Successful guselkumab treatment of a refractory psoriasis patient with Graves' disease: a case report.

Psoriasis is a chronic inflammatory skin disease. It is associated with many autoimmune diseases such as rheumatoid arthritis, Crohn's disease and thyroid diseases. Graves' disease (GD) is a common organ-specific autoimmune disease characterized by diffuse goitre and thyrotoxicosis. Management of psoriasis patients with GD is challenging. This current report presents the case of a 34-year-old female patient with refractory psoriasis with GD who was hospitalized for drug eruption and then experienced new-onset erythema and scaling following treatment with adalimumab and secukinumab. Despite the sequential move to phototherapy, tofacitinib and ustekinumab, the erythema and scaling continued unabated and exacerbated. Finally, switching to guselkumab resulted in the psoriasis lesions significantly improving. These findings suggest that guselkumab might be an effective treatment option for refractory psoriasis combined with GD.

[Association between habitual tea consumption and 10-year cardiovascular risk among Chinese mid-aged and elderly].

OBJECTIVE: To explore the association between habitual tea consumption and 10-year cardiovascular disease risk among middle-aged and elderly Chinese. METHODS: China Nutrition and Health Surveillance 2015 applied a stratified, multistage, and random sampling method. The current study selected middle-aged and elderly participants aged 45 and older, and they were investigated by basic information survey, dietary survey based on the food frequency questionnaire, physical measurements including height, weight, and blood pressure, and a laboratory examination with fasting blood samples. Habitual tea consumption was defined by asking about the number of cups of tea usually consumed per day in the past 12 months, and the risk of cardiovascular disease incidence was calculated using the Framingham risk score over a 10-year period. The association between tea consumption and 10-year risk of cardiovascular disease in this population was analyzed using multiple logistic regression, and further analyzed using gender as a stratification factor. RESULTS: A total of 42 704 Chinese middle-aged and elderly were included in this study, with an average age of(59.4±9.4) years, 20 104 males and 22 600 females, 17 194 in urban areas and 25 510 in rural areas. For tea drinking, there were 12 519(29.32%) tea drinkers in the included sample, of which 4153(9.73%) consumed 1-2 cups/d, 3336(7.81%) 3-4 cups/d, and 5030(11.78%) ≥5 cups/d. For 10-year cardiovascular risk, 28 267 participants(66.19%) were estimated to be low risk, while 14 437(33.81%) were in the high risk. After adjusting for age, sex, body mass index, place of residence, education, income, marital status, smoking, excessive alcohol consumption, physical activity, sedentary behavior, sleep, participation in medical examination within one year, DASH dietary score, energy intake and chronic disease status, the result showed a reduced risk of cardiovascular disease over a 10-year period among those who consumed 3-4 cups/d compared with those who did not consume tea(OR=0.820, 95%CI 0.719-0.934, P_(trend)=0.03). When stratified by gender, both gender showed participants who consumed 3-4 cups/d had a lower risk for cardiovascular disease than those who did not consume tea(males: OR=0.849, 95%CI 0.722-0.997; females: OR=0.697, 95%CI 0.527-0.922). And the result was more pronounced among females. CONCLUSION: Moderate habitual tea consumption could reduce the risk of cardiovascular disease among middle-aged and elderly Chinese people, and its protective effect is more pronounced among females.

A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury.

Acute kidney injury (AKI) exhibits high morbidity and mortality. Kidney injury molecule-1 (KIM1) is dramatically upregulated in renal tubules upon injury, and acts as a biomarker for various renal diseases. However, the exact role and underlying mechanism of KIM1 in the progression of AKI remain elusive. Herein, we report that renal tubular specific knockout of Kim1 attenuates cisplatin- or ischemia/reperfusion-induced AKI in male mice. Mechanistically, transcription factor Yin Yang 1 (YY1), which is downregulated upon AKI, binds to the promoter of KIM1 and represses its expression. Injury-induced KIM1 binds to the ECD domain of death receptor 5 (DR5), which activates DR5 and the following caspase cascade by promoting its multimerization, thus induces renal cell apoptosis and exacerbates AKI. Blocking the KIM1-DR5 interaction with rationally designed peptides exhibit reno-protective effects against AKI. Here, we reveal a YY1-KIM1-DR5 axis in the progression of AKI, which warrants future exploration as therapeutic targets.

Peri-Conceptional Folic Acid Supplementation and Children's Physical Development: A Birth Cohort Study.

BACKGROUND: Maternal lack of folic acid supplementation during pregnancy may increase the risk of low birth weight and preterm delivery. However, little is known about the relationship between folic acid supplementation during pregnancy and the physical development of offspring in the later stage. OBJECTIVE: This study aimed to explore the association between maternal folic acid supplementation status during pregnancy and the physical development of preschool children. METHODS: A total of 3064 mother-child pairs with data on maternal folic acid supplementation status during pregnancy and children's anthropometric measurements were recruited from the Ma'anshan-Anhui Birth Cohort (MABC) in China. Maternal folic acid supplementation status during pregnancy was the main exposure, and the primary outcomes were children's growth development trajectories. Children's growth development trajectories were fitted using group-based trajectory models. The association between maternal folic acid supplementation status during pregnancy and children's growth trajectories was performed using multiple logistic regression models. RESULTS: After adjusting for potential confounders, we found that the absence of maternal folic acid supplementation before pregnancy and in the first trimester was significantly associated with a "high level" trajectory (trajectory 3) and a "high rising level" trajectory (trajectory 4) of BMI-Z scores in children 0 to 6 years of age (OR = 1.423, 95%CI:1.022-1.982; OR = 1.654, 95%CI: 1.024-2.671). In children aged 4 to 6 years old, a "high level" trajectory (trajectory 3) of body fat ratio was substantially related to maternal no folic acid supplementation before pregnancy and in the first trimester (OR = 1.833, 95%CI:1.037-3.240). No significant additional benefits associated with physical developmental indicators in preschool children have been observed with continued folic acid supplementation after the first trimester of gestation. CONCLUSIONS: Maternal non-supplementation with folic acid during pregnancy is associated with a "high level" BMI trajectory and a "high level" body fat ratio trajectory in preschool-aged children.

Usual Intake of Micronutrients and Prevalence of Inadequate Intake among Chinese Adults: Data from CNHS 2015-2017.

Previous studies have used the traditional average-value method to calculate the usual dietary intake of a population, but the results may be biased due to the measurement errors. The aim of this study was to provide an assessment of the usual micronutrient intake and estimate the prevalence of inadequate intake among Chinese adults. Data from the Chinese Nutrition and Health Surveillance 2015−2017 as well as a total of 72,231 subjects aged 18 years and older were included in the analysis. The 24 h recall method combined with the condiment weighing method were used for three consecutive days to collect daily food and condiments intake. The daily intake of 16 micronutrients was calculated based on the Chinese Food Component Tables. The National Cancer Institute (NCI) method was used to estimate the usual intake of micronutrients, and the prevalence of inadequate intake was estimated using the estimated average requirement (EAR) cut-point method. The results showed that, except for sodium, copper, iron (only for males), vitamin E, and phosphorus, the usual intake of micronutrients in Chinese adults was low, and the prevalence of inadequate intake ranged from 38.67 to 97.63%. The prevalence of inadequate calcium and riboflavin intake was more than 90%, and the proportion of individuals with a usual intake of thiamine, vitamin A, potassium, and selenium below EAR also reached 80%. Manganese, magnesium, vitamin C, and zinc were potentially deficient micronutrients, with the prevalence of inadequate intake ranging from 38.67% to 77.09%. However, usual sodium intake was extremely high with an average of 5139.61 mg/day, and only a quarter of Chinese adults were below the World Health Organization (WHO) recommended value. For most micronutrients, the usual dietary intake declined with age and the prevalence of inadequate intake increased with age. Except for zinc, vitamin A, and B-vitamins, the prevalence of micronutrient deficiencies was higher in females than in males in the same age group (p < 0.05). Therefore, Chinese adults do not receive enough micronutrients. Effective nutrition supplementary strategies and measures are needed to address these problems.

Association between Habitual Tea Consumption and Metabolic Syndrome and Its Components among Chinese Adults Aged 18~59 Years: Based on China Nutrition and Health Surveillance 2015-2017.

BACKGROUND: Tea consumption is widely reported to have beneficial effects on metabolic functions. The current study is to evaluate the association between habitual tea consumption and risk for metabolic syndrome and its components among Chinese adults aged 18~59 years. METHODS: 43,757 participants aged 18~59 years from China Nutrition and Health Surveillance 2015-2017 were included and divided into four groups based on the amount of daily tea consumption in the current study. Using multiple-adjustment logistic regression to explore the relationship between habitual tea consumption and metabolic syndrome-related health outcomes. RESULTS: Compared with those who did not consume tea habitually, participants who drank over 5 cups of tea per day showed a significantly lower risk of metabolic syndrome (OR = 0.836, 95% CI = 0.771-0.905), blood pressure elevated (OR = 0.906, 95% CI = 0.845-0.972), triglyceride elevated (OR = 0.797, 95% CI = 0.741-0.857), and fasting plasma glucose elevated (OR = 0.772, 95% CI = 0.715-0.833), but higher risk for central obesity (OR = 1.354, 95% CI = 1.236-1.484). Regardless of gender, higher tea consumption was related to lower risk of triglyceride and fasting blood glucose elevated but higher risk for central obesity. While for protective effect on metabolic syndrome, blood pressure elevated, and HDL-C reduction only showed in females. CONCLUSIONS: Results from current study support that habitual tea consumption would benefit metabolic syndrome and its related components, especially among females.

Effects of selenium levels on placental oxidative stress and inflammation during pregnancy: a prospective cohort study.

BACKGROUND: Studies on the impact of Se levels in different pregnancy periods on placental function are limited. AIM: This cohort study sought to investigate the levels of the trace element Se and to assess their effects on placental oxidative stress (OS) and mRNA expression of inflammatory genes during pregnancy. METHODS: The study population consisted of 2519 pregnant women from the Ma'anshan birth cohort. Se levels were measured in the first and second trimesters of pregnancy and in cord blood using inductively coupled plasma-mass spectrometry (ICP-MS). Placental stress and mRNA expression of inflammatory genes were assessed using RT-PCR. RESULTS: A statistically significant negative association was noted between Se levels in the second trimester of pregnancy and mRNA expression of placental HO-1(ß = -0.009, p < .01), HIF1α (ß = -0.005, p = .010), GRP78 (ß = -0.011, p < .001), CRP (ß = -.007, p = .033) and CD68 (ß = -0.006, p = .019). A negative association was noted between Se levels in cord blood and mRNA expression of placental HO-1 (ß = -0.007, p = .004), HIF1α (ß = -0.006, p = .005) and GRP78 (ß = -0.009, p = .004). We found that prenatal Se status was associated with placental stress and mRNA expression of inflammatory genes. CONCLUSION: Se deficiency during pregnancy, especially in the second trimester, leads to the production of OS and an increase in inflammatory mediators, affecting the growth and development of the fetus. Monitoring of pregnant women's nutritional status is necessary to prevent nutritional imbalances and deficiencies in important micronutrients in the fetal.

Eradication of FIX inhibitor in haemophilia B children using low-dose immune tolerance induction with rituximab-based immunosuppressive agent(s) in China.

INTRODUCTION: Development of haemophilia B inhibitors (HBI) results in the ineffectiveness of FIX replacement therapy. Inhibitor eradication by immune tolerance induction (ITI) is therefore necessary. In HBI, ITI even at high FIX dose is less effective and has a higher risk of severe complications. AIM: To characterize clinical features and outcome of ITI on HBI. METHODS: This retrospective study was conducted in Haemophilia Paediatric Comprehensive Care Centre of China. We used low-dose ITI (25-50 FIX IU/kg/three-times-weekly to every-other-day) with domestic prothrombin complex concentrate (PCC), combined with two successive immunosuppressive (IS) regimens. RESULTS: Sixteen HBI children, representing 5.7% of all and 14.4% of our severe registered HB patients, were enroled. Seven cases reported allergic reactions (ARs) proximal to inhibitor development. The historic peak inhibitor titre was median 54.2 (range 4.7-512) BU, and 15 (93.8%) had high-titre inhibitors. Twelve patients adherent to ITI were analysable. Of the nine ITI patients who received rituximab/prednisone (IS Regimen-1), four achieved tolerization in 1.4-43.3 months. Two subsequently relapsed but re-tolerized after a second course of IS Regimen-1. During ITI, the median treated bleed was .39/month (82.7% reduction from before ITI), and the incidence of AR and nephrotic syndrome (NS) complications was each at 22% (2/9). Three ITI patients received modified 'Beutel' protocol (IS Regimen-2) using multiple-IS-drugs, and two had rapid tolerization (.8 and 1.8 months). CONCLUSIONS: Inhibitor eradication could be achieved by low-dose ITI protocol using PCC combined with IS. Larger studies are needed to confirm if ITI with IS Regimen-2 is more effective with less complications.

Integrative Multi-OMICs Identifies Therapeutic Response Biomarkers and Confirms Fidelity of Clinically Annotated, Serially Passaged Patient-Derived Xenografts Established from Primary and Metastatic Pediatric and AYA Solid Tumors.

Establishment of clinically annotated, molecularly characterized, patient-derived xenografts (PDXs) from treatment-naïve and pretreated patients provides a platform to test precision genomics-guided therapies. An integrated multi-OMICS pipeline was developed to identify cancer-associated pathways and evaluate stability of molecular signatures in a panel of pediatric and AYA PDXs following serial passaging in mice. Original solid tumor samples and their corresponding PDXs were evaluated by whole-genome sequencing, RNA-seq, immunoblotting, pathway enrichment analyses, and the drug−gene interaction database to identify as well as cross-validate actionable targets in patients with sarcomas or Wilms tumors. While some divergence between original tumor and the respective PDX was evident, majority of alterations were not functionally impactful, and oncogenic pathway activation was maintained following serial passaging. CDK4/6 and BETs were prioritized as biomarkers of therapeutic response in osteosarcoma PDXs with pertinent molecular signatures. Inhibition of CDK4/6 or BETs decreased osteosarcoma PDX growth (two-way ANOVA, p < 0.05) confirming mechanistic involvement in growth. Linking patient treatment history with molecular and efficacy data in PDX will provide a strong rationale for targeted therapy and improve our understanding of which therapy is most beneficial in patients at diagnosis and in those already exposed to therapy.

Hallstatt miners consumed blue cheese and beer during the Iron Age and retained a non-Westernized gut microbiome until the Baroque period.

We subjected human paleofeces dating from the Bronze Age to the Baroque period (18th century AD) to in-depth microscopic, metagenomic, and proteomic analyses. The paleofeces were preserved in the underground salt mines of the UNESCO World Heritage site of Hallstatt in Austria. This allowed us to reconstruct the diet of the former population and gain insights into their ancient gut microbiome composition. Our dietary survey identified bran and glumes of different cereals as some of the most prevalent plant fragments. This highly fibrous, carbohydrate-rich diet was supplemented with proteins from broad beans and occasionally with fruits, nuts, or animal food products. Due to these traditional dietary habits, all ancient miners up to the Baroque period have gut microbiome structures akin to modern non-Westernized individuals whose diets are also mainly composed of unprocessed foods and fresh fruits and vegetables. This may indicate a shift in the gut community composition of modern Westernized populations due to quite recent dietary and lifestyle changes. When we extended our microbial survey to fungi present in the paleofeces, in one of the Iron Age samples, we observed a high abundance of Penicillium roqueforti and Saccharomyces cerevisiae DNA. Genome-wide analysis indicates that both fungi were involved in food fermentation and provides the first molecular evidence for blue cheese and beer consumption in Iron Age Europe.

3-Indoleacetonitrile Is Highly Effective in Treating Influenza A Virus Infection In Vitro and In Vivo.

Influenza A viruses are serious zoonotic pathogens that continuously cause pandemics in several animal hosts, including birds, pigs, and humans. Indole derivatives containing an indole core framework have been extensively studied and developed to prevent and/or treat viral infection. This study evaluated the anti-influenza activity of several indole derivatives, including 3-indoleacetonitrile, indole-3-carboxaldehyde, 3-carboxyindole, and gramine, in A549 and MDCK cells. Among these compounds, 3-indoleacetonitrile exerts profound antiviral activity against a broad spectrum of influenza A viruses, as tested in A549 cells. Importantly, in a mouse model, 3-indoleacetonitrile with a non-toxic concentration of 20 mg/kg effectively reduced the mortality and weight loss, diminished lung virus titers, and alleviated lung lesions of mice lethally challenged with A/duck/Hubei/WH18/2015 H5N6 and A/Puerto Rico/8/1934 H1N1 influenza A viruses. The antiviral properties enable the potential use of 3-indoleacetonitrile for the treatment of IAV infection.

A Systematic Screening of Traditional Chinese Medicine Identifies Two Novel Inhibitors Against the Cytotoxic Aggregation of Amyloid Beta.

The toxic aggregates of amyloid beta (Aß) disrupt the cell membrane, induce oxidative stress and mitochondrial dysfunction, and eventually lead to Alzheimer's disease (AD). Intervening with this cytotoxic aggregation process has been suggested as a potential therapeutic approach for AD and other protein misfolding diseases. Traditional Chinese Medicine (TCM) has been used to treat AD and related cognitive impairment for centuries with obvious efficacy. Extracts or active ingredients of TCMs have been reported to inhibit the aggregation and cytotoxicity of Aß. However, there is a lack of systematic research on the anti-Aß aggregation effects of TCM components. In this study, we performed a systematic screening to identify the active ingredients of TCM against the cytotoxic aggregation of Aß42. Through a literature and database survey, we selected 19 TCM herbals frequently used in the treatment of AD, from which 76 major active chemicals without known anti-amyloid effects were further screened. This took place through two rounds of MTT-based screening detection of the cytotoxicity of these chemicals and their effects on Aß42-induced cytotoxicity, respectively. Tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) and sinapic acid (SA) were found to be less toxic, and they inhibited the cytotoxicity of Aß42. Further studies demonstrated that TSG and SA concentration-dependently attenuated the amyloidosis and membrane disruption ability of Aß42. Thus, we identified two novel chemicals (TSG and SA) against the cytotoxic aggregation of Aß42. Nonetheless, further exploration of their therapeutic potential is warranted.

Yin and Yang Regulation of Liver X Receptor α Signaling Control of Cholesterol Metabolism by Poly(ADP-ribose) polymerase 1.

Liver X receptor α (LXRα) controls a set of key genes involved in cholesterol metabolism. However, the molecular mechanism of this regulation remains unknown. The regulatory role of poly(ADP-ribose) polymerase 1 (PARP1) in cholesterol metabolism in the liver was examined. Activation of PARP1 in the liver suppressed LXRα sensing and prevented upregulation of genes involved in HCD-induced cholesterol disposal. Mechanistically, LXRα was poly(ADP-ribosyl)ated by activated PARP1, which decreased DNA binding capacity of LXRα, thus preventing its recruitment to the target promoter. Intriguingly, we found that unactivated PARP1 was indispensable for LXRα transactivation and target expression. Further exploration identified unactivated PARP1 as an essential component of the LXRα-promoter complex. Taken together, the results indicate that activated PARP1 suppresses LXRα activation through poly(ADP-ribosyl)ation, while unactivated PARP1 promotes LXRα activation through physical interaction. PARP1 is a pivotal regulator of LXRα signaling and cholesterol metabolism in the liver.

Prognostic factors of carbon monoxide poisoning in Taiwan: a retrospective observational study.

OBJECTIVES: To identify the risk factors related to the prognosis of carbon monoxide (CO)-poisoned patients in the hospital. DESIGN: Retrospective observational study. SETTING: Tri-Service General Hospital, Taiwan. METHODS: We conducted a review of the medical records of 669 CO-poisoned patients, who were admitted to the Department of Emergency, Tri-Service General Hospital, Taiwan, from 2009 to 2014. Demographic, clinical and laboratory data were collected for analysis. In the study, the end points for poor outcome were patients who either still had sequelae, were bedridden or died after treatment. The independent t-test, χ2 test and binary logistic regression were used to identify the association between the prognostic factors and the outcomes. RESULTS: The logistic regression analysis confirmed that the Glasgow Coma Scale (GCS) score (p=0.008) and blood urea nitrogen (BUN) (p=0.002) were related to poor outcomes. Furthermore, the receiver operating characteristic (ROC) curve showed that the cut-off point of intubation days was 1.5 days (area under the ROC curve [AUC]=0.793) for all patients and 2.5 days (AUC=0.817) for patients with intubation when predicting poor outcomes. CONCLUSION: We identified the factors that most strongly predict the prognosis of CO poisoning, including the GCS score, serum BUN and intubation days. Moreover, the number of hyperbaric oxygen treatments seems to have impact of the outcome.

Effects of anti-H. pylori triple therapy and a probiotic complex on intestinal microbiota in duodenal ulcer.

This study aimed to investigate the intestinal microbiota in duodenal ulcer (DU) patients, effects of proton pump inhibitors,clarithromycin and amoxicillin, PCA) for Helicobacter pylori (H. pylori) and Bacillus subtilis and Enterococcus faecium (BSEF) on intestinal microbiota. DU patients were randomly assigned to receive either PCA (group TT) or PCA plus BSEF(group TP). The fecal microbiome was conducted using high throughput 16S rDNA gene and internal transcribed spacer sequencings. The diversity and abundance of intestinal bacteria in the DU were significantly lower than health check control (HC) group. In the TT group, the abundance and diversity of both intestinal bacteria and fungi decreased after PCA treatment, compared with those before treatment, whereas in the TP group no obvious changes were observed. In the TT group at all the time points, both the intestinal bacteria and fungi were different from those in the HC group. However, in the TP group, at 10w the bacterial flora abundance was close to that in the HC group. The results indicate that anti- H. pylori treatment induced significant decrease in the diversity of intestinal microbiota, while the combined therapy supplemented with BSEF could protect and restore the intestinal microbiota.

Efficacy and safety of iron supplementation in patients with heart failure and iron deficiency: a meta-analysis.

Fe therapy can be effective in heart failure patients both with and without anaemia. However, the role of Fe therapy in such patients is still uncertain. In this review, the aim was to evaluate the efficacy and safety of Fe therapy in adult patients with heart failure who have reduced ejection fraction (HFrEF). Multiple databases (PubMed, Medline, EMBASE, the Cochrane Library and Clinical Trials) were searched up to December 2017 and the reference lists of relevant articles obtained from the search were reviewed. Data extracted from randomised control trials (RCT) selected for the review were pooled using a fixed effects model or a random effects model, according to heterogeneity between trials. Nine RCT were included in this meta-analysis which included a total of 789 patients who received Fe therapy and who in turn were compared with 585 controls. There was significant improvement in the 6-min walk test (19·05 m, 95 % CI 10·48, 27·62) and peak VO2/kg (0·93 ml/kg per min, 95 % CI 0·16, 1·69) in the Fe supplementation arm. With Fe therapy, fewer patients were hospitalised for heart failure (OR: 0·42, 95 % CI 0·27, 0·65), but no relationship was found for total re-hospitalisation (OR: 0·70, 95 % CI 0·32, 1·51) or mortality (OR: 0·70, 95 % CI 0·38, 1·28). Fe therapy has the potential to improve exercise tolerance, reduce re-hospitalisations for patients with HFrEF having Fe deficiency. In addition, Fe supplementation was found to be safe, with no increased rate of adverse events.

Simultaneous quantification combined with multivariate statistical analysis of multiple chemical markers of Wu Ji Bai Feng Pill by UHPLC-MS/MS.

Wu Ji Bai Feng Pill (WJBFP) is a traditional Chinese medicine (TCM) complex formula, which has been widely used in the treatment of various gynecological disorders. However, the quality control of multiple components in WJBFP is challengeable by using the methods applicable to analysis of several phytochemicals in single herbs or simple herbal preparations. The purpose of this study is to establish an ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-MS/MS) method for the quantitative determination of 20 bioactive compounds in WJBFP. The modified chromatographic conditions were achieved on an Agilent Poroshell 120 EC-C18 column with a gradient elution consisted of 0.1% formic acid in acetonitrile and 0.1% aqueous formic acid (v/v). All analytes were determined using a triple quadrupole mass spectrometry in positive or negative ionization modes with multiple reaction monitoring (MRM) mode. An UHPLC-MS/MS method was optimized and validated for linearity, limits of detection and quantification, precision, repeatability, stability and recovery. The proposed method was applied for the analysis of 20 compounds in 19 batches of commercial WJBFP products. principal component analysis and hierarchical cluster analysis were applied to evaluate intrinsic quality and to identify chemical markers most responsible for quality evaluation. In conclusion, the established method offered speedy and sensitive determination for 20 compounds and is helpful for chemical standardization of commercial WJBFP products.

Integrative cancer patient stratification via subspace merging.

MOTIVATION: Technologies that generate high-throughput omics data are flourishing, creating enormous, publicly available repositories of multi-omics data. As many data repositories continue to grow, there is an urgent need for computational methods that can leverage these data to create comprehensive clusters of patients with a given disease. RESULTS: Our proposed approach creates a patient-to-patient similarity graph for each data type as an intermediate representation of each omics data type and merges the graphs through subspace analysis on a Grassmann manifold. We hypothesize that this approach generates more informative clusters by preserving the complementary information from each level of omics data. We applied our approach to The Cancer Genome Atlas (TCGA) breast cancer dataset and show that by integrating gene expression, microRNA and DNA methylation data, our proposed method can produce clinically useful subtypes of breast cancer. We then investigate the molecular characteristics underlying these subtypes. We discover a highly expressed cluster of genes on chromosome 19p13 that strongly correlates with survival in TCGA breast cancer patients and validate these results in three additional breast cancer datasets. We also compare our approach with previous integrative clustering approaches and obtain comparable or superior results. AVAILABILITY AND IMPLEMENTATION: https://github.com/michaelsharpnack/GrassmannCluster. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Hyperbaric oxygen therapy restored traumatic stress-induced dysregulation of fear memory and related neurochemical abnormalities.

Individuals with posttraumatic stress disorder (PTSD) are characterized by fear memory problems and hypocortisolemia of which traumatic stress-induced monoaminergic disruption over infralimbic (IL) cortex is considered the key mechanism. Hyperbaric oxygen therapy (HBOT) has recently proven its utility in treating several mental disorders but remains unexplored for PTSD. The present study aimed to examine the effects of 5-day HBO paradigm on traumatic stress (single prolonged stress, SPS, an animal model of PTSD)-induced dysregulation of fear memory/anxiety profiles and related abnormalities in IL monoamines and plasma corticosterone. Rats were randomly assigned to four groups (CON-sham, CON-HBOT, SPS-sham, and SPS-HBOT) and received Pavlovian fear conditioning test or elevated-T maze (ETM). The extracellular and tissue levels of monoamines over the IL cortex and the activity of the hypothalamus-pituitary-adrenal axis (i.e., the plasma corticosterone level and expression of the glucocorticoid receptor (GR) in the IL, hippocampus, amygdala, and hypothalamus) were measured. The results demonstrated that HBOT restored behaviorally the SPS-impaired fear extinction retrieval ability and SPS-induced conditioned anxiety, and neurochemically the SPS-reduced IL monoamines efflux level, and the corticosterone profiles. The present study shows some positive effects of HBOT in both behavioral and neurochemical profiles of PTSD outcomes.

Prediction of sorafenib treatment-related gene expression for hepatocellular carcinoma: preoperative MRI and histopathological correlation.

PURPOSE: To investigate the feasibility of prediction for targeted therapy-related gene expression in hepatocellular carcinoma (HCC) using preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI). MATERIALS AND METHODS: Ninety-one patients (81 men, mean age 53.9 ± 12 years) with solitary HCC who underwent preoperative enhanced MRI were retrospectively analyzed. Features including tumor size, signal homogeneity, tumor capsule, tumor margin, intratumoral vessels, peritumor enhancement, peritumor hypointensity, signal intensity ratio on DWI, T1 relaxation times, and the reduction rate between pre- and post-contrast enhancement images were assessed. The operation and histopathological evaluation were performed within 2 weeks after MRI examination (mean time 7 days). The expression levels of BRAF, RAF1, VEGFR2, and VEGFR3 were evaluated. The associations between these imaging features and gene expression levels were investigated. RESULTS: Tumor incomplete capsules or non-capsules (p = 0.001) and intratumoral vessels (p = 0.002) were significantly associated with BRAF expression, and tumor incomplete capsules or non-capsules (p = 0.001) and intratumoral vessels (p = 0.013) with RAF1 expression. There was no significant association between the expression of VEGFR2, VEGFR3, and all examined MRI features. Multivariate logistic regression showed that incomplete tumor capsule (p = 0.002) and non-capsule (p = 0.004) were independent risk factors of HCC with high BRAF expression; incomplete tumor capsule (p < 0.001) and non-capsule (p = 0.040) were independent risk factors of HCC with high RAF1 expression. CONCLUSION: The presence of incomplete capsule or intratumoral vessels and the absence of capsule are potential indicators of high BRAF and RAF1 expression. Gadoxetic acid-enhanced MRI may facilitate the choice of gene therapy for patients with HCC. KEY POINTS: • Incomplete tumor capsule and non-capsule were independent risk factors of HCC with high BRAF and RAF1 expression. • The presence of intratumoral vessels was a potential indicator of high BRAF and RAF1 expression. • Gadoxetic acid-enhanced MRI may be a predictor of efficacy of treatment with sorafenib.