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Atopic dermatitis (AD), a prevalent Th2-dominant skin disease, involves complex genetic and environmental factors, including mutations in the Filaggrin gene and dysbiosis of skin microbiota characterized by an increased abundance of Staphylococcus aureus. Our recent findings emphasize the pivotal role of the skin barrier's integrity and microbial composition in infantile AD and allergic diseases. Early skin dysbiosis predisposes infants to AD, suggesting targeted skincare practices as a preventive strategy. The effects of skincare interventions, particularly the application of moisturizers with the appropriate molar concentration of ceramides, cholesterol, and fatty acids, play a crucial role in restoring the skin barrier. Notably, our study revealed that appropriate skincare can reduce Streptococcus abundance while supporting Cutibacterium acnes presence, thus directly linking skincare practices to microbial modulation in neonatal skin. Despite the mixed outcomes of previous Randomized Controlled Trials on the efficacy of moisturizers in AD prevention, our research points to the potential of skincare intervention as a primary preventive method against AD by minimizing the impact of genetic and environmental factors. Furthermore, our research supports the notion that early aggressive management of eczema may reduce the incidence of food allergies, highlighting the necessity for multifaceted prevention strategies that address both the skin barrier and immune sensitization. By focusing on repairing the skin barrier and adjusting the skin's microbiome from birth, we propose a novel perspective on preventing infantile AD and allergic diseases, opening new avenues for future studies, and practices in allergy prevention., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: Newborn screening using dried blood spot (DBS) samples for the targeted measurement of metabolites and nucleic acids has made a substantial contribution to public healthcare by facilitating the detection of neonates with genetic disorders. Here, we investigated the applicability of non-targeted quantitative proteomics analysis to newborn screening for inborn errors of immunity (IEIs)., Methods: DBS samples from 40 healthy newborns and eight healthy adults were subjected to non-targeted proteomics analysis using liquid chromatography-mass spectrometry after removal of the hydrophilic fraction. Subsequently, DBS samples from 43 IEI patients were analyzed to determine whether patients can be identified by reduced expression of disease-associated proteins., Results: DBS protein profiling allowed monitoring of levels of proteins encoded by 2912 genes, including 1110 listed in the Online Mendelian Inheritance in Man database, in healthy newborn samples, and was useful in identifying patients with IEIs by detecting reduced levels of disease causative proteins and their interacting proteins, as well as cell-phenotypical alterations., Conclusion: Our results indicate that non-targeted quantitative protein profiling of DBS samples can be used to identify patients with IEIs and develop a novel newborn screening platform for genetic disorders., (© 2024. The Author(s).)

Tissue factor pathway inhibitor-2 (TFPI2) is a Kunitz-type serine protease inhibitor and an ovarian clear cell carcinoma (CCC) biomarker. TFPI2 is expressed in several cancers and exerts tumor-suppressive effects; however, the role of TFPI2 in the CCC cell phenotype remains unclear. Therefore, in this study, we investigated the function of TFPI2 by establishing a gene knockout (KO) in ES-2 CCC cells and observed the change in phenotypes in vitro and in vivo. TFPI2 KO inhibited ES-2 cell proliferation, increased extracellular matrix protein adhesion, enhanced focal adhesion formation and activated integrin β1 cell surface clustering in vitro, and markedly increased ES-2 tumor growth and dissemination in the peritoneal cavity of a mouse xenograft model. These findings suggest a novel function of TFPI2 expression in suppressing the formation of focal adhesions in CCC cells, potentially by activating integrin β1. This function plays a role in the peritoneal growth characteristics of CCC cells., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yohei Miyagi reports financial support was provided by Tosoh Corporation. Shohei Myoba reports a relationship with Tosoh Corporation that includes: employment. Norihisa Ohtake reports a relationship with Tosoh Corporation that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background The production of inflammatory cytokines is reportedly increased in patients with coronavirus disease 2019 (COVID-19), causing the migration of neutrophils and monocytes to lung tissues. This disrupts the air-blood barrier by damaging the bronchial epithelial and vascular endothelial cells. As multiorgan dysfunction in sepsis is considered to be partly caused by complement activation, which can cause lung injury in patients with COVID-19. There are limited studies examining the link between complement activation in patients with COVID-19. This study aimed to AQinvestigate the association of complement activation with the pathophysiology of COVID-19. Twenty-seven patients with COVID-19 were enrolled in this study and classified into two groups depending on the indication for mechanical ventilation. Plasma complement factors (C3a, C5a, Ba, and sC5b-9), complement regulators (sCD59 and factor H), interleukin-6 (IL-6), and syndecan-1 levels were measured using Enzyme-linked immunosorbent assay (ELISA). Results: All complement factors and regulators, IL-6, and syndecan-1 levels were significantly elevated in patients with COVID-19 compared with those in healthy controls. C5a and sC5b-9 levels were decreased significantly in the invasive mechanical ventilation (IMV) group compared with those in the non-IMV group. Syndecan-1 levels were significantly increased in the IMV group compared with those in the non-IMV group. Conclusions: Complement activation is an exacerbating factor for lung injury in patients with COVID-19. Complement factors are nonessential predictors of mechanical ventilation; however, syndecan-1 could be a biomarker of COVID-19 severity in patients., (© 2024. The Author(s).)

Background: The ability to access health and medical information have implications for prognosis and quality of life. This study investigated the current communication environment and health literacy in chronic hemodialysis (HD) patients and their associations with patients' physical condition and clinical findings., Methods: This was a cross-sectional, single-arm, multicenter exploratory study. Data were collected from 211 patients (64 males) undergoing chronic HD at five facilities. This included a survey of communication environments, health literacy, dialysis management information, and clinical findings., Results: Among the participants, 145 (68.7%) reported using the Internet. They primarily collected health-related as well as everyday life information through the Internet. Health literacy fell within the problematic range. In terms of e-Health literacy, "understanding" and "easy" showed a positive trend, while "accessing," "appraising," and "applying" were perceived as "difficult." Three groups were identified based on Internet usage: good communication environment (CE) group (134 participants), poor-CE group (56 participants), and a group that did not respond (21 participants). Grip strength, serum albumin level, and "information acquisition" were significantly lower in the poor-CE group. Health literacy increases as the duration of dialysis extends, and decreases with advancing age., Conclusions: Patients who used the Internet gained a wide range of information, including health-related information, for their daily lives. The use of ICT is lower among patients with decreased physical activity, and further investigation is desired into how actively encouraging these patients to collect health information via the Internet can enhance their health literacy., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: Low-keV virtual monoenergetic images (VMIs) of dual-energy computed tomography (CT) enhances iodine contrast for detecting small arteries like the Adamkiewicz artery (AKA), but image noise can be problematic. Deep-learning image reconstruction (DLIR) effectively reduces noise without sacrificing image quality., Purpose: To evaluate whether DLIR on low-keV VMIs of dual-energy CT scans improves the visualization of the AKA., Material and Methods: We enrolled 29 patients who underwent CT angiography before aortic repair. VMIs obtained at 70 and 40 keV were reconstructed using hybrid iterative reconstruction (HIR), and 40 keV VMIs were reconstructed using DLIR. The image noise of the spinal cord, the maximum CT values of the anterior spinal artery (ASA), and the contrast-to-noise ratio (CNR) of the ASA were compared. The overall image quality and the delineation of the AKA were evaluated on a 4-point score (1 = poor, 4 = excellent)., Results: The mean image noise of the spinal cord was significantly lower on 40-keV DLIR than on 40-keV HIR scans; they were significantly higher than on 70-keV HIR images. The CNR of the ASA was highest on the 40-keV DLIR images among the three reconstruction images. The mean image quality scores for 40-keV DLIR and 70-keV HIR scans were comparable, and higher than of 40-keV HIR images. The mean delineation scores for 40-keV HIR and 40-keV DLIR scans were significantly higher than for 70-keV HIR images., Conclusion: Visualization of the AKA was significantly better on low-keV VMIs subjected to DLIR than conventional HIR images., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Earth is expected to have acquired a reduced proto-atmosphere enriched in H 2 and CH 4 through the accretion of building blocks that contain metallic Fe and/or the gravitational trapping of surrounding nebula gas. Such an early, wet, reduced atmosphere that covers a proto-ocean would then ultimately evolve toward oxidized chemical compositions through photochemical processes that involve reactions with H 2 O-derived oxidant radicals and the selective escape of hydrogen to space. During this time, atmospheric CH 4 could be photochemically reprocessed to generate not only C-bearing oxides but also organics. However, the branching ratio between organic matter formation and oxidation remains unknown despite its significance on the abiotic chemical evolution of early Earth. Here, we show via numerical analyses that UV absorptions by gaseous hydrocarbons such as C 2 H 2 and C 3 H 4 significantly suppress H 2 O photolysis and subsequent CH 4 oxidation during the photochemical evolution of a wet proto-atmosphere enriched in H 2 and CH 4 . As a result, nearly half of the initial CH 4 converted to heavier organics along with the deposition of prebiotically essential molecules such as HCN and H 2 CO on the surface of a primordial ocean for a geological timescale order of 10-100 Myr. Our results suggest that the accumulation of organics and prebiotically important molecules in the proto-ocean could produce a soup enriched in various organics, which might have eventually led to the emergence of living organisms.

Functional refinement of neural circuits is a crucial developmental process in the brain. However, how synaptic maturation and axon wiring proceed cooperatively to establish reliable signal transmission is unclear. Here, we combined nanotopography of release machinery at the active zone (AZ), nanobiophysics of neurotransmitter release, and single-neuron reconstruction of axon arbors of lemniscal fibers (LFs) in the developing mouse somatosensory thalamus. With development, the cluster of Cav2.1 enlarges and translocates closer to vesicle release sites inside the bouton, and LFs drastically shrink their arbors and form larger boutons on the perisomatic region of target neurons. Experimentally constrained simulations show that the nanotopography of mature synapses enables not only rapid vesicular release but also reliable transmission following repetitive firing. Sensory deprivation impairs the developmental shift of molecular nanotopography and axon wiring. Thus, we uncovered the cooperative nanotopographical and morphological mechanisms underlying the developmental establishment of reliable synaptic transmission., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To investigate an association between the gut microbiome and efficacy of poly(ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer., Methods: This study conducted fecal microbiome analysis (16S rRNA gene sequencing) and circulating tumor DNA (ctDNA) profiling for ovarian cancer patients who underwent PARPi maintenance therapy. Fecal and blood samples were collected at the baseline and the progressive disease (PD) or last follow-up. The relative abundance of gut microbes and progression-free survival (PFS) were analyzed using linear discriminant analysis of effect size and the Cox proportional hazard model according to BRCA1 / 2 mutation ( BRCA1 / 2 mut) status detected by ctDNA sequencing., Results: Baseline samples were available from 23 BRCA1 / 2 mut-positive patients and 33 BRCA1/2 mut-negative patients. The microbes enriched in the baseline samples with long PFS were Bifidobacterium , Roseburia , Dialister , Butyricicoccus , and Bilophila for BRCA1/2 mut-positive patients and Phascolarctobacterium for BRCA1/2 mut-negative patients. In multivariate analyses dividing patients by the median values of relative abundances, no bacteria were associated with PFS in BRCA1/2 mut-positive patients, whereas high Phascolarctobacterium abundances (≥1.11%) was significantly associated with longer PFS in BRCA1/2 mut-negative patients (median 14.0 vs. 5.9 months, hazard ratio=0.28; 95% confidence interval=0.11-0.69; p=0.014). In the last samples, the relative abundances of Phascolarctobacterium were significantly higher in patients without PD (n=5) than those with PD (n=15) (median 1.25% vs. 0.06%; p=0.016)., Conclusion: High fecal composition of Phascolarctobacterium was associated with prolonged PFS in patients with BRCA1/2 mut-negative ovarian cancer receiving PARPi therapy. Our results would provide new insights for future research., Competing Interests: Mika Okazawa-Sakai declares no competing interests. Shunsuke A. Sakai declares no competing interests. Ichinosuke Hyodo reports advisory roles for Asahi-Kasei, Ono, Taiho, Chugai, and Eisai Pharmaceutical Companies. Satoshi Horasawa declares no competing interests. Kentaro Sawada declares no competing interests. Takao Fujisawa reports honoraria from Amelieff Co. Ltd. Yasuko Yamamoto declares no competing interests. Shogen Boku reports honoraria from Nippon Kayaku Co., Ltd., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bristol-Myers Squibb Japan, and MSD. Yoh Hayasaki declares no competing interests. Masanori Isobe declares no competing interests. Daisuke Shintani declares no competing interests. Kosei Hasegawa reports honoraria from AstraZeneca, GSK, MSD, and Takeda; advisory role for GSK, MSD, and Takeda; research grants from MSD. Tomomi Egawa-Takata declares no competing interests. Kimihiko Ito reports honoraria from AstraZeneca. Kei Ihira declares no competing interests. Hidemichi Watari reports honoraria from AstraZeneca, Takeda, MSD, and Chugai. Kazuhiro Takehara reports honoraria from AstraZeneca, Takeda, MSD, Chugai, Eisai, and Sanofi. Hiroshi Yagi declares no competing interests. Kiyoko Kato declares no competing interests. Tatsuyuki Chiyoda reports research grants from Takeda Pharmaceutical Company. Kenichi Harano reports honoraria from AstraZeneca, Chugai, Eizai, MSD, Taiho and Takeda, and advisory roles for AstraZeneca, Chugai, Eizai, Taiho and Takeda. Yoshiaki Nakamura declares advisory role from Guardant Health Pte Ltd., Natera, Inc., Roche Ltd., Seagen, Inc., Premo Partners, Inc., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., Exact Sciences Corporation, Gilead Sciences, Inc.; speakers' bureau from Guardant Health Pte Ltd., MSD K.K., Eisai Co., Ltd., Zeria Pharmaceutical Co., Ltd., Miyarisan Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., CareNet, Inc., Hisamitsu Pharmaceutical Co., Inc., Taiho Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Becton, Dickinson and Company, Guardant Health Japan Corp; research funding from Seagen, Inc., Genomedia Inc., Guardant Health AMEA, Inc., Guardant Health, Inc., Tempus Labs, Inc., Roche Diagnostics K.K., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd. Riu Yamashita declares no competing interests. Takayuki Yoshino reports honoraria from Chugai Pharma, Takeda Pharma, Merck, Bayer Yakuhin, Ono Pharmaceutical and MSD K. K.; consulting fees from Sumitomo Corp.; and research grants from Amgen, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, FALCO Biosystems, Genomedia Inc., Medical & Biological Laboratories, Merus N.V., Molecular Health, MSD, Nippon Boehringer Ingelheim, Ono, Pfizer, Roche Diagnostics, Sanofi, Sysmex, Taiho and Takeda. Daisuke Aoki reports honoraria from AstraZeneca, Takeda, MSD, Chugai, and Myriad Genetics., (© 2025. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Aims: In addition to well-documented tachycardias involving twin atrioventricular (AV) nodes, tachycardias involving a single node have been clinically experienced in right atrial isomerism (RAI). This study aimed to characterize the AV node involvement patterns and evaluate the outcome of ablation therapy in RAI patients with tachycardias., Methods: We retrospectively analyzed the medical records of 16 RAI patients who underwent catheter ablation of tachycardias involving twin or single AV nodes at our center between April 2006 and March 2020., Results: A total of 22 ablation procedures were performed in 16 patients. The median age and body weight were 2 years (range 20 months-31 years) and 11.2 kg (range 7.4-42 kg), respectively. Two QRS complexes were confirmed in 11/16 patients, and a single QRS complex in 5/16. The dominant AV node was anterior in 7/16. Four patterns of tachycardias were identified: tachycardias reciprocating between two AV nodes with retrograde conduction through the anterior AV node (3/16) or through the posterior AV node (4/16); and reentrant tachycardias involving the anterior AV node only (3/16) or posterior AV node only (6/16). Ablation successfully eliminated the tachycardias in 15/16 patients (93.8%). Recurrence was reported in 7/16 (44%) during a median follow-up period of 96.5 months. Five of those 7 patients underwent additional ablation, and the tachycardias were eliminated in 3/5 patients. None of the patients developed ventricular asynchrony after ablation., Conclusion: Transcatheter ablation was effective in RAI patients with tachycardias involving twin or single AV nodes, and deterioration of the cardiac function was rare., (© 2024 Wiley Periodicals LLC.)

Achondroplasia is the most common form of human dwarfism caused by mutations in the FGFR3 receptor tyrosine kinase. Current therapy begins at two years of age and improves longitudinal growth but does not address the cranial malformations including midface hypoplasia and foramen magnum stenosis, which lead to significant otolaryngeal and neurologic compromise. A recent clinical trial found partial restoration of cranial defects with therapy starting at 3 months of age, but results are still inconclusive. The benefits of achondroplasia therapy are therefore controversial, increasing skepticism among the medical community and patients. We used a mouse model of achondroplasia to test treatment protocols aligned with human studies. Early postnatal treatment (from day 1) was compared to late postnatal treatment (from day 4, equivalent to ~5 months in humans). Animals were treated with the FGFR3 inhibitor infigratinib and the effect on skeleton was thoroughly examined. We show that premature fusion of the skull base synchondroses occurs immediately after birth and leads to defective cranial development and foramen magnum stenosis in the mouse model to achondroplasia. This phenotype appears significantly restored by early infigratinib administration when compared to late treatment, which provides weak to no rescue. In contrast, the long bone growth is similarly improved by both early and late protocols. We provide clear evidence that immediate postnatal therapy is critical for normalization of skeletal growth in both the cranial base and long bones and the prevention of sequelae associated with achondroplasia. We also describe the limitations of early postnatal therapy, providing a paradigm-shifting argument for the development of prenatal therapy for achondroplasia., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Lysine succinylation (Ksu) has recently emerged as a protein modification that regulates diverse functions in various biological processes. However, the systemically and precise role of lysine succinylation in erythropoiesis remains to be fully elucidated. In this study, we noted a prominent increase of succinyl-CoA and lysine succinylation during human erythroid differentiation. To explore the functional significance of succinylation, we inhibited succinylation by either knock downing key succinyltransferases or overexpressing desuccinylases. Succinylation inhibition led to suppressed cell proliferation, increased apoptosis, and disrupted erythroid differentiation. In vivo overexpression of the desuccinylases SIRT5 delayed erythroid differentiation. Furthermore, integrative proteome and succinylome analysis identifies 939 succinylated proteins with 3,562 Ksu sites, distributed across various cellular compartments and involved in multiple cellular processes. Significantly, inconsistencies between protein expression levels and succinylation levels were observed, indicating that the succinylation of certain proteins may function independently of expression. Mechanistically, we implicated KAT2A-mediated succinylation of histone H3 K79, leading to chromatin remodeling and subsequently erythropoiesis regulation. Specially, we identified CYCS as a key regulator of erythropoiesis, which depends on its succinylation sites K28/K40. Taken together, our comprehensive investigation of the succinylation landscape during erythropoiesis provides valuable insights into its regulatory role and offer potential implications for erythroid-related diseases.

Background: The oral cavity hosts numerous bacteria that are associated with various systemic diseases. The Oral Bacteria Counter (PHC Corporation, Tokyo, Japan), a microorganism quantitative analyzer that utilizes dielectrophoretic impedance measurements, enables rapid bacterial counting and is widely used in dental practice in Japan. However, it may also detect nonviable bacteria. This study aimed to assess the impact of disinfectants, electrolytes, and viscosity on the accuracy of the Oral Bacteria Counter and to determine whether it measures non-viable bacteria similarly to viable bacteria., Methods: To evaluate the effect of the disinfectants, samples of 7% povidone-iodine (PV-I), 0.2% benzethonium chloride, 5% chlorhexidine (CHX), 0.2% CHX, 0.05% CHX, sterile water, and saline were measured using the Oral Bacteria Counter. The effect of viscosity was assessed by mixing sterile water with glycerol in various ratios and measuring the dielectrophoretic impedance of the bacterial counts at different viscosities. For the electrolyte effects, samples of Staphylococcus aureus diluted in sterile water or saline were measured using the Oral Bacteria Counter. Additionally, samples of 7% PV-I or 5% CHX diluted in sterile water or saline were measured. Bacterial counts were then measured and compared using the Oral Bacteria Counter, our developed delayed real-time polymerase chain reaction (DR-PCR) method (which quantifies only viable bacteria), and culture methods., Results: Disinfectants such as 5% CHX and 7% PV-I produced high readings on the Oral Bacteria Counter, even when no viable bacteria were present. Higher glycerol concentrations, which increased the viscosity, resulted in lower bacterial counts. The presence of electrolytes, particularly saline, led to higher readings on the Oral Bacteria Counter, which detected both viable and non-viable bacteria, whereas DR-PCR and culture methods did not detect non-viable bacteria., Conclusion: The Oral Bacteria Counter may be influenced by disinfectants, viscosity, and electrolytes, leading to potential inaccuracies in bacterial quantification. For accurate bacterial measurements, it is essential to consider these factors and ideally combine the results from the Oral Bacteria Counter with methods such as DR-PCR for more reliable assessment., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Imakiire et al.)

Background: Recent guidelines recommend direct patient observation, pressure monitoring, and sensor devices to prevent extravasation during contrast media (CM) injection. However, it is impractical in terms of time and cost to install sensors for all patients., Purpose: To identify risk factors for CM extravasations during contrast-enhanced computed tomography (CECT) in a large population and to establish criteria for placing the sensor device on patients., Material and Methods: This retrospective study included 143,556 patients who underwent CECT at our hospital between April 2012 and July 2022. We performed multivariable logistic regression analysis between patients with (n = 350) and randomly selected patients without CM extravasation (n = 350). We investigated the percentage of patients with sensor devices and their sensitivity for detecting extravasation using receiver operating characteristic curve analysis., Results: The extravasation rate was 0.27%. Multivariable logistic regression analysis showed that the injection rate (adjusted odds ratio [AOR] = 1.61, 95% confidence interval [CI] = 1.33-1.95: P <0.001), catheter gauge (AOR = 3.86, 95% CI = 1.92-7.76; P <0.001), the use of anticancer drugs (AOR = 1.81, 95% CI = 1.32-2.50; P <0.001), and existing catheters (AOR = 1.52, 95% CI = 1.10-2.11; P  = 0.009) were significantly associated with extravasation. To achieve a sensitivity of 90%, 80%, 70%, 60%, and 50%, 80%, 65%, 50%, 40%, and 28% of all patients required the placement of a sensor device, respectively., Conclusion: Sensitivity analysis established criteria for effective placing sensor devices., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Recent technical developments have led to the invention of multiband functional magnetic resonance imaging (fMRI) sequences that allow for faster sampling rates. However, some studies have highlighted problems with these sequences, leading to a decreased temporal signal-to-noise ratio (tSNR). In addition, this temporal noise may interfere with detecting reward-related responses in mesolimbic regions. The blood-oxygen-level-dependent signal utilized in the majority of fMRI measurements is relatively slow. Furthermore, the cerebral response to gustatory stimuli would also be relatively slow. Therefore, given the temporal noise issues with multiband sequences, it is unclear whether multiband sequences are necessary for fMRI studies using gustatory stimuli. We thus conducted an fMRI experiment using a gustatory stimulus to investigate the effects of multiband sequences and increased sampling rates on statistical outcome measures. A single-band sequence with a repetition time (TR) of 2 s of phantom fMRI data and gustatory fMRI data from the gustatory regions exhibited the highest tSNR, although the tSNR of this sequence of gustatory fMRI was not statistically different from tSNR of multiband sequences with a TR of 2 s in any of the selected region of interests. Conventional general linear model analysis of fMRI showed that single-band sequences are more advantageous than multiband sequences for detecting brain responses to gustatory stimuli in the primary gustatory cortex. In addition, a Bayesian data comparison showed that data derived from a single-band sequence with a TR of 2 s was optimal for inferring neuronal connectivity in gustatory processing. Therefore, a conventional single-band sequence with a TR of 2 s is more appropriate for fMRI with gustatory stimuli. Image acquisition sequences should be selected aligned with the study objectives and target brain regions., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

We herein report the synthesis, characterizations, and synchrotron X-ray charge-density studies of oxo-centered triruthenium(II,III,III) clusters [Ru 3 O(CHCl 2 COO) 6 (py) 3 ] ( 1 ) and [Ru 3 O(CHCl 2 COO) 6 (CO)(py) 2 ] ( 2 ) (py = pyridine). Dichloroacetate was chosen for its large scattering factor of the Cl atom, and its electron-withdrawing nature results in significant stabilization of the targeted lower-valent Ru 3 II,III,III state in the cluster framework. Multipole analysis revealed that the difference in electron populations between two crystallographically independent Ru centers is small for 1 (Δ = 0.30 e) but large for 2 (Δ = 1.46 e). Remarkable differences between 1 and 2 are also found in their static deformation density maps; substantial local charge depletion was found around the central μ 3 O atom for 1 , which is less pronounced for 2 . According to the topological characterization of Ru-μ 3 O bonds associated with the bond critical point, bcp, the electron density, ρ bcp , is in the range of 0.79-0.89 e Å -3 , and the total energy density, H bcp , is in the range of -0.21 to -0.05 hartree Å -3 . These findings represent the first charge-density distribution analysis of mixed-valence multinuclear Ru complexes including comparison between 3d and 4d transition-metal systems.

Tongue pressure (TP) decreases significantly after esophagectomy in esophageal cancer patients (ECPs). Meanwhile, 2 weeks of gum-chewing training (GCT) significantly increased TP in healthy university students. We examined whether perioperative GCT would decrease the proportion of patients exhibiting a decline in TP at 2 weeks postoperatively, and prevent postoperative complications, in thoracic ECPs (TECPs). This was a single-center interventional study, and nonrandomized study with a historical control group (HCG). TECPs who underwent first-stage radical esophagectomy were recruited. Thirty-two patients of 40 in the gum-chewing group (GCG) were completed perioperative GCT in 3 times daily. Propensity score matching was performed with covariates related to TP including preoperative age, sex, body mass index, and the repetitive saliva swallowing test result, and yielded a matched cohort of 25 case pairs. Eleven GCG patients [44.0%] exhibited significantly lower TP at 2 weeks postoperatively than before esophagectomy was significantly fewer than that of 19 patients [76.0%] in the HCG. The median number of fever days (> 38 °C) in the 2 weeks after esophagectomy in the GCG was significantly fewer than those in the HCG. Perioperative GCT may prevent postoperative TP decline and postoperative dysphagia-related complications after esophagectomy., (© 2024. The Author(s).)

Background and Objectives: This study evaluated the effectiveness of a pocket-sized ultrasound device in preoperative planning for lymphaticovenular anastomosis (LVA) to enhance lymphedema treatment outcomes., Methods: A retrospective analysis was performed on 24 patients who underwent LVA for secondary upper extremity lymphedema between June 2020 and August 2022. Patients were categorized into two groups: the ultrasound group, which used a pocket-sized device (Vscan Air), for preoperative vein identification, and a control group that did not. Preoperative lymphatic mapping was performed using indocyanine green lymphography, and suitable veins for anastomosis were identified using ultrasound. Upper extremity lymphedema index and incision length were compared., Results: Participants in the ultrasound group had a shorter average incision length (2.85 ± 0.48 cm) than those in the control group (3.23 ± 0.78 cm, p = 0.038), indicating a more targeted and minimally invasive approach. Although volume reduction rates were not significantly different, the pocket ultrasound device facilitated more precise vein selection, enhancing surgical planning., Conclusion: Pocket-sized ultrasound devices provide a cost-effective and practical solution for vein identification during LVA, particularly in resource-limited settings. While high-frequency ultrasound offers superior resolution, portable devices could become standard tools for lymphatic surgery with continued technological advancement., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of function of maternal UBE3A. The major cause of AS is a maternal deletion in 15q11.2-q13, and the minor causes are a UBE3A mutation, uniparental disomy (UPD), and imprinting defect (ID). Previous reports suggest that all patients with AS exhibit developmental delay, movement or balance disorders, behavioral characteristics, and speech impairment. In contrast, a substantial number of AS patients with a UBE3A mutation, UPD, or ID were reported not to show these consistent features and to show age-dependent changes in their features. In this study, we investigated 134 patients with AS, including 57 patients with a UBE3A mutation and 48 patients with UPD or ID. Although developmental delay was present in all patients, 20% of patients with AS caused by UPD or ID did not exhibit movement or balance disorders. Differences were also seen in hypopigmentation and seizures, depending on the causes. Moreover, patients with a UBE3A mutation, UPD, or ID tended to show fewer of the specific phenotypes depending on their age. In particular, in patients with UPD or ID, easily provoked laughter and hyperactivity tended to become more pronounced as they aged. Therefore, the clinical features of AS based on cause and age should be understood, and genetic testing should not be limited to patients with the typical clinical features of AS., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Key Message: The N-terminal transmembrane domain of LPAT1 crosses the inner membrane placing the N terminus in the intermembrane space and the C-terminal enzymatic domain in the stroma. Galactolipids mono- and di-galactosyl diacylglycerol are the major and vital lipids of photosynthetic membranes. They are synthesized by five enzymes hosted at different sub-chloroplast locations. However, localization and topology of the second-acting enzyme, lysophosphatidic acid acyltransferase 1 (LPAT1), which acylates the sn-2 position of glycerol-3-phosphate (G3P) to produce phosphatidic acid (PA), remain unclear. It is not known whether LPAT1 is located at the outer or the inner envelope membrane and whether its enzymatic domain faces the cytosol, the intermembrane space, or the stroma. Even the size of mature LPAT1 in chloroplasts is not known. More information is essential for understanding the pathways of metabolite flow and for future engineering endeavors to modify glycerolipid biosynthesis. We used LPAT1 preproteins translated in vitro for import assays to determine the precise size of the mature protein and found that the LPAT1 transit peptide is at least 85 residues in length, substantially longer than previously predicted. A construct comprising LPAT1 fused to the Venus fluorescent protein and driven by the LPAT1 promoter was used to complement an Arabidopsis lpat1 knockout mutant. To determine the sub-chloroplast location and topology of LPAT1, we performed protease treatment and alkaline extraction using chloroplasts containing in vitro-imported LPAT1 and chloroplasts isolated from LPAT1-Venus-complemented transgenic plants. We show that LPAT1 traverses the inner membrane via an N-terminal transmembrane domain, with its N terminus protruding into the intermembrane space and the C-terminal enzymatic domain residing in the stroma, hence displaying a different membrane topology from its bacterial homolog, PlsC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The Bioinformation and DNA Data Bank of Japan Center (DDBJ Center, https://www.ddbj.nig.ac.jp) provides public databases that cover a wide range of fields in life sciences. As a founding member of the International Nucleotide Sequence Database Collaboration (INSDC), the DDBJ Center accepts and distributes nucleotide sequence data ranging from raw reads to assembled and annotated sequences with the National Center for Biotechnology Information and the European Bioinformatics Institute. Besides INSDC databases, the DDBJ Center provides databases for functional genomics (Genomic Expression Archive), metabolomics (MetaboBank), human genetic variations (TogoVar-repository) and human genetic and phenotypic data (Japanese Genotype-phenotype Archive). These database systems have been built on the National Institute of Genetics supercomputer, which is also a platform for the DDBJ Group Cloud (DGC) services for sharing and analysis of pre-publication data among research groups. This paper reports recent updates on the databases and the services of the DDBJ Center, highlighting the DGC service., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Anal fistula cancer is rare and definitive treatment has not yet been established. Laparoscopic abdominoperineal resection is generally the first choice of treatment if the cancer is determined to be resectable. However, complicated anal fistula cancer often requires extensive resection. Using a myocutaneous flap for reconstruction after resection in such cases, radical resection can be performed regardless of the size of the anal fistula cancer., Case Presentation: We report two cases in which we performed laparoscopic abdominoperineal resection with extensive buttock resection and myocutaneous flap reconstruction for widespread anal fistula cancer. One of the cases was reconstruction with a posterior thigh flap, the other was with a bilateral expanded gluteus maximus flap. Both cases were anal fistula cancers that developed from complicated anal fistulas., Conclusions: If the size of anal fistula cancer is large and extended buttock resection is necessary, radical resection of anal fistula cancer is possible using myocutaneous flap for reconstruction after extended abdominoperineal resection., (© 2024. The Author(s).)

Background: Neurolysis alone or administration of anti-adhesion products after neurolysis is performed to treat peripheral nerve adhesion; however, the recovery of nerve function is poor. This study aimed to investigate the efficacy of adipose-derived stem cells (ADSCs) for peripheral nerve adhesion in a rat model., Methods: As a nerve adhesion procedure, the neural bed was coagulated, and the epineurium of the sciatic nerve was sutured to the coagulated neural bed using nylon. Neurolysis was performed 6 weeks after the nerve adhesion procedure, and saline (control group) or ADSCs (ADSC group) were administered around the nerve where neurolysis was performed. Evaluations were performed 6 weeks after the administration., Results: The wet weight ratio of the tibialis anterior muscle and nerve conduction velocity, which are indicators of nerve regeneration, were significantly better, while tensile strength, which is an indicator of the severity of nerve adhesion, was significantly lower in the ADSC group than in the control group. In the nerve, the expression of interleukin-10 and transforming growth factor-β in the nerve was significantly higher and that of tumor necrosis factor-α was significantly lower in the ADSC group than in the control group. Furthermore, significantly fewer M1 macrophages and significantly more M2 macrophages were observed in the ADSC group than in the control group. In the perineural scar, significantly fewer perineural collagen fibers and significantly more vascularization were observed in the ADSC group than in the control group., Conclusions: ADSCs prevented peripheral nerve adhesion by reducing perineural scarring and enhancing vascularization. Additionally, ADSCs promoted nerve regeneration by decreasing inflammatory cytokine levels and increasing anti-inflammatory cytokine levels, as ADSCs regulated macrophage polarization from M1 to M2 macrophages. These findings hold promise for using ADSCs to treat nerve adhesion., Competing Interests: Declaration of competing interest The authors declare that this study was conducted without any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Introduction: We evaluated the efficacy and safety of brexpiprazole for the treatment of agitation in Alzheimer's dementia (AAD) in Japanese patients., Methods: This was a phase 2/3 multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Patients with AAD were randomized to receive brexpiprazole 1 mg/day or 2 mg/day, or placebo (3:4:4) for 10 weeks., Results: For the primary endpoint (change in Cohen-Mansfield Agitation Inventory [CMAI] total score from baseline to Week 10), both brexpiprazole 1 mg and 2 mg groups demonstrated statistically significant improvement versus placebo (2 mg: least squares [LS] mean difference -7.2 [95% confidence interval (CI): -10.0 to -4.3], p-value < 0.0001, 1 mg: LS mean difference -3.7 [95% CI: -6.8 to -0.7], p-value = 0.0175). The incidences of treatment-emergent adverse events reported in the brexpiprazole 1 mg, 2 mg, and placebo groups were 76.8%, 84.6%, and 73.8%, respectively., Discussion: Brexpiprazole 1 mg/day and 2 mg/day for 10 weeks was efficacious and well tolerated., Highlights: Brexpiprazole treatment for 10 weeks improved agitation in Alzheimer's dementia. The efficacy of brexpiprazole 1 mg/day has been confirmed for the first time. The incidence of adverse events was higher compared to the previous studies. Both brexpiprazole 1 mg/day and 2 mg/day were generally well tolerated., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Owing to the rapid increase in the number of people with severe heart failure, regenerative medicine is anticipated to play a role in overcoming the limitations inherent in existing surgical interventions. There are essentially two types of cardiac regenerative therapies for a failing heart. Cellular regenerative therapies using various stem cells improve the functional recovery of the heart mainly by cytokine paracrine effects. The implantation of induced pluripotent stem cell-derived cardiomyocytes can contribute not only to the inhibition of adverse heart remodeling by paracrine effects but also to the supply of newly born functional myocytes with the recipient myocardium as "mechanically working cells." Cell transplantation, including autologous myoblast transplantation, reduces heart failure exacerbations and benefits patients without the need for other treatment options. Although cellular therapy is currently the mainstream approach, it requires an in-house cell-processing center with an aseptic environment. In addition, these stem cells are usually introduced via several invasive delivery methods, including intracoronary administration, and cellular sheet implantation. Simplifying the culture methods for these cells is a crucial problem that needs to be resolved. Drug-induced regenerative therapy is another option that enhances self-endogenous regenerative systems in the human body and does not require invasive methods or cell cultures. Therefore, drug-induced regenerative therapies may overcome the disadvantages of these cellular therapies. The purpose of this report is to summarize cell transplantation therapy in the cardiovascular system and regenerative therapy for heart failure using an autologous endogenous regenerative system., Competing Interests: This work was partially funded by StemRIM Inc., (© 2024 The Author(s).)

Clostridium perfringens bacteremia is a rare but rapidly fatal condition, especially in patients exhibiting massive intravascular hemolysis (MIH), gas gangrene, and septic shock. Herein, we present an autopsy case of C. perfringens septicemia exhibiting MIH, gas gangrene, and cytokine storm. The patient was an 84-year-old female with a history of biliary reconstruction surgery for congenital biliary dilatation. She developed MIH, elevated inflammatory mediator levels, thrombocytopenia, and coagulopathy. She went into shock within 1 h of the presentation and died within a few hours. Rapid progression was associated with the transformation of liver abscesses into gas-filled abscesses on computed tomography scan, suggesting the rapid outgrowth of gas-producing bacteria. The patient was finally diagnosed with MIH and gas gangrene due to C. perfringens infection based on the presence of this bacterium in the blood and bile. On autopsy, gas gangrene was observed in almost all organs, originating from the bile duct. Polymerase chain reactions targeting C. perfringens toxins identified the isolated bacterium as C. perfringens type A expressing α-toxin (CPA), perfringolysin O (PFO), and collagenase (ColA). Elevated interleukin 6 and tumor necrosis factor-α expression levels were observed in the serum, and such proinflammatory responses were partially mediated by Toll-like receptor 2. This study elucidated the association between the toxin profiles of clinically isolated C. perfringens and the host cytokine responses in the patient., Competing Interests: The authors declare that they have no conflicts of interest., (© 2024 The Authors.)

In recent years, fatty acids have garnered significant attention as a natural phase-change material and a hydrophobizer due to their biocompatibility and biodegradability. In this study, the utilization of fatty acid is proposed as a polymerization medium for the first time. As a specific reaction, chemical oxidative polymerizations of pyrrole is conducted using ferric chloride as an oxidant in a stearic acid medium. The polymerizations resulted in the production of micrometer-sized polypyrrole (PPy) grains, which are aggregates of atypical primary particles with submicrometer size. The PPy grains are doped with stearic acid, suggesting that the stearic acid functioned as a dopant and a hydrophobizing agent as well as a polymerization medium. The dried PPy grains can adsorb at the air-water interface and function as a liquid marble stabilizer with light-to-heat photothermal properties. The liquid marble can move on a planar air-water interface by Marangoni flow induced by NIR laser light irradiation., (© 2024 Wiley‐VCH GmbH.)

Aims: Several algorithms can differentiate inferior axis premature ventricular contractions (PVCs) originating from the right side and left side on 12-lead electrocardiograms (ECGs). However, it is unclear whether distinguishing the origin should rely solely on PVC or incorporate sinus rhythm (SR). We compared the dual-rhythm model (incorporating both SR and PVC) to the PVC model (using PVC alone) and quantified the contribution of each ECG lead in predicting the PVC origin for each cardiac rotation., Methods and Results: This multicentre study enrolled 593 patients from 11 centres-493 from Japan and Germany, and 100 from Belgium, which were used as the external validation data set. Using a hybrid approach combining a Resnet50-based convolutional neural network and a transformer model, we developed two variants-the PVC and dual-rhythm models-to predict PVC origin. In the external validation data set, the dual-rhythm model outperformed the PVC model in accuracy (0.84 vs. 0.74, respectively; P < 0.01), precision (0.73 vs. 0.55, respectively; P < 0.01), specificity (0.87 vs. 0.68, respectively; P < 0.01), area under the receiver operating characteristic curve (0.91 vs. 0.86, respectively; P = 0.03), and F1-score (0.77 vs. 0.68, respectively; P = 0.03). The contributions to PVC origin prediction were 77.3% for PVC and 22.7% for the SR. However, in patients with counterclockwise rotation, SR had a greater contribution in predicting the origin of right-sided PVC., Conclusion: Our deep learning-based model, incorporating both PVC and SR morphologies, resulted in a higher prediction accuracy for PVC origin, considering SR is particularly important for predicting right-sided origin in patients with counterclockwise rotation., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Purpose: The rise of large language models such as generative pretrained transformers (GPTs) has sparked considerable interest in radiology, especially in interpreting radiologic reports and image findings. While existing research has focused on GPTs estimating diagnoses from radiologic descriptions, exploring alternative diagnostic information sources is also crucial. This study introduces the use of GPTs (GPT-3.5 Turbo and GPT-4) for information retrieval and summarization, searching relevant case reports via PubMed, and investigates their potential to aid diagnosis., Materials and Methods: From October 2021 to December 2023, we selected 115 cases from the "Case of the Week" series on the American Journal of Neuroradiology website. Their Description and Legend sections were presented to the GPTs for the 2 tasks. For the Direct Diagnosis task, the models provided 3 differential diagnoses that were considered correct if they matched the diagnosis in the diagnosis section. For the Case Report Search task, the models generated 2 keywords per case, creating PubMed search queries to extract up to 3 relevant reports. A response was considered correct if reports containing the disease name stated in the diagnosis section were extracted. The McNemar test was used to evaluate whether adding a Case Report Search to Direct Diagnosis improved overall accuracy., Results: In the Direct Diagnosis task, GPT-3.5 Turbo achieved a correct response rate of 26% (30/115 cases), whereas GPT-4 achieved 41% (47/115). For the Case Report Search task, GPT-3.5 Turbo scored 10% (11/115), and GPT-4 scored 7% (8/115). Correct responses totaled 32% (37/115) with 3 overlapping cases for GPT-3.5 Turbo, whereas GPT-4 had 43% (50/115) of correct responses with 5 overlapping cases. Adding Case Report Search improved GPT-3.5 Turbo's performance ( P  = .023) but not that of GPT-4 ( P  = .248)., Conclusions: The effectiveness of adding Case Report Search to GPT-3.5 Turbo was particularly pronounced, suggesting its potential as an alternative diagnostic approach to GPTs, particularly in scenarios where direct diagnoses from GPTs are not obtainable. Nevertheless, the overall performance of GPT models in both direct diagnosis and case report retrieval tasks remains not optimal, and users should be aware of their limitations., (© 2024 by American Journal of Neuroradiology.)

Objectives: To clarify the association of job stressor score (A score), psychological and physical stress response score (B score), and social support (C score), with the incidence of ≥10% weight gain., Methods: This study included 10,036 university employees who completed the brief job stress questionnaire (BJSQ) and annual health checkups between 2016 and 2021. The incidence of ≥10% weight gain from baseline weight was measured. Participants were classified into four categories based on their BJSQ dimension scores., Results: B score was significantly associated with the incidence of weight gain, whereas A and C scores were not. Participants of Q75-89, and Q90-100 categories of B score were at significantly high risk of the incidence of ≥10% weight gain., Conclusions: Psychological and physical stress response had an increasing risk of weight gain., Competing Interests: Conflict of Interest: Kaori Nakanishi received funding from the Smoking Research Foundation and has no relationships, conditions, or circumstances that present a potential conflict of interest to this research., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

We aimed to investigate the efficacy of romosozumab treatment compared with that of denosumab in especially male osteoporosis patients. This retrospective cohort study included 174 Japanese male patients receiving either denosumab or romosozumab for 12 months. Propensity score matching extracted 50 patients per treatment group for standardization of group characteristics. The endpoints include the rate of change in the bone mineral density (BMD) of the lumbar spine, total hip, and femoral neck after 12 months of treatment as well as the changes in serum bone metabolism markers. The mean 12-month percentage increase in the lumbar spine BMD from baseline was significantly greater with romosozumab (13.0% ±1.7%) than with denosumab (4.5%±0.6%) (P < 0.01). The total hip and femoral neck BMD exhibited a similar trend at 12 months; however, no significant between-group differences were observed. With denosumab, bone formation, and resorption marker levels significantly decreased at 6 and 12 months. Conversely, with romosozumab, the levels of bone formation markers increased transiently at 6 months before returning to baseline, whereas bone resorption markers significantly decreased at both time points. Romosozumab demonstrated significantly superior effects over denosumab in improving BMD, especially of the lumbar spine, suggesting that romosozumab can be used for treating male osteoporosis., (© 2024. The Author(s).)

Non-excitable cells express sodium voltage-gated channel alpha subunit 1 gene and protein (known as SCN1A and NaV1.1, respectively); however, the functions of NaV1.1 are unclear. In this study, we investigated the role of SCN1A and NaV1.1 in human mesenchymal stem cells (MSCs). We found that SCN1A was expressed in MSCs, and abundant expression of NaV1.1 was observed in the endoplasmic reticulum; however, this expression was not found to be related to Na+ currents. SCN1A-silencing reduced MSC proliferation and delayed the cell cycle in the S phase. SCN1A silencing also suppressed the protein levels of CDK2 and AKT (herein referring to total AKT), despite similar mRNA expression, and inhibited AKT phosphorylation in MSCs. A cycloheximide-chase assay showed that SCN1A-silencing induced CDK2 but not AKT protein degradation in MSCs. A proteolysis inhibition assay using epoxomicin, bafilomycin A1 and NH4Cl revealed that both the ubiquitin-proteasome system and the autophagy and endo-lysosome system were irrelevant to CDK2 and AKT protein reduction in SCN1A-silenced MSCs. The AKT inhibitor LY294002 did not affect the degradation and nuclear localization of CDK2 in MSCs. Likewise, the AKT activator SC79 did not attenuate the SCN1A-silencing effects on CDK2 in MSCs. These results suggest that NaV1.1 contributes to the cell cycle of MSCs by regulating the post-translational control of AKT and CDK2., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Background: Minimally invasive surgical techniques have been widely adopted in colorectal surgery. New technological breakthroughs have led to even less invasive alternatives like single-port surgery, but this has been hindered by technical challenges such as the collision of robotic arms within a limited space. The Intuitive da Vinci Single-Port robotic platform is a novel system that overcomes some of these challenges., Impact of Innovation: This study aimed to assess the safety and feasibility of the Intuitive da Vinci Single-Port robotic platform in right segmental colectomies among adult patients. These findings may set the stage for more widespread use of single-port robotic surgery., Technology, Materials, and Methods: The Intuitive da Vinci Single-Port robot is a system designed specifically for single-port robotic surgery. This platform enables flexible port location and efficient internal and external range of motion using a single C-shaped arm. In the present study, right colectomies were performed in adult patients using this platform between May 2022 and November 2022, and they were compared to right colectomies in adult patients performed using the standard multiport platform between January 2019 and December 2022. The main outcome measure was safety and quality event rates., Preliminary Results: Of 30 patients, 16.7% of patients (n = 5) underwent single-port robotic right colectomy and 83.3% (n = 25) underwent multiport right colectomy. In the single-port group, 40% of patients (n = 2) developed a safety/quality event (postoperative portal vein thrombosis and excessive postoperative pain). In the multiport group, 32% of patients (n = 8) developed 1 safety/quality event and 8% (n = 2) had more than 1 event., Conclusions and Future Directions: This preliminary study, one of the first Food and Drug Administration-approved, investigator-initiated uses of this platform in colorectal surgeries, shows that this platform is a safe and feasible option for right colectomies. On preliminary evaluation, it appears comparable in terms of relevant safety/quality events to the multiport platform., Clinical Trial Registration: Clinicaltrials.gov NCT05321134., (Copyright © The ASCRS 2024.)

We present a unique case of metastatic metaplastic breast carcinoma responding dramatically to immunochemotherapy. A 46-year-old Japanese woman with primary metaplastic carcinoma of the breast, which was immunohistochemically confirmed to be triple-negative breast cancer, underwent radical surgery, followed by adjuvant chemotherapy with an anthracycline and a taxane. Since multiple lung metastases were detected two months post-chemotherapy and the primary site was shown to be PD-L1-positive, the immune checkpoint inhibitor (ICI) pembrolizumab plus gemcitabine/carboplatin was initiated. While the treatment was discontinued after 15 days due to suspected drug-induced pneumonitis, the lung metastases significantly shrank with no development of new lesions for three months. The patient remained alive as of approximately 15 months after the recurrence date. This case highlights the potential of immunochemotherapy in treating metaplastic breast carcinomas., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: Identification of homologous recombination deficiency (HRD) remains a challenge in advanced pancreatic cancer (APC). We investigated the utility of circulating tumour DNA (ctDNA) profiling in the assessment of BRCA1/2 and ATM mutation status and treatment selection in APC., Methods: We analysed clinical and ctDNA data of 702 patients with APC enroled in GOZILA, a ctDNA profiling study using Guardant360., Results: Inactivating BRCA1/2 and ATM mutations were detected in 4.8% (putative germline, 3.7%) and 4.4% (putative germline, 0.9%) of patients, respectively. Objective response (63.2% vs. 16.2%) and PFS (HR 0.55, 95% CI 0.32-0.93) on platinum-containing chemotherapy were significantly better in patients with putative germline BRCA1/2 (gBRCA) mutation than those without. In contrast, putative gBRCA mutation had no impact on the efficacy of gemcitabine plus nab-paclitaxel. In 2 patients treated with platinum-containing therapy, putative BRCA2 reversion mutations were detected. Three of seven patients with somatic BRCA mutations responded to platinum-containing therapy, while only one of four with putative germline ATM mutations did. One-third of somatic ATM mutations were in genomic loci associated with clonal haematopoiesis., Conclusion: Comprehensive ctDNA profiling provides clinically relevant information regarding HRD status. It can be a practical, convenient option for HRD screening in APC., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Although gastric neuroendocrine tumors (NETs) are uncommon compared with gastric carcinomas, the incidence of NETs has been recently increasing. Gastric NETs are classified into three subgroups, and among these, gastrin-independent sporadic type 3 gastric NETs have a poor prognosis because of frequent lymph node or distant metastasis. We experienced a case of an early-stage type 3 gastric NET associated with lymphovascular and submucosal invasion. In a 54 year-old woman, esophagogastroduodenoscopy performed during a health screening identified an elevated lesion of the upper body of the stomach. The results of immunohistochemical analyses of endoscopic biopsy specimens obtained from the lesion were positive for chromogranin A and synaptophysin, indicating an NET. Because the patient's serum gastrin level was normal and she had no predisposing conditions for NET development, the tumor was diagnosed as a type 3 gastric NET. The patient underwent local resection of the tumor and regional lymph node dissection. The resected specimen indicated a diagnosis of type 3 gastric NET with invasion into the submucosa and lymphatic duct. This is an extremely rare case of an early-stage type 3 gastric NET. Our discussion provides insight into the pathogenesis and development of these tumors and the appropriate therapeutic strategy., (© 2024. Japanese Society of Gastroenterology.)

Despite the widespread recognition of the global concern regarding the onset of cardiovascular diseases in a significant number of patients following cancer treatment, definitive strategies for prevention and treatment remain elusive. In this study, we established systems to evaluate the influence of anti-cancer drugs on the quality control of mitochondria, pivotal for energy metabolism, using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor used for treatment in lung cancer, reportedly increases the risk of cardiovascular disease. However, its underlying mechanism is largely unknown. Here, we found that the treatment of hiPSC-CMs with osimertinib and doxorubicin, but not trastuzumab and cisplatin, revealed a concentration-dependent impairment of respiratory function accompanied by mitochondrial fission. We previously reported the significant role of sulfur metabolism in maintaining mitochondrial quality in the heart. Co-treatment with various inorganic sulfur donors (Na 2 S, Na 2 S 2 , Na 2 S 3 ) alongside anti-cancer drugs demonstrated that Na 2 S attenuated the cardiotoxicity of osimertinib but not doxorubicin. Osimertinib decreased intracellular reduced sulfur levels, while Na 2 S treatment suppressed the sulfur leakage, suggesting its potential in mitigating osimertinib-induced cardiotoxicity. These results imply the prospect of inorganic sulfides, such as Na 2 S, as a seed for precision pharmacotherapy to alleviate osimertinib's cardiotoxic effects., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Perovskite solar cells are actively investigated for their potential as highly efficient and cost-effective photovoltaic devices. However, a significant challenge in their practical application is enhancing their durability. Particularly, these cells are expected to be subjected to heating by sunlight in real-world operating environments. Therefore, high-temperature durability and device operation under such conditions are critical. Our study aims to improve the durability of perovskite solar cells for practical applications by examining their temperature coefficients at elevated temperatures using MA-free compositions. We assessed these coefficients and investigated their correlation with the ideality factor, revealing that carrier recombination markedly affects the temperature behavior of these cells. Our methodology involves simple J-V measurements to evaluate device degradation at high temperatures, paving the way for further research to enhance device performance in such environments., (© 2024 Wiley-VCH GmbH.)

Fucoxanthin (FX), a non-provitamin-A carotenoid, is a well-known major xanthophyll contained in edible brown algae. The nanoencapsulation of FX was motivated due to its multiple activities. Here, nano-encapsulated-FX (nano-FX) was prepared according to our early method by using whey protein and flaxseed gum as the biomacromolecule carrier material, then in vivo antitumor effect and mechanism of nano-FX on xenograft mice were investigated. Thirty 4-week-old male BALB/c nude mice were fed adaptively for 7 days to establish xenograft tumor model with Huh-7 cells. The tumor-bearing mice consumed nano-FX (50, 25, and 12.5 mg kg -1 ) and doxorubicin hydrochloride (DOX, 1 mg kg -1 ) or did not consume (Control) for 21 days, n = 6. The tumor inhibition rates of nano-FX were as high as 54.67 ± 1.04 %. Nano-FX intervention promoted apoptosis and induced hyperchromatic pyknosis and focal necrosis in tumor tissue by down-regulating the expression of p-JNK, p-ERK, PI3Kp85α, p-AKT, p-p38MAPK, Bcl-2, CyclinD1 and Ki-67, while up-regulating the expression of cleaved caspase-3 and Bax. Nano-FX inhibited tumor growth and protected liver function of tumor bearing mice in a dose-dependent manner, up-regulate the level of apoptosis-related proteins, inhibit the MAPK-PI3K/Akt pathways, and promote tumor cell apoptosis., Competing Interests: Declaration of competing interest The authors state that they have no known competing financial interests or interpersonal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Posttreatment detection of ctDNA is strongly predictive of recurrence. Most minimal/molecular residual disease assays require prior tissue testing to guide ctDNA analysis, resulting in lengthy time to initial results and unevaluable patients., Experimental Design: We assessed a tissue-free assay (Guardant Reveal) that bioinformatically evaluates >20,000 epigenomic regions for ctDNA detection in 1,977 longitudinally collected postoperative plasma samples from 342 patients with resected colorectal cancer., Results: We observed sensitive and specific detection of minimal/molecular residual disease associated with clinically meaningful differences in recurrence-free intervals at each time point evaluated with a median lead time of 5.3 months. The longitudinal sensitivity in stage II or higher colon cancer was 81%. Sensitivity increased with serial measurement and varied by recurrence site: higher for liver (100%) versus lung (53%) and peritoneal (40%). Sensitivity among patients with rectal cancer was 60% owing to a high proportion of lung metastases. Specificity was 98.2% among 1,461 posttreatment samples (99.1% among those with follow-up longer than the upper IQR of the lead time observed in this study)., Conclusions: Our data demonstrate the potential clinical utility of ctDNA as a tool to improve the management of stage II and higher colorectal cancer with a methodology that is noninvasive, accessible, and allows for rapid evaluation to inform clinical decisions., (©2024 The Authors; Published by the American Association for Cancer Research.)

Hydrophobic polymer plates with smooth and rough surfaces are used as a stabilizer for cubic liquid marbles (LMs) to study the effect of surface roughness on their formation. The smooth and rough polymer plates can stabilize LMs using liquids with surface tensions of 72.8-26.6 and 72.8-22.9 mN m -1 , respectively. It is clarified that the higher the surface roughness, the lower the surface tension of the liquids are stabilized to form the LMs. These results indicated that the introduction of surface roughness improves the hydrophobicity of the polymer plates and the rough polymer plates can stabilize LMs using liquids with a wider surface tension range. Electron microscopy studies and numerical analyses confirmed that the LMs can be formed, when the Cassie-Baxter wetting state, where θ Y >90° (θ Y : the contact angle on smooth surfaces) and θ R >90° (θ R : the contact angle on rough surfaces), and the metastable Cassie-Baxter wetting state, where θ Y <90° and θ R >90°, are realized. Finally, the synthesis of cubic polymer particles are succeeded by free radical polymerization of the cubic LMs containing a hydrophobic vinyl monomer (dodecyl acrylate) in a solvent-free manner., (© 2024 Wiley‐VCH GmbH.)

Background: Usual interstitial pneumonia (UIP) cases without honeycombing (possible UIP) included various CT features and was often difficult to diagnose., Purpose: This study aimed to classify the cases with possible UIP on CT features using cluster analysis and evaluate the features of subsets of participants and the correlation of prognosis., Materials and Methods: The study included 85 patients with possible UIP in the 2011 idiopathic pulmonary fibrosis (IPF) guideline with radiological diagnosis. All cases underwent surgical biopsies and were diagnosed by multidisciplinary discussion (MDD) from the nationwide registry in Japan. The readers evaluated pulmonary opacity, nodules, cysts, and predominant distribution which were reclassified by IPF guidelines in 2018. Additionally, cases were classified into four groups by cluster analysis based on CT findings. The differences in survival among IPF classification and the clusters were evaluated., Results: Cases were diagnosed as IPF (n = 55), NSIP (n = 4), unclassifiable (n = 23), and others (n = 3) by MDD. Cluster analysis revealed 4 clusters by CT features (n = 47, 16, 19 and 3, respectively). Cluster 1 had fewer lesions overall. Cluster 2 have many pure ground-glass opacities and ground-glass opacities with reticulation. Cluster 3 had many reticular opacities and nodules with few lower predominant distributions. Cluster 4 was characterized by peribronchovascular consolidation.The mean survival time of cluster 1 (4518 days) was significantly better than cluster 2, 3, and 4 (1843, 2196, and 1814 days, respectively) (p = 0.03)., Conclusion: In conclusion, UIP without honeycombing included various CT patterns and MDD diagnoses. Significangly differences in prognosis were observed among clusters classified by CT findings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [H.S. reports lectures fee from Eisai Co., Ltd. and Shionogi Co. Ltd., and expert testimony from Fujifilm Corporation, and support for attending meetings from Boehringer Ingelheim. T.J. reports lectures fee from Bohlinger Ingelheim, AstraZeneca and Kyorin Inc. R.E. reports lectures fee from Boehringer Ingelheim, KYORIN Pharmaceutical Co.,Ltd., Bayer Yakuhin, Ltd., Taiwan Shionogi & Co., Ltd. and AstraZeneca K.K., and expert testimony from DAIICHI SANKYO Co., Ltd. , and support for attending meetings from Boehringer Ingelheim. Y.N. reports lectures fee from Nippon Boehringer Ingelheim and Bristol Myers Squibb. H.S, C.S., T.T., M.N., A.K., N.T., T.F. and T.S. has nothing to disclose]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purposes: We performed a conversation analysis of the speech conducted among the surgical team during three-dimensional (3D)-printed liver model navigation for thrice or more repeated hepatectomy (TMRH)., Methods: Seventeen patients underwent 3D-printed liver navigation surgery for TMRH. After transcription of the utterances recorded during surgery, the transcribed utterances were coded by the utterer, utterance object, utterance content, sensor, and surgical process during conversation. We then analyzed the utterances and clarified the association between the surgical process and conversation through the intraoperative reference of the 3D-printed liver., Results: In total, 130 conversations including 1648 segments were recorded. Utterance coding showed that the operator/assistant, 3D-printed liver/real liver, fact check (F)/plan check (Pc), visual check/tactile check, and confirmation of planned resection or preservation target (T)/confirmation of planned or ongoing resection line (L) accounted for 791/857, 885/763, 1148/500, 1208/440, and 1304/344 segments, respectively. The utterance's proportions of assistants, F, F of T on 3D-printed liver, F of T on real liver, and Pc of L on 3D-printed liver were significantly higher during non-expert surgeries than during expert surgeries. Confirming the surgical process with both 3D-printed liver and real liver and performing planning using a 3D-printed liver facilitates the safe implementation of TMRH, regardless of the surgeon's experience., Conclusions: The present study, using a unique conversation analysis, provided the first evidence for the clinical value of 3D-printed liver for TMRH for anatomical guidance of non-expert surgeons., (© 2024. The Author(s).)