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Previous studies have demonstrated the efficacy and feasibility of an anti-viral vaccine strategy that takes advantage of pre-existing CD4+ helper T (Th) cells induced by Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination. This strategy uses immunization with recombinant fusion proteins comprised of a cell surface expressed viral antigen, such as a viral envelope glycoprotein, engineered to contain well-defined BCG Th cell epitopes, thus rapidly recruiting Th cells induced by prior BCG vaccination to provide intrastructural help to virus-specific B cells. In the current study, we show that Th cells induced by BCG were localized predominantly outside of germinal centers and promoted antibody class switching to isotypes characterized by strong Fc receptor interactions and effector functions. Furthermore, BCG vaccination also upregulated FcγR expression to potentially maximize antibody-dependent effector activities. Using a mouse model of Ebola virus (EBOV) infection, this vaccine strategy provided sustained antibody levels with strong IgG2c bias and protection against lethal challenge. This general approach can be easily adapted to other viruses, and may be a rapid and effective method of immunization against emerging pandemics in populations that routinely receive BCG vaccination.

Taï Forest virus (TAFV) is a negative-sense RNA virus in the Filoviridae family. TAFV has caused only a single human infection, but several disease outbreaks in chimpanzees have been linked to this virus. Limited research has been done on this human-pathogenic virus. We sought to establish an animal model to assess TAFV disease progression and pathogenicity at our facility. We had access to two different viral stock preparations from different institutions, both originating from the single human case. Type I interferon receptor knockout mice were inoculated with TAFV stock 1 or stock 2 by the intraperitoneal route. Inoculation resulted in 100% survival with no disease regardless of viral stock preparation or infectious dose. Next, cynomolgus macaques were inoculated with TAFV stock 1 or stock 2. Inoculation with TAFV stock 1 resulted in 100% survival and robust TAFV glycoprotein-specific IgG responses including neutralizing antibodies. In contrast, macaques infected with TAFV stock 2 developed disease and were euthanized 8-11 days after infection exhibiting viremia, thrombocytopenia, and increased inflammatory mediators identified by transcriptional analysis. Histopathologic analysis of tissue samples collected at necropsy confirmed classic filovirus disease in numerous organs. Genomic differences in both stock preparations were mapped to several viral genes which may have contributed to disease severity. Taken together, we demonstrate that infection with the two TAFV stocks resulted in no disease in mice and opposing disease phenotypes in cynomolgus macaques, highlighting the impact of viral stock propagation on pathogenicity in animal models.

This study investigates the complex interplay among innovation, research and development (R&D), and entrepreneurship within the context of European nations. The focus of the study is also on the contributory role of tertiary educational institutions in nurturing entrepreneurial activities. To deepen the understanding of these multifaceted relationships and their subsequent impact on regional economies, the research introduces a novel metric termed the Innovation Readiness Environment (IRE) index. This index combines various indicators such as R&D expenditure, patenting rates, firm size, and educational levels, thereby providing a framework for evaluating firms' innovative capabilities and entrepreneurial success in a given region. Utilization of this index offers policymakers and stakeholders a nuanced understanding of the regional innovation ecosystem, facilitating the identification of strengths and deficiencies. This, in turn, enables the formulation of targeted policy interventions to enhance innovation and entrepreneurship. One relevant conclusion drawn from this study is the pivotal role of tertiary education in catalyzing entrepreneurial ventures. The findings posit that higher levels of entrepreneurial education significantly supplement an individual's likelihood of entrepreneurial success by imparting the requisite skills and knowledge indispensable in a competitive business milieu. By fostering an environment conducive to innovation, higher education institutions emerge as critical agents in cultivating entrepreneurial acumen and stimulating economic expansion. The study further incorporates a spatial analytical framework to elucidate the regional specificities of innovation at the pan-European scale.

Krippendorff's Alpha is a measure for assessing inter-rater reliability, facilitating triangulated evaluations among multiple raters. Indeed, Krippendorff's Alpha is key in validating the dependability of human assessments, thereby reinforcing the robustness of human-based choices in contexts where interpretive variability could otherwise undermine the research outcomes. Despite its versatility across various data types, the procedure for computing this coefficient might limit its applicability for researchers unfamiliar with specialised statistical software. Addressing this issue, this paper introduces the “K-Alpha Calculator”—Krippendorff's Alpha Calculator—a freely accessible, user-friendly, web application available at https://www.k-alpha.org designed for easy computation of Krippendorff's Alpha. By offering a web interface without any software dependency, the K-Alpha Calculator seeks to promote the broader integration of such a reliability metric in research processes. We envisage that the tool's contribution could support researchers in enhancing methodological rigour, fostering conclusions are rooted in triangulated interpretations and assessments. The K-Alpha Calculator is both a computational tool and an educational resource, encouraging more researchers to include reliability measures in their studies. • Development of the K-Alpha Calculator.The study centres on the introduction of a web-based application: the K-Alpha Calculator. The tool is developed to simplify the calculation of Krippendorff's Alpha without any required software dependency. • User-friendly interface for diverse data types.The K-Alpha Calculator is characterised by its accessibility and user-friendliness, designed to simplify the procedures for computing the Krippendorff's Alpha. Its utility extends to various data types, which aligns with the intrinsic versatility of this coefficient.

BackgroundExtracellular particles (EPs), particularly extracellular vesicles, play a crucial role in regulating various pathological mechanisms, including immune dysregulations post-trauma. Their distinctive expression of cell-specific markers and regulatory cargo such as cytokines or micro-ribonucleic acid suggests their potential as early biomarkers for organ-specific damage and for identifying patients at risk for complications and mortality. Given the critical need for reliable and easily assessable makers to identify at-risk patients and guide therapeutic decisions, we evaluated the early diagnostic value of circulating EPs regarding outcomes in severely injured multiple-trauma patients.MethodsPlasma samples were collected from 133 severely injured trauma patients (Injury Severity Score (ISS) ≥16) immediately upon arrival at the emergency department (ED). Patients were categorized into survivors and non-survivors. Injury characteristics and outcomes related to sepsis, pneumonia, or early (

Actinomyces species are recognized as common mucosal bacteria in humans and as a newly discovered source of infection. Since its discovery in 1995, the subspecies Actinomyces turicensis has been reported as the causative pathogen of numerous infections. Only two instances of A. turicensis-related empyema, however, have been documented in the literature as of late. We report a unique case of polymicrobial empyema caused by A. turicensis shortly after a COVID-19 without any clear risk factors for anaerobic aspiration, along with a brief review of the literature. Tetracycline was successfully used for the first time to treat A. turicensis empyema, following chest drainage.

Emergency General Surgery (EGS) was identified as multidisciplinary surgery performed for traumatic and non-traumatic acute conditions during the same admission in the hospital by general emergency surgeons and other specialists. It is the most diffused surgical discipline in the world. To live and grow strong EGS necessitates three fundamental parts: emergency and elective continuous surgical practice, evidence generation through clinical registries and data accrual, and indications and guidelines production: the LIFE TRIAD.

Abstract Pooling publicly-available MRI data from multiple sites allows to assemble extensive groups of subjects, increase statistical power, and promote data reuse with machine learning techniques. The harmonization of multicenter data is necessary to reduce the confounding effect associated with non-biological sources of variability in the data. However, when applied to the entire dataset before machine learning, the harmonization leads to data leakage, because information outside the training set may affect model building, and potentially falsely overestimate performance. We propose a 1) measurement of the efficacy of data harmonization; 2) harmonizer transformer, i.e., an implementation of the ComBat harmonization allowing its encapsulation among the preprocessing steps of a machine learning pipeline, avoiding data leakage by design. We tested these tools using brain T1-weighted MRI data from 1740 healthy subjects acquired at 36 sites. After harmonization, the site effect was removed or reduced, and we showed the data leakage effect in predicting individual age from MRI data, highlighting that introducing the harmonizer transformer into a machine learning pipeline allows for avoiding data leakage by design.

Abstract Background Radiation-induced neurocognitive dysfunction is a major adverse effect of brain radiation therapy and has specific relevance in pediatric oncology, where serious cognitive deficits have been reported in survivors of pediatric brain tumors. Moreover, many pediatric patients receive proton therapy under general anesthesia or sedation to guarantee precise ballistics with a high oxygen content for safety. The present study addresses the relevant question of the potential effect of supplemental oxygen administered during anesthesia on normal tissue toxicity and investigates the anti-tumor immune response generated following conventional and FLASH proton therapy. Methods Rats (Fischer 344) were cranially irradiated with a single high dose of proton therapy (15 Gy or 25 Gy) using FLASH dose rate proton irradiation (257 ± 2 Gy/s) or conventional dose rate proton irradiation (4 ± 0.02 Gy/s), and the toxicities in the normal tissue were examined by histological, cytometric and behavioral analysis. Glioblastoma-bearing rats were irradiated in the same manner and tumor-infiltrating leukocytes were quantified by flow cytometry. Results Our findings indicate that supplemental oxygen has an adverse impact on both functional and anatomical evaluations of normal brain following conventional and FLASH proton therapy. In addition, oxygen supplementation in anesthesia is particularly detrimental for anti-tumor immune response by preventing a strong immune cell infiltration into tumoral tissues following conventional proton therapy. Conclusions These results demonstrate the need to further optimize anesthesia protocols used in radiotherapy with the goal of preserving normal tissues and achieving tumor control, specifically in combination with immunotherapy agents.

Abstract Background To assess physical activity (PA) there is a need of objective, valid and reliable measurement methods like accelerometers. Before these devices can be used for research, they need to be calibrated and validated for specific age groups as the locomotion differs between children and adults, for instance. Therefore, the aim of the present study was the calibration and validation of the Move4 accelerometer for children aged 8–13 years. Methods 53 normal weighted children (52% boys, 48%girls) aged 8–13 years (mean age = 10.69 ± 1.46, mean BMI = 17.93 kg/m− 2, 60th percentile), wore the Move4 sensor at four different body positions (thigh, hip, wrist and the Move4ecg including heart rate measurement at the chest). They completed nine activities that considered the four activity levels (sedentary behavior (SB), light PA (LPA), moderate PA (MPA) and vigorous PA (VPA)) within a test-retest design. Intensity values were determined using the mean amplitude deviation (MAD) as well as the movement acceleration intensity (MAI) metrics. Determination of activities and energy expenditure was validated using heart rate. After that, cut-off points were determined in Matlab by using the Classification and Regression Trees (CART) method. The agreement for the cut-off points between T1 and T2 was analyzed. Results MAD and MAI accelerometer values were lowest when children were lying on the floor and highest when running or doing jumping jacks. The mean correlation coefficient between acceleration values and heart rate was 0.595 (p = 0.01) for MAD metric and 0.611 (p = 0.01) for MAI metric, indicating strong correlations. Further, the MAD cut-off points for SB-LPA are 52.9 mg (hip), 62.4 mg (thigh), 86.4 mg (wrist) and 45.9 mg (chest), for LPA-MPA they are 173.3 mg (hip), 260.7 mg (thigh), 194.4 mg (wrist) and 155.7 mg (chest) and for MPA-VPA the cut-off points are 543.6 mg (hip), 674.5 mg (thigh), 623.4 mg (wrist) and 545.5 mg (chest). Test-retest comparison indicated good values (mean differences = 9.8%). Conclusion This is the first study investigating cut-off points for children for four different sensor positions using raw accelerometer metrics (MAD/MAI). Sensitivity and specificity revealed good values for all positions. Nevertheless, depending on the sensor position, metric values differ according to the different involvement of the body in various activities. Thus, the sensor position should be carefully chosen depending on the research question of the study.

BACKGROUND: Few data on the management of acute phase of traumatic spinal cord injury (tSCI) in patients suffering polytrauma are available. As the therapeutic choices in the first hours may have a deep impact on outcome of tSCI patients, we conducted an international survey investigating this topic. METHODS: The survey was composed of 29 items. The main endpoints of the survey were to examine: (1) the hemodynamic and respiratory management, (2) the coagulation management, (3) the timing of magnetic resonance imaging (MRI) and spinal surgery, (4) the use of corticosteroid therapy, (5) the role of intraspinal pressure (ISP)/spinal cord perfusion pressure (SCPP) monitoring and (6) the utilization of therapeutic hypothermia. RESULTS: There were 171 respondents from 139 centers worldwide. A target mean arterial pressure (MAP) target of 80-90 mmHg was chosen in almost half of the cases [n = 84 (49.1%)]. A temporary reduction in the target MAP, for the time strictly necessary to achieve bleeding control in polytrauma, was accepted by most respondents [n = 100 (58.5%)]. Sixty-one respondents (35.7%) considered acceptable a hemoglobin (Hb) level of 7 g/dl in tSCI polytraumatized patients. An arterial partial pressure of oxygen (PaO2) of 80-100 mmHg [n = 94 (55%)] and an arterial partial pressure of carbon dioxide (PaCO2) of 35-40 mmHg [n = 130 (76%)] were chosen in most cases. A little more than half of respondents considered safe a platelet (PLT) count > 100.000/mm3 [n = 99 (57.9%)] and prothrombin time (PT)/activated partial thromboplastin time (aPTT)

The purpose of this study was to investigate the relationship between transformational leadership and organizational intimacy with mediating role of organizational empathy. This study is an applied and correlation research method based on structural equation modeling. 105 teachers of Saravan city were studied by stratified random sampling method. To collect information, three questionnaires were used: transformational leadership, organizational intimacy and organizational empathy. For data analysis the Pearson correlation coefficient and structural equation modeling were used by SPSS and Lisrel software. Based on results the amount of correlation coefficient of transformational leadership with organizational empathy (r=0.459, p<0.01), transformational leadership with organizational intimacy (r=0.580, p<0.01), organizational empathy with organizational intimacy (r=0.516, p<0.01) was significant. The direct effect of transformational leadership on organizational intimacy ([beta]=0.43, t=3.93), direct effect of transformational leadership on organizational empathy ([beta]=0.48, t=4.19) and direct effect of organizational empathy on organizational intimacy ([beta]=0.36, t=3.373) was significant. The indirect effect of transformational leadership on organizational intimacy was also significant with the mediator role of organizational empathy ([beta]=0.172). Therefore, it can be concluded that transformational leadership has a positive and significant relationship, directly and indirectly, through the organizational empathy mediation variable with the organizational intimacy.