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Abstract Background Following acute and sub-acute rehabilitation from severe traumatic brain injury (TBI), minimal to no efficacious interventions to treat ongoing cognitive deficits are available. Aerobic exercise is a non-invasive behavioral intervention with promise to treat cognitive deficits in TBI populations. Methods Six individuals, aged 24–62 years, with chronic (> 8 months since injury) severe (Glasgow Coma Scale of 3–8) TBI were recruited from two outpatient rehabilitation centers. In an A-B-A study design, 20-weeks of supervised aerobic exercise interventions were delivered three times per week (phase B) in addition to participants typical rehabilitation schedules (phases A). The effect of phase B was tested on a trail making test part B (primary outcome measure of executive function) as well as objective daily physical activity (PA), using both group level (linear mixed effect models) and single subject statistics. Results Five of six participants increased trail-making test part B by more than 10% pre-to-post phase B, with three of six making a clinically meaningful improvement (+ 1SD in normative scores). A significant main effect of time was seen with significant improvement in trail-making test part B pre-to-post exercise (phase B). No significant effects in other planned comparisons were found. Statistically significant increases in daily moderate-to-vigorous PA were also seen during phase B compared to phase A with three of six individuals making a significant behaviour change. Conclusions The addition of supervised aerobic exercise to typical rehabilitation strategies in chronic survivors of severe TBI can improve executive set shifting abilities and increase voluntary daily PA levels. Trial registration Retrospective trial registration on July 11 2024 with trial number: ISRCTN17487462.

This research aims to analyse the self-perception of teachers and students on their digital readiness and their attitudes towards digital and distance learning, as well as the potential influence of other factors. The use of digital technologies is directly linked to the academic performance of students and teachers, while also enabling new modes of the teaching--learning process. Considering the pandemic disruptions, the self-perception of Croatian university students and teachers was analysed, exploring the relationship and differences between groups. The results indicate significant digital readiness gaps, considering gender and the field of study. From a substantive point of view, the use and application of digital tools show a disconnect between expectations of digital transformation in the learning environment and reality. Existing environments and practices are augmented digitally without building new and improved learning systems. The findings of this study provide insights to reduce the existing gaps and improve the digital teaching and learning environment. Higher education institutions have a unique opportunity to increase their antifragility by leveraging new experiences gained during the pandemic, while also valuing their pre-existing institutional agility. The research has practical implications that can assist educators and policymakers in creating a digital learning environment that is more inclusive and beneficial to all participants.

Abstract Background The differential gene expression profile of metastatic versus primary breast tumors represents an avenue for discovering new or underappreciated pathways underscoring processes of metastasis. However, as tumor biopsy samples are a mixture of cancer and non-cancer cells, most differentially expressed genes in metastases would represent confounders involving sample biopsy site rather than cancer cell biology. Methods By paired analysis, we defined a top set of differentially expressed genes in breast cancer metastasis versus primary tumors using an RNA-sequencing dataset of 152 patients from The Breast International Group Aiming to Understand the Molecular Aberrations dataset (BIG-AURORA). To filter the genes higher in metastasis for genes essential for breast cancer proliferation, we incorporated CRISPR-based data from breast cancer cell lines. Results A significant fraction of genes with higher expression in metastasis versus paired primary were essential by CRISPR. These 264 genes represented an essential signature of breast cancer metastasis. In contrast, nonessential metastasis genes largely involved tumor biopsy site. The essential signature predicted breast cancer patient outcome based on primary tumor expression patterns. Pathways underlying the essential signature included proteasome degradation, the electron transport chain, oxidative phosphorylation, and cancer metabolic reprogramming. Transcription factors MYC, MAX, HDAC3, and HCFC1 each bound significant fractions of essential genes. Conclusions Associations involving the essential gene signature of breast cancer metastasis indicate true biological changes intrinsic to cancer cells, with important implications for applying existing therapies or developing alternate therapeutic approaches.

Blueberries (Vaccinium corymbosum) undergo significant texture changes during development and ripening, notably a consistent decrease in firmness, which affects fruit quality, consumer preference, transportability, and shelf life. This study examined the composition and structural modifications of the cell wall in five commercially available blueberry varieties with differing firmness levels at harvest. Our approach integrated various biochemical techniques for a comprehensive analysis of cell wall components to elucidate firmness differences at the harvest stage. One of the conclusions was the relationship between a low degree of pectin methylesterification and the presence of increased egg-box structures, which correlated with increased firmness. The data suggest that low-abundance pectins in blueberry cell walls, such as rhamnogalacturonan-I participate in firmness modulation through their side branches or by linking to arabinogalactan proteins. Additionally, the xyloglucan structure can be one of the determinants of fruit firmness. Although, this work provides a broad insight into the relationship between cell wall composition and firmness in blueberry, a more detailed analysis, specifically focusing on pectin and hemicelluloses, would be of significant value.

Introduction: Breast cancer (BC) is a malignant disease that predominantly affects women, with known genetic components such as mutations in tumor suppressor genes BRCA1 and BRCA2. Other risk factors include unhealthy lifestyles, lack of physical activity, and consumption of alcohol and cigarettes. Aging also plays a role in BC development, with hormonal influences such as estrogen and progesterone promoting cancer growth. Material and Methods: Research was conducted using data collection tools for risk factors and tumor markers from primary healthcare unit records. The sample comprised 200 women, divided into two groups based on BC diagnosis, with complete medical documentation. Male BC cases were excluded. Results: Statistical significance was found between genetic components, family history, aging, obesity, alcohol and cigarette consumption, longer hormone exposure, and female BC development using the Chi-Square test, confirmed by Fisher’s Exact test. Tumor markers CA 15-3, CEA, CA 19-9, and CA 125 were useful for BC screening and metastasis detection, as determined by the One Sample T-test. In Sarajevo Canton, invasive ductal BC was the most common type among women, while lobular carcinoma in situ was the least common. Conclusion: Correlations between risk factors, including aging, unhealthy lifestyles, and hormone exposure, and increased BC risk were confirmed. Tumor markers CA 15-3, CEA, CA 19-9, and CA 125 were effective in diagnosis, screening, and metastasis detection in females, with sensitivity for regression detection at 81.8% and specificity at 100%.

Abstract Background Epirubicin/cyclophosphamide (EC) and docetaxel (D) are commonly used in a sequential regimen in the neoadjuvant treatment of early, high-risk or locally advanced breast cancer (BC). Novel approaches to increase the response rate combine this treatment with immunotherapies such as PD-1 inhibition. However, the expected stimulatory effect on lymphocytes may depend on the chemotherapy backbone. Therefore, we separately compared the immunomodulatory effects of EC and D in the setting of a randomized clinical trial. Methods Tumor and blood samples of 154 patients from the ABCSG-34 trial were available (76 patients received four cycles of EC followed by four cycles of D; 78 patients get the reverse treatment sequence). Tumor-infiltrating lymphocytes, circulating lymphocytes and 14 soluble immune mediators were determined at baseline and at drug change. Furthermore, six BC cell lines were treated with E, C or D and co-cultured with immune cells. Results Initial treatment with four cycles of EC reduced circulating B and T cells by 94% and 45%, respectively. In contrast, no comparable effects on lymphocytes were observed in patients treated with initial four cycles of D. Most immune mediators decreased under EC whereas D-treatment resulted in elevated levels of CXCL10, urokinase-type plasminogen activator (uPA) and its soluble receptor (suPAR). Accordingly, only the exposure of BC cell lines to D induced similar increases as compared to E. While treatment of BC cells with E was associated with cell shrinkage and apoptosis, D induced cell swelling and accumulation of cells in G2 phase. Conclusion The deleterious effect of EC on lymphocytes indicates strong immunosuppressive properties of this combination therapy. D, in contrast, has no effect on lymphocytes, but triggers the secretion of stimulatory proteins in vivo and in vitro, indicating a supportive effect on the immune system. Underlying differences in the induced cell death might be causal. These divergent immunomodulatory effects of epirubicin/cyclophosphamide and docetaxel should be considered when planning future combinations with immunotherapies in breast cancer.

Abstract Carious lesions are bacteria-caused destructions of the mineralised dental tissues, marked by the simultaneous activation of immune responses and regenerative events within the soft dental pulp tissue. While major molecular players in tooth decay have been uncovered during the past years, a detailed map of the molecular and cellular landscape of the diseased pulp is still missing. In this study we used single-cell RNA sequencing analysis, supplemented with immunostaining, to generate a comprehensive single-cell atlas of the pulp of carious human teeth. Our data demonstrated modifications in the various cell clusters within the pulp of carious teeth, such as immune cells, mesenchymal stem cells (MSC) and fibroblasts, when compared to the pulp of healthy human teeth. Active immune response in the carious pulp tissue is accompanied by specific changes in the fibroblast and MSC clusters. These changes include the upregulation of genes encoding extracellular matrix (ECM) components, including COL1A1 and Fibronectin (FN1), and the enrichment of the fibroblast cluster with myofibroblasts. The incremental changes in the ECM composition of carious pulp tissues were further confirmed by immunostaining analyses. Assessment of the Fibronectin fibres under mechanical strain conditions showed a significant tension reduction in carious pulp tissues, compared to the healthy ones. The present data demonstrate molecular, cellular and biomechanical alterations in the pulp of human carious teeth, indicative of extensive ECM remodelling, reminiscent of fibrosis observed in other organs. This comprehensive atlas of carious human teeth can facilitate future studies of dental pathologies and enable comparative analyses across diseased organs.

Introduction: COVID-19 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 and causes a series of respiratory symptoms. Considering the appearance and development of symptoms, the course of COVID-19 can go from mild to severe. Depending on the course of COVID-19, the laboratory parameters change a lot, trying to defend the organism against the foreign pathogen and all the changes it causes.Therefore, the aim of this study is to observe the differences between biochemical, hematological and coagulation parameters depending on the disease stage of COVID-19 patients. Material and methods: We conducted a cross-sectional study which included 160 COVID-19 patients from Sarajevo, Bosnia and Herzegovina. Biochemical, hematological and coagulation analyses were performed. Results: COVID-19 patients with a severe clinical course have higher average values of fibrinogen (6.53±4.47,p

This study explores the Hydrothermal Carbonization (HTC) treatment of lignocellulosic biomass blends, delving into the influence of several key parameters: temperature, additive nature and dosage, residence time, and biomass composition. Rapeseeds, Pinus radiata sawdust, oat husks, and pressed olive served as the studied biomasses. One hundred twenty-eight experiments were conducted to assess the effects on mass yield (MY), energy yield (EY), higher heating value (HHV), and final ash content (ASH) by a Factorial Experimental Design. The derived model equations demonstrated a robust fit to the experimental data, averaging an R2 exceeding 0.94, affirming their predictive accuracy. The observed energy yield ranged between 65% and 80%, notably with sawdust and olive blends securing EY levels surpassing 70%, while rapeseed blends exhibited the highest HHV at 25 MJ/kg. Temperature emerged as the most influential factor, resulting in an 11% decrease in MY and a substantial 2.20 MJ/kg increase in HHV. Contrastingly, blend composition and additive presence significantly impacted ASH and EY, with all blends exhibiting increased ASH in the presence of additives. Higher initial hemicellulose and aqueous extractive content in raw biomass correlated proportionally with heightened HHV.

AbstractIntroduction The objectives of this study were to determine the effects of the Mézières Method (MM) on pain and disability related to low back pain (LBP), compared to a program of heat, massage and exercise, and to understand the meaning of the bodily experience with the MM.Patients and methods Mixed methods convergent parallel design, combining an equivalent randomized clinical trial with a qualitative phenomenological approach. Sixty-one participants aged 18–65 years with chronic non-specific LBP lasting more than 3 months. Patients were randomized into two groups: the MM group (n = 29) and the comparison group (CG) who received heat, massage plus flexibility and strengthening exercises (n = 31). MM and CG participants underwent 10 one-hour physical therapy sessions over a 5-week period and were evaluated three times: pre-intervention, post-intervention and follow-up at 6 weeks after the end of treatment.Results Both groups reported positive effects on LBP . MM group showed superior effects in pain relief in the short term (Cohen’s D 0.80; p = 0.004). Participants interpreted the interaction with the MM as a teaching–learning process that allowed body awareness.Conclusion Both treatment were similarly beneficial but MM had superior effects on pain in the short term. MM is perceived by the participants as a teaching–learning process focused on body awareness that facilitate effective management of LBP.

The authors sought to test the fit of a new model of spirituality in music education by examining one jamming session through a hermeneutic phenomenological lens. In accordance with the work of Van der Merwe and Habron, the authors employ four lifeworld existentials as categories by which to organize the experience of the five musicians involved in a particular jam session. Participant researcher narratives are analyzed for fit with the model, and an analysis is reported. These narratives seem to support the existence of the guideposts inherent to the model. Furthermore, the researchers present a model as a way for situating the spirituality model in the context of an understanding of person, product, process, press, and position to inform the literature in creativity.

Abstract During COVID-19 pandemic, quality of living was impacted by social isolation, loneliness, and altered sleep habits. The aims of this study were (1) to examine the relationship between physical activity (PA) levels with insomnia and loneliness among adults during Spain’s first COVID-19 wave of lockdown and its impact on women and (2) to examine the digital technologic resources used to support both PA and other recreational activities in women. A cross-sectional design was used. An anonymous 15-min online survey was conducted in Spain to adults (≥ 18 years old) during the first COVID-19 lockdown, a 40-day period. A snowball distribution method was employed using personal email and social networks (Facebook, Whatsapp, Linkedin, Twitter). Variables studied included: socio-demographic items, insomnia, loneliness, PA, and digital technologic resources. A total of 996 adults (females = 663, 66.6%) completed the survey. Higher education levels were associated with greater PA levels (p-value

The main aim of this study was to assess the criterion validity of the Sedentary Behavior Questionnaire (SBQ) to measure SB in community-dwelling older adults using thigh-measured accelerometry as the criterion method. 801 participants (75.6 ± 6.1 years old, 57.6% females) provided valid thigh-based accelerometer data (activPAL/Axivity) and completed the SBQ. Criterion validity was assessed using Spearman's Rho coefficients. Bland--Altman plots, including 95% limits of agreement and Intraclass Correlation Coefficient (ICC), were used to assess the agreement between self-report and device-measured daily SB time. Strength of the association was examined using multiple linear regression. There was a weak correlation (Rho = 0.25, p < 0.001) between self-reported and device-based SB measures. The SBQ under-estimated daily SB time compared to accelerometry. Our results highlighted an overall weak-to-moderate correlation between measures, with significant differences between each country's version. Researchers should be cautious when using the SBQ to provide an estimation of SB time in older adults.

Conventional dendritic cells (cDCs) are antigen-presenting cells (APCs) that play a central role in linking innate and adaptive immunity. cDCs have been well described in a number of different mammalian species, but remain poorly characterised in the chicken. In this study, we use previously described chicken cDC specific reagents, a novel gene-edited chicken line and single-cell RNA sequencing (scRNAseq) to characterise chicken splenic cDCs. In contrast to mammals, scRNAseq analysis indicates that the chicken spleen contains a single, chemokine receptor XCR1 expressing, cDC subset. By sexual maturity the XCR1+ cDC population is the most abundant mononuclear phagocyte cell subset in the chicken spleen. scRNAseq analysis revealed substantial heterogeneity within the chicken splenic XCR1+ cDC population. Immature MHC class II (MHCII)LOW XCR1+ cDCs expressed a range of viral resistance genes. Maturation to MHCIIHIGH XCR1+ cDCs was associated with reduced expression of anti-viral gene expression and increased expression of genes related to antigen presentation via the MHCII and cross-presentation pathways. To visualise and transiently ablate chicken XCR1+ cDCs in situ, we generated XCR1-iCaspase9-RFP chickens using a CRISPR-Cas9 knockin transgenesis approach to precisely edit the XCR1 locus, replacing the XCR1 coding region with genes for a fluorescent protein (TagRFP), and inducible Caspase 9. After inducible ablation, the chicken spleen is initially repopulated by immature CD1.1+ XCR1+ cDCs. XCR1+ cDCs are abundant in the splenic red pulp, in close association with CD8+ T-cells. Knockout of XCR1 prevented this clustering of cDCs with CD8+ T-cells. Taken together these data indicate a conserved role for chicken and mammalian XCR1+ cDCs in driving CD8+ T-cells responses.