Pathformer: a biological pathway informed transformer for disease diagnosis and prognosis using multi-omics data.

MOTIVATION: Multi-omics data provide a comprehensive view of gene regulation at multiple levels, which is helpful in achieving accurate diagnosis of complex diseases like cancer. However, conventional integration methods rarely utilize prior biological knowledge and lack interpretability. RESULTS: To integrate various multi-omics data of tissue and liquid biopsies for disease diagnosis and prognosis, we developed a biological pathway informed Transformer, Pathformer. It embeds multi-omics input with a compacted multi-modal vector and a pathway-based sparse neural network. Pathformer also leverages criss-cross attention mechanism to capture the crosstalk between different pathways and modalities. We first benchmarked Pathformer with 18 comparable methods on multiple cancer datasets, where Pathformer outperformed all the other methods, with an average improvement of 6.3%-14.7% in F1 score for cancer survival prediction, 5.1%-12% for cancer stage prediction, and 8.1%-13.6% for cancer drug response prediction. Subsequently, for cancer prognosis prediction based on tissue multi-omics data, we used a case study to demonstrate the biological interpretability of Pathformer by identifying key pathways and their biological crosstalk. Then, for cancer early diagnosis based on liquid biopsy data, we used plasma and platelet datasets to demonstrate Pathformer's potential of clinical applications in cancer screening. Moreover, we revealed deregulation of interesting pathways (e.g. scavenger receptor pathway) and their crosstalk in cancer patients' blood, providing potential candidate targets for cancer microenvironment study. AVAILABILITY AND IMPLEMENTATION: Pathformer is implemented and freely available at https://github.com/lulab/Pathformer.

HCRNet: high-throughput circRNA-binding event identification from CLIP-seq data using deep temporal convolutional network.

Identifying genome-wide binding events between circular RNAs (circRNAs) and RNA-binding proteins (RBPs) can greatly facilitate our understanding of functional mechanisms within circRNAs. Thanks to the development of cross-linked immunoprecipitation sequencing technology, large amounts of genome-wide circRNA binding event data have accumulated, providing opportunities for designing high-performance computational models to discriminate RBP interaction sites and thus to interpret the biological significance of circRNAs. Unfortunately, there are still no computational models sufficiently flexible to accommodate circRNAs from different data scales and with various degrees of feature representation. Here, we present HCRNet, a novel end-to-end framework for identification of circRNA-RBP binding events. To capture the hierarchical relationships, the multi-source biological information is fused to represent circRNAs, including various natural language sequence features. Furthermore, a deep temporal convolutional network incorporating global expectation pooling was developed to exploit the latent nucleotide dependencies in an exhaustive manner. We benchmarked HCRNet on 37 circRNA datasets and 31 linear RNA datasets to demonstrate the effectiveness of our proposed method. To evaluate further the model's robustness, we performed HCRNet on a full-length dataset containing 740 circRNAs. Results indicate that HCRNet generally outperforms existing methods. In addition, motif analyses were conducted to exhibit the interpretability of HCRNet on circRNAs. All supporting source code and data can be downloaded from https://github.com/yangyn533/HCRNet and https://doi.org/10.6084/m9.figshare.16943722.v1. And the web server of HCRNet is publicly accessible at http://39.104.118.143:5001/.

Acupuncture and Doxylamine-Pyridoxine for Nausea and Vomiting in Pregnancy : A Randomized, Controlled, 2 × 2 Factorial Trial.

BACKGROUND: An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking. OBJECTIVE: To assess the efficacy and safety of acupuncture, doxylamine-pyridoxine, and a combination of both in women with moderate to severe NVP. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. (ClinicalTrials.gov: NCT04401384). SETTING: 13 tertiary hospitals in mainland China from 21 June 2020 to 2 February 2022. PARTICIPANTS: 352 women in early pregnancy with moderate to severe NVP. INTERVENTION: Participants received daily active or sham acupuncture for 30 minutes and doxylamine-pyridoxine or placebo for 14 days. MEASUREMENTS: The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at the end of the intervention at day 15 relative to baseline. Secondary outcomes included quality of life, adverse events, and maternal and perinatal complications. RESULTS: No significant interaction was detected between the interventions (P = 0.69). Participants receiving acupuncture (mean difference [MD], -0.7 [95% CI, -1.3 to -0.1]), doxylamine-pyridoxine (MD, -1.0 [CI, -1.6 to -0.4]), and the combination of both (MD, -1.6 [CI, -2.2 to -0.9]) had a larger reduction in PUQE score over the treatment course than their respective control groups (sham acupuncture, placebo, and sham acupuncture plus placebo). Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine-pyridoxine (odds ratio, 3.8 [CI, 1.0 to 14.1]). LIMITATION: The placebo effects of the interventions and natural regression of the disease were not evaluated. CONCLUSION: Both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe NVP. However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine-pyridoxine may yield a potentially larger benefit than each treatment alone. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Project of Heilongjiang Province "TouYan" Innovation Team.

Molecular Simulation for Guiding the Design and Optimization of Mixed Matrix Membranes (MMMs) in the Pervaporation Process.

Molecular simulation has been used extensively in the study of pervaporation membranes as a new economical and environmentally friendly research method. In this paper, A-SiO2/PDMS-PTFE mixed matrix membranes (MMMs) were prepared by molecular-simulation-guided experiments to achieve the separation of dimethyl carbonate/methanol (DMC/MeOH)) azeotropes. The interaction energy, X-ray diffraction pattern mean square displacement, and density field between PDMS and inorganic particles were analyzed by molecular dynamics simulations. The dissolution and diffusion processes of the DMC/MeOH azeotropes system in the MMM were simulated, and the surface-silylated silica (A-SiO2) with relatively better performance was screened. Based on the simulation results, A-SiO2/PDMS-PTFE MMMs were prepared by the coblending method, and the pervaporation separation performance of MMM membranes for DMC/MeOH azeotropes with different A-SiO2 loadings was investigated. When the A-SiO2 loading was 15 wt %, the separation factor of DMC/MeOH azeotropes at 50 °C was 4.74 and the flux was 1178 g m-2 h-1, which was consistent with the expected results of the simulation. The MMMs showed good stability in pervaporation over a period of up to 120 h. This study demonstrates that molecular simulations can provide a viable means for pretest screening and validation of experimental mechanisms, and to a certain extent, guide the design and optimization of pervaporation membranes.

RNANetMotif: Identifying sequence-structure RNA network motifs in RNA-protein binding sites.

RNA molecules can adopt stable secondary and tertiary structures, which are essential in mediating physical interactions with other partners such as RNA binding proteins (RBPs) and in carrying out their cellular functions. In vivo and in vitro experiments such as RNAcompete and eCLIP have revealed in vitro binding preferences of RBPs to RNA oligomers and in vivo binding sites in cells. Analysis of these binding data showed that the structure properties of the RNAs in these binding sites are important determinants of the binding events; however, it has been a challenge to incorporate the structure information into an interpretable model. Here we describe a new approach, RNANetMotif, which takes predicted secondary structure of thousands of RNA sequences bound by an RBP as input and uses a graph theory approach to recognize enriched subgraphs. These enriched subgraphs are in essence shared sequence-structure elements that are important in RBP-RNA binding. To validate our approach, we performed RNA structure modeling via coarse-grained molecular dynamics folding simulations for selected 4 RBPs, and RNA-protein docking for LIN28B. The simulation results, e.g., solvent accessibility and energetics, further support the biological relevance of the discovered network subgraphs.

Association between preconception serum lipid concentrations and treatment outcomes in women with PCOS who underwent ovulation induction.

RESEARCH QUESTION: What is the association between preconception serum lipid concentrations and reproductive outcomes after ovulation induction in women with polycystic ovary syndrome (PCOS)? DESIGN: A secondary analysis of a randomized controlled trial with 1000 PCOS women undergoing ovulation induction with clomiphene with or without acupuncture. Preconception serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) were measured. Outcomes were ovulation, conception, pregnancy, live birth and miscarriage. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI). RESULTS: In total, 780 women ovulated; 320 women achieved conception, 218 had a clinical pregnancy, 205 had a live birth and 115 had a miscarriage. Serum lipid concentrations per one unit increment were independently associated with reproductive outcomes after controlling for confounders. Increasing LDL-C (OR 0.79, 95% CI 0.63-0.99) was independently associated with a lower chance of ovulation. Increasing total cholesterol (OR 0.76, 95% CI 0.62-0.92), LDL-C (OR 0.73, 95% CI 0.57-0.93), triglycerides (OR 0.74, 95% CI 0.58-0.95) and ApoB (OR 0.34, 95% CI 0.16-0.74) were independently associated with a lower chance of clinical pregnancy. Increased total cholesterol (OR 0.78, 95% CI 0.64-0.96), LDL-C (OR 0.77, 95% CI 0.60-0.99), triglycerides (OR 0.76, 95% CI 0.59-0.96) and ApoB (OR 0.39, 95% CI 0.18-0.86) were independently associated with a lower chance of live birth. Furthermore, increased total cholesterol (OR 1.43, 95% CI 1.06-1.93), LDL-C (OR 1.51, 95% CI 1.04-2.19) and ApoB (OR 3.82, 95% CI 1.17-12.41) were independently associated with a higher chance of miscarriage. CONCLUSIONS: Increased serum lipids were negatively associated with the reproductive outcomes of PCOS women undergoing ovulation induction with clomiphene with or without acupuncture.

Reproducibility and feasibility of optic nerve diffusion MRI techniques: single-shot echo-planar imaging (EPI), readout-segmented EPI, and reduced field-of-view diffusion-weighted imaging.

BACKGROUND: Diffusion-weighted imaging (DWI) is an essential technique for optic nerve diseases. However, the image quality of optic nerve DWI is decreased by the distortions and artifacts associated with conventional techniques. In order to establish this method as a critical tool in optic nerve diseases, reproducibility and feasibility of new technical and conventional approaches of DWI need to be systematically investigated. METHODS: DWIs were acquired using ss-EPI, readout-segmented EPI (rs-EPI) DWI, and reduced field-of-view (rFOV) DWI. 26 volunteers (mean age 31.2 years) underwent repeated MRI examinations in order to assess scan-rescan reproducibility and accuracy. The apparent diffusion coefficient (ADC) values (three ROIs were measured on each side) were determined to evaluate the reproducibility of each sequence and the differences between the three techniques. To quantify the geometric distortion artifacts, the length of optic nerve and the maximum angle of optic nerve were defined and compared to T2-weighted imaging. In addition, two readers evaluated four different aspects of image quality on 5-point Likert scales. RESULTS: rs-EPI DWI (ICCs: 0.916, 0.797 and 0.781) and rFOV DWI (ICCs: 0.850, 0.595 and 0.750) showed higher reproducibility (ICCs: ROI1, ROI2 and ROI3) of mean ADC value in all three ROIs than ss-EPI DWI (ICCs: 0.810, 0.442 and 0.379). The quantitative analysis of geometric distortion yielded a higher agreement of both rs-EPI DWI and rFOV DWI with T2-weighted imaging than ss-EPI. rs-EPI DWI (2.38 ± 0.90) and rFOV DWI (2.46 ± 0.58) were superior to ss-EPI DWI (1.58 ± 0.64) with respect to overall image quality and other aspects of image quality, each with P < 0.05. The mean ADC values of rFOV DWI were significantly lower than those of rs-EPI DWI and ss-EPI DWI in all three ROIs (P < 0.001). CONCLUSIONS: Both rs-EPI DWI and rFOV-EPI DWI are suitable techniques for the assessment of diffusion restriction and provide significantly improved image quality compared with ss-EPI DWI. For methods using the same acquisition time, rFOV DWI is superior to ss-EPI DWI, while rs-EPI showed an overall superiority, although this technique took 47% longer to perform.

First case of Coxiella burnetii infection in Palaemonetes sinensis cultured in Liaoning, China.

The Palaemonetes sinensis aquaculture industry in Panjin City, Liaoning Province, China, experienced heavy losses in October 2018. Morbidity of cultured shrimp reached 50% and was characterized by cloudiness of muscle and the gradual spread of disease within the population. When the infection was mild, histopathological examinations revealed that the muscle cells contained a considerable number of microorganisms. In extreme cases, the structure of the hepatopancreatic glandular and muscle fiber was obscured or even vanished. Electron microscope observations revealed the presence of granular cytoplasmic inclusions in cells from hepatopancreas and muscle tissues. The 16S rDNA sequence of the intracytoplasmic organism was 94.7% identity to that of Coxiella burnetii. This is the first report of infection by C. burnetii in P. sinensis.

Metschnikowia bicuspidata isolated from milky diseased Eriocheir sinensis: Phenotypic and genetic characterization, antifungal susceptibility and challenge models.

A severe disease occurred in farmed Eriocheir sinensis characterized by milky liquid accumulation in the pectoral cavity, in the province of Liaoning, China, during October 2018-April 2019. Diseased crabs moved sluggishly, exhibited appetite loss and readily lost legs. Under the microscopic analysis, it was observed that the milky liquid contained a large number of yeastlike microorganisms (0.8-1.2 µm × 1.5-1.9 µm), which were also present in the muscle, hepatopancreas and gills. A dominant strain was isolated from the milky liquid and other tissues of diseased crabs. It grew on nutrient agar and formed 1- to 3-mm white opaque colonies, each with a protuberance in the centre. Besides, the results of TEM and SEM also demonstrate a typical multilateral budding model of the yeast clearly. We identified the strain, which we named 2EJM001, as Metschnikowia bicuspidata based on 18S rDNA, ITS and 26S rDNA sequence analyses and on its morphological, physiological and biochemical characteristics. Phylogenetic analysis revealed that 26S rDNA of 2EJM001 was clustered with M. bicuspidata (LNES0119) as reported by Bao et al. In addition, unlike Bao et al., two challenge experiments (injection and immersion) were used in this study. The results of challenge experiments show that 2EJM001 was pathogenic to E. sinensis and caused signs similar to those found in the naturally infected crabs. At the same time, the minimum inhibitory concentrations (MIC80 and MIC90 ) were determined. This study further confirms that M. bicuspidata 2EJM001 was the pathogen responsible for 'milky disease' in E. sinensis from Liaoning Province.

Type discrimination and concentration prediction towards ethanol using a machine learning-enhanced gas sensor array with different morphology-tuning characteristics.

A simple microwave-assisted method was applied to synthesize zinc oxide (ZnO) with controllable hierarchical structures. In a surfactant-free solvent system, the hierarchical structure of the ZnO precursor can be regulated by the concentration of urea at normal temperature and pressure. Upon annealing, ZnO with different morphologies shows its unique response towards six kinds of gases. The response data were clustered and analyzed by principal component analysis (PCA) to provide a basis for feature extraction. The classification to six kinds of gases was conducted through a model based on linear ridge classification (LRC), support vector machine (SVM). The prediction of ethanol concentration was achieved using backpropagation (BP) neural network and extreme learning machine (ELM). The results indicate that the six confusing gases can be distinguished clearly using SVM with an accuracy more than 0.99. Furthermore, the prediction of ethanol concentration shows a prominent performance (R2 > 0.98) by the ELM-based regressor, despite the nearly saturated response of the sensor array. This study explores the possibility of pattern recognition analysis based on machine learning to further improve the detection performance of the gas sensor array with different response characteristics regulated by the morphology.

First case of non-O1/O139 Vibrio cholerae infection in the pink-tailed chalceus Chalceus macrolepidotus in China.

A pathogen was isolated from diseased pink-tailed chalceus Chalceus macrolepidotus during a high-mortality outbreak in a freshwater culture farm in Liaoyang, China. The diseased fish were characterized by disoriented behaviors, exophthalmos, and redness and swelling of the top of the head. A Gram-negative, pure strain of bacteria (CM0428) was isolated from the brain, kidney, and liver. The isolate was identified as Vibrio cholerae based on ompW gene amplification and 16S rRNA and gyrB gene sequence analysis. Serogroup testing indicated that CM0428 was a non-O1/O139 strain of V. cholerae. The challenge test showed that CM0428 exhibited strong virulence to pink-tailed chalceus, and hlyA and toxR virulence-related genes were detected. The isolate was sensitive to multi-class antibiotics, but resistant to tetracycline. Histological examination revealed that V. cholerae CM0428 infection caused multiple organ and tissue lesions, and typical pathological features were cell degeneration and necrosis.

KSP: an integrated method for predicting catalyzing kinases of phosphorylation sites in proteins.

BACKGROUND: Protein phosphorylation by kinases plays crucial roles in various biological processes including signal transduction and tumorigenesis, thus a better understanding of protein phosphorylation events in cells is fundamental for studying protein functions and designing drugs to treat diseases caused by the malfunction of phosphorylation. Although a large number of phosphorylation sites in proteins have been identified using high-throughput phosphoproteomic technologies, their specific catalyzing kinases remain largely unknown. Therefore, computational methods are urgently needed to predict the kinases that catalyze the phosphorylation of these sites. RESULTS: We developed KSP, a new algorithm for predicting catalyzing kinases for experimentally identified phosphorylation sites in human proteins. KSP constructs a network based on known protein-protein interactions and kinase-substrate relationships. Based on the network, it computes an affinity score between a phosphorylation site and kinases, and returns the top-ranked kinases of the score as candidate catalyzing kinases. When tested on known kinase-substrate pairs, KSP outperforms existing methods including NetworKIN, iGPS, and PKIS. CONCLUSIONS: We developed a novel accurate tool for predicting catalyzing kinases of known phosphorylation sites. It can work as a complementary network approach for sequence-based phosphorylation site predictors.

Transplantation of platelet-derived mitochondria alleviates cognitive impairment and mitochondrial dysfunction in db/db mice.

Diabetes-associated cognitive impairment (DACI) can increase the risk of major cardiovascular events and death. Neuronal functionality is highly dependent on mitochondria and emerging evidence has shown that mitochondrial transplantation is a potential and effective strategy that can reduce brain injury and associated disorders. Platelets are abundant in blood and can be considered a readily available source of small-size mitochondria. These cells can be easily acquired from the peripheral blood with minimal invasion via simple venipuncture. The present study aimed to investigate whether transplantation of platelet-derived mitochondria (Mito-Plt) could improve DACI. Cognitive behaviors were assessed using the Morris water maze test in db/db mice. The results demonstrated that Mito-Plt was internalized into hippocampal neurons 24 h following intracerebroventricular injection. Importantly, one month following Mito-Plt transplantation, DACI was alleviated in db/db mice and the effect was accompanied with increased mitochondrial number, restored mitochondrial function, attenuated oxidative stress and neuronal apoptosis, as well as decreased accumulation of Aß and Tau in the hippocampus. Taken together, the data demonstrated that transplantation of Mito-Plt attenuated cognitive impairment and mitochondrial dysfunction in db/db mice. This method may be a potential therapeutic application for the treatment of DACI.

Current risk factors for HIV infection among blood donors in seven Chinese regions.

BACKGROUND: In China, there is a rising concern on the increasing trends of HIV infections in high-risk groups, who make blood donations that might potentially challenge the blood safety. Analyses on current risk factors for HIV infection among Chinese blood donors are urgently needed for developing effective strategies to defer high-risk donors and to warrant the safety of the blood supply. STUDY DESIGN AND METHODS: We recruited 313 HIV-positive and 762 HIV-negative donors from seven study sites in China and evaluated donor demographic characteristics, current medical and behavioral risk factors associated with HIV infection in a case-control survey. Univariable analyses examined the relationship between HIV infection and donor and donation characteristics, medical and behavioral risks, living conditions, and lifestyles. Multivariable logistic regression analyses evaluated the association between selected individual risks and HIV infection. Regression tree analysis was used to select covariates correlated with both HIV infection and individual risks and thus need to be controlled for in logistic regression models. RESULTS: Being a man who has sex with men was associated with the highest odds of HIV infection. Not using a condom, having sex with HIV-infected individuals, having sex partners with sexually transmitted diseases (STDs), having more than two concurrent sex partners, or having an STD were all associated with more than five times higher odds of having HIV. Having remunerated sex was associated with a 2.4 increased odds of having HIV infection. CONCLUSION: High-risk sexual behaviors were among the major risks for HIV infection among Chinese blood donors.

HIV prevalence and incidence estimates among blood donors in five regions in China.

BACKGROUND: Previous data, although scant, indicated that the incidence of HIV in China has increased over the past decade. There is a growing concern about the impact of the HIV epidemic on blood safety. METHODS AND MATERIALS: We used donation data from five geographically-disperse blood centers in 2013-2016 participating in the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) China program to estimate HIV prevalence and incidence among blood donors. Multivariable logistic regression model was used to examine factors associated with HIV infection in Chinese blood donors. RESULTS: The overall HIV prevalence among first-time donors from 2013 through 2016 was 68.04 per 100,000 donors (95% CI 61.68-74.40). The HIV incidence rate was estimated to be 37.93 per 100,000 person-years (95% CI 30.62-46.97) among first-time donors and 20.55 per 100,000 person-years (95% CI 16.95-24.91) among repeat donors. There was substantial variation in HIV prevalence and incidence rates across blood centers. Multivariable logistic regression results showed that among first-time donors, being male, older than 25 years, minority ethnicity, less than college education, and certain occupations (commercial services, factory workers, retired, unemployed, or self-employed) were associated with positive HIV confirmatory testing results. CONCLUSION: HIV prevalence and incidence among blood donors remain low in the selected five regions in China; however, an increasing trend is observed at some blood centers. It is important to monitor HIV epidemiology in Chinese blood donors on a continuous basis, especially among populations and regions of higher risk.

Effect of sedation with dexmedetomidine or propofol on gastrointestinal motility in lipopolysaccharide-induced endotoxemic mice.

BACKGROUND: Sepsis often accompanies gastrointestinal motility disorder that contributes to the development of sepsis in turn. Propofol and dexmedetomidine, as widely used sedatives in patients with sepsis, are likely to depress gastrointestinal peristalsis. We queried whether propofol or dexmedetomidine, at sedative doses, aggravated sepsis-induced ileus. METHODS: Sedative/Anesthetic Scores and vital signs of lipopolysaccharide (LPS)-induced endotoxemic mice were measured during sedation with propofol or dexmedetomidine. Endotoxemic mice were divided into 10% fat emulsion, propofol, saline, and dexmedetomidine group. The gastric emptying, small intestinal transit, tests of colonic motility, gastrointestinal transit and whole gut transit were evaluated at 15 mins and 24 h after intraperitoneal injection of sedatives/vehicles respectively. RESULTS: 40 mg·kg- 1propofol and 80 µg·kg- 1 dexmedetomidine induced a similar depth of sedation with comparable vital signs except that dexmedetomidine strikingly decreased heart rate in endotoxemic mice. Dexmedetomidine markedly inhibited gastric emptying (P = 0.006), small intestinal transit (P = 0.006), colonic transit (P = 0.0006), gastrointestinal transit (P = 0.0001) and the whole gut transit (P = 0.034) compared with the vehicle, whereas propofol showed no depression on all parts of gastrointestinal motility 15 mins after administration. The inhibitive effects of dexmedetomidine in these tests vanished 24 h after the administration. CONCLUSIONS: Deep sedation with dexmedetomidine, but not propofol, significantly inhibited gastrointestinal peristalsis in endotoxemic mice while the inhibitory effect disappeared 24 h after sedation. These data suggested that both propofol and dexmedetomidine could be applied in septic patients while dexmedetomidine should be used cautiously in patients with cardiac disease or ileus.

Proteomics advances for precision therapy in ovarian cancer.

Introduction: Due to the relatively low mutation rate and high frequency of copy number variation, finding actionable genetic drivers of high-grade serous carcinoma (HGSC) is a challenging task. Furthermore, emerging studies show that genetic alterations are frequently poorly represented at the protein level adding a layer of complexity. With improvements in large-scale proteomic technologies, proteomics studies have the potential to provide robust analysis of the pathways driving high HGSC behavior. Areas covered: This review summarizes recent large-scale proteomics findings across adequately sized ovarian cancer sample sets. Key words combined with 'ovarian cancer' including 'proteomics', 'proteogenomic', 'reverse-phase protein array', 'mass spectrometry', and 'adaptive response', were used to search PubMed. Expert opinion: Proteomics analysis of HGSC as well as their adaptive responses to therapy can uncover new therapeutic liabilities, which can reduce the emergence of drug resistance and potentially improve patient outcomes. There is a pressing need to better understand how the genomic and epigenomic heterogeneity intrinsic to ovarian cancer is reflected at the protein level and how this information could be used to improve patient outcomes.

Hepatitis C virus prevalence and incidence estimates among Chinese blood donors.

BACKGROUND: Hepatitis C virus (HCV) is an important transfusion-transmitted virus with global significance. The objective of this study was to evaluate the HCV prevalence and incidence among Chinese blood donors from 2013 to 2016. STUDY DESIGN AND METHODS: Whole blood and apheresis platelet donations collected from five Chinese blood centers from June 1, 2013, to December 31, 2016, were screened in parallel by two different enzyme-linked immunosorbent assays for anti-HIV 1/2, hepatitis B surface antigen, anti-HCV, and syphilis. Screening-reactive samples were further confirmed by western blot. Confirmatory positive rates among first-time and repeat donors were used to estimate the prevalence and incidence rates. Multivariable logistic regression modeling was used to examine factors associated with HCV infection. RESULTS: A total of 1,276,544 donations were collected from five Chinese blood centers, of which an estimated 1203 were confirmed HCV positive. The overall HCV prevalence among first-time donors was 166.56 per 100,000 donors (95% confidence interval, 156.04-177.08). The HCV incidence rate was estimated to be 15.21 (95% confidence interval, 11.83-19.56) per 100,000 person-years among repeat donors. Multivariable logistic regression results showed that increased age, lower educational levels, ethnicity, and occupation were all important factors associated with HCV confirmatory status among first-time donors (p < 0.01). CONCLUSIONS: HCV infection is still an important concern for transfusion safety in China. Our findings indicate that continued strong efforts are needed to monitor and control the risk of transfusion-transmitted HCV infection in China. Moreover, to reduce unnecessary donor loss, HCV donor screening procedures should be improved by incorporating confirmatory testing into routine blood center operations.

Effects of hyperhomocysteinaemia and metabolic syndrome on reproduction in women with polycystic ovary syndrome: a secondary analysis.

RESEARCH QUESTION: What is the association between hyperhomocysteinaemia (HHCY), metabolic syndrome, and reproductive outcomes among women with polycystic ovary syndrome (PCOS). DESIGN: A secondary analysis of PCOSAct with 21 sites in China. A total of 1000 women with PCOS were enrolled; 936 women with baseline homocysteine (HCY) were analysed. RESULTS: Higher HCY was associated with higher body mass index, free testosterone and lower FSH, fasting glucose (P < 0.001; P < 0.001; P = 0.005; P < 0.001) and ovulation rate among all participants (OR 0.59, 95% CI 0.41 to 0.86; OR 0.57, 95% CI 0.39 to 0.83 tertiles 2 and 3 versus tertile 1, respectively). The HHCY group had lower oestradiol and higher free testosterone (P = 0.04; P < 0.001) than the controls. In the metabolic syndrome group, LH, LH-FSH ratio and sex hormone-binding globulin were lowest in the metabolic syndrome group (all P < 0.001). In the HHCY group, ovulation rate decreased and the second or third trimester pregnancy loss rate increased compared with controls (OR 1.678, 95% CI 1.04 to 2.70; OR 0.03, 95% CI 0.00 to 0.42) with treatment adjustment. Compared with the controls, ovulation, conception, pregnancy, second or third trimester pregnancy loss and live birth rates were statistically lower in the metabolic syndrome group after adjusting treatment (OR 1.76, 95% CI 1.15 to 2.70; OR 1.75, 95% CI 1.15 to 2.65; OR 2.09, 95% CI 1.27 to 3.44; OR 0.02, 95% CI 0.00 to 0.33; OR 2.42 95% CI 1.42 to 4.10), and pregnancy, pregnancy loss and live birth rates remained significantly different after adjusting for treatment and sex-hormone factors (OR 1.77, 95% CI 1.05 to 2.99; OR 0.14, 95% CI 0.02 to 0.82; OR 2.02, 95% CI 1.16 to 3.50). CONCLUSIONS: In women with PCOS, HHCY contributes to increased pregnancy loss and reduced ovulation, and metabolic syndrome was related to defects in ovulation, conception, pregnancy, pregnancy loss and live birth, indicating that the two conditions lead to defects at various reproductive stages.