Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Mechanisms Driven by MT4-MMP in Cancer Progression

MT4-MMP (or MMP-17) belongs to the membrane-type matrix metalloproteinases (MT-MMPs), a distinct subset of the MMP family that is anchored to the cell surface, in this case by a glycosylphosphatidylinositol (GPI) motif. Its expression in a variety of cancers is well documented. However, the molecular mechanisms by which MT4-MMP contributes to tumor development need further investigation. In this review, we aim to summarize the contribution of MT4-MMP in tumorigenesis, focusing on the molecular mechanisms triggered by the enzyme in tumor cell migration, invasiveness, and proliferation, in the tumor vasculature and microenvironment, as well as during metastasis. In particular, we highlight the putative substrates processed and signaling cascades activated by MT4-MMP that may underlie these malignancy processes and compare this with what is known about its role during embryonic development. Finally, MT4-MMP is a relevant biomarker of malignancy that can be used for monitoring cancer progression in patients as well as a potential target for future therapeutic drug development.
PBAF Subunit Pbrm1 Selectively Influences the Transition from Progenitors to Pre-Myelinating Cells during Oligodendrocyte Development

Oligodendrocyte development is accompanied by defined changes in the state of chromatin that are brought about by chromatin remodeling complexes. Many such remodeling complexes exist, but only a few have been studied for their impact on oligodendrocytes as the myelin-forming cells of the central nervous system. To define the role of the PBAF remodeling complex, we focused on Pbrm1 as an essential subunit of the PBAF complex and specifically deleted it in the oligodendrocyte lineage at different times of development in the mouse. Deletion in late oligodendrocyte progenitor cells did not lead to substantial changes in the ensuing differentiation and myelination processes. However, when Pbrm1 loss had already occurred in oligodendrocyte progenitor cells shortly after their specification, fewer cells entered the pre-myelinating state. The reduction in pre-myelinating cells later translated into a comparable reduction in myelinating oligodendrocytes. We conclude that Pbrm1 and, by inference, the activity of the PBAF complex is specifically required at the transition from oligodendrocyte progenitor to pre-myelinating oligodendrocyte and ensures the generation of normal numbers of myelinating oligodendrocytes.
High-Impact Risk Factors for Mycobacterium avium ssp. paratuberculosis in Dairy Herds in Germany

Simple Summary Previous studies have investigated the role of different factors in paratuberculosis introduction in dairy farms or dairy cattle. Because paratuberculosis between-herd prevalence was shown to differ substantially between three regions of Germany, this study evaluated different management factors for their impact on the paratuberculosis status of a farm. The most obvious impact was found for an increase of 100 or more cows per herd, followed by the purchase of cattle with unknown paratuberculosis status and limitations in calf feeding management within the barn. These aspects should be prioritized in paratuberculosis control beneath a tailored control approach for individual farms and regions. Abstract In a cross-sectional study, it was identified that three regions in Germany differed with respect to their herd-level prevalence for paratuberculosis in dairy cattle. In the study presented here, the same farms were analyzed to identify those components of biosecurity and farm management with the highest impact on Mycobacterium avium ssp. paratuberculosis (MAP) introduction and establishment in a farm. Hence, the data analyzes included 183, 170 and 104 herds from the study regions north, east and south, respectively. A herd was considered MAP-positive if at least one fecal environmental sample was positive. Twenty-six different possible risk factors from five different components of biosecurity and farm management were analyzed. We show that the average management of calf feeding increased the odds for a MAP-positive farm by 5.22 times (95% confidence interval (CI) = 1.25–21.83). With every 100-cow increase in farm size, the risk for a farm to test MAP-positive increased by 1.94 times (CI = 1.15–3.27), 1.14 times (CI = 1.02–1.27) and 5.53 times (CI = 0.44–68.97) in the north, east and south study regions, respectively. Furthermore, the purchase of cattle with an unknown MAP status increased the risk for a farm testing MAP-positive by 2.86-fold (CI = 1.45–5.67). Our results demonstrate that herd size, unknown MAP status of the purchased cattle and different aspects of calf feeding play an important role in the MAP status of a farm and should be in focus in regions with different MAP between-herd prevalence. Additionally, farm individual risk patterns should be identified during (veterinary) biosecurity consultancy.
Immunosuppressant Adherence Factors Differentiating Compliant and Non-Compliant Kidney Transplant Recipients

The purpose of this study is to find out the psychological factor characteristic of non-adherence patients. The study population comprised kidney transplant recipients aged between 18 and 82 years at least 3 months post-transplant who voluntarily agreed to answer a couple of fully anonymous questionnaires that questions pertaining to basic data, type of immunosuppressive drugs taken, and standardized questionnaires. Participants were recruited using direct routine, free-of-charge visits to specialist doctors in transplant clinics. There was no significant difference in the percentage of men and women in both adherence and non-adherence groups. Non-adherence patients were significantly younger compared to adherence patients. There was also a significant difference in the patient’s level of education. Adherence patients were better educated. No significant differences in criteria such as place of residence, having children or a partner, or way of living were observed. However, the emotion scale correlated negatively with the level of life orientation in both groups, but the level of the emotions scale and distractions subscale was negatively correlated with the level of self-esteem only for the adherence group. In future research, it would be worthwhile to focus on lifestyle and health-promoting behaviors in juxtaposition with the propensity for adherence.
Spatial Heterogeneity in Cytoskeletal Mechanics Response to TGF-β1 and Hypoxia Mediates Partial Epithelial-to-Meshenchymal Transition in Epithelial Ovarian Cancer Cells

Simple Summary One major challenge to understanding and targeting deadly epithelial ovarian cancer is the heterogeneous nature of the disease, including intrinsic physical and genetic differences in cells and differences in the spatial microenvironmental cues in the tumor. In this study, we show that microenvironmental cues that mimic tumor promoting aspects of the in vivo tumor niche can alter the pattern of clustered epithelial cancer cells and induce the formation of invasive subpopulations. We identified the invasive subpopulations based on analysis of single cell physical characteristics and underlying structural protein organization. Our analysis highlights that peripheral cancer cells in a cluster display increased invasiveness in response to the external cues. Abstract Metastatic progression of epithelial ovarian cancer (EOC) involves the partial epithelial-to-mesenchymal transition (EMT) of cancer cells in the primary tumor and dissemination into peritoneal fluid. In part to the high degree of heterogeneity in EOC cells, the identification of EMT in highly epithelial cells in response to differences in matrix mechanics, growth factor signaling, and tissue hypoxia is very difficult. We analyzed different degrees of EMT by tracking changes in cell and nuclear morphology, along with the organization of cytoskeletal proteins. In our analysis, we see a small percentage of individual cells that show dramatic response to TGF-β1 and hypoxia treatment. We demonstrate that EOC cells are spatially aware of their surroundings, with a subpopulation of EOC cells at the periphery of a cell cluster in 2D environments exhibited a greater degree of EMT. These peripheral cancer cells underwent partial EMT, displaying a hybrid of mesenchymal and epithelial characteristics, which often included less cortical actin and more perinuclear cytokeratin expression. Collectively, these data show that tumor-promoting microenvironment conditions can mediate invasive cell behavior in a spatially regulated context in a small subpopulation of highly epithelial clustered cancer cells that maintain epithelial characteristics while also acquiring some mesenchymal traits through partial EMT.
A fiber tip label free biological sensing platform for in vivo applications

The novel platform presented in this paper is design to answer the unmet challenge of real time label free in-vivo sensing by bringing together a refractive index transducing mechanism based on Whispering Gallery Modes in dye doped microspheres combined with Microstructured Optical Fibers. In addition to providing the provides the remote excitation and collection of the WGM signal, the fibre also allows easily manipulation of the microresonator and the use this sensor in a dip sensing architecture, alleviating the need for a complex microfluidic interface. Here, we demonstrate the ability of this sensing platform to be operated above its lasing threshold, enabling enhanced performance.
Do Patients’ Psychosocial Characteristics Impact Antibiotic Prescription Rates?

Previous research suggests that the characteristics of both patients and physicians can contribute to the overuse of antibiotics. Until now, patients’ psychosocial characteristics have not been widely explored as a potential contributor to the overuse of antibiotics. In this study, the relationship between a patient’s psychosocial characteristics (self-reported in postal surveys in 2003) and the number of antibiotics they were prescribed (recorded in Finnish national registry data between 2004–2006) were analyzed for 19,300 working-aged Finns. Psychosocial characteristics included life satisfaction, a sense of coherence, perceived stress, hostility, and optimism. In a structural equation model, patients’ adverse psychosocial characteristics were not related to increased antibiotic prescriptions in the subsequent three years. However, these characteristics were strongly associated with poor general health status, which in turn was associated with an increased number of subsequent antibiotic prescriptions. Furthermore, mediation analysis showed that individuals who used healthcare services more frequently also received more antibiotic prescriptions. The current study does not support the view that patients’ adverse psychosocial characteristics are related to an increased number of antibiotic prescriptions. This could encourage physicians to actively discuss treatment options with their patients.
Reduction of EpCAM-Positive Cells from a Cell Salvage Product Is Achieved by Leucocyte Depletion Filters Alone

Intraoperative cell salvage reduces the need for allogeneic blood transfusion in complex cancer surgery, but concerns about the possibility of it re-infusing cancer cells have hindered its application in oncology. We monitored the presence of cancer cells on patient-salvaged blood by means of flow cytometry; next, we simulated cell salvage, followed by leucodepletion and irradiation on blood contaminated with a known amount of EpCAM-expressing cancer cells, assessing also residual cancer cell proliferation as well as the quality of salvaged red blood cell concentrates (RBCs). We observed a significant reduction of EpCAM-positive cells in both cancer patients and contaminated blood, which was comparable to the negative control after leucodepletion. The washing, leucodepletion and leucodepletion plus irradiation steps of cell salvage were shown to preserve the quality of RBCs in terms of haemolysis, membrane integrity and osmotic resistance. Finally, cancer cells isolated from salvaged blood lose their ability to proliferate. Our results confirm that cell salvage does not concentrate proliferating cancer cells, and that leucodepletion allows for the reduction of residual nucleated cells, making irradiation unnecessary. Our study gathers pieces of evidence on the feasibility of this procedure in complex cancer surgery. Nevertheless, it highlights the necessity of finding a definitive consensus through prospective trials.
Sport Anxiety, Fear of Negative Evaluation, Stress and Coping as Predictors of Athlete’s Sensitivity to the Behavior of Supporters

The aim of the study was to find predictors of athlete sensitivity to the positive or negative behaviors of supporters and determine a relationship between athletes’ sensitivity to the positive and negative behaviors of supporters and traits such as anxiety and stress or the strategies used to cope with stress. The sample consisted of 171 professional athletes. The study determined three variables that are predictors of athlete sensitivity to the positive behavior of supporters (SPS), i.e., strategies of coping with stress, such as high levels of coachability, confidence and achievement motivation and low levels of freedom from worry (change R2 = 0.15, F of change = 9.78, p of change < 0.001). The predictors of sensitivity to the negative behavior of supporters (SNS) are as follows: a low level of freedom from worry and a high level of fear of negative evaluation (change R2 = 0.31, F of change = 38.56, p of change < 0.001). In the context of the athlete’s position, the predictors of SPS for midfielders are as follows: high level of susceptibility to stress and two strategies of coping with stress, i.e., peaking under pressure and concentration. For forwarders they are as follows: high level of worry and coping with stress via goal-setting, while for defenders, the ways of coping with stress are confidence and achievement motivation. In terms of SNS, for defenders, the predictors are low levels of freedom from worry, coachability, and a high level of fear of negative evaluation. Forwarders, who are sensitive to the negative behavior of supporters, are characterized by a fear of negative evaluation.
Anti-Inflammatory and Antioxidant Effects of Leaves and Sheath from Bamboo (Phyllostacys edulis J. Houz)

Bamboo (Phyllostacys edulis J. Houz) has become an emerging forest resource of economic and ecological significance with health benefits. Since the beneficial effects of the non-edible parts of bamboo have not been thoroughly explored, we characterized in this study bamboo leaf (BL) and sheath (BS) extracts. The total phenol and flavonoid content (TPC and TFC), antioxidant activity (ABTS, DPPH, FRAP and β-carotene bleaching test) and anti-inflammatory properties were determined. Leaves exhibited a TPC value of 73.92 mg equivalent (eq) gallic acid/g fresh weight (FW) and a TFC value of 56.75 mg eq quercetin/g FW. Ultra-High-Performance Liquid Chromatography (UHPLC) coupled with photo diode array detector (PDA) analysis revealed evidence for the presence of protocatechuic acid, isoorientin, orientin and isovitexin in BL, whereas BS was rich in phenolic acids. Both samples demonstrated a significant ability to scavenge radicals against ABTS·+, with an inhibitory concentration of 50% of 3.07 μg/mL for BL and 6.78 μg/mL for BS. At a concentration of 0.1 and 0.2 mg/mL, BS decreased reactive oxygen species production without hampering cell viability in HepG2 liver cells, while at the same concentrations, BL exhibited cytotoxicity in HepG2 cells. In addition, 0.1 and 0.2 mg/mL BS and BL reduced Interleukin-6 and Monocyte Chemoattractant Protein-1 production in human lipopolysaccharide-stimulated THP-1 macrophages, without affecting cell viability. These findings highlight the anti-inflammatory and antioxidant properties of BL and BS, corroborating their different potential applications in the nutraceutical, cosmetic and pharmaceutical industries.
In the Wake of COVID-19: The Developmental and Mental Health Fallout Amongst South African University Students

Multiple studies have noted the impacts on student mental health of the COVID-19 pandemic, associated national lockdowns and emergency remote teaching. In light of COVID-19 shifting from pandemic to endemic status, this study investigates the developmental and mental health consequences of the pandemic for a group of South African undergraduate students. A qualitative design allowed for the thematic analysis of the narratives of 140 humanities students, gathered through an online survey. This paper presents the ‘voices’ of this group to convey the intensity of their COVID-19 experience. The results suggest a loss of a sense of freedom and opportunities to explore and experiment, high levels of depression with a notable sense of hopelessness regarding the future and decreased motivation, and significant reports of social anxiety related to delays in the development of social skills due to social isolation, particular to the first-year cohort.
Losing a Close Friend or Family Member Due to COVID-19 and Mental Health among LGBTQ Youth

This study examines the association between having lost a close friend or family member to COVID-19 and mental health outcomes among lesbian, gay, bisexual, transgender, or queer (LGBTQ) youth. Data come from 33,993 respondents in the United States, ages 13 to 24, who completed an online survey of LGBTQ youth mental health. Multivariate logistic regression was used to determine the adjusted odds of recent anxiety, depression, considering, or attempting suicide in the past year based on whether or not the youth reported having lost a close friend or family member to COVID-19. Among the full sample, experiences of COVID-19 loss were associated with recent anxiety (adjusted odds ratio (aOR) = 1.29, 95% confidence interval (CI) = 1.20–1.40), recent depression (aOR = 1.23, 95% CI [1.15, 1.32]), seriously considering suicide in the past year (aOR = 1.22, 95% CI (1.14, 1.30)), and attempting suicide in the past year (aOR = 1.55, 95% CI (1.41, 1.69)). These findings highlight the urgent need for investment in low-barrier, affirming mental health services for LGBTQ youth who have experienced COVID-19 loss to support their grief, overall mental health, and healthy development.
Differential Lipidomics, Metabolomics and Immunological Analysis of Alcoholic and Non-Alcoholic Steatohepatitis in Mice

Non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) are the leading causes of liver disease worldwide. To identify disease-specific pathomechanisms, we analyzed the lipidome, metabolome and immune cell recruitment in livers in both diseases. Mice harboring ASH or NASH had comparable disease severities regarding mortality rate, neurological behavior, expression of fibrosis marker and albumin levels. Lipid droplet size was higher in NASH than ASH and qualitative differences in the lipidome were mainly based on incorporation of diet-specific fatty acids into triglycerides, phosphatidylcholines and lysophosphatidylcholines. Metabolomic analysis showed downregulated nucleoside levels in both models. Here, the corresponding uremic metabolites were only upregulated in NASH suggesting stronger cellular senescence, which was supported by lower antioxidant levels in NASH as compared to ASH. While altered urea cycle metabolites suggest increased nitric oxide synthesis in both models, in ASH, this depended on increased L-homoarginine levels indicating a cardiovascular response mechanism. Interestingly, only in NASH were the levels of tryptophan and its anti-inflammatory metabolite kynurenine upregulated. Fittingly, high-content immunohistochemistry showed a decreased macrophage recruitment and an increased polarization towards M2-like macrophages in NASH. In conclusion, with comparable disease severity in both models, higher lipid storage, oxidative stress and tryptophan/kynurenine levels were seen in NASH, leading to distinct immune responses.
The Impact of Preclinical High Potent P2Y12 Inhibitors on Decision Making at Discharge and Clinical Outcomes in Patients with Acute Coronary Syndrome

Background: Purinergic signaling receptor Y12 (P2Y12) inhibitors are a fundamental part of pharmacological therapy in acute coronary syndrome (ACS) for preventing recurrent ischemic events. Current guidelines support the use of prasugrel over ticagrelor—however, ticagrelor is widely used for preclinical loading during ACS due to its ease of administration. In this regard, it remains unknown whether the preclinical loading with P2Y12 inhibitors impacts decision-making for the long-term dual antiplatelet strategy, as well as cardiovascular outcomes, including re-percutaneous coronary intervention in real-world settings. Methods: Within this population-based prospective observational study, all patients with ACS who received medical care via the Emergency Medical Service (EMS) in the city of Vienna between January 2018 and October 2020 were enrolled. Patients were stratified according to their P2Y12 inhibitor loading regimen. Subsequently, the association of P2Y12 inhibitor loading on long-term prescription at discharge and outcome was assessed. Results: The entire study cohort consisted of 1176 individuals with ST-elevation myocardial infarction (STEMI), of whom 47.5% received prasugrel and 52.5% ticagrelor. The likelihood of adhering to the initial P2Y12 inhibitor strategy during the clinical stay was high for both ticagrelor (84%; OR: 10.00; p < 0.001) and prasugrel (77%; OR: 21.26; p < 0.001). During patient follow-up (median follow-up time three years), 84 (7.1%) patients died due to cardiovascular causes, and 82 (7.0%) patients required re-PCI. Notably, there was no difference in cardiovascular mortality (6.6% ticagrelor vs. 7.7% prasugrel) or re-PCI rates (6.6% ticagrelor vs. 7.3% prasugrel) addressing the P2Y12 inhibition strategy. Conclusion: We observed that, regardless of the initial antiplatelet inhibitor strategy, the in-hospital P2Y12 adherence was exceedingly high, and there was a minimal occurrence of switching to another P2Y12 inhibitor. Most importantly, no significant difference in cardiovascular death/re-PCI between ticagrelor and prasugrel-based preclinical loading has been observed. Consequently, the choice of high potent P2Y12 did not influence the cardiac outcome from a long-term perspective.