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Type I X-ray bursts are rapid-brightening transient phenomena on the surfaces of accreting neutron stars (NSs). Some X-ray bursts, called clocked bursters, exhibit regular behavior with similar light-curve profiles in their burst sequences. The periodic nature of clocked bursters has the advantage of constraining X-ray binary parameters and physics inside the NS. In the present study, we compute numerical models, based on different equations of state and NS masses, which are compared with the observations of a recently identified clocked burster, 1RXS J180408.9−342058. We find that the relation between the accretion rate and the recurrence time is highly sensitive to the NS mass and radius. We determine, in particular, that 1RXS J180408.9−342058 appears to possess a mass less than 1.7 M ⊙ and favors a stiffer nuclear equation of state (with an NS radius ≳12.7 km). Consequently, the observations of this new clocked burster may provide additional constraints for probing the structure of NSs. [ABSTRACT FROM AUTHOR]

Background: Hypoattenuated area (HA) formation at the pancreatojejunostomy (PJ) site on contrast-enhanced computed tomography (CE-CT) is significantly associated with clinically relevant postoperative pancreatic fistula (CR-POPF) after open pancreaticoduodenectomy (PD) (O-PD). Here, we evaluated the impact of HA formation in robotic PD (R-PD) and surgical factors predictive of HA formation., Methods: The study retrospectively analyzed 66 patients who underwent either O-PD or R-PD and exhibited a drain amylase level exceeding three times the upper limit of normal range, with CE-CT assessment performed on postoperative days 3-14. Patients were divided into two groups, with evident HA (≥ 5 mm) (E-HA) and subtle HA (< 5 mm) (S-HA), and their data were analyzed by multivariate and propensity-score matching analyses., Results: Among the patients, 24 (36.3%) exhibited E-HA and 42 (63.7%) S-HA. The percentages of R-PD and CR-POPF in E-HA group were significantly lower and higher, respectively, than S-HA group (R-PD: 29.2% vs 54.8%, p = 0.0446; CR-POPF: 70.8% vs 4.8%, p < 0.0001). Multivariate analysis revealed the surgical approach as a significant factor associated with E-HA formation (odds ratio: 0.26; p = 0.0223). Propensity-score matching analysis revealed significantly fewer patients with E-HA formation and CR-POPF in R-PD group than O-PD group (E-HA: 14.3% vs 64.3%, p = 0.0068; CR-POPF: 14.3% vs 57.1%, p = 0.0180)., Conclusion: The impact of HA formation in predicting CR-POPF was confirmed in the patients undergoing PD, including O-PD and R-PD. Furthermore, the data suggest that R-PD, compared with O-PD, significantly decreased the incidence of E-HA formation, indicating an advantage of R-PD over O-PD in reducing CR-POPF via HA formation., Competing Interests: Declarations. Disclosures: Drs. Yoshito Tomimaru, Shogo Kobayashi, Kazuki Sasaki, Shinichiro Hasegawa, Daisaku Yamada, Hirofumi Akita, Takehiro Noda, Hidenori Takahashi, Hiroki Imamura, Yuichiro Doki, and Hidetoshi Eguchi have no conflicts of interest or financial ties to disclose., (© 2025. The Author(s).)

Clinical evidence of oral inotrope use for advanced heart failure (HF) is limited. This study investigated the contemporary use and association of oral inotropes with prognosis in the outpatient treatment of advanced HF using a nationwide administrative claims database in Japan. Patients hospitalized with acute HF between 2014 and 2021 were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Associations of the drug use after discharge with the 2-year prognosis were examined in a propensity-matching cohort, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Of the 428,650 patients discharged with HF in 4433 hospitals, 14,374 (3.4%) had taken oral inotropes, most of whom (95.0%) took pimobendan. Patients taking oral inotropes were younger and more likely to receive HF drugs. Cardiomyopathy as the etiology and the use of intravenous inotropes during hospitalization were more frequently observed. In the 2-year prognosis, oral inotrope use was associated with higher all-cause mortality and HF rehospitalization rates (HR [95% CI]: 1.59 [1.51, 1.66] and 1.54 [1.48, 1.61], respectively). Concomitant use of pimobendan and β-blockers was associated with lower mortality and HF rehospitalization (0.81 [0.74, 0.88] and 0.85 [0.79, 0.92], respectively) compared with pimobendan without β-blockers. Although no association was found between oral inotrope use and favorable prognosis, concomitant use of β-blockers may be a better strategy for oral inotrope use in advanced HF., (© 2025, The American College of Clinical Pharmacology.)

Background: The SARS-CoV-2 pandemic provided important insights into the relationship between infectious diseases and the human genome. A genomic region encoding the 2'-5'-oligoadenylate synthetase (OAS) family proteins that sense viral genomic RNAs and trigger an antiviral response contains single nucleotide polymorphisms (SNPs) associated with SARS-CoV-2 infection susceptibility. A high-risk SNP identified at the splice acceptor site of OAS1 exon 6-a terminal exon-alters the proportion of various splicing isoforms of OAS1 and its activity. However, the actual causality of this SNP or splicing to infection susceptibility remains unknown., Results: In this study, it was found that serine-arginine-rich splicing factor 6 (SRSF6) binds to the splice donor site of the human OAS1 exon 5. SRSF6 determines the selected alternative terminal exon when the risk allele disrupts the splice acceptor site. Subsequently, an inhibitor for CDC-like kinase was rationally selected as a candidate splicing modulator. RNA-Seq and RT-PCR analyses revealed that this inhibitor can induce splice switching of OAS1 mRNAs in the human lung adenocarcinoma cell line Calu-3. Under the inhibitor treatment, the cells exhibited reduced SARS-CoV-2 infection rates. Meanwhile, the colonic epithelial cell line Caco-2 expressed non-risk type OAS1 mRNA isoforms that did not undergo splice-switching or demonstrate altered SARS-CoV-2 sensitivity following treatment with the inhibitor., Conclusions: These results indicate that a high-risk SNP in OAS1 influences cell susceptibility to SARS-CoV-2 infection by inducing splice-switching at its terminal exon. Additionally, chemical splicing modifiers may prove beneficial in overcoming this genomic vulnerability., Competing Interests: Declarations. Ethics approval and consent to participate: This article does not contain any content that requires ethical approval or consent to participate. Consent for publication: This article does not contain any content that requires consent for publication. Competing interests: M.H. is a founder, shareholder, and member of the scientific advisory board of KinoPharma, Inc., and BTB Drug Development Research Center Co., Ltd. This work has been filed for a world patent application (WO2022/255411 A1); M.H., K.I., and T.N. are named as co-inventors. The authors have no other competing interests to declare., (© 2025. The Author(s).)

The Japanese Archipelago consists of a series of isolated yet interconnected islands off the Eurasian continent. The linear topography of the archipelago presents a unique biogeographic context for the dispersal of organisms from the continent. In this study, mitochondrial DNA (mtDNA) and single-nucleotide polymorphism (SNP) variation were employed to elucidate the dispersal history of the Japanese clouded butterfly (Parnassius glacialis) across the Japanese Archipelago, including the northern island (Hokkaido), the main island (Honshu), and Shikoku Island. Network analysis of 1192 bp of mtDNA (cytochrome oxidase I and II) regions revealed 49 haplotypes and three distinct haplotype groups, which correspond geographically to Eastern Japan, Western Japan, and Chugoku-Shikoku. The Chugoku-Shikoku group is the most ancient lineage. Divergence time estimates using whole-genome sequencing of mtDNA suggest that the Japanese lineage diverged from the continental P. glacialis approximately 3.08 million years ago (Ma). Subsequently, the Eastern Japan and Western Japan lineages diverged from the Chugoku-Shikoku lineage around 1.06 Ma, with subsequent divergence of the Eastern and Western Japan lineages at approximately 0.62 Ma. P. glacialis is estimated to have expanded its distribution via a land bridge that once connected China and the Japanese Archipelago. Population structure analysis based on 3067 SNP genotypes revealed five distinct genetic structures within the Japanese Archipelago, indicating geographical differentiation. Through mtDNA and SNP variation analyses, four primary genetic barriers were identified: between Hokkaido and Honshu, between Eastern and Central Japan, within the Kansai region, and in the Chugoku region. The first three barriers correspond to notable geographical features, the Blakiston Line, a line parallel to the Itoigawa-Shizuoka Tectonic Line, and a boundary crossing Lake Biwa. These findings suggest that Japanese P. glacialis diverged from the continental P. glacialis and expanded its range across the Japanese Archipelago via western routes, leading to its current distribution., 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 Author(s). Published by Elsevier Inc. All rights reserved.)

We investigated the potential of adipose-derived stem cells (ADSCs) in preventing post-hepatectomy liver failure, emphasizing the necessity of direct administration using a scaffold. A fibrin gel scaffold was employed for ADSCs (gelADSC) to assess their therapeutic impact on liver regeneration in both in vitro and in vivo settings. Experiments were conducted on C57BL/6 mice with normal livers and those with chronic hepatitis. We also explored the role of extracellular vesicles (EVs) secreted by ADSCs in conjunction with fibrin gel. GelADSC showed sustained release of hepatocyte growth factor, vascular endothelial growth factor, and stromal cell-derived factor 1 for at least 7 days in vitro. In vivo, gelADSC significantly enhanced postoperative liver regeneration by upregulating the cell cycle and fatty acid oxidation in both normal and chronically hepatitis-affected mice. The therapeutic effects of gelADSC were potentially favorable over those of intravenously administered ADSCs, especially in mice with chronic hepatitis. Increased EV secretion associated with fibrin gel use was significantly linked to enhanced liver regeneration post-surgery through the promotion of fatty acid oxidation. The findings underscore the enhanced therapeutic potential of gelADSC, particularly in the context of chronic hepatitis, possibly compared to intravenous administration., Competing Interests: Declarations. Competing interests: HI received a research fund from Rohto Pharmaceutical Co., Ltd., and SK (Shogo Kobayashi) received honoraria from AstraZeneca and Taiho. The other authors (YT, AH, SK (Shunbun Kita), KS, YI, DY, TN, HT, DH, TK, KT, TK, SS, IS, SM, YD, HE) declare no competing financial interests., (© 2025. The Author(s).)

A process technology was developed for transferring strained graphene sheets using an elastomer nanosheet to enhance the resonance characteristics of a graphene resonator. The strain-induced graphene resonator demonstrated a 1.80-fold improvement in the product of resonant frequency and Q -factor compared to the unstrained resonator. The system exhibited a frequency change in response to single inactivated SARS-CoV-2 whole virus by functionalizing the surface of the strained suspended graphene with a DNA aptamer, indicating a mass sensitivity of 0.99 zg Hz -1 , which is 3.5 × 10 6 times greater than conventional chemisorption-based resonant mass sensors.

Objectives: Although various kinematic parameters have been investigated as factors associated with shoulder and elbow injuries during pitching, the relationship between lower extremity flexibility and such injuries remains unclear. The objective of this meta-analysis was to examine the association between pitching injuries to the shoulder and elbow and lower extremity flexibility., Designs: A systematic review and meta-analysis., Date Sources: A comprehensive meta-analysis was conducted using data extracted from five databases (MEDLINE, Web of Science, CENTRAL, Scopus, and PEDro) following the method of Minds. The inclusion criteria were studies focusing on throwing injuries in the shoulder and elbow, specifically related to baseball, and the investigation of motion in the lower extremities. Owing to the presence of cross-sectional and cohort studies, meta-analyses were conducted for each study type., Main Results: Meta-analyses were performed using data from 11 reports. The results revealed a significant difference in lead-side hip internal rotation for both cross-sectional (P = 0.04) and cohort studies (P = 0.02), indicating a reduced range of motion (ROM) in athletes with shoulder and elbow injuries. In addition, a significant difference was observed in the hip internal rotation of the trail leg in the cross-sectional study (P = 0.04), similar to that of the lead leg. However, no significant differences were found in hip external rotation or straight leg raising (SLR) between players with and without shoulder or elbow injuries., Conclusions: This meta-analysis highlights the common occurrence of limited internal hip rotation ROM in baseball players with shoulder or elbow injuries. However, these injuries were not found to be associated with hip external rotation or SLR., Competing Interests: The authors report no conflicts of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Whether radiation should be added to neoadjuvant treatment remains controversial, and liquid biopsy has not been reported to predict radioresistance in pancreatic cancer (PC). We aimed to identify microRNAs (miRNAs) governing radioresistance in PC by utilizing peripheral plasma exosome samples and to verify their usefulness as biomarkers., Methods: miRNA microarray analysis was conducted using pretreatment peripheral plasma exosomes from 10 patients with PC receiving neoadjuvant chemoradiotherapy (NACRT) in the discovery cohort. Patients were categorized into two groups (good and poor responders) based on treatment responses, and candidate miRNAs exhibiting differential expression between the two groups were identified. The radiosensitivity of PC cells was examined after miR-6855-5p overexpression. Next-generation sequencing (NGS) and TargetScan were used to explore the mechanisms of radioresistance. We investigated the correlation between miR-6855-5p expression levels in the pretreatment peripheral plasma exosomes of 28 patients in the validation cohort and the response to NACRT., Results: miR-6855-5p expression was higher in poor responders than in good responders. miR-6855-5p induces radioresistance in PC cells. NGS showed that epithelial-mesenchymal transition (EMT) was involved in miR-6855-5p-related radioresistance. Forkhead box protein A1 (FOXA1) was identified as a direct target of miR-6855-5p using NGS and TargetScan. Clinical examination of samples from the validation cohort revealed a tendency for patients with higher expression of miR-6855-5p in peripheral plasma exosomes to exhibit increased radioresistance (r = -0.5964)., Conclusions: miR-6855-5p regulates the radioresistance of PC by inducing EMT via suppressing FOXA1, and miR-6855-5p in peripheral plasma exosomes may be a biomarker for radioresistance of PC., Competing Interests: Ethics Approval and Consent to Participate: This study was approved by the Institutional Review Board (IRB) of Osaka University Hospital (IRB No. 08226-12) and adhered to the principles outlined in the Declaration of Helsinki. Patient Consent for Publication: Written informed consent was obtained from all blood donors. Disclosures: Shogo Kobayashi received honoraria and speaker fees from AstraZeneca, Ethicon Inc., Intuitive, Olympus, and Taiho Pharmaceutical. Hiroki Ueda, Hidenori Takahashi, Masahiko Kubo, Kazuki Sasaki, Yoshifumi Iwagami, Daisaku Yamada, Yoshito Tomimaru, Tadafumi Asaoka, Takehiro Noda, Junzo Shimizu, Yuichiro Doki, and Hidetoshi Eguchi have no conflicts of interest that may be relevant to the contents of this study., (© 2024. Society of Surgical Oncology.)

Mammalian sperm cells travel from their origin in the male reproductive tract to fertilization in the female tract through a complex process driven by coordinated mechanical and biochemical mechanisms. Recent experimental and theoretical advances have illuminated the collective behaviors of sperm both in vivo and in vitro. However, our understanding of the underlying mechano-chemical processes remains incomplete. This review integrates current insights into sperm group movement, examining both immotile and motile states, which are essential for passive transport and active swimming through the reproductive tracts. We provide an overview of the current understanding of collective sperm movement, focusing on the experimental and theoretical mechanisms behind these behaviors. We also explore how sperm motility is regulated through the coordination of mechanical and chemical processes. Emerging evidence highlights the mechanosensitive properties of a sperm flagellum, suggesting that mechanical stimuli regulate flagellar beating at both individual and collective levels. This self-regulatory, mechano-chemical system reflects a broader principle observed in multicellular systems, offering a system-level insight into the regulation of motility and collective dynamics in biological systems., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Although the mechanism underlying flutamide- or bicalutamide-induced liver injury may be immune related, the details remain unclear. If this mechanism is immune related, steroid use may be considered as a treatment option., Aim: Disproportionality analysis was conducted to evaluate the effect of concomitant steroid use on flutamide- and bicalutamide-induced liver injury., Method: Male patients aged 20 years or older who were receiving nonsteroidal anti-androgens from April 2004 to October 2023 were screened from the Japanese Adverse Drug Event Report database. Data on liver injury, age, weight, height, steroid use, obesity, hepatic stenosis, alcohol-related hepatic disorders, hepatitis B and C, and common drugs known to cause drug-induced liver injury were analyzed. Liver injury was defined by the Standardized Medical Dictionary for Regulatory Activities query index (code 20000006, version 27.0)., Results: Among 142,430 patients, 2,316 were administered nonsteroidal anti-androgens. Reports of liver injury were disproportionate depending on the agents used (reporting odds ratio [ROR], 1.29; 95% confidence intervals [CI], 1.13-1.46), especially among flutamide or bicalutamide users (flutamide: ROR, 6.09; 95% CI, 4.51-8.23; bicalutamide: ROR, 1.24; 95% CI, 1.05-1.48). Multivariable logistic regression analysis correlated steroid use with a lower risk of flutamide- or bicalutamide-induced liver injury (flutamide: odds ratio, 0.07; 95% CI, 0.01-0.52; bicalutamide: odds ratio, 0.45; 95% CI, 0.21-0.96)., Conclusion: Our findings suggest that flutamide and bicalutamide may increase the risk of liver injury compared to enzalutamide, apalutamide, and darolutamide. Furthermore, our study indicated that steroid use could aid in the management of liver injury., Competing Interests: Conflicts of interest: The authors have no conflicts of interest to declare., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)