T-Duality Transformation and Universal Structure of Non-Critical String Field Theory

We discuss a T-duality transformation for the c=1/2 matrix model for the purpose of studying duality transformations in a possible toy example of nonperturbative frameworks of string theory. Our approach is to first investigate the scaling limit of the Schwinger-Dyson equations and the stochastic Hamiltonian in terms of the dual variables and then compare the results with those using the original spin variables. It is shown that the c=1/2 model in the scaling limit is T-duality symmetric in the sphere approximation. The duality symmetry is however violated when the higher-genus effects are taken into account, owing to the existence of global Z_2 vector fields corresponding to nontrivial homology cycles. Some universal properties of the stochastic Hamiltonians which play an important role in discussing the scaling limit and have been discussed in a previous work by the last two authors are refined in both the original and dual formulations. We also report a number of new explicit results for various amplitudes containing macroscopic loop operators.Comment: RevTex, 46 pages, 5 eps figure

Morphological evidence for an invasion-independent metastasis pathway exists in multiple human cancers

BACKGROUND: We have previously described an alternative invasion-independent pathway of cancer metastasis in a murine mammary tumor model. This pathway is initiated by intravasation of tumor nests enveloped by endothelial cells of sinusoidal vasculature within the tumor. In this study, we examined whether evidence for the invasion-independent pathway of metastasis is present in human cancers. METHODS: Archival specimens of 10 common types of human cancers were examined for the presence of sinusoidal vasculature enveloping tumor nests and subsequently generated endothelial-covered tumor emboli in efferent veins. RESULTS: A percentage of tumor emboli in all cancers was found to be enveloped by endothelial cells, but these structures were particularly prevalent in renal cell carcinomas, hepatocellular carcinomas and follicular thyroid carcinomas. A common feature of the vasculature in these tumors was the presence of dilated sinusoid-like structures surrounding tumor nests. A high mean vascular area within tumors, an indication of sinusoidal vascular development, was significantly related to the presence of endothelial-covered tumor emboli. CONCLUSIONS: These results suggest that an invasion-independent metastatic pathway is possible in a wide variety of human cancers. Further investigation of this phenomenon may present new therapeutic strategies for the amelioration of cancer metastasis

Pediatric differentiated thyroid carcinoma in stage I: risk factor analysis for disease free survival

<p>Abstract</p> <p>Background</p> <p>To examine the outcomes and risk factors in pediatric differentiated thyroid carcinoma (DTC) patients who were defined as TNM stage I because some patients develop disease recurrence but treatment strategy for such stage I pediatric patients is still controversial.</p> <p>Methods</p> <p>We reviewed 57 consecutive TNM stage I patients (15 years or less) with DTC (46 papillary and 11 follicular) who underwent initial treatment at Ito Hospital between 1962 and 2004 (7 males and 50 females; mean age: 13.1 years; mean follow-up: 17.4 years). Clinicopathological results were evaluated in all patients. Multivariate analysis was performed to reveal the risk factors for disease-free survival (DFS) in these 57 patients.</p> <p>Results</p> <p>Extrathyroid extension and clinical lymphadenopathy at diagnosis were found in 7 and 12 patients, respectively. Subtotal/total thyroidectomy was performed in 23 patients, modified neck dissection in 38, and radioactive iodine therapy in 10. Pathological node metastasis was confirmed in 37 patients (64.9%). Fifteen patients (26.3%) exhibited local recurrence and 3 of them also developed metachronous lung metastasis. Ten of these 15 achieved disease-free after further treatments and no patients died of disease. In multivariate analysis, male gender (p = 0.017), advanced tumor (T3, 4a) stage (p = 0.029), and clinical lymphadenopathy (p = 0.006) were risk factors for DFS in stage I pediatric patients.</p> <p>Conclusion</p> <p>Male gender, tumor stage, and lymphadenopathy are risk factors for DFS in stage I pediatric DTC patients. Aggressive treatment (total thyroidectomy, node dissection, and RI therapy) is considered appropriate for patients with risk factors, whereas conservative or stepwise approach may be acceptable for other patients.</p

Rapid Accumulation of Polymorphonuclear Neutrophils in the Corpus luteum during Prostaglandin F2α-Induced Luteolysis in the Cow

Prostaglandin F2α (PGF2α) induces luteolysis within a few days in cows, and immune cells increase in number in the regressing corpus luteum (CL), implying that luteolysis is an inflammatory-like immune response. We investigated the rapid change in polymorphonuclear neutrophil (PMN) numbers in response to PGF2α administration as the first cells recruited to inflammatory sites, together with mRNA of interleukin-8 (IL-8: neutrophil chemoattractant) and P-selectin (leukocyte adhesion molecule) in the bovine CL. CLs were collected by ovariectomy at various times after PGF2α injection. The number of PMNs was increased at 5 min after PGF2α administration, whereas IL-8 and P-selectin mRNA increased at 30 min and 2 h, respectively. PGF2α directly stimulated P-selectin protein expression at 5–30 min in luteal endothelial cells (LECs). Moreover, PGF2α enhanced PMN adhesion to LECs, and this enhancement by PGF2α was inhibited by anti-P-selectin antibody, suggesting that P-selectin expression by PGF2α is crucial in PMN migration. In conclusion, PGF2α rapidly induces the accumulation of PMNs into the bovine CL at 5 min and enhances PMN adhesion via P-selectin expression in LECs. It is suggested that luteolytic cascade by PGF2α may involve an acute inflammatory-like response due to rapidly infiltrated PMNs

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Complex Component of Oncocytic and Non-Oncocytic Lipoadenomas in the Parotid Gland: A Case Report

Oncocytic lipoadenoma of the salivary gland is a rare tumor that develops mainly in the parotid gland. We report a case of oncocytic lipoadenoma of the parotid gland in a 70-year-old woman. The tumor measured 30 × 20 mm and had a well-circumscribed tan-brown surface. The tumor was histologically composed of oncocytic and lipomatous lesions without atypia. In addition to the oncocytic lipoadenoma, a small lipomatous tumor, measuring 10 × 7 mm, was found in the resected parotid gland. Macroscopically, this tumor was yellow and indistinguishable from the parotid gland. Microscopically, the tumor was rich in fats and contained an area of conglomerated duct-like proliferation and salivary gland components. Therefore, the tumor was diagnosed as a non-oncocytic lipoadenoma with a sialoadenoma component. We report the first case of double component oncocytic and non-oncocytic lipoadenomas of the salivary gland

In Silico Identification of Genes Associated with Breast Cancer Progression and Prognosis and Novel Therapeutic Targets

Molecular mechanisms underlying breast cancer (BC) progression are complex and remain unclear. In this study, we used bioinformatic tools to identify genes associated with tumor progression mechanisms and novel therapeutic targets in BC. We identified genes with stepwise upregulated expression overlapping between the T and N stages during BC progression using LinkedOmics. We compared the expression level of each gene in BC tissues with that in normal breast tissues and evaluated differences in expression in their intrinsic subtypes and their prognostic value using UALCAN and GEPIA2. We also investigated the dependency of BC cell lines on these genes and whether they are potential therapeutic targets using DepMap. SPDEF, TRIM3, ABCB9, HSPB1, RHBG, SPINT1, EPN3, LRFN2, and PRPH were found to be involved in BC progression. High expression of ABCB9 and SPINT1 was associated with a poor prognosis. SPDEF, TRIM3, ABCB9, RHBG, SPINT1, and PRPH were found to be essential for survival in some BC cell lines (gene effect score PRPH was newly discovered to be involved in the progression of BC and the growth and survival of BC cell lines. Hence, SPDEF, TRIM3, ABCB9, RHBG, SPINT1, and PRPH may serve as novel potential therapeutic targets in BC

<i>ERBB2</i>-Mutant Gastrointestinal Tumors Represent Heterogeneous Molecular Biology, Particularly in Microsatellite Instability, Tumor Mutation Burden, and Co-Mutated Genes: An In Silico Study

During recent years, activating mutations in ERBB2 have been reported in solid tumors of various organs, and clinical trials targeting ERBB2-mutant tumors have been conducted. However, no effective treatment has been established for gastrointestinal tumors targeting ERBB2 mutations. ERBB2-mutant tumors have a higher tumor mutation burden (TMB) and microsatellite instability (MSI) than ERBB2 non-mutant tumors, but not all ERBB2-mutant tumors are TMB- and MSI-high. Thus, a more detailed classification of ERBB2-mutant tumors based on the underlying molecular mechanisms is required. Herein, we classified ERBB2 mutations into three groups—group 1: both ERBB2 mutations and amplifications; group 2: ERBB2 mutations annotated as putative driver mutations but without amplifications; group 3: ERBB2 mutations annotated as non-driver mutations (passenger mutations or unknown significance) and those that were not amplified in gastrointestinal tumors. Esophageal adenocarcinoma, gastric cancer, and colorectal cancer presented significantly higher MSI and TMB in the ERBB2-mutant group than in the ERBB2-wild-type group. The proportions of TMB- and MSI-high tumors and frequency of co-mutated downstream genes differed among the groups. We identified TMB- and MSI-high groups; this classification is considered important for guiding the selection of drugs for ERBB2-mutant tumors with downstream genetic mutations