Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutant p53, Stabilized by Its Interplay with HSP90, Activates a Positive Feed-Back Loop Between NRF2 and p62 that Induces Chemo-Resistance to Apigenin in Pancreatic Cancer Cells

Pancreatic cancer is one of the most aggressive cancers whose prognosis is worsened by the poor response to the current chemotherapies. In this study, we investigated the cytotoxic effect of Apigenin, against two pancreatic cell lines, namely Panc1 and PaCa44, harboring different p53 mutations. Apigenin is a flavonoid widely distributed in nature that displays anti-inflammatory and anticancer properties against a variety of cancers. Here we observed that Apigenin exerted a stronger cytotoxic effect against Panc1 cell line in comparison to PaCa44. Searching for mechanisms responsible for such different effect, we found that the higher cytotoxicity of Apigenin correlated with induction of higher level of intracellular ROS, reduction of mutant (mut) p53 and HSP90 expression and mTORC1 inhibition. Interestingly, we found that mutp53 was stabilized by its interplay with HSP90 and activates a positive feed-back loop between NRF2 and p62, up-regulating the antioxidant response and reducing the cytotoxicity of Apigenin. These results suggest that targeting the molecules involved in the mTOR-HSP90-mutp53-p62-NRF2-antioxidant response axis could help to overcome the chemo-resistance of pancreatic cancer to Apigenin.
Motivational determinants of physical education grades and the intention to practice sport in the future

Self-Determination Theory (SDT) is amongst motivational frameworks the most popular and contemporary approach to human motivation, being applied in the last decades in several domains, including sport, exercise and physical education (PE). Additionally, Achievement Goal Theory (AGT) has presented evidence of how contextual factors may influence student’s behavior in this particular context. The main purpose of this study was to analyze the motivational climate created by the teacher in the classroom, students’ satisfaction of Basic Psychological Needs (BPN), and how their behavioral regulation could explain PE grades and intention to practice sports in the future. Method: A total of 618 students (290 female; 328 male) from the 6th to the 9th school level, aged between 10 and 18 years (M = 13.3; SD = 1.7) participated in this study. The following surveys were used for the proposed variables: Learning and Performance Orientations in Physical Education Classes Questionnaire (LAPOPECQ); the Basic Psychological Needs in Exercise Scale (BPNESp); and the Perceived Locus of Causality (PLOCp). Intentions to practice sport/physical activity in the future were assessed through a single item. Students’ PE grade was obtained through his/her teacher final assessment. Structural Equation Analysis was performed via AMOS 23.0. Results: After analyzing modification indices and model adjustment, the final model emerged: learning climate > BPN > autonomous motivation > intentions/PE grade. Results interpretation seems to indicate that i) the satisfaction of BPN are influenced by motivational climate (i.e., learning climate), ii) the individuals’ motivation is influenced by the satisfaction of three basic psychological needs (i.e., particularly competence), and iii) the motivational regulations have direct and significant effects with intention to practice sports outside school in the future and PE grades. Discussion & Conclusion: The main results showed that a climate oriented for learning has a positive impact on basic psychological needs satisfaction of students. However, only competence satisfaction had a significant positive relationship with students’ autonomous motivation, which in turn had a significant positive relation with PE grade, as well as for intentions for leisure-time sport/physical activity practice.
A Motivational Perspective on Job Insecurity: Relationships Between Job Insecurity, Intrinsic Motivation, and Performance and Behavioral Outcomes

As a result of the global economic recession over the past decade, employees have been exposed to constant threats of job insecurity. Despite having conducted extensive research on job insecurity, scholars have paid little attention to the motivational processes underlying employees’ reactions to job insecurity. The purpose of the present study is to examine the relationship between job insecurity, intrinsic motivation, and performance and behavioral outcomes. Drawing on self-determination theory (SDT), we propose a mediated relationship in which job insecurity decreases intrinsic motivation, which, in turn, undermines job performance, organizational citizenship behavior (OCB), and change-oriented OCB. To test our propositions, we collected survey-based data from 152 R&D professionals employed in a South Korean manufacturing company. As predicted, job insecurity was negatively related to intrinsic motivation, which, in turn, had a positive relationship with all three outcomes. Furthermore, job insecurity exerted significant indirect effects on job performance, OCB, and change-oriented OCB through intrinsic motivation. These findings affirm SDT, which posits that motivation, as a key intermediary process, affects employees’ reactions to job stressors.
The Relationship Between the Left-Cradling Bias and Attachment to Parents and Partner

Mothers usually cradle their infants to the left of their body midline, an asymmetry that seems to be a typically female lateral preference. This bias is deemed to be an evolutionary facilitator of communication between cradling and cradled individuals and is believed to be strongly related to hemispheric specialization for complex socio-affective behaviors. Thus, left cradling might facilitate affective interactions in females with typical brain organization, probably due to a right-hemisphere dominance for social attachment. In this study, we investigated cradling-side preferences in 288 young females as a function of their attachment styles to parents and partners. A left-cradling bias was more frequent in participants experiencing positive relationships with their mother and romantic partners. These findings indicate that the left-cradling bias may be associated with high-quality social attachment behaviors in females and, therefore, can be considered as a natural index of socio-emotional attunement between the cradling and cradled individuals.
Caregiver Reports of Screen Time Use of Children with Autism Spectrum Disorder: A Qualitative Study

Screen based media have progressively become an integral part in the daily lives of children and youths with and without autism spectrum disorder (ASD). However, research that exclusively pursues the functionality of screen media use of children with ASD is extremely rare. Through a triangulated approach, the present study aims to fill this gap. We conducted 13 interviews with parents of children with ASD and supplemented this interview–study with an online survey including parents of children with ASD (n = 327). Children with ASD mostly used screen media (especially television) for their wellbeing, which is associated with chances and risks. Based on the parental interviews it is suggested that the media usage of children with ASD should be supervised. The results are discussed in terms of their practical implementation.
Adaptogenic properties of six rasayana herbs used in Ayurvedic medicine

Plants from all over the world such as Eleutherococcus senticosus, Panax ginseng, Raponticum carthamoides, Rhodiola rosea, Withania somnifera and Ocimum sanctum have been extensively evaluated for their adaptogenic potential. However, none of them has been successfully introduced as an adaptogen in the clinic. This paper discusses some of the problems in evaluation of adaptogens which have precluded their inclusion as clinically useful drugs. We further discuss our results with six rasayana plants from Ayurveda, which were studied for their adaptogenic potential.
3D analysis of child facial dimensions for design of medical devices in low-middle income countries (LMIC)

Background Facial anthropometric data are scarce in African children. However, such data may be useful for the design of medical devices for high disease burden settings. The aim of this study was to obtain 3D facial anthropometric data of Congolese children aged 0–5 years. Methods & findings The faces of 287 Congolese children were successfully scanned using a portable structured-light based 3D video camera, suitable for field work in low- income settings. The images were analyzed using facial analysis algorithms. Normal growth curves were generated for the following facial dimensions: distance between nares and distance from subnasion to upper lip. At birth, 1 year, and 5 years of age the median dimensions were: 13·92, 14·66, and 17.60 mm, respectively for distance between nares, and 10·16, 10.88, and 13·79 mm, respectively for distance from subnasion to upper lip. Modeled facial contours conveniently clustered into three average sizes which could be used as templates for the design of medical instruments. Conclusion Capturing of 3D images of infants and young children in LMICs is feasible using portable cameras and computerized analysis. This method and these specific data on Congolese pediatric facial dimensions may assist in the design of appropriately sized medical devices (thermometers, face masks, pulse oximeters, etc.) for this population.
A Serbian Version of Modified and Revised Experiences in Close Relationships Scale (SM–ECR–R)

We present details about the validation of the Serbian version of the Experiences in Close Relationships–Revised questionnaire modified to measure attachment in close relationships in general (SM–ECR–R). Its psychometric features were examined with 2 samples of students (N = 719 and N = 91) and 1 group of employed adults (N = 259). The results obtained in the student sample were equivalent to those obtained in validation studies worldwide, whereas in the more heterogeneous sample of employed adults, internal consistency of both avoidance and anxiety was lower and their intercorrelation was higher. Test–retest reliability was satisfactory, and relations with measures of attachment, empathy, and personality structure were meaningful. The results support the SM–ECR–R as a reliable and valid research instrument, but its internal structure and consistency might vary in different samples, depending on age, education, gender, and culture.
Transthoracic Needle Biopsy of Pulmonary Nodules: Meteorological Conditions and the Risk of Pneumothorax and Chest Tube Placement

The purpose of this paper is to evaluate whether meteorological variables influence rates of pneumothorax and chest tube placement after percutaneous transthoracic needle biopsy (PTNB) of pulmonary nodules. A retrospective review of 338 consecutive PTNBs of pulmonary nodules at a single institution was performed. All procedures implemented a coaxial approach, using a 19-gauge outer guide needle for access and a 20-gauge core biopsy gun with or without a small-gauge aspiration needle for tissue sampling. Correlation between age, sex, smoking history, lesion size, meteorological variables, and frequency of complications were evaluated. Fisher exact, trend and t tests were used to evaluate the relationship between each factor and rates of pneumothorax and chest tube placement. A p value of less than 0.05 was considered to indicate a statistically significant difference. Pneumothorax occurred in 115 of 338 patients (34%). Chest tube placement was required in 30 patients (8.9%). No significant relationship was found between pneumothorax rate and age (p = 0.172), sex (p = 0.909), smoking history (p = 0.819), or lesion location (p = 0.765). The presence or absence of special weather conditions did not correlate with the rate of pneumothorax (p = 0.241) or chest tube placement (p = 0.213). The mean atmospheric temperature (p = 0.619) and degree of humidity (p = 0.858) also did not correlate with differences in the rate of pneumothorax. Finally, mean atmospheric pressure on the day of the procedure demonstrated no correlation with the rate of pneumothorax (p = 0.277) or chest tube placement (p = 0.767). In conclusion, no correlation is demonstrated between the occurrence of pneumothorax after PTNB of pulmonary nodules and the studied meteorological variables.
Edaravone Protects HT22 Neurons from H2O2‐induced Apoptosis by Inhibiting the MAPK Signaling Pathway

Oxidative stress is frequently implicated in the pathology of neurodegenerative diseases. This study aimed to investigate the effects and their underlying mechanism(s) of edaravone upon hydrogen peroxide (H2O2)–induced oxidative stress and apoptosis in HT22 cells, a murine hippocampal neuronal model.
Inflammatory Immune Responses in the Pathogenesis of Tick-Borne Encephalitis

Clinical manifestations of tick-borne encephalitis (TBE) are thought to result from the host immune responses to infection, but knowledge of such responses is incomplete. We performed a detailed clinical evaluation and characterization of innate and adaptive inflammatory immune responses in matched serum and cerebrospinal fluid (CSF) samples from 81 adult patients with TBE. Immune responses were then correlated with laboratory and clinical findings. The inflammatory immune responses were generally site-specific. Cytokines and chemokines associated with innate and Th1 adaptive immune responses were significantly higher in CSF, while mediators associated with Th17 and B-cell responses were generally higher in serum. Furthermore, mediators associated with innate and Th1 adaptive immune responses were positively associated with disease severity, whereas Th17 and B cell immune responses were not. During the meningoencephalitic phase of TBE, innate and Th1 adaptive inflammatory mediators were highly concentrated in CSF, the site of the disease. The consequence of this robust immune response was more severe acute illness. In contrast, inflammatory mediators associated with B cell and particularly Th17 responses were concentrated in serum. These findings provide new insights into the immunopathogenesis of TBE and implicate innate and Th1 adaptive responses in severity and clinical presentation of acute illness.
A Dynamic Equilibrium Model of ETFs

I develop a dynamic general equilibrium model of exchange traded funds (ETFs) that accounts for the two-tier ETF market structure with both a centralized exchange (secondary market) and a creation/redemption mechanism (primary market) operating through market-making firms known as Authorized Participants (APs). The model is tractable and allows for any number of ETFs and basket securities. I show that the creation/redemption mechanism serves as a shock propagation channel through which temporary demand shocks may have long-lasting impacts on future prices. In particular, they may lead to a momentum in asset returns and a persistent ETF pricing gap. Improving liquidity in the primary market stimulates creation/redemption and therefore strengthens the shock propagation channel. As a result, it may amplify the volatility of both the underlying assets and the ETF pricing gap. At the same time, introducing new ETFs may reduce both the volatility and co-movement in the returns and may improve the liquidity of the underlying securities.
MUC 1 oncoprotein blocks nuclear targeting of c-Abl in the apoptotic response to DNA damage

The nonreceptor c-Abl tyrosine kinase binds to cytosolic 14-3-3 proteins and is targeted to the nucleus in the apoptotic response to DNA damage. The MUC1 oncoprotein is overexpressed by most human carcinomas and blocks the induction of apoptosis by genotoxic agents. Using human carcinoma cells with gain and loss of MUC1 function, we show that nuclear targeting of c-Abl by DNA damage is abrogated by a MUC1-dependent mechanism. The results demonstrate that c-Abl phosphorylates MUC1 on Tyr-60 and forms a complex with MUC1 by binding of the c-Abl SH2 domain to the pTyr-60 site. Binding of MUC1 to c-Abl attenuates phosphorylation of c-Abl on Thr-735 and the interaction between c-Abl and cytosolic 14-3-3. We also show that expression of MUC1 with a mutation at Tyr-60 (i) disrupts the interaction between MUC1 and c-Abl, (ii) relieves the MUC1-induced block of c-Abl phosphorylation on Thr-735 and binding to 14-3-3, and (iii) attenuates the MUC1 antiapoptotic function. These findings indicate that MUC1 sequesters c-Abl in the cytoplasm and thereby inhibits apoptosis in the response to genotoxic anticancer agents. The EMBO Journal (2006) 25, 3774–3783. doi:10.1038/ sj.emboj. 7601263; Published online 3 August 2006 Subject Categories: signal transduction
Interindividual variability and individual responses to exercise training in adolescents with obesity.

This study investigated the impact of exercise training on interindividual variability and response rates in body composition and cardiometabolic outcomes in adolescents with obesity. Postpubertal males and females (n=143) were randomly assigned to six-months of a diet-only Control or Aerobic, Resistance, or Combined exercise training. Body composition indices were percentages of body fat mass (%BFM) and lean body mass (%LBM), and waist circumference (WC). Biomarkers of cardiometabolic health were systolic blood pressure (SBP) and plasma fasting glucose, triglycerides, and high-density lipoprotein cholesterol. Interindividual variability was examined by comparing the standard deviation of individual responses (SDIR) to a smallest robust change (SRC). The typical error of measurement was used to classify responses. SDIR exceeded the SRC for %BFM in all exercise groups (SRC=1.04%; Aerobic SDIR=1.50%; Resistance SDIR=1.22%; Combined SDIR=2.29%), %LBM (SRC=1.38%; SDIR=3.2%,) and SBP (SRC=2.06 mmHg; SDIR=4.92 mmHg) in the Resistance group, and WC (SRC=2.33 cm; SDIR=4.09 cm) and fasting glucose (SRC=0.08 mmol/L; SDIR=0.28 mmol/L) in the Combined group. However, half of the reported variables (11/21) did not have a positive SDIR. Importantly, adverse response rates were significantly lower in all three exercise groups than control for body composition. Although exercise had a small influence on interindividual variability for indices of body composition, the rate of adverse responses did not increase for any outcome. -Interindividual variability and individual responses to exercise training have not been investigated in adolescents with obesity. -Six-months of exercise training does not increase interindividual variability in adolescents with obesity. -Exercise created a positive, uniform shift in responses.
Clinical outcomes under hydroxyurea treatment in polycythemia vera: a systematic review and meta-analysis

Hydroxyurea is the standard treatment in high-risk patients with polycythemia vera. However, estimates of its effect in terms of clinical outcomes (thrombosis, bleeding, hematologic transformations and mortality) are lacking. We performed a meta-analysis to determine the absolute risk of events in recent cases of patients under hydroxyurea treatment. We searched for relevant articles or abstracts in the following databases: Medline, EMBASE, clinicaltrials.gov, WHO International Clinical Trials Registry, LILACS. Sixteen studies published from 2008 to 2018 reporting number of events using World Health Organization diagnosis for polycythemia vera were selected. Through a random effect logistic model, incidences, study heterogeneity and confounder effects were estimated for each outcome at different follow ups. Overall, 3,236 patients were analyzed. While incidences of thrombosis and acute myeloid leukemia were stable over time, mortality and myelofibrosis varied depending on follow-up duration. Thrombosis rates were 1.9%, 3.6% and 6.8% persons/year at median ages 60, 70 and 80 years, respectively. Higher incidence of arterial events was predicted by previous cardiovascular complication. Leukemic transformation incidence was 0.4% persons/year. Incidence of transformation to myelofibrosis and mortality were significantly dependent on age and follow-up duration. For myelofibrosis, rates were 5.0 at five years and 33.7% at ten years; overall mortality was 12.6% and 56.2% at five and ten years, respectively. In conclusion, we provide reliable risk estimates for the main outcomes in polycythemia vera patients under hydroxyurea treatment. These findings can help design comparative clinical trials with new cytoreductive drugs and prove the feasibility of using critical end points for efficacy, such as major thrombosis.
Alexithymia in adults with brittle type 1 diabetes

Background: The term “brittle” is used to describe an uncommon subgroup of patients with type 1 diabetes whose lives are disrupted by severe glycaemic instability with repeated and prolonged hospitalization. Psychosocial problems and emotional disturbances are the major perceived underlying causes of brittle diabetes. Aim of this study is (a) to assess alexithymia in patients with brittle and non-brittle diabetes, and (2) to examine its relationship with specific parameters of general psychopathology. Methods: Participants comprised 44 patients with brittle diabetes and a case-control group of 88 individuals with stable (non-brittle) diabetes, matched for age, gender, years of education, and diabetes duration. Alexithymia and general psychopathology were assessed using the “20-item Toronto Alexithymia Scale” (TAS-20) and the “Symptom Checklist-90-Revised” (SCL-90-R). Results: Patients with brittle diabetes were more alexithymic than the control group. Alexithymia scores showed significant correlations with SCL-90-R anxiety and somatization subscales, but were relatively independent from gender, education, diabetes duration and complications, depression and glycaemic control. Conclusions: Given the impact of alexithymia on type 1 diabetes, the early detection and intervention of alexithymic subjects are very important for a better outcome of diabetes. (www.actabiomedica.it)
Leptospirosis as a risk factor for chronic kidney disease: A systematic review of observational studies

Background Leptospirosis is a worldwide prevalent zoonosis and chronic kidney disease (CKD) is a leading global disease burden. Because of pathophysiological changes in the kidney, it has been suggested that these conditions may be associated. However, the extent of this interaction has not been synthetized. We aimed to systematically review and critically appraise the evidence on the association between leptospirosis and CKD. Methodology/Principal findings Observational studies with a control group were selected. Leptospirosis, confirmed with laboratory methods, and CKD also based on a laboratory assessment, were the exposures and outcomes of interest. The search was conducted in EMBASE, MEDLINE, Global Health, Scopus and Web of Science. Studies selected for qualitative synthesis were assessed for risk of bias following the Newcastle-Ottawa Scale. 5,981 reports were screened, and 2 (n = 3,534) were included for qualitative synthesis. The studies were conducted in Taiwan and Nicaragua; these reported cross-sectional and longitudinal estimates. In the general population, the mean estimated glomerular filtration rate (eGFR) was lower (p<0.001) in people testing positive for antileptospira antibodies (eGFR = 98.3) than in negative controls (eGFR = 100.8). Among sugarcane applicants with high creatinine, those who were seropositive had lower eGFR (mean difference: -10.08). In a prospective analysis, people with high antileptospira antibodies titer at baseline and follow-up, had worse eGFR (p<0.05). Conclusion Although the available evidence suggests there may be a positive association between leptospirosis and CKD, whereby leptospirosis could be a risk factor for CKD, it is still premature to draw conclusions. There is an urgent need for research on this association.