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Field documentation of archaeological sites and built heritage by point-cloud is very effective in yielding arbitrary 3- dimensional shapes of various objects. There are several options for methods and devices such as TLSs, Mobile scanners, and SfM-MVS-based CRP. These are based on different technology, mechanism, and algorithm. Therefore, it is difficult to compare their precision, resolution, and measurement error in the same manner under practical conditions rather than catalog specification. The authors plan and carry out a field experiment of 3D point-cloud measurement in an archaeological site to obtain sample data for comparison between methods and devices under controlled conditions. Through comparative analysis, we evaluate character and advantage, as well as comparative measurement errors between methods and devices, then argue the combined use of different methods and devices under the “Multi-scale 3D scan strategy”.

We fabricated ytterbium-doped yttrium aluminum oxide (Yb:Y–Al–O) thin films by radio-frequency magnetron sputtering and evaluated their crystallinity and anti-Stokes photoluminescence (PL) properties for optical refrigeration. The Yb:Y–Al–O films that were grown on c-sapphire substrates had better transparency than the films deposited on fused-quartz substrates. The better transparency is considered to be a result of the smaller mismatch between the thermal expansion coefficients of Yb:Y–Al–O and c-sapphire. We found that the thin films on the c-sapphire substrates consist of densely packed sub-micron columnar crystals that are aligned perpendicular to the substrate. In these films, we confirmed the existence of perovskite, garnet, and monoclinic phases despite using a single-phase sputtering target. The excitation wavelength dependence of anti-Stokes PL is used to investigate the energy transfer process between trivalent Yb ions in neighboring columnar crystals. The data indicate that the resonant energy transfer from Yb3+ ions at a specific seven-coordinated site of the monoclinic phase to Yb3+ ions in neighboring columnar crystals is faster than the radiative relaxation at the energy-donor site.

Background: Oily fish and their extracted oils may be a source of polychlorinated biphenyls (PCBs) which can induce toxic effects on the consumers. The main aim of this survey was estimation of PCBs intake through fish oil-derived dietary supplements and prescription drugs in the Japanese population. Methods: PCBs levels were determined in 20 fish oil-derived dietary supplements and 6 oil-derived prescription drugs from the Japanese market using Gas Chromatography-Mass Spectrometry. Then, the daily exposure to PCBs was estimated. Data were statistically analyzed using JMP software suite. Results: Totally, 17 of the 26 fish oil-derived products were contaminated with PCBs. The median PCB concentrations in the total set of fish oil-derived products was 2.2 ng/g oil wt. with a range of

Abstract Reflection states are introduced in the vertical and horizontal modules of the Ding-Iohara-Miki (DIM) algebra (quantum toroidal gl1 $$ \mathfrak{g}{\mathfrak{l}}_1 $$). Webs of DIM representations are in correspondence with (p, q)-web diagrams of type IIB string theory, under the identification of the algebraic intertwiner of Awata, Feigin and Shiraishi with the refined topological vertex. Extending the correspondence to the vertical reflection states, it is possible to engineer the N=1 $$ \mathcal{N}=1 $$ quiver gauge theory of D-type (with unitary gauge groups). In this way, the Nekrasov instanton partition function is reproduced from the evaluation of expectation values of intertwiners. This computation leads to the identification of the vertical reflection state with the orientifold plane of string theory. We also provide a translation of this construction in the Iqbal-Kozcaz-Vafa refined topological vertex formalism.

Abstract Instanton partition functions of N=1 $$ \mathcal{N}=1 $$ 5d Super Yang-Mills reduced on S 1 can be engineered in type IIB string theory from the (p, q)-branes web diagram. To this diagram is superimposed a web of representations of the Ding-Iohara-Miki (DIM) algebra that acts on the partition function. In this correspondence, each segment is associated to a representation, and the (topological string) vertex is identified with the intertwiner operator constructed by Awata, Feigin and Shiraishi. We define a new intertwiner acting on the representation spaces of levels (1, n) ⊗ (0, m) → (1, n + m), thereby generalizing to higher rank m the original construction. It allows us to use a folded version of the usual (p, q)-web diagram, bringing great simplifications to actual computations. As a result, the characterization of Gaiotto states and vertical intertwiners, previously obtained by some of the authors, is uplifted to operator relations acting in the Fock space of horizontal representations. We further develop a method to build qq-characters of linear quivers based on the horizontal action of DIM elements. While fundamental qq-characters can be built using the coproduct, higher ones require the introduction of a (quantum) Weyl reflection acting on tensor products of DIM generators.

Despite their role in oceanic CaCO3production, the physiological processes responsible for calcification in foraminifera are poorly understood Here, the authors show that calcification is driven by rapid transformation of bicarbonate to carbonate inside the cytoplasm, achieved by active outward proton pumping.

BACKGROUND: In the absence of stimuli, most motile eukaryotic cells move by spontaneously coordinating cell deformation with cell movement in the absence of stimuli. Yet little is known about how cells change their own shape and how cells coordinate the deformation and movement. Here, we investigated the mechanism of spontaneous cell migration by using computational analyses. METHODOLOGY: We observed spontaneously migrating Dictyostelium cells in both a vegetative state (round cell shape and slow motion) and starved one (elongated cell shape and fast motion). We then extracted regular patterns of morphological dynamics and the pattern-dependent systematic coordination with filamentous actin (F-actin) and cell movement by statistical dynamic analyses. CONCLUSIONS/SIGNIFICANCE: We found that Dictyostelium cells in both vegetative and starved states commonly organize their own shape into three ordered patterns, elongation, rotation, and oscillation, in the absence of external stimuli. Further, cells inactivated for PI3-kinase (PI3K) and/or PTEN did not show ordered patterns due to the lack of spatial control in pseudopodial formation in both the vegetative and starved states. We also found that spontaneous polarization was achieved in starved cells by asymmetric localization of PTEN and F-actin. This breaking of the symmetry of protein localization maintained the leading edge and considerably enhanced the persistence of directed migration, and overall random exploration was ensured by switching among the different ordered patterns. Our findings suggest that Dictyostelium cells spontaneously create the ordered patterns of cell shape mediated by PI3K/PTEN/F-actin and control the direction of cell movement by coordination with these patterns even in the absence of external stimuli.

We propose a resonant-type LiNbO3 optical modulator with low halfwave voltage. We optimize the phase constant of the electric wave with thick electrodes to reduce the halfwave voltage. The halfwave voltage of the fabricated modulator with 20-μm-thick electrodes is 5.8 V at 10.6 GHz. [ABSTRACT FROM PUBLISHER]

We consider a geometrical model of a broken interface showing self-propelling motion. This model is constructed to comprise a static solution with a spontaneous curvature. Furthermore, by introducing a nonlocal interaction force into the geometrical model, we show that the static solution causes spontaneous drift motion even when the nonlocal force is infinitesimal. This drift motion appears via transcritical bifurcation. [ABSTRACT FROM AUTHOR]

The discovery and elucidation of the surface microstructure functions of living organisms are crucial to resolving issues, such as friction. We newly discovered that Necrophila japonica , a type of carrion beetle that lives on the ground surface, exhibited a hierarchical surface microstructure comprising a submicron-sized wrinkle structure on top of a micron-sized microstructure. The surface microstructure of this beetle improved wettability but did not exhibit superhydrophobicity, a well-known function of hierarchical structures, so it was expected to have a different function. By combining the insights in the field of structural mechanics that avoidance of stress concentration by the structural geometry affects deformation with the basic principles of friction, the frictional properties and mechanisms of the hierarchical surface microstructure of carrion beetle were investigated. The measurements of frictional force indicated that the mimicked structure exerted lower frictional forces than flat and single-layer microstructure surfaces. Analysis of finite element method simulations showed that even though the mimicked structure was prone to pressure concentration due to small contact points, the surface contact pressure was reduced more than that of the single-layer structure by hierarchical load dispersion like that of metamaterials. As a result, the suppression of the increase in the real contact area due to deformation suppression contributed to effective friction-reduction. The effective friction-reduction by the hierarchical structure provides not only new insight into the surface microstructure function of various organisms, but also new design for the lubricant-free friction reduction that has been the focus of attention in carbon neutrality and other fields.

Competing Interests: Disclosure There are no conflict of interest.

In yeast, multiprotein bridging factor 1 (Mbf1) has been proposed to function in the integrated stress response (ISR) as a transcriptional coactivator by mediating a direct interaction between general transcription machinery and the process's key effector, Gcn4. However, mounting evidence has demonstrated that Mbf1 (and its human homolog EDF1) is recruited to collided ribosomes, a known activator of the ISR. In this study, we connect these otherwise seemingly disparate functions of Mbf1. Our biochemical and structural analyses reveal that Mbf1 functions as a core ISR factor by interacting with collided ribosomes to mediate Gcn2 activation. We further show that Mbf1 serves no role as a transcriptional coactivator of Gcn4. Instead, Mbf1 is required for optimal stress-induced eukaryotic initiation factor 2α (eIF2α) phosphorylation and downstream de-repression of GCN4 translation. Collectively, our data establish that Mbf1 functions in ISR signaling by acting as a direct sensor of stress-induced ribosome collisions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Peripherally unsubstituted dioxadiaza[8]circulene, as the first example of structurally identified pristine hetero[8]circulene, was synthesized by the substituent detachment reactions. The solid-state structures and photophysical properties were analysed to elucidate intermolecular interactions. Herzberg-Teller type emission was considered to explain the optical behavior.

Background: Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients undergoing immunosuppressive therapy, such as glucocorticoid (GC) medication, for systemic autoimmune diseases like systemic lupus erythematosus (SLE). Despite the confirmed effectiveness of PCP prophylaxis, its clinical administration, especially in conjunction with GC dosage, remains unclear. We aimed to describe the clinical practice of PCP prophylaxis in association with SLE in Japan, evaluate the relationship between GC dosage and PCP prophylaxis, and explore the practice patterns associated with PCP prophylaxis., Methods: This cross-sectional study used data from the Lupus Registry of Nationwide Institutions in Japan from 2016 to 2021 and included patients diagnosed with SLE. Using descriptive statistics, multivariate analysis, and decision tree analysis, we examined the prevalence of PCP prophylaxis and its association with the GC dosage., Results: Out of 1,460 patients, 21% underwent PCP prophylaxis. The frequency of prophylaxis decreased with a decrease in GC dosage. After adjusting for confounders, logistic regression revealed the odds ratio of PCP prophylaxis increased with higher prednisolone (PSL) doses: 3.7 for 5 ≤ PSL < 7.5 mg, 5.2 for 7.5 ≤ PSL < 10 mg, 9.0 for 10 ≤ PSL < 20 mg, and 43.1 for PSL ≥ 20 mg, using PSL < 5 mg as the reference. Decision tree analysis indicated that a PSL dosage of < 11 mg/day and immunosuppressant use were key determinants of PCP prophylaxis., Conclusion: This study provides valuable insights into PCP prophylaxis practices in patients with SLE in Japan, underscoring the importance of GC dosage and concomitant immunosuppressant use., Competing Interests: Declarations Ethics approval and informed consent This study was conducted in accordance with the Declaration of Helsinki and Ethical Guidelines for Epidemiologic Research in Japan. The study protocol was approved by the Ethics Committee of Kakogawa Central City Hospital (authorization number: 2021–04). The patients provided written informed consent to participate in the and permission to publish their data. Consent for publication Not applicable. Competing interests KS received speaker fees from Glaxo Smith Kline and a research grant from Pfizer Inc. TY received speaker fees from Glaxo Smith Kline., (© 2024. The Author(s).)

Background: Although durvalumab has shown promise in improving survival rates in patients with locally advanced non-small cell lung cancer (NSCLC), the ideal duration of treatment has yet to be established., Objective: The primary objective of this study was to determine the optimal number of durvalumab cycles following definitive chemoradiotherapy for locally advanced NSCLC., Patients and Methods: A total of 178 patients who received chemoradiotherapy for stage III NSCLC at 15 institutions were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were assessed according to the number of consolidation durvalumab cycles by landmark analysis. Landmark analyses were performed at 3-month intervals from the start of durvalumab treatment to 9 months., Results: The median number of durvalumab cycles was 16 (range 1-27). PFS and OS were significantly better in patients who received ≥20 cycles of durvalumab than in those who did not (p < 0.001 and p < 0.001, respectively). In landmark analysis, significant differences were observed in PFS from 0 to 6 months and OS from 3 to 6 months between patients who continued durvalumab after the time point and those who did not. However, there were no significant differences in PFS or OS between patients who received 13-19 or ≥20 cycles of durvalumab at 9 months., Conclusions: Durvalumab should be administered for more than 6 months to contribute to the main benefits of consolidation therapy following chemoradiotherapy., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Creatine kinase (CK) levels decrease with cancer progression and muscle wasting, but its association with pancreatic ductal adenocarcinoma (PDAC) remains unclear. The aim of this study was to investigate CK as a prognostic biomarker and surrogate marker for muscle mass in patients with PDAC., Methods: A retrospective analysis of 476 patients with PDAC was conducted. CK levels were categorized into low and high groups using receiver-operating characteristic (ROC) curve analysis., Results: Among the 476 patients, 200 (42.0%) and 276 (58.0%) were classified into the low and high CK groups, respectively. The low CK group had significantly poorer overall survival (p < .001) and recurrence-free survival (p < .001) compared to the high CK group. Multivariate analysis identified low CK as an independent poor prognostic factor (p < .001). The low CK group had significantly lower skeletal muscle index (p = .048) than the high CK group; however, the difference was slight and not significantly associated with sarcopenia. Additionally, combined risk assessment incorporating CK and resectability facilitated a more nuanced prognostic stratification., Conclusions: CK served as a reliable prognostic marker independent from resectability but was less effective as a marker for sarcopenia in PDAC., (© 2024 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Non-conventional yeasts are increasingly being used in the production of fermented beverages owing to their ability to create unique and high-quality products. The yeast Lachancea thermotolerans is of great industrial significance, particularly in the production of l(+)-lactic acid, which is beneficial for acidifying wine, beer, and potentially sake. To explore its potential in sake brewing, three L. thermotolerans strains were isolated from natural environments and their physiological and fermentative characteristics were examined. The isolates surpassed the L. thermotolerans type strain (NBRC 1985) in lactic acid production under various culture conditions and exhibited comparable growth rates to that of Saccharomyces cerevisiae at 15-20 °C. Sake brewing tests using these isolates yielded approximately 3500 ppm of lactic acid, with a slightly lower production of aroma components compared to that produced by sake yeast, and an ethanol content of approximately 11-12 % was obtained. Reverse transcription-quantitative polymerase chain reaction revealed variable expression in putative lactate dehydrogenase genes depending on the culture conditions. Our findings suggest that L. thermotolerans strains can be used in sake brewing to produce unique sake., (Copyright © 2024 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Background: Hyperglycemia is involved in malignant transformation of pancreatic cancer via the hexosamine biosynthetic pathway (HBP). However, few studies have verified this mechanism based on clinical data. This study investigated the complementary effects of hyperglycemia and HBP on pancreatic cancer prognosis using detailed clinical data., Methods: The study analyzed data of 477 patients with pancreatic cancer who underwent pancreatectomy between 2006 and 2020. The patients were divided into normoglycemia and hyperglycemia groups based on their HbA1c levels. Immunostaining for glutamine fructose-6-phosphate transaminase-1 (GFAT-1), the rate-limiting enzyme in HBP, CD4, CD8, and Foxp3, was performed to evaluate the association between survival outcomes, HBP, and local tumor immunity., Results: Overall survival (OS) was significantly poorer in the hyperglycemia group than in the normoglycemia group (mean survival time [MST]: 35.0 vs. 47.9 months; p = 0.007). The patients in the hyperglycemia group with high GFAT-1 expression had significantly poorer OS than those with low GFAT-1 expression (MST, 49.0 vs. 27.6 months; p < 0.001). However, the prognosis did not differ significantly between the patients with high and low GFAT-1 expression in the normoglycemia group. In addition, the patients with hyperglycemia and high GFAT-1 expression had fewer CD4 + (p = 0.015) and CD8 + (p = 0.017) T cells and a lower CD8 + /Foxp3 + ratio (p = 0.032) than those with hyperglycemia and low GFAT-1 expression., Conclusions: The patients with hyperglycemia and high GFAT-1 expression levels had an extremely poor prognosis. Furthermore, the tumors in these patients were characterized as immunologically cold tumors., (© 2024. Society of Surgical Oncology.)

Proton-transfer mechanisms and hydration states were investigated in chitin films possessing the functionality of fuel-cell electrolytes. The absolute hydration number per chitin molecule (N) as a function of relative humidity (RH) was determined from the OH stretching bands of H2O molecules, and the proton conductivity was found to enhance above N = 2 (80%RH). The FIR spectrum at 500-900 cm-1 for 20%RH (N < 1) together with first-principles calculations clearly shows that the w1 site has the same hydration strength as the w2 site. The molecular dynamics simulations for N = 2 demonstrate that H2O molecules with tiny fluctuations are localized on w1 and w2, and the hydrogen-bond (HB) network is formed via the CH2OH group of chitin molecules. Shrinkage of the O-O distance (dOO), which synchronizes with the barrier height, is required for proton transfer from H3O+ to adjacent CH2OH groups or H2O molecules. Nevertheless, dOO is hardly modulated for N = 2 because H2O molecules are strongly constrained on w1 and w2, and therefore, the transfer probability becomes small. For N = 3, novel HBs emerged between the additional H2O molecules broadly distributed on the w3 site and H2O molecules on w1 and w2. The transfer probability is enhanced because large fluctuations and diffusions in the whole H2O molecule yield large modulations of dOO. Consequently, long-range proton hopping is driven by the Zundel-type protonated hydrates in the water network., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Particle therapy (PT) as an initial hepatocellular carcinoma (HCC) treatment has been reported to be effective; however, its efficacy for the treatment of recurrent HCC remains unclear., Objective: This study aimed to evaluate the efficacy of PT compared with repeat liver resection for treating recurrent HCC after initial LR, with a focus on prognostic outcomes., Methods: Between 2005 and 2019, 89 and 49 patients underwent repeat LR and PT for recurrent HCC after initial LR, respectively. The 5-year overall survival (OS) and recurrence-free survival (RFS) were evaluated using propensity score matching. Treatment-related complications were scored using the National Institute Common Terminology Criteria for Adverse Events (CTCAE) and were compared between the repeat LR and PT groups., Results: In the entire cohort, the 5-year OS was significantly better in the repeat LR group than in the PT group (75% vs. 48%; p = 0.0003), and the 5-year RFS was comparable in both groups (22% vs. 13%; p = 0.088). Propensity score matching created 34 pairs of patients; no significant differences in the 5-year OS (65% vs. 48%; p = 0.310) and RFS (21% vs. 8%; p = 0.271) were observed between the repeat LR and PT groups. The proportion of CTCAE grade ≥3 complications was 8.8% and 5.9% in the repeat LR and PT groups, respectively (p = 0.641)., Conclusions: After initial LR, the prognosis and treatment-related complications in patients with recurrent HCC were comparable between the repeat LR and PT groups in the matched cohort; therefore, PT may remain one of the multidisciplinary treatment options for recurrent HCC., (© 2024. Society of Surgical Oncology.)

Coenzyme Q (CoQ) or ubiquinone functions as an electron transporter in the electron transport system in both prokaryotes and eukaryotes. The isoprenyl side chain of CoQ is modified in some organisms, especially in fungi, for optimal electron transport performance under various conditions. In this study, we investigated the side chain saturated dihydro CoQ (CoQ10(H2)) in Aureobasidium pullulans EXF-150, Sydowia polyspora NBRC 30562, and naturally isolated Plowrightia sp. A37, all of which are melanized Dothideomycetes species within the Ascomycota, and also in filamentous fungi Aspergillus oryzae and Aspergillus terreus. Plowrightia sp. A37 produced the rarely synthesized tetrahydro type CoQ10(H4), especially in glucose-rich medium, during extended cultivation in contrast to CoQ10(H2) in time-limited cultivation. Using liquid chromatography-mass spectrometry, we identified demethoxyubiquinone-H2 (DMQ(H2)) as an indicative intermediate that suggests that the side chain-saturation of CoQ occurs after the formation of DMQ and not always in the last step as previously considered., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Background: CD200, a negative regulator of T cells as well as a marker for cancer stem cells, represents a significant prognostic factor and potential therapeutic target in certain cancers. However, its clinical significance remains unknown in pancreatic ductal adenocarcinoma (PDAC)., Methods: CD200 was assessed in 220 resected PDAC patients who underwent surgery with or without neoadjuvant chemoradiotherapy (NACRT). We examined the clinicopathological outcomes associated with CD200 and further assessed its clinical implications regarding immunological and cancer stem cell properties., Results: NACRT was associated with higher CD200 expression (66.4 % vs. 32.2 %, P < 0.001) compared to upfront surgery. CD200 was identified as an independent poor prognostic factor in NACRT (hazard ratio 1.90, 95 % confidence interval 1.12-3.23, P = 0.016), but not in upfront surgery patients. Post-recurrence survival was significantly worse in CD200+ patients compared to CD200- patients in the NACRT group, but there was no significant difference observed in the upfront surgery group. CD200 expression was correlated with significantly lower levels of CD4 + , CD8 + , and CD45RO +  tumor-infiltrating lymphocytes. Furthermore, the correlation of CD200 with pancreatic cancer stem cell markers CD44/CD24/ESA was stronger in irradiated human pancreatic cancer cells., Conclusions: Our data underscore novel roles for CD200 in immune evasion as well as therapy resistance in pancreatic cancer. CD200 may represent a novel poor prognostic predictive factor and potential therapeutic target for PDAC with NACRT., (Copyright © 2024. Published by Elsevier B.V.)

Background: Long-term data on the effectiveness and safety of omalizumab for chronic inducible urticaria (CIndU) in large populations are lacking., Objective: To evaluate the effectiveness, safety, estimated omalizumab treatment duration and its predictors, as well as differences between CIndU subtypes, in a large long-term CIndU cohort., Methods: A multinational multicenter study was conducted at 14 specialized urticaria centres (UCAREs), including all CIndU patients ever treated with omalizumab from 2009 until July 2022. Kaplan-Meier survival and regression analyses were performed., Results: Across 234 CIndU patients (55% female; mean age 37 years), 76% (n = 178) had standalone CIndU and 24% (n = 56) had predominant CIndU plus minor CSU, with an observation period up to 13 years. Most CIndU patients (73%, n = 145/200 with available data on response) had complete/good response to omalizumab treatment, without significant differences between CIndU subtypes. Sixty-two (26%) patients discontinued omalizumab; due to well-controlled disease (47%, n = 29), ineffectiveness (34%, n = 21), side effects (3%, n = 2), combination of ineffectiveness and side effects (3%, n = 2) and other reasons (13%, n = 8). The median estimated omalizumab treatment duration exceeded 5 years (54% drug survival at 5 years) and was mostly determined by well-controlled disease. Higher age predicted a lower chance to discontinue omalizumab due to well-controlled disease (HR 0.969, 95%CI 0.945-0.995). CIndU subtype and presence of minor CSU were not related to response and time until omalizumab discontinuation for any reason., Conclusion: Omalizumab is highly effective and safe in CIndU patients, with long estimated treatment duration mainly reflecting long disease duration. Our data show omalizumab's high potential as treatment in any subtype of CIndU and support its clinical use for these patients., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Aim: Persistent acute kidney injury (AKI) has not been investigated in patients undergoing liver resection. We aimed to identify the predictors of persistent AKI, its effect on postoperative outcomes and long-term renal function in patients following liver resection, and its impact on survival in patients with hepatocellular carcinoma (HCC)., Methods: We examined 990 patients who underwent liver resection, including a subgroup analysis of 384 patients with curative resection for initial HCC. Persistent AKI was defined as residual impairment of serum creatinine ≥ 0.3 mg/dL or ≥50% from baseline 1 month after surgery., Results: The persistent AKI group had significantly worse postoperative outcomes, including overall morbidity, major morbidity, longer hospital stay, and 90-day mortality. In the subgroup analysis of patients with HCC, persistent AKI was associated with a significantly poorer overall survival (OS) rate (p < 0.001), and the multivariate analysis confirmed persistent AKI as an independent poor prognostic factor for OS (p = 0.005). The long-term postoperative estimated glomerular filtration rate decline was significantly greater in the persistent AKI group than in the no AKI and transient AKI groups (p < 0.001 for both). Chronic kidney disease, albumin-bilirubin grade ≥2, and anatomical resection were independent predictors of persistent AKI (p = 0.001, p = 0.039, and p = 0.015, respectively)., Conclusions: Persistent AKI adversely affects postoperative outcomes and long-term renal function in patients undergoing liver resection. Furthermore, it is associated with poor prognosis in patients with HCC. Therapeutic strategies to prevent persistent AKI are critical for improving postoperative outcomes in these patients., (© 2024 Japan Society of Hepatology.)

Extraperitoneal colostomy is often selected to reduce the risk of parastomal hernia. However, its closure surgery is rare and seldom reported. Here, we report our unique experience with robotic left hemicolectomy and extraperitoneal colostomy closure. An 83-year-old female was diagnosed with descending colon cancer with stenosis. She had previously undergone abdominoperineal resection with extraperitoneal colostomy. After improving the intestinal obstruction with a self-expanding stent, we performed robotic left hemicolectomy and extraperitoneal colostomy closure. Thanks to the multijoint function of the robot, which enables the forceps to be angled up to 90° in all directions, we could dissect the stoma from the abdominal wall up to just beneath the rectus abdominis in an intra-abdominal procedure without enlarging the skin incision. This case suggests that robotic surgery with the articulating function is beneficial for procedures near the abdominal wall ceiling and effective for extraperitoneal colostomy closure., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background and Purpose: This study aims to externally validate a predictive model for distant metastasis (DM) with computed tomography (CT)-based radiomics features in prospectively enrolled non-small-cell lung cancer patients undergoing dynamic tumor-tracking stereotactic body radiation therapy (DTT-SBRT)., Materials and Methods: The study collected retrospective data from 567 patients across 11 institutions as the training dataset and prospectively enrolled 42 patients from four institutions as the external test dataset. Four clinical features were collected, and 944 CT-based radiomic features were extracted from gross tumor volumes. After standardization and feature selection, DM predictive models were developed using fine and gray regression (FG) and random survival forest (RSF), incorporating clinical and radiomic features, and their combinations within the training dataset. Then, the model was applied to the test dataset, dividing patients into high- and low-risk groups based on medians of risk scores. Model performance was assessed using the concordance index (C-index), and the statistical significance between groups was evaluated using Gray's test., Results: In the training dataset, 122 of 567 patients (21.5%) developed DM, compared to 9 of 42 patients (21.4%) in the test dataset. In the test dataset, the C-indices of the clinical, radiomics, and hybrid models with FG were 0.559, 0.544, and 0.560, respectively, whereas those with RSF were 0.576, 0.604, and 0.627, respectively. The hybrid model with RSF, which exhibited the best predictive performance of all models, identified 7 of 23 patients (30.4%) as high risk and 2 of 19 patients (10.5%) as low risk for DM incidence in the test dataset (p = 0.116)., Conclusion: Although predictive models for DM lack significance when applied to prospectively enrolled cases undergoing DTT-lung SBRT, the model with RSF exhibits a consistent capacity to effectively classify patients at a high risk of developing DM., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics is published by Wiley Periodicals, Inc. on behalf of The American Association of Physicists in Medicine.)

Aims: This study aimed to investigate the association between the time to achieve walkability after cardiac surgery and the risk of cardiovascular disease after hospital discharge., Methods: We conducted a prospective cohort study involving 553 ambulatory patients aged 71.5 (range, 64.0-77.0) years who underwent cardiac surgery. All patients were divided into five groups based on the time to achieve walkability ≥100 m within 1, 2, 3, 4 or 5 days after cardiac surgery. We examined the risk of post-cardiovascular disease outcomes, including readmission due to heart failure, ischaemic heart disease and other cardiovascular disease, according to the time to achieve walkability with reference to 5 days using the Fine and Gray regression model, considering competing risks., Results: In the survival curve analysis, we examined the time to experience post-cardiovascular disease incidence after hospital discharge. During a median of 3.3 years of follow-up, 118 patients developed cardiovascular disease. We observed a positive association between the time to achieve walkability and cardiovascular disease risk, particularly heart failure. The multivariate hazard ratios (95% confidence intervals) for heart failure readmission were N/A (not assessed due to the sample size being too small) for 1 day, 0.31 (0.10-0.99) for 2 days, 0.60 (0.21-1.79) for 3 days and 0.76 (0.22-2.72) for 4 days (P for trend = 0.032)., Conclusions: The shorter walkability achievement time was associated with a lower risk of cardiovascular diseases, more specifically heart failure readmission, among patients who underwent cardiac surgery. The time required to achieve walkability is a useful predictor for cardiovascular diseases after hospital discharge., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

We aimed to clarify the long-term safety and efficacy of rituximab (RTX) as a remission induction therapy following severe relapse in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We retrospectively collected the data of patients with severely relapsed AAV from a Japanese multicentre cohort. The primary exposure was RTX use; the primary outcome was complete remission (CR) proportions at week 24. Baseline characteristics were compared between the RTX and non-RTX groups. We performed multivariate logistic regression analysis and one-to-one propensity score matching analysis as a sensitivity analysis. Totally, 100 patients were enrolled: 52 in the RTX group and 48 in the non-RTX group. Baseline characteristics were comparable between the two groups, except for age, AAV subtype and ANCA serotype. The median age was 71 vs. 75 years, and the PR3-ANCA positivity rate was 44.2% vs. 18.8% in the RTX and non-RTX groups, respectively. No significant difference was observed in CR proportions at week 24 between the two groups (79.2% vs. 68.1%, p = 0.321), with an adjusted odds ratio of 1.27 (95% confidence interval [CI] 0.47-3.51). At week 48, CR proportions were significantly higher in the RTX group (91.7% vs. 64.9%, p = 0.005), with an adjusted odds ratio of 2.95 (95% CI 0.97-9.91). Serious infection rates were lower in the RTX group than in the non-RTX group, with no statistically significant difference. RTX was not superior to conventional immunosuppressive therapies at week 24 but showed significantly favourable results at week 48 for severely relapsed AAV., (© 2024. The Author(s).)

Purpose: Stereotactic body radiation therapy (SBRT) for patients with operable stage I non-small cell lung cancer (NSCLC) is less invasive than surgery. However, differences in lifetime costs and patient outcomes remain unclear. In this study, a cost-utility analysis of SBRT compared with surgery for Japanese patients with operable stage I NSCLC was conducted., Methods and Materials: A partitioned survival model was constructed using each treatment arm's overall survival (OS) and progression-free survival (PFS) data. The data for the SBRT arm were extracted from the Japanese multicenter cohort study, which enrolled 678 medically operable patients with stage I NSCLC, and patient registry data were used for the surgery arm. The 5-year OS rate was 78.2% for SBRT and 74.8% for surgery from both studies. The 5-year PFS rate was 57.0% for SBRT and 63.4% for surgery. The quality of life values of PFS and progressive disease were obtained from domestic and overseas literature (PFS: 0.74, progressive disease: 0.65). The time horizon was set to 10 years. The expected costs and quality-adjusted life years for each treatment group were calculated. All costs are expressed in Japanese yen converted to US dollars (USD)., Results: SBRT was the dominant strategy, reducing treatment costs by 4,443.8 USD and increasing quality-adjusted life years by 0.131 compared with surgery. According to probabilistic sensitivity analysis, the probability of SBRT being dominant and cost-effective was 50.6% and 72.4%, respectively. Under the budget impact analysis, the total savings for the patients with stage I NSCLC in Japan was 6,252,870.0 USD (n = 1,407)., Conclusions: SBRT is a more cost-effective option than surgery in patients with medically operable stage I NSCLC in Japan. Large-scale epidemiologic studies that reflect the latest clinical realities, such as OS/PFS, will be needed to validate this study's robustness., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Particle therapy is effective for the treatment of soft tissue sarcomas. However, the clinical outcomes of definitive particle therapy, particularly for dedifferentiated liposarcoma (DDLS), remain unknown., Purpose: To analyze the treatment outcomes of proton and carbon ion particle therapies for DDLS., Methods: We retrospectively included patients with DDLS who were treated with particle therapy between 2008 and 2022. The local control (LC), progression-free survival (PFS), and overall survival (OS) rates were evaluated., Results: Fifty-seven patients were included in this analysis. The median patient age was 68 years (range, 36-91 years). The most common tumor site was the retroperitoneum (n = 37), with a median gross tumor volume (GTV) of 181 cm 3 . Twenty-nine patients received proton therapy, and 28 patients received carbon ion therapy. The most common fractionation dose was 70.4 Gy (relative biological effectiveness) in 32 fractions (72.7 Gy equivalent dose in 2 Gy fractions [EQD2]). The median follow-up time was 33 months (range, 1-128 months). The 3-year LC, PFS, and OS rates were 73.1 %, 44.6 %, and 70.6 %, respectively. Patients who received a higher prescribed dose (≥72.7 Gy EQD2) showed significantly better LC (p = 0.04) than did those who received a lower prescribed dose. Moreover, those with a larger GTV (≥181 cm 3 ) had significantly worse OS (p = 0.04) than did those with a smaller GTV. Late adverse events occurred in five (9 %) patients., Conclusions: Particle therapy using protons or carbon ions for the treatment of DDLS is safe and provides good OS and LC. However, further studies with longer follow-up periods and larger cohorts are warranted., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Aims: There are limited data to support direct oral anticoagulant (DOAC) use in patients with hypertrophic cardiomyopathy (HCM) and non-valvular atrial fibrillation (NVAF). The current study investigated the safety and effectiveness of DOACs versus warfarin in patients in Japan., Methods: This retrospective observational study assessed a Japanese cohort of patients diagnosed with HCM and NVAF between July 2011 and June 2021 using a Japanese claims database. Propensity score (PS) matching (2:1 DOAC:warfarin) using the nearest-neighbour method was applied to balance demographic and clinical characteristics between treatment groups. The primary outcomes were the risk of major bleeding and any bleeding (major or minor). Secondary outcomes included describing baseline demographic and clinical characteristics and the risk of stroke/systemic embolism (SE)., Results: After PS matching, 2955 DOAC- and 1603 warfarin-treated patients were assessed. The mean [standard deviation (SD)] age in the DOAC and warfarin groups was 74.8 (10.5) and 75.3 (10.2) years, respectively. The majority of patients were male (DOAC, 58.8%; warfarin, 59.6%), had comorbidities (DOAC, 97.5%; warfarin, 96.6%), and were treated with β-blockers (DOAC, 62.5%; warfarin, 62.3%). The risk of major and any bleeding was similar across cohorts [hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.50-1.27; P = 0.336 and HR, 0.93; 95% CI, 0.78-1.11; P = 0.420] while the risk of stroke/SE was lower among patients treated with DOACs (HR, 0.67; 95% CI, 0.47-0.96; P = 0.027). Factors associated with an increased risk of major bleeding included prior bleeding (HR, 1.97; 95% CI, 1.22-3.17) and chronic kidney disease (HR, 1.87; 95% CI, 1.10-3.18). An increased risk of stroke/SE was associated with prior ischaemic stroke (HR, 2.97; 95% CI, 2.05-4.29), peripheral arterial disease (HR, 1.88; 95% CI, 1.22-2.88) and chronic kidney disease (HR, 1.87; 95% CI, 1.24-2.83)., Conclusions: DOAC-treated patients had a lower risk of stroke/SE and a comparable risk of bleeding compared with warfarin-treated patients. Prior stroke was shown to augment stroke risk by approximately three-fold. This large real-world study suggests that patients diagnosed with HCM and NVAF can be safely and effectively treated with DOACs in Japan., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose: Hepatocellular carcinoma (HCC) patients beyond the Milan criteria (MC) who undergo liver resection have high recurrence rates and poor prognosis, and sometimes experience very early recurrence (VER) within six months after surgery. This study aimed to identify predictive factors, including the newly proposed C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index, for VER after surgery for HCC beyond MC., Methods: We included patients who underwent initial liver resection for HCC beyond MC between 2000 and 2021. We defined VER as recurrence within six months after surgery and compared the clinicopathological factors and long-term prognosis between the VER and non-VER groups. Multivariate analysis identified risk factors for VER and evaluated the potential for prognostic stratification using these factors., Results: The overall survival (OS) and post-recurrence survival were significantly worse in the VER group compared to patients with recurrence in 7-12 months, over 12 months, and without recurrence (median survival time (MST) 1.16 vs. 5.14, 7.26, and undefined; and MST 0.81 vs. 4.34, and 5.48, respectively, P < 0.01). Alpha-fetoprotein (AFP) ≥ 200, non-simple nodule (SN) type on preoperative imaging, and CALLY index < 2.8 were independent prognostic factors (P < 0.01 for all). An increased risk factor count was correlated with poorer VER and OS rates, allowing for effective stratification., Conclusion: VER after hepatic resection for HCC beyond MC was associated with a significantly poorer prognosis. AFP, non-SN type on imaging, and CALLY index are valuable preoperative indicators. Patients with multiple risk factors have a worse prognosis and may be candidates for multimodal treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The cytoskeleton mediates fundamental cellular processes by organizing inter-organelle interactions. Pathogenic variants of inverted formin 2 (INF2) CAAX isoform, an actin assembly factor that is predominantly expressed in the endoplasmic reticulum (ER), are linked to focal segmental glomerulosclerosis (FSGS) and Charcot-Marie-Tooth (CMT) neuropathy. To investigate how pathogenic INF2 variants alter ER integrity, we used high-resolution live imaging of HeLa cells. Cells expressing wild-type (WT) INF2 showed a predominant tubular ER with perinuclear clustering. Cells expressing INF2 FSGS variants that cause mild and intermediate disease induced more sheet-like ER, a pattern similar to that seen for cells expressing WT-INF2 that were treated with actin and microtubule (MT) inhibitors. Dual CMT-FSGS INF2 variants led to more severe ER dysmorphism, with a diffuse, fragmented ER and coarse INF2 aggregates. Proper organization of both F-actin and MT was needed to modulate the tubule vs. sheet conformation balance, while MT arrays regulated spatial expansion of tubular ER in the cell periphery. Pathogenic INF2 variants also induced mitochondria fragmentation and dysregulated mitochondria distribution. Such mitochondrial abnormalities were more prominent for cells expressing CMT-FSGS compared to those with FSGS variants, indicating that the severity of the dysfunction is linked to the degree of cytoskeletal disorganization. Our observations suggest that pathogenic INF2 variants disrupt ER continuity by altering interactions between the ER and the cytoskeleton that in turn impairs inter-organelle communication, especially at ER-mitochondria contact sites. ER continuity defects may be a common disease mechanism involved in both peripheral neuropathy and glomerulopathy.

Chemical investigations of higher plants, with particular attention paid to their steroidal glycosides, present a promising approach for generating anti-cancer agents from natural products. We conducted a systematic phytochemical investigation of nine higher plants-whole plants and rhizomes of Convallaria majalis, whole plants of Agave utahensis, roots of Adonis amurensis, seeds of Adonis aestivalis, bulbs of Bessera elegans, bulbs of Fritillaria meleagris, seeds of Digitalis purpurea, underground parts of Yucca glauca, and bulbs of Lilium pumilum-which led to the discovery of novel steroidal glycosides. The structures of these new constituents were determined based on spectroscopic data and chemical transformations. The identification of the monosaccharides including their absolute configurations was carried out by direct HPLC analysis of their hydrolysates using an optical rotation detector. Cytotoxicity of the isolated steroidal glycosides was evaluated against various tumor cells (A549, ACHN, HepG-2, HL-60, HSC-2, HSC-3, HSC-4, HSG, and SBC-3) and normal cells (Fa2 N-4, HK-2, and TIG-3 cells). Certain steroidal glycosides exhibit selective cytotoxicity and synergistic effects, making them potential lead compounds for use as anti-cancer agents. We document the isolation of 139 steroidal glycosides from higher plants and assessment their cytotoxic activities., (© 2024. The Author(s).)

Background: The management of malignant ascites is critical for treating patients with advanced pancreatic cancer. The purpose of this study was to assess the safety of cell-free and concentrated ascites reinfusion therapy (CART) and its impact on the prognosis of patients with advanced pancreatic cancer who have massive malignant ascites., Methods: This study analyzed 47 procedures in 29 patients who underwent CART for ascites caused by pancreatic cancer between 2015 and 2022. Among them, 7 patients who received chemotherapy following CART were classified as the chemotherapy group, while 22 patients without chemotherapy after CART were classified as the palliative care group., Results: Among the 47 procedures, adverse events (AEs) were observed in 9 procedures (19 %). Grade 2 adverse events were observed only in one procedure, manifested as fever. There were no grade 3 or 4 AEs, nor were there any treatment-related deaths. The median survival time was 4.0 months in the chemotherapy group and 0.7 months in the palliative care group (p = 0.004). The albumin level in the chemotherapy group was significantly higher than that in the palliative care group., Conclusion: CART is feasible and might be the optimal option to enable prolonged use of chemotherapy to improve the prognosis for late-stage pancreatic cancer patients., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Posterior reversible encephalopathy syndrome (PRES) is known as a transfusion-related complication with typically favorable prognosis and no report fatalities. Pathological evaluation of PRES is also scarce., Case Report: An 88-year-old female with myelodysplastic syndromes (MDS) attended our hospital because of a compression fracture and chronic heart failure with chronic anemia. While her hemoglobin levels improved from 4.6 to 8.0 g/dL and the pleural effusions substantially decreased following six units of red blood cell transfusion and diuretic therapy, a gradual decline in cognitive function and speech reduction was noted. PRES was diagnosed by magnetic resonance imaging of the head. Despite treatment of intensive supportive care, the patient fell into a coma by the 20th day and passed away on the 22nd day. Although the pathophysiological link between blood-transfusion-related PRES and its impact on survival is not fully understood, autopsy findings confirmed the diagnosis of PRES and revealed multiple cerebral hemorrhages that were not detected in earlier imaging studies., Conclusion: This case highlights the importance of vigilant monitoring and management of PRES, especially in high-risk populations such as elderly patients with multiple comorbidities or those with thrombocytopenia. Further studies are needed to elucidate the mechanisms of PRES in patients with hematologic diseases., (© 2024 The Author(s). Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: PDAC cells upregulate carbonic anhydrase 9 (CA9) expression in order to survive in hypoxic tumor environments, which plays a key role in tumor progression. However, the relationship between CA9 expression and preoperative treatment has not been clarified. We evaluated the clinical impact of CA9 expression on the efficacy of neoadjuvant chemoradiotherapy (NACRT) in pancreatic ductal adenocarcinoma (PDAC)., Methods: We investigated CA9 expression in 273 surgical specimens and 20 serum samples obtained from patients with PDAC and evaluated their clinical outcomes. We analyzed the function of CA9 using human pancreatic cancer cell lines., Results: CA9 was positively expressed in 36.2 % of patients who underwent NACRT, which was significantly lower than those who underwent upfront surgery (US) (58.9 %, p < 0.001). Interestingly, patients who were CA9-positive in the US group had a significantly poorer prognosis than that of those in the NACRT group (median survival time [MST], 21.5 months vs. 49.2 months, p < 0.001), while there was no significant difference between patients who were CA9-negative in the US and NACRT groups (MST, 45.8 months vs. 46.3 months, p = 0.357). Moreover, serum CA9 levels tended to correlate positively with CA9 expression in cancer tissues. In-vitro experiments demonstrated that CA9 expression was reduced after treatments with radiation and chemoradiation therapy (RT/CRT), and that CA9 knockdown suppressed the impact of RT/CRT on cancer cell proliferation., Conclusions: CA9 may act as a target molecule for RT/CRT, highlighting its clinical importance as a valuable biomarker for more stringent indications for NACRT., Competing Interests: Declaration of competing interest The authors declare that they have no confict of interest., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)