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Abstract A solitonic ground state called a chiral soliton lattice (CSL) is realized in a supersymmetric theory with background magnetic field and finite chemical potential. To this end, we construct, in the superfield formalism, a supersymmetric chiral sine-Gordon model as a neutral pion sector of a supersymmetric two-flavor chiral Lagrangian with a Wess-Zumino-Witten term. The CSL ground state appears in the presence of either a strong magnetic field and/or large chemical potential, or a background fermionic condensate in the form of a fermion bilinear consisting of the gaugino and a superpartner of a baryon gauge field.

Abstract We study an analogue of the Drinfel’d double for algebroids associated with the O(D, D + n) gauged double field theory (DFT). We show that algebroids defined by the twisted C-bracket in the gauged DFT are built out of a direct sum of three (twisted) Lie algebroids. They exhibit a “tripled”, which we call the extended double, rather than the “doubled” structure appearing in (ungauged) DFT. We find that the compatibilities of the extended doubled structure result not only in the strong constraint but also the additional condition in the gauged DFT. We establish a geometrical implementation of these structures in a (2D + n)-dimensional product manifold and examine the relations to the generalized geometry for heterotic string theories and non-Abelian gauge symmetries in DFT.

The purpose of this paper is to construct a methodology which can produce a lightweight panel structure while being satisfied with more than one constraint by using some simple model. In this study, we chose a problem including bending stiffness and the 1st order eigen frequency as constraints and volume minimization as objective function among basic performances which a vehicle requires. So far, we have been trying to solve the problem by using a method consisting of Fully Stressed Design (FSD) and Genetic Algorithm (GA). FSD is an optimization which evaluates only stiffness of a structure based on relationship between thickness and stress, while GA, a broad array method, can have various number of objective functions and constraints. Prior to this study, the authors found a process was effective that stresses on the elements were to be equalized in the 1st step by applying FSD that made an individual superior on static stiffness. In this study, proposed method, which includes a process of equalization on normalized stresses on eigen vibrations, are added to that of static stresses in the 1st step. In the 2nd step, GA is selected. GA conducts operations, such as select, crossing, and mutation repeatedly until this attains a final solution. As for the model, we chose a sandwich panel which is equipped with top and bottom plates and interlayer lattice stiffeners. The reason for this selection is that the sandwich panel is lightweight and superior to stiffness, dumping, and strength. As a result, the obtained model presents a lightweight structure while being satisfied with the requirements of both stiffness and eigen frequency. Moreover, the proposed method attains optimized results earlier than GA without using FSD.

We study geometries for the NS5-, the KK5- and the 522-branes of codimension two in type II and heterotic string theories. The geometries are classified by monodromies that each brane has. They are the B-, the general coordinate and the β-transformations of the spacetime metric, the B-field and the dilaton (and the gauge fields). We show that the monodromy nature appears also in the geometric quantities such as the curvature and the complex structures of spacetime. They are linearly realized in the doubled (generalized) structures in the doubled space.

Abstract We study the O(D, D + n) generalized metric and the gauge symmetries in the gauged double field theory (DFT) in view of current algebras and sigma models. We show that the O(D, D + n) generalized metric in the gauged DFT is consistent with the heterotic sigma models at the leading order in the α′-corrections. We then study the non-Abelian gauge symmetries and current algebras of heterotic string theories. We show that the algebras exhibit the correct diffeomorphism, the B-field gauge transformations of the background fields together with the non-Abelian gauge transformations possibly with the appropriate local Lorentz transformations.

Abstract The detection and sequencing of the mutated ctDNA is one of the irreplaceable clinical measures in the postoperative management of colorectal cancer (CRC) cases. However, we are curious to comprehend the essential traits of mutated genes comprising metastatic sites out of whole mutated genes in primary sites. In the current retrospective study, we conducted target resequencing of ctDNA using 47 plasma samples and established a cancer panel carrying the commonly mutated genes between primary and recurrent tumors. We found that mutated genes in ctDNA indicated immune-resistance traits with respect to the impaired ability to present neoantigens by loss of expression or binding affinity to HLA in the primary tumor. Compared with the estimated neoantigens from all mutated genes in primary tumors, the neoantigen peptides from commonly mutated genes on the panel showed abundant expression but no binding affinity to HLA. Therefore, ctDNA mutations can be frequently and postoperatively detected to identify recurrence; however, these mutated genes were derived from immune-tolerated clones owing to the loss of neoantigen presentation in primary CRC tumors.

Abstract We study the vacuum structures of four-dimen-sional $$\mathcal {N} = 1$$ N = 1 old minimal supergravity with higher derivative corrections. We find that $$\mathcal {N} = 1$$ N = 1 supergravity with Riemann curvature square corrections and higher derivative matter chiral multiplets induces a non-trivial de Sitter vacuum, even in the absence of superpotentials. This vacuum generically breaks supersymmetry. We show that the auxiliary fields in the gravity and the chiral multiples play important roles to generate a potential in supersymmetric higher derivative theories.

Abstract Anal canal cancer (ACC) has been reported to be an uncommon cancer in Japan, as in the USA, Europe, and Australia. This retrospective multi‐institutional study was conducted to clarify the characteristics of ACC in Japan. First, the histological ACC type cases treated between 1991 and 2015 were collected. A detailed analysis of the characteristics of anal canal squamous cell carcinoma (SCC) cases was then conducted. The results of the histological types revealed that of the 1781 ACC cases, 435 cases (24.4%) including seven cases of adenosquamous cell carcinomas were SCC and 1260 cases (70.7%) were adenocarcinoma. However, the most common histological type reported in the USA, Europe, and Australia is SCC. Most ACC cases are adenocarcinomas and there is a low incidence of SCC in Japan which is different from the above‐mentioned countries. Moreover, we reclassified T4 into the following two groups based on tumor size: T4a (tumor diameter of 5 cm or less) and T4b (tumor diameter of more than 5 cm). The results of the TNM classification of SCC revealed that the hazard ratio (HR) to T1 of T2, T3, T4a, and T4b was 2.45, 2.28, 2.89, and 4.97, respectively. As T4b cases had a worse prognosis than T4a cases, we propose that T4 for anal canal SCC in Japan be subclassified into T4a and T4b.

Abstract We investigate doubled (generalized) complex structures in 2D-dimensional Born geometries where T-duality symmetry is manifestly realized. We show that Kähler, hyperkähler, bi-hermitian and bi-hypercomplex structures of spacetime are implemented in Born geometries as doubled structures. We find that the Born structures and the generalized Kähler (hyperkähler) structures appear as subalgebras of bi-quaternions and split-tetra-quaternions. We find parts of these structures are classified by Clifford algebras. We then study the T-duality nature of the worldsheet instantons in Born sigma models. We show that the instantons in Kähler geometries are related to those in bi-hermitian geometries in a non-trivial way.

Background: The prognostic nutritional index (PNI) is used to assess immune and nutritional status, and is a prognostic factor for several malignant tumors. However, little evidence exists regarding the predictive impact of prognostic nutritional index (PNI) after local ablation therapy for hepatocellular carcinoma (HCC). The aim of this study was to evaluate the value of PNI to predict recurrence and survival after operative microwave ablation in patients with early-stage HCC. Methods: This retrospective study included 341 patients who underwent operative microwave ablation for HCC in Barcelona Clinic Liver Cancer (BCLC) stage 0-A at our institute between 2007 and 2015. We analyzed overall survival (OS) and recurrence-free survival (RFS), and evaluated factors related to prognosis in multivariate Cox regression analyses. Results: The OS rates at 1, 3, 5, and 10 years after microwave ablation were 100%, 92.7%, 85.1%, and 57.5% in patients with high-PNI levels, and 96.5%, 78.2%, 59.7%, and 20.7% in patients with low-PNI levels, respectively (P

Abstract We study the membrane wrapping mode corrections to the Kaluza-Klein (KK) 6-brane in eleven dimensions. We examine the localized KK6-brane in the extended space in E 7(7) exceptional field theory. In order to discuss the physical origin of the localization in the extended space, we consider a probe M2-brane in eleven dimensions. We show that a three-dimensional N $$ \mathcal{N} $$ = 4 gauge theory is naturally interpreted as a membrane generalization of the two-dimensional N $$ \mathcal{N} $$ = (4, 4) gauged linear sigma model for the fundamental string. We point out that the vector field in the N $$ \mathcal{N} $$ = 4 model is identified as a dual coordinate of the KK6-brane geometry. We find that the BPS vortex in the gauge theory gives rise to the violation of the isometry along the dual direction. We then show that the vortex corrections are regarded as an instanton effect in M-theory induced by the probe M2-brane wrapping around the M-circle.

Vaccine confidence reflects social, individual, and political factors indicating confidence in vaccines and associated health systems. In Japan, the government ceased proactive recommendation of the human papillomavirus (HPV) vaccine in June 2013, only several months after the recommendation had begun. Seven years later, as of October 2020, the suspension persists and vaccine coverage has precipitously declined, resulting in many young women being continually exposed to the risk of preventable HPV-related diseases. Accordingly, understanding stakeholder opinions on HPV vaccination issues is critical for informing strategies to improve HPV vaccine confidence and acceptance. In October 2019, we performed a nationwide, web-based survey of 1646 mothers of HPV-vaccination–eligible girls, 562 female adolescents aged 15–19 years, and 919 healthcare professionals (HCPs) in Japan. This survey captured key elements of vaccine confidence (i.e., importance, effectiveness, and safety of the HPV vaccine), awareness, and the willingness to receive (in HPV-vaccination–eligible girls) or recommend (in HCPs) the HPV vaccine, and the factors responsible for these decisions. HPV vaccine confidence was generally higher among HCPs than among mothers or female adolescents. Nearly half of all stakeholders were neutral regarding their willingness to receive/recommend the HPV vaccine. The seriousness of cervical cancer and the HPV vaccine’s effectiveness or safety were important deciding factors for receiving/recommending the HPV vaccine. Besides these factors, sufficient information and free vaccination were crucial. Our results suggest several factors that could help shape public policy and communication strategies to improve HPV vaccine confidence and acceptance in Japan.

We exploit the doubled formalism to study comprehensive relations among T-duality, complex and bi-hermitian structures (J+,J−) in two-dimensional N=(2,2) sigma models with/without twisted chiral multiplets. The bi-hermitian structures (J+,J−) embedded in generalized Kähler structures (J+,J−) are organized into the algebra of the tri-complex numbers. We write down an analogue of the Buscher rule by which the T-duality transformation of the bi-hermitian and Kähler structures are apparent. We also study the bi-hypercomplex and hyperkähler cases in N=(4,4) theories. They are expressed, as a T-duality covariant fashion, in the generalized hyperkähler structures and form the split-bi-quaternion algebras. As a concrete example, we show the explicit T-duality relation between the hyperkähler structures of the KK-monopole (Taub-NUT space) and the bi-hypercomplex structures of the H-monopole (smeared NS5-brane). Utilizing this result, we comment on a T-duality relation for the worldsheet instantons in these geometries.

Abstract The geriatric nutritional risk index (GNRI) is widely used for nutritional assessment in older inpatients and is associated with postoperative complications and cancer prognosis. We investigated the use of GNRI to predict long-term outcomes in hepatocellular carcinoma of all etiologies after hepatectomy. Overall, 346 patients were examined after propensity score matching. We dichotomized the GNRI score into high GNRI (> 98: N = 173) and low GNRI (≤ 98: N = 173) and evaluated recurrence-free survival (RFS) and overall survival (OS) between both groups. Clinicopathological characteristics between the low- and high-GNRI groups were similar after propensity score matching except for the components of the GNRI score (body mass index and serum albumin level), Child–Pugh score (comprising serum albumin level), and preoperative alpha-fetoprotein level (p

Abstract We study the current algebras of the NS5-branes, the Kaluza-Klein (KK) five-branes and the exotic 5 2 2 $$ {5}_2^2 $$ -branes in type IIA/IIB superstring theories. Their worldvolume theories are governed by the six-dimensional N $$ \mathcal{N} $$ = (2, 0) tensor and the N $$ \mathcal{N} $$ = (1, 1) vector multiplets. We show that the current algebras are determined through the S- and T-dualities. The algebras of the N $$ \mathcal{N} $$ = (2, 0) theories are characterized by the Dirac bracket caused by the self-dual gauge field in the five-brane worldvolumes, while those of the N $$ \mathcal{N} $$ = (1, 1) theories are given by the Poisson bracket. By the use of these algebras, we examine extended spaces in terms of tensor coordinates which are the representation of ten-dimensional supersymmetry. We also examine the transition rules of the currents in the type IIA/IIB supersymmetry algebras in ten dimensions. Based on the algebras, we write down the section conditions in the extended spaces and gauge transformations of the supergravity fields.

Abstract Background Pancreatic trauma is a rare condition with a wide presentation, ranging from hematoma or laceration without main pancreatic duct involvement, to massive destruction of the pancreatic head. The optimal diagnosis of pancreatic trauma and its management approaches are still under debate. The East Association of Surgery for Trauma (EAST) guidelines recommend operative management for high-grade pancreatic trauma; however, several reports have reported successful outcomes with nonoperative management (NOM) for grade III/IV pancreatic injuries. Herein, we report a case of grade IV pancreatic injury that was nonoperatively managed through endoscopic and percutaneous drainage. Case presentation A 47-year-old Japanese man was stabbed in the back with a knife; upon blood examination, both serum amylase and lipase levels were within normal limits. Contrast-enhanced computed tomography (CT) showed extravasation of the contrast medium around the pancreatic head and a hematoma behind the pancreas. Abdominal arterial angiography revealed a pseudo aneurysm in the inferior pancreatoduodenal artery, as well as extravasation of the contrast medium in that artery; coil embolization was thus performed. On day 12, CT revealed a wedge-shaped, low-density area in the pancreatic head, as well as consecutive pseudocysts behind the pancreas; thereafter, percutaneous drainage was performed via the stab wound. On day 22, contrast radiography through the percutaneous drain revealed the proximal and distal parts of the main pancreatic duct. The injury was thus diagnosed as a grade IV pancreatic injury based on the American Association for the Surgery of Trauma guidelines. On day 26, an endoscopic nasopancreatic drainage tube was inserted across the disruption; on day 38, contrast-enhanced CT showed a marked reduction in the fluid collection. Finally, on day 61, the patient was discharged. Conclusions Although the EAST guidelines recommend operative treatment for high-grade pancreatic trauma, NOM with appropriate drainage by endoscopic and/or percutaneous approaches may be a promising treatment for grade III or IV trauma.

Background: It remains to be clarified whether combined hepatectomy and microwave ablation for multifocal hepatocellular carcinoma (HCC) is feasible. This aim of this study was to examine the perioperative and oncological outcomes after combined hepatectomy and microwave ablation for multifocal HCC. Methods: This retrospective study included 81 patients who underwent combined hepatectomy and microwave ablation for multifocal HCC in our institute between June 1998 and December 2017. We analyzed overall survival (OS) and recurrence-free survival (RFS), and evaluated factors related to prognosis. Results: Median follow-up time was 45.6 months for the entire cohort. OS rates were 1-year: 96%, 3-year: 72%, and 5-year: 54%; RFS rates were 1-year: 77%, 3-year: 37%, and 5-year: 22%. The major complication rate (Clavien–Dindo classification IIIa or above) after surgery was 10%, with one patient of in-hospital mortality. Multivariate analysis revealed that des-γ-carboxy prothrombin level >200 mAU/mL and >5 tumors were independent risk factors for OS, and des-γ-carboxy prothrombin level >200 mAU/mL, > 5 tumors, and maximum tumor size >5 cm were independent risk factors for RFS. Conclusions: Our results indicate that combined hepatectomy and microwave ablation is safe and feasible for selected patients with multifocal HCC.

Abstract We study world-volume effective theories of five-branes in type II string theories. We determine the bosonic zero-modes of the NS5-brane, the Kaluza-Klein monopole, the exotic Q5-, R5-branes and a space-filling brane, by direct calculations within the formalism of double field theory (DFT). We show that these zero-modes are Nambu-Goldstone modes associated with the spontaneously broken gauge symmetries in DFT. They are organized into the bosonic part of the six-dimensional N $$ \mathcal{N} $$ = (1) vector and the N $$ \mathcal{N} $$ = (2, 0) tensor multiplets. Among other things, we examine the locally non-geometric R5-branes and space-filling branes that are characterized by the winding space. We also study effective theories of five-branes with string worldsheet instanton corrections.

Abstract Background Glomus tumors (GTs) are mesenchymal neoplastic lesions arising from the glomus bodies and generally occur in the fingers and toes. Gastrointestinal GTs are rare, and most of them originate from the stomach; however, GT arising from the duodenum is exceedingly rare. Case presentation A 68-year-old man was admitted due to abdominal pain. Endoscopy showed a round, smooth, elevated mass in the second portion of the duodenum with central ulceration. Abdominal contrast computed tomography showed a hypervascular tumor measuring 26 mm in diameter in the second portion of the duodenum, and pancreatic invasion was suspected. Endoscopic ultrasonography of the lesion confirmed a hypoechoic mass arising from the fourth layer of the duodenal wall. A biopsy was performed for central ulceration, and immunochemical studies showed positive results for smooth muscle actin (SMA) and negative results for S100, C-Kit, and CD34. Leiomyoma or gastrointestinal stromal tumor was suspected and pancreatoduodenectomy was performed. The specimen exhibited a vascular-rich tumor, 24 × 24 × 19 mm in size, with deep ulceration in the duodenum. Histological examination showed uniform small round cells with central nuclei and a pale cytoplasm (glomus cell) with perivascular proliferation. Immunochemical studies showed that the tumor was positive for SMA and collagen type IV, and negative for C-Kit, CD34, desmin, and S100. We diagnosed the tumor as a GT of the duodenum. Conclusion GTs of the duodenum are exceedingly rare, but should be considered in the differential diagnoses of duodenal submucosal lesions.

Abstract Background Tumor thrombus in the superior mesenteric vein secondary to colon cancer is rare. We report a case of tumor thrombus in the superior mesenteric vein and liver metastasis due to advanced colon cancer that was treated with chemotherapy and complete surgical resection. Case presentation A 72-year-old man after transverse colectomy with lymph node dissection for advanced colon cancer was diagnosed with tumor thrombus in the superior mesenteric vein and liver metastasis. He underwent adjuvant chemotherapy and had complete surgical tumor resection involving tumor thrombectomy and hepatectomy. There has been no recurrence at 36 months after surgery. Conclusion Herein, we report a rare case of tumor thrombus in the superior mesenteric vein related to advanced colon cancer. The combination of chemotherapy and complete surgical tumor resection may provide long-term survival.

Abstract Background Gastroenteric neuroendocrine carcinomas (NECs) account for 6.2% of gastroenteric neuroendocrine tumors (NETs), and only 1% or less of gastroenteric NETs occur in the ampulla of Vater (AoV). Clinical features of NEC of the AoV remain obscure. Case presentation A 65-year-old man visited a general practitioner because of jaundice, and an abdominal contrast-enhanced computed tomography scan revealed a tumor of 11 mm in diameter, which was enhanced in the arterial phase at the duodenal papilla, with dilation of the upstream bile duct. Gastrointestinal scope revealed an unexposed tumor of the AoV. Based on a biopsy of the site, a moderately differentiated tubular adenocarcinoma was suspected, and pancreatoduodenectomy was performed. Histopathological examination revealed dysplasia and highly proliferative small tumor cells, with solid and nodular formation at the AoV. Histological analysis showed a high mitotic count, and immunohistochemical staining revealed a Ki-67 index of 40–50% and cells positive for synaptophysin, chromogranin A, and p53. Small cell-type NEC was finally diagnosed. Four months post pancreatoduodenectomy, multiple liver metastases developed, and systemic chemotherapy was administered. Salvage liver resection for liver metastases was performed 14 months after the pancreatoduodenectomy. Unfortunately, multiple liver metastases developed 2 months after liver resection, and the patient died 18 months after the pancreatoduodenectomy. Conclusions Neuroendocrine carcinoma originating from the bile duct is very rare; therefore, in this article, we provide a review of the literature and a case report.

A 73-year-old male was initially treated with sorafenib for advanced stage HCC. However, the disease progressed 2 months after starting sorafenib. Progressive disease (PD) was confirmed by radiological examination, which revealed mediastinal and abdominal lymph node metastasis, pulmonary metastasis, and intrahepatic recurrence. The patient was enrolled in the REACH-2 (NCT02435433) trial and randomized to receive ramucirumab (8 mg/kg div. every 2 weeks). The patient had a Child–Pugh score of 6A and his AFP level was found to be 1,256.8 ng/mL at initiation. Radiological examination revealed PD, 5 months after starting ramucirumab. Ramucirumab treatment was continued after the confirmation of radiological PD, not but clinical progression, as allowed by the study protocol. His AFP level increased after continuous ramucirumab treatment, however, it suddenly decreased from 7,653 ng/mL to within normal limits 10 months after initiation of ramucirumab treatment. Radiological evaluation revealed a significant decrease in the size of the tumors, which constituted a partial response (PR). We reported a rare case of advanced HCC with PR to a continuous ramucirumab treatment after radiological PD.

Abstract Background Carcinoma of the ampulla of Vater with distant metastases is regarded as unresectable. Systemic chemotherapy is basically the treatment of choice for such tumors. Case presentation A 68-year-old woman was referred to our hospital and diagnosed with carcinoma of the ampulla of Vater with lymph node and multiple liver metastases. She underwent systemic chemotherapy with a combination of gemcitabine and cisplatin. After 19 months of treatment, the primary tumor and liver metastases were difficult to detect on follow-up images. Shrinkage of the enlarged lymph nodes was also confirmed. Surgical resection was performed with curative intent after a multidisciplinary meeting. Pathological examination of the resected specimen showed no residual tumors. Systemic chemotherapy achieved a pathological complete response. The postoperative course was uneventful, and the patient remained free of recurrent disease at 10 months of follow-up. Conclusion This case shows the possibility of conversion surgery after systemic chemotherapy for carcinoma of the ampulla of Vater.

Abstract Background Liver is a common location of colorectal metastasis, but intrabiliary growth of liver metastasis is not well recognized. Furthermore, intrabiliary metastasis that discovered over 10 years after excision has rarely been described. Case presentation An 80-year-old man was admitted due to the presence of a liver mass in segment 5 (S5) concomitant with elevated carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19–9. He underwent right hemicolectomy for colon cancer 12 years prior. Enhanced computed tomography (CT) showed dilated bile ducts with periductal enhancement in S5; hence, cholangiocarcinoma was suspected. Upon anterior segmentectomy, we observed that the cut surface of the specimen exhibited a yellowish-white tumor within the bile ducts. Histologically, the tumor formed within the papillary process, extended along the lumen, and replaced the normal bile duct epithelium. Immunohistochemical studies showed that the liver tumor and primary colon cancer were negative for cytokeratin (CK) 7 and positive for CK20 and Caudal-type homeobox transcription factor 2 (CDX-2). In addition, both tumors showed a same KRAS mutation. We diagnosed the liver tumor as liver metastasis recurrence from colon cancer. Conclusion Intrabiliary growth type of metastasis (IGM) is difficult to distinguish from cholangiocarcinoma, and sometimes develops long after surgery; thus, careful examination of a patient’s history is needed in such cases.

Abstract We establish a double dualization in two-dimensional supersymmetric gauge theory. We construct a gauged linear sigma model (GLSM) which contains a complex twisted linear superfield coupled to two sets of Abelian vector superfields. In the IR regime, the GLSM provides a string sigma model whose target spaces are a defect NS5-brane, a Kaluza-Klein vortex and an exotic 5 2 2 -brane. All of them are five-branes of codimension two and are related by T-duality. This model is a natural extension of the GLSM proposed by Tong which gives a sigma model for an H-monopole, i.e., a smeared NS5-brane of codimension three. This is also regarded as an alternative system of the GLSM for exotic five-branes proposed by the present authors. In this analysis, we confirm that the T-duality transformation procedure in terms of the complex twisted linear superfield is applicable to dualize both the real and imaginary parts of the twisted chiral superfield even at the UV level, beyond the IR limit. This indicates that the T-duality transformations at finite gauge couplings can be performed in terms of reducible superfields in the same way as irreducible (twisted) chiral superfields. Furthermore, we study quantum vortex corrections to the GLSM at the UV level. In the IR limit, these corrections are mapped to string worldsheet instanton corrections to the five-branes of codimension two. The result completely agrees with those in double field theory analysis.

A Darwinian evolutionary shift occurs early in the neutral evolution of advanced colorectal carcinoma (CRC), and copy number aberrations (CNA) are essential in the transition from adenoma to carcinoma. In light of this primary evolution, we investigated the evolutionary principles of the genome that foster postoperative recurrence of CRC. CNA and neoantigens (NAG) were compared between early primary tumors with recurrence (CRCR) and early primary tumors without recurrence (precancerous and early; PCRC). We compared CNA, single nucleotide variance (SNV), RNA sequences, and T-cell receptor (TCR) repertoire between 9 primary and 10 metastatic sites from 10 CRCR cases. We found that NAG in primary sites were fewer in CRCR than in PCRC, while the arm level CNA were significantly higher in primary sites in CRCR than in PCRC. Further, a comparison of genomic aberrations of primary and metastatic conditions revealed no significant differences in CNA. The driver mutations in recurrence were the trunk of the evolutionary phylogenic tree from primary sites to recurrence sites. Notably, PD-1 and TIM3, T cell exhaustion-related molecules of the tumor immune response, were abundantly expressed in metastatic sites compared to primary sites along with the increased number of CD8 expressing cells. The postoperative recurrence-free survival period was only significantly associated with the NAG levels and TCR repertoire diversity in metastatic sites. Therefore, CNA with diminished NAG and diverse TCR repertoire in pre-metastatic sites may determine postoperative recurrence of CRC.

BackgroundAcute fibrinous and organizing pneumonia (AFOP) is a rare histologic pattern of acute lung involvement with intra-alveolar fibrin deposition. However, the clinical significance of the pathological findings of AFOP remains unclear. This study aimed to explore the clinical significance of AFOP through a comprehensive clinical examination.MethodsThe medical records of patients with lung diseases accompanied by the pathological finding of intra-alveolar organization between January 2010 and December 2019 were retrospectively reviewed. The clinical and radiological findings were compared between the groups with and without the histologic pattern of AFOP.ResultsWe identified 34 patients with AFOP (AFOP group) and 143 without AFOP (non-AFOP group). The underlying diseases of the AFOP group were as follows: 19 patients had cryptogenic organizing pneumonia (OP), 5 had connective tissue diseases, 3 had radiation pneumonitis, 3 had chronic eosinophilic pneumonia, 2 had myelodysplastic syndromes, and 2 had drug-induced pneumonia. Fever was more common, the time from symptom onset to biopsy was shorter, and the serum C-reactive protein level was higher in the AFOP group than in the non-AFOP group. On high-resolution computed tomography, 85% of patients had OP pattern, and halo sign was more common in the AFOP group. Corticosteroids were effective in 94% of the patients in the AFOP group; however, recurrences were more frequent, and a higher corticosteroid dose was needed during recurrence.ConclusionsAFOP might be an early phase of a histologic pattern associated with known etiologies. In addition, it could be a marker indicating intense inflammatory diseases with a tendency of recurrence.

Abstract Spatial modulation has been studied for a long time in condensed matter, nuclear matter and quark matter, where the manifest Lorentz invariance is lost due to the finite density/temperature effects and so on. In this paper, spatially modulated vacua at zero temperature and zero density are studied in Lorentz invariant field theories. We first propose an adaptation of the Nambu–Goldstone theorem to higher derivative theories under the assumption of the absence of ghosts: when a global symmetry is spontaneously broken due to vacuum expectation values of space-time derivatives of fields, a Nambu–Goldstone (NG) boson appears without a canonical kinetic (quadratic derivative) term with a quartic derivative term in the modulated direction while a Higgs boson appears with a canonical kinetic term. We demonstrate this in a simple model allowing (meta)stable modulated vacuum of a phase modulation (Fulde–Ferrell state), where an NG mode associated with spontaneously broken translational and U(1) symmetries appears.

Abstract We make a comprehensive study on the string winding corrections to supergravity solutions in double field theory (DFT). We find five-brane and wave solutions of diverse codimensions in which the winding coordinates are naturally included. We discuss a physical interpretation of the winding coordinate dependence. The analysis based on the geometric structures behind the solutions leads to an interpretation of the winding dependence as string worldsheet instanton corrections. We also give a brief discussion on the origins of these winding corrections in gauged linear sigma model. Our analysis reveals that for every supergravity solution, one has DFT solutions that include string winding corrections.

This was a randomized, placebo-controlled, Phase I/II study conducted in a Japanese cohort to assess the safety and immunogenicity of Clostridium difficile vaccine (the same formulation as that used in the ongoing global Phase III study). Healthy Japanese adults aged 40–75 years were randomized to receive either C. difficile vaccine (N = 67) or placebo (N = 34) by intramuscular injection on Days 0, 7, and 30. Serum IgG specific for toxins A and B was measured by enzyme-linked immunosorbent assay (ELISA) and in vitro functional activity by toxin neutralizing assay (TNA). The seroconversion rate (percentage of participants with a ≥4-fold rise in antibody levels from baseline) was high for both toxin A (ELISA and TNA) and toxin B (ELISA), approaching 100% for each by Day 60. For toxin B assessed by TNA, however, the response was lower, with the seroconversion rate not rising significantly beyond the value of 42.9% seen on Day 14 (44.4% at Day 60). Although the response in the participants who were seronegative at baseline was slower than that in those who were seropositive, seroconversion was seen in nearly all (100%) subjects by Day 60, with the exception of the response to toxin B evaluated using TNA (16–18% on Days 14–60). The proportion of participants with solicited local reactions, solicited systemic reactions, and vaccine-related unsolicited reactions were 67.6%, 19.1%, and 20.6%, respectively. Most of the adverse reactions were mild to moderate in intensity, occurring within 3 days post-vaccination, and resolving by 3–6 days post-vaccination. There were no withdrawals due to adverse events and no serious adverse events. These data confirm the safety and immunogenicity of C. difficile vaccine in Japanese adults.

This study retrospectively compared the perioperative bleeding, hemodynamics, and clinical outcomes of total knee arthroplasty (TKA) performed with and without a tourniquet between two age groups. We grouped 103 patients with knee osteoarthritis who underwent primary TKA based on age at surgery:

Abstract We continue to study the BPS gauge five-brane solutions of codimension two in ten-dimensional heterotic supergravity. The geometry including the dilaton and the NS-NS B-field are sourced from the monopole chain in ℝ 2 × S 1. We find that the geometry is asymptotically Ricci flat and the dilaton is no longer imaginary valued. These properties are contrasted with the smeared counterpart discussed in our previous paper. We perform the T-duality transformations of the solution and find that it never results in a non-geometric object.

We study the ADHM construction of (anti-)self-dual instantons in eight dimensions. We propose a general scheme to construct the (anti-)self-dual gauge field configurations F∧F=±⁎8F∧F whose finite topological charges are given by the fourth Chern number. We show that our construction reproduces the known SO(8) one-instanton solution. We also construct multi-instanton solutions of the 't Hooft and the Jackiw–Nohl–Rebbi (JNR) types in the dilute instanton gas approximation. The well-separated configurations of multi-instantons reproduce the correct topological charges with high accuracy. We also show that our construction is generalized to (anti-)self-dual instantons in 4n (n=3,4,…) dimensions.

[This corrects the article DOI: 10.1371/journal.pgen.1005778.].

Understanding intratumor heterogeneity is clinically important because it could cause therapeutic failure by fostering evolutionary adaptation. To this end, we profiled the genome and epigenome in multiple regions within each of nine colorectal tumors. Extensive intertumor heterogeneity is observed, from which we inferred the evolutionary history of the tumors. First, clonally shared alterations appeared, in which C>T transitions at CpG site and CpG island hypermethylation were relatively enriched. Correlation between mutation counts and patients' ages suggests that the early-acquired alterations resulted from aging. In the late phase, a parental clone was branched into numerous subclones. Known driver alterations were observed frequently in the early-acquired alterations, but rarely in the late-acquired alterations. Consistently, our computational simulation of the branching evolution suggests that extensive intratumor heterogeneity could be generated by neutral evolution. Collectively, we propose a new model of colorectal cancer evolution, which is useful for understanding and confronting this heterogeneous disease.

Pneumatosis cystoides intestinalis (PCI) is a rare gastrointestinal complication of systemic sclerosis (SSc) characterized by intramural accumulation of gas within thin-walled cysts. We report the case of an 82-year-old female patient with pneumoperitoneum due to PCI associated with SSc and review the features of the 39 Japanese cases. The median patient age was 57 years (range 24–83 years) and the male/female ratio was 1 : 12. In the recent decade, 14 out of 15 cases (93.3%) evaluated with CT scans were diagnosed with PCI. The results suggest that CT scan may be a useful diagnostic tool for detecting PCI. PCI in patients with SSc is usually benign and requires only conservative therapy. However, two patients (5.1%) with signs of peritoneal irritation required surgery. When peritoneal irritation secondary to additional pathology is observed, surgical treatment may be warranted; a precise diagnosis for this condition is therefore essential.