Somatic and germline aberrations in homologous recombination repair genes among Chinese high-risk breast cancer patients by multi-gene next-generation sequencing.

INTRODUCTION: Recently, genes involved in homologous recombination repair (HRR) pathway have been extensively studied. However, the landscapes of HRR gene mutations remain poorly defined in Chinese high-risk breast cancer (BC) patients. Our study aims to identify the status of germline and somatic HRR gene mutations and their association with clinicopathological features in these patients. MATERIALS AND METHODS: A total of 100 high-risk BC patients from our institution who underwent paired peripheral blood germline and BC tissues somatic 26 genes next-generation sequencing (NGS) from January 2018 to July 2023 were enrolled for retrospective analysis. RESULTS: Out of 100 high-risk BC patients, 55 (55%) had at least one germline or somatic mutation in HRR genes. Among them, 22% carried germline pathogenic variants (19 BRCA1/2 and 3 non-BRCA genes), 9% harbored somatic pathogenic mutations (3 BRCA1/2 and 6 non-BRCA genes). Among high-risk factors, family history and early onset BC showed a correlation with HRR gene mutations (p < 0.05). BRCA1 germline and HRR gene somatic mutations showed a correlation with TNBC, but BRCA2 germline mutations were associated with Luminal B/HER2-negative BC (p < 0.05). Patients with HRR gene somatic pathogenic variant more likely had a lympho-vascular invasion and distant metastasis (p < 0.05). CONCLUSION: The prevalence of HRR gene germline and somatic mutations were higher in Chinese BC patients with high risk factors. We strongly recommend that these high-risk BC patients receive comprehensive gene mutation testing, especially HRR genes, which are not only related to genetic consultation for BC patients and provide a theoretical basis for necessary prevention and individualized treatment.

Characterization of Brain Inflammation, Apoptosis, Hypoxia, Blood-Brain Barrier Integrity and Metabolism in Venezuelan Equine Encephalitis Virus (VEEV TC-83) Exposed Mice by In Vivo Positron Emission Tomography Imaging.

Traditional pathogenesis studies of alphaviruses involves monitoring survival, viremia, and pathogen dissemination via serial necropsies; however, molecular imaging shifts this paradigm and provides a dynamic assessment of pathogen infection. Positron emission tomography (PET) with PET tracers targeted to study neuroinflammation (N,N-diethyl-2-[4-phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide, [18F]DPA-714), apoptosis (caspase-3 substrate, [18F]CP-18), hypoxia (fluormisonidazole, [18F]FMISO), blood-brain barrier (BBB) integrity ([18F]albumin), and metabolism (fluorodeoxyglucose, [18F]FDG) was performed on C3H/HeN mice infected intranasally with 7000 plaque-forming units (PFU) of Venezuelan equine encephalitis virus (VEEV) TC-83. The main findings are as follows: (1) whole-brain [18F]DPA-714 and [18F]CP-18 uptake increased three-fold demonstrating, neuroinflammation and apoptosis, respectively; (2) [18F]albumin uptake increased by 25% across the brain demonstrating an altered BBB; (3) [18F]FMISO uptake increased by 50% across the whole brain indicating hypoxic regions; (4) whole-brain [18F]FDG uptake was unaffected; (5) [18F]DPA-714 uptake in (a) cortex, thalamus, striatum, hypothalamus, and hippocampus increased through day seven and decreased by day 10 post exposure, (b) olfactory bulb increased at day three, peaked day seven, and decreased day 10, and (c) brain stem and cerebellum increased through day 10. In conclusion, intranasal exposure of C3H/HeN mice to VEEV TC-83 results in both time-dependent and regional increases in brain inflammation, apoptosis, and hypoxia, as well as modest decreases in BBB integrity; however, it has no effect on brain glucose metabolism.

Association of hemoglobin A1C with circulating metabolites in Dutch with European, African Surinamese and Ghanaian background.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) varies significantly across ethnic groups. A better understanding of the mechanisms underlying the variation in different ethnic groups may help to elucidate the pathophysiology of T2DM. The present work aims to generate a hypothesis regarding "why do subjects with African background have excess burden of T2DM?". METHODS: In the current study, we performed metabolite profiling of plasma samples derived from 773 subjects of three ethnic groups (Dutch with European, Ghanaian and African Surinamese background). We performed Bayesian lognormal regression analyses to assess associations between HbA1c and circulating metabolites. RESULTS: Here we show that subjects with African Surinamese and Ghanaian background had similar associations of HbA1c with circulating amino acids and triglyceride-rich lipoproteins as subjects with European background. In contrast, subjects with Ghanaian and African Surinamese background had different associations of HbA1c with acetoacetate, small LDL particle and small HDL particle concentrations, compared to the subjects with European background. CONCLUSIONS: On the basis of the observations, we hypothesize that the excess burden of T2DM in subjects with African background may be due to impaired cholesterol efflux capacity or abnormal cholesterol uptake.

Managing carbon sinks in rubber (Hevea brasilensis) plantation by changing rotation length in SW China.

Extension of the rotation length in forest management has been highlighted in Article 3.4 of the Kyoto Protocol to help the countries in their commitments for reduction in greenhouse gas emissions. CO2FIX Model Ver.3.2 was used to examine the dynamics of carbon stocks (C stocks) in a rubber plantation in South Western China with the changing rotation lengths. To estimate the efficiency of increasing the rotation length as an Article 3.4 activity, study predicted that the rubber production and C stocks of the ecosystem increased with the increasing rotation (25, 30, 35, 40 and 45 years). While comparing the pace of growth both in economical (rubber production) and ecological (C stocks) terms in each rotation, 40 years rotation length showed maximum production and C stocks. After elongation of 40 year rotation to four consecutive cycles, it was concluded that the total C stocks of the ecosystem were 186.65 Mg ha(-1). The longer rotation lengths showed comparatively increased C stocks in below ground C stock after consecutive four rotations. The pace of C input (Mg C ha(-1) yr(-1)) and rubber production indicated that 40 years rotation is best suited for rubber plantation. The study has developed carbon mitigation based on four rotation scenarios. The possible stimulated increase in C stocks of the entire ecosystem after consecutive long rotations indicated that the emphasis must be paid on deciding the rotation of rubber plantation in SW China for reporting under article 3.4 of the Kyoto Protocol.

A cross-national factor analytic comparison of three models of PANSS symptoms in schizophrenia.

The 30-item Positive and Negative Syndrome Scale (PANSS) is used worldwide in the assessment of symptom severity in schizophrenia. The present study uses confirmatory factor analysis (CFA) to compare three different factorial models and to evaluate the best-fitting representation of schizophrenia symptom structure on the PANSS across four samples of patients diagnosed with schizophrenia from the US (the CATIE schizophrenia trial), São Paulo, Brazil, and from Beijing and Changsha, China. We examine the goodness of fit of several previously proposed models. The traditional trifactorial model for the PANSS and two five-factor models were evaluated using absolute and incremental indices. Single group CFA found that the five-factor model proposed by NIMH researchers based on an extensive literature review demonstrates the best fit in each of the four samples. This model used 20 of the 30 PANSS items grouped into five factors: positive, negative, disorganized, excited, and depressed symptoms. Subgroups defined by age, gender, nationality, hospitalization status, and severity of illness also did not differ in overall symptom structure as assessed by several standard indices. Our findings suggest that the five factor NIMH model showed the best representation among all four samples from different countries and potentially contrasting cultures.

Assessing potential miRNA targets based on a Markov model.

At present, studies on microRNA mainly focus on the identification of microRNA genes and their mRNA targets. Although researchers have identified many microRNA genes, relatively few microRNA targets have been identified by experimental methods. Computational programs designed for predicting potential microRNA targets provide numerous targets for experimental validation. We used a Markov model to examine base-pairing binding patterns of known microRNA targets. Using this model, potential microRNA targets in human species predicted by four well-known computational programs were assessed. Each potential target was assigned a score reflecting consistency with known target binding patterns. Targets with scores higher than the cutoff value would be identified by our model. The predicted targets identified by our model have base-pairing binding patterns consistent with known targets. This model was efficient for evaluating the extent to which a potential target was accurately predicted.