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In thrombotic diseases, coagulation, anticoagulation, and fibrinolysis are three key physiological processes that interact to maintain blood in an appropriate state within blood vessels. When these processes become imbalanced, such as excessive coagulation or reduced anticoagulant function, it can lead to the formation of blood clots. Genetic factors play a significant role in the onset of thrombotic diseases and exhibit regional and ethnic variations. The decision of whether to initiate prophylactic anticoagulant therapy is a matter that clinicians must carefully consider, leading to the development of various thrombotic risk assessment scales in clinical practice. Given the considerable heterogeneity in clinical diagnosis and treatment, researchers are exploring the application of artificial intelligence in medicine, including disease prediction, diagnosis, treatment, prevention, and patient management. This paper reviews the research progress on various genetic factors involved in thrombotic diseases, analyzes the advantages and disadvantages of commonly used thrombotic risk assessment scales and the characteristics of ideal scoring scales, and explores the application of artificial intelligence in the medical field, along with its future prospects. [ABSTRACT FROM AUTHOR]

Background: Intermittent theta burst stimulation (iTBS) when applied over the left dorsolateral prefrontal cortex (DLPFC) has been shown to be equally effective and safe to treat depression compared to traditional repetitive transcranial magnetic stimulation (rTMS) paradigms. This protocol describes a funded single-centre, double-blind, randomized placebo-controlled, clinical trial to investigate the antidepressive effects of iTBS and factors associated with an antidepressive response. Methods: In this trial, outpatients (N = 96, aged 22–65 years) meeting the diagnostic criteria for at least moderate depression (Montgomery and Aasberg Depression Rating Scale score ≥ 20) will be enrolled prospectively and receive ten, once-a-day sessions of either active iTBS or sham iTBS to the left DLPFC, localized via a neuronavigation system. Participants may have any degree of treatment resistance. Prior to stimulation, participants will undergo a thorough safety screening and a brief diagnostic assessment, genetic analysis of brain-derived neurotropic factor, 5-HTTLPR and 5-HT1A, and cerebral MRI assessments. A selection of neuropsychological tests and questionnaires will be administered prior to stimulation and after ten stimulations. An additional follow-up will be conducted 4 weeks after the last stimulation. The first participant was enrolled on June 4, 2022. Study completion will be in December 2027. The project is approved by the Regional Ethical Committee of Medicine and Health Sciences, Northern Norway, project number 228765. The trial will be conducted according to Good Clinical Practice and published safety guidelines on rTMS treatment. Discussion: The aims of the present trial are to investigate the antidepressive effect of a 10-session iTBS protocol on moderately depressed outpatients and to explore the factors that can explain the reduction in depressive symptoms after iTBS but also a poorer response to the treatment. In separate, but related work packages, the trial will assess how clinical, cognitive, brain imaging and genetic measures at baseline relate to the variability in the antidepressive effects of iTBS. Trial registration: ClinicalTrials.gov NCT05516095. Retrospectively registered on August 25, 2022. [ABSTRACT FROM AUTHOR]

Background: Low birth weight (LBW) is a leading cause of neonatal morbidity and mortality, and increases various disease risks across life stages. Prediction models of LBW have been developed before, but have limitations including small sample sizes, absence of genetic factors and no stratification of neonate into preterm and term birth groups. In this study, we challenged the development of early prediction models of LBW based on environmental and genetic factors in preterm and term birth groups, and clarified influential variables for LBW prediction. Methods: We selected 22,711 neonates, their 21,581 mothers and 8,593 fathers from the Tohoku Medical Megabank Project Birth and Three-Generation cohort study. To establish early prediction models of LBW for preterm birth and term birth groups, we trained AI-based models using genetic and environmental factors of lifestyles. We then clarified influential environmental and genetic factors for predicting LBW in the term and preterm groups. Results: We identified 2,327 (10.22%) LBW neonates consisting of 1,077 preterm births and 1,248 term births. Our early prediction models archived the area under curve 0.96 and 0.95 for term LBW and preterm LBW models, respectively. We revealed that environmental factors regarding eating habits and genetic features related to fetal growth were influential for predicting LBW in the term LBW model. On the other hand, we identified that genomic features related to toll-like receptor regulations and infection reactions are influential genetic factors for prediction in the preterm LBW model. Conclusions: We developed precise early prediction models of LBW based on lifestyle factors in the term birth group and genetic factors in the preterm birth group. Because of its accuracy and generalisability, our prediction model could contribute to risk assessment of LBW in the early stage of pregnancy and control LBW risk in the term birth group. Our prediction model could also contribute to precise prediction of LBW based on genetic factors in the preterm birth group. We then identified parental genetic and maternal environmental factors during pregnancy influencing LBW prediction, which are major targets for understanding the LBW to address serious burdens on newborns' health throughout life. [ABSTRACT FROM AUTHOR]

Background: Vogt‒Koyanagi‒Harada (VKH) disease is a multifactorial systemic autoimmune disorder against melanocytes that is characterized by panuveitis. Familial occurrence of VKH disease is rare. Here, we report two cases of a father and his son with characteristic manifestations of VKH disease. Case presentation: A 53-year-old male with typical clinical symptoms of VKH disease was referred to Tangshan Eye Hospital. Examination showed the presence of ciliochoroidal effusion and exudative retinal detachment in both eyes. The patient was given intravenous methylprednisolone 120 mg for 2 days and intravenous methylprednisolone 80 mg for 1 day followed by 48 mg (1 mg/kg/day) oral methylprednisolone daily, accompanied by oral azathioprine 50 mg daily. Cycloplegic agent (0.5% tropicamide three times daily [TID]) was added. The patient was free of symptoms and recurrence within more than 1-year-follow-up period, the best corrected visual acuity (BVCA) was increased and maintained in both eyes with complete resolution of subretinal fluid. One year and nine months later, case 2 (his son) also presented with the typical clinical symptoms of VKH disease at 29 years of age. The son also recovered from VKH disease after routine and standard treatment. Conclusions: To the best of our knowledge, this is the first VKH disease case report of a father-son relationship. Although genetic factors have been demonstrated to be involved in the pathogenesis of VKH disease, the different inheritance modes of VKH patients need to be further explored and studied. [ABSTRACT FROM AUTHOR]

Background: A family history of arterial hypertension is an important risk factor for arterial hypertension. This study aimed to verify the mediating role of high central adiposity in the relationship between family history of arterial hypertension and blood pressure in schoolchildren.Methods: Cross-sectional study with 118 schoolchildren of both sexes aged between 11 and 17 years. Weight, height, waist circumference and body mass index z score were verified. Somatic maturation was predicted by age for peak growth velocity. The family history of arterial hypertension was verified and defined as hypertensive schoolchildren with systolic blood pressure or diastolic blood pressure. Mediation analysis was used with linear regression models applied by PROCESS macro for SPSS (version 22.0), with significance p < 0.05.Results: It was observed that 34.7% of the students have family history of arterial hypertension, 36% of the girls and 44.2% of the boys have arterial hypertension. In girls, the relationship between waist circumference and systolic blood pressure was direct (β = 0.535 p = 0.005), and those with a family history of arterial hypertension and who had a waist circumference greater than those without a family history of arterial hypertension was significant (β = -5,437 p = 0.009). Likewise, the relationship between family history of arterial hypertension and systolic blood pressure was attenuated when waist circumference was included in the model (β = -5.544; p = 0.103), indicating waist circumference as a mediator with an influence percentage of 19%. For boys, waist circumference is not a mediator of the relationship between family history of arterial hypertension and blood pressure.Conclusions: Elevated central adiposity was a mediator of the relationship between family history of arterial hypertension and high blood pressure in girls, indicating the importance of family health strategies in the prevention and management of arterial hypertension in children and adolescents. [ABSTRACT FROM AUTHOR]

Background: Legg-Calvé-Perthes Disease (LCPD) is a necrosis of the femoral head which affects the range of motion of the hips. Its incidence is variable, ranging from 0.4/100,000 to 29.0/ 100,000 children. Although LCPD was first described in the beginning of the past century, limited is known about its etiology. Our objective is to describe the main areas of interest in Legg-Calve-Perthes disease.Methods: A review of the literature regarding LCPD etiology was performed, considering the following inclusion criteria: Studies reporting clinical or preclinical results. The research group carried out a filtered search on the PubMed and Science Direct databases. To maximize the suitability of the search results, we combined the terms ''Perthes disease" OR "LCPD" OR "children avascular femoral head necrosis" with "diagnostic" OR "treatment" OR "etiology" as either key words or MeSH terms.Results: In this article been described some areas of interest in LCPD, we include topics such as: history, incidence, pathogenesis, diagnosis, treatment and possible etiology, since LCPD has an unknown etiology.Conclusions: This review suggests that LCPD has a multifactorial etiology where environmental, metabolic and genetic agents could be involved. [ABSTRACT FROM AUTHOR]

Following cervical and uterine cancer, ovarian cancer (OC) has the third rank in gynecologic cancers. It often remains non-diagnosed until it spreads throughout the pelvis and abdomen. Identification of the most effective risk factors can help take prevention measures concerning OC. Therefore, the presented review aims to summarize the available studies on OC risk factors. A comprehensive systematic literature search was performed to identify all published systematic reviews and meta-analysis on associated factors with ovarian cancer. Web of Science, Cochrane Library databases, and Google Scholar were searched up to 17th January 2020. This study was performed according to Smith et al. methodology for conducting a systematic review of systematic reviews. Twenty-eight thousand sixty-two papers were initially retrieved from the electronic databases, among which 20,104 studies were screened. Two hundred seventy-seven articles met our inclusion criteria, 226 of which included in the meta-analysis. Most commonly reported genetic factors were MTHFR C677T (OR=1.077; 95 % CI (1.032, 1.124); P-value<0.001), BSML rs1544410 (OR=1.078; 95 %CI (1.024, 1.153); P-value=0.004), and Fokl rs2228570 (OR=1.123; 95 % CI (1.089, 1.157); P-value<0.001), which were significantly associated with increasing risk of ovarian cancer. Among the other factors, coffee intake (OR=1.106; 95 % CI (1.009, 1.211); P-value=0.030), hormone therapy (RR=1.057; 95 % CI (1.030, 1.400); P-value<0.001), hysterectomy (OR=0.863; 95 % CI (0.745, 0.999); P-value=0.049), and breast feeding (OR=0.719, 95 % CI (0.679, 0.762) and P-value<0.001) were mostly reported in studies. Among nutritional factors, coffee, egg, and fat intake significantly increase the risk of ovarian cancer. Estrogen, estrogen-progesterone, and overall hormone therapies also are related to the higher incidence of ovarian cancer. Some diseases, such as diabetes, endometriosis, and polycystic ovarian syndrome, as well as several genetic polymorphisms, cause a significant increase in ovarian cancer occurrence. Moreover, other factors, for instance, obesity, overweight, smoking, and perineal talc use, significantly increase the risk of ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Frailty has been identified as a risk factor for cognitive impairment and dementia. However, it is not known whether familial factors, such as genetics and shared environmental factors, underlie this association. We analyzed the association between frailty and the risk of dementia in a large twin cohort and examined the role of familial factors in the association.Methods: The Rockwood frailty index (FI) based on 44 health deficits was used to assess frailty. The population-level association between FI and the risk of all-cause dementia was analyzed in 41,550 participants of the Screening Across the Lifespan Twin (SALT) study (full sample, aged 41-97 years at baseline), using Cox and competing risk models. A subsample of 10,487 SALT participants aged 65 and older who received a cognitive assessment (cognitive sample) was used in a sensitivity analysis to assess the effect of baseline cognitive level on the FI-dementia association. To analyze the influence of familial effects on the FI-dementia association, a within-pair analysis was performed. The within-pair model was also used to assess whether the risk conferred by frailty varies by age at FI assessment.Results: A total of 3183 individuals were diagnosed with dementia during the 19-year follow-up. A 10% increase in FI was associated with an increased risk of dementia (hazard ratio [HR] 1.17 (95% confidence interval [CI] 1.07, 1.18)) in the full sample adjusted for age, sex, education, and tobacco use. A significant association was likewise found in the cognitive sample, with an HR of 1.13 (95% CI 1.09, 1.20), adjusted for age, sex, and cognitive level at baseline. The associations were not attenuated when adjusted for APOE ɛ4 carrier status or considering the competing risk of death. After adjusting for familial effects, we found no evidence for statistically significant attenuation of the effect. The risk conferred by higher FI on dementia was constant after age 50 until very old age.Conclusions: A higher level of frailty predicts the risk of dementia and the association appears independent of familial factors. Targeting frailty might thus contribute to preventing or delaying dementia. [ABSTRACT FROM AUTHOR]

Background: Multimorbidities greatly increase the global health burdens, but the landscapes of their genetic risks have not been systematically investigated. Methods: We used the hospital inpatient data of 385,335 patients in the UK Biobank to investigate the multimorbid relations among 439 common diseases. Post-GWAS analyses were performed to identify multimorbidity shared genetic risks at the genomic loci, network, as well as overall genetic architecture levels. We conducted network decomposition for the networks of genetically interpretable multimorbidities to detect the hub diseases and the involved molecules and functions in each module. Results: In total, 11,285 multimorbidities among 439 common diseases were identified, and 46% of them were genetically interpretable at the loci, network, or overall genetic architecture levels. Multimorbidities affecting the same and different physiological systems displayed different patterns of the shared genetic components, with the former more likely to share loci-level genetic components while the latter more likely to share network-level genetic components. Moreover, both the loci- and network-level genetic components shared by multimorbidities converged on cell immunity, protein metabolism, and gene silencing. Furthermore, we found that the genetically interpretable multimorbidities tend to form network modules, mediated by hub diseases and featuring physiological categories. Finally, we showcased how hub diseases mediating the multimorbidity modules could help provide useful insights for the genetic contributors of multimorbidities. Conclusions: Our results provide a systematic resource for understanding the genetic predispositions of multimorbidities and indicate that hub diseases and converged molecules and functions may be the key for treating multimorbidities. We have created an online database that facilitates researchers and physicians to browse, search, or download these multimorbidities (https://multimorbidity.comp-sysbio.org). [ABSTRACT FROM AUTHOR]

Background: The microbiome of the digestive tract of ruminants contains microbial ecosystem that is affected by both environmental and genetic factors. The subject of this study concerns the influence of selected genetic factors, such as species of animals and "host" individual differences on the digestive tract microbiome composition. The results show the core microbiological composition (Firmicutes and Bacteroidetes) of ruminants digestive tract (based on feces) depending on breed and "host". The Bacteroidetes and Firmicutes phyla are the most abundant in ruminants digestive tract. The aim of the study was to determine the differences prevalence level of Bacteroidetes and Firmicutes phyla in feces of Charolaise cattle and Polish Olkuska Sheep with respect to intra- and inter-species variability. Results: The research group in the experiment consisted of animals at the age of 3 months kept in the same environmental conditions – rams of Polish Olkuska Sheep (n = 10) and Charolaise bulls (n = 10). Feces were collected individually from each animal (animals without disease symptoms were selected), living on the same environmental conditions. The analysis of the results in terms of species showed differences in the Firmicutes phylum level and Lactobacillaceae family between rams and bulls. Subsequently, the analysis performed for the "host effect" showed differentiation in the levels of the Bacteroidetes and Firmicutes phyla between individuals in a group and also between the groups. Conclusion: The obtained results suggest that, apart from the diet and the environment, the species and the individual host are equally important factors influencing the microbiological composition of the digestive system of ruminants. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress has been suggested as a major cause of elevated blood pressure (BP) and reduced heart rate variability (HRV) due to air pollution. We hypothesized that the associations of air pollution exposure with BP and HRV are modified by oxidative stress gene polymorphisms.Methods: Between 2008 and 2010, we conducted up to 5 surveys of 547 elderly participants, measured their BP and HRV, and genotyped 47 single nucleotide polymorphisms (SNPs) in 18 oxidative stress genes. Linear mixed models were constructed to evaluate the associations of particulate matter ≤10 μm, nitrogen dioxide, and sulfur dioxide with BP and HRV, as well as the modifications of these associations by the genotyped SNPs.Results: Single-SNP analyses revealed interactions between air pollution and 15 SNPs (for BP) and 33 SNPs (for HRV) (all, P for interaction < 0.05). When we generated genetic risk scores for BP and HRV, using the SNPs with interactions in the single-SNP models, we found that associations of air pollution exposure with BP and HRV were modified by the genetic risk scores (P for interaction < 0.05).Conclusions: These results strongly suggest that the associations of air pollution with BP and HRV are mediated by oxidative stress pathways. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder caused by complex interaction of genetic and environmental factors. Besides mutations in the filaggrin gene, leading to impaired skin barrier function, variation in genes encoding additional skin proteins has been suggested to contribute to disease risk. Laminin 5, playing an important role in skin integrity, is composed of three subunits encoded by the LAMA3, LAMB3 and LAMC2 genes in which biallelic mutations cause epidermolysis bullosa junctionalis. We aimed at evaluating the role of variation in the LAMA3, LAMB3 and LAMC2 genes for AD pathogenesis. Methods: 29 single nucleotide polymorphisms (SNPs) were genotyped in the three genes in a German AD case–control cohort comprising 470 unrelated AD patients and 320 non-atopic controls by means of restriction enzyme digestion. Allele, genotype and haplotype frequencies were compared between cases and controls using chi-square testing and the Haploview software. Results: Several SNPs in the LAMA3 gene showed significant association with AD in our cohort (p <0.01), while we did not detect association with variations in the LAMB3 and LAMC2 genes. Haplotype analysis additionally revealed several significantly associated haplotypes in the LAMA3 gene. Due to extensive linkage disequilibrium, though, we were not able to further differentiate the specific disease causing variation(s) in this region. Conclusions: We established the LAMA3 gene as novel potential susceptibility gene for AD. Additional studies in independent cohorts are needed to replicate these results. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress has been suggested as a major cause of elevated blood pressure (BP) and reduced heart rate variability (HRV) due to air pollution. We hypothesized that the associations of air pollution exposure with BP and HRV are modified by oxidative stress gene polymorphisms., Methods: Between 2008 and 2010, we conducted up to 5 surveys of 547 elderly participants, measured their BP and HRV, and genotyped 47 single nucleotide polymorphisms (SNPs) in 18 oxidative stress genes. Linear mixed models were constructed to evaluate the associations of particulate matter ≤10 μm, nitrogen dioxide, and sulfur dioxide with BP and HRV, as well as the modifications of these associations by the genotyped SNPs., Results: Single-SNP analyses revealed interactions between air pollution and 15 SNPs (for BP) and 33 SNPs (for HRV) (all, P for interaction < 0.05). When we generated genetic risk scores for BP and HRV, using the SNPs with interactions in the single-SNP models, we found that associations of air pollution exposure with BP and HRV were modified by the genetic risk scores (P for interaction < 0.05)., Conclusions: These results strongly suggest that the associations of air pollution with BP and HRV are mediated by oxidative stress pathways.