Miracle-dz/UniFAR-FTUs huggingface dataset:
SILVI, an open-source pipeline for T-cell epitope selection

High-throughput screening of available genomic data and identification of potential antigenic candidates have promoted the development of epitope-based vaccines and therapeutics. Several immunoinformatic tools are available to predict potential epitopes and other immunogenicity-related features, yet it is still challenging and time-consuming to compare and integrate results from different algorithms. We developed the R script SILVI (short for: from in silico to in vivo), to assist in the selection of the potentially most immunogenic T-cell epitopes from Human Leukocyte Antigen (HLA)-binding prediction data. SILVI merges and compares data from available HLA-binding prediction servers, and integrates additional relevant information of predicted epitopes, namely BLASTp alignments with host proteins and physical-chemical properties. The two default criteria applied by SILVI and additional filtering allow the fast selection of the most conserved, promiscuous, strong binding T-cell epitopes. Users may adapt the script at their discretion as it is written in open-source R language. To demonstrate the workflow and present selection options, SILVI was used to integrate HLA-binding prediction results of three example proteins, from viral, bacterial and parasitic microorganisms, containing validated epitopes included in the Immune Epitope Database (IEDB), plus the Human Papillomavirus (HPV) proteome. Applying different filters on predicted IC50, hydrophobicity and mismatches with host proteins allows to significantly reduce the epitope lists with favourable sensitivity and specificity to select immunogenic epitopes. We contemplate SILVI will assist T-cell epitope selections and can be continuously refined in a community-driven manner, helping the improvement and design of peptide-based vaccines or immunotherapies. SILVI development version is available at: github.com/JoanaPissarra/SILVI2020 and https://doi.org/10.5281/zenodo.6865909.
Effect of bromelain on sperm quality, testicular oxidative stress and expression of oestrogen receptors in bisphenol‐A treated male mice

Bisphenol A (BPA) as an endocrine‐disrupting chemical (EDC) with low estrogenic activity increases oxidative stress and testicular damage. Bromelain is a mixture of different thiol endopeptidases and other components with many uses as a natural anti‐inflammatory enzyme. The present study aimed to evaluate the effect of bromelain on male reproductive failure induced by BPA. A total of 60 healthy adult male mice were randomly divided into six groups (n = 6), including control, bromelain (70 mg/kg), BPA (5 and 600 mg/kg), and BPA (5 and 600 mg/kg) + bromelain. BPA and bromelain were administrated orally for 35 days. Then, the epididymis and testes were removed to evaluate sperm parameters, oxidative stress markers, serum levels of testosterone concentrations, and oestrogen receptors expression. The BPA significantly (P < 0.05) decreased sperm count, motility, viability, and normal sperm morphology, as well as testosterone levels, oestrogen receptors alpha (ERα) and beta (ERβ), GPx, CAT, and SOD activity than control. Also, BPA significantly (P < 0.05) increased the sperm anomalies, and MDA concentration. Co‐administration of bromelain + BPA caused a significantly (P < 0.05) increase sperm count, normal sperm morphology, testosterone levels, expression of ERα and ERβ, and GPx, CAT, and SOD activity than the BPA group (P < 0.05). Also, Bromelain significantly (P < 0.05) decreased sperm anomalies and MDA concentration than control. Based on the results of this study, it appears that BPA causes side effects on male reproduction. While, bromelain has the potential to reduce the side effects of BPA on the male reproductive system.
Aortic remodeling, distal stent‐graft induced new entry and endoleak following frozen elephant trunk: A systematic review and meta‐analysis

The introduction of the frozen elephant trunk (FET) technique for total arch replacement (TAR) has revolutionized the field of aortovascular surgery. However, although FET yields excellent results, the risk of certain complications requiring secondary intervention remains present, negating its one‐step hybrid advantage over conventional techniques. This systematic review and meta‐analysis sought to evaluate controversies regarding the incidence of FET‐related complications, with a focus on aortic remodeling, distal stent‐graft induced new entry (dSINE) and endoleak, in patients with type A aortic dissection (TAAD) and/or thoracic aortic aneurysm.
Surgeon volume and patient-reported urinary incontinence after radical prostatectomy. Population-based register study in Sweden

Abstract Objective To investigate the association between surgeon volume and urinary incontinence after radical prostatectomy. Methods A total of 8326 men in The National Prostate Cancer Register of Sweden (NPCR) underwent robot-assisted radical prostatectomy (RARP) between 2017 and 2019 of whom 56% (4668/8 326) had responded to a questionnaire one year after RARP. The questionnaire included the question: ‘How much urine leakage do you experience? ’ with the response alternatives ‘Not at all’, ‘A little’, defined as continence and ‘Moderately’, ‘Much/Very much’ as incontinence. Association between incontinence and mean number of RARPs/year/surgeon was analysed with multivariable logistic regression including age, Charlson Comorbidity Index (CCI), PSA, prostate volume, number of biopsy cores with cancer, cT stage, Gleason score, lymph node dissection, nerve sparing intent and response rate to the questionnaire. Results 14% (659/4 668) of the men were incontinent one year after RARP. There was no statistically significant association between surgeon volume and incontinence. Older age (>75 years vs. < 65 years, OR 2.29 [95% CI 1.48–3.53]), higher CCI (CCI 2+ vs. CCI 0, OR 1.37 [95% CI 1.04–1.80]) and no nerve sparing intent (no vs. yes OR 1.53 [95% CI 1.26–1.85]) increased risk of incontinence. There were large differences in the proportion of incontinent men between surgeons with similar annual volumes, which remained after adjustment. Conclusions The lack of association between surgeon volume and incontinence and the wide range in outcome between surgeons with similar volumes underline the importance of individual feedback to surgeons on functional results.
Machine learning methods detect arm movement impairments in a patient with parieto-occipital lesion using only early kinematic information

Patients with lesions of the parieto-occipital cortex typically misreach visual targets that they correctly perceive (optic ataxia). Although optic ataxia was described more than 30 years ago, distinguishing this condition from physiological behavior using kinematic data is still far from being an achievement. Here, combining kinematic analysis with machine learning methods, we compared the reaching performance of a patient with bilateral occipitoparietal damage with that of 10 healthy controls. They performed visually guided reaches toward targets located at different depths and directions. Using the horizontal, sagittal, and vertical deviation of the trajectories, we extracted classification accuracy in discriminating the reaching performance of patient from that of controls. Specifically, accurate predictions of the patient's deviations were detected after the 20% of the movement execution in all the spatial positions tested. This classification based on initial trajectory decoding was possible for both directional and depth components of the movement, suggesting the possibility of applying this method to characterize pathological motor behavior in wider frameworks.
Effects of aging on neural processing during an active listening task

Factors affecting successful listening in older adults and the corresponding electrophysiological signatures are not well understood. The present study investigated age-related differences in attention and temporal processing, as well as differences in the neural activity related to signal degradation during a number comparison task. Participants listened to digits presented in background babble and were tested at two levels of signal clarity, clear and degraded. Behavioral and electrophysiological measures were examined in 30 older and 20 younger neurologically-healthy adults. Relationships between performance on the number comparison task, behavioral measures, and neural activity were used to determine correlates of listening deficits associated with aging. While older participants showed poorer performance overall on all behavioral measures, their scores on the number comparison task were largely predicted (based on regression analyses) by their sensitivity to temporal fine structure cues. Compared to younger participants, older participants required higher signal-to-noise ratios (SNRs) to achieve equivalent performance on the number comparison task. With increasing listening demands, age-related changes were observed in neural processing represented by the early-N1 and later-P3 time windows. Source localization analyses revealed age differences in source activity for the degraded listening condition that was located in the left prefrontal cortex. In addition, this source activity negatively correlated with task performance in the older group. Together, these results suggest that older adults exhibit reallocation of processing resources to complete a demanding listening task. However, this effect was evident only for poorer performing older adults who showed greater posterior to anterior shift in P3 response amplitudes than older adults who were good performers and younger adults. These findings might reflect less efficient recruitment of neural resources that is associated with aging during effortful listening performance.
Recruitment characteristics of randomised trials in critical care: A systematic review

Background/Aims: To summarise the temporal trends of recruitment and methodological characteristics of critical care randomised controlled trials with the primary outcome of mortality. Methods: PubMed was searched for articles meeting inclusion and exclusion criteria. Randomised controlled trials, with primary outcome of mortality, of adult and paediatric critical care patients treated in an intensive care unit, were included. Neonatal intensive care unit trials, non-English publications and conference proceedings or abstracts without full-length publications were excluded. Duplicate literature search, article selection and quality assessment were performed by two reviewers with disputes resolved through discussion. Data were extracted into a custom-designed Research Electronic Data Capture database. Results: The search identified 67,199 records of which 230 were included. The annual number of critical care randomised controlled trials published increased gradually over a 30-year period from 0 in 1990 to 19 in 2014 with stabilisation at 8–11 between 2015 and 2020. Twenty-seven percent of randomised controlled trials were low risk in all categories using the Cochrane Risk of Bias tool. Methodological characteristics such as registration on clinical trials registries and data safety monitoring committee presence significantly (p < 0.001) increased over time. The median recruitment was 376 patients (interquartile range 125–895) with significant increase (p = 0.002) from 62 (interquartile range: 33–486) in 1991 to 725 (interquartile range: 537–2600) in 2020. This was accompanied by an increase in recruitment times. Thus overall, recruitment rates did not increase. Early cessation occurred in 23% (54/230) of randomised controlled trials with no temporal trend. Conclusion: The number, size and some methodological qualities of critical randomised controlled trials with primary outcome of mortality have increased over time, but rates of recruitment and early cessation have been unchanged.
New foundations and unification of basic plasma physics by means of classical mechanics

The derivation of Debye shielding and Landau damping from the $N$-body description of plasmas requires many pages of heavy kinetic calculations in classical textbooks and is done in distinct, unrelated chapters. Using Newton's second law for the $N$-body system, we perform this derivation in a few steps with elementary calculations using standard tools of calculus, and no probabilistic setting. Unexpectedly, Debye shielding is encountered on the way to Landau damping. The theory is extended to accommodate a correct description of trapping or chaos due to Langmuir waves, and to avoid the small amplitude assumption for the electrostatic potential. Using the shielded potential, collisional transport is computed for the first time by a convergent expression including the correct calculation of deflections for all impact parameters. Shielding and collisional transport are found to be two related aspects of the repulsive deflections of electrons.
Sublethal exposure to spinetoram impacts life history traits and dengue virus replication in Aedes aegypti

Insecticides are anthropogenic environmental stressors and also a common stressor for mosquito vectors. However, the use of insecticides is often guided by short‐term efficacy, and the sublethal effect on their target or nontarget species has long been ignored. Here, we analyzed how sublethal exposure of the promising vector‐control bioinsecticide spinetoram to Aedes aegypti larvae alter adult performance and susceptibility to dengue virus (DENV) infection. We found that the surviving adult mosquitoes were significantly smaller and exhibited weaker blood‐feeding capacity than control females, apart from the extended immature development period. In terms of reproductive potential, although the F0 generation produced a similar number of eggs and offspring during the first gonotrophic cycle, the survival rates of the F1 generations were significantly lower as compared to the control group, suggesting transgenerational sublethal effects on the F1 generation. Notably, surviving adult females had higher DENV‐2 viral loads than the control group after spinetoram sublethal exposure. Mechanistically, transcriptomic analysis showed that inhibition of oxidative phosphorylation may function in stimulating DENV production in adult Ae. aegypti. In Aag2 cells, significant accumulation of apoptosis, mitochondrial reactive oxygen species production, and DENV‐2 replication by spinetoram exposure consistently support our conclusion. Our study highlights the threat of sublethal spinetoram exposure on outbreaks of mosquito‐borne viruses.
Neural networks for classification of cervical vertebrae maturation: a systematic review.

OBJECTIVE To assess the accuracy of identification and/or classification of the stage of cervical vertebrae maturity on lateral cephalograms by neural networks as compared with the ground truth determined by human observers. MATERIALS AND METHODS Search results from four electronic databases (PubMed [MEDLINE], Embase, Scopus, and Web of Science) were screened by two independent reviewers, and potentially relevant articles were chosen for full-text evaluation. Articles that fulfilled the inclusion criteria were selected for data extraction and methodologic assessment by the QUADAS-2 tool. RESULTS The search identified 425 articles across the databases, from which 8 were selected for inclusion. Most publications concerned the development of the models with different input features. Performance of the systems was evaluated against the classifications performed by human observers. The accuracy of the models on the test data ranged from 50% to more than 90%. There were concerns in all studies regarding the risk of bias in the index test and the reference standards. Studies that compared models with other algorithms in machine learning showed better results using neural networks. CONCLUSIONS Neural networks can detect and classify cervical vertebrae maturation stages on lateral cephalograms. However, further studies need to develop robust models using appropriate reference standards that can be generalized to external data.
Dialysate calcium, alfacalcidol, and clinical outcomes: A post-hoc analysis of the J-DAVID trial

The selection of dialysate calcium concentration (D-Ca) is still controversial among chronic hemodialysis (HD) regimens. We examined the trajectories of CKD MBD parameters among the J-DAVID trial participants to see the effect of D-Ca and alfacalcidol. The trial was an open-label randomized clinical trial including 976 HD patients with intact PTH of 180 pg/mL or lower which compared the users of vitamin D receptor activator (oral alfacalcidol) and non-users over a median of 4 years. The main D-Ca used at baseline were 3.0 mEq/L in 70% and 2.5 mEq/L in 25%, respectively. The primary endpoint was the composite of fatal and non-fatal cardiovascular events and the secondary endpoint was all-cause mortality. Multivariable Cox proportional hazard regression analyses in which D-Ca was included as a possible effect modifier and serum laboratory data as time-varying covariates showed no significant effect modification for composite cardiovascular events or all-cause mortality. This post hoc analysis showed that the effects of alfacalcidol on cardiovascular outcomes were not significantly modified by D-Ca.
Slow Down to Go Better: A Survey on Slow Feature Analysis

Temporal data contain a wealth of valuable information, playing an essential role in various machine-learning tasks. Slow feature analysis (SFA), one of the most classic temporal feature extraction models, has been deeply explored in two decades of development. SFA extracts slowly varying features as high-level representations of temporal data. Its core idea of “slow” has been proven to be consistent with the nature of biological vision and beneficial in capturing significant temporal information for various tasks. So far, SFA has evolved into numerous improved versions and is widely applied in many fields such as computer vision, industrial control, remote sensing, signal processing, and computational biology. However, there currently lacks an insightful review of SFA. In this article, a comprehensive overview of SFA and its extensions is provided for the first time. The formulation and optimization of SFA are introduced. Two mainstream solutions, geometric interpretation, and a gradient-based training method of SFA are presented and discussed. Following that, a taxonomy of the current progress of SFA is proposed. We classify improved versions of SFA into six categories, including dual-input SFA (DISFA), online slow feature analysis (OSFA), probabilistic SFA (PSFA), multimode SFA, nonlinear SFA, and discrete labeled SFA. For each category, we illustrate its main ideas, mathematical principles, and applicable scenarios. In addition, the practical applications of SFA are summarized and presented. Finally, we bring new insights into SFA according to its research status and provide potential research directions, which may serve as a good reference for promoting future work.
Lecture 5 : Waves in shallow water , part I : the theory

We saw in Lecture 2 a linearized model of water waves, in which all waves (necessarily) have very small amplitude, and the longest waves (with wavenumbers near k = 0) propagate with essentially no dispersion. The next step towards a more realistic description of water waves is to introduce weakly dispersive and weakly nonlinear effects. The derivation of the Korteweg – de Vries (KdV) equation, which follows this approach, is the topic of the first part of this lecture. The properties of the KdV equation are presented in a second part, followed by a third part which discusses the accuracy of this equation for water waves in real-life settings and its relevance as an approximation of the water wave equations. Let us recall the notations used so far:
Neural Basis of the Implicit Learning of Complex Artificial Grammar with Nonadjacent Dependencies

Abstract The capacity for the implicit learning/processing of complex grammar with nonadjacent dependencies is an important feature of human language learning. In this fMRI study, using an implicit AGL paradigm, we explored the neural basis of the implicit learning of the nonadjacent dependency rule, disentangling from sequence-based chunk knowledge (i.e., local sequential regularities or substring) by focusing on the low chunk strength items (which were naturally less similar to training strings), based on tracking neural responses during training and test phases. After listening to and memorizing a series of strings of 10 syllables generated from nonadjacent artificial grammar in the training phase, participants implicitly acquired the knowledge of grammar and chunks. Regarding grammaticality, Broca's area was specifically related to low chunk strength grammatical strings relative to nongrammatical strings in the test phase. This region showed decreased activity with time in the training phase, and a lesser decrease in activity was associated with higher performance in grammar learning. Furthermore, Broca's area showed significantly higher strength of functional connectivity with the left superior temporal gyrus in the low chunk strength grammatical string compared with nongrammatical strings, and this functional connectivity increased with the training time. For the chunks, the performance of accurate discrimination of high chunk strength from low chunk strength nongrammatical strings was predicted by hippocampal activity in the training phase. Converging evidence from the training and test phases showed that Broca's area and its functional connectivity with the left superior temporal gyrus were engaged in the implicit learning/processing of the nonadjacent dependency rule, separating the effects of chunks.
Long-term health-related quality of life, healthcare utilisation and back-to-work activities in intensive care unit survivors: Prospective confirmatory study from the Frisian aftercare cohort

Purpose More substantial information on recovery after Intensive Care Unit (ICU) admission is urgently needed. In a previous retrospective study, the proportion of non-recovery patients was 44%. The aim of this prospective follow-up study was to evaluate changes in Health-Related Quality of Life (HRQoL) in the first year after ICU-admission. Methods Long-stay adult ICU-patients (≥ 48 hours) were included. HRQoL was evaluated with the Dutch translation of the RAND-36 item Health Survey (RAND-36) at baseline via proxy measurement, and at three, six, and twelve months after ICU admission. Subsequently, the relation between physical functioning, healthcare utilisation, and work activities was explored. Results A total of 81 patients were included in this study. Fifty-five percent of patients did not meet criteria for full recovery and were allocated to the Non Recovery (NR)-group (Physical Functioning domain-score: 35 [15–55]). Baseline physical HRQoL differed significantly between the Recovery (R) and NR-group. Patients in the NR-group received home care more often and had higher healthcare utilisation (44 versus 17% in the first three months post-ICU, p = 0.013). Only fourteen percent of NR-patients were able to participate in work activities. Moreover, NR-patients persistently showed impaired overall HRQoL throughout the year after critical illness. Conclusions Limited recovery in ICU survivors is reflected in overall impaired HRQoL, as well as in far-reaching consequences for patients’ healthcare needs and their ability to reintegrate into society. In our study, baseline HRQoL appeared to be an important predictor of long-term outcomes, but not Clinical Frailty Scale (CFS) score. And, (proxy-derived) HRQoL may help to identify patients at risk of long-term non-recovery.