From the Berkovits formulation to the Witten formulation in open superstring field theory

The Berkovits formulation of open superstring field theory is based on the large Hilbert space of the superconformal ghost sector. We discuss its relation to the Witten formulation based on the small Hilbert space. We introduce a one-parameter family of conditions for partial gauge fixing of the Berkovits formulation such that the cubic interaction of the theory under the partial gauge fixing reduces to that of the Witten formulation in a singular limit. The local picture-changing operator at the open-string midpoint in the Witten formulation is regularized in our approach, and the divergence in on-shell four-point amplitudes coming from collision of picture-changing operators is resolved. The quartic interaction inherited from the Berkovits formulation plays a role of adjusting different behaviors of the picture-changing operators in the $s$ channel and in the $t$ channel of Feynman diagrams with two cubic vertices, and correct amplitudes in the world-sheet theory are reproduced. While gauge invariance at the second order in the coupling constant is obscured in the Witten formulation by collision of picture-changing operators, it is well defined in our approach and is recovered by including the quartic interaction inherited from the Berkovits formulation.Comment: 50 pages, 2 figures; v2: references added, minor changes, version published in JHE

Is Adjuvant Chemotherapy Necessary in Patients with Early Endometrial Cancer?

Background: We investigated whether there was a difference in prognosis between patients with stage IA endometrial cancer with and without lymphovascular space invasion. Methods: We enrolled patients with stage IA (pT1aN0M0) endometrial cancer admitted to our hospital from 2009 to 2018. All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and systematic pelvic lymphadenectomy. We immunopathologically evaluated the presence or absence of lymphovascular space invasion in the tumor tissue using hematoxylin and eosin, Elastica-van Gieson, and podoplanin staining. We analyzed disease-free and overall survival and calculated patients’ survival distribution using the Kaplan–Meier method and log-rank test. The multivariate analysis was performed to determine the prognostic factors. Results: A total of 116 patients were included. The median age of the patients was 57 (range, 30–78) years, and the histological subtype revealed 98 and 18 cases of types 1 and 2, respectively. The median follow-up period was 71.9 (range, 10.8–149) months, and the 3-year disease-free and 3-year overall survival rates were 94% and 99%, respectively. The disease-free and overall survival rates were significantly shorter in type 2 patients than in type 1 patients (type 2 vs. type 1; 77% vs. 97%, P < 0.01, 94% vs. 100%, P = 0.014, respectively). The univariate and multivariate analyses showed that there were no significant differences in disease-free survival between the lymphovascular space invasion-positive and -negative groups among type 1 cases. Conclusion: There was no difference in prognosis between patients with stage IA and type 1 endometrial cancer with and without lymphovascular space invasion

Guided parent-delivered cognitive behavioural therapy for Japanese children and parents: a single-arm uncontrolled study

Background: Guided parent-delivered cognitive behavioural therapy (GPD-CBT) is an effective low-intensity treatment for childhood anxiety disorder in Western countries and can increase access to evidence-based psychological therapies. Aim: This study aimed to examine its feasibility in a Japanese sample. Method: Twelve children with anxiety disorders and their parents participated in the study, and ten children and parents completed the program. Participants were assessed at pre-, post- and one-month follow-up using a diagnostic interview for anxiety disorders, self- and parent-report measures for anxiety, depression, parental behaviour, and parental anxiety. Results: Four children (40% of completers) were free from their primary diagnoses immediately following the brief treatment, and seven children (70%) at the one-month follow-up. Changes in disorder severity, child and parent reported anxiety symptoms, and child reported depression symptoms were consistent with those found in Western trials of GPD-CBT and of Japanese trials of more intensive CBT for child anxiety disorders that involves both the child and the parent. Moderate increases were also found in child reported parental autonomy behaviours; however, there were only small changes in parent self-reported anxiety. Conclusion: These results support the potential of GPD-CBT to increase access to evidence-based treatments for anxiety disorders in Japanese children

Cancer activity and bleeding events post-PCI

Purpose : Limited data exist about clinically relevant bleeding events related to antiplatelet therapy after percutaneous coronary intervention (PCI) in cancer patients. We investigated the risk factors for clinically relevant bleeding events in patients with cancer after PCI with stent implantation. Patients and Methods : Patients with solid cancer subjected to first PCI were divided into active (n = 45) and non-active cancer groups (n = 44). The active group included non-operable patients on treatment or with metastasis ; the non-active included those already subjected to or for whom radical surgery was planned within 3 months after the index PCI. Results : During a median follow-up of 2.2 years, 11 bleeding events occurred, with only one occurring in the non-active cancer group. Half of them occurred during the dual-antiplatelet therapy (DAPT) period, and the rest occurred during single-antiplatelet therapy (SAPT) period. Kaplan-Meier analysis showed significantly more bleeding events in the active cancer group (p = 0.010). Multivariate Cox regression hazard analysis revealed cancer activity as a significant independent risk factor for bleeding (p = 0.023) ; but not for three-point major adverse cardiovascular events. Conclusion : Clinically relevant bleeding risk after PCI was significantly lower in non-active cancer. Active cancer group had clinically relevant bleeding during both DAPT and SAPT periods

Immuno-Genomic Profiling of Biopsy Specimens Predicts Neoadjuvant Chemotherapy Response in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and is primarily treated with platinum-based neoadjuvant chemotherapy (NAC). Some ESCCs respond well to NAC. However, biomarkers to predict NAC sensitivity and their response mechanism in ESCC remain unclear. We perform whole-genome sequencing and RNA sequencing analysis of 141 ESCC biopsy specimens before NAC treatment to generate a machine-learning-based diagnostic model to predict NAC reactivity in ESCC and analyzed the association between immunogenomic features and NAC response. Neutrophil infiltration may play an important role in ESCC response to NAC. We also demonstrate that specific copy-number alterations and copy-number signatures in the ESCC genome are significantly associated with NAC response. The interactions between the tumor genome and immune features of ESCC are likely to be a good indicator of therapeutic capability and a therapeutic target for ESCC, and machine learning prediction for NAC response is useful

Comparative Analyses Define Differences Between Bhd-Associated Renal Tumour and Sporadic Chromophobe Renal Cell Carcinoma

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome, caused by germline alteration of folliculin (FLCN) gene, develops hybrid oncocytic/chromophobe tumour (HOCT) and chromophobe renal cell carcinoma (ChRCC), whereas sporadic ChRCC does not harbor FLCN alteration. To date, molecular characteristics of these similar histological types of tumours have been incompletely elucidated. METHODS: To elucidate renal tumourigenesis of BHD-associated renal tumours and sporadic renal tumours, we conducted whole genome sequencing (WGS) and RNA-sequencing (RNA-seq) of sixteen BHD-associated renal tumours from nine unrelated BHD patients, twenty-one sporadic ChRCCs and seven sporadic oncocytomas. We then compared somatic mutation profiles with FLCN variants and RNA expression profiles between BHD-associated renal tumours and sporadic renal tumours. FINDINGS: RNA-seq analysis revealed that BHD-associated renal tumours and sporadic renal tumours have totally different expression profiles. Sporadic ChRCCs were clustered into two distinct clusters characterized by L1CAM and FOXI1 expressions, molecular markers for renal tubule subclasses. Increased mitochondrial DNA (mtDNA) copy number with fewer variants was observed in BHD-associated renal tumours compared to sporadic ChRCCs. Cell-of-origin analysis using WGS data demonstrated that BHD-associated renal tumours and sporadic ChRCCs may arise from different cells of origin and second hit FLCN alterations may occur in early third decade of life in BHD patients. INTERPRETATION: These data further our understanding of renal tumourigenesis of these two different types of renal tumours with similar histology. FUNDING: This study was supported by JSPS KAKENHI Grants, RIKEN internal grant, and the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research

マクロファージの一酸化窒素(NO)産生に及ぼす酵母マンナンの影響

In this study we examined in vitro effect of yeast mannans on nitric oxide (NO) production in a macrophage cell line, RAW264.7. The acidic mannan fraction (WAM025) from bakers\u27 yeast, Saccharomyces cerevisiae, increased the production of NO in RAW264.8 cells. This effect was stronger than that of the neutral mannan fraction (WNM) from the same yeast. On the other hand, the whole mannan from Candida albicans NIH A-207 strain did not increase the production of NO in RAW264.7 cells and inhibited lipopolysaccharide-induced NO production in the cells

Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder

Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p &lt; 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements