Miracle-dz/UniFAR-FTUs huggingface dataset:
Adherence to the Mediterranean Diet in Spanish Population and Its Relationship with Early Vascular Aging according to Sex and Age: EVA Study

The objective of this study is to analyze the influence of adherence to the Mediterranean diet (MDA) and its components on early vascular aging (EVA) in a Spanish population sample free of cardiovascular disease and to analyze the differences by sex. Methods: We recruited 501 individuals aged 35–75 without cardiovascular disease by random sampling (55.90 ± 14.24 years, 49.70% men). EVA was defined in two steps: Step 1: subjects with vascular damage in carotid arteries or peripheral artery disease were classified as EVA. Step 2: subjects at the percentile of the combined Vascular Aging Index (VAI) were classified; ≥ p90 was considered EVA and < p90 was considered normal vascular aging (NVA), estimated using the following formula (VAI = (log (1.09) × 10 cIMT + log (1.14) cfPWV) × 39.1 + 4.76 by age and sex. Carotid-femoral pulse wave velocity (cfPWV) was measured by SphigmoCor System® and carotid intima-media thickness by Sonosite Micromax® ultrasound and classified thus: values ≥ Percentile 90 were considered EVA and those < Percentile 90 as NVA, with population percentiles analyzed. The principal result variable was assessed using the 14-item MEDAS questionnaire, developed and validated by the PREDIMED group, comprising 12 questions about the frequency of food consumption and two questions regarding the Spanish population’s typical eating habits. Results: MDA was observed by 25% (17% men and 34% women). EVA was present in 17% (29% men and 4% women). The adjusted logistic regression models showed that an increase in MDA decreases the probability of EVA in the global analysis (OR = 0.36; 95% CI: 0.16–0.82). In the analysis by sex, this association was only seen in men (OR = 0.33; 95% CI: 0.12–0.86), but not in women (OR = 0.31; 95% CI: 0.04–2.50). Conclusion: The results of this study suggest that a greater adherence to the Mediterranean diet decreases the probability of presenting EVA. In the analysis by sex, this association applies only to men.
Assorted dysfunctions of endosomal alkali cation/proton exchanger SLC9A6 variants linked to Christianson syndrome

Genetic screening has identified numerous variants of the endosomal solute carrier family 9 member A6 (SLC9A6)/(Na+,K+)/H+ exchanger 6 (NHE6) gene that cause Christianson syndrome, a debilitating X-linked developmental disorder associated with a range of neurological, somatic, and behavioral symptoms. Many of these variants cause complete loss of NHE6 expression, but how subtler missense substitutions or nonsense mutations that partially truncate its C-terminal cytoplasmic regulatory domain impair NHE6 activity and endosomal function are poorly understood. Here, we describe the molecular and cellular consequences of six unique mutations located in the N-terminal cytoplasmic segment (A9S), the membrane ion translocation domain (L188P and G383D), and the C-terminal regulatory domain (E547*, R568Q, and W570*) of human NHE6 that purportedly cause disease. Using a heterologous NHE6-deficient cell expression system, we show that the biochemical, catalytic, and cellular properties of the A9S and R568Q variants were largely indistinguishable from those of the WT transporter, which obscured their disease significance. By contrast, the L188P, G383D, E547*, and W570* mutants exhibited variable deficiencies in biosynthetic post-translational maturation, membrane sorting, pH homeostasis in recycling endosomes, and cargo trafficking, and they also triggered apoptosis. These findings broaden our understanding of the molecular dysfunctions of distinct NHE6 variants associated with Christianson syndrome.
Editorial. Neurosurgery in the storm of COVID-19: suggestions from the Lombardy region, Italy (ex malo bonum)

1Department of Neurosurgery, Grande Ospedale Metropolitano Niguarda, Milan; 2Department of Pathophysiology and Transplantation University of Milan; 3Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Besta, Milan, Italy; 4Department of Neurological Surgery, Johns Hopkins Medical School, Baltimore, Maryland; 5Department of Neurosurgery, Spedali Civili and University of Brescia; 6Department of Neurosurgery, Ospedale di Circolo ASST Sette Laghi, University of Insubria, Varese; and 7Department of Neurosurgery, Humanitas Research Hospital and University, Milan, Italy
Canoeing Motion Tracking and Analysis via Multi-Sensors Fusion

Coaches and athletes are constantly seeking novel training methodologies in an attempt to improve athletic performance. This paper proposes a method of rowing sport capture and analysis based on Inertial Measurement Units (IMUs). A canoeist’s motion was collected by multiple miniature inertial sensor nodes. The gradient descent method was used to fuse data and obtain the canoeist’s attitude information after sensor calibration, and then the motions of canoeist’s actions were reconstructed. Stroke quality was performed based on the estimated joint angles. Machine learning algorithm was used as the classification method to divide the stroke cycle into different phases, including propulsion-phase and recovery-phase, a quantitative kinematic analysis was carried out. Experiments conducted in this paper demonstrated that our method possesses the capacity to reveal the similarities and differences between novice and coach, the whole process of canoeist’s motions can be analyzed with satisfactory accuracy validated by videography method. It can provide quantitative data for coaches or athletes, which can be used to improve the skills of rowers.
Assessment of the genotoxic potential of a migraine-specific drug by comet and cytokinesis-block micronucleus assays

ABSTRACT Background: Eletriptan is a migraine-specific drug-containing the triptan group. In terms of drug safety, the present study aimed to investigate the genotoxic potential of eletriptan. Research design & methods: We conducted our study by using the cytokinesis-block micronucleus cytome (CBMN) assay, a comprehensive method for measuring micronucleus formation, and a sensitive method for detecting DNA-strand breaks. In the assay, cytokinesis-block proliferation index and the frequency of micronuclei were evaluated in lymphocytes treated with three different concentrations (1, 10 and 25 µg/ml) of eletriptan for 48 hours. In comet assays, DNA damage was evaluated in leucocytes treated with three different concentrations (1, 10 and 25 µg/ml) of eletriptan for an hour. Results: Eletriptan did not induce cytotoxicity nor any increased micronuclei frequencies. While the comet parameters % DNA in tail, tail moment, and the olive moment was found to be significantly increased at 10 and 25 µg/ml, the cytokinesis-block proliferation index values were not. Conclusion: These findings suggest that eletriptan is non-cytotoxic but potentially weakly genotoxic at higher concentrations (10 and 25 µg/ml).
Evaluation of Heavy-Ion-Induced Single Event Upset Cross Sections of a 65-nm Thin BOX FD-SOI Flip-Flops Composed of Stacked Inverters

Cross sections that cause single event upsets by heavy ions are sensitive to doping concentration in the source and drain regions, and the structure of the raised source and drain regions especially in FDSOI. Due to the parasitic bipolar effect (PBE), radiation-hardened flip flops with stacked transistors in FDSOI tend to have soft errors, which is consistent with measurement results by heavy-ion irradiation. Device-simulation results in this study show that the cross section is proportional to the silicon thickness of the raised layer and inversely proportional to the doping concentration in the drain. Increasing the doping concentration in the source and drain region enhance the Auger recombination of carriers there and suppresses the parasitic bipolar effect. PBE is also suppressed by decreasing the silicon thickness of the raised layer. Cgg-Vgs and Ids-Vgs characteristics change smaller than soft error tolerance change. Soft error tolerance can be effectively optimized by using these two determinants with only a small impact on transistor characteristics. key words: single event effect, soft error, heavy ion irradiation, FDSOI, flip flop, device simulation.
Data Clustering via Uncorrelated Ridge Regression

Ridge regression is frequently utilized by both supervised and semisupervised learnings. However, the trivial solution might occur, when ridge regression is directly applied for clustering. To address this issue, an uncorrelated constraint is introduced to the ridge regression with embedding the manifold structure. In particular, we choose uncorrelated constraint over orthogonal constraint, since the closed-form solution can be obtained correspondingly. In addition to the proposed uncorrelated ridge regression, a soft pseudo label is utilized with $\ell _{1}$ ball constraint for clustering. Moreover, a brand new strategy, i.e., a rescaled technique, is proposed such that optimal scaling within the uncorrelated constraint can be achieved automatically to avoid the inconvenience of tuning it manually. Equipped with the rescaled uncorrelated ridge regression with the soft label, a novel clustering method can be developed based on solving the related clustering model. Consequently, extensive experiments are provided to illustrate the effectiveness of the proposed method.
Establishing recurrence indicators and stratifying pancreatic ductal adenocarcinoma based on routine laboratory exams. Is it time to incorporate these parameters in daily clinical practice?

PURPOSE Systemic inflammation plays a crucial role in carcinogenesis and progression of pancreatic cancer, due to its influence on tumor angiogenesis, invasion and metastasis. The association of CA 19-9, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) can identify patients with different prognoses. METHODS We reviewed 148 pancreatic cancer patients' charts diagnosed from January 2006 to December 2018 in a tertiary hospital. Cox proportional survival models were used to evaluate the impact of each factor on recurrence-free and overall survival (OS). RESULTS When assessing risk of relapse, the presence of angiolymphatic invasion was associated with an 80% chance of recurrence in 5 years. Among other factors associated with OS, the estimated risk of death in patients with CA 19-9>300 U/mL was 2.37-fold higher compared to lower values. In addition, the risk of death was 60% and 76% higher in patients with NLR>3 and PLR>150, respectively. Patients within these 3 categories had a median OS of only 7.5 months, lower than all-comer patients with stage IV disease, with median OS estimated at 9.84 months. CONCLUSION The laboratory variables CA 19-9, NLR and PLR together can contribute to a better stratification of patients with pancreatic adenocarcinoma beyond conventional staging. Prospective initiatives using these factors together can demonstrate different subgroups of patients who benefit from new treatment strategies.
Predicting response to topical non-steroidal anti-inflammatory drugs in osteoarthritis: an individual patient data meta-analysis of randomized controlled trials

Abstract Objectives To identify predictors of the specific (difference between treatment and placebo) and overall (change from baseline in treatment arm) treatment effects of topical NSAIDs in OA. Methods Randomized controlled trials (RCTs) of topical NSAIDs in OA were identified through systematic literature searching and inquiry to pharmaceutical companies. The raw, de-identified data were analysed in one-stage individual patient data meta-analysis (IPD-MA). Negative values for treatment effects (0–100 scale) indicate pain reduction. Results Of 63 eligible RCTs, 15 provided IPD (n = 1951 on topical NSAID), including 11 placebo-controlled RCTs (n = 1587 on topical NSAIDs, 1553 on placebo). Seven potential predictors of response were examined. Topical NSAIDs were superior to placebo [−6 (95% CI −9, −4)], with a small, but statistically significant greater effect in women than men [difference −4 (95% CI −8, −1)]. The overall treatment effect was 4-fold larger than the specific effect [−25 (95% CI −31, −19)] and increased with greater baseline pain severity (P < 0.001). No differences in efficacy were observed for age, BMI, features of inflammation, duration of complaints or radiographic OA severity. Conclusion Topical NSAIDs are effective for OA pain relief. Greater overall pain relief in individuals with more baseline pain might be due to contextual and non-specific effects, including regression to the mean. Additional factors that have been linked either mechanistically or through empirical evidence to outcomes should be selected for inclusion across future RCTs in order to facilitate the identification of response predictors through IPD-MA.
High-Resolution Chest X-Ray Bone Suppression Using Unpaired CT Structural Priors

There is clinical evidence that suppressing the bone structures in Chest X-rays (CXRs) improves diagnostic value, either for radiologists or computer-aided diagnosis. However, bone-free CXRs are not always accessible. We hereby propose a coarse-to-fine CXR bone suppression approach by using structural priors derived from unpaired computed tomography (CT) images. In the low-resolution stage, we use the digitally reconstructed radiograph (DRR) image that is computed from CT as a bridge to connect CT and CXR. We then perform CXR bone decomposition by leveraging the DRR bone decomposition model learned from unpaired CTs and domain adaptation between CXR and DRR. To further mitigate the domain differences between CXRs and DRRs and speed up the learning convergence, we perform all the aboved operations in Laplacian of Gaussian (LoG) domain. After obtaining the bone decomposition result in DRR, we upsample it to a high resolution, based on which the bone region in the original high-resolution CXR is cropped and processed to produce a high-resolution bone decomposition result. Finally, such a produced bone image is subtracted from the original high-resolution CXR to obtain the bone suppression result. We conduct experiments and clinical evaluations based on two benchmarking CXR databases to show that (i) the proposed method outperforms the state-of-the-art unsupervised CXR bone suppression approaches; (ii) the CXRs with bone suppression are instrumental to radiologists for reducing their false-negative rate of lung diseases from 15% to 8%; and (iii) state-of-the-art disease classification performances are achieved by learning a deep network that takes the original CXR and its bone-suppressed image as inputs.
A simple model of epileptic seizure propagation: Potassium diffusion versus axo-dendritic spread

The mechanisms of epileptic discharge generation and spread are not yet fully known. A recently proposed simple biophysical model of interictal and ictal discharges, Epileptor-2, reproduces well the main features of neuronal excitation and ionic dynamics during discharge generation. In order to distinguish between two hypothesized mechanisms of discharge propagation, we extend the model to the case of two-dimensional propagation along the cortical neural tissue. The first mechanism is based on extracellular potassium diffusion, and the second is the propagation of spikes and postsynaptic signals along axons and dendrites. Our simulations show that potassium diffusion is too slow to reproduce an experimentally observed speed of ictal wavefront propagation (tenths of mm/s). By contrast, the synaptic mechanism predicts well the speed and synchronization of the pre-ictal bursts before the ictal front and the afterdischarges in the ictal core. Though this fact diminishes the role of diffusion and electrodiffusion, the model nevertheless highlights the role of potassium extrusion during neuronal excitation, which provides a positive feedback that changes at the ictal wavefront the balance of excitation versus inhibition in favor of excitation. This finding may help to find a target for a treatment to prevent seizure propagation.
Ozone efficacy for the control of airborne viruses: Bacteriophage and norovirus models

This study was designed to test the efficacy of an air treatment using ozone and relative humidity (RH) for the inactivation of airborne viruses. Four phages (φX174, PR772, MS2 and φ6) and one eukaryotic virus (murine norovirus MNV-1) were exposed to low ozone concentrations (1.23 ppm for phages and 0.23 ppm for MNV-1) and various levels of RH for 10 to 70 minutes. The inactivation of these viruses was then assessed to determine which of the tested conditions provided the greatest reduction in virus infectivity. An inactivation of at least two orders of magnitude for φX174, MS2 and MNV-1 was achieved with an ozone exposure of 40 minutes at 85% RH. For PR772 and φ6, exposure to the reference condition at 20% RH for 10 minutes yielded the same results. These findings suggest that ozone used at a low concentration is a powerful disinfectant for airborne viruses when combined with a high RH. Air treatment could therefore be implemented inside hospital rooms ventilated naturally.
Clinical associations of quarterly Patient Health Questionnaire‐9 depression screening results in adolescents with type 1 diabetes

Awareness of comorbid depression in type 1 diabetes (T1D) patients is necessary to optimize health and diabetes care. Depression can occur or recur requiring regular review for depression symptoms. A validated tool to screen adolescents for symptoms of depression is the Patient Health Questionnaire (PHQ)‐9 Modified for Teens (PHQ91‐9).
Evaluating Discrimination of a Lung Cancer Risk Prediction Model Using Partial Risk-Score in a Two-Phase Study

Background: Independent validation of risk prediction models in prospective cohorts is required for risk-stratified cancer prevention. Such studies often have a two-phase design, where information on expensive biomarkers are ascertained in a nested substudy of the original cohort. Methods: We propose a simple approach for evaluating model discrimination that accounts for incomplete follow-up and gains efficiency by using data from all individuals in the cohort irrespective of whether they were sampled in the substudy. For evaluating the AUC, we estimated probabilities of risk-scores for cases being larger than those in controls conditional on partial risk-scores, computed using partial covariate information. The proposed method was compared with an inverse probability weighted (IPW) approach that used information only from the subjects in the substudy. We evaluated age-stratified AUC of a model including questionnaire-based risk factors and inflammation biomarkers to predict 10-year risk of lung cancer using data from the Prostate, Lung, Colorectal, and Ovarian Cancer (1993–2009) trial (30,297 ever-smokers, 1,253 patients with lung cancer). Results: For estimating age-stratified AUC of the combined lung cancer risk model, the proposed method was 3.8 to 5.3 times more efficient compared with the IPW approach across the different age groups. Extensive simulation studies also demonstrated substantial efficiency gain compared with the IPW approach. Conclusions: Incorporating information from all individuals in a two-phase cohort study can substantially improve precision of discrimination measures of lung cancer risk models. Impact: Novel, simple, and practically useful methods are proposed for evaluating risk models, a critical step toward risk-stratified cancer prevention.
Adenosine leakage from perforin-burst extracellular vesicles inhibits perforin secretion by cytotoxic T-lymphocytes

Extracellular vesicles (EVs) in the tumor microenvironment facilitate intercellular communication. Cancer cell-derived EVs act as an immunosuppressor by transporting cargos and presenting transmembrane proteins. By contrast, CD8+ cytotoxic T-lymphocytes (CTLs) exert anti-cancer cytotoxicity via the pore-forming protein perforin. Here, we hypothesize that although EVs are destroyed by perforin, cancer cell-derived EVs might possess mechanisms that enable them to avoid this destruction. We used a breast cancer cell line, MDA-MB-231-luc-D3H2LN (D3H2LN), to generate EVs. Destruction of the EVs by perforin was demonstrated visually using atomic force microscopy. To investigate immunosuppressive metabolites within cancer cell-derived EVs, we performed metabolomic profiling of EVs from D3H2LN cells cultured for 48 h with or without IFN-γ, which induces metabolic changes in the cells. We found that both types of EV from IFN-γ treated D3H2LN cells and non-treated D3H2LN cells contained adenosine, which has immunosuppressive effects. When we exposed cancer cell-derived EVs to CTLs, perforin secretion by CTLs fell significantly. In addition, the decreases in perforin secretion were ameliorated by treatment with adenosine deaminase, which degrades extracellular adenosine. Taken together, these results suggest that after perforin secreted by CTLs disrupts the membrane of EVs, adenosine released from the EVs acts as an immunosuppressive metabolite by binding to the adenosine receptor on the CTL membrane. This mechanism provides a novel survival strategy using cancer cell-derived EVs.
Protein dynamics and molecular motions study in relation to molecular interaction between proteins from sulfur oxidizing proteobacteria Allochromatium vinosum

Abstract The gamma-proteobacteria Allochromatium vinosum DSM 180T (A. vinosum) encodes the sulfur oxidizing dsr operon comprising of 15 genes. Dsr proteins are involved in oxidation of sulfur globules produced as an obligatory intermediate during the sulfur oxidation process. The dsrA and dsrB gene products are known to function as a α2β2 hetero-tetramer and the protein complex plays the catalytic role in sulfur oxidation process. DsrC has a highly conserved C-terminal domain that forms a flexible arm, where two strictly conserved cysteines were found to act as a substrate donating residue for DsrAB instead of being a subunit of this redox enzyme. Therefore, to elucidate the molecular mechanism of the sulfur oxidation process here an attempt was made to study the dynamics, stability and binding mechanisms of DsrAB and DsrC proteins through computational docking and molecular dynamics (MD) simulations. This structure function relationship investigation revealed that the C-terminal domain of DsrC interacts with DsrA of DsrAB protein complex for catalytic functions. Some basic amino acid residues of DsrC are found to form the catalytic pockets along with DsrAB protein complex where the sulfur anions bind to get oxidized. Structural dynamics and fluctuations as well as the secondary structural alterations study revealed the possible regions responsible for protein-protein interactions. Principal Component Analysis (PCA) of protein motions displayed that the collective motions of DsrAB-DsrC complex was higher and more anti-correlated than the unbound DsrAB form. The present molecular insight study would therefore help researchers to predict the plausible biochemical mechanism of sulfur oxidation process in sulfur metabolic pathways in near future. Communicated by Ramaswamy H. Sarma
Human Serum Albumin Labelled with Sterically-Hindered Nitroxides as Potential MRI Contrast Agents

Four albumin-nitroxide conjugates were prepared and tested as metal-free organic radical contrast agents (ORCAs) for magnetic resonance imaging (MRI). Each human serum albumin (HSA) carrier bears multiple nitroxides conjugated via homocysteine thiolactones. These molecular conjugates retain important physical and biological properties of their HSA component, and the resistance of their nitroxide groups to bioreduction was retained or enhanced. The relaxivities are similar for these four conjugates and are much greater than those of their individual components: the HSA or the small nitroxide molecules. This new family of conjugates has excellent prospects for optimization as ORCAs.