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Introduction: The microbiota-gut-brain axis is implicated in Alzheimer's disease. Gut microbiota alterations in mild cognitive impairment (MCI) are inconsistent and remain to be understood. This study aims to investigate the gut microbial composition associated with MCI, cognitive functions, and structural brain differences. Methods: A nested case-control study was conducted in a community-based prospective cohort where detailed cognitive functions and structural brain images were collected. Thirty-one individuals with MCI were matched to sixty-five cognitively normal controls by age strata, gender, and urban/rural area. Fecal samples were examined using 16S ribosomal RNA (rRNA) V3-V4 sequencing. Compositional differences between the two groups were identified and correlated with the cognitive functions and volumes/thickness of brain structures. Results: There was no significant difference in alpha and beta diversity between MCIs and cognitively normal older adults. However, the abundance of the genus Ruminococcus, Butyricimonas, and Oxalobacter decreased in MCI patients, while an increased abundance of nine other genera, such as Flavonifractor, were found in MCIs. Altered genera discriminated MCI patients well from controls (AUC = 84.0%) and were associated with attention and executive function. Conclusion: This study provides insights into the role of gut microbiota in the neurodegenerative process. [ABSTRACT FROM AUTHOR]

Portable magnetic-assisted capsule endoscopy (MACE) provides satisfactory patient experience and safety with comparable performance in diagnosis of organic lesions when compared to conventional upper gastrointestinal endoscopy. In this study, a total of 58 homecare patients were included for MACE either in the hospital (n = 42) or at home (n = 16), with mean age of 71.1 ± 12.4 years. A total of 55 patients (94.83%) had completed the MACE with diagnosis of reflux esophagitis (43.6%), gastritis (54.5%), erosions (21.8%), fundic polyps (14.5%), peptic ulcers (25.9%), etc. Most patients (n = 47, 85.5%) were satisfied with the experience, and all patients who received MACE at home (n = 15, 100%) appreciated the convenience of endoscopy at home. Less than half of the patients (n = 24, 43.6%) could afford MACE if the expense was not covered by health insurance (USD 714). Time consumption from both traffic and capsule manipulation was also challenging for the physicians, as it took an average of 24.7 min to complete MACE, but it added up to a total of 92.7 min at home, which is about 15 times that of conventional endoscopy in hospital. More efforts are needed to ease the financial burden of patients, and optimization of workflow in community practice may help lift the obstacles revealed in this study. [ABSTRACT FROM AUTHOR]

Transcription factor and microRNA (miRNA) can mutually regulate each other and jointly regulate their shared target genes to form feed-forward loops (FFLs).While there are many studies of dysregulated FFLs in a specific cancer, a systematic investigation of dysregulated FFLs across multiple tumor types (pan-cancer FFLs) has not been performed yet. In this study, using The Cancer Genome Atlas data, we identified 26 pan-cancer FFLs, which were dysregulated in at least five tumor types. These pan-cancer FFLs could communicate with each other and form functionally consistent subnetworks, such as epithelial to mesenchymal transition-related subnetwork. Many proteins and miRNAs in each subnetwork belong to the same protein and miRNA family, respectively. Importantly, cancer-associated genes and drug targets were enriched in these pan-cancer FFLs, in which the genes and miRNAs also tended to be hubs and bottlenecks. Finally, we identified potential anticancer indications for existing drugs with novel mechanismof action. Collectively, this study highlights the potential of pan-cancer FFLs as a novel paradigmin elucidating pathogenesis of cancer and developing anticancer drugs. [ABSTRACT FROM AUTHOR]

Background Recently, a number of large-scale cancer genome sequencing projects have generated a large volume of somatic mutations; however, identifying the functional consequences and roles of somatic mutations in tumorigenesis remains a major challenge. Researchers have identified that protein pocket regions play critical roles in the interaction of proteins with small molecules, enzymes, and nucleic acid. As such, investigating the features of somatic mutations in protein pocket regions provides a promising approach to identifying new genotype-phenotype relationships in cancer. Methods In this study, we developed a protein pocket-based computational approach to uncover the functional consequences of somatic mutations in cancer. We mapped 1.2 million somatic mutations across 36 cancer types from the COSMIC database and The Cancer Genome Atlas (TCGA) onto the protein pocket regions of over 5,000 protein three-dimensional structures. We further integrated cancer cell line mutation profiles and drug pharmacological data from the Cancer Cell Line Encyclopedia (CCLE) onto protein pocket regions in order to identify putative biomarkers for anticancer drug responses. Results We found that genes harboring protein pocket somatic mutations were significantly enriched in cancer driver genes. Furthermore, genes harboring pocket somatic mutations tended to be highly co-expressed in a co-expressed protein interaction network. Using a statistical framework, we identified four putative cancer genes (RWDD1, NCF1, PLEK, and VAV3), whose expression profiles were associated with overall poor survival rates in melanoma, lung, or colorectal cancer patients. Finally, genes harboring protein pocket mutations were more likely to be drug-sensitive or drug-resistant. In a case study, we illustrated that the BAX gene was associated with the sensitivity of three anticancer drugs (midostaurin, vinorelbine, and tipifarnib). Conclusions This study provides novel insights into the functional consequences of somatic mutations during tumorigenesis and for anticancer drug responses. The computational approach used might be beneficial to the study of somatic mutations in the era of cancer precision medicine. [ABSTRACT FROM AUTHOR]

Summary Chronic subdural hematoma (SDH) is a common clinical entity in neurosurgery. Craniostomy, including twist-drill holes or burr holes with or without drainage, is the treatment of choice for SDH. Despite convincing results from this surgical procedure, unexpected complications may still develop such as acute epidural hematoma, acute SDH, intracerebral hemorrhage (ICH), tension pneumocephalus, and empyema. We present a rare complication of an acute SDH located between the dura and the outer membrane instead of within the previous hematoma cavity (i.e., between the outer and the inner membrane), which occurred after chronic SDH burr-hole evacuation with closed-system drainage. This complication resulted from misplacement of the drainage catheter and superimposed coagulopathy. In conclusion, precisely inserting the drainage catheter in the chronic SDH space and reversing coagulopathy before and after the surgical procedure are necessary to prevent such complications. [ABSTRACT FROM AUTHOR]

Background: Gene expression profiles have been frequently integrated with the human protein interactome to uncover functional modules under specific conditions like disease state. Beyond traditional differential expression analysis, differential co-expression analysis has emerged as a robust approach to reveal condition-specific network modules, with successful applications in a few human disease studies. Hepatocellular carcinoma (HCC), which is often interrelated with the Hepatitis C virus, typically develops through multiple stages. A comprehensive investigation of HCC progression-specific differential co-expression modules may advance our understanding of HCC's pathophysiological mechanisms. Results: Compared with differentially expressed genes, differentially co-expressed genes were found more likely enriched with Hepatitis C virus binding proteins and cancer-mutated genes, and they were clustered more densely in the human reference protein interaction network. These observations indicated that a differential co-expression approach could outperform the standard differential expression network analysis in searching for disease-related modules. We then proposed a differential co-expression network approach to uncover network modules involved in HCC development. Specifically, we discovered subnetworks that enriched differentially co-expressed gene pairs in each HCC transition stage, and further resolved modules with coherent co-expression change patterns over all HCC developmental stages. Our identified network modules were enriched with HCC-related genes and implicated in cancer-related biological functions. In particular, APC and YWHAZ were highlighted as two most remarkable genes in the network modules, and their dynamic interaction partnership was resolved in HCC development. Conclusions: We demonstrated that integration of differential co-expression with the protein interactome could outperform the traditional differential expression approach in discovering network modules of human diseases. In our application of this approach to HCC's gene expression data, we successfully identified subnetworks with marked differential co-expression in individual HCC stage transitions and network modules with coherent coexpression change patterns over all HCC developmental stages. Our results shed light on subtle HCC mechanisms, including temporal activation and dismissal of pivotal functions and dynamic interaction partnerships of key genes. [ABSTRACT FROM AUTHOR]

MicroRNAs, which are small endogenous RNA regulators, have been associated with various types of cancer. Breast cancer is a major health threat for women worldwide. Many miRNAs were reported to be associated with the progression and carcinogenesis of breast cancer. In this study, we aimed to discover novel breast cancer-related miRNAs and to elucidate their functions. First, we identified confident miRNA-target pairs by combining data from miRNA target prediction databases and expression profiles of miRNA and mRNA. Then, miRNA-regulated protein interaction networks (PINs) were constructed with confident pairs and known interaction data in the human protein reference database (HPRD). Finally, the functions of miRNA-regulated PINs were elucidated by functional enrichment analysis. From the results, we identified some previously reported breast cancer-related miRNAs and functions of the PINs, e.g., miR-125b, miR-125a, miR-21, and miR-497. Some novel miRNAs without known association to breast cancer were also found, and the putative functions of their PINs were also elucidated. These include miR-139 and miR-383. Furthermore, we validated our results by receiver operating characteristic (ROC) curve analysis using our miRNA expression profile data, gene expression-based outcome for breast cancer online (GOBO) survival analysis, and a literature search. Our results may provide new insights for research in breast cancer-associated miRNAs. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are a class of endogenous, small and highly conserved noncoding RNAs that control gene expression either by degradation of target mRNAs or by inhibition of protein translation. They play important roles in cancer progression. A single miRNA can provoke a chain reaction and further affect protein interaction network (PIN). Therefore, we developed a novel integrative approach to identify the functional roles and the regulated PIN of oncomirs. Results: We integrated the expression profiles of miRNA and mRNA with the human PIN to reveal miRNA-regulated PIN in specific biological conditions. The potential functions of miRNAs were determined by functional enrichment analysis and the activities of miRNA-regulated PINs were evaluated by the co-expression of protein-protein interactions (PPIs). The function of a specific miRNA, miR-148a, was further examined by clinical data analysis and cell-based experiments. We uncovered several miRNA-regulated networks which were enriched with functions related to cancer progression. One miRNA, miR-148a, was identified and its function is to decrease tumor proliferation and metastasis through its regulated PIN. Furthermore, we found that miR-148a could reduce the invasiveness, migratory and adhesive activities of gastric tumor cells. Most importantly, elevated miR-148a level in gastric cancer tissues was strongly correlated with distant metastasis, organ and peritoneal invasion and reduced survival rate. Conclusions: This study provides a novel method to identify active oncomirs and their potential functions in gastric cancer progression. The present data suggest that miR-148a could be a potential prognostic biomarker of gastric cancer and function as a tumor suppressor through repressing the activity of its regulated PIN. [ABSTRACT FROM AUTHOR]

Background: Molecular networks represent the backbone of molecular activity within cells and provide opportunities for understanding the mechanism of diseases. While protein-protein interaction data constitute static network maps, integration of condition-specific co-expression information provides clues to the dynamic features of these networks. Dilated cardiomyopathy is a leading cause of heart failure. Although previous studies have identified putative biomarkers or therapeutic targets for heart failure, the underlying molecular mechanism of dilated cardiomyopathy remains unclear. Results: We developed a network-based comparative analysis approach that integrates protein-protein interactions with gene expression profiles and biological function annotations to reveal dynamic functional modules under different biological states. We found that hub proteins in condition-specific co-expressed protein interaction networks tended to be differentially expressed between biological states. Applying this method to a cohort of heart failure patients, we identified two functional modules that significantly emerged from the interaction networks. The dynamics of these modules between normal and disease states further suggest a potential molecular model of dilated cardiomyopathy. Conclusions: We propose a novel framework to analyze the interaction networks in different biological states. It successfully reveals network modules closely related to heart failure; more importantly, these network dynamics provide new insights into the cause of dilated cardiomyopathy. The revealed molecular modules might be used as potential drug targets and provide new directions for heart failure therapy. [ABSTRACT FROM AUTHOR]

Ultraviolet (UV) irradiation has emerged as a viable alternative for water/wastewater disinfection. Laboratory dose-response data from collimated-beam tests are commonly used as a basis for determining the necessary delivered UV dose for full-scale UV systems as measured by UV intensity and exposure time. While researchers often think that germicidal dose can be estimated confidently in a collimated beam system, the reported dose-response relationships vary considerably. Numerous factors may affect the test results to some extent. They include apparatus setup, column dimensions, UV lamp type and output, intensity measurement, shutter type and operation, petri dish specifications, sample volume and depth of the liquid, mixing condition, laboratory settings, microbial organism preparation and testing, and water quality. The methodology used to calculate the UV dose for collimated beam tests is also a critical factor. To ensure reproducibility or to have a meaningful comparison of results from different collimated beam tests, a standardized protocol for collimated beam testing and its dose calculation is necessary. The standardized collimated beam test can then serve as a tool to ''calibrate'' the dose calculation models for field-scale UV reactors and, consequently, to meaningfully compare the dose values derived from these models. A comprehensive standardized collimated beam testing protocol is warranted to advance applications of UV disinfection for water/ wastewater. However, development of such a protocol is a significant research effort that will require input from researchers of various technical and disciplinary backgrounds. In addition, some technical issues still need to be clarified by further research. This paper presents important issues associated with collimated beam testing in the context of developing a standard protocol as well as future research needs. The main objective is to serve as a starting point for development of a standardized... [ABSTRACT FROM AUTHOR]

The magnetic assisted capsule endoscope (MACE) with a hand-held magnetic field navigator (MFN) for upper gastrointestinal examination achieved satisfactory results in a healthy volunteer study. We evaluated the feasibility of upper gastrointestinal examination in the home care setting with the MACE system. Home care patients with upper gastrointestinal symptoms that received an MACE exam were enrolled in the study. MACE procedure time; completeness of observation of important anatomical landmarks; endoscopic diagnosis; patient tolerance during the procedure; and patient data, including age, sex, comorbidities, symptoms, body weight, and height, were retrieved from hospital information system for data analysis. A total of 16 participants were enrolled with a mean age 74.3 ± 15.4 years (47 to 99 years). One patient failed to swallow the capsule and was excluded. The average procedure time was 23.7 ± 10.0 min (14.1 to 42.5 min) to complete each endoscopic exam for the remaining 15 patients. The overall maneuverability in the esophagus, stomach, and duodenum was 93.75%, 87.5%, and 75%, respectively. Overall completeness in the aforementioned regions was 93.75%, 81.25%, and 75%, respectively. No severe adverse events were noted. The results clearly demonstrate the promise of using this MACE system to perform endoscopic examination outside the hospital for patients confined to the community and home. [ABSTRACT FROM AUTHOR]

The article focuses on acute bleeding into the outer dural membrane space after burr hole craniotomy for chronic subdural hemorrhage. There are reports of unexpected postoperative complications, such as acute epidural hemorrhage, acute chronic subdural hemorrhage, intracranial hematoma, tension pneumocephalus and ischaemic cerebral infarction after twist drill or burr hole craniotomy. The twist drill or burr hole craniotomy with closed system drainage was suggested by T. M. Markwalder in 1981.