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Background: Obesity and frailty are prevalent geriatric conditions that share some pathophysiological mechanisms and are associated with adverse clinical outcomes. The relationship between frailty, obesity, and polymorphism remains inadequately explored. Single nucleotide polymorphisms (SNPs) offer insights into genetic predispositions that may influence the development of both frailty and obesity. Methods: We aimed at investigating whether SNPs associated with frailty also play a role in obesity. Data were collected from the FRASNET cross-sectional study, which included community-dwelling older individuals residing in Milan and nearby areas. Participants were recruited through random sampling. They underwent multidimensional geriatric assessments, which included the collection of blood samples for SNP analysis. Frailty was assessed using the frailty index, and body composition was evaluated using bioelectrical impedance analysis and anthropometric measures. Results: SNPs related to frailty and linked to the renin-angiotensin system (CYP11B2 rs1799998, AGT rs5051, and AGTR1 rs2131127), apoptosis pathways (CASP8 rs6747918), growth hormone signaling (GHR rs6180), inflammation (TLR4 rs5030717, CD33 rs3865444, and FN1 rs7567647), adducin (ADD3 rs3731566), and the 9p21-23 region (rs518054) were found to be associated with various measures of obesity in community-dwelling older adults. Conclusions: Frailty-related SNPs contribute to obesity in community-dwelling older adults. We identified a novel association between adducin SNPs and visceral fat, which has not been previously reported. Detecting genetic predispositions to obesity and frailty early could aid in identifying individuals at risk, facilitating the adoption of preventive interventions. This represents an initial step toward promoting early intervention strategies. [ABSTRACT FROM AUTHOR]

It is heavily suggested that one IFNL4 gene polymorphism, rs12979860 (T/C), exerts influence on the outcome of HBV infection, with the rs12979860-T allele being classified as a risk predictor, and the rs12979860-C allele being classified as a protective one. This study investigated whether the rs12979860 IFNL4 gene polymorphism presented any association with the clinical severity for HBV carriers in an admixed population in Northern Brazil. A total of 69 samples were investigated from infected people from the city of Belém-Pará. The rs12979860-T allele was positively associated with HBV infection, suggesting a higher risk of chronicity. This research's importance is that the polymorphism influence was investigated in a population of HBV carriers with a heterogeneous genetic profile, formed through the extensive admixture of different ethnic groups, including Europeans, Africans, and Natives with indigenous heritage. This analysis is particularly important since highly mixed populations do not always follow the same association patterns previously established by studies using populations classified as more genetically homogeneous, due to a different formation process. [ABSTRACT FROM AUTHOR]

Abstract Background Telehealth services are essential to expand healthcare coverage for all in the era of modern technology. Knowledge, willingness, and involvement with the service are also significantly important in the utilization of the service. This study investigated factors associated with knowledge, perceived benefits, perceived concerns, and predisposition to use telehealth services in Bangladesh. This web-based survey was conducted among 1266 adults in Bangladesh. Respondents were enrolled by following a convenience sampling technique. Results Demographic, telehealth service, and perceived health related information were significantly associated with respondents’ knowledge, perceived benefits, perceived concerns, and predispositions. The knowledge was significantly positively correlated with the perceived benefit (p

Background: Telehealth services are essential to expand healthcare coverage for all in the era of modern technology. Knowledge, willingness, and involvement with the service are also significantly important in the utilization of the service. This study investigated factors associated with knowledge, perceived benefits, perceived concerns, and predisposition to use telehealth services in Bangladesh. This web-based survey was conducted among 1266 adults in Bangladesh. Respondents were enrolled by following a convenience sampling technique. Results: Demographic, telehealth service, and perceived health related information were significantly associated with respondents' knowledge, perceived benefits, perceived concerns, and predispositions. The knowledge was significantly positively correlated with the perceived benefit (p <0.05) and predisposition of telehealth (p <0.05). Albeit, knowledge was significantly negatively correlated with perceived concerns of telehealth (p <0.05). Conclusion: The findings of the study may assist policymakers in implementing telehealth services by addressing the associated factors of knowledge, perceived benefits, perceived concerns, and predispositions. [ABSTRACT FROM AUTHOR]

[Display omitted] • Risk factors shaping host-parasite interactions impact the clinical management of canine leishmaniosis. • Renal and ocular findings are major risk factors for LeishVet stages III and IV. • Diagnosis of comorbidities is key to managing dogs with leishmaniosis, although independent of their clinical outcome. • A complex polygenic component underlies the development of severe clinical forms of leishmaniosis in certain purebred dogs. • Protective immunity against Leishmania parasites is related to genetic factors involved in the ER stress and UPR pathways. Canine leishmaniosis (CanL), caused by Leishmania infantum , is a complex disease of growing importance in Europe. Clinical manifestations result from the down-modulation of the host immune response through multiple host-parasite interactions. Although several factors might influence CanL progression, this is the first known study evaluating risk factors for its different clinical stages in a large referral hospital population (n = 35.669) from an endemic area, over a 20 year period. Genome-wide scans for selection signatures were also conducted to explore the genomic component of clinical susceptibility to L. infantum infection. The prevalence of CanL was 3.2% (16.7% stage I; 43.6% stage II; 32.1% stage III; 7.6% stage IV). Dog breed (crossbreed), bodyweight (<10 kg), living conditions (indoors), regular deworming treatment, and being vaccinated against Leishmania significantly decreased the transmission risk and the risk for developing severe clinical forms. Conversely, the detection of comorbidities was associated with advanced clinical forms, particularly chronic kidney disease, neoplasia, cryptorchidism, infectious tracheobronchitis and urate urolithiasis, although those did not impact the clinical outcome. Significant associations between an increased risk of severe clinical stages and findings in the anamnesis (renal or skin-related manifestations) and physical examination (ocular findings) were also detected, highlighting their diagnostic value in referred cases of CanL. Sixteen breeds were found to be significantly more susceptible to developing severe stages of leishmaniosis (e.g. Great Dane, Rottweiler, English Springer Spaniel, Boxer, American Staffordshire Terrier, Golden Retriever), while 20 breeds displayed a clinical resistantance phenotype and, thus, are more likely to mount an efficient immune response against L. infantum (e.g. Pointer, Samoyed, Spanish Mastiff, Spanish Greyhound, English Setter, Siberian Husky). Genomic analyses of these breeds retrieved 12 regions under selection, 63 candidate genes and pinpointed multiple biological pathways such as the IRE1 branch of the unfolded protein response, which could play a critical role in clinical susceptibility to L. infantum infection. [ABSTRACT FROM AUTHOR]

Bark beetle outbreaks and forest mortality have rocketed in European forests because of warmer winters, intense droughts, and poor management. The methods developed to predict a bark beetle outbreak have three main limitations: (i) a small-spatial-scale implementation; (ii) specific field-based input datasets that are usually hard to obtain at large scales; and (iii) predictive models constrained by coarse climatic factors. Therefore, a methodological approach accounting for a comprehensive set of environmental traits that can predict a bark beetle outbreak accurately is needed. In particular, we aimed to (i) analyze the influence of environmental traits that cause bark beetle outbreaks; (ii) compare different machine learning architectures for predicting bark beetle attacks; and (iii) map the attack probability before the start of the bark beetle life cycle. Random Forest regression achieved the best-performing results. The predicted bark beetle damage reached a high robustness in the test area (F1 = 96.9, OA = 94.4) and showed low errors (CE = 2.0, OE = 4.2). Future improvements should focus on including additional variables, e.g., forest age and validation sites. Remote sensing-based methods contributed to detecting bark beetle outbreaks in large extensive forested areas in a cost-effective and robust manner. [ABSTRACT FROM AUTHOR]

BackgroundObesity and frailty are prevalent geriatric conditions that share some pathophysiological mechanisms and are associated with adverse clinical outcomes. The relationship between frailty, obesity, and polymorphism remains inadequately explored. Single nucleotide polymorphisms (SNPs) offer insights into genetic predispositions that may influence the development of both frailty and obesity.MethodsWe aimed at investigating whether SNPs associated with frailty also play a role in obesity. Data were collected from the FRASNET cross-sectional study, which included community-dwelling older individuals residing in Milan and nearby areas. Participants were recruited through random sampling. They underwent multidimensional geriatric assessments, which included the collection of blood samples for SNP analysis. Frailty was assessed using the frailty index, and body composition was evaluated using bioelectrical impedance analysis and anthropometric measures.ResultsSNPs related to frailty and linked to the renin–angiotensin system (CYP11B2 rs1799998, AGT rs5051, and AGTR1 rs2131127), apoptosis pathways (CASP8 rs6747918), growth hormone signaling (GHR rs6180), inflammation (TLR4 rs5030717, CD33 rs3865444, and FN1 rs7567647), adducin (ADD3 rs3731566), and the 9p21–23 region (rs518054) were found to be associated with various measures of obesity in community-dwelling older adults.ConclusionsFrailty-related SNPs contribute to obesity in community-dwelling older adults. We identified a novel association between adducin SNPs and visceral fat, which has not been previously reported. Detecting genetic predispositions to obesity and frailty early could aid in identifying individuals at risk, facilitating the adoption of preventive interventions. This represents an initial step toward promoting early intervention strategies.

Summary: Infection is a commonplace, usually self-limiting, condition but can lead to sepsis, a severe life-threatening dysregulated host response. We investigate the individual phenotypic predisposition to developing uncomplicated infection or sepsis in a large cohort of non-infected patients undergoing major elective surgery. Whole-blood RNA sequencing analysis was performed on preoperative samples from 267 patients. These patients developed postoperative infection with (n = 77) or without (n = 49) sepsis, developed non-infectious systemic inflammatory response (n = 31), or had an uncomplicated postoperative course (n = 110). Machine learning classification models built on preoperative transcriptomic signatures predict postoperative outcomes including sepsis with an area under the curve of up to 0.910 (mean 0.855) and sensitivity/specificity up to 0.767/0.804 (mean 0.746/0.769). Our models, confirmed by quantitative reverse-transcription PCR (RT-qPCR), potentially offer a risk prediction tool for the development of postoperative sepsis with implications for patient management. They identify an individual predisposition to developing sepsis that warrants further exploration to better understand the underlying pathophysiology.

The contribution of Eucalyptus globulus plantations to timber production for pulp, paper and energy production may be hampered by climate change. It is expected that Eucalyptus productivity may be affected through drought stress and changes to both pathogen distribution/pathogenicity and host–pathogen interactions. The impact of the fungal pathogen Neofusicoccum kwambonambiense on E. globulus, causing cankers and dieback, is well known but the impact of drought on disease development is still understudied. Our aim was to study the effect of drought on N. kwambonambiense infection by inoculating E. globulus plants under well‐watered conditions or with water limitation. Non‐infected plants for both water regimes were also analysed. Morphophysiological, biochemical and hormonal parameters were assessed 65 days post‐inoculation. Inoculation under conditions of water stress decreased water potential and photosynthetic efficiency and increased abscisic acid, jasmonic acid and lipid peroxidation. Water‐stressed infected plants also showed higher fungal colonization and external lesion length in comparison with well‐watered inoculated plants. Our results indicate that drought increased E. globulus predisposition to N. kwambonambiense infection and may also have promoted a change in the lifestyle of the fungus. Identifying host–pathogen interaction responses under different stress conditions is necessary to provide knowledge for decision‐making in the management of forest systems in general and of Eucalyptus production in particular. [ABSTRACT FROM AUTHOR]

Introduction: Chordoma is a rare slow-growing tumor that occurs along the length of the spinal axis and arises from primitive notochordal remnants (Stepanek et al., Am J Med Genet 75:335–336, 1998). Most chordomas are sporadic, but a small percentage of cases are due to hereditary cancer syndromes (HCS) such as tuberous sclerosis 1 and 2 (TSC1/2), or constitutional variants in the gene encoding brachyury T (TBXT) (Pillay et al., Nat Genet 44:1185–1187, 2012; Yang et al., Nat Genet 41:1176–1178, 2009). Purpose: The genetic susceptibility of these tumors is not well understood; there are only a small number of studies that have performed germline genetic testing in this population. Methods: We performed germline genetic in chordoma patients using genomic DNA extracted by blood or saliva. Conclusion: We report here a chordoma cohort of 24 families with newly found germline genetic mutations in cancer predisposing genes. We discuss implications for genetic counseling, clinical management, and universal germline genetic testing for cancer patients with solid tumors. [ABSTRACT FROM AUTHOR]

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Southern California experienced unprecedented megadrought between 2012 and 2018. During this time, Malosma laurina, a chaparral species normally resilient to single‐year intense drought, developed extensive mortality exceeding 60% throughout low‐elevation coastal populations of the Santa Monica Mountains. We assessed the physiological mechanisms by which the advent of megadrought predisposed M. laurina to extensive shoot dieback and whole‐plant death. We found that hydraulic conductance of stem xylem (Ks, native) was reduced seven to 11‐fold in dieback adult and resprout branches, respectively. Staining of stem xylem vessels revealed that dieback plants experienced 68% solid‐blockage, explaining the reduction in water transport. Following Koch's postulates, persistent isolation of a microorganism in stem xylem of dieback plants but not healthy controls indicated that the causative agent of xylem blockage was an opportunistic endophytic fungus, Botryosphaeria dothidea. We inoculated healthy M. laurina saplings with fungal isolates and compared hyphal elongation rates under well‐watered, water‐deficit, and carbon‐deficit treatments. Relative to controls, we found that both water deficit and carbon‐deficit increased hyphal extension rates and the incidence of shoot dieback. Summary statement: We conclude that the ultimate cause of mortality of Malosma laurina in field populations was megadrought and that the proximal cause of mortality was the transition of endemic Botryosphaeria dothidea to an opportunistic pathogen that amplified protracted water stress through physical blockage of xylem water transport. [ABSTRACT FROM AUTHOR]

This exome sequencing study of 293 men with familial or bilateral testicular germ cell tumor (TGCT) and 3157 cancer-free controls is the largest of its kind. Using a gene-agnostic approach, we identified germline coding changes associated with TGCT. Testicular germ cell tumor (TGCT) is the most common cancer among young White men. TGCT is highly heritable, although there are no known high-penetrance predisposition genes. CHEK2 is associated with moderate TGCT risk. To identify coding genomic variants associated with predisposition to TGCT. The study involved 293 men with familial or bilateral (high risk; HR)-TGCT representing 228 unique families and 3157 cancer-free controls. We carried out exome sequencing and gene burden analysis to identify associations with TGCT risk. Gene burden association identified several genes, including loss-of-function variants of NIN and QRSL 1. We identified no statistically significant association with the sex- and germ-cell development pathways (hypergeometric overlap test: p = 0.65 for truncating variants, p = 0.47 for all variants) or evidence of associations with the regions previously identified via genome-wide association studies (GWAS). When considering all significant coding variants together with genes associated with TGCT on GWAS, there were associations with three major pathways: mitosis/cell cycle (Gene Ontology identity GO:1903047: observed/expected variant ratio [O/E] 6.17, false discovery rate [FDR] 1.53 × 10−11), co-translational protein targeting (GO:0006613: O/E 18.62, FDR 1.35 × 10−10), and sex differentiation (GO:0007548: O/E 5.25, FDR 1.90 × 10−4). To the best of our knowledge, this study is the largest to date on men with HR-TGCT. As in previous studies, we identified associations with variants for several genes, suggesting multigenic heritability. We identified associations with co-translational protein targeting, and chromosomal segregation and sex determination, identified via GWAS. Our results suggest potentially druggable targets for TGCT prevention or treatment. We searched for gene variations that increase the risk of testicular cancer and found numerous new specific variants that contribute to this risk. Our results support the idea that many gene variants inherited together contribute to the risk of testicular cancer. [ABSTRACT FROM AUTHOR]

Childhood eye cancers, although rare, present substantial health challenges, affecting the pediatric population with a remarkable impact on their lives and families. This comprehensive review provides insights into the various types of ocular tumors, primarily focusing on malignant eye tumors, their genetic predispositions, and advancements in managing these conditions. Understanding the genetic risk factors is crucial for early detection, risk assessment, and the development of targeted therapies. This review discusses genome-wide association (GWAS) and next-generation sequencing (NGS) studies to find common and rare genetic variants. Furthermore, it also explores the outcomes and implications of these genetic discoveries in treating pediatric ocular cancer. These findings underscore the significance of genetic research in guiding early interventions and improving outcomes in children with ocular cancers. [ABSTRACT FROM AUTHOR]

IntroductionGenetic disposition is a major etiologic factor in childhood cancer. More than 100 cancer predisposing syndromes (CPS) are known. Surveillance protocols seek to mitigate morbidity and mortality. To implement recommendations in patient care and to ascertain that the constant gain of knowledge forces its way into practice specific pediatric CPS programs were established.Patients and methodsWe retrospectively analyzed data on children, adolescents, and young adults referred to our pediatric CPS program between October 1, 2021, and March 31, 2023. Follow-up ended on December 31, 2023.ResultsWe identified 67 patients (30 male, 36 female, 1 non-binary, median age 9.5 years). Thirty-five patients were referred for CPS surveillance, 32 for features suspicious of a CPS including café-au-lait macules (n = 10), overgrowth (n = 9), other specific symptoms (n = 4), cancer suspicious of a CPS (n = 6), and rare neoplasms (n = 3). CPS was confirmed by clinical criteria in 6 patients and genetic testing in 7 (of 13). In addition, 6 clinically unaffected at-risk relatives were identified carrying a cancer predisposing pathogenic variant. A total of 48 patients were eventually diagnosed with CPS, surveillance recommendations were on record for 45. Of those, 8 patients did not keep their appointments for various reasons. Surveillance revealed neoplasms (n = 2) and metachronous tumors (n = 4) by clinical (n = 2), radiological examination (n = 2), and endoscopy (n = 2). Psychosocial counselling was utilized by 16 (of 45; 35.6%) families.ConclusionsThe diverse pediatric CPSs pose several challenges necessitating interdisciplinary care in specified CPS programs. To ultimately improve outcome including psychosocial well-being joint clinical and research efforts are necessary.

It is heavily suggested that one IFNL4 gene polymorphism, rs12979860 (T/C), exerts influence on the outcome of HBV infection, with the rs12979860-T allele being classified as a risk predictor, and the rs12979860-C allele being classified as a protective one. This study investigated whether the rs12979860 IFNL4 gene polymorphism presented any association with the clinical severity for HBV carriers in an admixed population in Northern Brazil. A total of 69 samples were investigated from infected people from the city of Belém-Pará. The rs12979860-T allele was positively associated with HBV infection, suggesting a higher risk of chronicity. This research’s importance is that the polymorphism influence was investigated in a population of HBV carriers with a heterogeneous genetic profile, formed through the extensive admixture of different ethnic groups, including Europeans, Africans, and Natives with indigenous heritage. This analysis is particularly important since highly mixed populations do not always follow the same association patterns previously established by studies using populations classified as more genetically homogeneous, due to a different formation process.

AbstractThe importance of Vitamin D in ovarian cancer (OC) has been well documented, and lower levels have been associated with susceptibility to OC. Vitamin D exerts its effect through the vitamin D receptor (VDR). Common genetic variants in the VDR gene (Fok I, TaqI, BamI and ApaI) have been linked with the susceptibility to the development of OC; however, the reports remain contradictory. To draw a valid conclusion, we performed a meta-analysis of the earlier published reports in the present study. The literature search was performed in PubMed, Google Scholar, and Scopus databases. All relevant articles were screened, and eligible reports were identified based on prefixed inclusion and exclusion criteria. Data such as author’s details, year of publication, ethnicity, genotype and allele prevalence in cases and controls were extracted from the eligible reports. The meta-analysis was performed using Comprehensive Meta-analysis Software (CMA) V3. Eight articles, including data from fourteen independent cohorts, comprised 4276 cases and 6739 healthy controls considered for the analysis. VDR FokI and BamI variants revealed a significant association with an increased risk of OC. Other VDR polymorphisms (TaqI and ApaI) failed to demonstrate such an association with OC. Interestingly, the sensitivity analysis revealed minimal deviation from the parent meta-analysis, supporting the robustness of the present analysis. The trial sequential analysis revealed the inclusion of a sufficient number of studies for FokI polymorphism. It highlighted the requirement for additional case-control studies in VDR (ApaI, BamI and TaqI) to draw a definitive conclusion. FokI and BamI polymorphisms are associated with susceptibility to OC. [ABSTRACT FROM AUTHOR]

Familial non-medullary thyroid carcinoma (FNMTC) accounts for 3% to 9% of all thyroid cancer cases, yet its genetic mechanisms remain unknown. Our study aimed to screen and identify novel susceptibility genes for FNMTC. Whole-exome sequencing (WES) was conducted on a confirmed FNMTC pedigree, comprising four affected individuals across two generations. Variants were filtered and analyzed using ExAC and 1000 Genomes Project, with candidate gene pathogenicity predicted using SIFT, PolyPhen, and MutationTaster. Validation was performed through Sanger sequencing in affected pedigree members and sporadic patients (TCGA database) as well as general population data (gnomAD database). Ultimately, we identified the mutant PPP4R3A (NC_000014.8:g.91942196C>T, or NM_001366432.2(NP_001353361.1):p.(Asp409Asn), based on GRCH37) as an FNMTC susceptibility gene. Subsequently, a series of functional experiments were conducted to investigate the impact of PPP4R3A and its Asp409Asn missense variant in thyroid cancer. Our findings demonstrated that wild-type PPP4R3A exerted tumor-suppressive effects via the Akt-mTOR-P70 S6K/4E-BP1 axis. However, overexpression of the PPP4R3A Asp409Asn mutant resulted in loss of tumor-suppressive function, ineffective inhibition of cell invasion, and even promotion of cell proliferation and migration by activating the Akt/mTOR signaling pathway. These results indicated that the missense variant PPP4R3A Asp409Asn is a candidate susceptibility gene for FNMTC, providing new insights into the diagnosis and intervention of FNMTC. [ABSTRACT FROM AUTHOR]

The World Health Organization warns of alarmingly high levels of sedentary behavior in our current society. In terms of the adolescent population, a substantial percentage of them do not meet the global recommendations for weekly physical activity. Therefore, this qualitative study aimed to analyze the predisposition and future preferences for physical activity and sports (PAS) and leisure practices of 142 adolescents, as well as identifying the challenges and proposed improvements, while considering gender differences. The participants' reflections were gathered through semistructured interviews and focus groups and subjected to an inductive analysis. The main findings indicate a high intention to engage in future PAS and leisure activity. Individual sports were predominantly mentioned by girls, while team sports were mainly favored by boys. Additionally, boys expressed a preference for technology-related leisure activities, whereas girls leaned towards artistic activities. The participants emphasized the necessity to renew sports and recreational facilities and to adapt to the range of activities offered. At the same time, they acknowledged that reallocating economic resources would improve the quality of sports and health-care services. Consequently, institutions should tailor their programs of PAS and leisure activities to align with the preferences, ages, and genders of the youth population. [ABSTRACT FROM AUTHOR]

Simple Summary: The genetic variants responsible for lethal recurrent breast cancer are not yet recognized. Five sets of cousins with recurrent breast cancer who belonged to high-risk pedigrees were sequenced to identify rare, shared candidate predisposition variants in the pedigrees. The candidates were tested for association with breast cancer risk in other populations, and additional breast cancer cases were assayed for some of the candidate variants to test for co-segregation of the variants in pedigrees. One hundred and eighty-one rare candidate predisposition variants were shared in at least one cousin pair. A rare variant in MDH2 was found to segregate with breast-cancer-affected relatives in one extended pedigree. This small sequencing study identified a set of strong candidate variants for inherited predisposition for breast cancer recurrence, including MDH2, which should be pursued in other resources. A significant fraction of breast cancer recurs, with lethal outcome, but specific genetic variants responsible have yet to be identified. Five cousin pairs with recurrent breast cancer from pedigrees with a statistical excess of recurrent breast cancer were sequenced to identify rare, shared candidate predisposition variants. The candidates were tested for association with breast cancer risk with UKBiobank data. Additional breast cancer cases were assayed for a subset of candidate variants to test for co-segregation. Three-dimensional protein structure prediction methods were used to investigate how the mutation under consideration is predicted to change structural and electrostatic properties in the mutated protein. One hundred and eighty-one rare candidate predisposition variants were shared in at least one cousin pair from a high-risk pedigree. A rare variant in MDH2 was found to segregate with breast-cancer-affected relatives in one extended pedigree. MDH2 is an estrogen-stimulated gene encoding the protein malate dehydrogenase, which catalyzes the reversible oxidation of malate to oxaloacetate. The molecular simulation results strongly suggest that the mutation changes the NAD+ binding pocket electrostatics of MDH2. This small sequencing study, using a powerful approach based on recurrent breast cancer cases from high-risk pedigrees, identified a set of strong candidate variants for inherited predisposition for breast cancer recurrence, including MDH2, which should be pursued in other resources. [ABSTRACT FROM AUTHOR]

Tick-borne encephalitis (TBE) is a neuroviral disease that ranges in severity from a mild febrile illness to a severe and life-threatening meningoencephalitis or encephalomyelitis. There is increasing evidence that susceptibility to tick-borne encephalitis virus (TBEV)-induced disease and its severity are largely influenced by host genetic factors, in addition to other virus- and host-related factors. In this study, we investigated the contribution of selected single nucleotide polymorphisms (SNPs) in innate immunity genes to predisposition to TBE in humans. More specifically, we investigated a possible association between SNPs rs304478 and rs303212 in the gene Interferon Induced Protein With Tetratricopeptide Repeats 1 (IFIT1), rs7070001 and rs4934470 in the gene Interferon Induced Protein With Tetratricopeptide Repeats 2 (IFIT2), and RIG-I (Retinoic acid-inducible gene I) encoding gene DDX58 rs311795343, rs10813831, rs17217280 and rs3739674 SNPs with predisposition to TBE in population of the Czech Republic, where TBEV is highly endemic. Genotypic and allelic frequencies for these SNPs were analyzed in 247 nonimmunized TBE patients and compared with 204 control subjects. The analysis showed an association of IFIT1 rs304478 SNP and DDX58 rs3739674 and rs17217280 SNPs with predisposition to TBE in the Czech population indicating novel risk factors for clinical TBE but not for disease severity. These results also highlight the role of innate immunity genes in TBE pathogenesis. [ABSTRACT FROM AUTHOR]

The increase in the number of dogs as pets poses the challenge for veterinary specialists to find new approaches to prevent their morbidity and early mortality. Age and breed are considered to be the main risk criteria for the formation of tumours in dogs, so the aim of this study was to investigate the impact of these and a number of other factors on the susceptibility to cancer in this species. The research was based on the analysis of a single database of veterinary clinics in Bishkek, which includes 328 confirmed cases of cancer in dogs. The most common breeds were German (n=48) and Central Asian Shepherds (n=23), Rottweilers (n=18), Dachshunds (n=18), Poodles (n=17), Shar Pei (n=14), Pekingese (n=14), and a group of outbred dogs (n=70). Benign neoplasms were recorded in 140 cases, accounting for 54.3% of the total number of tumours in pure-bred dogs. Benign tumours predominated in large breed dogs (n=75), or 53.6% of the total number of benign tumours, and the highest growth of malignant tumours was detected in small breed dogs (59%) (n=29). Dogs, regardless of breed, were more vulnerable to tumour formation between the ages of 6 and 12 years. The database analysis revealed that females were more likely to develop cancer than males, with mammary tumours being the main diagnosis in females (36.3%). Small dog breeds had a higher risk of developing mammary tumours than large dogs. The obtained results revealed breed-specific features of the manifestation of morphological types of tumours in dogs and made it possible to determine the critical periods of their formation

Background Telehealth is comprised of telecommunications and electronic information systems to support and maintain long-distance healthcare services. Although it has not been thoroughly explored, the intention of using the service among the general public is critical to its success. We investigated the factors associated with the intention to utilize telehealth services among the general population of Bangladesh. Methods This cross-sectional study was conducted between May 22, 2021 and June 15, 2021 in Bangladesh, where the total number of participants was 1038. The Pearson chi-square test and Kruskal-Wallis H tests were used to examine the unadjusted relationship between the explanatory variables and the intention to use telehealth services. A multinomial logistic regression model was fitted to determine the adjusted association. Shapiro-Wilk tests were used to check the normality of continuous data. Data were processed and analyzed by software STATA-16. Results The probability of utilizing the service increased significantly with increasing knowledge, perceived benefit, and predisposition levels among respondents. However, when perceived concern increased, the likelihood of utilizing the service dropped significantly. Age, marital status, educational status, profession, residence, and perceived health status were significantly associated with the participants’ intention to utilize the telehealth service. Conclusions The influencing aspects of telehealth service utilization should be recognized by the respective authorities. Possible activities to enhance usability among people are also recommended.

Bark beetle outbreaks and forest mortality have rocketed in European forests because of warmer winters, intense droughts, and poor management. The methods developed to predict a bark beetle outbreak have three main limitations: (i) a small-spatial-scale implementation; (ii) specific field-based input datasets that are usually hard to obtain at large scales; and (iii) predictive models constrained by coarse climatic factors. Therefore, a methodological approach accounting for a comprehensive set of environmental traits that can predict a bark beetle outbreak accurately is needed. In particular, we aimed to (i) analyze the influence of environmental traits that cause bark beetle outbreaks; (ii) compare different machine learning architectures for predicting bark beetle attacks; and (iii) map the attack probability before the start of the bark beetle life cycle. Random Forest regression achieved the best-performing results. The predicted bark beetle damage reached a high robustness in the test area (F1 = 96.9, OA = 94.4) and showed low errors (CE = 2.0, OE = 4.2). Future improvements should focus on including additional variables, e.g., forest age and validation sites. Remote sensing-based methods contributed to detecting bark beetle outbreaks in large extensive forested areas in a cost-effective and robust manner.

Background Telehealth is comprised of telecommunications and electronic information systems to support and maintain long-distance healthcare services. Although it has not been thoroughly explored, the intention of using the service among the general public is critical to its success. We investigated the factors associated with the intention to utilize telehealth services among the general population of Bangladesh. Methods This cross-sectional study was conducted between May 22, 2021 and June 15, 2021 in Bangladesh, where the total number of participants was 1038. The Pearson chi-square test and Kruskal-Wallis H tests were used to examine the unadjusted relationship between the explanatory variables and the intention to use telehealth services. A multinomial logistic regression model was fitted to determine the adjusted association. Shapiro-Wilk tests were used to check the normality of continuous data. Data were processed and analyzed by software STATA-16. Results The probability of utilizing the service increased significantly with increasing knowledge, perceived benefit, and predisposition levels among respondents. However, when perceived concern increased, the likelihood of utilizing the service dropped significantly. Age, marital status, educational status, profession, residence, and perceived health status were significantly associated with the participants’ intention to utilize the telehealth service. Conclusions The influencing aspects of telehealth service utilization should be recognized by the respective authorities. Possible activities to enhance usability among people are also recommended.

Asthma, which affects some 300 million people worldwide and caused 455,000 deaths in 2019, is a significant burden to suffers and to society. It is the most common chronic disease in children and represents one of the major causes for years lived with disability. Significant efforts are made by organizations such as WHO in improving the diagnosis, treatment and monitoring of asthma. However asthma prevention has been less studied. Currently there is a concept of pre- diabetes which allows a reduction in full blown diabetes if diet and exercise are undertaken. Similar predictive states are found in Alzheimer's and Parkinson's diseases. In this paper we explore the possibilities for asthma prevention, both at population level and also investigate the possibility of defining a state of pre-asthma, in which intensive treatment could reduce progression to asthma. Since asthma is a heterogeneous condition, this paper is concerned with allergic asthma. A subsequent one will deal with late onset eosinophilic asthma.

Alcohol use is a growing global health concern and economic burden. Alcohol involvement (i.e., initiation, use, problematic use, alcohol use disorder) has been reliably associated with broad spectrum grey matter differences in cross‐sectional studies. These findings have been largely interpreted as reflecting alcohol‐induced atrophy. However, emerging data suggest that brain structure differences also represent pre‐existing vulnerability factors for alcohol involvement. Here, we review evidence from human studies with designs (i.e., family‐based, genomic, longitudinal) that allow them to assess the plausibility that these correlates reflect predispositional risk factors and/or causal consequences of alcohol involvement. These studies provide convergent evidence that grey matter correlates of alcohol involvement largely reflect predisposing risk factors, with some evidence for potential alcohol‐induced atrophy. These conclusions highlight the importance of study designs that can provide causal clues to cross‐sectional observations. An integrative model may best account for these data, in which predisposition to alcohol use affects brain development, effects which may then be compounded by the neurotoxic consequences of heavy alcohol use. [ABSTRACT FROM AUTHOR]

Musical training has long been viewed as a model for experience‐dependent brain plasticity. Reports of musical training‐induced brain plasticity are largely based on cross‐sectional studies comparing musicians to non‐musicians, which cannot address whether musical training itself is sufficient to induce these neurobiological changes or whether pre‐existing neuroarchitecture before training predisposes children to succeed in music. Here, in a longitudinal investigation of children from infancy to school age (n = 25), we find brain structure in infancy that predicts subsequent music aptitude skills at school‐age. Building on prior evidence implicating white matter organization of the corticospinal tract as a neural predisposition for musical training in adults, here we find that structural organization of the right corticospinal tract in infancy is associated with school‐age tonal and rhythmic musical aptitude skills. Moreover, within the corpus callosum, an inter‐hemispheric white matter pathway traditionally linked with musical training, we find that structural organization of this pathway in infancy is associated with subsequent tonal music aptitude. Our findings suggest predispositions prior to the onset of musical training from as early as infancy may serve as a scaffold upon which ongoing musical experience can build. Research Highlights: Structural organization of the right corticospinal tract in infancy is associated with school‐age musical aptitude skills.Longitudinal associations between the right corticospinal tract in infancy and school‐age rhythmic music aptitude skills remain significant even when controlling for language ability.Findings support the notion of predispositions for success in music, and suggest that musical predispositions likely build upon a neural structural scaffold established in infancy.Findings support the working hypothesis that a dynamic interaction between predisposition and experience established in infancy shape the trajectory of long‐term musical development. [ABSTRACT FROM AUTHOR]

European forest ecosystems are increasingly exposed to stressors such as storm, drought episodes and mass attack of forest insect pests. Sustainable forest management requires a fundamental understanding of causal relationships between forest structures and the occurrence of disturbance events, as well as a well-functioning transfer of scientific knowledge into practice. Risk or predisposition assessment, phenological models or prediction of deficits in stand water supply can serve as decision support for prophylactic and protective measures in forestry. This overview addresses the theoretical approaches to insect pest-related mortality in forests that form the basis for such models. Many insect herbivore species benefit from increased temperatures and drought. For example, there is a clear correlation between bark beetle infestation and summer temperatures, storm damage and precipitation deficits. Drought stress is one of the main factors predisposing conifer forests to bark beetle infestation and significantly impacts interactions among Picea abies, Ips typographus and its associated ophiostomatoid fungi. A multi-year study focused on the effects of drought on the defence capacity and attractiveness of Norway spruce to I. typographus. The empirical dataset gained in field and laboratory experiments provides new insights into defence responses of this important tree species against biotic infestations under drought.

A unique approach with rare resources was used to identify candidate variants predisposing to familial nonsquamous nonsmall‐cell lung cancers (NSNSCLC). We analyzed sequence data from NSNSCLC‐affected cousin pairs belonging to high‐risk lung cancer pedigrees identified in a genealogy of Utah linked to statewide cancer records to identify rare, shared candidate predisposition variants. Variants were tested for association with lung cancer risk in UK Biobank. Evidence for linkage with lung cancer was also reviewed in families from the Genetic Epidemiology of Lung Cancer Consortium. Protein prediction modeling compared the mutation with reference. We sequenced NSNSCLC‐affected cousin pairs from eight high‐risk lung cancer pedigrees and identified 66 rare candidate variants shared in the cousin pairs. One variant in the FGF5 gene also showed significant association with lung cancer in UKBiobank. This variant was observed in 3/163 additional sampled Utah lung cancer cases, 2 of whom were related in another independent pedigree. Modeling of the predicted protein predicted a second binding site for SO4 that may indicate binding differences. This unique study identified multiple candidate predisposition variants for NSNSCLC, including a rare variant in FGF5 that was significantly associated with lung cancer risk and that segregated with lung cancer in the two pedigrees in which it was observed. FGF5 is an oncogenic factor in several human cancers, and the mutation found here (W81C) changes the binding ability of heparan sulfate to FGF5, which might lead to its deregulation. These results support FGF5 as a potential NSNSCLC predisposition gene and present additional candidate predisposition variants. [ABSTRACT FROM AUTHOR]

Background Current WHO strategies for reaching soil-transmitted helminths (STH) elimination as a public health problem excludes treating certain adult populations in endemic areas, creating infection reservoirs that drive 'bounce back' of STH infection to pretreatment levels post-mass drug administration (MDA). Predisposition is a widespread, but poorly understood phenomena among helminth infections where individuals are predisposed to reinfection after repeated treatments. Methods This analysis uses Geshiyaro project data, an STH control programme exploring transmission interruption by community-wide MDA and enhanced water, sanitation and hygiene during 2019–2023. Parasitological survey data from longitudinal cohorts are analysed using Kendall's Tau-b rank correlation to assess the evidence for predisposition to light or heavy infection between four consecutive rounds of MDA. Results Correlation analyses revealed the strongest evidence for predisposition to heavy or light Ascaris lumbricoides infection was between survey 1 and 2 (Tau-b 0.29; p<0.001). Overall patterns were not observed for Trichuris trichiura or hookworm infections, however, some significant and notable correlations were recorded for some stratifications and time points. Conclusions Evidence for predisposition in endemic settings in southern Ethiopia with low STH prevalence suggests that more targeted approaches to MDA in those predisposed to infection may be a sensible control strategy if cheap, point of care diagnostics are available. [ABSTRACT FROM AUTHOR]

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Children and minors in most criminal legislations in the world enjoy a privileged status due to their psychological and physical immaturity. While children belong to the category of completely criminally irresponsible persons, minors are subject to liability, but under specific conditions, defined by the Criminal Code of the Republic of Serbia and the Law on juvenile offenders and the criminal protection of minors. The latest events that have taken place in the Republic of Serbia have encouraged thinking about whether the age limit for criminal responsibility should be reduced, whether punitive measures should be tightened and what preventive measures should be taken to reduce the issue of children and minors committing crimes and prevent tragedies like the tragedy from happening again in the model elementary school "Vladislav Ribnikar" in Belgrade.

Coronavirus disease 2019 (COVID-19) is a lethal disease caused by the coronavirus SARS-CoV-2, which can result in a broad clinical spectrum of respiratory symptoms. While many clinical risk factors such as concomitant chronic diseases play roles in the pathophysiology of COVID-19, genetic predisposition factors have not been widely studied. The aim of this study was, therefore, to evaluate the relationship between some singlenucleotide polymorphisms (SNPs) of the human genes TYK2 and ACE2 and the severity of SARS-CoV-2 infection. Genomic DNA was isolated from 200 SARS-CoV-2-infected individuals with severe (n = 100) or mild (n = 100) disease. Owing to the importance of ACE2 and TYK2 genes in regulating the immune response to SARS-CoV-2 infection, TYK2 gene SNPs, i.e. rs2304255, rs2304256, rs12720270, and rs12720354 and ACE2 rs382746 variants, were genotyped in the samples. To confirm the results, the expression of different TYK2 genotypes was investigated using real-time PCR. The presence of the nucleotide T at the locus rs2304255 was shown to be a risk factor linked to disease severity (OR [95% CI] = 3.2485 [2.1554–4.8961]). Similarly, the presence of A at the locus rs12720354 increased the risk of severity (OR [95% CI]) = 3.9721 [2.6075–6.0509]). In contrast, the presence of A at the loci rs2304256 and rs12720270 was observed to reduce the severity risk (OR [95% CI] = 0.2495 [0.1642–0.3793] and 0.1668 [0.1083–0.2569], respectively). Real-time PCR results also demonstrated that the expression level of TYK2 in samples with the TT genotype of rs2304255 and the AA genotype of rs12720354 and in samples with the GG genotype of rs12720207 was significantly lower than in those with other genotypes. The results of this study suggest that TYK2 SNPs might be utilized to identify individuals who are at risk for severe COVID-19, in order to better manage their health care. It is predicted that the presence of some alleles (T in rs2304255, A in rs12720354, and G in rs12720207) of TYK2 can affect COVID-19 severity by reducing TYK2 expression and thereby affecting the regulatory role of TYK2 in the immune response. [ABSTRACT FROM AUTHOR]

Simple Summary: There remains a lack of identification of genes responsible for the most aggressive of prostate cancers. A unique resource consisting of sampled, related men who died from their confirmed prostate cancer and who were members of pedigrees shown to have a significant excess of prostate cancer cases has allowed the identification of multiple rare candidate predisposition variants for prostate cancer. Strong candidate variants are presented, including a rare, validated variant in the gene LRBA, all of which can be examined further in additional studies. There is evidence for contribution of inherited factors to prostate cancer, and more specifically to lethal prostate cancer, but few responsible genes/variants have been identified. We examined genetic sequence data for 51 affected cousin pairs who each died from prostate cancer and who were members of high-risk prostate cancer pedigrees in order to identify rare variants shared by the cousins as candidate predisposition variants. Candidate variants were tested for association with prostate cancer risk in UK Biobank data. Candidate variants were also assayed in 1195 additional sampled Utah prostate cancer cases. We used 3D protein structure prediction methods to analyze structural changes and provide insights into mechanisms of pathogenicity. Almost 4000 rare (<0.005) variants were identified as shared in the 51 affected cousin pairs. One candidate variant was also significantly associated with prostate cancer risk among the 840 variants with data in UK Biobank, in the gene LRBA (p = 3.2 × 10−5; OR = 2.09). The rare risk variant in LRBA was observed to segregate in five pedigrees. The overall predicted structures of the mutant protein do not show any significant overall changes upon mutation, but the mutated structure loses a helical structure for the two residues after the mutation. This unique analysis of closely related individuals with lethal prostate cancer, who were members of high-risk prostate cancer pedigrees, has identified a strong set of candidate predisposition variants which should be pursued in independent studies. Validation data for a subset of the candidates identified are presented, with strong evidence for a rare variant in LRBA. [ABSTRACT FROM AUTHOR]

Les leucémies aiguës myéloïdes (LAM) de l'enfant de moins de 15 ans touchent 65 à 85 patients par an en France. Le diagnostic de la LAM nécessite une analyse morphologique précise des blastes leucémiques et de leur environnement cellulaire, un immunophénotypage qui définit le stade de lignage et une analyse cytogénétique et moléculaire complète qui déterminent des facteurs pronostiques et permettent d'établir le niveau de risque et de prédire l'issue de la maladie. La rareté et l'hétérogénéité des LAM pédiatriques rend difficile la caractérisation de facteurs pronostiques sans études collaboratives internationales. Les anomalies génétiques associées aux LAM pédiatriques sont différentes des anomalies associées à celles des patients adultes, de même que la présentation clinique diffère un peu. Certaines anomalies génétiques prédisposent aux LAM ou sont en lien avec un syndrome d'insuffisance médullaire héréditaire. Les LAM rencontrées chez l'enfant de moins de 2 ans, et en particulier les néonatales, celles diagnostiquées chez un enfant atteint d'un syndrome de Down ou encore les aspects morphologiques spécifiques des LAM pédiatriques sont autant de particularités qu'il est nécessaire de connaître pour une prise en charge optimale du diagnostic et du suivi de cette entité clinico-biologique. Acute myeloid leukaemia (AML) in children under 15 years old affects 65-85 patients per year in France. Diagnosis of AML requires accurate morphological analysis of leukaemic blasts and their cellular environment, immunophenotyping to define the lineage stage and comprehensive cytogenetic and molecular analysis to determine prognostic factors and establish the level of risk and predict the outcome of the disease. The rarity and heterogeneity of paediatric AML makes it difficult to characterise prognostic factors without international collaborative studies. The genetic abnormalities associated with paediatric AML are different from those associated with AML in adult patients, and the clinical presentation differs somewhat from that in adults. Some genetic abnormalities predispose to AML or are associated with an inherited bone marrow failure syndrome. AML in children under 2 years old, including infant AML, AML diagnosed in children with Down syndrome and the specific morphological aspects of paediatric AML are all features that should be known for optimal diagnosis and follow-up management of this entity. [ABSTRACT FROM AUTHOR]

Equine recurrent uveitis (ERU) is an ocular inflammatory disease that can be difficult to manage clinically. As such, it is the leading cause of bilateral blindness for horses. ERU is suspected to have a complex autoimmune etiology with both environmental and genetic risk factors contributing to onset and disease progression in some or all cases. Work in recent years has aimed at unraveling the primary triggers, such as infectious agents and inherited breed‐specific risk factors, for disease onset, persistence, and progression. This review has aimed at encompassing those factors that have been associated, implicated, or substantiated as contributors to ERU, as well as identifying areas for which additional knowledge is needed to better understand risk for disease onset and progression. A greater understanding of the risk factors for ERU will enable earlier detection and better prognosis through prevention and new therapeutics. [ABSTRACT FROM AUTHOR]

Uterine leiomyomas (ULs) are benign smooth muscle tumors that are common in premenopausal women. Somatic alterations in MED12 , HMGA2 , FH , genes encoding subunits of the SRCAP complex, and genes involved in Cullin 3-RING E3 ligase neddylation are mutually exclusive UL drivers. Established predisposition genes explain only partially the estimated heritability of leiomyomas. Here, we examined loss-of-function variants across 18,899 genes in a cohort of 233,614 White European women, revealing variants in four genes encoding SRCAP complex subunits (YEATS4 , ZNHIT1 , DMAP1 , and ACTL6A) with a significant association to ULs, and YEATS4 and ZNHIT1 strikingly rank first and second, respectively. Positive mutation status was also associated with younger age at diagnosis and hysterectomy. Moderate-penetrance UL risk was largely attributed to rare non-synonymous mutations affecting the SRCAP complex. To examine this disease phenotype more closely, we set out to identify inherited mutations affecting the SRCAP complex in our in-house sample collection of Finnish individuals with ULs (n = 860). We detected one individual with an ACTL6A splice-site mutation, two individuals with a YEATS4 missense mutation, and four individuals with DMAP1 mutations: one splice-site, one nonsense, and two missense variants. These individuals had large and/or multiple ULs, were often diagnosed at an early age, and many had family history of ULs. When a somatic second hit was found, ACTL6A and DMAP1 were silenced in tumors by somatic mutation and YEATS4 by promoter hypermethylation. Decreased H2A.Z staining was observed in the tumors, providing further evidence for the pathogenic nature of the germline mutations. Our results establish inactivation of genes encoding SRCAP complex subunits as a central contributor to moderate-penetrance UL predisposition. UK Biobank whole-exome data revealed an association between mutations in genes encoding the SRCAP complex and uterine leiomyomas (ULs). In our collection of 860 individuals, we identified seven women with inherited mutations in ACTL6A , YEATS4 , and DMAP1. Our results establish these genes as central contributors to moderate-penetrance UL predisposition. [ABSTRACT FROM AUTHOR]

Familial non-medullary thyroid carcinoma (FNMTC) accounts for 3% to 9% of all thyroid cancer cases, yet its genetic mechanisms remain unknown. Our study aimed to screen and identify novel susceptibility genes for FNMTC. Whole-exome sequencing (WES) was conducted on a confirmed FNMTC pedigree, comprising four affected individuals across two generations. Variants were filtered and analyzed using ExAC and 1000 Genomes Project, with candidate gene pathogenicity predicted using SIFT, PolyPhen, and MutationTaster. Validation was performed through Sanger sequencing in affected pedigree members and sporadic patients (TCGA database) as well as general population data (gnomAD database). Ultimately, we identified the mutant PPP4R3A (NC_000014.8:g.91942196C>T, or NM_001366432.2(NP_001353361.1):p.(Asp409Asn), based on GRCH37) as an FNMTC susceptibility gene. Subsequently, a series of functional experiments were conducted to investigate the impact of PPP4R3A and its Asp409Asn missense variant in thyroid cancer. Our findings demonstrated that wild-type PPP4R3A exerted tumor-suppressive effects via the Akt-mTOR-P70 S6K/4E-BP1 axis. However, overexpression of the PPP4R3A Asp409Asn mutant resulted in loss of tumor-suppressive function, ineffective inhibition of cell invasion, and even promotion of cell proliferation and migration by activating the Akt/mTOR signaling pathway. These results indicated that the missense variant PPP4R3A Asp409Asn is a candidate susceptibility gene for FNMTC, providing new insights into the diagnosis and intervention of FNMTC.

The World Health Organization warns of alarmingly high levels of sedentary behavior in our current society. In terms of the adolescent population, a substantial percentage of them do not meet the global recommendations for weekly physical activity. Therefore, this qualitative study aimed to analyze the predisposition and future preferences for physical activity and sports (PAS) and leisure practices of 142 adolescents, as well as identifying the challenges and proposed improvements, while considering gender differences. The participants’ reflections were gathered through semistructured interviews and focus groups and subjected to an inductive analysis. The main findings indicate a high intention to engage in future PAS and leisure activity. Individual sports were predominantly mentioned by girls, while team sports were mainly favored by boys. Additionally, boys expressed a preference for technology-related leisure activities, whereas girls leaned towards artistic activities. The participants emphasized the necessity to renew sports and recreational facilities and to adapt to the range of activities offered. At the same time, they acknowledged that reallocating economic resources would improve the quality of sports and health-care services. Consequently, institutions should tailor their programs of PAS and leisure activities to align with the preferences, ages, and genders of the youth population.

Background: Predisposition to myeloid malignancies is a field at the border of hematology and genetics. Knowledge in this domain has so rapidly increased that WHO defined in 2016 the new "Myeloid Neoplasms with Germline Predisposition" category of tumors. High throughput sequencing is frequently performed in tumors either for diagnosis or prognosis, but this approach may identify potential germline variants that have to be confirmed on non-infiltrated tissues. Method: In this study, we systematically compared NGS data from genetic analysis performed on all sample types (bone marrow, blood, saliva, skin fibroblasts and hair follicles) in 29 patients, and 44 of their relatives (blood and saliva). Results: We showed that saliva was usable for relatives, but only for 24% (7/29) of our patients. Most of patients' saliva were either "non-contributive" (14/29 i.e., 48% because clearly or probably infiltrated) or "inconclusive" (8/29 corresponding to 28%). Conclusion: The recommendations for the use of saliva we present here focus on the importance of collecting saliva during remission when possible. Moreover, we propose hair follicles as an alternative to skin biopsy, that remains the gold standard especially in case of allogenic hematopoietic stem cells transplantation. Technological progresses have revolutionized the diagnosis of predisposition to solid or hematological malignancies, and it is very likely that new techniques will help to manage the familial predisposition in the future. [ABSTRACT FROM AUTHOR]