Miracle-dz/UniFAR-FTUs huggingface dataset:
Pre-Therapeutic VEGF Level in Plasma Is a Prognostic Bio-Marker in Head and Neck Squamous Cell Carcinoma (HNSCC)

Simple Summary In the context of a growing variety in treatment strategies for patients with cancer, especially approaches based on antiangiogenetic pathways, we aimed to identify a useful biomarker for patients with head and neck squamous cell carcinoma (HNSCC). Our experimental results detected vascular endothelial growth factor (VEGF) in patients’ pre-therapeutic plasma, and not serum, which serves as a suitable biomarker for outcome prognostication. Results were validated in an independent cohort, confirming VEGF as an independent predictor (Pi) of outcomes in HNSCC patients. Therefore, pre-therapeutic VEGF in plasma may be an attractive biomarker in future HNSCC studies. Abstract Vascular endothelial growth factor (VEGF) is centrally involved in cancer angiogenesis. We hypothesized that pre-therapeutic VEGF levels in serum and plasma differ in their potential as biomarkers for outcomes in head and neck squamous cell carcinoma (HNSCC) patients. As prospectively defined in the study protocols of TRANSCAN-DietINT and NICEI-CIH, we measured VEGF in pretreatment serum and plasma of 75 HNSCC test cohort (TC) patients. We analyzed the prognostic value of VEGF concentrations in serum (VEGFSerum) and plasma (VEGFPlasma) for event-free survival (EFS) utilizing receiver-operating characteristics (ROC). Mean VEGF concentrations in plasma (34.6, 95% CI 26.0–43.3 ng/L) were significantly lower (p = 3.35 × 10−18) than in serum (214.8, 95% CI 179.6–250.0 ng/L) but, based on ROC (area under the curve, AUCPlasma = 0.707, 95% CI 0.573–0.840; p = 0.006 versus AUCSerum = 0.665, 95% CI 0.528–0.801; p = 0.030), superiorly correlated with event-free survival (EFS) of TC patients. Youden indices revealed optimum binary classification with VEGFPlasma 26 ng/L and VEGFSerum 264 ng/L. Kaplan–Meier plots demonstrated superiority of VEGFPlasma in discriminating patients regarding outcome. Patients with VEGFPlasma < 26 ng/L had superior nodal (NC), local (LC) and loco-regional control (LRC) leading to significant prolonged progression-free survival (PFS) and EFS. We successfully validated VEGFPlasma according the cut-off <26 ng/L as predictive for superior outcome in an independent validation cohort (iVC) of 104 HNSCC patients from the studies DeLOS-II and LIFE and found better outcomes including prolonged tumor-specific (TSS) and overall survival (OS). Outcomes in TC and iVC combined again was related to VEGFPlasma, and multivariate Cox regression revealed that VEGFPlasma was an independent outcome predictor. In HNSCC, pre-therapeutic VEGFPlasma is prognostic for outcomes.
Should I Stay or Should I Go? The Impact of Social Networks on the Choice to Play for a National Team in Football

In the course of their careers, elite athletes are faced with crucial decisions. This applies particularly to adolescent athletes who additionally have to cope with a variety of age-related developmental tasks. For young top football players with a migrant background, this can be even more challenging as they often attract the interest of national associations. From a network-theoretical perspective, it can be considered likely that the decision to join a top national association is not taken independently of the players’ networks. This article addresses the role of network actors within the players’ decision-making process. Our analysis is guided by constructivist network theory and based on a qualitative research approach that used guided expert interviews as its core research tool. Ten interviews with German-born youth internationals with a migrant background were conducted. The present analysis reveals several network actors such as family, coaches and players’ agents involved in the ‘national team question’. Evidently, most relevant networks of players with a migrant background are sports-related. These networks turned out to be highly functionalized and leave only limited room for manoeuvring. At the same time, the interviews reveal ‘structural holes’ within the players’ networks and indicate a considerable need for the optimization of talent counselling.
Association of Vital Pulp Therapy Outcomes with Tooth Type, Arch Location, Treatment Type, and Number of Surfaces Destroyed in Deciduous Teeth: A Retrospective Study

There is a paucity of information concerning vital pulp treatment outcomes in the undergraduate teaching setting. This study aimed to determine which type of deciduous molar, arch location, type of vital pulp therapy, and the number of carious surfaces involved had a better prognosis when carried out by undergraduate dental students. The method used was the review of clinical records of 590 patients with 600 deciduous molars, that visited the outpatient undergraduate dental clinics for vital pulp therapy. Statistical analysis used to determine the associations of tooth type, arch location, treatment type, and the number of carious surfaces involved in successful outcomes was logistic regression analysis with significance set at p < 0.05. According to the regression analysis model results, there was a significant association based on tooth type (p < 0.05) and arch location (p = 0.003). In addition, there was a significant association based on the type of treatment performed (p = 0.036). However, there was no significant association in success rates based on the number of carious surfaces involved (p = 0.873). In conclusion, second deciduous molars and maxillary deciduous molars had a better overall prognosis, and indirect pulp therapy was revealed to be more highly associated with successful treatment outcomes in comparison to ferric sulfate pulpotomy in our setting.
Rotavirus A infection in pre- and post-vaccine period: Risk factors, genotypes distribution by vaccination status and age of children in Nampula Province, Northern Mozambique (2015-2019)

Mozambique introduced the monovalent rotavirus vaccine (Rotarix®, GSK Biologicals, Rixensart, Belgium) in September 2015. Previous analysis, showed that Nampula province continues reporting a high frequency of Rotavirus A (RVA) infection and the emergence of G9P[6], G9P[4] and G3P[4] genotypes. This analysis aimed to determine the RVA frequency; risk factors; genotype distribution by vaccination status and age between pre- and post-vaccine periods in children under-five years old with diarrhea in Nampula. A cross-sectional, hospital-based surveillance study was conducted in the Hospital Central de Nampula in Mozambique. Socio-demographic and clinical data were collected to assess factors related to RVA infection in both periods. Stool specimens were screened to detect RVA by ELISA, and positive samples were genotyped. Between 2015 (pre-vaccine period) and 2016–2019 (post-vaccine period), 614 stool specimens were collected and tested for RVA in which 34.9% (67/192) were positive in pre-vaccine period and 21.8% (92/422) in post-vaccine (p = 0.001). In the post-vaccine period, age, year, and contact with different animal species (chicken, duck, or multiple animals) were associated with RVA infection. RVA infection was higher in children partially vaccinated (40.7%, 11/27) followed by the fully vaccinated (29.3%, 56/191) and the unvaccinated (15.3%, 21/137) (p = 0.002). G1P[8] and G9P[4] were common in vaccinated children less than 12 months. The present analysis showed that RVA infection reduced slightly in the post-vaccine period, with a high proportion of infection and genotype diversity in children, under 12 months of age, vaccinated. Further research on factors associated with RVA infection on vaccinated compared to unvaccinated children and vaccination optimization should be done.
Acid Microenvironment in Bone Sarcomas

Simple Summary Although rare, malignant bone sarcomas have devastating clinical implications for the health and survival of young adults and children. To date, efforts to identify the molecular drivers and targets have focused on cancer cells or on the interplay between cancer cells and stromal cells in the tumour microenvironment. On the contrary, in the current literature, the role of the chemical-physical conditions of the tumour microenvironment that may be implicated in sarcoma aggressiveness and progression are poorly reported and discussed. Among these, extracellular acidosis is a well-recognized hallmark of bone sarcomas and promotes cancer growth and dissemination but data presented on this topic are fragmented. Hence, we intended to provide a general and comprehensive overview of the causes and implications of acidosis in bone sarcoma. Abstract In bone sarcomas, extracellular proton accumulation is an intrinsic driver of malignancy. Extracellular acidosis increases stemness, invasion, angiogenesis, metastasis, and resistance to therapy of cancer cells. It reprograms tumour-associated stroma into a protumour phenotype through the release of inflammatory cytokines. It affects bone homeostasis, as extracellular proton accumulation is perceived by acid-sensing ion channels located at the cell membrane of normal bone cells. In bone, acidosis results from the altered glycolytic metabolism of bone cancer cells and the resorption activity of tumour-induced osteoclasts that share the same ecosystem. Proton extrusion activity is mediated by extruders and transporters located at the cell membrane of normal and transformed cells, including vacuolar ATPase and carbonic anhydrase IX, or by the release of highly acidic lysosomes by exocytosis. To date, a number of investigations have focused on the effects of acidosis and its inhibition in bone sarcomas, including studies evaluating the use of photodynamic therapy. In this review, we will discuss the current status of all findings on extracellular acidosis in bone sarcomas, with a specific focus on the characteristics of the bone microenvironment and the acid-targeting therapeutic approaches that are currently being evaluated.
De-Palmitoylation of Tissue Factor Regulates Its Activity, Phosphorylation and Cellular Functions

Simple Summary The relationship between cancer and blood clotting has been well established. The activation of blood coagulation proteins regulates the fate of cells and is known to be used by cancer cells to enhance survival and proliferation. Cells strictly regulate the initiation of coagulation through controlling the action of the protein “tissue factor (TF)”. In addition to initiating clotting, TF also acts as a deciding factor to determine the extent of damage and instructs cells to proliferate and repair or, when severely damaged, to die. Therefore, normal cells keep TF in a dormant state, achieved through mechanisms called “TF encryption”. Understanding the mechanisms by which the cells control the activity of TF is crucial, especially since cancer cells bypass these regulatory mechanisms, ensuring survival and tumour growth. This study has elucidated essential molecular mechanisms by which cells regulate TF clotting activity, and also the cellular signals arising from these. Abstract In this study, the role of de-palmitoylation of tissue factor (TF) in the decryption of its activity was explored. TF-tGFP constructs were prepared by mutagenesis-substitution at Cys245 to prevent or mimic palmitolyation. Additionally, to reduce TF de-palmitoylation, the expression of palmitoyl-protein thioesterases (PPT) was suppressed. Other TF mutants were prepared with altered flexibility, hydrophobicity or length of the transmembrane domain. The outcome of these alterations on fXa-generation, fVIIa binding, Ser253 phosphorylation and TF-microvesicle release were assessed in endothelial cells, and the influence on endothelial and MCF-7 cell proliferation and apoptosis was analysed. Preventing TF palmitoylation (TFSer245-tGFP), increasing the hydrophobicity (TFPhe241-tGFP) or lengthening (TFLongTM-tGFP) of the transmembrane domain enhanced fXa-generation in resting cells compared to cells expressing TFWt-tGFP, but fXa-generation was not further increased following PAR2 activation. Extending the available length of the transmembrane domain enhanced the TF-tGFP release within microvesicles and Ser253 phosphorylation and increased cell proliferation. Moreover, prevention of PKCα-mediated Ser253 phosphorylation with Gö6976 did not preclude fXa-generation. Conversely, reducing the hydrophobicity (TFSer242-tGFP), shortening (TFShortTM-tGFP) or reducing the flexibility (TFVal225-tGFP) of the transmembrane domain suppressed fXa-generation, fVIIa-HRP binding and Ser253 phosphorylation following PAR2 activation. PPT knock-down or mimicking palmitoylation (TFPhe245-tGFP) reduced fXa-generation without affecting fVIIa binding. This study has for the first time shown that TF procoagulant activity is regulated through de-palmitoylation, which alters the orientation of its transmembrane domain and is independent of TF phosphorylation. However, Ser253 phosphorylation is facilitated by changes in the orientation of the transmembrane domain and can induce TF-cellular signalling that influences cellular proliferation/apoptosis.
Shorter Leukocyte Telomere Length Is Associated with Worse Survival of Patients with Bladder Cancer and Renal Cell Carcinoma

Simple Summary Intrinsic telomere shortening promotes tumorigenesis in cells with impaired DNA damage repair mechanisms, as dysfunctional telomeres lead to chromosomal instability. More recent data show that the telomere length of peripheral blood leukocyte (PBL) cells can be a prognostic marker for survival of patients with solid tumors. However, reports on bladder cancer (BC) and renal cell carcinoma (RCC) are not consistent and partly contradictory. Our results show, first, that telomere length is shorter in patients with BC or RCC compared to patients without malignant disease. More importantly, the relative telomere length (RTL) of PBL cells is associated with survival of patients with BC and RCC. Thus, telomere length in PBL cells could be an auxiliary prognostic marker in BC and RCC. Abstract Background: Telomeres are protein–DNA complexes at the tips of linear chromosomes. They protect the DNA from end-to-end fusion and exonucleolytic degradation. Shortening of telomeric DNA during aging can generate dysfunctional telomeres, promoting tumorigenesis. More recent data indicate that both short and long telomeres of peripheral blood leukocyte (PBL) cells can serve as prognostic biomarkers for cancer risk and may be associated with survival of patients with solid cancers. Telomere length in PBL cells could also be a potential prognostic biomarker for survival in bladder cancer (BC) or renal cell carcinoma (RCC). Methods: The relative telomere length (RTL) of PBL cells was assessed in patients with BC (n = 144) and RCC (n = 144) by using qPCR. A control population of patients without malignant disease (NC, n = 73) was included for comparison. The correlation and association of RTL with histopathological parameters and overall survival (OS) were evaluated. Results: Patients with BC and RCC had significantly shorter telomeres compared to patients without malignant disease. Within the cancer cohorts, multivariate analysis revealed that short RTL is an independent predictor of worse survival in BC (p = 0.039) and RCC (p = 0.041). Conclusion: Patients with BC and RCC had significantly shorter telomeres compared to the normal population. Shorter RTL in BC and RCC was an independent predictor of reduced survival.
TB Antigen-Stimulated CXCR3 Ligand Assay for Diagnosis of Tuberculous Lymphadenitis

The diagnosis of tuberculous lymphadenitis (TB-LAP) is challenging. We evaluated the role of blood CXC chemokine receptor 3 (CXCR3) ligands in its diagnosis. A total of 65 lymphadenopathy patients were enrolled and lymph node sampling was performed. We also recruited 113 control subjects, consisting of 27 with positive results and 86 with negative results, in the interferon (IFN)-γ release assay (IGRA). In all study subjects, whole-blood samples were collected using the IGRA methodology. After incubation, plasma levels of IFN-γ and two CXCR3 ligands, IFN-inducible T-cell a chemoattractant (I-TAC) and monokine induced by IFN-γ (MIG), were measured using immunoassay. Fifty-three TB-LAP patients were enrolled. TB antigen-stimulated IFN-γ, I-TAC, and MIG levels were all significantly higher in the TB-LAP patients than in the controls and non-TB-LAP patients. The levels of I-TAC and MIG, but not IFN-γ, showed significant differences between the TB-LAP patients and IGRA-positive controls. Area under the receiver operating characteristic curves (AUROCs) of IFN-γ, I-TAC, and MIG were 0.955, 0.958, and 0.959, respectively, for differentiating TB-LAP from control group, and were 0.912, 0.956, and 0.936, respectively, for differentiating TB-LAP from non-TB-LAP. In conclusion, the TB antigen-stimulated MIG and I-TAC could be useful biomarkers in the diagnosis of TB-LAP.
Assessment of Body Composition, Lower Limbs Power, and Anaerobic Power of Senior Soccer Players in Portugal: Differences According to the Competitive Level

Background. During a soccer game, the most diversified stimuli occur all the time, the physical condition level plays a determinant role, and there may be variations according to the competitive level. In this sense, the present study aimed to verify differences in body composition, lower limbs power, and anaerobic power, comparing senior soccer players of different competitive levels. Methods. Participants were 81 players belonging to six soccer teams, aged between 18 and 35 years, with a mean age of 23.14 ± 4.23 years, who were divided into three distinct competitive levels: Elite, Sub-Elite and Non-Elite. The players performed bioimpedance evaluations on a tetrapolarInbody270 scale (body composition), the Countermovement Jump (CMJ) through the ChronoJump (lower limbs power), and Running Anaerobic Sprint Test (RAST) (anaerobic power). Results. Based on the competitive level analysis, we verified that the players present body composition values similar to each other regardless of the competitive level in which they play. Concerning the performance evaluations, we verified that the elite players present higher values of highest jump (p = 0.012; d = 0.76, moderate; and p = 0.022; d = 0.71, moderate) and maximum force produced (p = 0.05; d = 0.64, moderate; and p = 0.002; d = 1.00, moderate), together with higher values of anaerobic power (p < 0.001; d = 2.43, very large; and p < 0.001; d = 2.22, very large), compared to the others. Conclusions. We can thus conclude that there is a homogeneity regarding the body composition of soccer players, regardless of their competitive level; in turn, elite players show better performance indicators in all variables.
Impact of IL-1β and the IL-1R antagonist on relapse risk and survival in AML patients undergoing immunotherapy for remission maintenance

ABSTRACT Interleukin-1 beta (IL-1β), a pro-inflammatory cytokine, has been ascribed a role in the expansion of myeloid progenitors in acute myeloid leukemia (AML) and in promoting myeloid cell-induced suppression of lymphocyte-mediated immunity against malignant cells. This study aimed at defining the potential impact of IL-1β in the post-remission phase of AML patients receiving immunotherapy for relapse prevention in an international phase IV trial of 84 patients (ClinicalTrials.gov; NCT01347996). Consecutive serum samples were collected from AML patients in first complete remission (CR) who received cycles of relapse-preventive immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2). Low IL-1β serum levels before and after the first HDC/IL-2 treatment cycle favorably prognosticated leukemia-free survival and overall survival. Serum levels of IL-1β were significantly reduced in patients receiving HDC/IL-2. HDC also reduced the formation of IL-1β from activated human PBMCs in vitro. Additionally, high serum levels of the IL-1 receptor antagonist IL-1RA were associated with favorable outcome, and AML patients with low IL-1β along with high IL-1RA levels were strikingly protected against leukemic relapse. Our results suggest that strategies to target IL-1β might impact on relapse risk and survival in AML.
Romanian Students’ Environment-Related Routines during COVID-19 Home Confinement: Water, Plastic, and Paper Consumption

The disruptive force of the COVID-19 pandemic is lessening in power and plans are being made for the postcrisis period, among which increasing the sustainability of higher education is of significant importance. The study aims at establishing students’ existing environment-related routines during their home confinement, as a basis for applying green measures to campus living once academic life is resumed with the physical presence of students. The collected data rely on self-reported information provided by 816 students from Politehnica University of Timisoara (Romania), collected via an online, anonymous survey. The novelty of the approach is that household environment-related routines are investigated during a crisis period, with the possibility to build upon the results to implement tailored measures to encourage or diminish environmentally relevant consumption by young, highly skilled individuals. The students display a moderate awareness of environmental issues and indicate consumption routines that may be steered towards an increased sustainability-conscious campus life, through the combined intervention of the university, city administration, and stakeholder involvement. The findings are used to explore the possible directions for action towards increasing or contributing to the territorial sustainability in the socio-ecological context of Timisoara, the largest university city in the western part of Romania via educational, managerial and policy interventions.
Sociodemographic Determinants of Nonadherence to Depression and Anxiety Medication among Individuals Experiencing Homelessness

Psychiatric medication nonadherence continues to be a leading cause of poor health outcomes for individuals experiencing homelessness. Identifying the sociodemographic factors that contribute to medication nonadherence may help guide strategies to care for and support this group. This study examined 200 adults with depression diagnoses and active anti-depressant prescriptions (Mage = 43.98 ± 12.08, 59.4% Caucasian, 58.5% male, 70% uninsured, 89.5% unemployed) and 181 adults with anxiety diagnoses and active anti-anxiety prescriptions (Mage = 43.45 ± 11.02, 54.4% Caucasian, 57.5% male, 66.3% uninsured, 88.9% unemployed) recruited from six homeless-serving agencies in Oklahoma City. Self-reported sociodemographic variables included: age, sex, race/ethnicity, education, monthly income, employment status, and health insurance status. Adjusted logistic regression analyses revealed that employed (OR = 4.022, CI0.95: 1.244–13.004) and insured (OR = 2.923, CI0.95: 1.225–6.973) participants had greater odds of depression medication nonadherence. For anxiety, being employed (OR = 3.573, CI0.95: 1.160–11.010) was associated with greater odds of anxiety medication nonadherence, whereas having depression and anxiety diagnostic comorbidity (OR = 0.333, CI0.95: 0.137–0.810) was associated with lower odds of anxiety medication nonadherence. Interventions aimed at facilitating accessible prescription acquisition or otherwise reducing barriers to prescription medications for employed adults, including those with health insurance, may benefit adherence, but more research is needed. Future studies would benefit from using a qualitative approach to better delineate nuanced barriers to psychiatric medication adherence.