinib safety from an integrated analysis of randomized controlled trials (RCTs) in patients with ankylosing spondylitis (AS). Method Pooled data from Phase 2 (NCT01786668; 04/2013–03/2015)/Phase 3 (NCT03502616; 06/2018–08/2020) RCTs in AS patients were analyzed (3 overlapping cohorts): 16-week placebo-controlled (tofacitinib 5 mg twice daily [BID] [n = 185]; placebo [n = 187]); 48-week only-tofacitinib 5 mg BID (n = 316); 48-week all-tofacitinib (≥ 1 dose of tofacitinib 2, 5, or 10 mg BID; n = 420). Baseline 10-year atherosclerotic cardiovascular disease (ASCVD) risk was determined in patients without history of ASCVD (48-week cohorts). Adverse events (AEs)/AEs of special interest were evaluated/compared with findings from other tofacitinib programs (16 Phase 2/Phase 3 rheumatoid arthritis [RA]; 2 Phase 3 psoriatic arthritis [PsA] RCTs) and a real-world cohort of AS patients initiating biologic disease-modifying antirheumatic drugs (US MarketScan). Results Most patients (> 75%; 48-week cohorts) without history of ASCVD had low baseline 10-year ASCVD risk. One patient (tofacitinib 5 mg BID; in all 3 cohorts) had a serious infection (aseptic meningitis). Herpes zoster (non-serious) occurred in the 48-week only-tofacitinib 5 mg BID (n = 5 [1.6%]) and all-tofacitinib (n = 7 [1.7%]; one multi-dermatomal [tofacitinib 10 mg BID]) cohorts. No deaths, opportunistic infections, tuberculosis, malignancies, major adverse cardiovascular events, thromboembolic events, gastrointestinal perforations occurred. Limitations: short RCT durations/low patient numbers within cohorts. Conclusion Tofacitinib 5 mg BID was well tolerated to 48 weeks in AS patients; safety profile was consistent with RA/PsA clinical programs and a cohort of AS patients from US routine clinical practice. Clinical trial registration numbers NCT01786668 (2013-02-06); NCT03502616 (2018-04-11).

The East African country of Djibouti is known to host an important seasonal feeding aggregation of whale sharks that allows the frequent observation of their surface feeding behaviour. The influence of environmental factors on the different whale shark feeding strategies (passive, active, and vertical) was studied over a four-year period (2017, 2020, 2022, 2024) in the Gulf of Tadjoura. Across 81 immature male whale sharks identified and 1082 surface feeding behaviours recorded in this period, the chlorophyll-a concentration was the main parameter predicting the choice of the filter-feeding technique. Active and vertical feeding behaviours were associated with rainfall, lower sea surface temperature, worse sea conditions, and low wind speed during the morning, all factors positively correlated to chlorophyll-a concentration. On the contrary, passive feeding behaviour was favoured in the inverse environmental conditions. Both passive and vertical feeding behaviours occurred during El Niño events, whereas active feeding was more common during La Niña events. Since it is known that whale shark abundance and distribution are associated with food availability at coastal locations, it is fundamental to understand environmental drivers of filter-feeding strategies when managing conservation efforts for this endangered species. Recommendations for future research work at this site are presented.

Voluntary blood donation plays a crucial role in public health by ensuring a stable supply of blood and its components, essential for medical treatments including surgeries, trauma care, and chronic disease management. Voluntary donors, often healthier individuals, enhance the safety of the blood supply and play a vital role in emergency preparedness. Beyond its societal benefits, regular blood donation may offer health advantages for donors, including improved cardiovascular health due to reduced iron levels and psychological benefits stemming from altruism and a sense of social responsibility. Public health initiatives are instrumental in fostering blood donation through education, awareness campaigns, and targeted donor recruitment strategies. These efforts encourage a culture of social responsibility, inspiring community participation and improving overall healthcare system sustainability. Despite these efforts, challenges such as fluctuating donation rates, aging populations, and shifting demographics underscore the need for ongoing initiatives to ensure a sufficient blood supply. As a public health priority, voluntary blood donation demands continuous promotion and innovation to meet the growing demand for blood products and maintain healthcare system resilience. This review highlights the public health significance of voluntary blood donation, with particular focus on its benefits for donors and its role in supporting healthcare systems.

Nonbreeding white rhino bulls are traditionally housed individually in zoos, but space limitations require the exploration of alternative techniques. There are no studies of group-housed bulls, and the feasibility of managing a bachelor group is unknown. Six bulls (two bulls each of 3-, 5-, and 8-yr-olds) in a 3.1 ha enclosure were observed for 30 min each 2×/wk for 20–31 wks. The 3-yr-olds were relocated after the first 20 weeks. Rhino location, nearest neighbor, aggressive behaviors, and dominance interactions were recorded. There was no evidence of habitat spatial segregation. The 3- and 5-yr-olds grouped together by age; 8-yr-olds did not associate as much as younger rhinos. Aggressive vocalizations and physical aggression were infrequent (range 0–1.5/h/bull and 0–1/h/bull, respectively). Eight-year-olds displayed and received aggressive vocalizations the most; three-year-olds displayed and received physical aggression the most. After the 3-yr-olds were removed, the habitat usage and social proximity of the remaining bulls did not change. Aggressive behaviors increased, but vocalizations (range 0.18–3.1/h/bull) remained more frequent than physical aggression (range 0.18–0.73/h/bull). The highest-ranking 8-yr-old engaged in physical altercations the least. The bulls shared space, and the use of vocalizations more than physical aggression deterred injury. These findings indicate that bachelor group management is feasible in a large enclosure with young bulls.

Abstract Background Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, characterized by impairments in social interaction and communication with restricted and repetitive behavior. Postural and motor disturbances occur more often in ASD, in comparison to typically developing subjects, affecting the quality of life. Linear and non-linear indexes derived from the trajectory of the center of pressure (COP) while subjects stand on force platforms are commonly used to assess postural stability. The aim of the present feasibility study was to investigate whether combining linear and non-linear parameters of the COP during stance in subjects with ASD, could provide insight on specific features of motor dysfunction possibly linked to ASD cognition and clinical characteristics. Methods Twenty-two males, aged 10–15 years, including subjects with ASD and healthy controls (N = 11, respectively), were studied. They all had normal cognitive level and independent walking ability. A piezoelectric force platform was used to evaluate posture over three feet positions, with eyes open, closed and during visually-guided saccades. Linear (sway path, total area and root mean square) and non-linear parameters (fractal dimension and sample entropy) of the COP were measured to determine postural stability and the complexity and regularity of the COP signals. GLMM analyses were performed to assess COP parameter changes across experimental conditions and subject groups. Finally, Spearman correlations evaluated the significance of potential relationships between linear and non-linear measures as well as between non-linear parameters and clinical data in patients with ASD. Results Compared to controls, subjects with ASD showed reduced postural stability and complexity, with higher regularity of COP trajectories, particularly in the most unstable feet positions, during visually-guided saccades and in the medial-lateral direction. Spearman correlations indicated that, in the patients’ group, postural instability was associated with a decrease in the geometric complexity and an increase in the regularity of the COP trajectory. Moreover, the increase in regularity of the COP trajectory was associated to the severity of restricted and repetitive behavior. Conclusions The results of this study highlight the importance of combining linear and non-linear measures in evaluating postural control in patients with ASD, also with respect to the outcome of interventions on these patients targeting postural balance.

Abstract This pragmatic double-blind randomized clinical trial aims to assess the impact of vascular photobiomodulation on post-COVID-19 patients experiencing tension-type headache, orofacial pain, or both persisting for more than 3 months. Participants were divided into two groups: vascular photobiomodulation (VPBM) and simulated VPBM. Their conditions were evaluated using the Brief Pain Inventory (BPI), Visual Analogue Scale, and Headache Impact Test (HIT-6). Data analysis included both inter and intragroup assessments, employing per-protocol and intention-to-treat analyses. Significant differences were observed in pain levels pre- and post-treatment and between the two groups. These differences were evident in the average pain experienced in the previous week (p = 0.010) and various dimensions of the BPI questionnaire, such as the degree of pain interference with walking (p = 0.011), work (p = 0.009), sleep (p = 0.012), and enjoyment of life (p = 0.016). However, there was no statistically significant difference in headache impact on activities of daily living as measured by the HIT. Vascular photobiomodulation shows promise in reducing pain and enhancing the ability to engage in daily activities among post-COVID-19 patients experiencing persistent headaches and orofacial pain.

Abstract Background All for Them is a theory-based and evidence-informed multilevel, multicomponent program delivered through schools to increase HPV vaccination among medically underserved youth across Texas. Given the potential logistical challenges of program implementation, understanding how to best support the implementation and sustainment of the program is critical. The overall goals of this study are twofold: 1) develop a multifaceted implementation strategy, Implementing All for Them (IM-AFT); and 2) evaluate the impact of IM-AFT on implementation outcomes for schools and healthcare providers to successfully implement All for Them in their respective settings. Methods This study is underpinned by a comprehensive and synergistic conceptual framework. We will use Social Cognitive Theory and the Interactive Systems Framework for Dissemination and Implementation to inform important individual and organizational factors to target as part of implementation strategy development. We will use this formative work and Implementation Mapping, a systematic, iterative process that guides the use of theories, models, and frameworks, to develop IM-AFT. The three core aims of the present study are connected to the five tasks of Implementation Mapping. For Aim 1, we will develop IM-AFT using a community-based participatory research-informed approach, including a qualitative assessment of needs and assets associated with program implementation and identification of behavioral and psychosocial objectives to determine implementation outcomes. For Aim 2, we will use a mixed-methods approach to assess user experience with the IM-AFT prototype to test its feasibility, usability, and acceptability. For Aim 3, we will use a descriptive checklist to assess the impact of IM-AFT on user fidelity of program implementation. Discussion This paper presents the detailed protocol for developing and evaluating IM-AFT to successfully implement All for Them, leveraging a systematic, community- and theory-based approach and user experience with the strategy prototype. This study will contribute to expanding limited scientific knowledge about using multiple sources to develop and evaluate specified implementation strategies for effective implementation of school-based vaccination programs. Theory-based IM-AFT will guide collaborations between schools and community health centers to improve HPV and other adolescent vaccination rates in underserved communities in Texas.

Abstract Background COVID-19 drastically affected healthcare services world-wide. In the UK, many cancer services were overwhelmed as oncology staff were reassigned, and cancer diagnoses and treatments were delayed. The impact of these pressures on end-of-life care for patients with advanced cancer and their relatives is not well understood. Methods Secondary thematic analysis of qualitative survey and interview data, collected from family members and close friends bereaved by cancer, as part of a national COVID-19 bereavement study (Survey N = 156; Interview N = 10). Results Four key themes were identified: The impact of COVID-19 on contact with patients towards the end of life; Mixed experiences of support for family members; Variable communication quality from health and social care professionals; Prioritisation of COVID-19 and its impact on patient care. Hospital care was perceived more negatively than community care in almost all areas, while support from cancer charities and district nurses was appreciated the most. Almost all participants felt that COVID-19 was detrimentally prioritised over care for their relative/friend. Conclusions People bereaved by cancer were uniquely affected by pandemic-restrictions and disruptions to services. As services re-build post-pandemic, improvements in palliative care in hospitals, investment into community care, and ensuring compassionate communication with patients and families must be prioritised, alongside preparedness for future pandemics or similar events.

Abstract Background Post-traumatic stress disorder (PTSD) in the postpartum period is a prevalent yet under-researched mental health condition. To date, many women who suffer from postpartum PTSD remain unrecognized and untreated. To enhance the accessibility of help for these women, it is crucial to offer tailored treatment and counselling services that align with their needs. This study aimed to understand how support preferences differ between women with and without postpartum PTSD, considering the two subgroups of postpartum PTSD: childbirth-related PTSD (CB-PTSD) and general PTSD (gPTSD). Methods This study used data from the cross-sectional INVITE study, comprising telephone interviews with N = 3,874 women conducted six weeks to six months after childbirth. The City Birth Trauma Scale (City BiTS) was used to assess CB-PTSD, while the Primary Care Posttraumatic Stress Disorder Screen for DSM-5 (PC-PTSD-5) was used to assess gPTSD. Service preferences and preferred modes of service provision were measured with self-developed questionnaires. Analyses of variance were used to identify differences between groups. Results The support services (family-)midwives and family, friends, or colleagues and the service provision mode as in person communication were preferred most by women across groups. The analyses revealed that women with CB-PTSD had lower overall preferences for services compared to women without postpartum PTSD. Women with CB-PTSD also showed less preference for psychotherapeutic services (e.g. outpatient treatment, inpatient clinics) compared to women without postpartum PTSD. Regarding modes of service provision, women with gPTSD had a higher preference for all service modes compared to women with CB-PTSD and those without postpartum PTSD, with a stronger preference for both direct (e.g. in person, video conference) and delayed communication (e.g. chat, e-mail). Conclusion This study was the first to explore the support preferences of women experiencing symptoms of postpartum PTSD. Findings suggest that women differ in their preferences, contingent upon the subgroup of postpartum PTSD. According to women's overall preferences, the expansion and further training of (family-)midwife services is recommended. By tailoring support services accordingly to women’s preferences, it may be possible to bridge the treatment gap for postpartum PTSD and to improve the well-being of affected women and their families.

BACKGROUND: Lenalidomide (LEN), also known as Revlimid, is a drug used to treat multiple myeloma (MM), smoldering myeloma, and myelodysplastic syndromes. It is used as a first-line treatment for MM, along with dexamethasone. OBJECTIVE: To investigate the effects of LEN on the function of bone marrow (BM) by monitoring the changes in the number of white blood cells (WBCs), hemoglobin levels, and platelet counts in people who were getting treatment. MATERIALS AND METHODS: Includes 90 blood samples from 30 cancer patients before treatment and 30 cancer patients after treatment and 30 healthy individuals aged 60–75 years and is conducted at City Medical Hospital. The blood samples are analyzed to detect Erythrocyte Sedimentation Rate (ESR) by using an ESR fast detector, and detect WBC, red blood cell, and platelets by Mindray CBC-21S. Tests are performed weekly initially, and then biweekly or monthly, taking into account ethical issues such as obtaining consent and criteria for adjusting treatment based on side effects or changes in blood counts. RESULTS: The findings revealed a notable change in the amount of WBCs at the start of the study. These cells significantly decreased and then level off a few months after treatment (2–5) months. Before and after medication, the levels of hemoglobin were changing. The results also showed that the number of platelets in some cases dropped by a large amount. CONCLUSION: Adding LEN could help patients with BM cancer since it reduces microvascularization and most likely increases the particular T cell-driven anti-leukemic response.

Abstract Objective To systematically evaluate which lesion‐based imaging features and methods allow for the best statistical prediction of poststroke deficits across independent datasets. Methods We utilized imaging and clinical data from three independent datasets of patients experiencing acute stroke (N1 = 109, N2 = 638, N3 = 794) to statistically predict acute stroke severity (NIHSS) based on lesion volume, lesion location, and structural and functional disconnection with the lesion location using normative connectomes. Results We found that prediction models trained on small single‐center datasets could perform well using within‐dataset cross‐validation, but results did not generalize to independent datasets (median R2N1 = 0.2%). Performance across independent datasets improved using large single‐center training data (R2N2 = 15.8%) and improved further using multicenter training data (R2N3 = 24.4%). These results were consistent across lesion attributes and prediction models. Including either structural or functional disconnection in the models outperformed prediction based on volume or location alone (P

Abstract Introduction Enteropathy‐associated T‐cell lymphoma (EATL) is a peripheral T‐cell lymphoma (PTCL) with a poor prognosis. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without etoposide consolidated by autologous stem cell transplantation (ASCT) are recommended for fit PTCL patients. The role of etoposide and ASCT in EATL is unclear. Methods This study reports the incidence, treatment, and outcome of EATL patients using the Netherlands Cancer Registry, with nationwide coverage of >95%. Results All patients diagnosed in 1989–2021 (n = 351, 77% treated) were identified (median age 67 years, 56% male, 50% limited stage). Time period analysis assessed trends in primary therapy and overall survival (OS). Treatment included chemotherapy (CT) (34%), surgery (18%), surgery and CT (19%) or CT followed by ASCT (7%). The 5‐year OS for treated patients with limited versus advanced stage was 19% and 9% respectively. The 2‐year OS improved over time (21%–33%, p = 0.06). Surgery only (hazard ratio [HR] 2.16; 95% confidence interval [CI] 1.55–3.01, p

Abstract Background Quantification of Amyloid beta (Aβ) oligomers in plasma enables early diagnosis of Alzheimer’s Disease (AD) and improves our understanding of underlying pathologies. However, quantification necessitates an extremely sensitive and selective technology because of very low Aβ oligomer concentrations and possible interference from matrix components. Methods In this report, we developed and validated a surface-based fluorescence distribution analysis (sFIDA) assay for quantification of Aβ oligomers in plasma. Results The blood-based sFIDA assay delivers a sensitivity of 1.8 fM, an inter- and intra-assay variation below 20% for oligomer calibration standards and no interference with matrix components. Quantification of Aβ oligomers in 359 plasma samples from the DELCODE cohort reveals lower oligomer concentrations in subjective cognitive decline and AD patients than healthy Control participants. Conclusions Correlation analysis between CSF and plasma oligomer concentrations indicates an impaired clearance of Aβ oligomers that is dependent on the ApoE ε4 status.

Abstract We developed and tested an automated measurement platform which can fit multiple samples for their investigation in transmission mode using terahertz time-domain spectroscopy. The temperature inside the platform can be varied to simulate different storage conditions of the samples, in our case, pharmaceuticals. As a proof-of-concept, the setup was successfully tested to monitor the crystallization process of amorphous nifedipine, as a model drug, at 24 °C, 30 °C and 35 °C for over 144 h. To the best of our knowledge, this is the first study to follow the crystallization of nifedipine with quasi-continuous measurements over a time frame of several days. The influence of the storage temperature on the crystallization rate was monitored including the appearance of polymorphic intermediate states of nifedipine throughout the process. The platform developed in combination with terahertz time-domain spectroscopy is a helpful tool for deepening the understanding of the crystallization behavior of amorphous and polymorphic materials and can be, for example, of great importance for the development of novel amorphous pharmaceutical formulations.

Abstract Background Atypical teratoid rhabdoid tumors (ATRT) are incurable high-grade pediatric brain tumors. Despite intensive research efforts, the prognosis for ATRT patients under currently established treatment protocols is poor. While novel therapeutic strategies are urgently needed, the generation of molecular-driven treatment concepts is a challenge mainly due to the absence of actionable genetic alterations. Results We here use a functional genomics approach to identify genetic dependencies in ATRT, validate selected hits using a functionally instructed small molecule drug library, and observe preferential activity in ATRT cells without subgroup-specific selectivity. CDK4/6 inhibitors are among the most potent drugs and display anti-tumor efficacy due to mutual exclusive dependency on CDK4 or CDK6. Chemogenetic interactor screens reveal a broad spectrum of G1 phase cell cycle regulators that differentially enable cell cycle progression and modulate response to CDK4/6 inhibition in ATRT cells. In this regard, we find that the ubiquitin ligase substrate receptor AMBRA1 acts as a context-specific inhibitor of cell cycle progression by regulating key components of mitosis including aurora kinases. Conclusions Our data provide a comprehensive resource of genetic and chemical dependencies in ATRTs, which will inform further preclinical evaluation of novel targeted therapies for this tumor entity. Furthermore, this study reveals a unique mechanism of cell cycle inhibition as the basis for tumor suppressive functions of AMBRA1.

Abstract Background Multiplexed Assays of Variant Effects (MAVEs) can test all possible single variants in a gene of interest. The resulting saturation-style functional data may help resolve variant classification disparities between populations, especially for Variants of Uncertain Significance (VUS). Methods We analyzed clinical significance classifications in 213,663 individuals of European-like genetic ancestry versus 206,975 individuals of non-European-like genetic ancestry from All of Us and the Genome Aggregation Database. Then, we incorporated clinically calibrated MAVE data into the Clinical Genome Resource’s Variant Curation Expert Panel rules to automate VUS reclassification for BRCA1, TP53, and PTEN. Results Using two orthogonal statistical approaches, we show a higher prevalence (p ≤ 5.95e − 06) of VUS in individuals of non-European-like genetic ancestry across all medical specialties assessed in all three databases. Further, in the non-European-like genetic ancestry group, higher rates of Benign or Likely Benign and variants with no clinical designation (p ≤ 2.5e − 05) were found across many medical specialties, whereas Pathogenic or Likely Pathogenic assignments were increased in individuals of European-like genetic ancestry (p ≤ 2.5e − 05). Using MAVE data, we reclassified VUS in individuals of non-European-like genetic ancestry at a significantly higher rate in comparison to reclassified VUS from European-like genetic ancestry (p = 9.1e − 03) effectively compensating for the VUS disparity. Further, essential code analysis showed equitable impact of MAVE evidence codes but inequitable impact of allele frequency (p = 7.47e − 06) and computational predictor (p = 6.92e − 05) evidence codes for individuals of non-European-like genetic ancestry. Conclusions Generation of saturation-style MAVE data should be a priority to reduce VUS disparities and produce equitable training data for future computational predictors.

Abstract Forty-six ceramic shards from the Early Bronze Age (EBA) archaeological site of Tappeh Gabri (the archaeological site 013), dated back to the latter half of the third millennium BCE and located at the Varzaneh Plain, central Iran, were studied using micro energy dispersive X-ray fluorescence (µ-EDXRF) and petrographic analysis. The precision and accuracy of quantitative data obtained by µ-EDXRF were tested using a series of geological certified reference materials (CRM). The expanded uncertainty and the Mantel test on data obtained by µ-EDXRF showed accurate and precise quantitative µ-EDXRF estimation of elements present in the CRMs above their quantification limit. We show that the majority of the ceramics at the Varzaneh Plain is most probably local product. Discussions prompted collecting further compositional data and performing petrographic investigation from the ceramic shards from southern and south-western Iran in order to shed light on the origin of the ceramic shards excavated at the Varzaneh Plain.

Abstract Background Memory responses to the antigens that an individual encounters throughout life may vary with the intensity and duration of antigen contacts or even with changes in immune status over time. This work aims to characterise specific responses to latent CMV, seasonal influenza and novel SARS-CoV-2 infections in immunocompetent individuals over 60 years of age. Specific cellular and humoral responses were identified by IFN-γ and granzyme B release by ELISpot and antibody level measurement. T lymphocyte subpopulation phenotypes were characterised by flow cytometry. Results Cellular and humoral responses to these viruses were detected in almost all patients. Influenza and SARS-CoV-2 cellular responses were positively correlated. There was no significant correlation between CMV and influenza or SARS-CoV-2 responses although both were consistently lower in CMV-seropositive patients. CMV responses were negatively correlated with the levels of the least differentiated subsets of T lymphocytes, and positively correlated with the most differentiated ones, contrary to what happened with the influenza responses. Nevertheless, SARS-CoV-2 cellular responses were negatively correlated with the most differentiated CD8+ T lymphocytes, while humoral responses were negatively correlated with the least differentiated T lymphocytes. Responses to the three viruses were correlated with a Th1/Th2/Th17 balance in favour of Th1. Conclusions The results indicate that memory responses differ depending on the durability of the antigen stimulus. Cellular responses to novel pathogens resemble those generated by seasonal but not CMV infection. Subpopulation distribution and the level of specific T lymphocytes against previous pathogens could be used as immunocompetent status biomarkers in older adults reflecting their ability to generate memory responses to new pathogens.

Objective: Acquired hemophilia A (AHA) is a rare autoimmune disease characterized by the presence of autoantibodies against coagulation factor VIII, leading to spontaneous hemorrhage in patients without a prior family or personal history of bleeding. This study describes the demographics, diagnosis, underlying disorders, bleeding characteristics, treatment, and outcomes of 41 AHA patients together with specific case reports. Materials and Methods: Diagnosis and treatment of these patients occurred between 2005 and 2023. The median age at diagnosis was 67.8 (range: 15-93) years. Among the 41 patients, 10 (24%) cases were idiopathic, 4 (10%) were postpartum, 18 (44%) involved autoimmune diseases, and 9 (22%) involved a diagnosis of cancer. Results: The diagnostic delay exceeded 30 days in 15 of the 41 cases (36.5%). A total of 38 of the 41 (93%) patients presented with spontaneous bleeding, with mucocutaneous bleeding being the most common presentation (23/41, 56%). Four patients experienced postpartum bleeding. Clinical remission was achieved by 100% of patients and no patients died. Conclusion: Hemostatic and immunosuppressive therapy is essential in AHA, and it should be started as soon as possible in patients with bleeding. However, a significant delay in diagnosis was observed in these cases. The absence of mortality is likely attributable to the management of the disease within a specialized hemostasis and thrombosis unit, which offers a clinical ward, a specialized laboratory, and a dedicated ambulatory service. The Italian Society for the Study of Haemostasis and Thrombosis is working to secure recognition of this essential role in every hospital.

The synthesis of silver nanoparticles with controlled physicochemical properties is essential for governing their intended functionalities and safety profiles. However, synthesis process involves multiple parameters that could influence the resulting properties. This challenge could be addressed with the development of predictive models that forecast endpoints based on key synthesis parameters. In this study, we manually extracted synthesis-related data from the literature and leveraged various machine learning algorithms. Data extraction included parameters such as reactant concentrations, experimental conditions, as well as physicochemical properties. The antibacterial efficiencies and toxicological profiles of the synthesized nanoparticles were also extracted. In a second step, based on data completeness, we employed regression algorithms to establish relationships between synthesis parameters and desired endpoints and to build predictive models. The models for core size and antibacterial efficiency were trained and validated using a cross-validation approach. Finally, the features’ impact was evaluated via Shapley values to provide insights into the contribution of features to the predictions. Factors such as synthesis duration, scale of synthesis and the choice of capping agents emerged as the most significant predictors. This study demonstrated the potential of machine learning to aid in the rational design of synthesis process and paves the way for the safe-by-design principles development by providing insights into the optimization of the synthesis process to achieve the desired properties. Finally, this study provides a valuable dataset compiled from literature sources with significant time and effort from multiple researchers. Access to such datasets notably aids computational advances in the field of nanotechnology.

Background: Self-efficacy expresses a learner’s perception of how well they can do in the online academic setting. Although students’ academic successes can be measured by online learning self-efficacy, there is a scarcity of evidence targeted toward allied health students. Objective: The primary aim of this study is to determine the level of online self-efficacy among students from skill-based allied health programs. The secondary aim is to correlate online self-efficacy with age, sex, year level, and program of the students. Methods: This cross-sectional analytic study utilized the Online Learning Self-Efficacy Scale (OLSE) to determine students’ level of self-efficacy via a survey conducted with students who underwent the Enriched Virtual Mode of learning. Descriptive statistics was used to characterize the study participants, describe the level of self-efficacy, and compare the subscales of OLSE. Inferential statistics using Spearman’s rho was performed to determine the correlation. Results: A total of 117 respondents with a mean age ± SD of 20.59 ± 0.11 years old, predominantly female (71%) were included in the study. The students from allied health programs had an online self-efficacy overall mean score of 3.83 ([Formula: see text]; range 2.64–5.00) with the use of technology subscales weighted the highest mean score (4.24). Females have a higher average OLSE score ([Formula: see text], [Formula: see text]) compared to males. Significant correlation was found between OLSE scores to sex ([Formula: see text], [Formula: see text]) and year level ([Formula: see text], [Formula: see text]) while nonsignificant correlation was found between OLSE scores to the program ([Formula: see text], [Formula: see text]) and age ([Formula: see text], [Formula: see text]). Conclusion: Students of allied health programs generally have a very good level of online self-efficacy. This study assists educators in developing proactive strategies and approaches to promote students’ self-confidence across all domains and encourage them to adopt a dynamic remote learning-based approach. Educational institutions should use this opportunity to assess how well they have implemented remote learning to ensure educational continuity, especially in times of crisis.

Background Surveillance on nasopharyngeal Streptococcus pneumoniae carriage in older children would be informative in determining whether a single priming and booster dose of pneumococcal conjugate vaccine (PCV) provides durable protection against pneumococcal disease compared with traditional dosing schedules.Methods and objectives We report on the secondary study objective to evaluate overall, vaccine-serotype (VT), and non-vaccine serotype (NVT) S. pneumoniae colonization at 3, 4, and 5 years of age in children who were randomized to receive 10-valent or 13-valent PCV formulations at 6 (6w + 1) or 14 (14w + 1) weeks compared with a two-dose primary series (2 + 1), with all children receiving a booster dose at 9 months of age, using a multiplex nanofluidic qPCR assay.Results The prevalence of overall, VT, or NVT at 5 years of age between the 2 + 1 compared with the 6w + 1 or 14w + 1 groups for both PCV10 and PCV13 did not differ.Conclusion Although inconclusive, our findings suggest that a reduced 1 + 1 PCV dosing schedule is unlikely to increase breakthrough cases of VT pneumococcal disease in older children, which can inform decision-making on transitioning to a 1 + 1 schedule in South Africa.Clinical trial registration: The trial is registered at www.clinicaltrials.gov (identifier is NCT04275284).

The clinical relevance of the colorectal cancer serrated pathway is evident, but the screening of serrated lesions remains challenging. We aimed to characterize the serum methylome of the serrated pathway and to evaluate circulating cell‐free DNA (cfDNA) methylomes as a potential source of biomarkers for the non‐invasive detection of serrated lesions. We collected serum samples from individuals with serrated adenocarcinoma (SAC), traditional serrated adenomas, sessile serrated lesions, hyperplastic polyps and individuals with no colorectal findings. First, we quantified cfDNA methylation with the MethylationEPIC array. Then, we compared the methylation profiles with tissue and serum datasets. Finally, we evaluated the utility of serum cfDNA methylation biomarkers. We identified a differential methylation profile able to distinguish high‐risk serrated lesions from no serrated neoplasia, showing concordance with tissue methylation from SAC and sessile serrated lesions. Serum methylation profiles are pathway‐specific, clearly separating serrated lesions from conventional adenomas. The combination of ninjurin 2 (NINJ2) and glutamate‐rich 1 (ERICH1) methylation discriminated high‐risk serrated lesions and SAC with 91.4% sensitivity (64.4% specificity), while zinc finger protein 718 (ZNF718) methylation reported 100% sensitivity for the detection of SAC (96% specificity). This is the first study exploring the serum methylome of serrated lesions. Differential methylation of cfDNA can be used for the non‐invasive detection of colorectal serrated lesions.

Background The work experience of seafarers differs significantly from other land-based occupations due to several factors, particularly remoteness and the restricted work environment. This study seeks to examine the impact of burnout and health impairment in the maritime industry, using the Job Demand-Resources theory as a framework. Methods To investigate these phenomena, an online questionnaire was sent to 239 Italian seafarers (94.6% men, Mage = 39.44, SD = 12.8). We tested a mediated Structural Equation Model (SEM) aimed at predicting negative health outcomes. Results The results show that burnout plays a mediating role between job demands (such as workload and cognitive strain) and resources (such as social support and transformational leadership), influencing variables related to health impairment (such as sleep quality and physical well-being). Furthermore, the findings highlight the direct influence of occupational resources on seafarers’ health. Conclusions The discussion highlights the urgent need for more research in the field of organisational psychology in the maritime industry and the discrepancies between these findings, which are consistent with the existing maritime literature, and other studies that do not include seafarers in their sample groups.

The need for sleep is universal, and the ability to meet this need impacts the quality of life for patients, families, and caregivers. Although substantial progress has been made in treating rare diseases, many patients have unmet medical sleep needs, and current regulatory policy makes it prohibitively difficult to address those needs medically. This opinion reviews the rare disease experience with sleep disorders and explores potential solutions. First, we provide case profiles for the rare diseases Wilson’s Disease, Angelman Syndrome, and Prader–Willi Syndrome. These profiles highlight challenges in rare disease diagnosis and barriers to pinpointing disease pathophysiology, including biomarkers that intersect with sleep disorders. Second, we transition to a bird’s eye view of sleep disorders and rare diseases by reporting input from a stakeholder discussion with the U.S. Food and Drug Administration regarding abnormal sleep patterns in various rare diseases. Last, in response to the profound unmet medical needs of patients with rare diseases and sleep disorders, we propose adapting and using the clinical trial design known as a “basket trial”. In this case, a basket trial would include patients with different rare diseases but the same debilitating symptoms. This research approach has the potential to benefit many rare disease patients who are otherwise left with profound unmet medical needs.

In this study, we aimed to integrate a genetic repository with an existing longitudinal national burn database. We set out two primary objectives, namely (1) to develop standard operating procedures for genetic sample collection and storage, DNA isolation, and data integration into an existing multicenter database; and (2) to demonstrate the feasibility of correlating genetic variation to functional outcomes in a pilot study, using the catechol-O-methyltransferase (COMT) gene. Dubbed the worrier/warrior gene, COMT variants have been associated with varying phenotypes of post-traumatic stress, wellbeing, and resilience. Between August 2018 and July 2020, COMT variants were identified for 111 participants from three sites and correlated with their outcome data. We found no association between COMT variants and functional outcomes, likely due to the inadequate sample size. We also asked all potential participants why they consented to or refused genetic analysis. A thematic analysis of responses revealed altruism and personal interest/enthusiasm in the study as top reasons for consenting. Privacy concerns were the most common reason for refusal. In conclusion, we successfully developed standard operating procedures for genetic sample collection and storage, DNA isolation, and data integration into an existing database, and we demonstrated the feasibility of conducting a multicenter collaborative study using a centralized lab location.

RESUMO O WHOQOL-bref é a versão reduzida do instrumento de avaliação da qualidade de vida desenvolvido pela Organização Mundial da Saúde. Este instrumento foi estabelecido a partir de um esforço de centros de pesquisas de países distintos, buscando abranger atributos variados do construto qualidade de vida em uma perspectiva transcultural. O objetivo deste estudo foi apresentar as propriedades psicométricas do WHOQOL-bref para o contexto da segurança pública brasileira e evidências de validade convergente com o SF-36. Participaram 10.914 agentes da segurança pública de diferentes estados brasileiros, com predominância do sexo masculino (81,8%) e idade média de 41 anos (DP=0,08). Os resultados indicaram a validade e a confiabilidade do WHOQOL-bref para o contexto da segurança pública, com predominância da solução tetrafatorial, a qual apresentou semelhanças e diferenças quanto à distribuição dos itens encontradas no estudo original. Em complemento, foram apresentadas evidências de validade convergente com outra medida de qualidade de vida (SF-36).

In this study, novel fluorinated carboxylic acid esters of the generic structure TfO–CH2–(CF2)n–COOCH3 (n = 2,4,6, Tf = triflate) were synthesized. The triflates were reacted with 2-hydroxy-3,4,5-trimethoxybenzaldehyde via Williamson ether syntheses. The resulting electron-rich compounds were used as aldehydes in the Rothemund reaction with pyrrole to form ester-substituted porphyrins. After metalation with Ni(acac)2 and hydrolysis electron-rich porphyrins were obtained, that are equipped with covalently attached long chain acid substituents. The target compounds have potential applications in catalysis, sensing, and materials science. The fluorinated aliphatic carboxylic acids (TfO–CH2–(CF2)n–COOCH3) with triflate as leaving group in terminal position are easily accessible and versatile building blocks for attaching long chain acids (pKa 0–1) to substrates in Williamson ether-type reactions.

Abstract Purpose To provide a prospective 2 year follow-up of a previously enrolled adolescent high school sample, regarding body image and eating concerns, and patterns of sports type and physical activity. Methods Sports type, weekly time devoted to it, and psychopathological self-reports (Eating Disorders Examination Questionnaire 6.0, Body Uneasiness Test, and Muscle Dysmorphia Disorder Inventory) were evaluated longitudinally in a general population sample enrolled in a previous study, testing prospective variations in an observational setting. Results At follow-up, girls expressed increased dietary restraint and body uneasiness as compared to baseline, whereas boys expressed increased body uneasiness—and specifically in the avoidance, depersonalisation and compulsive self-monitoring dimensions. Among both sexes, a significant shift towards individual activities or lack of activity was observed after 2 years, with a reduction in team sports involvement. Among girls, time devoted to exercise significantly decreased at follow-up. Conclusions The present findings indirectly confirm an increased vulnerability to dietary, bodily and appearance-based concerns among adolescents. The role of different patterns of physical activity and exercise time may interact bidirectionally with these problematic areas, considering that previous studies point out increased concerns among inactive subjects, and among those who choose individual activities. Level of evidence: Level IV-longitudinal observational study.