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The metabolic syndrome, which covers a wide variety of pathological concerns, is rapidly becoming a global pandemic. This syndrome is difficult to treat pharmacologically. Physiotherapy techniques, which have both local and systemic effects, can be employed as a suitable substitute. The purpose of this study was to investigate the therapeutic effects of a program of simultaneous physiotherapy that included migrant transcranial magnetic stimulation (TMS) and the exposure to an alternating low-frequency electrostatic field (LFEF) in the treatment of metabolic syndrome patients. Ninety patients were randomly assigned to three study groups. While continuing the usual drug therapy the first group (30 patients) received LFEF intervention, the second group (30 patients) received TMS, and the third group (30 patients) underwent the simultaneous use of these non-invasive techniques (LFEF + TMS). All treatments involved 10 sessions with daily frequency. In all the patients before and after treatment body weight, blood pressure parameters, levels of insulin, cortisol, glucose, total cholesterol, high density lipoproteins, malondialdehyde, and Schiff bases, the activity of the antioxidant enzymes catalase and of the superoxide dismutase were studied. The changes in the outcomes assessed revealed a different reaction to therapy with LFEF or TMS, as well as a greater benefit when both treatments were used at the same time. A simultaneous LFEF and TMS intervention seems a promising resource for the treatment of the metabolic syndrome, particularly of the lipid and carbohydrate metabolism disorders. However, further studies are needed to confirm these findings and investigate the underlying mechanisms.

Abstract Contrary to expert readers, children learning to read have limited ability to preprocess letters in parafoveal vision. Parafoveal letters induce crowding cost: the features of neighboring letters interfere with target letter identification. We longitudinally studied the weight of parafoveal cost and benefit in two group of children (N = 42), during their first school year (Group 1) and at the end of second school year (Groupe 2). Using a novel digit-tracking method, a blurred text was presented and rendered unblurred by touching the screen, allowing the user to discover a window of visible text as the finger moved along it. We compared two conditions: (1) a large window, where crowding was enhanced by the presence of parafoveal information; (2) a small window, where crowding was suppressed by blurred parafoveal information. Finger kinematics were simultaneously recorded. We found that at the beginning of first-grade, digital fixations - brief slowing or stopping of the finger on a specific point - are significantly longer in the large compared to the small window condition, as parafoveal crowding increases text processing difficulty. This effect diminishes and disappears at the end of second-grade as reading performance improves. In the large window condition, longer digital saccades - rapid movements of the finger changing position - appear by the end of first grade suggesting that parafoveal exposure become more beneficial than harmful when children acquire basic reading skills. Our results show that in beginning readers, crowding has a cognitive cost that interfere with the speed of the learning reading process. Our findings are relevant to the field of education by showing that visual crowding in first grade should not be underestimated.

Doping is considered a critical deviant behavior in competitive sports, and particularly in cycling, even though the phenomenon remains limited in sports in general. Previous qualitative studies have contributed to identify situations of vulnerability to doping in athletes. However, much of the research tends to focus on singular dimensions of vulnerability, such as physical or psychological aspects. The present study aimed to extend existing knowledge by concurrently exploring and attempting to categorize different types of situations of vulnerability that predispose elite cyclists to engage in doping. Ten high-level French-speaking doped cyclists were recruited (Mage = 49; SD = 14.63, two women). Semi-structured interviews were conducted. Both deductive and inductive thematic analyses were performed. Our results highlighted four types of vulnerability situations: (a) psychological (e.g., negative affects, maladaptive motivation, depression), (b) physical (e.g., exhaustion, impairments, injuries), (c) relational (e.g., organized doping, control, psychological or sexual harassment, social approval of doping), and (d) contextual (e.g., cycling culture, weather conditions, competitive stakes). By providing a clearer categorization of the situations of vulnerability that converge toward doping in sport, this comprehensive study allows for a holistic understanding of the various vulnerabilities. It paves the way for future research on related vulnerabilities and dispositional factors. Practically, it should also improve doping screening and prevention, and provide more favorable conditions for athletes.

The development of new drugs is a lengthy and complex process regarding its conception and ideation, passing through in silico studies, synthesis, in vivo studies, clinical trials, approval, and commercialization, with an exceptionally low success rate. The lack of efficacy, safety, and suboptimal pharmacokinetic parameters are commonly identified as significant challenges in the discovery of new drugs. To help address these challenges, various approaches have been explored in medicinal chemistry, including the use of prodrug strategies. As a well-established approach, prodrug design remains the best option for improving physicochemical properties, reducing toxicity, and increasing selectivity, all while minimizing costs and saving on biological studies. This review article aims to analyze the current advances using the prodrug approach that has allowed the advance of drug candidates to clinical trials in the last 10 years. The approaches presented here aim to inspire further molecular optimization processes and highlight the potential of this strategy to facilitate the advancement of new compounds to clinical study phases.

While extinction risk categorization is fundamental for building robust conservation planning for marine fishes, empirical data on occurrence and vulnerability to disturbances are still lacking for most marine teleost fish species, preventing the assessment of their International Union for the Conservation of Nature (IUCN) status. In this article, we predicted the IUCN status of marine fishes based on two machine learning algorithms, trained with available species occurrences, biological traits, taxonomy, and human uses. We found that extinction risk for marine fish species is higher than initially estimated by the IUCN, increasing from 2.5% to 12.7%. Species predicted as Threatened were mainly characterized by a small geographic range, a relatively large body size, and a low growth rate. Hotspots of predicted Threatened species peaked mainly in the South China Sea, the Philippine Sea, the Celebes Sea, the west coast Australia and North America. We also explored the consequences of including these predicted species' IUCN status in the prioritization of marine protected areas through conservation planning. We found a marked increase in prioritization ranks for subpolar and polar regions despite their low species richness. We suggest to integrate multifactorial ensemble learning to assess species extinction risk and offer a more complete view of endangered taxonomic groups to ultimately reach global conservation targets like the extending coverage of protected areas where species are the most vulnerable.

The metabolic syndrome, which covers a wide variety of pathological concerns, is rapidly becoming a global pandemic. This syndrome is difficult to treat pharmacologically. Physiotherapy techniques, which have both local and systemic effects, can be employed as a suitable substitute. The purpose of this study was to investigate the therapeutic effects of a program of simultaneous physiotherapy that included migrant transcranial magnetic stimulation (TMS) and the exposure to an alternating low-frequency electrostatic field (LFEF) in the treatment of metabolic syndrome patients. Ninety patients were randomly assigned to three study groups. While continuing the usual drug therapy the first group (30 patients) received LFEF intervention, the second group (30 patients) received TMS, and the third group (30 patients) underwent the simultaneous use of these non-invasive techniques (LFEF + TMS). All treatments involved 10 sessions with daily frequency. In all the patients before and after treatment body weight, blood pressure parameters, levels of insulin, cortisol, glucose, total cholesterol, high density lipoproteins, malondialdehyde, and Schiff bases, the activity of the antioxidant enzymes catalase and of the superoxide dismutase were studied. The changes in the outcomes assessed revealed a different reaction to therapy with LFEF or TMS, as well as a greater benefit when both treatments were used at the same time. A simultaneous LFEF and TMS intervention seems a promising resource for the treatment of the metabolic syndrome, particularly of the lipid and carbohydrate metabolism disorders. However, further studies are needed to confirm these findings and investigate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Distance learning has an impact on moving image education. The videos and the interactions between participants are changed by the distance. The analysis of the activity of two teachers, applied to four virtual classroom sessions given at the university during the confinement (2021), highlights two essential elements: the management of material and legal problems; the impact on mediation. Technical and pedagogical remedial solutions are possible. They open perspectives to accompany the gaze and educate to moving images in a distance learning context. These solutions take into account the impact of distance on the globality of the teachers’ professional gestures and invite to rethink the didactics of visual literacy.

Retail dealers whose major business is in the products of a single manufacturer form an organizational system with that manufacturer. For this system to operate effectively as an integrated whole and to compete with similar manufacturer-dealer systems, certain administrative functions must be performed for the system, over and above the administration of the formally separate manufacturer and dealer organizations. This paper examines the interdependent roles of manufacturer and dealer and the administrative attempts to control quasiindependent units. [ABSTRACT FROM AUTHOR]

Abstract Awake surgery for low-grade gliomas is currently considered the best procedure to improve the extent of resection and guarantee a "worth living life" for patients, meaning avoiding not only motor but also cognitive deficits. However, tumors located in the right hemisphere, especially in the right frontal lobe, are still rarely operated on in awake condition; one of the reasons possibly being that there is little information in the literature describing the rates and nature of long-lasting neuropsychological deficits following resection of right frontal glioma. To investigate long-term cognitive deficits after awake surgery in right frontal IDH-mutated glioma. We retrospectively analyzed a consecutive series of awake surgical resections between 2012 and 2020 for right frontal IDH-mutated glioma. We studied the patients' subjective complaints and objective neuropsychological evaluations, both before and after surgery. Our results were then put in perspective with the literature. Twenty surgical cases (including 5 cases of redo surgery) in eighteen patients (medium age: 42.5 [range 26–58]) were included in the study. The median preoperative volume was 37 cc; WHO grading was II, III and IV in 70%, 20%, and 10% of cases, respectively. Preoperatively, few patients had related subjective cognitive or behavioral impairment, while evaluations revealed mild deficits in 45% of cases, most often concerning executive functions, attention, working memory and speed processing. Immediate postoperative evaluations showed severe deficits of executive functions in 75% of cases but also attentional deficits (65%), spatial neglect (60%) and behavioral disturbances (apathy, aprosodia/amimia, emotional sensitivity, anosognosia). Four months after surgery, although psychometric z-scores were unchanged at the group level, individual evaluations showed a slight decrease of performance in 9/20 cases for at least one of the following domains: executive functions, speed processing, attention, semantic cognition, social cognition. Our results are generally consistent with those of the literature, confirming that the right frontal lobe is a highly eloquent area and suggesting the importance of operating these patients in awake conditions.

BackgroundTesticular sperm extraction (TESE) is an essential therapeutic tool for the management of male infertility. However, it is an invasive procedure with a success rate up to 50%. To date, no model based on clinical and laboratory parameters is sufficiently powerful to accurately predict the success of sperm retrieval in TESE. ObjectiveThe aim of this study is to compare a wide range of predictive models under similar conditions for TESE outcomes in patients with nonobstructive azoospermia (NOA) to identify the correct mathematical approach to apply, most appropriate study size, and relevance of the input biomarkers. MethodsWe analyzed 201 patients who underwent TESE at Tenon Hospital (Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris), distributed in a retrospective training cohort of 175 patients (January 2012 to April 2021) and a prospective testing cohort (May 2021 to December 2021) of 26 patients. Preoperative data (according to the French standard exploration of male infertility, 16 variables) including urogenital history, hormonal data, genetic data, and TESE outcomes (representing the target variable) were collected. A TESE was considered positive if we obtained sufficient spermatozoa for intracytoplasmic sperm injection. After preprocessing the raw data, 8 machine learning (ML) models were trained and optimized on the retrospective training cohort data set: The hyperparameter tuning was performed by random search. Finally, the prospective testing cohort data set was used for the model evaluation. The metrics used to evaluate and compare the models were the following: sensitivity, specificity, area under the receiver operating characteristic curve (AUC-ROC), and accuracy. The importance of each variable in the model was assessed using the permutation feature importance technique, and the optimal number of patients to include in the study was assessed using the learning curve. ResultsThe ensemble models, based on decision trees, showed the best performance, especially the random forest model, which yielded the following results: AUC=0.90, sensitivity=100%, and specificity=69.2%. Furthermore, a study size of 120 patients seemed sufficient to properly exploit the preoperative data in the modeling process, since increasing the number of patients beyond 120 during model training did not bring any performance improvement. Furthermore, inhibin B and a history of varicoceles exhibited the highest predictive capacity. ConclusionsAn ML algorithm based on an appropriate approach can predict successful sperm retrieval in men with NOA undergoing TESE, with promising performance. However, although this study is consistent with the first step of this process, a subsequent formal prospective multicentric validation study should be undertaken before any clinical applications. As future work, we consider the use of recent and clinically relevant data sets (including seminal plasma biomarkers, especially noncoding RNAs, as markers of residual spermatogenesis in NOA patients) to improve our results even more.