Predictive model and risk analysis for coronary heart disease in people living with HIV using machine learning.

OBJECTIVE: This study aimed to construct a coronary heart disease (CHD) risk-prediction model in people living with human immunodeficiency virus (PLHIV) with the help of machine learning (ML) per electronic medical records (EMRs). METHODS: Sixty-one medical characteristics (including demography information, laboratory measurements, and complicating disease) readily available from EMRs were retained for clinical analysis. These characteristics further aided the development of prediction models by using seven ML algorithms [light gradient-boosting machine (LightGBM), support vector machine (SVM), eXtreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), decision tree, multilayer perceptron (MLP), and logistic regression]. The performance of this model was assessed using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was further applied to interpret the findings of the best-performing model. RESULTS: The LightGBM model exhibited the highest AUC (0.849; 95% CI, 0.814-0.883). Additionally, the SHAP plot per the LightGBM depicted that age, heart failure, hypertension, glucose, serum creatinine, indirect bilirubin, serum uric acid, and amylase can help identify PLHIV who were at a high or low risk of developing CHD. CONCLUSION: This study developed a CHD risk prediction model for PLHIV utilizing ML techniques and EMR data. The LightGBM model exhibited improved comprehensive performance and thus had higher reliability in assessing the risk predictors of CHD. Hence, it can potentially facilitate the development of clinical management techniques for PLHIV care in the era of EMRs.

Effect of electroacupuncture on neuronal programmed necrosis by regulating RIP1/RIP3/MLKL pathway in rats with cerebral ischemia reperfusion injury. / 电针调节RIP1/RIP3/MLKLé€šè·¯å¯¹è„‘ç¼ºè¡€å†çŒæ³¨æŸä¼¤å¤§é¼ ç¥žç»å ƒç¨‹åºæ€§åæ­»çš„å½±å“.

OBJECTIVES: To investigate the neuroprotective effect of electroacupuncture (EA) at "Quchi"(LI11) and "Zusanli"(ST36) in the rats with cerebral ischemia reperfusion injury and its influence on programmed necrosis of cerebral cortical neurons. METHODS: Sixty male SD rats were randomly divided into sham-operation group, model group, EA group and inhibitor group, with 15 rats in each group. Left middle cerebral artery occlusion model was established using the modified thread embolism method. In the sham-operation group, the carotid artery was exposed and dissociated in each rat. EA was applied to "Quchi"(LI11) and "Zusanli"(ST36) on the right side for 30 min each time, once daily for 7 days in the rats of the EA group. The rats in the inhibitor group were intraperitoneally injected with norstatin-1 (0.6 mg/kg) for consecutive 7 days. The neurological deficit score of rats in each group was observed. HE staining was adopted to detect the degree of pathological damage of the cerebral cortex in the infarction area. Using TUNEL staining, the apoptosis of cortical neurons in the infarction area was determined；the contents of tumor necrosis factor α (TNF-α), interleukin (IL)-1ß and IL-6 were detected by ELISA；the mRNA and protein expression of the receptor interacting protein-1 (RIP1), the receptor interacting protein-3 (RIP3) and the substrate mixed lineage kinase like protein (MLKL) were detected by fluorescence quantitative PCR and Western blot, respectively. RESULTS: In comparison with the sham-operation group, the neurological deficit score in the model group was higher(P<0.01)；HE staining showed that there was the pathological damage in the infarction area；the neuron apoptosis rate, the contents of TNF-α, IL-1ß and IL-6, and the mRNA and protein expressions of RIP1, RIP3 and MLKL increased(P<0.01) in the model group. In the EA group, the neurological deficit score was reduced(P<0.01)；HE staining showed that the pathological damage was ameliorated in the infarction area；the neuron apoptosis rate, the contents of TNF-α, IL-1ß and IL-6, and the mRNA and protein expressions of RIP1, RIP3, MLKL decreased(P<0.05, P<0.01) when compared with those in the model group. CONCLUSIONS: EA can attenuate cerebral ischemia reperfusion injury and display its neuroprotective effect probably through inhibiting programmed necrosis of cerebral cortical neurons in the rats.

HERVK-mediated regulation of neighboring genes: implications for breast cancer prognosis.

Human endogenous retroviruses (HERVs) are the remnants of ancient retroviral infections integrated into the human genome. Although most HERVs are silenced or rendered inactive by various regulatory mechanisms, they retain the potential to influence the nearby genes. We analyzed the regulatory map of 91 HERV-Ks on neighboring genes in human breast cancer and investigated the impact of HERV-Ks on the tumor microenvironment (TME) and prognosis of breast cancer. Nine RNA-seq datasets were obtained from GEO and NCBI SRA. Differentially expressed genes and HERV-Ks were analyzed using DESeq2. Validation of high-risk prognostic candidate genes using TCGA data. These included Overall survival (multivariate Cox regression model), immune infiltration analysis (TIMER), tumor mutation burden (maftools), and drug sensitivity analysis (GSCA). A total of 88 candidate genes related to breast cancer prognosis were screened, of which CD48, SLAMF7, SLAMF1, IGLL1, IGHA1, and LRRC8A were key genes. Functionally, these six key genes were significantly enriched in some immune function-related pathways, which may be associated with poor prognosis for breast cancer (p = 0.00016), and the expression levels of these genes were significantly correlated with the sensitivity of breast cancer treatment-related drugs. Mechanistically, they may influence breast cancer development by modulating the infiltration of various immune cells into the TME. We further experimentally validated these genes to confirm the results obtained from bioinformatics analysis. This study represents the first report on the regulatory potential of HERV-K in the neighboring breast cancer genome. We identified three key HERV-Ks and five neighboring genes that hold promise as novel targets for future interventions and treatments for breast cancer.

Gastric acid-responsive deformable sodium alginate/Bletilla striata polysaccharide in situ gel for the protection and treatment of alcohol-induced peptic ulcers.

First-line drugs for peptic ulcer (PU) treatment are typically limited by poor targeting and adverse effects associated with long-term use. Despite recent advancements in novel therapeutic approaches for PU, the development of sustained-release delivery systems tailored to specific pathological characteristics remains challenging. Persistent inflammation, particularly gastric inflammatory microenvironment imbalance, characterizes the PU. In this study, we prepared an in situ gel composed of sodium alginate, deacetylated gellan gum, calcium citrate, and Bletilla striata polysaccharide (BSP) to achieve sustained release of BSP. The BSP in situ gel demonstrated favorable fluidity in vitro and completed self-assembly in vivo in response to the acidic milieu at a pH of 1.5. Furthermore, the shear, extrusion, and deformation properties increased by 26.4 %, 103.7 %, and 46.3 %, respectively, with long-term gastric retention (4 h) and mucosal adaptation. Animal experiments confirmed that the BSP in situ gel could attenuate necrotic injury and inflammatory cell infiltration, maintain mucosal barrier integrity, regulate cytokine imbalance and inflammation-associated hyperapoptosis, thus effectively alleviate the inflammatory microenvironmental imbalance in PU without significant side effects. Overall, our findings demonstrated that the BSP in situ gel is a promising therapeutic strategy for PU and opens avenues for developing self-assembled formulations targeting the pathological features of PUs.

Effect of Yiyuan moxibustion on urodynamics and TRPV4/ATP/P2X5 signal pathway of bladder tissue in rats with neurogenic bladder after sacral cord injury. / ç›Šå ƒç¸å¯¹éª¶é«“æŸä¼¤åŽç¥žç»æºæ€§è†€èƒ±å¤§é¼ å°¿æµåŠ¨åŠ›å­¦åŠè†€èƒ±ç»„ç»‡TRPV4/ATP/P2X5信号通路的影响.

OBJECTIVES: To observe the effect of Yiyuan moxibustion on urodynamics and the expressions of transient receptor potential vanilloid 4 (TRPV4), adenosine triphosphate (ATP), tyrosine protein kinase KIT (C-Kit) and adenosine triphosphate receptor P2X5 in bladder tissue of rats with detrusor reflex-free neurogenic bladder (NB) after sacral cord injury (SCI), so as to explore its mechanism in promoting the recovery of urination function of NB rats. METHODS: Female SD rats were randomly divided into sham operation, model, Yiyuan moxibustion, Yiyuan moxibustion+inhibitor (combination) and inhibitor groups, with 12 rats in each group. The model of detruser reflex-free NB after sacral SCI was established by modified Hassan Shaker spinal cord transection method. The behavioral score of Basso Beasttie Bresnahan (BBB) and urodynamic indexes were used to evaluate the model of rats after operation. Fifteen days after modeling, Yiyuan moxibustion was applied to "Shenque" (CV8) and "Guanyuan" (CV4) for 20 min, once daily for 14 days. Rats of the inhibitor and combination groups were given intravesical instillation of HC067047 (1 mL, 1 µmol/L, 30 min). After the interventions, urodynamics was used to evaluate the bladder function of rats. HE staining was used to observe the morphology of bladder tissue. ATP content in bladder tissue was detected by colorimetric method. The positive expression rates of C-Kit and their receptor P2X5 in bladder tissue were observed by immunofluorescence double labeling method, and TRPV4, C-Kit, and P2X5 protein expression levels in bladder tissue were detected by Western blot. RESULTS: Compared with the sham operation group, the maximum bladder capacity and bladder compliance of rats in the model group were increased (P<0.01), the leak point pressure, ATP content, the possitive expression rates of C-Kit and P2X5, and the protein expression levels of TRPV4, C-Kit, P2X5 in bladder tissue were decreased (P<0.01). In comparison with the model and combination groups, the Yiyuan moxibustion group showed a decrease in maximum bladder capacity and bladder compliance (P<0.01), an increase in leakage point pressure, ATP content, the possitive expression rates of C-Kit and P2X5, and TRPV4, C-Kit, and P2X5 protein expression levels (P<0.01, P<0.05)；However, these indicators showed opposite trends in the inhibitor group (P<0.01, P<0.05). CONCLUSIONS: Yiyuan moxibustion can improve the urodynamics and bladder function in rats with bladder detrusor nonreflective after SCI, which may be related to its effect in activating the TRPV4 channel in bladder tissue, promoting the release of ATP from bladder epithelium, thus increasing the expression of bladder Cajal interstitial cells and their purinergic P2X5 receptors.

[Efficacy differences between electroacupuncture and moxibustion for neurogenic bladder after spinal cord injury: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy between electroacupuncture(EA) and moxibustion for neurogenic bladder (NB) after spinal cord injury (SCI). METHODS: One hundred and twenty patients with NB after SCI were randomly divided into an EA group, a moxibustion group, and an intermittent catheterization group, with 40 patients in each group. The patients in the intermittent catheterization group were treated with routine treatment and intermittent catheterization, while the patients in the EA group and the moxibustion group were treated with additional treatments of EA (discontinuous wave, with a frequency of 1.3-1.6 Hz, and intensity based on patient tolerance) and moxibustion, respectively. The acupoints used in both groups were Zhongji (CV 3) and Guanyuan (CV 4), bilateral Zusanli (ST 36), Yinlingquan (SP 9), and Baliao points. Each session lasted for 30 min, once daily, six times a week, for a total of six weeks.The maximum bladder capacity (MBC), residual urine vdume (RUV), detrusor pressure (Pdet) during the filling phase, bladder compliance (BC), maximum renal pelvis separation width of both kidneys, urine white blood cell count, TCM syndrome score, and World Health Organization quality of life assessment-BREF (WHOQOL-BREF) score were compared before and after treatment in the 3 groups. The number of patients in each group who achieved bladder functional balance was recorded, and the clinical efficacy was assessed after treatment. RESULTS: After treatment, the MBC, Pdet, BC, and WHOQOL-BREF scores in the EA group and the moxibustion group were increased (P<0.05), while the RUV, maximum renal pelvis separation width of both kidneys, urine white blood cell count, and TCM syndrome scores were decreased (P<0.05, P<0.01). In the intermittent catheterization group, MBC, RUV, maximum renal pelvis separation width of both kidneys, and urine white blood cell count were decreased (P<0.05), while BC and WHOQOL-BREF score were increased (P<0.05) after treatment. After treatment, the MBC, Pdet, BC, and WHOQOL-BREF scores in the EA group and the moxibustion group were higher than those in the intermittent catheterization group (P<0.05), while the RUV and TCM syndrome scores were lower than those in the intermittent catheterization group (P<0.05). Moreover, after treatment, the MBC and Pdet in the moxibustion group were higher than those in the EA group (P<0.05), while the RUV, maximum renal pelvis separation width of both kidneys, and TCM syndrome score in the EA group were lower than those in the moxibustion group (P<0.05). The number of patients who achieved bladder functional balance after treatment in the EA group and the moxibustion group was higher than that in the intermittent catheterization group (P<0.05). The cured and effective rate was 85.0% (34/40) in the EA group and 82.5% (33/40) in the moxibustion group, which were both higher than 65.0% (26/40) in the intermittent catheterization group (P<0.05), there was no significant difference between the EA group and the moxibustion group (P>0.05). CONCLUSION: EA and moxibustion could effectively improve the functional state of bladder in patients with NB after SCI. EA is more effective in reducing residual urine volume and excessive activity of the urethral sphincter, and relieving TCM syndromes, while moxibustion is more effective in increasing the pressure of the detrusor during the filling period and establishing the detrusor reflex.

Ultrasound radiomics nomogram for predicting large-number cervical lymph node metastasis in papillary thyroid carcinoma.

Purpose: To evaluate the value of preoperative ultrasound (US) radiomics nomogram of primary papillary thyroid carcinoma (PTC) for predicting large-number cervical lymph node metastasis (CLNM). Materials and methods: A retrospective study was conducted to collect the clinical and ultrasonic data of primary PTC. 645 patients were randomly divided into training and testing datasets according to the proportion of 7:3. Minimum redundancy-maximum relevance (mRMR) and least absolution shrinkage and selection operator (LASSO) were used to select features and establish radiomics signature. Multivariate logistic regression was used to establish a US radiomics nomogram containing radiomics signature and selected clinical characteristics. The efficiency of the nomogram was evaluated by the receiver operating characteristic (ROC) curve and calibration curve, and the clinical application value was assessed by decision curve analysis (DCA). Testing dataset was used to validate the model. Results: TG level, tumor size, aspect ratio, and radiomics signature were significantly correlated with large-number CLNM (all P< 0.05). The ROC curve and calibration curve of the US radiomics nomogram showed good predictive efficiency. In the training dataset, the AUC, accuracy, sensitivity, and specificity were 0.935, 0.897, 0.956, and 0.837, respectively, and in the testing dataset, the AUC, accuracy, sensitivity, and specificity were 0.782, 0.910, 0.533 and 0.943 respectively. DCA showed that the nomogram had some clinical benefits in predicting large-number CLNM. Conclusion: We have developed an easy-to-use and non-invasive US radiomics nomogram for predicting large-number CLNM with PTC, which combines radiomics signature and clinical risk factors. The nomogram has good predictive efficiency and potential clinical application value.

Prevalence and Biological Characteristics of Listeria Species Isolated from Livestock and Poultry Meat in Gansu Province, China.

Listeria monocytogenes is a widespread foodborne pathogen contaminating foods during their production or processing stages. Fresh meat is susceptible to such contamination if it is not properly preserved. Our study was conducted to reveal the level of contamination and prevalence of Listeria spp. present in livestock and poultry meat from Gansu province. A total of 1,387 samples were collected from five cities in Gansu Province according to standard sampling procedures, of which 174 samples (12.5%) were positive for Listeria species. Among them, 14 isolates of L. monocytogenes (1.0%), 150 isolates of Listeria innocua (10.8%), and ten isolates of Listeria welshimeri (0.7%) were identified by conventional bacteriological and molecular identification methods. All isolates were subjected to serological assays, antimicrobial susceptibility tests, growth curve assays, determination of biofilm-forming capacity, and cluster analysis of the 16S rRNA gene sequences. Four predominant serotypes of L. monocytogenes were identified, including 1/2a (35.7%, 5/14), 1/2b (14.3%, 2/14), 1/2c (42.9%, 6/14), and 4b (7.1%, 1/14). All L. monocytogenes isolates were resistant to tetracycline and cefoxitin. Most L. innocua isolates (63.6%, 14/22) and L. welshimeri (40%, 4/10) were resistant to tetracycline. The high biofilm-forming ability was observed among 1/2c and 1/2a serotype isolates. The cluster analysis of the 16S rRNA gene sequences revealed a close genetic relationship between the three Listeria species. This study fills the gap in the knowledge of livestock and poultry meat that carry Listeria in slaughterhouses and markets in Gansu Province.

A nomogram based on ultrasound characteristics to predict large-number cervical lymph node metastasis in papillary thyroid carcinoma.

To establish a nomogram for predicting large-number cervical lymph node metastases (LNMs) of primary papillary thyroid carcinoma (PTC) based on ultrasound characteristics. This retrospective study included patients with PTC diagnosed by pathological examination and who underwent surgery between August 2015 and May 2021 at Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo, China). Large-number LNM was defined as >5 lymph nodes with metastases. The patients were propensity score-matched (PSM) for age and sex. A multivariable analysis was used to determine the risk factors for massive LNM. After PSM, the 78 patients with large-number LNM were matched with 312 patients with small-number LNM. Compared with the patients with small-number LNM, those with large-number LNM had larger tumors (13.0 ± 7.7 vs. 6.8 ± 3.8 mm, p < 0.001), and higher frequencies of multifocal nodules (42.3% vs. 22.4%, p < 0.001), taller-than-wide shape (82.1% vs. 56.7%, p < 0.001), calcifications (76.9% vs. 47.4%, p < 0.001), microcalcifications (68.0% vs. 36.5%, p < 0.001), capsule invasion (32.1% vs. 17.6%, p = 0.005), and ultrasound diagnosis of LNM (44.9% vs. 9.3%, p < 0.001). The multivariable analysis showed that nodule size (OR = 1.19, 95%CI: 1.11-1.27, p < 0.001), multifocal disease (OR = 2.50, 95%CI: 1.30-4.80, p = 0.006), taller-than-wide shape (OR = 0.45, 95%CI: 0.22-0.93, p = 0.032), and ultrasound diagnosis of LNM (OR = 5.57, 95%CI: 2.73-11.37, p < 0.001) were independently associated with large-number LNM. A nomogram was built, and the area under the receiver operating characteristics curve was 0.86 (95%CI: 0.81-0.90). A nomogram was successfully built to predict large-number LNM in patients with PTC, based on nodule size, multifocality, taller-than-wide shape, and ultrasound diagnosis of LNM.

The Application of Ultrasound Image-Based Radiomics in the Diagnosis of Mild Carpal Tunnel Syndrome.

OBJECTIVES: The ultrasound diagnosis of mild carpal tunnel syndrome (CTS) is challenging. Radiomics can identify image information that the human eye cannot recognize. The purpose of our study was to explore the value of ultrasound image-based radiomics in the diagnosis of mild CTS. METHODS: This retrospective study included 126 wrists in the CTS group and 88 wrists in the control group. The radiomics features were extracted from the cross-sectional ultrasound images at the entrance of median nerve carpal tunnel, and the modeling was based on robust features. Two radiologists with different experiences diagnosed CTS according to two guidelines. The area under receiver (AUC) operating characteristic curve, sensitivity, specificity, and accuracy were used to evaluate the diagnostic efficacy of the two radiologists and the radiomics model. RESULTS: According to guideline one, the AUC values of the two radiologists for CTS were 0.72 and 0.67, respectively; according to guideline two, the AUC were 0.73 and 0.68, respectively. The radiomics model achieved the best accuracy when 16 important robust features were selected. The AUC values of training set and test set were 0.92 and 0.90, respectively. CONCLUSIONS: The radiomics label based on ultrasound images had excellent diagnostic efficacy for mild CTS. It is expected to help radiologists to identify early CTS patients as soon as possible, especially for inexperienced doctors.

A nomogram based on ultrasound radiomics for predicting the invasiveness of cN0 single papillary thyroid microcarcinoma.

Background: Up to 15.3% of papillary thyroid microcarcinoma (PTMC) patients with negative clinical lymph node metastasis (cN0) were confirmed to have pathological lymph node metastasis in level VI. Conventional ultrasound (US) focuses on the characteristics of tumor capsule and the periphery to determine whether the tumor has invasive growth. However, due to its small size, the typical features of invasiveness shown by conventional 2-dimensional (2D) US are not well visualized. US-based radiomics makes use of artificial intelligence and big data to build a model that can help improving diagnostic accuracy and providing prognostic implication of the disease. We hope to establish and assess the value of a nomogram based on US radiomics combined with independent risk factors in predicting the invasiveness of a single PTMC without clinical lymph node metastasis (cN0). Methods: A total of 317 patients with cN0 single PTMC who underwent US examination and operation were included in this retrospective cohort study. Patients were randomly divided into training and testing set in the ratio of 8:2. The US images of all patients were segmented, and the radiomics features were extracted. In the training dataset, the US with features of minimum redundancy maximum relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO) were selected and radiomics signatures were then established according to their respective weighting coefficients. Univariate and multivariate logistic regression analyses were employed to generate the risk factors of possible invasive PTMC. The nomogram is then made by combining high risk factors and the radiomics signature. The efficiency of the nomogram was evaluated by the receiver operating characteristic (ROC) curve and calibration curve, and its clinical application value was assessed by decision curve analysis (DCA). The testing dataset was used to validate the model. Results: In the model, seven radiomics features were selected to establish the radiomics signature. A nomogram was made by incorporating clinically independent risk factors and the radiomics signature. Both the ROC curve and calibration curve showed good prediction efficiency. The area under the curve (AUC), accuracy, sensitivity, and specificity of the nomogram in the training data were 0.76 [95% confidence interval (CI): 0.71-0.82], 0.811, 0.914, and 0.727, respectively whereas the results of the testing dataset were 0.71 (95% CI: 0.58-0.84), 0.841, 0.533, and 0.868. As such, the efficacy of the nomogram in predicting the invasiveness of PTMC was subsequently validated by the DCA. Conclusions: Nomogram based on thyroid US radiomics has an excellent predictive value of the potential invasiveness of a single PTMC without clinical lymph node metastasis. With these promising results, it can potentially be the imaging marker used in daily clinical practice.

Characterization and Preliminary Application of Phage Isolated From Listeria monocytogenes.

Listeria monocytogenes (LM) is one of the four major foodborne bacteria that cause bacteremia and meningitis. To explore the control of listeriosis with natural phages, we used the double-layer agar plate method to isolate LM from slaughterhouse sewage and designated LP8. The result of electron microscopy indicated that the phage belonged to the family of Myoviridae. Whole-genome sequencing indicated that the genome size of LP8 is 87,038 bp and contains 120 genes. Mice were infected with LM and treated with penicillin G sodium, LP8, and the combination of these two. From the levels of lymphocyte subsets (CD4+, CD8+), the expression of cytokines (TNF-α, IL1ß, IL-10, and IFN-γ), observation of pathological changes in organs (heart, liver, spleen, kidney, and brain), and the bacterial load of the spleen, we concluded the therapeutic effect of LP8 against listeriosis and demonstrate the feasibility of a combined therapy to reduce the use of antibiotics. This provides a new avenue for the treatment of listeriosis.

The Characteristics and Function of Internalin G in Listeria monocytogenes.

In order to clarified characteristics and function of internalin G (inlG) in Listeria monocytogenes ATCC®19111 (1/2a) (LM), the immune protection of the inlG was evaluated in mice, the homologous recombination was used to construct inlG deletion strains, and their biological characteristics were studied by the transcriptomics analysis. As a result, the immunization of mice with the purified protein achieved a protective effect against bacterial infection. The deletion strain LM-AinlG was successfully constructed with genetic stability. The mouse infection test showed that the virulence of LM was decreased after the deletion of the inlG gene. The deletion strain showed enhanced adhesion to and invasion of Caco-2 cells. Compared to the wild strain, 18 genes were up-regulated, and 24 genes were down-regulated in the LM-AinlG. This study has laid a foundation for further research on the function of inlG and the pathogenesis of LM. In this study, immunization of mice with the purified inlG protein achieved a protective effect against Listeria monocytogenes infection. The virulence of LM-ΔinlG was decreased by mouse infection. However, the adhesion and invasion ability to Caco-2 cell were enhanced. Compared to the wild strain, 18 genes were up-regulated, and 24 genes were down-regulated in the LM-ΔinlG. This study has laid a foundation for further study of the function of the inlG and the listeriosis.

Screening and Identification of Human Endogenous Retrovirus-K mRNAs for Breast Cancer Through Integrative Analysis of Multiple Datasets.

Objective: Human endogenous retroviruses (HERVs) make up 8% of the human genome. HERVs are biologically active elements related to multiple diseases. HERV-K, a subfamily of HERVs, has been associated with certain types of cancer and suggested as an immunologic target in some tumors. The expression levels of HERV-K in breast cancer (BCa) have been studied as biomarkers and immunologic therapeutic targets. However, HERV-K has multiple copies in the human genome, and few studies determined the transcriptional profile of HERV-K copies across the human genome for BCa. Methods: Ninety-one HERV-K indexes with entire proviral sequences were used as the reference database. Nine raw sequencing datasets with 243 BCa and 137 control samples were mapped to this database by Salmon software. The differential proviral expression across several groups was analyzed by DESeq2 software. Results: First, the clustering of each dataset demonstrated that these 91 HERV-K proviruses could well cluster the BCa and control samples when the normal controls were normal cells or healthy donor tissues. Second, several common HERV-K proviruses that are closely related with BCa risk were significantly differentially expressed (p adj < 0.05 and absolute log2FC > 1.5) in the tissues and cell lines. Additionally, almost all the HERV-K proviruses had higher expression in BCa tissue than in healthy donor tissue. Notably, we first found the expression of 17p13.1 provirus that located with TP53 should regulate TP53 expression in ER+ and HER2+ BCa. Conclusion: The expression profiling of these 91 HERV-K proviruses can be used as biomarkers to distinguish individuals with BCa and healthy controls. Some proviruses, especially 17p13.1, were strongly associated with BCa risk. The results suggest that HERV-K expression profiles may be appropriate biomarkers and targets for BCa.

Bayesian fusion and multimodal DCM for EEG and fMRI.

This paper asks whether integrating multimodal EEG and fMRI data offers a better characterisation of functional brain architectures than either modality alone. This evaluation rests upon a dynamic causal model that generates both EEG and fMRI data from the same neuronal dynamics. We introduce the use of Bayesian fusion to provide informative (empirical) neuronal priors - derived from dynamic causal modelling (DCM) of EEG data - for subsequent DCM of fMRI data. To illustrate this procedure, we generated synthetic EEG and fMRI timeseries for a mismatch negativity (or auditory oddball) paradigm, using biologically plausible model parameters (i.e., posterior expectations from a DCM of empirical, open access, EEG data). Using model inversion, we found that Bayesian fusion provided a substantial improvement in marginal likelihood or model evidence, indicating a more efficient estimation of model parameters, in relation to inverting fMRI data alone. We quantified the benefits of multimodal fusion with the information gain pertaining to neuronal and haemodynamic parameters - as measured by the Kullback-Leibler divergence between their prior and posterior densities. Remarkably, this analysis suggested that EEG data can improve estimates of haemodynamic parameters; thereby furnishing proof-of-principle that Bayesian fusion of EEG and fMRI is necessary to resolve conditional dependencies between neuronal and haemodynamic estimators. These results suggest that Bayesian fusion may offer a useful approach that exploits the complementary temporal (EEG) and spatial (fMRI) precision of different data modalities. We envisage the procedure could be applied to any multimodal dataset that can be explained by a DCM with a common neuronal parameterisation.

Development of a 90-Minute Integrated Noninvasive Urinary Assay for Bladder Cancer Detection.

PURPOSE: Despite suboptimal sensitivity urine cytology is often performed as an adjunct to cystoscopy for bladder cancer diagnosis. We aimed to develop a noninvasive, fast molecular diagnostic test for bladder cancer detection with better sensitivity than urine cytology while maintaining adequate specificity. MATERIALS AND METHODS: Urine specimens were collected at 18 multinational sites from subjects prior to cystoscopy or tumor resection, and from healthy and other control subjects without evidence of bladder cancer. The levels of 10 urinary mRNAs were measured in a training cohort of 483 subjects and regression analysis was used to identify a 5-mRNA model to predict cancer status. The performance of the GeneXpert® Bladder Cancer Assay, an assay labeled for investigational use only to detect the 5 mRNAs ABL1, CRH, IGF2, ANXA10 and UPK1B, was evaluated in an independent test cohort of 450 participants. RESULTS: In the independent test cohort the assay ROC curve AUC was 0.87 (95% CI 0.81-0.92). At an example cutoff point of 0.4 overall sensitivity was 73% while specificity was 90% and 77% in the hematuria and surveillance patient populations, respectively. CONCLUSIONS: We developed a 90-minute, urine based test that is simple to perform for the detection of bladder cancer. The test can help guide physician decision making in the management of bladder cancer. Additional evaluation in a prospective study is needed to establish the clinical usefulness of this assay.

Altered Effective Connectivity among Core Neurocognitive Networks in Idiopathic Generalized Epilepsy: An fMRI Evidence.

Idiopathic generalized epilepsy (IGE) patients with generalized tonic-clonic seizures (GTCS) suffer long-term cognitive impairments, and present a higher incidence of psychosocial and psychiatric disturbances than healthy people. It is possible that the cognitive dysfunctions and higher psychopathological risk in IGE-GTCS derive from disturbed causal relationship among core neurocognitive brain networks. To test this hypothesis, we examined the effective connectivity across the salience network (SN), default mode network (DMN), and central executive network (CEN) using resting-state functional magnetic resonance imaging (fMRI) data collected from 27 IGE-GTCS patients and 29 healthy controls. In the study, a combination framework of time domain and frequency domain multivariate Granger causality analysis was firstly proposed, and proved to be valid and accurate by simulation experiments. Using this method, we then observed significant differences in the effective connectivity graphs between the patient and control groups. Specifically, between-group statistical analysis revealed that relative to the healthy controls, the patients established significantly enhanced Granger causal influence from the dorsolateral prefrontal cortex to the dorsal anterior cingulate cortex, which is coherent both in the time and frequency domains analyses. Meanwhile, time domain analysis also revealed decreased Granger causal influence from the right fronto-insular cortex to the posterior cingulate cortex in the patients. These findings may provide new evidence for functional brain organization disruption underlying cognitive dysfunctions and psychopathological risk in IGE-GTCS.

[Advances in the application of smart phones in modern medicine].

Since smart phones have been developed, significant advances in the function of mobile phone due to the development of software, hardware and accessories have been reached. Till now, smart phones have been engaged in daily life with an increasing impact. As a new medical model, mobile phone medicine is emerging and has found wide spread applications in medicine, especially in diagnosing, monitoring and screening various diseases. In addition, mo bile phone medical application shows great potential trend to improve healthcare in resource-limited regions due to its advantageous features of portability and information communication capability. Nowadays, the scientific and technological issues related to mobile phone medicine have attracted worldwide attention. In this review, we summarize state-of-the-art advances of mobile phone medicine with focus on its diagnostics applications in order to expand the fields of their applications and promote healthcare informatization.

Crude caffeine reduces memory impairment and amyloid ß(1-42) levels in an Alzheimer's mouse model.

Alzheimer's disease (AD), a chronic neurodegenerative disorder associated with the abnormal accumulations of amyloid ß (Aß) peptide and oxidative stress in the brain, is the most common form of dementia among the elderly. Crude caffeine (CC), a major by-product of the decaffeination of coffee, has potent hydrophilic antioxidant activity and may reduce inflammatory processes. Here, we showed that CC and pure caffeine intake had beneficial effects in a mouse model of AD. Administration of CC or pure caffeine for 2months partially prevented memory impairment in AD mice, with CC having greater effects than pure caffeine. Furthermore, consumption of CC, but not pure caffeine, reduced the Aß(1-42) levels and the number of amyloid plaques in the hippocampus. Moreover, CC and caffeine protected primary neurons from Aß-induced cell death and suppressed Aß-induced caspase-3 activity. Our data indicate that CC may contain prophylactic agents against the cell death and the memory impairment in AD.

Rapid gene splicing and multi-sited mutagenesis by one-step overlap extension polymerase chain reaction.

Gene splicing and site-directed mutagenesis (SDM) are important to introduce desired sequences in target DNA. However, introducing mutations at multiple sites requires multiple steps of DNA manipulation, which is time-consuming and labor-intensive. Here, we present a rapid efficient gene splicing and multi-sited mutagenesis method that introduces mutations at two distant sites via sequential connection of DNA fragments by one-step overlap extension polymerase chain reaction (OE-PCR). This bottom-up approach for DNA engineering can be broadly used to study protein structure-function, to optimize codon use for protein expression, and to assemble genes of interest.