Genome Wide Association Study of Age at Menarche in the Japanese Population

Age at menarche (AAM) is a complex trait involving both genetic and environmental factors. To identify the genetic factors associated with AAM, we conducted a large-scale meta-analysis of genome-wide association studies using more than 15,000 Japanese female samples. Here, we identified an association between SNP (single nucleotide polymorphism) rs364663 at the LIN28B locus and AAM, with a P-value of 5.49×10−7 and an effect size of 0.089 (year). We also evaluated 33 SNPs that were previously reported to be associated with AAM in women of European ancestry. Among them, two SNPs rs4452860 and rs7028916 in TMEM38B indicated significant association with AAM in the same directions as reported in previous studies (P = 0.0013 with an effect size of 0.051) even after Bonferroni correction for the 33 SNPs. In addition, six loci in or near CCDC85A, LOC100421670, CA10, ZNF483, ARNTL, and RXRG exhibited suggestive association with AAM (P<0.05). Our findings elucidated the impact of genetic variations on AAM in the Japanese population

The Combination of D-dimer and Glasgow Prognostic Score Can Be Useful in Predicting VTE in Patients with Stage IIIC and IVA Ovarian Cancer

Cancer patients have increased risk of venous thromboembolism (VTE) that must be assessed before treatment. This study aimed to determine effective VTE biomarkers in gynecologic cancer (GC). We investigated the correlation between D-dimer levels, Khorana risk score (KRS), Glasgow prognostic score (GPS), and VTE in 1499 GC patients (583 cervical cancer (CC), 621 endometrial cancer (EC), and 295 ovarian cancer (OC) patients) treated at our institution between January 2008 and December 2019. χ2 and Mann–Whitney U-tests were used to determine statistical significance. We used receiver operating characteristic-curve analysis to evaluate the discriminatory ability of each parameter. D-dimer levels were significantly correlated with KRS and GPS in patients with GC. VTE was diagnosed in 11 CC (1.9%), 27 EC (4.3%), and 39 OC patients (13.2%). Optimal D-dimer cut-off values for VTE were 3.1, 3.2, and 3.9 μg/ml in CC, EC and OC patients, respectively. D-dimer could significantly predict VTE in all GC patients. Furthermore, D-dimer combined with GPS was more accurate in predicting VTE than other VTE biomarkers in stage IIIC and IVA OC (AUC: 0.846; p<0.001). This study demonstrates that combined D-dimer and GPS are useful in predicting VTE in patients with OC

Genome Wide Association Study of Age at Menarche in the Japanese Population

Age at menarche (AAM) is a complex trait involving both genetic and environmental factors. To identify the genetic factors associated with AAM, we conducted a large-scale meta-analysis of genome-wide association studies using more than 15,000 Japanese female samples. Here, we identified an association between SNP (single nucleotide polymorphism) rs364663 at the LIN28B locus and AAM, with a P-value of 5.49×10−7 and an effect size of 0.089 (year). We also evaluated 33 SNPs that were previously reported to be associated with AAM in women of European ancestry. Among them, two SNPs rs4452860 and rs7028916 in TMEM38B indicated significant association with AAM in the same directions as reported in previous studies (P = 0.0013 with an effect size of 0.051) even after Bonferroni correction for the 33 SNPs. In addition, six loci in or near CCDC85A, LOC100421670, CA10, ZNF483, ARNTL, and RXRG exhibited suggestive association with AAM (P<0.05). Our findings elucidated the impact of genetic variations on AAM in the Japanese population.</p

Not taking sick leave for gynecologic cancer treatment is negatively associated with returning to the same workplace

Background: Gynecologic cancers are one of the most common types of malignancies in working-age women. We aimed to determine the factors that impede women from returning to the same workplace after treatment for such cancers. Methods: A questionnaire-based survey was conducted on 194 women who underwent treatment for gynecologic cancer at the Okayama University (≥1 year after cancer treatment and Results: The median age at diagnosis was 49.0 years, and the median time from cancer treatment to questionnaire completion was 3.8 years. Not returning to the same workplace was positively associated with not being regularly employed (P = 0.018), short work time per day (P = 0.023), low personal income (P = 0.004), not taking sick leave (P Conclusions: Not taking sick leave likely was negatively associated with returning to the same workplace after the treatment for gynecologic cancer. Therefore, we suggest that steps be taken to formally introduce a sick leave system over and above the paid leave system in Japan

High Efficacy of Preoperative Low-Dose Radiotherapy with Sanazole (AK-2123) for Extraskeletal Ewing's Sarcoma: A Case Report

Extraskeletal Ewing's sarcoma is a rare soft tissue tumor that is morphologically indistinguishable from Ewing's sarcoma of bone. We report a case of extraskeletal Ewing's sarcoma with several systemic problems. A 69-year-old man presented with a 5-month history of a rapidly enlarging mass in the right thigh. Because preoperative radiotherapy with sanazole (AK-2123) contributed the tumor mass reduction down to 40% in size, the tumor was successfully resected with clear surgical margins and repaired with a musculocutaneous flap. The high efficacy of pre-operative low-dose radiotherapy with sanazole was histologically confirmed that the resected tumor specimen involved no viable tumor cells and showed 100% necrosis. Based on clinical outcomes in this case, the combined modality of pre-operative low-dose radiotherapy with hypoxic cell radiosensitizer and adequate surgical resection might provide for the useful clinical application of extraskeletal Ewing's sarcoma treatment

Effective Potential of Higgs Field in Warped Gauge-Higgs Unification

The gauge-Higgs unification is one of influential scenarios to solve the hierarchy problem in the Standard Model. Recently, the scenario on the warped background attracts many attentions due to a large possibility to construct a realistic model naturally in this framework. It is, however, well known that the effective potential for the Higgs field, which is the most important prediction of the scenario, is not easy to calculate on the warped background, because masses of Kaluza-Klein particles are not obtained analytically. In this article, we derive useful formulae for the effective potential. The formulae allow us to calculate the Higgs mass easily, thus to construct a realistic model in the gauge-Higgs unification scenario on the warped background. Using obtained formulae, we calculate contributions from bulk fermions with several boundary conditions. We also show bulk fermions, which have boundary conditions not allowed in the orbifold picture, do not contribute to the effective potential.Comment: 28 pages, 6 figure

Quantum transport theory of anomalous electric, thermoelectric, and thermal Hall effects in ferromagnets

The mechanism of the anomalous Hall transport phenomena, if it is of the intrinsic or extrinsic origin, has been controversial. We present a unified theory of them for ferromagnetic metals with dilute impurities at the zero temperature, in terms of a quantum transport theory with the self-consistent T-matrix approximation. With the Fermi energy E_F and the spin-orbit interaction energy E_{SO} being fixed (E_F > E_{SO}), three regimes are found as a function of the scattering rate \hbar/\tau. (i) In the superclean case \hbar/\tau < u_{imp} E_{SO}D, the skew scattering from the vertex correction dominates the anomalous Hall conductivity \sigma_{xy}, where u_{imp} is the impurity potential strength and D is the density of states. With increasing \hbar/\tau, this extrinsic skew-scattering contribution rapidly decays. (ii) In the moderately dirty regime u_{imp}E_{SO}D < \hbar/\tau < E_{SO}, \sigma_{xy} is dominated by the intrinsic dissipationless Berry-phase contribution, which is resonantly enhanced to the order of e^2/\hbar when an accidental degeneracy of band dispersions around the Fermi level is lifted by the spin-orbit interaction. (iii) Further increasing \hbar/\tau, a \sigma_{xy}\propto\sigma_{xx}^{1.6} scaling appears, which has been verified by recent experiments. The themal and thermoelectric Hall conductivities are also discussed.Comment: 21 pages, including 12 figures; minor modifications; to appear in Physical Review

Frequent p53 Accumulation in the Chronically Sun-Exposed Epidermis and Clonal Expansion of p53 Mutant Cells in the Epidermis Adjacent to Basal Cell Carcinoma

p53 expression was studied immunohistochemically to identify a precursor lesion of basal cell carcinoma (BCC) in the epidermis adjacent to BCC. With two different anti-p53 antibodies of CM1 and DO7, p53 expression was frequently detected in the epidermis adjacent to BCCs arising on the face and in the normal epidermis with usual sun exposure. In the epidermis adjacent to BCC, stained cells were occasionally clustered in a small area, but no cluster was found in the normal epidermis with usual sun exposure. The expression was less frequent in the normal epidermis with rare sun exposure. Ten cases of normal skin with usual sun exposure, showing CM1 staining in the epidermis, were screened for p53 gene mutations with polymerase chain reaction-single- strand conformation polymorphism analysis using DNAs obtained from the epidermis. No mutation was detected in exons 2 to 10 of the p53 gene in these 10 cases. The epidermis flanking three BCCs that was stained with CM1, on the other hand, carried a missense mutation of C to G transversIon at a dipyrimidine site of codon 249. This alteration replaced arginine with threonine. The mutation of codon 249 was not detected in the three BCCs. Our results first suggest that ultraviolet light irradiating the skin in a daily life induces p53 accumulation in the epidermis and secondly that the frequent clonal expansion of p53 mutant cells occurs in the epidermis adjacent to BCCs. This clonal expansion of mutant p53 may provide a molecular basis for high risk of developing subsequent new skin cancers in patients with BCC

Partial Gauge Symmetry Breaking via Bare Mass

We study gauge symmetry breaking patterns in supersymmetric gauge models defined on $M^4\times S^1$. Instead of utilizing the Scherk-Schwarz mechanism, supersymmetry is broken by bare mass terms for gaugino and squarks. Though the matter content is the same, depending on the magnitude of the bare mass, the gauge symmetry breaking patterns are different. We present two examples, in one of which the partial gauge symmetry breaking $SU(3)\to SU(2)\times U(1)$ is realized.Comment: 11 pages, 2 figures, version to appear in Phys. Lett.