Prognostic Role of Claudin-1 Immunohistochemistry in Malignant Solid Tumors: A Meta-Analysis

Background Although the correlation between low claudin-1 expression and worse prognosis has been reported, details on the prognostic implications of claudin-1 expression in various malignant tumors remain unclear. The present study aimed to elucidate the prognostic roles of claudin- 1 immunohistochemistry (IHC) in various malignant tumors through a meta-analysis. Methods The study included 2,792 patients from 22 eligible studies for assessment of the correlation between claudin-1 expression and survival rate in various malignant tumors. A subgroup analysis based on the specific tumor and evaluation criteria of claudin-1 IHC was conducted. Results Low claudin-1 expression was significantly correlated with worse overall survival (OS) (hazard ratio [HR], 1.851; 95% confidence interval [CI], 1.506 to 2.274) and disease-free survival (DFS) (HR, 2.028; 95% CI, 1.313 to 3.134) compared to high claudin-1 expression. Breast, colorectal, esophageal, gallbladder, head and neck, and lung cancers, but not cervical, liver or stomach cancers, were significantly correlated with worse OS. Breast, colorectal, esophageal, and thyroid cancers with low claudin-1 expression were associated with poorer DFS. In the lower cut-off subgroup (< 25.0%) with respect to claudin-1 IHC, low claudin-1 expression was significantly correlated with worse OS and DFS. Conclusions Taken together, low claudin-1 IHC expression is significantly correlated with worse survival in various malignant tumors. More detailed criteria for claudin-1 IHC expression in various malignant tumors are needed for application in daily practice

Impact of ovarian preservation in women with endometrial cancer

AbstractBackgroundBilateral salpingo-oophorectomy (BSO) is standardly performed in the treatment of endometrial cancer. The purpose of this study was to evaluate the impact of ovarian preservation on the outcome of patients with endometrial cancer.MethodsA retrospective cohort study was performed using the 2000–2010 database of endometrial cancer patients who were treated at Taipei Veterans General Hospital. Information regarding patient age, pathologic reports, and follow-up results was abstracted from medical records.ResultsFive hundred and twenty-nine patients were reviewed in this study. Mean age and follow-up duration were 55.7 ± 11.4 years and 37.5 ± 30.1 months, respectively. The median disease-free survival was 31.2 months (range 0.2–126.9 months). There were no significant differences in disease-free survival between stage I patients with ovarian preservation versus those with oophorectomy (p = 0.473). In a multivariate Cox model, ovarian preservation had no effect on disease-free survival [hazard ratio (HR) = 2.72; 95% confidence interval (CI), 0.48–15.59]; however, it was not significantly related to stage and para-aortic lymph node involvement.ConclusionOvarian preservation may be considered in premenopausal women with early-stage low-risk endometrial cancer

Breakpoint mapping by whole genome sequencing identifies PTH2R gene disruption in a patient with midline craniosynostosis and a de novo balanced chromosomal rearrangement

Background: Craniosynostosis (CRS) is a premature closure of calvarial sutures caused by gene mutation or environmental factors or interaction between the two. Only a small proportion of non-syndromic CRS (NSC) patients have a known genetic cause, and thus, it would be meaningful to search for a causative gene disruption for the development NSC. We applied a whole genome sequencing approach on a 15-month-old boy with sagittal and metopic synostosis to identify a gene responsible for the development of the disease. Methods and results Conventional chromosome study revealed a complex paracentric inversion involving 2q14.3 and 2q34. Array comparative genomic hybridisation did not show any copy number variation. Multicolour banding analysis was carried out and the breakpoints were refined to 2q14 and 2q34. An intronic break of the PTH2R gene was detected by whole genome sequencing and fluorescence in situ hybridisation analysis confirmed disruption of PTH2R. Conclusions: We report PTH2R as a gene that is disrupted in NSC. The disruption of the PTH2R gene may cause uncontrolled proliferation and differentiation of chondrocytes, which in turn results in premature closure of sutures. This addition of PTH2R to the list of genes associated with NSC expands our understanding of the development of NSC

Sequencing and characterization of Varicella-Zoster virus vaccine strain SuduVax

<p>Abstract</p> <p>Background</p> <p>Varicella-zoster virus (VZV) causes chickenpox in children and shingles in older people. Currently, live attenuated vaccines based on the Oka strain are available worldwide. In Korea, an attenuated VZV vaccine has been developed from a Korean isolate and has been commercially available since 1994. Despite this long history of use, the mechanism for the attenuation of the vaccine strain is still elusive. We attempted to understand the molecular basis of attenuation mechanism by full genome sequencing and comparative genomic analyses of the Korean vaccine strain SuduVax.</p> <p>Results</p> <p>SuduVax was found to contain a genome that was 124,759 bp and possessed 74 open reading frames (ORFs). SuduVax was genetically most close to Oka strains and these Korean-Japanese strains formed a strong clade in phylogenetic trees. SuduVax, similar to the Oka vaccine strains, underwent T- > C substitution at the stop codon of ORF0, resulting in a read-through mutation to code for an extended form of ORF0 protein. SuduVax also shared certain deletion and insertion mutations in ORFs 17, 29, 56 and 60 with Oka vaccine strains and some clinical strains.</p> <p>Conclusions</p> <p>The Korean VZV vaccine strain SuduVax is genetically similar to the Oka vaccine strains. Further comparative genomic and bioinformatics analyses will help to elucidate the molecular basis of the attenuation of the VZV vaccine strains.</p

The Observation of Electrical Hysteric Behavior in Synthesized V 2

The anomalous electrical conductance for the V2O5 foam synthesized via a foaming process was measured. In the annealing process, the synthesized V2O5 foam is recrystallized with the increase of annealing temperature. The recrystallization procedure was characterized by using physical analysis tools such as thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), and X-ray diffractometer. In the electrical analysis technique of current-voltage characteristics as a function of annealing temperature, an anomalous hysteric behavior appears at the annealing temperature of 400°C. We conclude that the recrystallization of V2O5 nanoplates results in the anomalous behavior in voltage-dependent current characteristics

Comparison of single-incision mini-slings (Ajust) and standard transobturator midurethral slings (Align) in the management of female stress urinary incontinence: A 1-year follow-up

AbstractObjectiveTo investigate the effectiveness and safety of a new single-incision mini-sling (SIMS)—Ajust—compared with the standard transobturator midurethral sling (SMUS)—Align—for the treatment of female stress urinary incontinence (SUI).Materials and MethodsA retrospective cohort study was conducted between January 1, 2010 and August 31, 2012. Women with SUI who underwent either SMUS-Align or SIMS-Ajust were recruited. The primary outcomes included operation time, estimated operative blood loss, postoperative pain, and complications. The secondary outcomes included subjective and objective success, defined as an International Consultation on Incontinence Questionnaire (ICIQ) score of 0 or improvement as felt by the patient and a long-term complication, such as dyspareunia and mesh erosion after 6 months and 12 months of follow-up.ResultsA total of 136 patients were enrolled, including 76 receiving SMUS-Align and 60 receiving SIMS-Ajust. Baseline characteristics of the patients in both groups were similar, without a statistically significant difference. Primary outcomes between both groups were similar, except that women treated with SIMS-Ajust had statistically significantly shorter operation time (p = 0.003), less intent to treat (p < 0.05), and earlier postoperative discharge (p = 0.001) than women treated with SMUS-Align. Secondary outcomes were similar without a significant difference between the two groups (93% vs. 88% success rate in each group).ConclusionOur results showed that SIMS-Ajust was not inferior to SMUS-Align with respect to success rate, and might have a slight advantage in early discharge. A long-term follow-up or prospective study is needed to confirm the above findings

Mycobacterium tuberculosis Eis Regulates Autophagy, Inflammation, and Cell Death through Redox-dependent Signaling

The “enhanced intracellular survival” (eis) gene of Mycobacterium tuberculosis (Mtb) is involved in the intracellular survival of M. smegmatis. However, its exact effects on host cell function remain elusive. We herein report that Mtb Eis plays essential roles in modulating macrophage autophagy, inflammatory responses, and cell death via a reactive oxygen species (ROS)-dependent pathway. Macrophages infected with an Mtb eis-deletion mutant H37Rv (Mtb-Δeis) displayed markedly increased accumulation of massive autophagic vacuoles and formation of autophagosomes in vitro and in vivo. Infection of macrophages with Mtb-Δeis increased the production of tumor necrosis factor-α and interleukin-6 over the levels produced by infection with wild-type or complemented strains. Elevated ROS generation in macrophages infected with Mtb-Δeis (for which NADPH oxidase and mitochondria were largely responsible) rendered the cells highly sensitive to autophagy activation and cytokine production. Despite considerable activation of autophagy and proinflammatory responses, macrophages infected with Mtb-Δeis underwent caspase-independent cell death. This cell death was significantly inhibited by blockade of autophagy and c-Jun N-terminal kinase-ROS signaling, suggesting that excessive autophagy and oxidative stress are detrimental to cell survival. Finally, artificial over-expression of Eis or pretreatment with recombinant Eis abrogated production of both ROS and proinflammatory cytokines, which depends on the N-acetyltransferase domain of the Eis protein. Collectively, these data indicate that Mtb Eis suppresses host innate immune defenses by modulating autophagy, inflammation, and cell death in a redox-dependent manner

CMS physics technical design report : Addendum on high density QCD with heavy ions

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