Preservation of Patient Level Privacy: Federated Classification and Calibration Models

With the launching of the Precision Medicine Initiative in the United States, by the National Institute of Health, and the emergence of a large volume of electronic health records, there are many opportunities to improve clinical decision support systems. A large number of samples are needed to build predictive models that have adequate discrimination and calibration. However, protecting patient privacy is also an important issue. Patient data are typically protected in localized silos, and consolidation of datasets from different healthcare systems is difficult. Federated learning allows the training of a global model by amassing intermediate calculations from localized medical systems. The knowledge learned from the data can be transferred and aggregated to achieve better performance than the one achieved by individual local models. Federated learning may help build better models, providing more accurate predictions. There are two types of measures to assess how well a model performs: discrimination and calibration. While most papers report discrimination measures, calibration has often been neglected but it is a critical metric for evaluation. In this dissertation, I show a novel way to build classifiers and calibration models in a federated manner. I also show how I can evaluate and improve model calibration in this manner. Federated modeling enables the accumulation of knowledge and information that are otherwise locked behind local medical systems

Privacy-Preserving Predictive Modeling: Harmonization of Contextual Embeddings From Different Sources

Background: Data sharing has been a big challenge in biomedical informatics because of privacy concerns. Contextual embedding models have demonstrated a very strong representative capability to describe medical concepts (and their context), and they have shown promise as an alternative way to support deep-learning applications without the need to disclose original data. However, contextual embedding models acquired from individual hospitals cannot be directly combined because their embedding spaces are different, and naive pooling renders combined embeddings useless. Objective: The aim of this study was to present a novel approach to address these issues and to promote sharing representation without sharing data. Without sacrificing privacy, we also aimed to build a global model from representations learned from local private data and synchronize information from multiple sources. Methods: We propose a methodology that harmonizes different local contextual embeddings into a global model. We used Word2Vec to generate contextual embeddings from each source and Procrustes to fuse different vector models into one common space by using a list of corresponding pairs as anchor points. We performed prediction analysis with harmonized embeddings. Results: We used sequential medical events extracted from the Medical Information Mart for Intensive Care III database to evaluate the proposed methodology in predicting the next likely diagnosis of a new patient using either structured data or unstructured data. Under different experimental scenarios, we confirmed that the global model built from harmonized local models achieves a more accurate prediction than local models and global models built from naive pooling. Conclusions: Such aggregation of local models using our unique harmonization can serve as the proxy for a global model, combining information from a wide range of institutions and information sources. It allows information unique to a certain hospital to become available to other sites, increasing the fluidity of information flow in health care

Causal relationship between Butyricimonas and allergic asthma: a two-sample Mendelian randomization study

BackgroundGrowing evidence has well documented the close association between the gut microbiome and allergic respiratory disease, which has been notably represented by allergic asthma. However, it is unclear whether this association is a causal link. Therefore, we investigated the potential causal associations between the gut microbiome and allergic asthma or other allergic diseases.MethodsIn this study, we performed two-sample Mendelian randomization (MR) analyses by using the publicly available genome-wide association study (GWAS) summary data. Single-nucleotide polymorphisms (SNPs) that significantly correlated were selected as instrumental variables. The inverse variance weighted (IVW) method was used to examine the potential causal gut microbial genera for allergic asthma and other allergic diseases. The robustness of the primary findings of the MR analyses was ensured by using different sensitivity analyses.ResultsCombining the findings from multiple analyses, the host genetic-driven increases in Butyricimonas at the genus level were positively correlated with the risk of allergic asthma. In addition, phylum Bacteroidetes and class Bacteroidia were also found to have negative associations with the risk of allergic asthma; genus Slackia was identified as having potential causal effects with allergic asthma. No clear evidence of pleiotropy and heterogeneity was observed in genus Butyricimonas. Butyricimonas was also found to have an association with allergic rhinitis, but not with other allergic diseases.ConclusionOur findings indicate that there are new gut microbial genera that were causally associated with the risk of allergic asthma and other allergic diseases, and offer novel insights into the pathogenesis of allergic respiratory diseases

Periodontal health: A national cross‐sectional study of knowledge, attitudes and practices for the public oral health strategy in China

Aim To assess the status of periodontal health knowledge, attitudes and practices (KAP) among Chinese adults. Materials and Methods A cross‐sectional study was conducted in a nationally representative sample of adults (N = 50,991) aged 20 years or older from ten provinces, autonomous regions, and municipalities. Percentages of Chinese adults with correct periodontal knowledge, positive periodontal attitudes, and practices were estimated. Multiple logistic regression analyses were used to examine the related factors. Results Less than 20% of Chinese adults were knowledgeable about periodontal disease. Very few (2.6%) of Chinese adults use dental floss ≥once a day and undergo scaling ≥once a year and visit a dentist (6.4%) in the case of gingival bleeding. Periodontal health KAP was associated with gender, age, body mass index, marital status, place of residence, education level, income, smoking status, and history of periodontal disease. Conclusions Periodontal health KAP are generally poor among the Chinese adult population. Community‐based health strategies to improve periodontal health KAP need to be implemented. Increasing knowledge of periodontal disease, the cultivation of correct practices in response to gingival bleeding, and the development of good habits concerning the use of dental floss and regular scaling should be public oral health priorities

The DNA Replication Factor RFC1 Is Required for Interference-Sensitive Meiotic Crossovers in Arabidopsis thaliana

During meiotic recombination, induced double-strand breaks (DSBs) are processed into crossovers (COs) and non-COs (NCO); the former are required for proper chromosome segregation and fertility. DNA synthesis is essential in current models of meiotic recombination pathways and includes only leading strand DNA synthesis, but few genes crucial for DNA synthesis have been tested genetically for their functions in meiosis. Furthermore, lagging strand synthesis has been assumed to be unnecessary. Here we show that the Arabidopsis thaliana DNA REPLICATION FACTOR C1 (RFC1) important for lagging strand synthesis is necessary for fertility, meiotic bivalent formation, and homolog segregation. Loss of meiotic RFC1 function caused abnormal meiotic chromosome association and other cytological defects; genetic analyses with other meiotic mutations indicate that RFC1 acts in the MSH4-dependent interference-sensitive pathway for CO formation. In a rfc1 mutant, residual pollen viability is MUS81-dependent and COs exhibit essentially no interference, indicating that these COs form via the MUS81-dependent interference-insensitive pathway. We hypothesize that lagging strand DNA synthesis is important for the formation of double Holliday junctions, but not alternative recombination intermediates. That RFC1 is found in divergent eukaryotes suggests a previously unrecognized and highly conserved role for DNA synthesis in discriminating between recombination pathways

Formation of interference-sensitive meiotic cross-overs requires sufficient DNA leading-strand elongation

Meiosis is essential for eukaryotic sexual reproduction, and meiotic recombination redistributes genetic variations among progeny. Homologous recombination is also important for DNA repair and genome stability. Current recombination models include DNA synthesis, particularly leading-strand synthesis, but its role has not been tested experimentally. Here, we showed that mutations in a DNA polymerase required for leading-strand elongation caused reduced fertility, defects in meiotic chromosome fragmentation and segregation, and reduction of interference-sensitive cross-overs (COs). Because the majority of meiotic COs are produced from the interference-sensitive pathway in budding yeast, mammals, and flowering plants, the discovery of leading-strand elongation in the differentiation of meiotic recombination pathways has important implications in understanding of human reproductive health and crop breeding

Defective sphingosine-1-phosphate receptor 1 (S1P1) phosphorylation exacerbates TH17-mediated autoimmune neuroinflammation

Sphingosine-1-phosphate (S1P) signaling regulates lymphocyte egress from lymphoid organs into systemic circulation. Sphingosine phosphate receptor 1 (S1P1) agonist, FTY-720 (Gilenya™) arrests immune trafficking and prevents multiple sclerosis (MS) relapses. However, alternative mechanisms of S1P-S1P1 signaling have been reported. Phosphoproteomic analysis of MS brain lesions revealed S1P1 phosphorylation on S351, a residue crucial for receptor internalization. Mutant mice harboring a S1pr1 gene encoding phosphorylation-deficient receptors [S1P1(S5A)] developed severe experimental autoimmune encephalomyelitis (EAE) due to T helper (TH) 17-mediated autoimmunity in the peripheral immune and nervous system. S1P1 directly activated Janus-like kinase–signal transducer and activator of transcription 3 (JAK-STAT3) pathway via interleukin 6 (IL-6). Impaired S1P1 phosphorylation enhances TH17 polarization and exacerbates autoimmune neuroinflammation. These mechanisms may be pathogenic in MS

The oyster genome reveals stress adaptation and complexity of shell formation

The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa. © 2012 Macmillan Publishers Limited. All rights reserved

The fruits of Xanthium sibiricum Patr: A review on phytochemistry, pharmacological activities, and toxicity

In recent years, drug development and research have gradually shifted from chemical synthesis to biopharmaceutical and natural drugs. Natural medicines, such as traditional Chinese medicine, have been among the first studied because of their long medicinal history, simplicity, and the relatively low cost of research. Among them, Xanthii Fructus (XF) is famous for the treatment of sinusitis. In this article, the achievements of research on XF from 1953 to 2020 are systematically reviewed, focusing on the aspects of chemical constituents, pharmacological effects, clinical applications, toxicity and side effects, and processing methods. To date, there have been significant advances in both the phytochemistry and pharmacology of XF. Some traditional uses have been validated and clarified in modern pharmacological studies. However, its mechanism of action in the treatment of allergic diseases has not been satisfactorily explained. Further in vitro and in vivo studies are required to rationally develop new drugs and to elucidate the therapeutic potential of XF. A comprehensive evaluation of XF and an understanding of network pharmacology are also needed. © 2020 World Journal of Traditional Chinese Medicine | Published by Wolters Kluwer ‑ Medknow