SpadaHC: a database to improve the classification of variants in hereditary cancer genes in the Spanish population.

Accurate classification of genetic variants is crucial for clinical decision-making in hereditary cancer. In Spain, genetic diagnostic laboratories have traditionally approached this task independently due to the lack of a dedicated resource. Here we present SpadaHC, a web-based database for sharing variants in hereditary cancer genes in the Spanish population. SpadaHC is implemented using a three-tier architecture consisting of a relational database, a web tool and a bioinformatics pipeline. Contributing laboratories can share variant classifications and variants from individuals in Variant Calling Format (VCF) format. The platform supports open and restricted access, flexible dataset submissions, automatic pseudo-anonymization, VCF quality control, variant normalization and liftover between genome builds. Users can flexibly explore and search data, receive automatic discrepancy notifications and access SpadaHC population frequencies based on many criteria. In February 2024, SpadaHC included 18 laboratory members, storing 1.17 million variants from 4306 patients and 16 343 laboratory classifications. In the first analysis of the shared data, we identified 84 genetic variants with clinically relevant discrepancies in their classifications and addressed them through a three-phase resolution strategy. This work highlights the importance of data sharing to promote consistency in variant classifications among laboratories, so patients and family members can benefit from more accurate clinical management. Database URL: https://spadahc.ciberisciii.es/.

On-Machine LTS Integration for Layer-Wise Surface Quality Characterization in MEX/P.

Material Extrusion (MEX) currently stands as the most widespread Additive Manufacturing (AM) process, but part quality deficiencies remain a barrier to its generalized industrial adoption. Quality control in MEX is a complex task as extrusion performance impacts the consistency of mechanical properties and the surface finish, dimensional accuracy, and geometric precision of manufactured parts. Recognizing the need for early-stage process monitoring, this study explores the potential of integrating Laser Triangulation Sensors (LTS) into MEX/P manufacturing equipment for layer-wise 3D inspections. Using a double-bridge architecture, an LTS-based sub-micrometric inspection system operates independently from the manufacturing process, enabling comprehensive digitization and autonomous reconstruction of the target layer's topography. Surface texture is then computed using standardized indicators and a new approach that provides insight into layer quality uniformity. A case study evaluating two alternative extruder head designs demonstrates the efficacy of this integrated approach for layer quality characterization. Implementing a generalized layer-wise procedure based on this integration can significantly mitigate quality issues in MEX manufacturing and optimize process parameter configurations for enhanced performance.

Locomotor and Physiological Demands of Small-Sided Soccer Games in Wildcard and Regular Players: Effects of Goalkeepers and Type of Wildcard.

BACKGROUND: Small-sided games (SSGs) are frequent training drills in soccer. This study investigated whether type of game (ie, with/without goalkeepers) and wildcard ( without vs internal vs external wildcard) impact the physiological (heartrate [HR]) and locomotor (total distance [TD] covered) demands in regular and wildcard players and to evaluate between-player and within-player variability. HYPOTHESIS: Demands are influenced by wildcard and game type, with higher demand (distance covered at high intensities and sprint speed) in regular players and with higher variability in SSG with wildcard players. STUDY DESIGN: Descriptive/comparative study. LEVEL OF EVIDENCE: Level 4. METHODS: Twenty-four soccer players completed 6 SSG as 3 versus 3 without (NG) or with (GK) goalkeepers, and with internal (NG+IW and GK+IW) and external (NG+EW and GK+EW) wildcard. Average HR (HRavg), rate of perceived exertion, and locomotor demands (TD, medium [MID = 7.0-13.9 km h-1], high [HID = 14.0-20.9 km h-1] and sprint [SPD >21.0 km h-1] distance and peak speed [PS]) were registered. RESULTS: The inclusion of GK and internal wildcard led to decreased HRavg and TD in regular players. Wildcard players positioned internally exhibited higher TD, PS, and lower HRavg than externally positioned wildcards. Regular players demonstrated higher TD, PS, MID, HID, HRavg and time spent in Z3 (>90% HRmax) compared with wildcard players in SSG played with external wildcard. Regular and wildcard players displayed great between- and within-player variability in high-intensity metrics. CONCLUSION: Specific game type and wildcard inclusion impact the physiological and locomotor demands in SSG, with variations observed between regular and wildcard players. CLINICAL RELEVANCE: This study provides comprehensive information on the physiological and locomotor demands of SSG depending on the inclusion and position of goalkeepers and wildcards, which can be useful for strength and conditioning coaches when designing specific training tasks, individualizing training load and applying return-to-play programs.

Comparison of the ABC and ACMG systems for variant classification.

The ABC and ACMG variant classification systems were compared by asking mainly European clinical laboratories to classify variants in 10 challenging cases using both systems, and to state if the variant in question would be reported as a relevant result or not as a measure of clinical utility. In contrast to the ABC system, the ACMG system was not made to guide variant reporting but to determine the likelihood of pathogenicity. Nevertheless, this comparison is justified since the ACMG class determines variant reporting in many laboratories. Forty-three laboratories participated in the survey. In seven cases, the classification system used did not influence the reporting likelihood when variants labeled as "maybe report" after ACMG-based classification were included. In three cases of population frequent but disease-associated variants, there was a difference in favor of reporting after ABC classification. A possible reason is that ABC step C (standard variant comments) allows a variant to be reported in one clinical setting but not another, e.g., based on Bayesian-based likelihood calculation of clinical relevance. Finally, the selection of ACMG criteria was compared between 36 laboratories. When excluding criteria used by less than four laboratories (<10%), the average concordance rate was 46%. Taken together, ABC-based classification is more clear-cut than ACMG-based classification since molecular and clinical information is handled separately, and variant reporting can be adapted to the clinical question and phenotype. Furthermore, variants do not get a clinically inappropriate label, like pathogenic when not pathogenic in a clinical context, or variant of unknown significance when the significance is known.

Plyometric Jump Training Effects on Maximal Strength in Soccer Players: A Systematic Review with Meta-analysis of Randomized-Controlled Studies.

BACKGROUND: Maximal strength may contribute to soccer players' performance. Several resistance training modalities offer the potential to improve maximal strength. During recent years, a large number of plyometric jump training (PJT) studies showed evidence for maximal strength improvements in soccer players. However, a comprehensive summary of the available data is lacking. OBJECTIVE: To examine the effects of PJT compared with active, passive or intervention controls on the maximal strength of soccer players, irrespective of age, sex or competitive level. METHODS: To perform a systematic review with meta-analysis following PRISMA 2020. Three electronic databases (PubMed, Web of Science, and SCOPUS) were systematically searched. Studies published from inception until March 2023 were included. A PICOS approach was used to rate studies for eligibility. The PEDro scale was used to assess risk of bias. Meta-analyses were performed using the DerSimonian and Laird random-effects model if ≥ 3 studies were available. Moderator and sensitivity analyses were performed, and meta-regression was conducted when ≥ 10 studies were available for a given comparison. We rated the certainty of evidence using GRADE. RESULTS: The search identified 13,029 documents, and from these 30 studies were eligible for the systematic review, and 27 for the meta-analyses. Overall, 1,274 soccer players aged 10.7-25.0 years participated in the included studies. Only one study recruited females. The PJT interventions lasted between 5 and 40 weeks (median = 8 weeks), with 1-3 weekly sessions. Compared to controls, PJT improved maximal dynamic strength (18 studies, 632 participants [7 females], aged 12.7-24.5 y; effect size [ES] = 0.43, 95% confidence interval [CI] = 0.08-0.78, p = 0.017, impact of statistical heterogeneity [I2] = 77.9%), isometric strength (7 studies; 245 participants, males, aged 11.1-22.5 y; ES = 0.58, 95% CI = 0.28-0.87, p < 0.001, I2 = 17.7%), and isokinetic peak torque (5 studies; 183 participants, males, aged 12.6-25.0 y; ES = 0.51, 95% CI = 0.22-0.80, p = 0.001, I2 = 0.0%). The PJT-induced maximal dynamic strength changes were independent of participants' age (median = 18.0 y), weeks of intervention (median = 8 weeks), and total number of training sessions (median = 16 sessions). The certainty of evidence was considered low to very low for the main analyses. CONCLUSIONS: Interventions involving PJT are more effective to improve maximal strength in soccer players compared to control conditions involving traditional sport-specific training. Trial Registration The trial registration protocol was published on the Open Science Framework (OSF) platform in December 2022, with the following links to the project ( https://osf.io/rpxjk ) and to the registration ( https://osf.io/3ruyj ).

In vivo cyclic overexpression of Yamanaka factors restricted to neurons reverses age-associated phenotypes and enhances memory performance.

In recent years, there has been success in partially reprogramming peripheral organ cells using cyclic Yamanaka transcription factor (YF) expression, resulting in the reversal of age-related pathologies. In the case of the brain, the effects of partial reprogramming are scarcely known, and only some of its effects have been observed through the widespread expression of YF. This study is the first to exclusively partially reprogram a specific subpopulation of neurons in the cerebral cortex of aged mice. The in vivo model demonstrate that YF expression in postmitotic neurons does not dedifferentiate them, and it avoids deleterious effects observed with YF expression in other cell types. Additionally, our study demonstrates that only cyclic, not continuous, expression of YF result in a noteworthy enhancement of cognitive function in adult mice. This enhancement is closely tied to increased neuronal activation in regions related to memory processes, reversed aging-related epigenetic markers and to increased plasticity, induced by the reorganization of the extracellular matrix. These findings support the therapeutic potential of targeted partial reprogramming of neurons in addressing age-associated phenotypes and neurodegenerative diseases correlated with aging.

In-and-out Technique: An In-house Efficient Predictive Hole Fabrication Workflow.

Virtual surgical planning (VSP) and three-dimensional (3D) printing can increase precision and reduce surgical time in craniofacial reconstruction. However, the elevated cost and manufacturing time of outsourced workflows is increasing the development of in-house solutions. One of the main challenges in in-house workflows is to create cutting guides that hold plate position information. This is due to the fact that hospitals usually lack the infrastructure required to design and 3D print custom-made plates. Including plate-positioning information in resection guides is especially relevant in complex reconstructions and when tumor extension limits plate placement before resection. Current in-house workflows revolve around the idea of 3D scanning the bent plate's shape and to fuse it with the VSP. The goal of this article is to share our technique to transfer plate position information to resection guides. Our protocol uses a 3D model of the reconstruction as an intermediate step to transfer the plate position of a bent stock reconstruction plate to cutting guides. Two patients who required mandibular reconstruction with fibula flap are presented to illustrate the technique. This workflow requires a 3D-printed model of the desired outcome, cutting guides, and a stock plate. Results were satisfactory in terms of cutting location and angulation, plate adaptation and condylar position. This technique allows for a simple, safe, cheap, and quick alternative to add reconstruction plate information to cutting guides.

Life cycle assessment of a LiFePO4 cylindrical battery.

Reduction of the environmental impact, energy efficiency and optimization of material resources are basic aspects in the design and sizing of a battery. The objective of this study was to identify and characterize the environmental impact associated with the life cycle of a 7.47 Wh 18,650 cylindrical single-cell LiFePO4 battery. Life cycle assessment (LCA), the SimaPro 9.1 software package, the Ecoinvent 3.5 database and the ReCiPe 2016 impact assessment method were used for this purpose. Environmental impacts were modelled and quantified using the dual midpoint-endpoint approach and the "cradle-to-gate" model. The results showed the electrodes to be the battery components with the highest environmental impact (41.36% of the total), with the negative electrode being the most unfavourable (29.8 mPt). The ageing, calibration and testing process (53.97 mPt) accounts for 97.21% of the total impact associated with the production process's consumption of energy, and 41.20% of the total impact associated with the battery. This new knowledge will allow a more detailed view of the environmental impact of cylindrical cell LiFePO4 batteries, favouring the identification of critical points to enhance their sustainable production.

Is there a preferred platinum and fluoropyrimidine regimen for advanced HER2-negative esophagogastric adenocarcinoma? Insights from 1293 patients in AGAMENON-SEOM registry.

BACKGROUND: The optimal chemotherapy backbone for HER2-negative advanced esophagogastric cancer, either in combination with targeted therapies or as a comparator in clinical trials, is uncertain. The subtle yet crucial differences in platinum-based regimens' safety and synergy with combination treatments need consideration. METHODS: We analyzed cases from the AGAMENON-SEOM Spanish registry of HER2-negative advanced esophagogastric adenocarcinoma treated with platinum and fluoropyrimidine from 2008 to 2021. This study focused exclusively on patients receiving one of the four regimens: FOLFOX (5-FU and oxaliplatin), CAPOX (capecitabine and oxaliplatin), CP (capecitabine and cisplatin) and FP (5-FU and cisplatin). The aim was to determine the most effective and tolerable platinum and fluoropyrimidine-based chemotherapy regimen and to identify any prognostic factors. RESULTS: Among 1293 patients, 36% received either FOLFOX (n = 468) or CAPOX (n = 466), 20% CP (n = 252), and 8% FP (n = 107). FOLFOX significantly increased PFS (progression free survival) compared to CP, with a hazard ratio of 0.73 (95% CI 0.58-0.92, p = 0.009). The duration of treatment was similar across all groups. Survival outcomes among regimens were similar, but analysis revealed worse ECOG-PS (Eastern Cooperative Oncology Group-Performance Status), > 2 metastatic sites, bone metastases, hypoalbuminemia, higher NLR (neutrophil-to-lymphocyte ratio), and CP regimen as predictors of poor PFS. Fatigue was common in all treatments, with the highest incidence in FOLFOX (77%), followed by FP (72%), CAPOX (68%), and CP (60%). Other notable toxicities included neuropathy (FOLFOX 69%, CAPOX 62%), neutropenia (FOLFOX 52%, FP 55%), hand-foot syndrome in CP (46%), and thromboembolic events (FP 12%, CP 11%). CONCLUSIONS: FOLFOX shown better PFS than CP. Adverse effects varied: neuropathy was more common with oxaliplatin, while thromboembolism was more frequent with cisplatin.

Prostate Cancer and the Mevalonate Pathway.

Antineoplastic therapies for prostate cancer (PCa) have traditionally centered around the androgen receptor (AR) pathway, which has demonstrated a significant role in oncogenesis. Nevertheless, it is becoming progressively apparent that therapeutic strategies must diversify their focus due to the emergence of resistance mechanisms that the tumor employs when subjected to monomolecular treatments. This review illustrates how the dysregulation of the lipid metabolic pathway constitutes a survival strategy adopted by tumors to evade eradication efforts. Integrating this aspect into oncological management could prove valuable in combating PCa.

Comparative Effects of Two High-Intensity Intermittent Training Programs on Sub-Elite Male Basketball Referees' Fitness Levels.

This study aimed to compare the effects of an 8-week short-term training program, comprising repeated sprints or running-based high-intensity intermittent training (HIIT), on the aerobic fitness and repeated sprint ability (RSA) performance of sub-elite basketball referees. Twenty male referees participated in supervised training sessions twice a week. They were randomly assigned to either the RSA-based group (RSAG) or the running-based HIIT group (HIITG). The RSAG conducted 3-4 sets of 8 × 20-m all-out sprints, while the HIITG performed 2-3 sets of 6 × 20-s runs at 90% of their maximal velocity achieved in the 30-15 intermittent fitness test (30-15IFT). Referees underwent a graded exercise test on a treadmill, the 30-15IFT, and an RSA test before and after the training program. Both groups showed significant improvement (~3%) in the fastest (22.6 ± 1.4 vs. 23.4 ± 1.7 and 22.0 ±1.9 vs. 22.4 ± 1.7 km·h-1 in RSAG and HIITG, respectively) and mean (21.5 ± 1.2 vs. 22.4 ± 1.4 and 21.3 ± 1.8 vs. 21.7 ± 1.6 km·h-1 in RSAG and HIITG, respectively) sprint velocity of the RSA test (p < 0.05). Moreover, positive changes (p < 0.05) were observed in the 30-15IFT maximal velocity (18.6 ± 1.1 vs. 19.3 ± 1.0 and 19.4 ± 0.9 vs. 20.5 ± 0.9 km·h-1 in RSAG and HIITG, respectively). In conclusion, an 8-week training intervention using either RSA or running-based HIIT led to similar improvements in referees' RSA performance and specific aerobic fitness measures. These findings could assist in devising tailored training programs for basketball referees.

Digital Microscopy Augmented by Artificial Intelligence to Interpret Bone Marrow Samples for Hematological Diseases.

Analysis of bone marrow aspirates (BMAs) is an essential step in the diagnosis of hematological disorders. This analysis is usually performed based on a visual examination of samples under a conventional optical microscope, which involves a labor-intensive process, limited by clinical experience and subject to high observer variability. In this work, we present a comprehensive digital microscopy system that enables BMA analysis for cell type counting and differentiation in an efficient and objective manner. This system not only provides an accessible and simple method to digitize, store, and analyze BMA samples remotely but is also supported by an Artificial Intelligence (AI) pipeline that accelerates the differential cell counting process and reduces interobserver variability. It has been designed to integrate AI algorithms with the daily clinical routine and can be used in any regular hospital workflow.

ARGEN SHOCK: Mortality related to the use of Swan Ganz and to the hemodynamic pattern found in patients with AMICS.

The Swan Ganz Catheter (SGC) allows us to diagnose different types of cardiogenic shock (CS). OBJECTIVES: 1) Determine the frequency of use of SGC, 2) Analyze the clinical characteristics and mortality according to its use and 3) Analyze the prevalence, clinical characteristics and mortality according to the type of Shock. METHODS: The 114 patients (p) from the ARGEN SHOCK registry were analyzed. A "classic" pattern was defined as PCP > 15 mm Hg, CI < 2.2 L/min/ m2, SVR > 1,200 dynes × sec × cm-5. A "vasoplegic/mixed" pattern was defined when p did not meet the classic definition. CS due to right ventricle (RV) was excluded. RESULTS: SGC was used in 35 % (n:37). There were no differences in clinical characteristics according to SGC use, but those with SGC were more likely to receive dobutamine, levosimendan, and intra aortic balloon pump (IABP). Mortality was similar (59.4 % vs 61.3 %). The pattern was "classic" in 70.2 %. There were no differences in clinical characteristics according to the type of pattern or the drugs used. Mortality was 54 % in patients with the classic pattern and 73 % with the mixed/vasoplegic pattern, but the difference did not reach statistical significance (p:0.23). CONCLUSIONS: SGC is used in one third of patients with CS. Its use does not imply differences in the drugs used or in mortality. Most patients have a classic hemodynamic pattern. There are no differences in mortality or in the type of vasoactive agents used according to the CS pattern found.

Validation of ActiGraph and Fitbit in the assessment of energy expenditure in Huntington's disease.

BACKGROUND: Consumer and research activity monitors have become popular because of their ability to quantify energy expenditure (EE) in free-living conditions. However, the accuracy of activity trackers in determining EE in people with Huntington's Disease (HD) is unknown. RESEARCH QUESTION: Can the ActiGraph wGT3X-B or the Fitbit Charge 4 accurately measure energy expenditure during physical activity, in people with HD compared to Indirect Calorimetry (IC) (Medisoft Ergo Card)? METHODS: We conducted a cross-sectional, observational study with fourteen participants with mild-moderate HD (mean age 55.7 ± 11.4 years). All participants wore an ActiGraph and Fitbit during an incremental test, running on a treadmill at 3.2 km/h and 5.2 km/h for three minutes at each speed. We analysed and compared the accuracy of EE estimates obtained by Fitbit and ActiGraph against the EE estimates obtained by a metabolic cart, using with Intra-class correlation (ICC), Bland-Altman analysis and correlation tests. RESULTS: A significant correlation and a moderate reliability was found between ActiGraph and IC for the incremental test (r = 0.667)(ICC=0.633). There was a significant correlation between Fitbit and IC during the incremental test (r = 0.701), but the reliability was poor at all tested speeds in the treadmill walk. Fitbit significantly overestimated EE, and ActiGraph underestimated EE compared to IC, but ActiGraph estimates were more accurate than Fitbit in all tests. SIGNIFICANCE: Compared to IC, Fitbit Charge 4 and ActiGraph wGT3X-BT have reduced accuracy in estimating EE at slower walking speeds. These findings highlight the need for population-specific algorithms and validation of activity trackers.

Sumoylation in astrocytes induces changes in the proteome of the derived small extracellular vesicles which change protein synthesis and dendrite morphology in target neurons.

Emerging evidence highlights the relevance of the protein post-translational modification by SUMO (Small Ubiquitin-like Modifier) in the central nervous system for modulating cognition and plasticity in health and disease. In these processes, astrocyte-to-neuron crosstalk mediated by extracellular vesicles (EVs) plays a yet poorly understood role. Small EVs (sEVs), including microvesicles and exosomes, contain a molecular cargo of lipids, proteins, and nucleic acids that define their biological effect on target cells. Here, we investigated whether SUMOylation globally impacts the sEV protein cargo. For this, sEVs were isolated from primary cultures of astrocytes by ultracentrifugation or using a commercial sEV isolation kit. SUMO levels were regulated: 1) via plasmids that over-express SUMO, or 2) via experimental conditions that increase SUMOylation, i.e., by using the stress hormone corticosterone, or 3) via the SUMOylation inhibitor 2-D08 (2',3',4'-trihydroxy-flavone, 2-(2,3,4-Trihydroxyphenyl)-4H-1-Benzopyran-4-one). Corticosterone and 2-D08 had opposing effects on the number of sEVs and on their protein cargo. Proteomic analysis showed that increased SUMOylation in corticosterone-treated or plasmid-transfected astrocytes increased the presence of proteins related to cell division, transcription, and protein translation in the derived sEVs. When sEVs derived from corticosterone-treated astrocytes were transferred to neurons to assess their impact on protein synthesis using the fluorescence non-canonical amino acid tagging assay (FUNCAT), we detected an increase in protein synthesis, while sEVs from 2-D08-treated astrocytes had no effect. Our results show that SUMO conjugation plays an important role in the modulation of the proteome of astrocyte-derived sEVs with a potential functional impact on neurons.

The formulation and in vitro evaluation of WS Biotin, a novel encapsulated form of D-Biotin with improved water solubility for hair and skin treatment applications.

OBJECTIVE: To develop and evaluate the efficacy of WS Biotin, a novel water-soluble form of D-Biotin, for cosmetic use. METHODS: A new encapsulated form of D-Biotin was developed with the purpose of improving the water solubility of biotin. This novel form of encapsulated biotin was characterized by its physicochemical properties: particle size, D-Biotin content and solubility in water. Also, proliferation and gene expression in vitro tests in cell culture were performed to evaluate its effectiveness in promoting hair growth, an ELISA test was conducted for hair keratinization and skin lightening property was tested by analysing the intracellular melanin content. RESULTS: The developed WS Biotin microcapsules exhibit a particle size range of 2-30 µm with D-Biotin content of ~50% (w/w). The water solubility of WS Biotin was found to be 20-fold greater than free biotin. The obtained in vitro results indicated that WS Biotin enhances the expression of hair-related keratins in hair follicle keratinocytes, as well as the expression of hair growth-promoting genes in dermal papilla cells. Moreover, the melanin content in UVA-exposed epidermal melanocytes was reduced upon exposure to WS Biotin. CONCLUSION: In this work, a novel form of encapsulated biotin, WS Biotin, was developed in order to improve the water solubility of free biotin and was found to be effective for cosmetic use in both hair and skin applications.

OBJECTIF: Développer et évaluer l'efficacité de la WS Biotin, une nouvelle forme hydrosoluble de D-biotine, à usage cosmétique. MÉTHODES: Une nouveau format gélules de D-biotine a été développé dans le but d'améliorer la propriété d'hydrosolubilité de la biotine. Ce nouveau format de gélules de biotine a été caractérisé pour ses propriétés physicochimiques : taille des particules, teneur en D-biotine et solubilité dans l'eau. En outre, des tests in vitro de prolifération et d'expression génique en culture cellulaire ont été réalisés pour évaluer son efficacité à favoriser la croissance des cheveux, un test ELISA a été réalisé pour la kératinisation des cheveux et la propriété d'éclaircissement de la peau a été testée en analysant la teneur en mélanine intracellulaire. RÉSULTATS: Les microgélules de WS Biotin développées présentent une plage de tailles de particules de 2 à 30 micromètres avec une teneur en biotine D d'environ 50 % (p/p). L'hydrosolubilité de WS Biotin s'est avérée 20 fois plus élevée que celle de la biotine libre. Les résultats in vitro obtenus ont indiqué que WS Biotin améliorait l'expression des kératines capillaires dans les kératinocytes des follicules pileux, ainsi que l'expression des gènes favorisant la croissance dans les cellules papillaires dermiques. En outre, la teneur en mélanine dans les mélanocytes épidermiques exposés aux UVA a été réduite lors de l'exposition à WS Biotin. CONCLUSION: Dans ce travail, une nouvelle forme de biotine en gélule, WS Biotin, a été développée afin d'améliorer l'hydrosolubilité de la biotine libre et s'est avérée efficace pour une utilisation cosmétique dans les applications capillaires et cutanées.

A New Set of in Silico Tools to Support the Interpretation of ATM Missense Variants Using Graphical Analysis.

Establishing the pathogenic nature of variants in ATM, a gene associated with breast cancer and other hereditary cancers, is crucial for providing patients with adequate care. Unfortunately, achieving good variant classification is still difficult. To address this challenge, we extended the range of in silico tools with a series of graphical tools devised for the analysis of computational evidence by health care professionals. We propose a family of fast and easy-to-use graphical representations in which the impact of a variant is considered relative to other pathogenic and benign variants. To illustrate their value, the representations are applied to three problems in variant interpretation. The assessment of computational pathogenicity predictions showed that the graphics provide an intuitive view of prediction reliability, complementing and extending conventional numerical reliability indexes. When applied to variant of unknown significance populations, the representations shed light on the nature of these variants and can be used to prioritize variants of unknown significance for further studies. In a third application, the graphics were used to compare the two versions of the ATM-adapted American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines, obtaining valuable information on their relative virtues and weaknesses. Finally, a server [ATMision (ATM missense in silico interpretation online)] was generated for users to apply these representations in their variant interpretation problems, to check the ATM-adapted guidelines' criteria for computational evidence on their variant(s) and access different sources of information.