Miracle-dz/UniFAR-FTUs huggingface dataset:
Image denoising by directional averaging of wavelet coefficients

In this paper a new denoising technique for gray valued images is presented. The proposed technique is best suited for flat or textured images affected by relatively low noise levels, where we aim at high quality reconstruction of tiny image structures and fine details. To avoid the attenuation of these fine image details, we replace the common wavelet thresholding and shrinking rules by an averaging step over a certain region of consistent edge directions. This region is obtained by first extracting the pixels that belong to an "oriented structure". We develop a classification algorithm which extracts the oriented structures by using directional information from the wavelet detail images. After this classification step we perform an adaptive averaging: each pixel is averaged over a window that depends on the detected structures in its neighbourhood. We demonstrate the visual improvement of our method over two spatially adaptive wavelet shrinkage methods.
Oligomeric, phosphorylated, and truncated tau and spliceosome pathology within the entorhinal–hippocampal connectome across stages of Alzheimer's disease

Neurofibrillary tangles (NFTs) contain abnormally phosphorylated tau proteins, which spread within components of the medial temporal lobe (MTL) memory circuit in Alzheimer's disease (AD). Here, we used quantitative immunohistochemistry to determine the density of posttranslational oligomeric (TOC1 and TNT1), phosphorylated (AT8), and late truncated (TauC3) tau epitopes within the MTL subfields including entorhinal cortex (EC) layer II, subiculum, Cornu Ammonis (CA) subfields, and dentate gyrus (DG) in subjects who died with a clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), and AD. We also examined whether alterations of the nuclear alternative splicing protein, SRSF2, are associated with tau pathology. Although a significant increase in TOC1, TNT1, and AT8 neuron density occurred in the EC in MCI and AD, subicular, DG granule cell, and CA1 and CA3 densities were only significantly higher in AD. TauC3 counts were not different between connectome regions and clinical groups. SRSF2 intensity in AT8‐positive cells decreased significantly in all regions independent of the clinical groups examined. CA1 and subicular AT8, TauC3, and oligomeric densities correlated across clinical groups. EC AT8 counts correlated with CA subfields and subicular and DG values across clinical groups. Oligomeric and AT8 CA1, EC, and subicular density correlated with Braak stage. Decreased nuclear SRSF2 in the presence of cytoplasmic phosphorylated tau suggests a dual‐hit process in NFT formation within the entorhinal hippocampal connectome during the onset of AD. Although oligomeric and phosphorylated tau follow a stereotypical pattern, clinical disease stage determined density of tau deposition and not anatomic location within the entorhinal–hippocampal connectome.
How a highly acidic SH3 domain folds in the absence of its charged peptide target

Charged residues on the surface of proteins are critical for both protein stability and interactions. However, many proteins contain binding regions with a high net-charge that may destabilize the protein but are useful for binding to oppositely charged targets. We hypothesized that these domains would be marginally stable, as electrostatic repulsion would compete with favorable hydrophobic collapse during folding. Furthermore, by increasing the salt concentration we predict that these protein folds would be stabilized by mimicking some of the favorable electrostatic interactions that take place during target binding. We varied the salt and urea concentrations to probe the contributions of electrostatic and hydrophobic interactions for the folding of the 60-residue yeast SH3 domain found in Abp1p. The SH3 domain was significantly stabilized with increased salt concentrations according to the Debye-Huckel limiting law. Molecular dynamics and NMR show that sodium ions interact with all 15 acidic residues but do little to change backbone dynamics or overall structure. Folding kinetics experiments show that the addition of urea or salt primarily affects the folding rate, indicating that almost all the hydrophobic collapse and electrostatic repulsion occurs in the transition state. After the transition state formation, modest yet favorable short-range salt-bridges are formed along with hydrogen bonds, as the native state fully folds. Thus, hydrophobic collapse offsets electrostatic repulsion to ensure this highly charged binding domain can still fold and be ready to bind to its charged peptide targets, a property that is likely evolutionarily conserved over one billion years. Statement for broader audience Some protein domains are highly charged because they are adapted to bind oppositely charged proteins and nucleic acids. However, it is unknown how these highly charged domains fold as during folding there will be significant repulsion between like-charges. We investigate how one of these highly charged domains folds in the presence of salt, which can screen the charge repulsion and make folding easier, allowing us to understand how folding occurs despite the protein’s high charge. Supplementary material Supplementary material document containing additional details on protein expression methods, thermodynamics and kinetics equations, and the effect of urea on electrostatic interactions, as well as 4 supplemental figures and 4 supplemental data tables. (Supplementary_Material.docx), 15 pages Supplemental excel file containing covariation data across AbpSH3 orthologs (FileS1.xlsx)
Intraventricular conduction delays as a predictor of mortality in acute coronary syndromes

Abstract Aims Initial proof suggests that a non-specific intraventricular conduction delay (NIVCD) is a risk factor for mortality. We explored the prognosis of intraventricular conduction delays (IVCD)—right bundle branch block (RBBB), left bundle branch block (LBBB), and the lesser-known NIVCD—in patients with acute coronary syndrome (ACS). Methods and results This is a retrospective registry analysis of 9749 consecutive ACS patients undergoing coronary angiography and with an electrocardiographic (ECG) recording available for analysis (2007–18). The primary outcome was cardiac mortality. Mortality and cause of death data (in ICD-10 format) were received from the Finnish national register with no losses to follow-up (until 31 December 2020). The risk associated with IVCDs was analysed by calculating subdistribution hazard estimates (SDH; deaths due to other causes being considered competing events). The mean age of the population was 68.3 years [standard deviation (Sd) 11.8]. The median follow-up time was 6.1 years [interquartile range (IQR) 3.3–9.4], during which 3156 patients died. Cardiac mortality was overrepresented among IVCD patients: 76.9% for NIVCD (n = 113/147), 67.6% for LBBB (n = 96/142), 55.7% for RBBB (n = 146/262), and 50.1% for patients with no IVCD (n = 1275/2545). In an analysis adjusted for age and cardiac comorbidities, the risk of cardiac mortality was significantly higher in all IVCD groups than among patients with no IVCD: SDH 1.37 (1.15–1.64, P < 0.0001) for RBBB, SDH 1.63 (1.31–2.03 P < 0.0001) for LBBB, and SDH 2.68 (2.19–3.27) for NIVCD. After adjusting the analysis with left ventricular ejection fraction, RBBB and NIVCD remained significant risk factors for cardiac mortality. Conclusion RBBB, LBBB, and NIVCD were associated with higher cardiac mortality in ACS patients.
Whole body insulin sensitivity is increased in systemic sclerosis

Objectives In the present study, we aimed to evaluate whole-body insulin sensitivity in systemic sclerosis (SSc) patients and to compare the results with controls with no autoimmune rheumatic disease (non-ARD) and with patients affected by rheumatoid arthritis (RA). Methods In all patients and controls, oral glucose tolerance test (OGTT) was performed according to the World Health Organization (WHO) recommendations. Plasma glucose and insulin concentrations were measured at time 0 and then after 30, 60, 90, and 120 minutes. Whole-body insulin sensitivity (ISI), insulinogenic index (IGI), oral disposition index (ODI), and insulin resistance (HOMA-IR) were estimated accordingly. Results A total of 41 SSc patients were evaluated and, for comparison, 41 individuals with RA and 82 non-ARD control patients were recruited. OGTT yielded a proportion of normotolerant individuals among SSc patients higher than in RA controls (p = 0.040) but lower than in the non-ARD group (p = 0.028). The ISI was significantly higher in SSc patients compared with RA controls (p <0.001) and with non-ARD patients (p <0.001). Significant differences emerged also when analysing the HOMA-IR, which was lower in SSc patients than in RA (p <0.001) and non-ARD (p <0.001) groups. Additionally, IGI was lower in SSc patients compared with RA (p = 0.011) and with non-ARD controls (p <0.001), whereas ODI was not significantly different between groups. Conclusions Interestingly, we found that SSc patients are more insulin sensitive than those with RA and even than individuals without inflammatory diseases. In contrast, no significant difference was found in terms of β-cell function.
The role of multiple high-risk human papillomavirus infections for cervical biopsies and findings in colposcopic procedures

Objective: The clinical outcome of high-risk HPV (hr-HPV) infection varies according to genotype(s). Patients may harbor either one single hr-HPV (s-HPV) or multiple HPV (m-HPV) genotypes. Recently, the relationship between m-HPV infections and high-grade dysplasia has been investigated, and controversial results have been obtained. Therefore, the clinical significance of m-HPV is not clear. This study aimed to evaluate which group is associated with higher grade dysplasia by analyzing colposcopic punch biopsies. Material and Methods: A total of 690 patients who were scheduled for a diagnostic excisional procedure between April 2016 and January 2019 due to the detection of high-grade cervical intraepithelial neoplasia (CIN 2/3) in colposcopy were included. Patients who were not scheduled for colposcopic examination or cervical punch biopsy, or who were scheduled for an excisional procedure due to smear-biopsy incompatibility or persistent low-grade dysplasia were excluded. Patients with a negative HPV test and an unknown HPV genotype were also excluded. Results: Among the patients scheduled for excision (n=404), 74.5% had a s-HPV and 25.5% had a m-HPV infection. The proportion of CIN 1, 2 and 3 per patient in the m-HPV group was significantly higher than the s-HPV group (p=0.017). When this analysis was made for the number of CIN 2+3 per patient in the s-HPV and m-HPV groups, it was 1.29 (389/301) and 1.36 (140/103), respectively, and no difference was found (p=0.491). Conclusion: Patients in the m-HPV group, who underwent more colposcopic cervical biopsies, had higher numbers of CIN lesions, regardless of age and cytology results.
Eight-year longitudinal falls trajectories and associations with modifiable risk factors: evidence from The Irish Longitudinal Study on Ageing (TILDA)

Abstract Background The label ‘faller’ and the associated stigma may reduce healthcare-seeking behaviours. However, falls are not inevitably progressive and many drivers are modifiable. This observational study described the 8-year longitudinal trajectories of self-reported falls in The Irish Longitudinal Study on Ageing (TILDA) and studied associations with factors, including mobility, cognition, orthostatic hypotension (OH), fear of falling (FOF) and use of antihypertensive and antidepressant medications. Methods Participants aged ≥50 years at each wave were categorised by whether they averaged ≥2 falls in the previous year (recurrent fallers) or not (≤1 fall). Next-wave transition probabilities were estimated with multi-state models. Results 8,157 (54.2% female) participants were included, of whom 586 reported ≥2 falls at Wave 1. Those reporting ≥2 falls in the past year had a 63% probability of moving to the more favourable state of ≤1 fall. Those reporting ≤1 fall had a 2% probability of transitioning to ≥2 falls. Besides older age and higher number of chronic conditions, factors that increased the risk of transitioning from ≤1 fall to ≥2 falls were lower Montreal Cognitive Assessment score, FOF and taking antidepressants. Conversely, male sex, higher timed up and go time, the presence of OH and being on antidepressants reduced the probability of improving from ≥2 falls to ≤1 fall. Conclusion The majority of recurrent fallers experienced favourable transitions. Improvements in cognitive and psychological status, psychotropic prescribing, mobility and OH may help improve trajectories. Findings may help combat stigma associated with falling and promote preventative healthcare-seeking behaviours.
Smoking Cessation After Diagnosis of Kidney Cancer Is Associated With Reduced Risk of Mortality and Cancer Progression: A Prospective Cohort Study

PURPOSE To investigate whether postdiagnosis smoking cessation may affect the risk of death and disease progression in patients with renal cell carcinoma (RCC) who smoked at the time of diagnosis. METHODS Two hundred twelve patients with primary RCC were recruited between 2007 and 2016 from the Urological Department in N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia. Upon enrollment, a structured questionnaire was completed, and the patients were followed annually through 2020 to repeatedly assess their smoking status and disease progression. Survival probabilities and hazards for all-cause and cancer-specific mortality and disease progression were investigated using extended the Kaplan-Meier method, time-dependent Cox proportional hazards regression, and Fine-Gray competing-risk models. RESULTS Patients were followed for a median of 8.2 years. During this time, 110 cases of disease progression, 100 total deaths, and 77 cancer-specific deaths were recorded. Eighty-four patients (40%) quit smoking after diagnosis. The total person-years at risk for this analysis were 748.2 for continuing smoking and 611.2 for quitting smoking periods. At 5 years of follow-up, both overall survival (85% v 61%) and progression-free survival (80% v 57%) rates were higher during the quitting than continuing smoking periods (both P < .001). In the multivariable time-dependent models, quitting smoking was associated with lower risk of all-cause mortality (hazard ratio [HR], 0.51; 95% CI, 0.31 to 0.85), disease progression (HR, 0.45; 95% CI, 0.29 to 0.71), and cancer-specific mortality (HR, 0.54; 95% CI, 0.31 to 0.93). The beneficial effect of quitting smoking was evident across all subgroups, including light smokers versus moderate-heavy smokers and those with early-stage versus late-stage tumors. CONCLUSION Quitting smoking after RCC diagnosis may significantly improve survival and reduce the risk of disease progression and cancer mortality among patients who smoke.
A standardized database of Chinese emotional short videos based on age and gender differences

Most of the existing emotion elicitation databases use the film clips as stimuli and do not take into account the age and gender differences of participants. Considering the short videos have the advantages of short in time, easy to understand and strong emotional appeal, we choose them to construct a standardized database of Chinese emotional short videos by the joint analysis of age and gender differences. Two experiments are performed to establish and validate our database. In the Experiment 1, we selected 240 stimuli from 2700 short videos and analyzed the subjective evaluation results of 360 participants with different ages and genders. As a result, a total of 54 short videos with three categories of emotions were picked out for 6 groups of participants, including the male and female respectively aged in 20-24, 25-29 and 30-34. In the Experiment 2, we recorded the EEG signals and subjective experience scores of 81 participants while watching different video stimuli. Both the results of EEG emotion recognition and subjective evaluation indicate that our database of 54 short videos can achieve better emotion elicitation effects compared with film clips. Furthermore, the targeted delivery of specific short videos has also been verified to be effective, helping the researchers choose appropriate emotional elicitation stimuli for different participants and promoting the study of individual differences in emotion responses.
Leveraging cross-view geo-localization with ensemble learning and temporal awareness

The Global Navigation Satellite System (GNSS) is unreliable in some situations. To mend the poor GNSS signal, an autonomous vehicle can self-localize by matching a ground image against a database of geotagged aerial images. However, this approach has challenges because of the dramatic differences in the viewpoint between aerial and ground views, harsh weather and lighting conditions, and the lack of orientation information in training and deployment environments. In this paper, it is shown that previous models in this area are complementary, not competitive, and that each model solves a different aspect of the problem. There was a need for a holistic approach. An ensemble model is proposed to aggregate the predictions of multiple independently trained state-of-the-art models. Previous state-of-the-art (SOTA) temporal-aware models used heavy-weight network to fuse the temporal information into the query process. The effect of making the query process temporal-aware is explored and exploited by an efficient meta block: naive history. But none of the existing benchmark datasets was suitable for extensive temporal awareness experiments, a new derivative dataset based on the BDD100K dataset is generated. The proposed ensemble model achieves a recall accuracy R@1 (Recall@1: the top most prediction) of 97.74% on the CVUSA dataset and 91.43% on the CVACT dataset (surpassing the current SOTA). The temporal awareness algorithm converges to R@1 of 100% by looking at a few steps back in the trip history.
Therapeutic Potentials of Aconite-like Alkaloids - Bioinformatics and Experimental Approaches.

Compounds from plants that are used in traditional medicine may have medicinal properties. It is well known that plants belonging to the genus Aconitum are highly poisonous. Utilizing substances derived from Aconitum sp. has been linked to deadly negative effects. In addition to their toxicity, the natural substances derived from Aconitum species may have a range of biological effects on humans, such as analgesic, anti-inflammatory, and anti-cancer characteristics. Multiple in silico, in vitro, and in vivo studies have demonstrated the effectiveness of their therapeutic effects. In this review, the clinical effects of natural compounds extracted from Aconitum sp. , focusing on aconite-like alkaloids, are investigated particularly by bioinformatics tools such as the quantitative structure-activity relationship method, molecular docking, and predicted pharmacokinetic and pharmacodynamic profiles. The experimental and bioinformatics aspects of aconitine's pharmacogenomic profile are discussed. Our review could help shed light on the molecular mechanisms of Aconitum sp. compounds. The effects of several aconite-like alkaloids such as aconitine, methyllycacintine, or hypaconitine on specific molecular targets, including voltage-gated sodium channels, CAMK2A and CAMK2G during anaesthesia, or BCL2, BCL-XP, and PARP-1 receptors during cancer therapy, are evaluated. According to the reviewed literature, aconite and aconite derivatives have a high affinity for the PARP-1 receptor. The toxicity estimations for aconitine indicate hepatotoxicity and hERG II inhibitor activity; however, this compound is not predicted to be AMES toxic or a hERG I inhibitor. The efficacy of aconitine and its derivatives in treating many illnesses has been proven experimentally. Toxicity occurs as a result of the large ingested dose; however, a valuable component of the usage of this drug in future research is based on the small quantity of an active compound that fulfils a therapeutic role.
A combined in silico approaches of 2D-QSAR, molecular docking, molecular dynamics and ADMET prediction of anti-cancer inhibitor activity for actinonin derivatives

Abstract Inhibition of human mitochondrial peptide deformylase (HsPDF) plays a major role in reducing growth, proliferation, and cellular cancer survival. In this work, a series of 32 actinonin derivatives for HsPDF (PDB: 3G5K) inhibitor’s anticancer activity was computationally analyzed for the first time, using an in silico study considering 2D-QSAR modeling, and molecular docking studies, and validated by molecular dynamics and ADMET properties. The results of multilinear regression (MLR) and artificial neural networks (ANN) statistical analysis reveal a good correlation between pIC50 activity and the seven (7) descriptors. The developed models were highly significant with cross-validation, the Y-randomization test and their applicability range. In addition, all considered data sets show that the AC30 compound, exhibits the best binding affinity (docking score = −212.074 kcal/mol and H-bonding energy = −15.879 kcal/mol). Furthermore, molecular dynamics simulations were performed at 500 ns, confirming the stability of the studied complexes under physiological conditions and validating the molecular docking results. Five selected actinonin derivatives (AC1, AC8, AC15, AC18 and AC30), exhibiting best docking score, were rationalized as potential leads for HsPDF inhibition, in well agreement with experimental outcomes. Furthermore, based on the in silico study, new six molecules (AC32, AC33, AC34, AC35, AC36 and AC37) were suggested as HsPDF inhibition candidates, which would be combined with in-vitro and in-vivo studies to perspective validation of their anticancer activity. Indeed, the ADMET predictions indicate that these six new ligands have demonstrated a fairly good drug-likeness profile.