Miracle-dz/UniFAR-FTUs huggingface dataset:
β-Synuclein: An Enigmatic Protein with Diverse Functionality

α-Synuclein (αS) is a small, unstructured, presynaptic protein expressed in the brain. Its aggregated form is a major component of Lewy bodies, the large proteinaceous deposits in Parkinson’s disease. The closely related protein, β-Synuclein (βS), is co-expressed with αS. In vitro, βS acts as a molecular chaperone to inhibit αS aggregation. As a result of this assignation, βS has been largely understudied in comparison to αS. However, recent reports suggest that βS promotes neurotoxicity, implying that βS is involved in other cellular pathways with functions independent of αS. Here, we review the current literature pertaining to human βS in order to understand better the role of βS in homeostasis and pathology. Firstly, the structure of βS is discussed. Secondly, the ability of βS to (i) act as a molecular chaperone; (ii) regulate synaptic function, lipid binding, and the nigrostriatal dopaminergic system; (iii) mediate apoptosis; (iv) participate in protein degradation pathways; (v) modulate intracellular metal levels; and (vi) promote cellular toxicity and protein aggregation is explored. Thirdly, the P123H and V70M mutations of βS, which are associated with dementia with Lewy bodies, are discussed. Finally, the importance of post-translational modifications on the structure and function of βS is reviewed. Overall, it is concluded that βS has both synergistic and antagonistic interactions with αS, but it may also possess important cellular functions independent of αS.
Descriptive Sensory Profile and Consumer Study Impact of Different Nutritive and Non-Nutritive Sweeteners on the Descriptive, Temporal Profile, and Consumer Acceptance in a Peach Juice Matrix

The study evaluated the effect of peach juice sweetened with sucrose, widely used non-nutritive sweeteners, the artificial sucralose, neotame blend, and the natural stevia extract with different rebaudioside A concentrations on the temporal and quantitative descriptive profile, and consumer acceptance of the beverage. The sensory profiling was determined by quantitative descriptive and time–intensity analyses. The results showed that the sweeteners neotame and sucralose present higher sweetening power, and the different rebaudioside A concentrations did not affect the sweetening power of the stevia extract. The samples sweetened with stevia with 40% and 95% of rebaudioside A were characterized by the sensory attributes bitter taste, bitter aftertaste, astringency, and black tea flavor, with a negative influence on the consumers’ acceptance. The different concentrations of rebaudioside A in stevia interfered substantially in the descriptors bitter taste and bitter aftertaste, showing that the higher the percentage of rebaudioside A, the lower bitterness of peach juice.
High expression of HOXB7 is an unfavorable prognostic factor for solid malignancies

Supplemental Digital Content is available in the text Abstract Background: HOXB7 is abnormally expressed in a variety of tumors, but its prognostic value remains unclear due to sample size limitation and outcome inconsistency in previous studies. This meta-analysis was performed to explore the effect of HOXB7 expression on prognoses and clinicopathological factors in range of the whole solid tumors. Methods: PubMed, EMBASE, and Web of Science databases were searched to identify included studies. Hazard ratios (HR) with its 95% confidence interval (CI) and clinicopathological factors were extracted. Subgroup analyses were performed according to histopathological type, tumor occurrence systems, and HOXB7 detection methods. Results: A total of 3430 solid tumors patients from 20 studies (21 cohorts) were included in the meta-analysis. The results showed that high HOXB7 expression was significantly associated with worse survival (overall survival: HR = 1.98, 95%CI: 1.74–2.26, P < .001 and disease-free survival: HR = 1.59, 95%CI: 1.21–2.09, P = .001), more advanced tumor-node-metastasis (TNM) stage (odds ratio [OR] = 2.14, 95%CI: 1.68–2.73, P < .001), positive lymph node metastasis (OR = 2.16, 95%CI: 1.74–2.70, P < .001), more distant metastasis (OR = 1.63, 95%CI: 1.01–2.63, P = .048), poorer differentiation (OR = 1.48, 95%CI: 1.14–1.91, P = .003), and higher Ki-67 expression (OR = 2.53, 95%CI: 1.68–3.84, P < .001). Subgroup analysis showed that survival of patients with HOXB7 high expression was worse in either squamous cell carcinomas or non-squamous cell carcinomas, digestive tumors or non-digestive tumors, and protein level or mRNA level. Conclusion: High HOXB7 expression might be a valuable biomarker of poor prognosis for solid tumors. HOXB7 promotes tumor proliferation and metastasis, and is associated with poorer differentiation, more advanced stage, even the chemotherapy resistance, suggesting that HOXB7 is a potential therapeutic target for solid tumors.
Optical analysis of glutamate spread in the neuropil

Abstract Fast synaptic communication uses diffusible transmitters whose spread is limited by uptake mechanisms. However, on the submicron-scale, the distance between two synapses, the extent of glutamate spread has so far remained difficult to measure. Here, we show that quantal glutamate release from individual hippocampal synapses activates extracellular iGluSnFr molecules at a distance of >1.5 μm. 2P-glutamate uncaging near spines further showed that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-Rs and N-methyl-D-aspartate (NMDA)-Rs respond to distant uncaging spots at approximately 800 and 2000 nm, respectively, when releasing the amount of glutamate contained in approximately five synaptic vesicles. The uncaging-induced remote activation of AMPA-Rs was facilitated by blocking glutamate transporters but only modestly decreased by elevating the recording temperature. When mimicking release from neighboring synapses by three simultaneous uncaging spots in the microenvironment of a spine, AMPA-R-mediated responses increased supra-additively. Interfering with extracellular glutamate diffusion through a glutamate scavenger system weakly reduced field synaptic responses but not the quantal amplitude. Together, our data suggest that the neuropil is more permissive to short-range spread of transmitter than suggested by theory, that multivesicular release could regularly coactivate nearest neighbor synapses and that on this scale glutamate buffering by transporters primarily limits the spread of transmitter and allows for cooperative glutamate signaling in extracellular microdomains.
Application of the Truncated Zero-Inflated Double Poisson for Determining of the Effecting Factors on the Number of Coronary Artery Stenosis

Background Risk factors of coronary heart disease have been discussed in the literature; however, conventional statistical models are not appropriate when the outcome of interest is number of vessels with obstructive coronary artery disease. In this paper, a novel statistical model is discussed to investigate the risk factors of number of vessels with obstructive coronary artery disease. Methods This cross-sectional study was conducted on 633 elderly cardiovascular patients at Ghaem Hospital, Mashhad, Iran from September 2011 to May 2013. Clinical outcome is number of vessels with obstructive coronary artery disease (=0, 1, 2, 3), and predictor variables are baseline demographics and clinical features. A right-truncated zero-inflated double Poisson regression model is performed which can accommodate both underdispersion and excess zeros in the outcome. The goodness-of-fit of the proposed model is compared with conventional regression models. Results Out of 633 cardiovascular patients, 327 were male (51.7%). Mean age was ~65 ± 7 years (for individuals with zero, one ,and two coronary artery stenosis) and ~66 ± 7 years (for individuals with three coronary artery stenosis). BMI (0.04 ± 0.01, p = 0.011) and female gender (0.19 ± 0.09, p = 0.032) were significant associated with the count part of the model, and only BMI (−0.47 ± 0.2, p = 0.011) was significantly predictive of logit part of the model. The goodness-of-fit measurements indicate that the proposed model outperforms the conventional regression models. Conclusion The proposal regression model shows a better fit compared to the standard regression analysis in modeling number of vessels with obstructive coronary artery disease. Hence, using truncated zero-inflated double Poisson regression model—as an alternative model—is advised to study the risk factors of number of involved vessels of coronary artery stenosis.
Resistome and Virulome of Multi-Drug Resistant E. coli ST131 Isolated from Residents of Long-Term Care Facilities in the Northern Italian Region

Long-term care facilities (LTCFs) are important reservoirs of antimicrobial-resistant (AMR) bacteria which colonize patients transferred from the hospital, or they may emerge in the facility as a result of mutation or gene transfer. In the present study, we characterized, from a molecular point of view, 43 E. coli strains collected from residents of LTCFs in Northern Italy. The most common lineage found was ST131, followed by sporadic presence of ST12, ST69, ST48, ST95, ST410 and ST1193. All strains were incubators of several virulence factors, with iss, sat, iha and senB being found in 84%, 72%, 63% and 51% of E. coli, respectively. Thirty of the ST131 analyzed were of the O25b:H4 serotype and H30 subclone. The ST131 isolates were found to be mainly associated with IncF plasmids, CTX-M-1, CTX-M-3, CTX-M-15, CTX-M-27 and gyrA/parC/parE mutations. Metallo-β-lactamases were not found in ST131, whereas KPC-3 carbapenemase was found only in two ST131 and one ST1193. In conclusion, we confirmed the spread of extended-spectrum β-lactamase genes in E. coli ST131 isolated from colonized residents living inside LTCFs. The ST131 represents an incubator of fluoroquinolones, aminoglycosides and other antibiotic resistance genes in addition to different virulence factors.
A Smoothed Version of the Lassosum Penalty for Fitting Integrated Risk Models Using Summary Statistics or Individual-Level Data

Polygenic risk scores are a popular means to predict the disease risk or disease susceptibility of an individual based on its genotype information. When adding other important epidemiological covariates such as age or sex, we speak of an integrated risk model. Methodological advances for fitting more accurate integrated risk models are of immediate importance to improve the precision of risk prediction, thereby potentially identifying patients at high risk early on when they are still able to benefit from preventive steps/interventions targeted at increasing their odds of survival, or at reducing their chance of getting a disease in the first place. This article proposes a smoothed version of the “Lassosum” penalty used to fit polygenic risk scores and integrated risk models. The smoothing allows one to obtain explicit gradients everywhere for efficient minimization of the Lassosum objective function while guaranteeing bounds on the accuracy of the fit. An experimental section on both Alzheimer’s disease and COPD (chronic obstructive pulmonary disease) demonstrates the increased accuracy of the proposed smoothed Lassosum penalty compared to the original Lassosum algorithm, allowing it to draw equal with state-of-the-art methodology such as LDpred2 when evaluated via the AUC (area under the ROC curve) metric.
The perils of plurality rule in democratic presidential systems: A replication and extension

Recent research suggests that country-years where presidents won their previous election with an absolute majority are more likely to be associated with high government respect for human rights, in comparison to country-years where presidents won their previous election by a mere plurality. With this follow-up article, I replicate these findings with a greatly expanded dataset, and I explore whether country-years where presidents have been elected using a majoritarian system are more likely to be associated with high government respect for human rights, in comparison to country-years where presidents have been elected using a non-majoritarian system. Ultimately, I find that not only are presidents elected with a plurality associated with comparatively lower levels of human rights respect, but so are presidents elected via a non-majoritarian system. These findings suggest that policymakers seeking to improve human rights practices may want to consider directing their efforts towards promoting electoral reform with an emphasis on mandating a minimum of a majority in order to win an election.
Teamwork to Survive in Hostile Soils: Use of Plant Growth-Promoting Bacteria to Ameliorate Soil Salinity Stress in Crops

Plants and their microbiomes, including plant growth-promoting bacteria (PGPB), can work as a team to reduce the adverse effects of different types of stress, including drought, heat, cold, and heavy metals stresses, as well as salinity in soils. These abiotic stresses are reviewed here, with an emphasis on salinity and its negative consequences on crops, due to their wide presence in cultivable soils around the world. Likewise, the factors that stimulate the salinity of soils and their impact on microbial diversity and plant physiology were also analyzed. In addition, the saline soils that exist in Mexico were analyzed as a case study. We also made some proposals for a more extensive use of bacterial bioinoculants in agriculture, particularly in developing countries. Finally, PGPB are highly relevant and extremely helpful in counteracting the toxic effects of soil salinity and improving crop growth and production; therefore, their use should be intensively promoted.
The Effect of Microphone Frequency Response on Spectral and Cepstral Measures of Voice: An Examination of Low-Cost Electret Headset Microphones.

PURPOSE The purpose of this study was to establish the frequency response of a selection of low-cost headset microphones that could be given to subjects for remote voice recordings and to examine the effect of microphone type and frequency response on key acoustic measures related to voice quality obtained from speech and vowel samples. METHOD The frequency responses of three low-cost headset microphones were evaluated using pink noise generated via a head-and-torso model. Each of the headset microphones was then used to record a series of speech and vowel samples prerecorded from 24 speakers who represented a diversity of sex, age, fundamental frequency (F o), and voice quality types. Recordings were later analyzed for the following measures: smoothed cepstral peak prominence (CPP; dB), low versus high spectral ratio (L/H ratio; dB), CPP F o (Hz), and cepstral spectral index of dysphonia (CSID). RESULTS The frequency response of the microphones under test was observed to have nonsignificant effects on measures of the CPP and CPP F o, significant effects on the CSID in speech contexts, and strong and significant effects on the measure of spectral tilt (L/H ratio). However, the correlations between the various headset microphones and a reference precision microphone were excellent (rs > .90). CONCLUSIONS The headset microphones under test all showed the capability to track a wide range of diversity in the voice signal. Though the use of higher quality microphones that have demonstrated specifications is recommended for typical research and clinical purposes, low-cost electret microphones may be used to provide valid measures of voice, specifically when the same microphone and signal chain is used for the evaluation of pre- versus posttreatment change or intergroup comparisons.
Afamin Levels and Their Correlation with Oxidative and Lipid Parameters in Non-diabetic, Obese Patients

Background: Afamin is a liver-produced bioactive protein and features α- and γ-tocopherol binding sites. Afamin levels are elevated in metabolic syndrome and obesity and correlate well with components of metabolic syndrome. Afamin concentrations, correlations between afamin and vitamin E, afamin and lipoprotein subfractions in non-diabetic, obese patients have not been fully examined. Methods: Fifty non-diabetic, morbidly obese patients and thirty-two healthy, normal-weight individuals were involved in our study. The afamin concentrations were measured by ELISA. Lipoprotein subfractions were determined with gel electrophoresis. Gas chromatography–mass spectrometry was used to measure α- and γ tocopherol levels. Results: Afamin concentrations were significantly higher in the obese patients compared to the healthy control (70.4 ± 12.8 vs. 47.6 ± 8.5 μg/mL, p < 0.001). Positive correlations were found between afamin and fasting glucose, HbA1c, hsCRP, triglyceride, and oxidized LDL level, as well as the amount and ratio of small HDL subfractions. Negative correlations were observed between afamin and mean LDL size, as well as the amount and ratio of large HDL subfractions. After multiple regression analysis, HbA1c levels and small HDL turned out to be independent predictors of afamin. Conclusions: Afamin may be involved in the development of obesity-related oxidative stress via the development of insulin resistance and not by affecting α- and γ-tocopherol levels.
Predictive Model of Quality of Life in Patients with Parkinson’s Disease

Parkinson’s disease is a chronic, progressive, and disabling neurodegenerative disease which evolves until the end of life and triggers different mood and organic alterations that influence health-related quality of life. The objective of our study was to identify the factors that negatively impact the quality of life of patients with Parkinson’s disease and construct a predictive model of health-related quality of life in these patients. Methods: An analytical, prospective observational study was carried out, including Parkinson’s patients at different stages in the Albacete Health Area. The sample consisted of 155 patients (T0) who were followed up at one (T1) and two years (T2). The instruments used were a purpose-designed data collection questionnaire and the “Parkinson’s Disease Questionnaire” (PDQ-39), with a global index where a higher score indicates a worse quality of life. A multivariate analysis was performed by multiple linear regression at T0. Next, the model’s predictive capacity was evaluated at T1 and T2 using the area under the ROC curve (AUROC). Results: Predictive factors were: sex, living in a residence, using a cane, using a wheelchair, having a Parkinson’s stage of HY > 2, having Alzheimer’s disease or a major neurocognitive disorder, having more than five non-motor symptoms, polypharmacy, and disability greater than 66%. This model showed good predictive capacity at one year and two years of follow-up, with an AUROC of 0.89 (95% CI: 0.83–0.94) and 0.83 (95% CI: 0.76–0.89), respectively. Conclusions: A predictive model constructed with nine variables showed a good discriminative capacity to predict the quality of life of patients with Parkinson’s disease at one and two years of follow-up.
Conscientiousness moderates the relationship between neuroticism and health-risk behaviors among adolescents.

Health-Risk-Behaviors (HRBs) are considered significant antecedent conditions of adolescents' poor health and mortality. Prevention of any adverse health outcome requires an in-depth understanding of the risk and protective factors associated with its development and maintenance. Among other potential causal pathways, the "neuroticism- HRBs-adverse health" link has been supported in previous studies. Trait neuroticism has been associated with poor health and HRBs, but several moderators were also observed, which might transform neuroticism into a desirable phenomenon, that is, healthy neuroticism, that leads to better health. Conscientiousness is one such potential moderator; however, the moderating effect of conscientiousness in the neuroticism-HRBs link has not been explored extensively among adolescents, especially in India; therefore, no conclusive evidence is available. Thus, the present study was planned to explore the moderating effect of conscientiousness in the relationship between neuroticism and HRBs among adolescents. The study was conducted in India and its cross-sectional sample, procured through a multi-stage stratified random sampling, consists of 648 (364 males) adolescents (Mage = 16.08). Participants provided relevant information on standardized questionnaires. Moderated regression analysis was applied to test the stated hypotheses. Individuals high on neuroticism and low on conscientiousness reported more indulgence in health-risk behaviors than individuals high on both neuroticism and conscientiousness. It indicates that a higher level of conscientiousness may reduce the negative impact that neuroticism has on HRBs. The findings imply that the assessment of conscientiousness and strategies to increase the same should be part of interventional programs to achieve adolescents' wellbeing.
Association of Dietary Patterns with MRI Markers of Hepatic Inflammation and Fibrosis in the MAST4HEALTH Study

Whereas the etiology of non-alcoholic fatty liver disease (NAFLD) is complex, the role of nutrition as a causing and preventive factor is not fully explored. The aim of this study is to associate dietary patterns with magnetic resonance imaging (MRI) parameters in a European population (Greece, Italy, and Serbia) affected by NAFLD. For the first time, iron-corrected T1 (cT1), proton density fat fraction (PDFF), and the liver inflammation fibrosis score (LIF) were examined in relation to diet. A total of 97 obese patients with NAFLD from the MAST4HEALTH study were included in the analysis. A validated semi-quantitative food frequency questionnaire (FFQ) was used to assess the quality of diet and food combinations. Other variables investigated include anthropometric measurements, total type 2 diabetes risk, physical activity level (PAL), and smoking status. Principal component analysis (PCA) was performed to identify dietary patterns. Six dietary patterns were identified, namely “High-Sugar”, “Prudent”, “Western”, “High-Fat and Salt”, “Plant-Based”, and “Low-Fat Dairy and Poultry”. The “Western” pattern was positively associated with cT1 in the unadjusted model (beta: 0.020, p-value: 0.025) and even after adjusting for age, sex, body mass index (BMI), PAL, smoking, the center of the study, and the other five dietary patterns (beta: 0.024, p-value: 0.020). On the contrary, compared with low-intake patients, those with medium intake of the “Low-Fat Dairy and Poultry” pattern were associated with lower values of cT1, PDFF, and LIF. However, patients with a “Low-Fat Dairy and Poultry” dietary pattern were negatively associated with MRI parameters (cT1: beta: −0.052, p-value: 0.046, PDFF: beta: −0.448, p-value: 0.030, LIF: beta: −0.408, p-value: 0.025). Our findings indicate several associations between MRI parameters and dietary patterns in NAFLD patients, highlighting the importance of diet in NAFLD.