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The article reports of sudden increase in the number of measles patients in Japan because of an exposure to H1 genotype measles virus and presents the detailed investigation done by the Surveillance officers and Field Epidemiology Training Program people.

New mixed-valence trinuclear iron pentafluorobenzoate complexes were synthesized. Their valencedetrapping and/or valence-trapping phenomena were studied by 57Fe Mössbauer spectroscopy and X-ray crystallography. For [Fe3O(C6F5CO2)6(py)3].CH2Cl2 (1), a valence-trapped state was observed at low temperatures, while the valence-detrapped state was observed at room temperature. Removal of CH2Cl2 from 1 gives the de-solvated [Fe3O(C6F5CO2)6(py)3] (2) where the valence was trapped at room temperature. The CH2Cl2-free 2 can reversibly absorb and desorb CH3CN; the process was followed by 57Fe Mössbauer spectroscopy by monitoring valence-trapping and valence-detrapping phenomena. Organic molecules such as benzene, toluene, ethylbenzene, cumene, and xylene are also trapped by 2 and affect the iron valence states. However, small molecules such as H2O and CO2 do not affect the valencetrapped state of 2. Three xylene isomers trapped within the nano-void of 2 were distinguished by 57Fe Mössbauer spectroscopy at room temperature. [ABSTRACT FROM AUTHOR]

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease that is characterized by gastrointestinal hamartomatous polyposis and mucocutaneous melanin spots. The tumor suppressor gene, STK11/LKB1, which is located on chromosome 19p13.3, has been reported to be responsible for this condition. PJS is complicated by benign and malignant tumors of various organs and complications from rare diseases, including sex cord tumor with annular tubules (SCTAT) and minimal deviation adenocarcinoma (MDA), which have also recently attracted attention in the field of gynecology. Among the total MDA cases, 10% are complications of PJS, and mutations in the STK11 gene are closely associated with the development and prognosis of MDA. Furthermore, a new type of uterine cervical tumor, lobular endocervical glandular hyperplasia (LEGH), has been identified and has been predicted to be a precancerous lesion of MDA. The first case of LEGH induced by a germline STK11 mutation has also been described. A high risk of endometrial cancer in PJS has also been reported. These developments suggest that PJS is an important syndrome of hereditary gynecological tumors that requires further study. [ABSTRACT FROM AUTHOR]

Endometrial cancer is a common gynecological malignant tumor in Western countries and its incidence has also been on the increase in Asia. Genetic abnormalities related to onset and progression of malignancy in the endometrial membrane and signaling system have been identified and the developmental mechanism of endometrial cancer is becoming elucidated. The identification of the molecules related to these abnormalities has led to new potential treatment regimens for endometrial cancer, using molecular-targeted drugs. The current chemotherapy for endometrial cancer often causes systemic side effects that require discontinuation of the treatment. Furthermore, a treatment regimen for cancers of rare histological types has not been established. Recent studies on endometrial cancer revealed patterns of genetic disorders that differ among the histological types. Genetic and molecular information that underlie pathological changes and is associated with DNA mismatch repair genes and epigenetic regulation was also identified. Targeting of these mechanisms with molecular-targeted drugs has been performed with the aim of linking treatment to the carcinogenic mechanism at the molecular and genetic levels. However, the response rates with single-agent therapy are generally low and several problems remain unresolved. Trials of combinations of molecular-targeted drugs with currently available treatments and identification of factors determining sensitivity are required to overcome these difficulties. [ABSTRACT FROM AUTHOR]

In a weighted independence system, an independent set is said to be α-robust if, for all p, the total weight of its heaviest p elements is at least α times the maximum weight of a p-independent set. Here a p-independent set is an independent set with at most p elements. The set of matchings in a weighted graph is a typical example of a weighted independence system, and Hassin and Rubinstein [SIAM J. Discrete Math., 15 (2002), pp. 530-537] showed that every graph has a 1/√2-robust matching and it can be found by a kth power algorithm in polynomial time. In this paper, we show that it can be extended to the matroid intersection problem; i.e., there always exists a 1/√2-robust matroid intersection, which is polynomially computable. We also study the time complexity of the robust matching problem. We show that a 1-robust matching can be computed in polynomial time (if one exists), and, for any fixed number α with 1/√2 < α < 1, the problem to determine whether a given weighted graph has an a-robust matching is NP-complete. These together with the positive result for α = 1/√2 in [R. Hassin and S. Rubinstein, SIAM J. Discrete Math., 15 (2002), pp. 530-537] give us a sharp border for the complexity for the robust matching problem. Moreover, we show that the problem is strongly NP-complete when a is α part of the input. Finally, we show the limitations of the kth power algorithm for robust matchings; i.e., for any ε > 0, there exists a weighted graph such that no kth power algorithm outputs a (1/√2 + ε)-approximation for computing the most robust matching. [ABSTRACT FROM AUTHOR]

Endometrial cancer is the seventh most common cancer in women worldwide. Therefore elucidation of the pathogenesis and development of effective treatment for endometrial cancer are important. However, several aspects of the mechanism of carcinogenesis in the endometrium remain unclear. Associations with genetic variation and mutations of cancer-related genes have been shown, but these do not provide a complete explanation. Therefore, in recent years, epigenetic mechanisms that do not involve changes in DNA sequences have been examined. Studies aimed at detection of aberrant DNA hypermethylation in cancer cells present in microscopic amounts in vivo and application of the results to cancer diagnosis have also started. Breakdown of the DNA mismatch repair mechanism is thought to play a large role in the development of endometrial cancer, with changes in the expression of the hMLH1 gene being particularly important. Silencing of genes such as APC and CHFR, Sprouty 2, RASSF1A, GPR54, CDH1, and RSK4 by DNA hypermethylation, onset of Lynch syndrome due to hereditary epimutation of hMLH1 and hMSH2 mismatch repair genes, and regulation of gene expression by microRNAs may also underlie the carcinogenic mechanisms of endometrial cancer. Further understanding of these issues may permit development of new therapies. [ABSTRACT FROM AUTHOR]

An efficient method for constructing quinoxalinone-N-oxides from cyanoacetanilides has been developed. This transformation can be achieved using inexpensive reagents and molecular oxygen under mild conditions, thus offering a practical pathway to quinoxalinone-containing pharmaceuticals such as ataquimast and opaviraline. [ABSTRACT FROM AUTHOR]

Abstract  Given a 2k-edge-connected undirected graph, we consider to find a minimum cost orientation that yields a k-arc-connected directed graph. This minimum cost k-arc-connected orientation problem is a special case of the submodular flow problem. Frank (1982) devised a combinatorial algorithm that solves the problem in O(k 2 n 3 m) time, where n and m are the numbers of vertices and edges, respectively. Gabow (1995) improved Frank’s algorithm to run in O(kn 2 m) time by introducing a new sophisticated data structure. We describe an algorithm that runs in O(k 3 n 3+kn 2 m) time without using sophisticated data structures. In addition, we present an application of the algorithm to find a shortest dijoin in O(n 2 m) time, which matches the current best bound. [ABSTRACT FROM AUTHOR]

The laser-induced fluorescence spectrum of jet-cooled l-tyrosine exhibits more than 20 vibronic bands in the 35450−35750 cm-1region. We attribute these bands to eight conformers by using results of UV−UV hole-burning spectroscopy. These isomers are classified into four groups; each group consists of two rotational isomers that have a similar side-chain conformation but different orientations of the phenolic OH. The splitting of band origins of rotational isomers is 31, 21, 5, and 0 cm-1for these groups. IR−UV spectra suggest that conformers belonging to two of the four groups have an intramolecular OH···N hydrogen bond between the COOH and NH2groups. By comparing experimental and theoretical results of l-tyrosine with those of l-phenylalanine, we propose probable conformers of l-tyrosine. [ABSTRACT FROM AUTHOR]

To determine the characteristics of pediatric patients 0-19 years of age who died after onset of SARS-CoV-2 infection in Japan during January 1-September 30, 2022, we reviewed multiple sources. We identified 62 cases, collected detailed information from medical records and death certificates, and conducted interviews, resulting in 53 patients with detailed information for our study. Among 46 patients with internal causes of death (i.e., not external causes such as trauma), 15% were <1 year of age, 59% had no underlying disease, and 88% eligible for vaccination were unvaccinated. Nonrespiratory symptoms were more common than respiratory symptoms. Out-of-hospital cardiac arrest affected 46% of patients, and time from symptom onset to death was <7 days for 77%. Main suspected causes of death were central nervous system abnormalities (35%) and cardiac abnormalities (20%). We recommend careful follow-up of pediatric patients after SARS-CoV-2 infection during the first week after symptom onset, regardless of underlying diseases. [ABSTRACT FROM AUTHOR]

The article discusses the role of medical students from the University of Hawai'i John A. Burns School of Medicine in tuberculosis control in Micronesia.

We proposed an Schottky barrier diode wall integrated trench MOSFET (SWITCH-MOS) for the purposes of shrinking the cell pitch and suppressing the forward degradation of the body diode. A trench Schottky barrier diode (SBD) was integrated into a trench gate MOSFET with a wide shielding p+ region that protected the trench bottoms of both the SBD and the MOS gate from high electrical fields in the off state. The SBD was placed on the trench sidewall of the plane (m-face). Static and transient simulations revealed that SWITCH-MOS sufficiently suppressed the bipolar current that induced forward degradation, and we determined that the optimum Schottky barrier height (SBH) was from 0.8 to 2.0 eV. The SBH depends on the crystal planes in 4H-SiC, but the SBH of the m-face was unclear. We fabricated a planar m-face SBD for the first time, and we obtained SBHs from 1.4 to 1.8 eV experimentally with titanium or nickel as a Schottky metal. [ABSTRACT FROM AUTHOR]

To suppress the electric field in the gate oxide in a trench gate MOSFET (UMOSFET) with small cell pitch, we developed a technique to form the p+ region using self-aligned ion implantation under the gate trench. To prevent Al+ injection into the trench sidewalls, conditions of thin oxide layer deposition and Al+ implantation were optimized by process simulation. The resulting SiC trench MOS capacitors exhibited long-term reliability, with no degradation in lifetime by the p+ shielding region, and a specific on-resistance of 9.4 mΩ cm2 with a blocking voltage of 3800 V was achieved in the UMOSFET. [ABSTRACT FROM AUTHOR]

Cigarette smoking is a major risk factor for atherosclerosis. We previously reported that DNA damage was accumulated in atherosclerotic plaque, and was increased in human mononuclear cells by smoking. As vascular endothelial cells are known to modulate inflammation, we investigated the mechanism by which smoking activates innate immunity in endothelial cells focusing on DNA damage. Furthermore, we sought to characterize the plasma level of cell-free DNA (cfDNA), a result of mitochondrial and/or genomic DNA damage, as a biomarker for atherosclerosis. Cigarette smoke extract (CSE) increased DNA damage in the nucleus and mitochondria in human endothelial cells. Mitochondrial damage induced minority mitochondrial outer membrane permeabilization, which was insufficient for cell death but instead led to nuclear DNA damage. DNA fragments, derived from the nucleus and mitochondria, were accumulated in the cytosol, and caused a persistent increase in IL-6 mRNA expression via the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. cfDNA, quantified with quantitative PCR in culture medium was increased by CSE. Consistent with in vitro results, plasma mitochondrial cfDNA (mt-cfDNA) and nuclear cfDNA (n-cfDNA) were increased in young healthy smokers compared with age-matched nonsmokers. Additionally, both mt-cfDNA and n-cfDNA were significantly increased in patients with atherosclerosis compared with the normal controls. Our multivariate analysis revealed that only mt-cfDNA predicted the risk of atherosclerosis. In conclusion, accumulated cytosolic DNA caused by cigarette smoke and the resultant activation of the cGAS-STING pathway may be a mechanism of atherosclerosis development. The plasma level of mt-cfDNA, possibly as a result of DNA damage, may be a useful biomarker for atherosclerosis. [ABSTRACT FROM AUTHOR]

Background. The presence of silent brain infarction (SBI) increases the risk of symptomatic stroke and dementia. The association between SBI and chronic kidney disease (CKD) has not been clarified. Moreover, little is known about what factors are related to SBI in CKD patients and whether the prevalence of SBI differs in CKD stage or cause of CKD. Methods. This is a cross-sectional study. A total of 375 subjects—335 with CKD and 40 with essential hypertension—were included. All subjects underwent magnetic resonance imaging (MRI) of the brain to detect SBI. Glomerular filtration rate (GFR) was estimated using Modification of Diet in Renal Disease equation, and cardiovascular risk factors were examined. Results. The prevalence of SBI was 56.5% in all subjects. Among causes of CKD, hypertensive nephrosclerosis had a strong association with SBI. According to the estimated GFR (eGFR) stage, the more severe the stage of eGFR, the higher the prevalence of SBI (age-adjusted odds ratio [95% confidence interval] for eGFR 30–59, 15–29 and P = 0.025). However, other traditional and non-traditional risk factors were not. Conclusion. There was an independent association between eGFR and SBI. CKD patients should receive active detection of SBI and more intensive preventive management, especially for hypertension, should be needed in CKD patients to prevent SBI. [ABSTRACT FROM AUTHOR]

Objective: Human papillomavirus subtypes are predictive indicators of cervical intraepithelial neoplasia (CIN) progression. While colposcopy is also an essential part of cervical cancer prevention, its accuracy and reproducibility are limited because of subjective evaluation. This study aimed to develop an artificial intelligence (AI) algorithm that can accurately detect the optimal lesion associated with prognosis using colposcopic images of CIN2 patients by utilizing objective AI diagnosis. Methods: We identified colposcopic findings associated with the prognosis of patients with CIN2. We developed a convolutional neural network that can automatically detect the rate of high-grade lesions in the uterovaginal area in 12 segments. We finally evaluated the detection accuracy of our AI algorithm compared with the scores by multiple gynecologic oncologists. Results: High-grade lesion occupancy in the uterovaginal area detected by senior colposcopists was significantly correlated with the prognosis of patients with CIN2. The detection rate for high-grade lesions in 12 segments of the uterovaginal area by the AI system was 62.1% for recall, and the overall correct response rate was 89.7%. Moreover, the percentage of high-grade lesions detected by the AI system was significantly correlated with the rate detected by multiple gynecologic senior oncologists (r=0.61). Conclusion: Our novel AI algorithm can accurately determine high-grade lesions associated with prognosis on colposcopic images, and these results provide an insight into the additional utility of colposcopy for the management of patients with CIN2. [ABSTRACT FROM AUTHOR]

Objective: Precursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer. Methods: We analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease. Results: TP53pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer. Conclusion: The sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Endometriosis is defined as the growth of ectopic endometrial tissue beyond the uterine cavity, and endometriosis on the uterine cervix is a rare variant. Although asymptomatic patients with cervical endometriosis or those with minor symptoms are treated conservatively, there are reports of life-threatening hemorrhage due to cervical endometriosis. Here, we report 2 cases of massive genital bleeding caused by cervical endometriotic cysts and we performed a literature review. Case Reports: Case 1: A 32-year-old woman presented to our hospital due to massive genital bleeding on her 11th day of menstruation. An arterial hemorrhage in a cervical endometriotic cyst was suspected. As pressure hemostasis proved difficult, urgent uterine artery embolization (UAE) by interventional radiology was performed. Angiography during the UAE showed extravascular leakage from the branch of the left uterine artery. After embolization, hemostasis was achieved. No further genital bleeding was observed, and transvaginal ultrasound showed the cyst has continued to shrink for 9 months after the UAE with sequential dienogest, a progesterone receptor agonist, treatment. Case 2: A 43-year-old woman presented to our hospital with increasing massive genital bleeding after completing a 12-day course of 0.5 mg of norgestrel and 0.05 mg of ethinyl estradiol as a treatment for irregular intermenstrual bleeding. We suspected cervical endometriotic cyst rupture on imaging and performed an urgent laparoscopic total hysterectomy. In the excised uterine specimen, a cystic lesion that contained old, blood-like fluid was macroscopically observed in the cervix and was diagnosed pathologically as endometriosis. Conclusions: Cervical endometriotic cyst rupture is rare; however, it should be kept in mind as a differential diagnosis when treating massive genital bleeding because urgent intervention is sometimes required to control the bleeding. [ABSTRACT FROM AUTHOR]

To provide insight into the mortality burden of coronavirus disease (COVID-19) in Japan, we estimated the excess all-cause deaths for each week during the pandemic, January-May 2020, by prefecture and age group. We applied quasi-Poisson regression models to vital statistics data. Excess deaths were expressed as the range of differences between the observed and expected number of all-cause deaths and the 95% upper bound of the 1-sided prediction interval. A total of 208-4,322 all-cause excess deaths at the national level indicated a 0.03%-0.72% excess in the observed number of deaths. Prefecture and age structure consistency between the reported COVID-19 deaths and our estimates was weak, suggesting the need to use cause-specific analyses to distinguish between direct and indirect consequences of COVID-19. [ABSTRACT FROM AUTHOR]

ARID1A is a tumor suppressor gene that belongs to the switch/sucrose non-fermentable chromatin remodeling gene family. It is mutated in many types of human cancer with the highest frequency in endometrium-related ovarian and uterine neoplasms including ovarian clear cell, ovarian endometrioid, and uterine endometrioid carcinomas. We have previously reported that mutations in the promoter of human telomerase reverse transcriptase (TERT) rarely co-occur with the loss of ARID1A protein expression, suggesting a potential role of ARID1A in telomere biology. In this study, we demonstrate that ARID1A negatively regulates TERT transcriptional regulation and activity via binding to the regulatory element of TERT and promotes a repressive histone mode. Induction of ARID1A expression was associated with increased occupancy of SIN3A and H3K9me3, known transcription repressor and histone repressor marks, respectively. Thus, loss of ARID1A protein expression caused by inactivating mutations reactivates TERT transcriptional activity and confers a survival advantage of tumor cells by maintaining their telomeres. [ABSTRACT FROM AUTHOR]

Background: It is recognized that colonization by Staphylococcus aureus (SA) on the skin is one of the factors that can worsen atopic dermatitis (AD). Antibiotics and germicides are not the best choice to remove bacteria from the skin of AD patients, because of problems of irritation to the skin and bacterial resistance. We therefore turned our attention to the biofilm of SA with the aim of removing only SA from the skin surface of AD patients. We found that xylitol (X) and farnesol (F) synergistically inhibited biofilm formation by SA and dissolved biofilm formed in vivo (Part 1)., Objective: To test whether application of AD for 1 week with FX cream can reduce SA without affecting Staphylococcus epidermidis., Methods: A randomized, double-blind, placebo-controlled right-and-left comparison study was performed. The arms of 17 patients with dry-type AD were applied with skin-care cream including/or not including a 0.02% F and 5% X combination for 1 week. The clinical response, biophysical assessment of the skin surface and counts of skin microflora were recorded before and after 1 week of therapy., Results: The ratio of SA in total bacteria at sites to which FX cream had been applied was significantly decreased after 1 week (P = 0.007), compared with before application and with placebo sites (P = 0.045). The mean skin conductance (a parameter indicating the state of hydration of the skin surface) of FX cream sites was increased significantly compared with the conductance before application (P = 0.0001) and at placebo sites (P = 0.002)., Conclusion: This study provides evidence supporting the idea that cream containing F and X is a useful skin-care agent for atopic dry skin colonized by SA.