SIRT2 as a potential new therapeutic target for Alzheimer's disease

Alzheimer's disease is the most common cause of dementia globally with an increasing incidence over the years,bringing a heavy burden to individuals and society due to the lack of an effective treatment.In this context,sirtuin 2,the sirtuin with the highest expression in the brain,has emerged as a potential therapeutic target for neurodegenerative diseases.This review summarizes and discusses the complex roles of sirtuin 2 in different molecular mechanisms involved in Alzheimer's disease such as amyloid and tau pathology,microtubule stability,neuroinflammation,myelin formation,autophagy,and oxidative stress.The role of sirtuin 2 in all these processes highlights its potential implication in the etiology and development of Alzheimer's disease.However,its presence in different cell types and its enormous variety of substrates leads to apparently contra dictory conclusions when it comes to understanding its specific functions.Further studies in sirtuin 2 research with selective sirtuin2 modulators targeting specific sirtuin 2 substrates are necessary to clarify its specific functions under different conditions and to validate it as a novel pharmacological target.This will contribute to the development of new treatment strategies,not only for Alzheimer's disease but also for other neurodegenerative diseases.

Context-dependent role of sirtuin 2 in inflammation

Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.

The immune system:uncharted pathways between senses and the brain

Humans and animals use the classic five senses-sight,hearing,touch,smell,and taste-to detect and monitor their environment,with the sense of position and movement often referred to as the sixth sense.The perception of external signals through the senses is essential to an organism's survival,transmitting signals to the central nervous system(CNS)and prompting physiological changes in other biological systems.In addition to the direct effects of sense-induced mediators in the brain.

Data-driven drug repositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

Data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:Neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous system.These diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual death.Despite the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining currency.This last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.

Interactivity software tools for teaching in ophthalmology

The use of interactive audience software,such as audience response systems(ARS),in medical education has become increasingly popular in recent years.This technology allows instructors to engage students in real time,encouraging active participation and promoting effective learning.The benefits of interactive audience software in medical education include increased student engagement,promotion of active learning,and enhanced learning outcomes.However,there are also several challenges to its implementation,including technical difficulties,careful planning and preparation,over-reliance on technology,and ethical concerns related to privacy and data security.The cost of implementing interactive audience software may also be a barrier for some institutions.This paper specifically reviews six interactive software platforms,including Socrative,Quizizz,Pear Deck,Slido,Wooclap and ClassPoint.These platforms allow for real-time assessment of student understanding,feedback,and participation.They also enable instructors to adjust their teaching strategies based on student responses and feedback.Overall,interactive audience software has shown great potential to enhance learning and engagement in medical education.It is important for instructors to carefully consider the benefits and challenges of its implementation.While the cost of implementing interactive audience software may be a barrier for some institutions,there are free and low-cost options available.

A texture-modified dessert with high nutritional value designed for people with dysphagia:effect of refrigeration and frozen storage

Dysphagia is commonly associated with malnutrition and an increased choking risk.To overcome these complications,food designed for people with dysphagia should have an appropriate texture and a high nutritional value.In this study,six formulations of a strawberry dessert enriched in protein(calcium caseinate)and fiber(wheat dextrin or inulin)were developed using different hydrocolloids(xanthan gum,carboxymethyl cellulose or modified starch)to provide desirable texture and stability.Nutritional value was calculated and total phenolic content and antioxidant activity of the samples were analyzed.Back-extrusion test,rheological measurements and sensory analysis were performed in refrigerated and frozen samples to characterize their textural and viscoelastic properties.The high content in protein(14.7 g/100 g)and fiber(7.9-8.7 g/100 g)made possible to use the claims“high protein”and“high fiber”.Phytochemicals supplied by strawberries contributed to the antioxidant properties of the dessert.Loss tangent ranged 0.28-0.35 for all the formulations,indicating a weak gel behavior,which could be considered safe to swallow.The formulations with dextrin in combination with carboxymethyl cellulose or xanthan gum seemed to be less susceptible to structural changes during frozen storage.This work provides insights for the development of a nutrient-dense dessert that meets the requirements of people with dysphagia.

Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resilience in Tg2576 mice.

Global prevalence and gender inequalities in at least 60 min of self-reported moderate-to-vigorous physical activity 1 or more days per week:An analysis with 707,616 adolescents

Background:Guidelines recommend that adolescents should accumulate an average of 60 min per day of moderate-to-vigorous physical activity(MVPA).However,using only this cut-off could hide important information.For instance,from a population-level point of view,increasing physical activity for those with no or low physical activity could provide more health benefits than increasing physical activity for those with intermediate levels.Also,including a more sensitive cut-point of≥1 days per week could be an additional strategy for identifying those with low access/opportunities for physical activity practice.Thus,the current study aims to estimate the prevalence of≥60 min of MVPA≥1 days per week among adolescents globally,and to describe any relevant gender inequalities.Methods:We used representative datasets from 146 countries/territories collected between 2003 and 2019.MVPA was self-reported.Participants were grouped into younger(≤14 years old)and older(>14 years old)adolescents.Crude Poisson regression models were used to identify the relative differences in≥60 min of MVPA≥1 days per week between boys and girls,and random-effects meta-analysis models were used to identify the pooled estimates.Analyses were stratified by country and region.Results:Approximately 80%of both younger and older adolescents reported≥60 min of MVPA≥1 days per week.This prevalence was≥94%in Europe and Central Asia and North America,while the estimates for the other regions were<77%.The prevalence of≥60 min of MVPA≥1 days per week was higher among boys than girls,with the largest differences occurring among the oldest adolescents(Prevalence ratio_(≤14y)=1.04(95%confidence interval(95%CI)):1.03-1.04)vs.Prevalence ratio_(>14y)=1.09(95%CI:1.08-1.10)).Conclusion:Approximately 8 out of 10 adolescents reported accumulating≥60 min of MVPA≥1 days per week,with notable differences between regions.Gender differences were observed in several countries,especially among the oldest adolescents.Priorities for physical activity promotion among adolescents should include increasing access/opportunities for physical activity among those who do not achieve≥60 min of MVPA≥1 days per week and reducing gender inequalities.

Exercise training-induced changes in exerkine concentrations may be relevant to the metabolic control of type 2 diabetes mellitus patients:A systematic review and meta-analysis of randomized controlled trials

Background:This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription.Methods:A systematic search for relevant studies was performed in 3 databases.Randomized controlled trials investigating the effects of exercise training on at least one of the following exerkines were included:adiponectin,apelin,brain-derived neurotrophic factor,fetuin-A,fibroblast growth factor-21,follistatin,ghrelin,interleukin(IL)-6,IL-8,IL-10,IL-15,IL-18,leptin,myostatin,omentin,resistin,retinol-binding protein 4,tumor necrosis factor-α,and visfatin.Results:Forty randomized controlled trials were selected for data extraction(n=2160).Exercise training induces changes in adiponectin,fetuin-A,fibroblast growth factor-21,IL-6,IL-10,leptin,resistin,and tumor necrosis factor-a levels but has no significant effects on apelin,IL-18,and ghrelin compared to controls.Physical exercise training favored large and positive changes in pooled exerkines(i.e.,an overall effect size calculated from several exerkine s)(Hedge’s g=1.02,95%confidence interval(95%CI):0.76-1.28),which in turn were related to changes in glycated hemoglobin(mean difference(MD)=-0.81%,95%CI:-0.95%to-0.67%),fasting glucose(MD=-23.43 mg/dL,95%CI:-30.07 mg/dL to-16.80 mg/dL),waist circumference(MD=-3.04 cm,95%CI:-4.02 cm to-2.07 cm),and body mass(MD=-1.93 kg,95%CI:-2.00 kg to-1.86 kg).Slightly stronger effects were observed with aerobic,resistance,or high-intensity interval protocols at moderate-to vigorous-intensity and with programs longer than 24 weeks that comprise at least 3 sessions per week and more than 60 min per session.Conclusion:Exercise training represents an anti-inflammatory therapy and metabolism-improving strategy with minimal side effects for patients with type 2 diabetes mellitus.

Twenty-four-hour movement guidelines during middle adolescence and their association with glucose outcomes and type 2 diabetes mellitus in adulthood

Purpose:The aim of the present study was to determine the association between adherence to the 24-h movement guidelines during middle adolescence and glucose outcomes(glycated hemoglobin and fasting glucose)and type 2 diabetes mellitus(T2DM)in adulthood,14 and 22 years later.Methods:We analyzed data from apparently healthy adolescents aged 12-18 years who participated in WavesⅠandⅡ(1994-1996,n=14,738),WaveⅣ(2008-2009,n=8913),and Wave V(2016-2018,n=3457)of the National Longitudinal Study of Adolescent to Adult Health(Add Health)in the United States.Physical activity,screen time,and sleep duration were measured using questionnaires,and the 24-h guidelines were defined as:5 or more times moderate-to-vigorous physical activity per week,≤2 h per day of screen time,and 9-11 h of sleep for 12-13 years and 8-10 h for 14-17 years.Capillary and venous whole blood was collected and analyzed to determine glycated hemoglobin and fasting glucose for WavesⅣandⅤ,respectively.Results:Only 2.1%of the adolescents met all the 3 guidelines,and 37.8%met none of them.In both wavesⅣandⅤ,adolescents who met physical activity and screen time guidelines had lower odds of T2DM in adulthood than those who did not meet any of these guidelines(WaveⅣ;prevalence ratio(PR)=0.57,95%confidence interval(95%CI):0.21-0.89;Wave V:PR=0.43,95%CI:0.32-0.74).Only for Wave V did adolescents who met all 3 guidelines have lower odds of T2DM at follow-up compared with those who did not meet any of these guidelines(PR=0.47,95%CI:0.24-0.91).Also,for each increase in meeting one of the 24-h recommendations,the odds of T2DM decreased by 18%(PR=0.82,95%CI:0.61-0.99)and 15%(PR=0.85,95%CI:0.65-0.98)in adulthood for WavesⅣandⅤ,respectively.Conclusion:Promoting all 24-h movement guidelines in adolescence,especially physical activity and screen time,is important for lowering the potential risk of T2DM in adulthood.

Olfactory proteotyping: towards the enlightenment of the neurodegeneration

Although phylogenetically ancient,the olfactory system has received less attention than other sensorial systems.However,olfactory dysfunction is considered an early prodromal event in neurodegenerative diseases(NDs)(Doty,2012;Attems et al.,2014),which may vary from severe smell loss(e.g.,Alzheimer’s and Parkinson’s diseases)to relatively moderate loss(e.g.,progressive supranuclear palsy)(Doty,2017).Recently,a cluster of neuropathological and functional discoveries has evidenced the relevant role of the olfactory bulb(OB)during the neurodegenerative process(Attems et al.,2014;Rey et al.,2018).For instance,the double-transgenic APP/PS1 mouse model of Alzheimer’s disease(AD)develops early proteomic disturbances accompanied by a specific modulation of the focal adhesion kinase(FAK)and mitogen-activated protein kinase(MAPK)dynamics at the level of the OB,demonstrating that olfactory molecular alterations occur prior toβ-amyloid plaque appearance and memory impairments in APP/PS1 transgenic mice(Lachen-Montes et al.,2016).

Cardiorespiratory fitness measured with cardiopulmonary exercise testing and mortality in patients with cardiovascular disease:A systematic review and meta-analysis

Background Cardiorespiratory fitness(CRF)is inversely associated with mortality in apparently healthy subjects and in some clinical populations,but evidence for the association between CRF and all-cause and/or cardiovascular disease(CVD)mortality in patients with established CVD is lacking.This study aimed to quantify this association.Methods We searched for prospective cohort studies that measured CRF with cardiopulmonary exercise testing in patients with CVD and that examined all-cause and CVD mortality with at least 6 months of follow-up.Pooled hazard ratios(HRs)were calculated using random-effect inverse-variance analyses.Results Data were obtained from 21 studies and included 159,352 patients diagnosed with CVD(38.1%female).Pooled HRs for all-cause and CVD mortality comparing the highest vs.lowest category of CRF were 0.42(95%confidence interval(95%CI):0.28–0.61)and 0.27(95%CI:0.16–0.48),respectively.Pooled HRs per 1 metabolic equivalent(1-MET)increment were significant for all-cause mortality(HR=0.81;95%CI:0.74–0.88)but not for CVD mortality(HR=0.75;95%CI:0.48–1.18).Coronary artery disease patients with high CRF had a lower risk of all-cause mortality(HR=0.32;95%CI:0.26–0.41)than did their unfit counterparts.Each 1-MET increase was associated with lower all-cause mortality risk among coronary artery disease patients(HR=0.83;95%CI:0.76–0.91)but not lower among those with heart failure(HR=0.69;95%CI:0.36–1.32).Conclusion A better CRF was associated with lower risk of all-cause mortality and CVD.This study supports the use of CRF as a powerful predictor of mortality in this population.

Prevalence of meeting 24-Hour Movement Guidelines from pre-school to adolescence: A systematic review and meta-analysis including 387,437 participants and 23 countries

Background:Meeting the 24-Hour Movement Guidelines(physical activity,screen time,and sleep duration) has been associated with positive health indicators.However,there are no previous meta-analyses that have examined the overall adherence to the 24-Hour Movement Guidelines from pre-school to adolescence across the world.Therefore,the main purpose of this systematic review and meta-analysis was to examine the overall(non)adherence to the 24-Hour Movement Guidelines among preschoolers,children,and adolescents worldwide.Methods:Four electronic databases(MEDLINE,Scopus,Web of Science,and Cochrane Database of Systematic Reviews) were searched for quantitative studies published in Spanish and English between January 2016 and May 2021.Studies that were conducted with apparently healthy participants and reported the overall(non)adherence to the 24-Hour Movement Guidelines in preschoolers and/or children and/or adolescents were included.Results:Sixty-three studies comprising 387,437 individuals(51% girls) aged 3-18 years from 23 countries were included.Overall,7.12%(95%confidence interval(95%CI):6.45%-7.78%) of youth met all three 24-Hour Movement Guidelines,and 19.21%(95%CI:16.73%-21.69%)met none of the 3 recommendations.Concerning sex,adherence to all recommendations was significantly lower in girls(3.75%,95%CI:3.23%-4.27%) than in boys(6.89%,95%CI:5.89%-7.89%)(p <0.001).However,there were no sex differences regarding adherence to any of the 3 individual recommendations(girls,15.66%,95%CI:8.40%-22.92%;boys,12.95%,95%CI:6.57%-19.33%).In terms of age group,adherence to the 3 recommendations was 11.26%(95%CI:8.68%-13.84%),10.31%(95%CI:7.49%-13.12%),and 2.68%(95%CI:1.78%-3.58%) in preschoolers,children,and adolescents,respectively.Conversely,8.81%(95%CI:5.97%-11.64%) of preschoolers,15.57%(95%CI:11.60%-19.54%) of children,and 28.59%(95%CI:22.42%-34.75%) of adolescents did not meet any of the recommendations.South America was the region with the lowest adherence(all:2.93%;none:31.72%).Overall adherence to the 24-Hour Movement Guidelines was positively related to country Human Development Index(β=-0.37,95%CI:-0.65 to-0.09;p=0.010).Conclusion:Most young people fail to meet the three 24-Hour Movement Guidelines,particularly adolescents,girls,and those who are from countries with a lower Human Development Index.Moreover,1 in 5 young people did not meet any of these recommendations.Therefore,these results highlight the need to develop age-and sex-specific strategies to promote these movement behaviors from the early stages of life.

Is device-measured vigorous physical activity associated with health-related outcomes in children and adolescents? A systematic review and meta-analysis

Objective:This study sought to analyze the prospective association between vigorous-intensity physical activity(VPA)and health-related outcomes in children and adolescents.Methods:Studies reporting associations between device-measured VPA and health-related factors in children and adolescents aged 318 years were identified through database searches(MEDLINE,EMBASE,and SPORTDiscus).Correlation coefficients were pooled if outcomes were reported by at least 3 studies,using DerSimonian-Laird random effects models.Results:Data from 23 studies including 13,674 participants were pooled using random effects models.Significant associations were found between VPA at baseline and overall adiposity(r=0.09,95%confidence interval(95%CI):0.15 to0.03;p=0.002;I^(2)=89.8%),cardiometabolic risk score(r=0.13,95%CI:0.24 to0.02,p=0.020;I^(2)=69.6%),cardiorespiratory fitness(r=0.25,95%CI:0.150.35;p<0.001;I^(2)=57.2%),and total body bone mineral density(r=0.16,95%CI:0.06 to 0.25;p=0.001;I^(2)=0%).Conclusion:VPA seems to be negatively related to adiposity and cardiometabolic risk score and positively related to cardiorespiratory fitness and total body bone mineral density among children and adolescents at follow-up.Therefore,our findings support the need to strengthen physical activity recommendations regarding VPA due to its health benefits in children and adolescents.

Healthy diet,depression and quality of life:A narrative review of biological mechanisms and primary prevention opportunities

Unipolar depressive disorder(UDD)affects more than 264 million people worldwide and was projected well before the severe acute respiratory syndrome coronavirus 2 pandemic to be the leading cause of disability-adjusted life years lost in 2030.It is imperative for leading economies to implement preventive strategies targeted towards UDD,given consistent policies are currently lacking.Recently established similarities between the aetiological hypotheses of depression and cardiometabolic diseases are shifting paradigms within this field.It is believed that dietary practices could potentially reduce the incidence of depression;similar to their effects on metabolism.Thus,the aim of this review was to compile current evidence on healthy dietary patterns as suitable contributors towards primary prevention strategies against UDD.Most of the well-known biological mechanisms behind depression have been positively associated with healthful diets and dietary patterns to varying degrees.Interestingly,a common factor of UDD is the production and overall effects of inflammatory cytokines,such as interleukin-6,tumor necrosis factor-α,and Creactive protein.These compounds have been associated with depressive symptoms,disturbances in neuroendocrine function,leaky gut,monoamine activity and brain function,while also being key factors in the development of cardiometabolic diseases.The Mediterranean diet(MD)in particular,is well supported by first-level evidence regarding its preventive qualities against metabolic and cardiovascular diseases and thus considered a model for healthy eating by various organizations.In one of the few clinical trials investigating these associations,the PREDIMED trial,individuals with diabetes assigned to a MD supplemented with mixed tree nuts experienced a 41%relative risk reduction for developing depression.Lastly,there is a need to include health related quality of life as an indicator of physical and mental well-being,considering its putative associations with depression and suicide risk.Going forward,focusing on clinical trials,using precise nutritional assessments,and identifying nutritional biomarkers which may be related to depression are needed to fully support the implementation of dietary recommendations in the field of psychiatry.

The effects of plyometric jump training on physical fitness attributes in basketball players:A meta-analysis`

Background:There is a growing body of experimental evidence examining the effects of plyometric jump training(PJT)on physical fitness attributes in basketball players;however,this evidence has not yet been comprehensively and systematically aggregated.Therefore,our objective was to meta-analyze the effects of PJT on physical fitness attributes in basketball players,in comparison to a control condition.Methods:A systematic literature search was conducted in the databases PubMed,Web of Science,and Scopus,up to July 2020.Peer-reviewed controlled trials with baseline and follow-up measurements investigating the effects of PJT on physical fitness attributes(muscle power,i.e.,jumping performance,linear sprint speed,change-of-direction speed,balance,and muscle strength)in basketball players,with no restrictions on their playing level,sex,or age.Hedge’s g effect sizes(ES)were calculated for physical fitness variables.Using a random-effects model,potential sources of heterogeneity were selected,including subgroup analyses(age,sex,body mass,and height)and single training factor analysis(program duration,training frequency,and total number of training sessions).Computation of metaregression was also performed.Results:Thirty-two studies were included,involving 818 total basketball players.Significant(p<0.05)small-to-large effects of PJT were evident on vertical jump power(ES=0.45),countermovement jump height with(ES=1.24)and without arm swing(ES=0.88),squat jump height(ES=0.80),drop jump height(ES=0.53),horizontal jump distance(ES=0.65),linear sprint time across distances≤10 m(ES=1.67)and>10 m(ES=0.92),change-of-direction performance time across distances≤40 m(ES=1.15)and>40 m(ES=1.02),dynamic(ES=1.16)and static balance(ES=1.48),and maximal strength(ES=0.57).The meta-regression revealed that training duration,training frequency,and total number of sessions completed did not predict the effects of PJT on physical fitness attributes.Subgroup analysis indicated greater improvements in older compared to younger players in horizontal jump distance(>17.15 years,ES=2.11;≤17.15 years,ES=0.10;p<0.001),linear sprint time>10 m(>16.3 years,ES=1.83;≤16.3 years,ES=0.36;p=0.010),and change-of-direction performance time≤40 m(>16.3 years,ES=1.65;≤16.3 years,ES=0.75;p=0.005).Greater increases in horizontal jump distance were apparent with>2 compared with≤2 weekly PJT sessions(ES=2.12 and ES=0.39,respectively;p<0.001).Conclusion:Data from 32 studies(28 of which demonstrate moderate-to-high methodological quality)indicate PJT improves muscle power,linear sprint speed,change-of-direction speed,balance,and muscle strength in basketball players independent of sex,age,or PJT program variables.However,the beneficial effects of PJT as measured by horizontal jump distance,linear sprint time>10 m,and change-of-direction performance time≤40 m,appear to be more evident among older basketball players.

GOECP/SEOR radiotherapy guidelines for thymic epithelial tumours

Thymic epithelial tumours(TET)are rare,heterogeneous neoplasms that range from resectable indolent tumours to aggressive thymic carcinomas with a strong tendency to metastasize.The pathological diagnosis is complex,in part due to the management of TETs is scant and mainly based on non-randomised studies and retrospective series.Consequently,the clinical management of TETs tends to be highly heterogenous,which makes it difficult to improve the evidence level.The role of technological advances in the field of radiotherapy and new systemic therapies in the treatment of TETs has received little attention to date.In the present clinical guidelines,developed by the GOECP/SEOR,we review recent developments in the diagnosis and classification of TETs.We also present a consensus-based therapeutic strategy for each disease stage that takes into consideration the best available evidence.These guidelines focus primarily on the role of radiotherapy,including recent advances,in the management of TETs.The main aim of this document is to promote the standardisation of clinical practice and lay the foundations for future studies to clarify the main unresolved questions related to the optimal management of TET.

The differential benefit of laparoscopic over open minor liver resection for lesions situated in the anterolateral or posterosuperior segments

Background:It is well known that laparoscopic liver surgery can offer advantages over open liver surgery in selected patients.However,what type of procedures can benefit most from a laparoscopic approach has been investigated poorly thus far.The aim of this study is thus to define the extent of advantages of laparoscopic over open liver surgery for lesions in the anterolateral(AL)and posterosuperior(PS)segments.Methods:In this international multicentre retrospective cohort study,laparoscopic and open minor liver resections for lesions in the AL and PS segments were compared after propensity score matching.The differential benefit of laparoscopy over open liver surgery,calculated using bootstrap sampling,was compared between AL and PS resections and expressed as a Delta of the differences.Results:After matching,3,040 AL and 2,336 PS resections were compared,encompassing open and laparoscopic procedures in a 1:1 ratio.AL and PS laparoscopic liver resections were more advantageous in comparison to open in terms of blood loss,transfusion rate,complications,and length of stay.However,AL resections benefitted more from laparoscopy than PS in terms of overall and severe complications(D-difference were 4.8%,P=0.046 and 3%,P=0.046)and blood loss(D-difference was 195 mL,P<0.001).Similar results were observed in the subset for high-volume centres,while in recent years no significant differences were found in the differential benefit between AL and PS segments.Conclusions:The advantage of laparoscopic over open liver surgery is greater in the AL segments than in the PS segments.

LIBRA:an adaptative integrative tool for paired single-cell multi-omics data

Background:Single-cell multi-omics technologies allow a profound system-level biology understanding of cells and tissues.However,an integrative and possibly systems-based analysis capturing the different modalities is challenging.In response,bioinformatics and machine learning methodologies are being developed for multi-omics single-cell analysis.It is unclear whether current tools can address the dual aspect of modality integration and prediction across modalities without requiring extensive parameter fine-tuning.Methods:We designed LIBRA,a neural network based framework,to learn translation between paired multi-omics profiles so that a shared latent space is constructed.Additionally,we implemented a variation,aLIBRA,that allows automatic fine-tuning by identifying parameter combinations that optimize both the integrative and predictive tasks.All model parameters and evaluation metrics are made available to users with minimal user iteration.Furthermore,aLIBRA allows experienced users to implement custom configurations.The LIBRA toolbox is freely available as R and Python libraries at GitHub(TranslationalBioinformaticsUnit/LIBRA).Results:LIBRA was evaluated in eight multi-omic single-cell data-sets,including three combinations of omics.We observed that LIBRA is a state-of-the-art tool when evaluating the ability to increase cell-type(clustering)resolution in the integrated latent space.Furthermore,when assessing the predictive power across data modalities,such as predictive chromatin accessibility from gene expression,LIBRA outperforms existing tools.As expected,adaptive parameter optimization(aLIBRA)significantly boosted the performance of learning predictive models from paired data-sets.Conclusion:LIBRA is a versatile tool that performs competitively in both“integration”and“prediction”tasks based on single-cell multi-omics data.LIBRA is a data-driven robust platform that includes an adaptive learning scheme.

Mutated trimeric RBD vaccines:a platform against variants of concern

He et al.recently reported in Nature Communications1 the development of a protein vaccine against SASR-CoV-2 Omicron variant consisting of a trimer of the spike protein receptor-binding domain(RBD)of the Delta variant fused to heptad-repeat sequences 1 and 2.This vaccine induced broad-spectrum neutralizing antibodies and fully protected mice and non-human primates against challenge with live Delta and Omicron virus.