UNASSIGNED: There is evidence from observational studies that skin microbiota is linked to skin cancers. Nevertheless, the causal association between skin microbiota and skin cancers is yet to be fully clarified.
UNASSIGNED: A bidirectional two-sample Mendelian randomization (MR) was performed to determine the causal relationship between skin microbiota and skin cancers. A total of 294 skin microbial taxa were identified from the first genome-wide association study across three skin microenvironments of two German population cohorts. Summary data of three skin cancers (malignant melanoma, squamous cell carcinoma, and basal cell carcinoma) were obtained from the FinnGen consortium. Moreover, sensitivity analysis examined horizontal pleiotropy and heterogeneity, and microenvironment-based meta-analysis confirmed the reliability of the results.
UNASSIGNED: We identified 65 nominal causalities and 5 strong causal associations between skin microbiota and skin cancers. Among them, the class Bacilli revealed a bidirectional positive relationship with malignant melanoma. The class Betaproteobacteria and class Gammaproteobacteria demonstrated a causal association with an elevated risk of malignant melanoma and basal cell carcinoma, respectively. In the reverse MR analysis, malignant melanoma was associated with a lower abundance of phylum Bacteroidetes. There were no indications of significant heterogeneity in instrumental variables or evidence of horizontal pleiotropy.
UNASSIGNED: Our MR analysis indicated bidirectional causal associations between skin microbiota and skin cancers, and had the potential to offer novel perspectives on the mechanistic of microbiota-facilitated carcinogenesis.

OBJECTIVE: Osteoarthritis (OA) is a complex multifactorial disease. The association of knee OA risk with ACE gene rs4343 polymorphism, gene environment synergistic effect, and angiotensin II serum level has not been previously examined. Therefore, we investigate the ACE gene rs4343 polymorphism in knee OA, and its association with severity of knee OA, and angiotensin II serum level.
METHODS: Using a case-control design, we recruited 200 subjects (100 cases and 100 controls) and all were subjected to genotyping of rs4343 SNP by real-time polymerase chain reaction and assay of serum angiotensin II level by ELISA.
RESULTS: G containing genotypes (AG and GG) and G allele frequencies of the ACE rs4343 polymorphism were significantly higher in the case group than that in the control group. There was significant association between ACE rs4343 genotypes and risk of knee OA under the following genetic inheritance models: GG vs. AA (P=0.003), AA vs. GG/AG (P=0.014), AG/AA vs. GG (P=0.037), and G vs. A (P<0.001). Stratified analyses showed ACE rs4343 polymorphism was evidently associated with a significantly increased risk of knee OA among those had BMI≥25% (adjusted OR=3.016; 95% CI 1.052-8.648; P=0.040). Additionally, knee OA patients with GG genotype had greater knee specific WOMAC index, Kellgren score, and serum angiotensin II level than those with AA or GA genotypes.
CONCLUSIONS: The investigated polymorphism in the ACE gene rs4343 may reflect the risk and severity of knee OA in the Egyptian population, particularly with the GG genotype. The interaction between ACE gene rs4343 polymorphism and obesity further increased the risk of knee OA. Moreover, the higher angiotensin II level may be involved in the pathogenesis of knee OA.

暂无摘要。

Phenotyping of animals is a routine task in agriculture which can provide large datasets for the functional annotation of genomes. Using the livestock farming sector to study complex traits enables genetics researchers to fully benefit from the digital transformation of society as economies of scale substantially reduces the cost of phenotyping animals on farms. In the agricultural sector genomics has transitioned towards a model of \'Genomics without the genes\' as a large proportion of the genetic variation in animals can be modelled using the infinitesimal model for genomic breeding valuations. Combined with third generation sequencing creating pan-genomes for livestock the digital infrastructure for trait collection and precision farming provides a unique opportunity for high-throughput phenotyping and the study of complex traits in a controlled environment. The emphasis on cost efficient data collection mean that mobile phones and computers have become ubiquitous for cost-efficient large-scale data collection but that the majority of the recorded traits can still be recorded manually with limited training or tools. This is especially valuable in low- and middle income countries and in settings where indigenous breeds are kept at farms preserving more traditional farming methods. Digitalization is therefore an important enabler for high-throughput phenotyping for smaller livestock herds with limited technology investments as well as large-scale commercial operations. It is demanding and challenging for individual researchers to keep up with the opportunities created by the rapid advances in digitalization for livestock farming and how it can be used by researchers with or without a specialization in livestock. This review provides an overview of the current status of key enabling technologies for precision livestock farming applicable for the functional annotation of genomes.

The perinatal maternal environment is important for the normal development of the fetus. Epigenetic modifications that influence developmental control genes and signalling pathways for proper fetal development have been associated with maternal illnesses brought on by viruses, bacteria, or even parasitic protozoa. It is crucial to provide details on the onset, length, and timing of the mother\'s fever because these factors may influence the kind of certain abnormalities. Although fever is a primarily benign disease, it has been linked to negative health outcomes in children and has occasionally resulted in a substantial referral to critical care. This case report presents a 15-year-old female patient with repaired cleft palate and tetralogy of Fallot (TOF) who approached for esthetic rehabilitation of lower anterior teeth. The teeth (31, 32, 43) were tender on percussion. Radiographic evaluation showed the presence of periapical radiolucency. The root canal procedure was performed under local anaesthesia, and the supernumerary maxillary teeth were extracted. After cleaning and disinfecting, these teeth were used as biologic posts with respect to 32 and 33. A follow-up examination was performed after 12 months. The results of this case indicate that using autologous heterodontic biologic posts can lead to a favourable outcome.

OBJECTIVE: To investigate the approach taken by clinicians involved in the diagnosis and management of individuals with Differences of Sex Development (DSD), particularly with regard to genomic testing, and identify perceived gaps/strengths/barriers in current practice.
METHODS: An anonymous online survey was developed, with questions exploring demographics, perceptions of genomic testing, availability of genetics services and opinions on the role and utility of genomic testing in DSD. All responses were anonymous. Clinicians involved in the diagnosis and management of individuals with DSD were recruited from relevant societies and departments across Australia and New Zealand.
RESULTS: 79 eligible clinicians commenced the survey, with 63 completing it and 16 providing a partial response. The perceived benefit of having a genetic diagnosis for DSD was almost unanimous (97%). Almost half (48%) of respondents reported barriers in genomic testing. 81% of respondents reported they order genomic tests currently. Approaches to genomic testing when faced with four different clinical scenarios varied across respondents. Clinicians perceived genomic testing to be underutilised (median 36 on sliding scale from 0 to 100).
CONCLUSIONS: Despite 97% of respondents reporting benefit of a genetic diagnosis for individuals with DSD, this was not reflected throughout the survey with regard to clinical implementation. When faced with clinical scenarios, the recommendations for genomic testing from respondents was much lower, indicating the discrepancy between perception and clinical practice. Genomic testing in the context of DSD is seen as both beneficial and desired, yet there are multiple barriers impacting its integration into standard clinical care.

OBJECTIVE: To develop consensus-based algorithms for genetic testing in patients with common craniofacial conditions.
METHODS: An online collaborative consisting of online meetings, independent work, and feedback across groups. Setting/Participants: A collaborative of genetics and pediatrics providers from three regional craniofacial centers (four institutions).
METHODS: Collaborative participants agreed upon a shared initial framework, developed algorithms independently, and presented/tested the algorithms with a national audience. Algorithms were modified based on consensus feedback.
RESULTS: The collaborative group developed final algorithms for genetic testing in patients with orofacial cleft, branchial arch conditions, and craniosynostosis.
CONCLUSIONS: Timely and accurate diagnosis of genetic conditions can support medical management recommendations that result in safer surgical interventions. Algorithms can help guide best-practices for testing, particularly in institutions without easy access to genetics providers.

UNASSIGNED: Specific genetic factors might serve as markers for risk stratification of AMD progression, but their association with key features of AMD has not been fully elucidated. Thus, we investigated the association between overall and pathway-specific genetic risk scores (GRS) and lead loci (ARMS2, CFH) with AMD stages and features of high-risk nonlate AMD, including reticular pseudodrusen (RPD) and large drusen area (LDA).
UNASSIGNED: We performed a cross-sectional analysis of data from the Rhineland Study, a population-based study in Bonn, Germany. We included 4016 individuals aged 50 years and older of European descent. GRS and pathway-specific subscores were constructed based on a large genome-wide association study of AMD. Subscores were generated based on gene-pathways associations (complement, extracellular matrix remodeling (ECM) and lipid metabolism). Associations were assessed using logistic and multinomial regression.
UNASSIGNED: The mean age of participants was 63.36 years and 1813 (45.1%) were men. The GRS was positive in 48.1% of individuals and increased, but did not fully overlap, across AMD stages. Pathway-specific subscores increased across AMD stages except for the ECM subscore, which only showed a trend for increasing in late AMD. Increasing overall GRS was associated with RPD and LDA (OR [95%CI] for RPD: 1.70 [1.33-2.15], for LDA: 1.64 [1.29-2.07]) among individuals with AMD. Similarly, higher complement and ECM subscores was associated with RPD, while for LDA, only an association with complement subscore was observed.
UNASSIGNED: In a population-based setting, we confirmed higher genetic risk to be associated with more severe AMD and identified associations with high-risk features of intermediate AMD. Conjoint analyses suggested that high-risk features and late AMD might be differentially associated with genetic architecture in AMD, such as ECM remodeling. Incorporation of genetic information such as GRSs might improve AMD risk prediction strategies.

OBJECTIVE: Two-sample Mendelian randomization methods were used to explore the causal effects of cognitive reserve proxies, such as educational attainment, occupational attainment, and physical activity (PA), on biological (leukocyte telomere length), phenotypic (sarcopenia-related features), and functional (frailty index and cognitive performance) aging levels.
RESULTS: Educational attainment had a potential protective effect on the telomere length (β = 0.10, 95% CI: 0.08-0.11), sarcopenia-related features (β = 0.04-0.24, 95% CI: 0.02-0.27), frailty risk (β = -0.31, 95% CI: -0.33 to -0.28), cognitive performance (β = 0.77, 95% CI: 0.75-0.80). Occupational attainment was causally related with sarcopenia-related features (β = 0.07-0.10, 95% CI: 0.05-0.14), and cognitive performance (β = 0.30, 95% CI: 0.24-0.36). Device-measured PA was potentially associated with one sarcopenia-related feature (β = 0.14, 95% CI: 0.03-0.25).
CONCLUSIONS: Our findings support the potential causality of educational attainment on biological, phenotypic, and functional aging outcomes, of occupational attainment on phenotypic and functional aging-related outcomes, and of PA on phenotypic aging-related outcomes.

Fetal death is defined as the spontaneous cessation of cardiac activity after fourteen weeks of amenorrhea. In France, the prevalence of fetal death after 22 weeks is between 3.2 and 4.4/1000 births. Regarding the prevention of fetal death in the general population, it is not recommended to counsel for rest and not to prescribe vitamin A, vitamin D nor micronutrient supplementation for the sole purpose of reducing the risk of fetal death (Weak recommendations; Low quality of evidence). It is not recommended to prescribe aspirin (Weak recommendation; Very low quality of evidence). It is recommended to offer vaccination against influenza in epidemic periods and against SARS-CoV-2 (Strong recommendations; Low quality of evidence). It is not recommended to systematically look for nuchal cord encirclements during prenatal screening ultrasounds (Strong Recommendation; Low Quality of Evidence) and not to perform systematic antepartum monitoring by cardiotocography (Weak Recommendation; Very Low Quality of Evidence). It is not recommended to ask women to perform an active fetal movement count to reduce the risk of fetal death (Strong Recommendation; High Quality of Evidence). Regarding evaluation in the event of fetal death, it is suggested that an external fetal examination be systematically offered (Expert opinion). It is recommended that a fetopathological and anatomopathological examination of the placenta be carried out to participate in cause identification (Strong Recommendation. Moderate quality of evidence). It is recommended that chromosomal analysis by microarray testing be performed rather than conventional karyotype, in order to be able to identify a potentially causal anomaly more frequently (Strong Recommendation, moderate quality of evidence); to this end, it is suggested that postnatal sampling of the placental fetal surface for genetic purposes be preferred (Expert Opinion). It is suggested to test for antiphospholipid antibodies and systematically perform a Kleihauer test and a test for irregular agglutinins (Expert opinion). It is suggested to offer a summary consultation, with the aim of assessing the physical and psychological status of the parents, reporting the results, discussing the cause and providing information on monitoring for a subsequent pregnancy (Expert opinion). Regarding announcement and support, it is suggested to announce fetal death without ambiguity, using simple words and adapting to each situation, and then to support couples with empathy in the various stages of their care (Expert opinion). Regarding management, it is suggested that, in the absence of a situation at risk of disseminated intravascular coagulation or maternal vitality, the patient\'s wishes should be taken into account when determining the time between the diagnosis of fetal death and induction of birth. Returning home is possible if it\'s the patient wish (Expert opinion). In all situations excluding maternal life-threatening emergencies, the preferred mode of delivery is vaginal delivery, regardless the history of cesarean section(s) history (Expert opinion). In the event of fetal death, it is recommended that mifepristone 200mg be prescribed at least 24hours before induction, to reduce the delay between induction and delivery (Low recommendation. Low quality of evidence). There are insufficient data in the literature to make a recommendation regarding the route of administration (vaginal or oral) of misoprostol, neither the type of prostaglandin to reduce induction-delivery time or maternal morbidity. It is suggested that perimedullary analgesia be introduced at the start of induction if the patient asks, regardless of gestational age. It is suggested to prescribe cabergoline immediately in the postpartum period in order to avoid lactation, whatever the gestational age, after discussing the side effects of the treatment with the patient (Expert opinion). The risk of recurrence of fetal death after unexplained fetal death does not appear to be increased in subsequent pregnancies, and data from the literature are insufficient to make a recommendation on the prescription of aspirin. In the event of a history of fetal death due to vascular issues, low-dose aspirin is recommended to reduce perinatal morbidity, and should not be combined with heparin therapy (Low recommendation, very low quality of evidence). It is suggested not to recommend an optimal delay before initiating another pregnancy just because of the history of fetal death. It is suggested that the woman and co-parent be informed of the possibility of psychological support. Fetal heart rate monitoring is not indicated solely because of a history of fetal death. It is suggested that delivery not be systematically induced. However, induction can be considered depending on the context and parental request. The gestational age will be discussed, taking into account the benefits and risks, especially before 39 weeks. If a cause of fetal death is identified, management will be adapted on a case-by-case basis (expert opinion). In the event of fetal death occurring in a twin pregnancy, it is suggested that the surviving twin be evaluated as soon as the diagnosis of fetal death is made. In the case of dichorionic pregnancy, it is suggested to offer ultrasound monitoring on a monthly basis. It is suggested not to deliver prematurely following fetal death of a twin. If fetal death occurs in a monochorionic twin pregnancy, it is suggested to contact the referral competence center, in order to urgently look for signs of acute fetal anemia on ultrasound in the surviving twin, and to carry out weekly ultrasound monitoring for the first month. It is suggested not to induce birth immediately.