A three-miRNA signature as promising non-invasive diagnostic marker for gastric cancer

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Circulating microRNAs as Specific Biomarkers for Breast Cancer Detection

Background: We previously showed microRNAs (miRNAs) in plasma are potential biomarkers for colorectal cancer detection. Here, we aimed to develop specific blood-based miRNA assay for breast cancer detection. Methodology/Principal Findings: TaqMan-based miRNA profiling was performed in tumor, adjacent non-tumor, corresponding plasma from breast cancer patients, and plasma from matched healthy controls. All putative markers identified were verified in a training set of breast cancer patients. Selected markers were validated in a case-control cohort of 170 breast cancer patients, 100 controls, and 95 other types of cancers and then blindly validated in an independent set of 70 breast cancer patients and 50 healthy controls. Profiling results showed 8 miRNAs were concordantly up-regulated and 1 miRNA was concordantly down-regulated in both plasma and tumor tissue of breast cancer patients. Of the 8 up-regulated miRNAs, only 3 were significantly elevated (p<0.0001) before surgery and reduced after surgery in the training set. Results from the validation cohort showed that a combination of miR-145 and miR-451 was the best biomarker (p<0.0001) in discriminating breast cancer from healthy controls and all other types of cancers. In the blind validation, these plasma markers yielded Receiver Operating Characteristic (ROC) curve area of 0.931. The positive predictive value was 88% and the negative predictive value was 92%. Altered levels of these miRNAs in plasma have been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS) cases was 96%. Conclusions: These results suggested that these circulating miRNAs could be a potential specific biomarker for breast cancer screening. © 2013 Ng et al.published_or_final_versio

Acquired craniomeningocele in an infant with craniosynostosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Craniosynostosis can affect the skull in various ways. The most common forms are abnormal skull shape and beaten copper pattern, while Lückenschädel (or lacunar skull) is one of the least common forms.</p> <p>Case presentation</p> <p>We report the case of a 3-month-old Caucasian boy with multiple suture craniosynostosis and with acquired craniomeningocele presenting as a bulging mass in the lateral occipital area.</p> <p>Conclusion</p> <p>To the best of our knowledge, this is the first report of a patient with multiple suture craniosynostosis and acquired craniomeningocele.</p

Treatment of congenital extrahepatic portosystemic shunts in dogs : a systematic review and meta‐analysis

Background Several options have been proposed for the treatment of congenital extrahepatic portosystemic shunts (cEHPSS) in dogs, but formal comparisons among different treatment options are currently unavailable. A previous evidence-based review (2012) found low quality of evidence for papers assessing the treatment of cEHPSS in dogs. Objectives To assess the quality of evidence available in the treatment of cEHPSS, summarize the current state of knowledge with respect to outcome after cEHPSS management, and compare different treatment techniques. Animals Not used. Methods A bibliographic search was performed without date or language restrictions. Studies were assessed for quality of evidence (study design, study group sizes, subject enrollment quality, and overall risk of bias) and outcome measures reported (perioperative outcome, clinical outcome, and surgical or interventional outcome), all reported with 95% confidence intervals. A network meta-analysis was performed. Results Forty-eight studies were included. Six retrospective studies (grade 4b) compared 2 techniques and 7 were abstracts (grade 5). The quality of evidence was low and risk of bias high. Regarding surgical outcome, statistically significant superiority of ameroid constrictor over thin film band was observed (P = .003). No other comparisons were statistically significant. Conclusions and Clinical Importance The evidence base of choice of treatment of cEHPSS in dogs remains weak despite recent publications on the subject. Ameroid is superior to thin film band in causing EHPSS closure. Blinded randomized studies comparing different treatment modalities, which routinely include postoperative imaging to assess cEHPSS closure and acquired portosystemic shunt development are essential

Suitability of databases in the Asia-Pacific for collaborative monitoring of vaccine safety

Introduction: Information regarding availability of electronic healthcare databases in the Asia-Pacific region is critical for planning vaccine safety assessments particularly, as COVID-19 vaccines are introduced. This study aimed to identify data sources in the region, potentially suitable for vaccine safety surveillance. This manuscript is endorsed by the International Society for Pharmacoepidemiology (ISPE). Methods: Nineteen countries targeted for database reporting were identified using published country lists and review articles. Surveillance capacity was assessed using two surveys: a 9-item introductory survey and a 51-item full survey. Survey questions related to database characteristics, covariate and health outcome variables, vaccine exposure characteristics, access and governance, and dataset linkage capability. Other questions collated research/regulatory applications of the data and local publications detailing database use for research. Results: Eleven databases containing vaccine-specific information were identified across 8 countries. Databases were largely national in coverage (8/11, 73%), encompassed all ages (9/11, 82%) with population size from 1.4 to 52 million persons. Vaccine exposure information varied particularly for standardized vaccine codes (5/11, 46%), brand (7/11, 64%) and manufacturer (5/11, 46%). Outcome data were integrated with vaccine data in 6 (55%) databases and available via linkage in 5 (46%) databases. Data approval processes varied, impacting on timeliness of data access. Conclusions: Variation in vaccine data availability, complexities in data access including, governance and data release approval procedures, together with requirement for data linkage for outcome information, all contribute to the challenges in building a distributed network for vaccine safety assessment in the Asia-Pacific and globally. Common data models (CDMs) may help expedite vaccine safety research across the region

Spread of Mutant Middle East Respiratory Syndrome Coronavirus with Reduced Affinity to Human CD26 during the South Korean Outbreak

The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe respiratory infection with a high mortality rate (similar to 35%). MERS-CoV has been a global threat due to continuous outbreaks in the Arabian peninsula and international spread by infected travelers since 2012. From May to July 2015, a large outbreak initiated by an infected traveler from the Arabian peninsula swept South Korea and resulted in 186 confirmed cases with 38 deaths (case fatality rate, 20.4%). Here, we show the rapid emergence and spread of a mutant MERS-CoV with reduced affinity to the human CD26 receptor during the South Korean outbreak. We isolated 13 new viral genomes from 14 infected patients treated at a hospital and found that 12 of these genomes possess a point mutation in the receptor-binding domain (RBD) of viral spike (S) protein. Specifically, 11 of these genomes have an I529T mutation in RBD, and 1 has a D510G mutation. Strikingly, both mutations result in reduced affinity of RBD to human CD26 compared to wild-type RBD, as measured by surface plasmon resonance analysis and cellular binding assay. Additionally, pseudotyped virus bearing an I529T mutation in S protein showed reduced entry into host cells compared to virus with wild-type S protein. These unexpected findings suggest that MERS-CoV adaptation during human-to-human spread may be driven by host immunological pressure such as neutralizing antibodies, resulting in reduced affinity to host receptor, and thereby impairs viral fitness and virulence, rather than positive selection for a better affinity to CD26. IMPORTANCE Recently, a large outbreak initiated by an MERS-CoV-infected traveler from the Middle East swept South Korea and resulted in 186 confirmed cases with 38 deaths. This is the largest outbreak outside the Middle East, and it raised strong concerns about the possible emergence of MERS-CoV mutations. Here, we isolated 13 new viral genomes and found that 12 of them possess a point mutation in the receptor-binding domain of viral spike protein, resulting in reduced affinity to the human cognate receptor, CD26, compared to the wild-type virus. These unexpected findings suggest that MERS-CoV adaptation in humans may be driven by host immunological pressure.111819Ysciescopu

Intraventricular glioneuronal tumor with disseminated lesions at diagnosis - a case report -

A 55-year-old man presented with a large tumor in his lateral ventricles. Magnetic resonance imaging revealed disseminated lesions in the third and fourth ventricles at the time of diagnosis. The patient underwent a partial removal of the tumor in the lateral ventricles. Histologically, the surgical specimens showed glioneuronal differentiation with ganglion or ganglioid cells, Rosenthal fibers, oligodendroglia-like honeycomb appearances, a spongy pattern, perivascular pseudorosettes, and many hyalinized blood vessels. Papillary structure was not observed. The neuronal component showed a moderately high labeling index of Ki-67/MIB-1. We diagnosed this tumor as atypical intraventricular glioneuronal tumor. The disseminated lesions disappeared after chemoradiation therapy with temozolomide, and the residual tumors in the lateral ventricles remained stable for 3 years after the surgery. We discuss the pathological diagnosis, therapy and clinical course with review of the literatures

The inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex.

The inner centromere is a region on every mitotic chromosome that enables specific biochemical reactions that underlie properties, such as the maintenance of cohesion, the regulation of kinetochores and the assembly of specialized chromatin, that can resist microtubule pulling forces. The chromosomal passenger complex (CPC) is abundantly localized to the inner centromeres and it is unclear whether it is involved in non-kinase activities that contribute to the generation of these unique chromatin properties. We find that the borealin subunit of the CPC drives phase separation of the CPC in vitro at concentrations that are below those found on the inner centromere. We also provide strong evidence that the CPC exists in a phase-separated state at the inner centromere. CPC phase separation is required for its inner-centromere localization and function during mitosis. We suggest that the CPC combines phase separation, kinase and histone code-reading activities to enable the formation of a chromatin body with unique biochemical activities at the inner centromere

Lifestyle and geographic insights into the distinct gut microbiota in elderly women from two different geographic locations

BACKGROUND: A large number of microorganisms reside within the gastrointestinal tract, especially in the colon, and play important roles in human health and disease. The composition of the human gut microbiota is determined by intrinsic host factors and environmental factors. While investigating environmental factors to promote human health is of great interest, few studies have focused on their effect on the gut microbiota. This study aimed to investigate differences in gut microbiota composition according to lifestyle and geographical area, even in people with similar genetic background. METHODS: We enrolled ten and nine elderly women in their seventies from island and inland areas, respectively. Fecal samples were obtained from individuals, and bacterial 16S ribosomal RNA genes were analyzed by next-generation sequencing to define the gut microbiota composition. We assessed their diet, which can influence the gut microbial community. We also conducted physical examination and determined the physical activity levels of the subjects. RESULTS: The inland subjects had a significantly higher rectal temperature, systolic blood pressure, and heart rate and a significantly lower physical activity score than the island subjects. Fecal samples from the island group showed a tendency to have greater microbial diversity than those from the inland group. Interestingly, the microbial community composition differed significantly between the two groups. Catenibacterium was enriched in subjects from the island area. Catenibacterium showed a negative correlation with rectal temperature and a positive correlation with the dietary level of animal fat. In contrast, Butyricimonas was enriched in the inland subjects. A positive correlation was found between Butyricimonas and mean arterial pressure. CONCLUSIONS: This study identified differences in the gut microbiota composition between elderly women from different parts of South Korea, and our findings suggest that further studies of the human gut microbiota should evaluate aspects of the living environment