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Radiation therapy (RT) has the potential to activate the tumor-microenvironment (TME) and promote the efficacy of immune checkpoint blockade therapy. Tumor cell-intrinsic expression of cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) plays an important role in regulations of radiation-induced activation of immune cells in the TME. However, the role of tumor cell-intrinsic cGAS-STING in radiation-mediated remodeling of the TME in esophageal squamous cell carcinoma (ESCC) is not completely understood; thus, we investigated its effect on the radiation-mediated remodeling of the TME in ESCC.We assessed the effect of tumor cell-intrinsic cGAS-STING on the expression of mediators of the immune system, including type I interferon, T-cell chemo-attractants, colony-stimulating factor-1, and interleukin 34 (IL-34), induced by radiation in ESCC cell lines. We also quantified the association between tumor cell-intrinsic expression of cGAS-STING and infiltrations of immune cells, including CD8We found that tumor cell-intrinsic expression of cGAS-STING was involved in radiation-induced infiltration of CD8The tumor cell-intrinsic expression of cGAS-STING is essential for radiation-induced activation of immune cells in the TME, but it is also involved in the recruitment of tumor-promoting M2-TAMs in ESCC. Therefore, blocking of M2-TAM infiltration by targeting IL-34 might improve the efficacy of RT and combination therapy of RT with immune checkpoint inhibitors in ESCC.

Univariate and multivariate analyses of risk factors for OS and RFS after NAC in patients with ESCC

Broadcast Encryption (BE) is public-key encryption allowing a sender to encrypt a message by specifing recipients, and only the specified recipients can decrypt the message. In several BE applications, since the privacy of recipients allowed to access the message is often as important as the confidentiality of the message, anonymity is introduced as an additional but important security requirement for BE. Kiayias and Samari (IH 2013) presented an asymptotic lower bound on the ciphertext sizes in BE schemes satisfying anonymity (ANO-BE for short). More precisely, their lower bound is derived under the assumption that ANO-BE schemes have a special property. However, it is insufficient to show their lower bound is asymptotically tight since it is unclear whether existing ANO-BE schemes meet the special property. In this work, we derive asymptotically tight lower bounds on the ciphertext size in ANO-BE by assuming only properties that most existing ANO-BE schemes satisfy. With a similar technique, we first derive asymptoticallyPlease provide MSC codes. For more details, please visit http://www.ams.org/msc/. tight lower bounds on the authenticator sizes in Anonymous Broadcast Authentication (ABA). Furthermore, we extend the above result and present (non-asymptotically) tight lower and upper bounds on thePlease check and confirm the Running title. ciphertext sizes in ANO-BE. We show that a variant of ANO-BE scheme proposed by Li and Gong (ACNS 2018) is optimal. We also provide tight bounds on the authenticator sizes in ABA via the same approach as ANO-BE, and propose an optimal construction for ABA.

S1. Measurement of the number of CD163+ cells and their expression intensities in ESCC specimens. S2. IHC staining of CSF-1, IL-34, E-cadherin, and vimentin in ESCC specimens. S3. Correlation between mRNA expression of CD163 and CSF-1 in patients with ESCC who underwent curative esophagectomy without any preoperative therapy. S4. The effect of CSF-1 expression of NAC responsivity and tumor progression after NAC in ESCC. S5. Involvement of higher fold-change of IL-34 expression after CDDP treatment to poorer chemo-sensitivity in ESCC cells. S6. Enhanced mRNA expression of IL-34 in CDDP-resistant human ESCC cells.

The tumor microenvironment (TME) plays a key role in the efficacy of neoadjuvant chemotherapy (NAC) in solid tumors including esophageal squamous cell carcinoma (ESCC). However, the TME profile of ESCC treated with NAC is not fully understood. In this study, we investigated the effect of NAC on the TME especially tumor-associated macrophages (TAM), the important immunosuppressive components of the TME, in ESCC. We quantified the expression of CD163, a crucial marker of TAM, in pretherapeutic biopsy and surgically resected ESCC specimens from patients who received NAC (n = 33) or did not receive NAC (n = 12). We found that NAC dramatically increased the expression of CD163 on TAMs in ESCC. Colony-stimulating factor 1 (CSF-1) and IL34 are crucial cytokines that recruit monocytes into tumor sites and differentiate them into TAMs. Interestingly, NAC significantly upregulated the expression of IL34 but not CSF-1 on tumor cells, and the frequencies of CD163+ TAMs were significantly correlated with IL34 expression in ESCC after NAC. The expression of IL34 in NAC-nonresponsive patients was significantly higher than that in NAC-responsive patients, and patients with IL34-high ESCC exhibited worse prognosis as compared with patients with IL34-low ESCC. We also demonstrated that 5-fluorouracil (5-FU)/cisplatin preferentially increased mRNA expression of IL34 on human ESCC cell lines. Human peripheral blood monocytes co-cultured with ESCC cells treated with 5-FU/cisplatin increased the expression of CD163, which was attenuated by the treatment with CSF-1R inhibitors. These data suggest that IL34 expression by NAC shifts the TME toward CD163+ TAM-rich immunosuppressive and chemo-insensitive microenvironment in ESCC.Implications:The blockade of IL34 signaling may offer a novel therapeutic strategy against chemoresistance in ESCC by inhibiting M2-TAM polarization.

Card-based cryptography is a variety of secure multiparty computation (MPC). Recently, a new technique called private operations was introduced because the protocol can be implemented with fewer cards than that by using the conventional technique called the shuffle. For example, Nakai et al. showed that if the private operations are available, secure computations of AND and OR operations for two inputs can be realized simultaneously by using four cards, and the protocol is applied to a four-card majority voting protocol with three inputs. This paper shows that only three cards are sufficient to construct a majority voting protocol with three inputs. Specifically, we propose two constructions of three-input majority voting protocols. One is a protocol assuming that players can announce their output, and the other is not allowed. Compared to Nakai et al.’s protocol, the protocol with the announcement is realized without any additional private operations and communications. On the other hand, the second construction requires two more private operations and communications because it removes the assumption on the announcement from the first construction. More importantly, the idea of the second protocol can be extended to an n-input majority voting protocol with n cards, which is the main result of this paper.

Background Postoperative pneumonia is one of the major complications after esophagectomy. The aim of this study was to determine whether bacterial cultures before esophagectomy could predict occurrence of postoperative pneumonia and help treatment strategies for postoperative pneumonia. Methods Sixty-nine patients who underwent subtotal esophagectomy at Fukushima Medical University hospital between January 2017 and May 2021 were included in this study. We collected sputum, oral and/or nasopharyngeal swabs for bacterial culture preoperatively from all patients and from those who were suspected of postoperative pulmonary infections. We compared cultured pathogenic bacteria obtained preoperatively and postoperatively from patients who developed postoperative pneumonia, and investigated their association with incidence of postoperative pneumonia. Fisher’s exact test was used to compare categorical variables between groups, and Wilcoxon test was used to compare continuous variables. Risk factors for postoperative pneumonia and severe pneumonia were analyzed using multivariate logistic regression models. Results Postoperative pneumonia occurred in 22 (31%) of the 69 patients, and 13 of the 22 patients were classified as with severe pneumonia. Multivariate analysis revealed that longer operative duration (for 30 minutes increase; odds ratio 1.27, 95% confidence interval 1.01–1.51, p=0.039) and positivity for preoperative bacterial culture (odds ratio 5.03, 95% confidence interval 1.31–19.2, p=0.018) were independent risk factors for severe postoperative pneumonia, but not for all incidence of postoperative pneumonia. Of note, in only 5 out of the 22 patients with pneumonia, the same pathogen species were detected preoperatively and after the onset of pneumonia. Conclusions In conclusion, our results implied that preoperative bacterial culture may be useful to predict severe postoperative pneumonia. However, it may not be useful in determining pathogenic bacteria responsible for postoperative pneumonia.

Background: Laparoscopic and endoscopic cooperative surgery (LECS) is a well-recognized surgical procedure for gastric gastrointestinal stromal tumor (GIST). In this report, we describe the clinical outcomes of LECS procedures for gastric GIST in our institution. Methods: We performed LECS procedures, including classical LECS, inverted LECS, closed LECS, and combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique (CLEAN-NET), in 40 gastric intraluminal and intramural type GIST patients, whose tumors were ≤ 50 mm in diameter, between September 2012 and December 2020. The patient background, surgical outcomes, postoperative morbidity and mortality, as well as the tumors' clinicopathological characteristics were analyzed retrospectively. Results: Pathological findings showed that most patients had a low or very low risk of tumor recurrence, while one patient had a high risk according to the modified-Fletcher's classification. The median length of postoperative hospital stay was 7 days. Only one patient had severe postoperative grade III complications according to the Clavien-Dindo (C-D) classification, after closed LECS, but was treated successfully with endoscopic hemostasis for postoperative hemorrhage. The remaining patients treated with LECS did not have severe complications. During the follow-up period (median, 31 months), all patients were disease-free, with no tumor recurrence or metastases. Conclusion: LECS is a safe surgical procedure for gastric intraluminal and intramural type GIST ≤ 50 mm in diameter, with good clinical outcomes.

Trastuzumab deruxtecan (T-DXd), a HER2-targeting antibody–drug conjugate with a topoisomerase I inhibitor deruxtecan (DXd), exhibits an excellent anti-tumor effect in previously treated HER2-positive tumors. A recent study demonstrated that T-DXd not only suppressed tumor growth but also enhanced anti-tumor immunity through increasing the number of tumor-infiltrating CD8+ T cells and enhancement of major-histocompatibility-complex class I expression on tumor cells in a mouse model. However, the effect of T-DXd on anti-tumor immune responses in human cancers is largely unknown. We investigated the effect of T-DXd on the expression of HLA class I and CXCL9/10/11, T-cell chemoattractants, in HER2-positive human gastric cancer (GC) cells. We found that T-DXd significantly inhibited GC cell proliferation in a HER2-dependent manner, while it slightly increased the expression of HLA class I in HER2-positive GC cells. Moreover, we revealed that T-DXd significantly induced mRNA expression of CXCL9/10/11 in HER2-positive GC cells. T-DXd-triggered up-regulation of these chemokines was mediated through the activation of DNA damage signaling pathways. These results suggest that T-DXd triggers anti-tumor immune responses at least in part through induction of the expression of HLA class I and CXCL9/10/11 on HER2-positive GC cells, resulting in the enhancement of anti-tumor immunity in human GC.

Revocable identity-based encryption (RIBE) is an extension of IBE with an efficient key revocation mechanism. Revocable hierarchical IBE (RHIBE) is its further extension with key delegation functionality. Although there are various adaptively secure pairing-based RIBE schemes, all known hierarchical analogues only satisfy selective security. In addition, the currently known most efficient adaptively secure RIBE and selectively secure RHIBE schemes rely on non-standard assumptions, which are referred to as the augmented DDH assumption and q-type assumptions, respectively. In this paper, we propose a simple but effective design methodology for RHIBE schemes. We provide a generic design framework for RHIBE based on an HIBE scheme with a few properties. Fortunately, several state-of-the-art pairing-based HIBE schemes have the properties. In addition, our construction preserves the sizes of master public keys, ciphertexts, and decryption keys, as well as the complexity assumptions of the underlying HIBE scheme. Thus, we obtain the first RHIBE schemes with adaptive security under the standard k-linear assumption. We prove adaptive security by developing a new proof technique for RHIBE. Due to the compactness-preserving construction, the proposed R(H)IBE schemes have similar efficiencies to the most efficient existing schemes.

Revocation functionality is vital to real-world cryptographic systems for managing their reliability. In the context of identity-based encryption (IBE), Boldyreva, Goyal, and Kumar (ACM CCS 2008) first showed an efficient revocation method for IBE, and such an IBE scheme with the scalable revocation method is called revocable IBE (RIBE). Seo and Emura (PKC 2013) introduced a new security notion, called decryption key exposure resistance (DKER), which is a desirable security notion for RIBE. However, all existing RIBE schemes that achieve adaptive security with DKER require long public parameters or composite-order bilinear groups. In this paper, we first show an RIBE scheme that (1) satisfies adaptive security; (2) achieves DKER; (3) realizes constant-size public parameters; and (4) is constructed over prime-order bilinear groups. Our core technique relies on Seo and Emura's one (PKC 2013), which transform the Waters IBE (EUROCRYPT 2005) to the corresponding RIBE scheme. Specifically, we construct an IBE scheme that satisfies constant-size public parameters over prime-order groups and some requirements for the Seo-Emura technique, and then transform the IBE scheme to an RIBE scheme. We also discuss how to extend the proposed RIBE scheme to a chosen-ciphertext secure one and server-aided one (ESORICS 2015).

The tumor microenvironment (TME) plays a key role in the efficacy of neoadjuvant chemotherapy (NAC) in solid tumors including esophageal squamous cell carcinoma (ESCC). However, the TME profile of ESCC treated with NAC is not fully understood. In this study, we investigated the effect of NAC on the TME especially tumor-associated macrophages (TAM), the important immunosuppressive components of the TME, in ESCC. We quantified the expression of CD163, a crucial marker of TAM, in pretherapeutic biopsy and surgically resected ESCC specimens from patients who received NAC (n = 33) or did not receive NAC (n = 12). We found that NAC dramatically increased the expression of CD163 on TAMs in ESCC. Colony-stimulating factor 1 (CSF-1) and IL34 are crucial cytokines that recruit monocytes into tumor sites and differentiate them into TAMs. Interestingly, NAC significantly upregulated the expression of IL34 but not CSF-1 on tumor cells, and the frequencies of CD163+ TAMs were significantly correlated with IL34 expression in ESCC after NAC. The expression of IL34 in NAC-nonresponsive patients was significantly higher than that in NAC-responsive patients, and patients with IL34-high ESCC exhibited worse prognosis as compared with patients with IL34-low ESCC. We also demonstrated that 5-fluorouracil (5-FU)/cisplatin preferentially increased mRNA expression of IL34 on human ESCC cell lines. Human peripheral blood monocytes co-cultured with ESCC cells treated with 5-FU/cisplatin increased the expression of CD163, which was attenuated by the treatment with CSF-1R inhibitors. These data suggest that IL34 expression by NAC shifts the TME toward CD163+ TAM-rich immunosuppressive and chemo-insensitive microenvironment in ESCC. Implications: The blockade of IL34 signaling may offer a novel therapeutic strategy against chemoresistance in ESCC by inhibiting M2-TAM polarization.

Infant gut microbiota development affects the host physiology throughout life, and short-chain fatty acids (SCFAs) are promising key metabolites mediating microbiota-host relationships. Here, we investigated dense longitudinally collected faecal samples from 12 subjects during the first 2 years (n = 1048) to identify early life gut SCFA patterns and their relationships with the microbiota. Our results revealed three distinct phases of progression in the SCFA profiles: early phase characterised by low acetate and high succinate, middle-phase characterised by high lactate and formate and late-phase characterised by high propionate and butyrate. Assessment of the SCFA–microbiota relationships revealed that faecal butyrate is associated with increased Clostridiales and breastfeeding cessation, and that diverse and personalised assemblage of Clostridiales species possessing the acetyl-CoA pathway play major roles in gut butyrate production. We also found an association between gut formate and some infant-type bifidobacterial species, and that human milk oligosaccharides (HMO)-derived fucose is the substrate for formate production during breastfeeding. We identified genes upregulated in fucose and fucosylated HMO utilisation in infant-type bifidobacteria. Notably, bifidobacteria showed interspecific and intraspecific variation in the gene repertoires, and cross-feeding of fucose contributed to gut formate production. This study provides an insight into early life SCFA–microbiota relationships, which is an important step for developing strategies for modulating lifelong health.