Miracle-dz/UniFAR-FTUs huggingface dataset:
Affinity Captured Urinary Extracellular Vesicles Provide mRNA and miRNA Biomarkers for Improved Accuracy of Prostate Cancer Detection: A Pilot Study

Serum prostate-specific antigen (sPSA) testing has helped to increase early detection of and decrease mortality from prostate cancer. However, since sPSA lacks specificity, an invasive prostate tissue biopsy is required to confirm cancer diagnosis. Using urinary extracellular vesicles (EVs) as a minimally invasive biomarker source, our goal was to develop a biomarker panel able to distinguish prostate cancer from benign conditions with high accuracy. We enrolled 56 patients in our study, 28 negative and 28 positive for cancer based on tissue biopsy results. Using our Vn96 peptide affinity method, we isolated EVs from post-digital rectal exam urines and used quantitative polymerase chain reaction to measure several mRNA and miRNA targets. We identified a panel of seven mRNA biomarkers whose expression ratio discriminated non-cancer from cancer with an area under the curve (AUC) of 0.825, sensitivity of 75% and specificity of 84%. We also identified two miRNAs whose combined score yielded an AUC of 0.744. A model pairing the seven mRNA and two miRNA panels yielded an AUC of 0.843, sensitivity of 79% and specificity of 89%. Addition of EV-derived PCA3 levels and clinical characteristics to the biomarker model further improved test accuracy. An AUC of 0.955, sensitivity of 86% and specificity of 93% were obtained. Hence, Vn96-isolated urinary EVs are a clinically applicable and minimally invasive source of mRNA and miRNA biomarkers with potential to improve on the accuracy of prostate cancer screening and diagnosis.
Correlation between Oral Health-Related Quality of Life and Objectively Measured Oral Health in People with Ehlers–Danlos Syndromes

It is a well-known fact that people with Ehlers–Danlos syndromes (EDS) report a worse oral health-related quality of life (OHRQoL) than the general population. The aim of this study was to examine whether there is a correlation between the subjective OHRQoL and the objectively measured oral health in people with EDS. To determine the subjective OHRQoL, the German version of the 14-item Oral Health Impact Profile (OHIP-14) questionnaire was used. Furthermore, all participants in the study were clinically examined, and the measured parameters were recorded using the Physical Oral Health Index (PhOX). Altogether, records of 46 participants were collected. The median (interquartile range (IQR)) of the OHIP-14 was 17 (23) points and the median of the PhOX was 73 (16) points. However, a statistically significant correlation could not be demonstrated (r = −0.240, p = 0.108). In the observed cohort, for participants who reported having pain often or very often, the OHIP score (median = 24, IQR = 18, p < 0.01) was higher than the score of the group given by participants who never or intermittently experienced pain (median = 8, IQR = 18). In conclusion, patients with EDS showed a reduced OHRQoL, although it was not possible to observe an association between the subjective OHRQoL and the objective oral health. However, participants who often or very often suffer from pain in their tooth, mouth, and jaw areas showed a reduced OHRQoL.
Relationship between Pre-Competition Mental State and Sport Result of Disabled Boccia Athletes

The relationship between sport result and pre-competition mental state of 109 boccia athletes was analyzed. Mental state was described by: athletic identity, self-esteem, self-efficacy for sports, hope for success, fear of failure, anxiety, and expectancy of success. Correlation analyses were made for all four boccia classes (BC1, BC2, BC3, and BC4) and revealed that only athletic identity was associated with sport result in class BC4. Four hierarchical multiple regression models (for BC1, BC2, BC3, and BC4 boccia classes) were created, with sport result as the dependent variable. Only the BC4 model was significant and included athletic identity, anxiety, self-efficacy for sports, and expectancy of success, which explained 49% of variance in sport result. BC4 class results indicate that psychological variables have a potential impact on sport performance in boccia, and the type and level of disability should be taken into account.
Association of Proteinuria and Hematuria with Acute Kidney Injury and Mortality in Hospitalized Patients with COVID-19

Introduction: Acute kidney injury (AKI) is strongly associated with poor outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19), but data on the association of proteinuria and hematuria are limited to non-US populations. In addition, admission and in-hospital measures for kidney abnormalities have not been studied separately. Methods: This retrospective cohort study aimed to analyze these associations in 321 patients sequentially admitted between March 7, 2020 and April 1, 2020 at Stony Brook University Medical Center, New York. We investigated the association of proteinuria, hematuria, and AKI with outcomes of inflammation, intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and in-hospital death. We used ANOVA, t test, χ2 test, and Fisher’s exact test for bivariate analyses and logistic regression for multivariable analysis. Results: Three hundred patients met the inclusion criteria for the study cohort. Multivariable analysis demonstrated that admission proteinuria was significantly associated with risk of in-hospital AKI (OR 4.71, 95% CI 1.28–17.38), while admission hematuria was associated with ICU admission (OR 4.56, 95% CI 1.12–18.64), IMV (OR 8.79, 95% CI 2.08–37.00), and death (OR 18.03, 95% CI 2.84–114.57). During hospitalization, de novo proteinuria was significantly associated with increased risk of death (OR 8.94, 95% CI 1.19–114.4, p = 0.04). In-hospital AKI increased (OR 27.14, 95% CI 4.44–240.17) while recovery from in-hospital AKI decreased the risk of death (OR 0.001, 95% CI 0.001–0.06). Conclusion: Proteinuria and hematuria both at the time of admission and during hospitalization are associated with adverse clinical outcomes in hospitalized patients with COVID-19.
AMPKα1 Regulates Lung and Breast Cancer Progression by Regulating TLR4-Mediated TRAF6-BECN1 Signaling Axis

Simple Summary TRAF6-BECN1 signaling axis in TLR4 signal plays an essential role for the autophagy induction, thereby it regulates cancer migration and invasion. Here we show that AMPKα1, one of the isoforms of AMPK, is functionally involved in autophagy induction by regulating the TRAF6-BECN1 signaling axis. In this context, AMPKα1-knockout lung or breast cancer cells exhibited the attenuation of cancer cell migration and invasion induced by TLR4 simulation. Additionally, we could find that the expression of AMPKα1 is positively associated with gene expressions related to autophagy, migration, and metastasis of cancer cells in primary non-small cell lung cancers (NSCLCs). These findings demonstrate that AMPKα1 plays a pivotal role in cancer progression by regulating the TRAF6-BECN1 signaling axis for autophagy induction. Abstract TRAF6-BECN1 signaling axis is critical for autophagy induction and functionally implicated in cancer progression. Here, we report that AMP-activated protein kinase alpha 1 (AMPKα1, PRKAA1) is positively involved in autophagy induction and cancer progression by regulating TRAF6-BECN1 signaling axis. Mechanistically, AMPKα1 interacted with TRAF6 and BECN1. It also enhanced ubiquitination of BECN1 and autophagy induction. AMPKα1-knockout (AMPKα1KO) HEK293T or AMPKα1-knockdown (AMPKα1KD) THP-1 cells showed impaired autophagy induced by serum starvation or TLR4 (Toll-like receptor 4) stimulation. Additionally, AMPKα1KD THP-1 cells showed decreases of autophagy-related and autophagosome-related genes induced by TLR4. AMPKα1KO A549 cells exhibited attenuation of cancer migration and invasion induced by TLR4. Moreover, primary non-small cell lung cancers (NSCLCs, n = 6) with low AMPKαl levels showed markedly decreased expression of genes related to autophagy, cell migration and adhesion/metastasis, inflammation, and TLRs whereas these genes were significantly upregulated in NSCLCs (n = 5) with high AMPKαl levels. Consistently, attenuation of cancer migration and invasion could be observed in AMPKα1KO MDA-MB-231 and AMPKα1KO MCF-7 human breast cancer cells. These results suggest that AMPKα1 plays a pivotal role in cancer progression by regulating the TRAF6-BECN1 signaling axis for autophagy induction.
Evolution of Antibody Immunity to SARS-CoV-2

SARS-CoV-2 has infected 47 million individuals and is responsible for over 1.2 million deaths to date. Infection is associated with development of variable levels of antibodies with neutralizing activity that can protect against infection in animal models. Antibody levels decrease with time, but the nature and quality of the memory B cells that would be called upon to produce antibodies upon re-infection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection. We find that IgM, and IgG anti-SARS-CoV-2 spike protein receptor binding domain (RBD) antibody titers decrease significantly with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by five-fold in pseudotype virus assays. In contrast, the number of RBD-specific memory B cells is unchanged. Memory B cells display clonal turnover after 6.2 months, and the antibodies they express have greater somatic hypermutation, increased potency and resistance to RBD mutations, indicative of continued evolution of the humoral response. Analysis of intestinal biopsies obtained from asymptomatic individuals 3 months after COVID-19 onset, using immunofluorescence, electron tomography or polymerase chain reaction, revealed persistence of SARS-CoV-2 in the small bowel of 7 out of 14 volunteers. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.
Puberty, a sensitive window of hypothalamic development and plasticity.

Puberty is a developmental period characterized by a broad range of physiologic changes necessary for the acquisition of adult sexual and reproductive maturity. These changes mirror complex modifications within the central nervous system, including within the hypothalamus. These modifications result in the maturation of a fully active hypothalamo-pituitary-gonadal (HPG) axis, the neuroendocrine cascade ensuring gonadal activation, sex steroid secretion and gametogenesis. A complex and finely regulated neural network overseeing the HPG axis, particularly the pubertal reactivation of GnRH secretion, has been progressively unveiled in the last three decades. This network includes kisspeptin, neurokinin B, GABAergic and glutamatergic neurons as well as glial cells. In addition to substantial modifications in the expression of key targets, several changes in neuronal morphology, neural connections and synapse organization occur to establish mature and coordinated neurohormonal secretion, leading to puberty initiation. The aim of this review is to outline the current knowledge of the major changes that neurons secreting GnRH and their neuronal and glial partners undergo before and after puberty. Emerging mediators upstream of GnRH, uncovered in recent years, are also addressed herein. In addition, the effects of sex steroids, particularly estradiol, on changes in hypothalamic neurodevelopment and plasticity are discussed.
A Notch-Dependent Inflammatory Feedback Circuit between Macrophages and Cancer Cells Regulates Pancreatic Cancer Metastasis

This study provides potential therapeutic targets and robust preclinical evidence for PDAC treatment by interrupting feedback signaling between cancer cells and macrophages with targeted inhibitors. Notch activation has been detected in pancreatic ductal adenocarcinoma (PDAC). However, its role in PDAC metastasis remains unknown. In this study, we identify a Notch-dependent feedback circuit between pancreatic cancer cells and macrophages, which contributes to PDAC metastasis. In this circuit, miR-124 regulated Notch signaling in cancer cells by directly targeting the Notch ligand Jagged 1. Autoamplified Notch signaling promoted the recruitment and activation of macrophages to a tumor-supporting M2-like phenotype via downstream IL8, CCL2, IL1α, and uPA paracrine signaling. In turn, activated macrophage-derived IL6 activated the oncogenic transcription factor STAT3 that directly repressed miR-124 genes via a conserved STAT3-binding site in their promoters, thereby promoting cancer cell epithelial–mesenchymal transition and invasion. Disrupting this circuit suppressed liver metastasis in mouse models. Thus, our study suggests that manipulation of this Notch-dependent circuit has a therapeutic potential for the treatment of PDAC metastasis. Significance: This study provided potential therapeutic targets and robust preclinical evidence for PDAC treatment by interrupting feedback signaling between cancer cells and macrophages with targeted inhibitors.
The reproductive strategies of clausiliid land snails from Northern Vietnam (Gastropoda: Stylommatophora)

Under laboratory conditions we scrutinized the reproduction and development of two clausiliid land snail species from northern Vietnam: Phaedusa paviei (Morlet, 1892) and Oospira vanbuensis (Bavay and Dautzenberg, 1899). These species, very similar in shell size and shape, feature different reproductive modes. The former is viviparous, giving birth to one or two neonates on a single occasion, with the number of developing embryos retained in the reproductive tract ranging from 1 to 11. The embryonic shells are 1.8–4.7 mm in height. The latter species is oviparous and produces eggs in clutches (four to six per clutch). Hatching occurs 18–21 days after egg-laying. Both species exhibit a similar growth pattern: the ultimate shell size is attained after 6.5–8.5 months and reproduction starts 5–7 months later. The distribution of viviparous reproduction among the Phaedusinae and its taxonomic importance are discussed.
Adverse drug reactions in elderly: a five-year review of spontaneous reports to the Portuguese pharmacovigilance system

ABSTRACT Background: Adverse drug reactions (ADRs) are responsible for considerable morbidity and mortality in elderly. This study aimed to characterize the ADRs profile in Portuguese elderly patients, thus enhancing ADRs knowledge in this vulnerable population. Methods: All spontaneous ADRs reported to the Portuguese Pharmacovigilance System from 2013 to 2017 were examined. However, considering the aim of this study, ADRs referring to patients aged 65 and over were analyzed in higher detail and compared with those reported in non-elderly adults. Results: Considering the age of 65 years and above, 3692 spontaneous reports of suspected ADRs were analyzed. The suspected ADRs most frequently reported fall within the categories of general disorders and administration site conditions, and skin and subcutaneous tissue complaints. Regarding therapeutic agents, the antineoplastic drugs were the most common involved. Among the 2458 cases of serious ADRs reported, 34.0% led to hospitalization and in 5.8% of them occurred a fatal outcome. The antineoplastic and antithrombotic drugs were the most represented pharmacotherapeutic groups of suspected drugs involved in patient’s death (25.0% and 13.6%, respectively). Conclusions: Most of the suspected ADRs were classified as serious. The majority of them were expected, so preventable, highlighting the importance of improving medication use in elderly.
Electrodeposition of ZnNi Alloys from Choline Chloride/Ethylene Glycol Deep Eutectic Solvent and Pure Ethylene Glycol for Corrosion Protection

The present work follows the trend to develop non-aqueous electrolytes for the deposition of corrosion resistant ZnNi alloys. It investigates the use of the choline chloride/ethylene glycol (1:2 molar ratio) eutectic mixture and of pure ethylene glycol as solvents for ZnNi electroplating. The electrochemical behavior of Zn and Ni is investigated via cyclic voltammetry, and potentiostatic ZnNi deposition is performed. Ni content is found to be precisely tunable in the 10–20% wt range, which presents the highest industrial interest for corrosion protection. ZnNi coatings obtained are characterized from the morphological and phase composition point of view. Evidence of the formation of a metastable γ ZnNi phase is observed for both choline chloride/ethylene glycol and pure ethylene glycol. Finally, potentiodynamic corrosion tests are performed to assess their corrosion properties.
Prevalence and Population Attributable Risk for Chronic Airflow Obstruction in a Large Multinational Study.

Rationale: The Global Burden of Disease programme identified smoking, and ambient and household air pollution as the main drivers of death and disability from Chronic Obstructive Pulmonary Disease (COPD). Objective: To estimate the attributable risk of chronic airflow obstruction (CAO), a quantifiable characteristic of COPD, due to several risk factors. Methods: The Burden of Obstructive Lung Disease study is a cross-sectional study of adults, aged≥40, in a globally distributed sample of 41 urban and rural sites. Based on data from 28,459 participants, we estimated the prevalence of CAO, defined as a post-bronchodilator one-second forced expiratory volume to forced vital capacity ratio < lower limit of normal, and the relative risks associated with different risk factors. Local RR were estimated using a Bayesian hierarchical model borrowing information from across sites. From these RR and the prevalence of risk factors, we estimated local Population Attributable Risks (PAR). Measurements and Main Results: Mean prevalence of CAO was 11.2% in men and 8.6% in women. Mean PAR for smoking was 5.1% in men and 2.2% in women. The next most influential risk factors were poor education levels, working in a dusty job for ≥10 years, low body mass index (BMI), and a history of tuberculosis. The risk of CAO attributable to the different risk factors varied across sites. Conclusions: While smoking remains the most important risk factor for CAO, in some areas poor education, low BMI and passive smoking are of greater importance. Dusty occupations and tuberculosis are important risk factors at some sites.
Alpha-satellite RNA transcripts are repressed by centromere–nucleolus associations

Although originally thought to be silent chromosomal regions, centromeres are instead actively transcribed. However, the behavior and contributions of centromere-derived RNAs have remained unclear. Here, we used single-molecule fluorescence in-situ hybridization (smFISH) to detect alpha-satellite RNA transcripts in intact human cells. We find that alpha-satellite RNA-smFISH foci levels vary across cell lines and over the cell cycle, but do not remain associated with centromeres, displaying localization consistent with other long non-coding RNAs. Alpha-satellite expression occurs through RNA polymerase II-dependent transcription, but does not require established centromere or cell division components. Instead, our work implicates centromere–nucleolar interactions as repressing alpha-satellite expression. The fraction of nucleolar-localized centromeres inversely correlates with alpha-satellite transcripts levels across cell lines and transcript levels increase substantially when the nucleolus is disrupted. The control of alpha-satellite transcripts by centromere-nucleolar contacts provides a mechanism to modulate centromere transcription and chromatin dynamics across diverse cell states and conditions.
High magnitude of food insecurity and malnutrition among people living with HIV/AIDS in Ethiopia: A call for integration of food and nutrition security with HIV treatment and care Programme

Background: Food insecurity and malnutrition has been reported to have a strong connection with human immunodeficiency viruses (HIV); this is more pervasive in Sub-Saharan Africa including Ethiopia. In this study, we examined the predictors of food insecurity and factors associated with malnutrition among people living with HIV (PLHIV) in Benishangul Gumuz Regional State, Ethiopia. Methods: We conducted a cross-sectional study at outpatient antiretroviral therapy (ART) clinics. Data were collected using participant interview, anthropometry, and participants’ chart review. Interviews were carried out with 390 PLHIVs who were on antiretroviral treatment follow-up. Four robust multivariate linear regression models were used to identify predictors of food insecurity and factors associated with malnutrition. Results: The prevalence of food insecurity and malnutrition among PLHIV were found to be 76% and 60%, respectively. The predictors of food insecurity were: urban residence; household dependency; average monthly income below 53.19 USD; poor asset possession; CD4 count below 350 cell/μL; and recurrent episodes of opportunistic infections (OIs). Correspondingly, malnutrition among PLHIV was found strongly associated with: female gender; urban residence; income below 53.19 USD; poor asset possession; duration of less than one year on ART; and recurrent episodes of OIs. Conclusion: The study findings suggest that the higher prevalence of food insecurity and malnutrition among PLHIV underscore: the need for economic and livelihood intervention; addressing contextual factors including the gender dimensions; adoption of nutrition-specific and sensitive interventions; and integration of food and nutrition security with HIV treatment and care programmes.
An Investigation of Insider Threat Mitigation Based on EEG Signal Classification

This study proposes a scheme to identify insider threats in nuclear facilities through the detection of malicious intentions of potential insiders using subject-wise classification. Based on electroencephalography (EEG) signals, a classification model was developed to identify whether a subject has a malicious intention under scenarios of being forced to become an insider threat. The model also distinguishes insider threat scenarios from everyday conflict scenarios. To support model development, 21-channel EEG signals were measured on 25 healthy subjects, and sets of features were extracted from the time, time–frequency, frequency and nonlinear domains. To select the best use of the available features, automatic selection was performed by random-forest-based algorithms. The k-nearest neighbor, support vector machine with radial kernel, naïve Bayes, and multilayer perceptron algorithms were applied for the classification. By using EEG signals obtained while contemplating becoming an insider threat, the subject-wise model identified malicious intentions with 78.57% accuracy. The model also distinguished insider threat scenarios from everyday conflict scenarios with 93.47% accuracy. These findings could be utilized to support the development of insider threat mitigation systems along with existing trustworthiness assessments in the nuclear industry.