Miracle-dz/UniFAR-FTUs huggingface dataset:
CAR-NK Cells Targeting HER1 (EGFR) Show Efficient Anti-Tumor Activity against Head and Neck Squamous Cell Carcinoma (HNSCC)

Simple Summary Despite new therapeutic approaches in the last decades, prognosis and survival rates for head and neck squamous cell carcinomas (HNSCC) remain poor. Due to its high immune cell infiltration, immunotherapy has become a valuable tool for HNSCC, yet only three monoclonal antibodies have been approved to treat HNSCC. The aim of this study was to develop novel immunotherapeutic strategies for HNSCC employing CAR-NK cells that target HER1/epidermal growth factor receptor (EGFR), which is overexpressed in over 80% of HNSCC patients. We confirmed CAR-NK cell function by assessing cytotoxic killing, IFNγ secretion and CD107a degranulation in 2D and 3D co-culture models. Analyses of primary HNSCC cells that were still viable after anti-HER1 CAR-NK-92 cell challenge showed a high percentage of CD44v6-positive cells, indicating that targeting HER1 alone was not sufficient to eliminate this potential cancer stem cell population, which could contribute to disease progression such as metastasis. We conclude that CAR-NK cell therapy may be a useful tool for HNSCC treatment in combinatorial therapeutic regimens. Abstract (1) Background: HNSCC is a highly heterogeneous and relapse-prone form of cancer. We aimed to expand the immunological tool kit against HNSCC by conducting a functional screen to generate chimeric antigen receptor (CAR)-NK-92 cells that target HER1/epidermal growth factor receptor (EGFR). (2) Methods: Selected CAR-NK-92 cell candidates were tested for enhanced reduction of target cells, CD107a expression and IFNγ secretion in different co-culture models. For representative HNSCC models, patient-derived primary HNSCC (pHNSCC) cell lines were generated by employing an EpCAM-sorting approach to eliminate the high percentage of non-malignant cells found. (3) Results: 2D and 3D spheroid co-culture experiments showed that anti-HER1 CAR-NK-92 cells effectively eliminated SCC cell lines and primary HNSCC (pHNSCC) cells. Co-culture of tumor models with anti-HER1 CAR-NK-92 cells led to enhanced degranulation and IFNγ secretion of NK-92 cells and apoptosis of target cells. Furthermore, remaining pHNSCC cells showed upregulated expression of putative cancer stem cell marker CD44v6. (4) Conclusions: These results highlight the promising potential of CAR-NK cell therapy in HNSCC and the likely necessity to target multiple tumor-associated antigens to reduce currently high relapse rates.
Examining the New-Member Effect to an Established Community-Based Physical Activity Program for Older Adults in England

Community-based group physical activity programs promote exercise opportunities for older people. The aim of this study was to examine the short-term, new participant effect after joining Vitality, a community-based group physical activity program available in the East of England for older adults. Two independent groups of participants were assessed before and after an 8 week period: a group recruited from the ‘Vitality’ program (VP) (n 15, age: Age = 69.4 ± 6.4 y), and; a non-intervention control (CON) group (n 14, age: 64.5 ± 5.8 y). Assessment outcomes included basic physical health measures, a fitness test battery, and three psychological scales. The VP group recorded statistically significant improvements on the following outcomes: body mass (VP: −1.39 kg/CON: −0.2 kg), body mass index (VP: −1.5 kg/CON: −0.2 kg), 6 min walk (VP: +42.81 m/CON: −0.45 m), 30 s sit-to-stand (VP: −1.7 s/CON: −0.7 s), the chair sit-and-reach (VP: +3.12 cm/CON: +1.90 cm), and the 30 s arm curl test (VP: + 2 reps/CON: +0.9 reps). No significant differences were found with the other outcomes assessed. New members to the Vitality program achieved several physical and functional benefits without regression on any aspects of physical or psychological health.
Clinical Implications of Immune Checkpoints and the RANK/RANK-L Signaling Pathway in High-Grade Canine Mast Cell Tumors

Simple Summary This study aimed to characterize the molecular profiles of immune checkpoints RANK/RANK-L and IFN-γ in high-grade mast cell tumors and lymph node metastases to understand the complex activities occurring in the tumor microenvironment. All tumors showed moderate or intense immunolabeling of PD-L1, CTLA-4, RANK, RANK-L, and IFN-γ, and the lymph node metastases presented moderate or intense immunolabeling of checkpoint proteins. In conclusion, the high-grade MCTs were characterized as immunosuppressive microenvironments, showing an increase in the RANK/RANK-L signaling pathway and intensified immune checkpoint immunoreactivity, which may explain an intratumoral escape mechanism and indicating high sensitivity to immunotherapy. Therefore, PD-L1, RANK/RANK-L and IFN-γ may be useful in the clinical management of dogs with high-grade MCT. Abstract Mast cell tumors (MCTs) are the most common malignant cutaneous tumors in dogs, and they present extremely variable biological behavior. The interaction between RANK, RANK-L, and immune checkpoints is frequently detected in the tumor microenvironment, and, together, they participate in every stage of cancer development. Thus, the aim of this study was to characterize the molecular profiles of PD-L1, CTLA-4, RANK/RANK-L signaling pathway, and IFN-γ in primary tumors and lymph node metastases. Formalin-fixed, paraffin-embedded slides of MCTs and metastatic lymph nodes of ten dogs were submitted to immunohistochemical investigations. The results demonstrated that the tumor microenvironment of the high-grade mast cell tumors showed moderate or intense immunolabeling of all proteins, and the lymph node metastases also showed moderate or intense immunolabeling of checkpoint proteins. In addition, MCTs larger than 3 cm were associated with intensified PD-L1 (p = 0.03) in metastatic lymph nodes and RANK-L (p = 0.049) immunoreactivity in the tumor. Furthermore, dogs with a survival time of less than 6 months showed higher PD-L1 immunoreactivity (p = 0.042). In conclusion, high-grade MCT is associated with an immunosuppressive microenvironment that exhibits elevated RANK/RANK-L signaling and enhanced immune checkpoint immunoreactivity, potentially facilitating intratumorally immune escape. These biomarkers show promise as clinical indicators of disease progression and might response to immunotherapy in dogs with high-grade MCTs, thus emphasizing their importance for guiding treatment decisions and improving outcomes.
Factors Impacting the Use or Rejection of Hearing Aids—A Systematic Review and Meta-Analysis

Purpose: To examine the prevalence of adherence to hearing aids and determine their rejection causes. Methods: This study was conducted according to the Preferred Reporting terms for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed an electronic search using PubMed, BVS, and Embase. Results: 21 studies that met the inclusion criteria were selected. They analyzed a total of 12,696 individuals. We observed that the most common causes for positive adherence to hearing aid use included having a higher degree of hearing loss, patients being aware of their condition, and requiring the device in their daily life. The most common causes for rejection were the lack of perceived benefits or discomfort with the use of the device. The results from the meta-analysis show a prevalence of patients who used their hearing aid of 0.623 (95% CI 0.531, 0.714). Both groups are highly heterogeneous (I2 = 99.31% in each group, p < 0.05). Conclusions: A significant proportion of patients (38%) do not use their hearing aid devices. Homogeneous multicenter studies using the same methodology are needed to analyze the causes of rejection of hearing aids.
Engaging Industry in Health Professions’ Education: Benefits and Challenges

Effective partnerships between universities and industry facilitate health-profession students’ learning and work readiness. However, developing sustainable industry engagement in academic curricula remains challenging. This study utilised Social Exchange Theory (SET) to explore the benefits of and barriers to industry engagement within health-profession preparation programs. A realist evaluation framework was used to consider factors that impacted experiences and outcomes for academics and clinicians who engaged in the development and delivery of curriculum for a new health professional preparation program in speech pathology. A sequential mixed-methods design was adopted to explore factors influencing clinicians’ motivation to engage with the university, using an online survey (n = 18) and focus group (n = 5). Clinicians rated “personal development” and contributing to the “future workforce” as the highest personal benefits. “Sharing knowledge” was the highest team benefit, and “staff satisfaction” was the highest employer benefit. Time and workload were perceived barriers. Academics (n = 2) and clinicians (n = 3) who collaborated in learning and teaching experiences also participated in a post-engagement focus group. Three Context Mechanism Outcome configurations were shown to facilitate engagement outcomes: engagement as opportunity, partnership, and work readiness. In accordance with SET, the nature of exchange processes and professional relationships contributed to positive engagement outcomes for clinicians, academics, and enhanced health-profession education.
Low-Field Magnetic Stimulation Alleviates MPTP-Induced Alterations in Motor Function and Dopaminergic Neurons in Male Mice

Recent studies show that repetitive transcranial magnetic stimulation (rTMS) improves cognitive and motor functions in patients with Parkinson’s Disease (PD). Gamma rhythm low-field magnetic stimulation (LFMS) is a new non-invasive rTMS technique that generates diffused and low-intensity magnetic stimulation to the deep cortical and subcortical areas. To investigate the potential therapeutic effects of LFMS in PD, we subjected an experimental mouse model to LFMS (as an early treatment). We examined the LFMS effect on motor functions as well as neuronal and glial activities in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated male C57BL/6J mice. Mice received MPTP injection (30 mg/kg, i.p., once daily for 5 days) followed by LFMS treatment, 20 min each day for 7 days. LFMS treatment improved motor functions compared with the sham-treated MPTP mice. Further, LFMS significantly improved tyrosine hydroxylase (TH) and decreased glial fibrillary acidic protein (GFAP) levels in substantia nigra pars compacta (SNpc) and non-significantly in striatal (ST) regions. LFMS treatment improved neuronal nuclei (NeuN) levels in SNpc. Our findings suggest that early LFMS treatment improves neuronal survival and, in turn, motor functions in MPTP-treated mice. Further investigation is required to clearly define the molecular mechanisms by which LFMS improves motor and cognitive function in PD patients.
The Unfolded Protein Response Sensor IRE1 Regulates Activation of In Vitro Differentiated Type 1 Conventional DCs with Viral Stimuli

Type 1 conventional dendritic cells (cDC1s) are leukocytes competent to coordinate antiviral immunity, and thus, the intracellular mechanisms controlling cDC1 function are a matter of intense research. The unfolded protein response (UPR) sensor IRE1 and its associated transcription factor XBP1s control relevant functional aspects in cDC1s including antigen cross-presentation and survival. However, most studies connecting IRE1 and cDC1 function are undertaken in vivo. Thus, the aim of this work is to elucidate whether IRE1 RNase activity can also be modeled in cDC1s differentiated in vitro and reveal the functional consequences of such activation in cells stimulated with viral components. Our data show that cultures of optimally differentiated cDC1s recapitulate several features of IRE1 activation noticed in in vivo counterparts and identify the viral analog Poly(I:C) as a potent UPR inducer in the lineage. In vitro differentiated cDC1s display constitutive IRE1 RNase activity and hyperactivate IRE1 RNase upon genetic deletion of XBP1s, which regulates production of the proinflammatory cytokines IL-12p40, TNF-α and IL-6, Ifna and Ifnb upon Poly(I:C) stimulation. Our results show that a strict regulation of the IRE1/XBP1s axis regulates cDC1 activation to viral agonists, expanding the scope of this UPR branch in potential DC-based therapies.
The Influence of Decision-Making Logic on Employees’ Innovative Behaviour: The Mediating Role of Positive Error Orientation and the Moderating Role of Environmental Dynamics

Purpose The derivation of employees’ innovative behaviour is a complex multi-stage process influenced by decision logic. However, previous research on the relationship between the two has not been comprehensive without considering the individual level of employees, and the mechanism of action between the two is still unclear. Based on the behavioral decision theory, the broaden-and-build theory of positive emotions and triadic reciprocal determinism. This study investigates the mediating effects of positive error orientation between decision-making logic and employees’ innovative behavior, and the moderating effects of environmental dynamics between decision-making logic and employees’ innovative behavior, focusing on the individual level. Methods The questionnaire data was obtained from 403 employees randomly selected from 100 companies in Nanchang, China, in various industries such as manufacturing, transportation, storage and postal services, trade, and wholesale and retail trade. Hypotheses were tested using structural equation modeling. Results Effectual logic had a significantly positive impact on employees’ innovative behavior. The direct effect of causal logic on employees’ innovative behavior was not significant, but the total effect was significantly positive. Positive error orientation played a mediating role between both types of decision-making logic and employees’ innovative behavior. Moreover, environmental dynamics played a negative moderating role between effectual logic and employees’ innovative behavior. Originality/Value This study expands the application of behavioral decision theory, the broaden-and-build theory of positive emotions and triadic reciprocal determinism in employees’ innovative behaviour, enriches the research on the mediating and moderating mechanism between employees’ decision-making logic and innovative behaviour, and provides a new research perspective and empirical support for subsequent related research. Practical Implications The results of this study provide practical suggestions for promoting employees’ innovative behaviour. For example, employees need to cultivate logical thinking, train their decision-making ability, form a positive error orientation, and objectively assess the external environment.
On The Exact and JWKB Solution of 1D Quantum Harmonic Oscillator by Mathematica

Although being the fundamental semiclassical approximation method mainly used in quantum mechanics and optical waveguides, JWKB method along with the application of the associated JWKB asymptotic matching rules is known to give exact solutions for the Quantum Harmonic Oscillator (QHO). Asymptotically matched JWKB solutions are typically accurate or exact in the entire domain except for a narrow domain around the classical turning points where potential energy equals the total energy of the related quantum mechanical system. So, one has to cope with this diverging behavior at the classical turning points since it prohibits us from using continuity relations at the related boundaries to determine the required JWKB coefficients. Here, a computational diagram and related mathematica codes to surmount the problem by applying parity matching for even and odd JWKB solutions rather than boundary continuities are being presented. In effect, JWKB coefficients as well as the conversion factor for the dimensionless form of the Schrodingers equation, which is common to both exact and JWKB solutions, is being successfully obtained.
A Scoping Review of Economic Evaluations to Inform the Reorientation of Preventive Health Services in Australia

The Australian National Preventive Health Strategy 2021–2030 recommended the establishment of evidence-based frameworks to enable local public health services to identify strategies and interventions that deliver value for money. This study aimed to review the cost-effectiveness of preventive health strategies to inform the reorientation of local public health services towards preventive health interventions that are financially sustainable. Four electronic databases were searched for reviews published between 2005 and February 2022. Reviews that met the following criteria were included: population: human studies, any age or sex; concept 1: primary and/or secondary prevention interventions; concept 2: full economic evaluation; context: local public health services as the provider of concept 1. The search identified 472 articles; 26 were included. Focus health areas included mental health (n = 3 reviews), obesity (n = 1), type 2 diabetes (n = 3), dental caries (n = 2), public health (n = 4), chronic disease (n = 5), sexual health (n = 1), immunisation (n = 1), smoking cessation (n = 3), reducing alcohol (n = 1), and fractures (n = 2). Interventions that targeted obesity, type 2 diabetes, smoking cessation, and fractures were deemed cost-effective, however, more studies are needed, especially those that consider equity in priority populations.
Disruption of Bacterial Thiol-Dependent Redox Homeostasis by Magnolol and Honokiol as an Antibacterial Strategy

Some traditional Chinese medicines (TCMs) possess various redox-regulation properties, but whether the redox regulation contributes to antibacterial mechanisms is not known. Here, ginger juice processed Magnoliae officinalis cortex (GMOC) was found to show strong antibacterial activities against some Gram-positive bacteria, but not Gram-negative bacteria including E. coli, while the redox-related transcription factor oxyR deficient E. coli mutant was sensitive to GMOC. In addition, GMOC and its main ingredients, magnolol and honokiol, exhibited inhibitory effects on the bacterial thioredoxin (Trx) system, a major thiol-dependent disulfide reductase system in bacteria. The effects of magnolol and honokiol on cellular redox homeostasis were further verified by elevation of the intracellular ROS levels. The therapeutic efficacies of GMOC, magnolol and honokiol were further verified in S. aureus-caused mild and acute peritonitis mouse models. Treatments with GMOC, magnolol and honokiol significantly reduced the bacterial load, and effectively protected the mice from S. aureus-caused peritonitis infections. Meanwhile, magnolol and honokiol produced synergistic effects when used in combination with several classic antibiotics. These results strongly suggest that some TCMs may exert their therapeutic effects via targeting the bacterial thiol-dependent redox system.
Evaluation of Different Registration Algorithms to Reduce Motion Artifacts in CT-Thermography (CTT)

Computed tomography (CT)-based Thermography (CTT) is currently being investigated as a non-invasive temperature monitoring method during ablation procedures. Since multiple CT scans with defined time intervals were acquired during this procedure, interscan motion artifacts can occur between the images, so registration is required. The aim of this study was to investigate different registration algorithms and their combinations for minimizing inter-scan motion artifacts during thermal ablation. Four CTT datasets were acquired using microwave ablation (MWA) of normal liver tissue performed in an in vivo porcine model. During each ablation, spectral CT volume scans were sequentially acquired. Based on initial reconstructions, rigid or elastic registration, or a combination of these, were carried out and rated by 15 radiologists. Friedman’s test was used to compare rating results in reader assessments and revealed significant differences for the ablation probe movement rating only (p = 0.006; range, 5.3–6.6 points). Regarding this parameter, readers assessed rigid registration as inferior to other registrations. Quantitative analysis of ablation probe movement yielded a significantly decreased distance for combined registration as compared with unregistered data. In this study, registration was found to have the greatest influence on ablation probe movement, with connected registration being superior to only one registration process.
Hyperleukocytosis in Childhood Acute Leukemia: Early Complications and Survival Outcomes

Simple Summary Hyperleukocytosis (WBC > 100 × 109/L) has been associated with unfavorable outcomes. Few studies have focused on childhood acute leukemia with hyperleukocytosis in developing countries, where the treatment outcomes remain poorer than in developed countries. Our study reviewed the medical records of 690 children who were diagnosed with acute leukemia between January 1998 and December 2017. The incidence of hyperleukocytosis was 16.6% in acute lymphoblastic leukemia (ALL) patients and 20.3% in acute myeloid leukemia (AML) patients. Hyperleukocytosis, extreme hyperleukocytosis (WBC > 200 × 109/L), age less than 1 year, age greater than 10 years, and male sex were independently associated with overall survival in the ALL group, while extreme hyperleukocytosis and age less than 1 year were independently associated with overall survival in the AML group. We believe that to improve survival outcomes for children with hyperleukocytosis, the recommended treatment regimen must be modified, while early treatment-related complications, which are more likely to develop, should raise concerns. Abstract Hyperleukocytosis and extreme hyperleukocytosis, defined as initial white blood cell counts greater than 100 × 109/L and 200 × 109/L, respectively, have been associated with unfavorable outcomes. This study aimed to determine the early complications and survival outcomes of childhood leukemia patients with hyperleukocytosis. The medical records of 690 children newly diagnosed with acute leukemia between January 1998 and December 2017 were retrospectively reviewed. The Kaplan–Meier method and log-rank test were used to assess and compare the survival outcomes. Multivariate Cox proportional hazards regression was used to determine associated risk factors for overall survival. We found that 16.6% of 483 childhood acute lymphoblastic leukemia (ALL) patients and 20.3% of 207 childhood acute myeloid leukemia (AML) patients had hyperleukocytosis at diagnosis. ALL patients with hyperleukocytosis had more early complications than those without hyperleukocytosis (p < 0.05). Among the ALL group, the 5-year overall survival rate for those with hyperleukocytosis was significantly lower than for those without hyperleukocytosis (37.2% vs. 67.8%, p < 0.0001), while the difference was not statistically significant in the AML group (19.0% vs. 30.2%, respectively, p = 0.26). Hyperleukocytosis (hazard ratio [HR]: 2.04), extreme hyperleukocytosis (HR: 2.71), age less than 1 year (HR: 3.05), age greater than 10 years (HR: 1.64), and male sex (HR: 1.37) were independently associated with poorer overall survival in childhood ALL patients. Extreme hyperleukocytosis (HR: 2.63) and age less than 1 year (HR: 1.82) were independently associated with poorer overall survival in AML patients. Hyperleukocytosis was associated with adverse survival outcomes in childhood leukemia.