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The secondary plastoquinone (PQ) electron acceptor Q B in photosystem II (PSII) undergoes a two-step photoreaction through electron transfer from the primary PQ electron acceptor Q A , converting into plastoquinol (PQH 2 ). However, the detailed mechanism of the Q B reactions remains elusive. Here, we investigated the reaction mechanism of Q B in cyanobacterial PSII core complexes using two time-revolved infrared (TRIR) methods: dispersive-type TRIR spectroscopy and rapid-scan Fourier transform infrared spectroscopy. Upon the first flash, the ∼140 μs phase is attributed to electron transfer from Q A •- to Q B , while the ∼2.2 and ∼440 ms phases are assigned to the binding of an internal PQ in a nearby cavity to the vacant Q B site and an external PQ traveling to the Q B site through channels, respectively, followed by immediate electron transfer. The resultant Q B •- is suggested to be in equilibrium with Q B H • , which is protonated at the distal oxygen. Upon the second flash, the ∼130 μs and ∼3.3 ms phases are attributed to electron transfer to Q B H • and the protonation of Q B •- followed by electron transfer, respectively, forming Q B H - , which then immediately accepts a proton from D1-H215 at the proximal oxygen to become Q B H 2 . The resultant D1-H215 anion is reprotonated in ∼22 ms via a pathway involving the bicarbonate ligand. The final ∼490 ms phase may reflect the release of PQH 2 and its replacement with PQ. The present results highlight the importance of time-resolved infrared spectroscopy in elucidating the mechanism of Q B reactions in PSII.

Background and Aim: Chronic constipation negatively impacts work productivity and patients' quality of life. This retrospective study assessed the correlation between symptoms of chronic constipation and work/activity impairment with and without the use of laxative treatment., Methods: This cross-sectional, observational, web-based survey was conducted using the Work Productivity and Activity Impairment-Chronic Constipation Questionnaire and included Japanese patients with chronic constipation receiving prescribed medication. Outcomes of interest included total work productivity and activity impairment and their correlation with constipation symptoms., Results: Among the 2351 analyzed patients (mean [SD] age, 51.7 [13.8] years), 80.7% were females, 63.3% had a disease duration of ≥10 years, and 1424 were working. The averages of total activity impairment, total work productivity impairment, presenteeism, and absenteeism were 39.2%, 33.9%, 31.2%, and 5.0%, respectively. The annual work productivity loss per patient was estimated to be 1.343 million Japanese Yen. Symptoms that had a statistically significant positive correlation with total work impairment ( P  < 0.05) were abdominal discomfort/nausea, abdominal pain, abdominal bloating, and unpredictable defecation timing. Total activity impairment was significantly ( P  < 0.05) affected by abdominal discomfort/nausea, abdominal bloating, abdominal pain, incomplete defecation, unpredictable defecation timing, loss of defecation desire, and straining. Work productivity and daily activity had improved in 71.2% and 72.6% of patients, respectively, after they received treatment., Conclusion: Symptoms of constipation, particularly abdominal symptoms and unpredictable defecation timing, can have a negative impact on work productivity and daily activity. Treatment focused on these symptoms may reduce the socio-economic burden of chronic constipation in Japan., (© 2024 The Author(s). JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Globally, prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing, and there is an urgent need to develop innovative therapies that promote liver regeneration following hepatectomy for this disease. Surgical excision is a key therapeutic approach with curative potential for liver tumors. However, hepatic steatosis can lead to delayed liver regeneration and higher post-operative complication risk. Mesenchymal stem cells-conditioned medium (MSC-CM) is considered a rich source of paracrine factors that can repair tissues and restore function of damaged organs. Meanwhile, hydrogels have been widely recognized to load MSC secretome and achieve sustained release. This study aimed to evaluate the therapeutic effect of hydrogel-encapsulated MSC-CM on liver regeneration following partial hepatectomy (PHx) in a rodent model of diet-induced hepatic steatosis., Methods: Male Lewis rats were fed with a methionine and choline-deficient diet. After 3 weeks of feeding, PHx was performed and rats were randomly allocated into two groups that received hydrogel-encapsulated MSC-CM or vehicle via the intra-mesenteric space of the superior mesenteric vein (SMV)., Results: The regeneration of the remnant liver at 30 and 168 h after PHx was significantly accelerated, and the expressions of proliferating cell nuclear antigen were significantly enhanced in the MSC-CM group. MSC-CM treatment significantly increased hepatic ATP and β-hydroxybutyrate content at 168 h after PHx, indicating that MSC-CM fosters regeneration not only in volume but also in functionality. The number of each TUNEL- and cleaved caspase-3 positive nuclei in hepatocytes at 9 h after PHx were significantly decreased in the MSC-CM group, suggesting that MSC-CM suppressed apoptosis. MSC-CM increased serum immunoregulatory cytokine interleukin-10 and interleukin-13 at 30 h after PHx. Additionally, mitotic figures and cyclin D1 expression decreased and hepatocyte size increased in the MSC-CM group, implying that this mode of regeneration was mainly through cell hypertrophy rather than cell division., Conclusions: MSC-CM represents a novel therapeutic approach for patients with MASLD requiring PHx., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Scorpion venom contains linear peptides without disulfide bonds in addition to peptides with disulfide bonds. Many such linear peptides have an amphiphilic α-helical structure, often with antimicrobial activity and can be classified into three groups based on their molecular size. Among them, long-chain antimicrobial peptides consisting of more than 40 residues have not been thoroughly studied due to the difficulty of synthesizing them. We have previously reported a transcriptome analysis of the venom gland of Liocheles australasiae that revealed precursor sequences of long-chain antimicrobial peptides. In the study reported here, we identified the mature structure of one such long-chain antimicrobial peptide, LaCT1, which we synthesized using chemical ligation to confirm its structure and evaluate its biological activities. The result showed that LaCT1 exhibited significant antimicrobial activity. In addition, we identified its partial peptides consisting of an N- or C-terminal region, which may be generated by enzymatic cleavage in the venom. Among them, only the peptide containing the N-terminal half region was active. LaCT1 also not only showed insecticidal activity but also synergistically enhanced the effects of another insecticidal peptide identified in L. australasiae venom as well. These results provide insights into the role of antimicrobial peptides in scorpion venom., (© 2024 European Peptide Society and John Wiley & Sons Ltd.)

Recent studies have linked Ruminococcus gnavus to inflammatory bowel disease and Fusobacterium nucleatum to various cancers. Agarooligosaccharides (AOS), derived from the acid hydrolysis of agar, have shown significant inhibitory effects on the growth of R. gnavus and F. nucleatum at concentrations of 0.1 and 0.2%, respectively. RNA sequencing and quantitative reverse-transcription PCR analyses revealed the downregulation of fatty acid biosynthesis genes ( fab genes) in these bacteria when exposed to 0.1% AOS. Furthermore, AOS treatment altered the fatty acid composition of R. gnavus cell membranes, increasing medium-chain saturated fatty acids (C8, C10) and C18 fatty acids while reducing long-chain fatty acids (C14, C16). In contrast, no significant growth inhibition was observed in several strains of Bifidobacteria and Lactobacillales at AOS concentrations of 0.2 and 2%, respectively. Co-culture experiments with R. gnavus and Bifidobacterium longum in 0.2% AOS resulted in B. longum dominating the population, constituting over 96% post-incubation. In vivo studies using mice demonstrated a significant reduction in the Lachnospiraceae family, to which R. gnavus belongs, following AOS administration. Quantitative PCR also showed lower levels of the nan gene, potentially associated with immune disorders, in the AOS group. These findings suggest that AOS may introduce a novel concept in prebiotics by selectively inhibiting potentially pathogenic bacteria while preserving beneficial bacteria such as Bifidobacteria and Lactobacillales.

Flexible thermoelectric generators (TEGs) with pn-junction single-walled carbon nanotube (SWCNT) films on a polyimide substrate have attracted considerable attention for energy harvesting. This is because they generate electricity through the photo-thermoelectric effect by self-generated temperature gradient under uniform sunlight irradiation. To increase the performance and durability of the pn-junction TEGs, n-type films need to be improved as a priority. In this study, bismuth telluride (Bi 2 Te 3 ) nanoplates synthesized by the solvothermal method were added to the n-type SWCNT films, including a cationic surfactant to form the nanocomposite films because Bi 2 Te 3 has high n-type thermoelectric properties and high durability. The performances of the pn-junction TEGs were investigated by varying the heat treatment times. When the artificial sunlight was uniformly irradiated to the pn-junction TEGs, a stable output voltage of 0.47 mV was observed in the TEG with nanocomposite films heat-treated at 1 h. The output voltage decreased with increasing heat treatment time due to the decrease in the p-type region. The output voltage of TEG at 1 h is higher than that of the TEGs without Bi 2 Te 3 nanoplates under the same conditions. Therefore, the addition of Bi 2 Te 3 nanoplates was found to improve the performance of the pn-junction TEGs. These findings may aid in the development of facile and flexible optical devices, including photodetectors and hybrid devices integrating solar cells.

Significance: Confocal microscopy is an indispensable tool for biologists to observe samples and is useful for fluorescence imaging of living cells with high spatial resolution. Recently, phase information induced by the sample has been attracting attention because of its applicability such as the measurability of physical parameters and wavefront compensation. However, commercially available confocal microscopy has no phase imaging function., Aim: We reborn an off-the-shelf confocal microscope as a phase measurement microscope. This is a milestone in changing the perspective of researchers in this field. We would meet the demand of biologists if only they had measured the phase with their handheld microscopes., Approach: We proposed phase imaging based on the transport of intensity equation (TIE) in commercially available confocal microscopy. The proposed method requires no modification using a bright field imaging module of a commercially available confocal microscope., Results: The feasibility of the proposed method is confirmed by evaluating the phase difference of a microlens array and living cells of the moss Physcomitrium patens and living mammalian cultured cells. In addition, multi-modal imaging of fluorescence and phase information is demonstrated., Conclusions: TIE-based quantitative phase imaging (QPI) using commercially available confocal microscopy is proposed. We evaluated the feasibility of the proposed method by measuring the microlens array, plant, and mammalian cultured cells. The experimental result indicates that QPI can be realized in commercially available confocal microscopy using the TIE technique. This method will be useful for measuring dry mass, viscosity, and temperature of cells and for correcting phase fluctuation to cancel aberration and scattering caused by an object in the future., (© 2024 The Authors.)

Quantum information processors benefit from high clock frequencies to fully harness quantum advantages before they are lost to decoherence. All-optical systems offer unique benefits due to their inherent 100-THz carrier frequency, enabling the development of THz-clock frequency processors. However, the bandwidth of quantum light sources and measurement devices has been limited to the MHz range, with nonclassical state generation rates in the kHz range. In this study, we demonstrated broadband generation and quantum tomography of non-Gaussian states using an optical parametric amplifier (OPA) as a squeezed light source and an optical phase-sensitive amplifier (PSA). Our system includes a 6-THz squeezed-light source, a 6-THz PSA, and a 66-GHz homodyne detector. We successfully generated non-Gaussian states at a 0.9 MHz rate with sub-nanosecond wave packets using a continuous-wave laser. The performance is currently limited by the jitter of superconducting detectors, restricting the usable bandwidth to 1 GHz. Our technique extends the bandwidth to GHz, potentially increasing non-Gaussian state generation rates for practical optical quantum processors using OPAs., (© 2024. The Author(s).)

Purpose: Surgeons' adaptability to robotic manipulation remains underexplored. This study evaluated the participants' first-touch robotic training skills using the hinotori surgical robot system and its simulator (hi-Sim) to assess adaptability., Methods: We enrolled 11 robotic surgeons (RS), 13 laparoscopic surgeons (LS), and 15 novices (N). After tutorial and training, participants performed pegboard tasks, camera and clutch operations, energizing operations, and suture sponge tasks on hi-Sim. They also completed a suture ligation task using the hinotori surgical robot system on a suture simulator. Median scores and task completion times were compared., Results: Pegboard task scores were 95.0%, 92.0%, and 91.5% for the RS, LS, and N groups, respectively, with differences between the RS group and LS and N groups. Camera and clutch operation scores were 93.1%, 49.7%, and 89.1%, respectively, showing differences between the RS group and LS and N groups. Energizing operation scores were 90.9%, 85.2%, and 95.0%, respectively, with a significant difference between the LS and N groups. Suture sponge task scores were 90.6%, 43.1%, and 46.2%, respectively, with differences between the RS group and LS and N groups. For the suture ligation task, completion times were 368 s, 666 s, and 1095 s, respectively, indicating differences among groups. Suture scores were 12, 10, and 7 points, respectively, with differences between the RS and N groups., Conclusion: First-touch simulator-based robotic skills were partially influenced by prior robotic surgical experience, while suturing skills were affected by overall surgical experience. Thus, robotic training programs should be tailored to individual adaptability., (© 2024. The Author(s).)

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a central kinase involved in energy homeostasis. Increased intracellular AMP levels result in AMPK activation through the binding of AMP to the γ-subunit of AMPK. Recently, we reported that AMP-induced AMPK activation is impaired in the kidneys in chronic kidney disease (CKD) despite an increase in the AMP/ATP ratio. However, the mechanisms by which AMP sensing is disrupted in CKD are unclear. Here, we identified mechanisms of energy homeostasis in which Unc-51-like kinase 1 (ULK1)-dependent phosphorylation of AMPKγ1 at Ser260/Thr262 promoting AMP sensitivity of AMPK. AMPK activation by AMP was impaired in Ulk1 knockout mice despite an increased AMP/ATP ratio. ULK1 expression is markedly downregulated in CKD kidneys, leading to AMP sensing failure. Additionally, MK8722, an allosteric AMPK activator, stimulated AMPK in the kidneys of a CKD mouse model (5/6th nephrectomy) via a pathway that is independent of AMP sensing. Thus, our study shows that MK8722 treatment significantly attenuates the deterioration of kidney function in CKD and may be a potential therapeutic option in CKD therapeutics., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Alcohol-related liver disease and metabolic-dysfunction-associated steatotic liver disease are the most common causes of chronic liver disease. Globally, alcohol intake, and metabolic syndrome driven by excessive caloric intake and sedentary lifestyle have steadily increased over the past decades. Given the high prevalence rates of both excessive alcohol consumption and components of metabolic syndrome, both can frequently coexist in the same individuals and impact their lives. In this article, we review the impact of alcohol and metabolic syndrome on liver-related outcomes., Competing Interests: Disclosure Dr Z. M. Younossi is a consultant to BMS, GSK, Cymabay, Ipsen, Abbott, Novo Nordisk, Madrigal, Merck, Siemens, and Intercept. Other authors have no conflict of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This is the English version of the guidelines for the diagnosis and treatment of idiopathic portal hypertension, extrahepatic portal obstruction, and Budd-Chiari syndrome, which were established and revised in 2018 by the Aberrant Portal Hemodynamics Study Group under the jurisdiction of the Ministry of Health, Labor, and Welfare in Japan. These guidelines are excerpts, and the full version consists of 86 clinical questions and explanations, totaling 183 pages in Japanese., (© 2024 Japan Society of Hepatology.)

Bisphenol A (BPA) is widely used in manufacturing plastic products, and it has been reported that exposure through the airway or orally aggravates allergic airway inflammation. Because BPA is detected in the atmosphere and indoor environments, the eyes can also be exposed to BPA. After ocular exposure to BPA and antigen via eye drops, we observed enhanced antigen uptake of antigen-presenting cells (APCs) in tear duct-associated lymphoid tissue (TALT). Additionally, we observed the formation of germinal center (GC) B cells in TALT and induction of allergic airway inflammation in mice sensitized with BPA and antigen via eye drops, followed by airway antigen exposure. We also found that DNAX-activating protein of 12 kDa (DAP12)-deficient mice displayed impaired activation of APCs enhanced by ocular exposure to BPA. These results indicate that ocular sensitization to BPA and allergen triggers allergic inflammation via TALT activation, and that DAP12 might be a key molecule for modulating the ocular immune system., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Endothelial dysfunction plays an important role in the pathogenesis of chronic kidney disease. Prostacyclin (PGI 2 ), an endothelial cell-produced endogenous prostaglandin, plays a crucial role in maintaining endothelial function. However, its effects on intestinal microcirculation and barrier function are not fully understood. We hypothesized that PGI 2 improves intestinal microcirculation and barrier function via endothelial protective effects., Methods: ICR and ICGN (a spontaneous nephrotic model) mice were used in this study. Intestinal microcirculation was visualized in vivo to investigate PGI 2 effects. Beraprost served as PGI 2 . PGI 2 administration spanned 4 weeks, following which we assessed its influence on intestinal endothelial, intestinal barrier, and renal functions., Results: We visualized intestinal microcirculation and endothelial glycocalyx in the intestinal blood vessels. Beraprost administration induced a 1.2-fold dilatation of the vascular diameter of the small intestine. Intestinal blood flow in ICGN mice was significantly reduced compared that in ICR mice but improved with beraprost administration. ICGN mice exhibited reduced serum albumin levels, decreased ambulation, an imbalance in intestinal reactive oxygen species (ROS)/nitric oxide (NO), and impaired tight junctions; all were ameliorated by beraprost administration., Conclusions: Beraprost improves intestinal microcirculation and barrier function by ameliorating ROS/NO imbalances, thereby reducing physical inactivity during renal failure., (© 2024 The Author(s). Microcirculation published by John Wiley & Sons Ltd.)

Introduction: Typical atrial flutter (AFL) is a macroreentrant tachycardia in which intracardiac conduction rotates counterclockwise around the tricuspid annulus. Typical AFL has specific electrocardiographic characteristics, including a negative sawtooth-like wave in the inferior lead and a positive F wave in lead V1. This study aimed to analyze the origin of the positive F wave in lead V1, which has not been completely understood., Methods: This study enrolled 10 patients who underwent radiofrequency catheter ablation for a typical AFL. Electroanatomical mapping was performed both during typical AFL and entrainment from the right atrial appendage (RAA). The 12-lead electrocardiogram (ECG) and three-dimensional (3D) electroanatomical maps were analyzed., Results: The positive F wave in lead V1 changed during entrainment from the RAA in all the cases. The 3D map during entrainment from the RAA revealed an area of antidromic capture around the RAA, which collided with the orthodromic wave in the anterior right atrium. This area of antidromic capture around the RAA was the only difference from the 3D electroanatomical map of AFL and is considered the cause of the change in the F wave in lead V1 during entrainment., Conclusion: The analysis of the differences in the 12-lead ECG and 3D maps between tachycardia and entrainment from the RAA clearly demonstrated that activation around the RAA is responsible for the generation of the positive F wave in lead V1 of typical AFL., (© 2024 Wiley Periodicals LLC.)

Background: The oncological efficacy of laparoscopic surgery for advanced gastric cancer (AGC) has been evaluated by several randomized trials. However, the inclusion of earlier-stage disease was a limitation in previous studies., Methods: Patients with cT3-4 gastric cancer, determined by surgical staging to minimize migration of earlier stages, treated at a tertiary cancer center from 2009 to 2018 were included. Based on the surgical approach, the patients were divided into two groups: the laparoscopic gastrectomy (LG) and the open gastrectomy (OG) and matched for age, sex, macroscopic appearance (type 4 or non-type 4), body mass index, estimated tumor size, clinical stage T3'T4, clinical N stage, pathologic T stage (T3 or T4), and type of surgery (total or distal gastrectomy)., Results: 588 patients (221 LG, 367 OG) were included in the analysis. After 1:1 propensity-score matching, 386 patients (193 LG, 193 OG) were assigned for analysis. In the LG group, operation time was longer with lower blood loss. The incidence of postoperative complications (≥ grade III) did not differ significantly between the groups (OG: 8.3%, vs. LG: 9.3%). Overall survival (OS) was longer in the LG group (5-year OS: 79.3 vs. 73% HR 0.66, 95% CI 0.44-0.99, P = 0.0497). Relapse-free survival (RFS) did not show a statistical difference (5-year RFS: 69.5 vs. 68.7 HR 0.88, 95% CI 0.62-1.26, P = 0.487). Subgroup analysis for OS also demonstrated equivalent outcomes., Conclusion: LG demonstrates comparable safety and efficacy to OG for advanced gastric cancer at surgical staging, with similar rates of severe complications and long-term oncological outcomes. Further research is needed to validate these findings, particularly for total gastrectomy and for patients from Western populations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Hemorrhage management is crucial for surgical resection of pediatric posterior-fossa tumors (PPFTs). Tumor volume and vascularity on preoperative magnetic resonance imaging (MRI) can help predict and control intraoperative blood loss (IBL). The present study aimed to assess the correlation between MRI features and IBL in PPFTs., Methods: Eleven patients treated for PPFTs at our hospital using the transcerebellomedullary fissure approach were enrolled, including five (45.5%) males and six (54.5%) females, with a median age of 10 (range, 4-16) years. Nine patients with medulloblastoma, one with ependymoma, and one with atypical teratoid/rhabdoid tumor were included. Using susceptibility-weighted imaging-based intratumoral susceptibility signal (ITSS) grade as an index of tumor vascularity, we performed univariate analysis of the association of degree of vascularity (ITSS grade 0-2 vs. 3) and multivariate analysis of IBL., Results: Univariate analysis showed that the high vascularity group (ITSS grade 3) had significantly larger tumor volume (p = 0.009) and higher IBL (p = 0.004). In multivariate analysis of age, tumor volume, ITSS grade, cerebral blood volume, and extent of resection, tumor volume was the only significant factor (p = 0.001); however, ITSS grade was also positively associated with IBL (p = 0.074)., Conclusion: In this study, tumor volume and vascularity of PPFTs were strongly correlated, and tumor volume was the sole factor significantly associated with IBL. This study suggests that ITSS grade and tumor volume collaboratively influence IBL in surgical resection of PPFTs. IBL should be assessed based on MRI features, and suitable treatment strategies should be established., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The authors aim to provide a comprehensive overview of the advancements in head and neck reconstructive surgery using thinned perforator flaps. The article categorizes these flaps based on thickness and discusses the importance of standardized terminology. Critical aspects like flap vascularity, pre-operative planning, and imaging technologies for perforator mapping are examined with practical considerations. The article then delves into various thinning techniques and their applications in head and neck reconstructions, highlighting challenges and concerns. In conclusion, significant progress in reconstructive surgery using thinned perforator flaps has brought advancements in improving surgical precision and patient outcomes in head and neck reconstructions., Competing Interests: Disclosures Authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The development of acquired middle ear cholesteatoma is associated with a single nucleotide polymorphism, 538G>A, in the human adenosine triphosphate-binding cassette transporter C11 (ABCC11) gene, which is a determinant of the earwax morphotype, such as wet- and dry-type earwax; however, the mechanism underlying this association is unclear. We focused on the earwax pH and aimed to elucidate the mechanism between ABCC11 genotypes and acquired middle ear cholesteatoma., Study Design: Prospective observational study., Setting: Single-center, academic hospital., Methods: We recruited 40 patients with acquired middle ear cholesteatoma who underwent surgery and 115 controls with no history of middle ear cholesteatoma. We assessed the earwax pH and ABCC11 genotypes in all participants. Clinical information was collected from the patients with cholesteatoma., Results: The earwax pH was significantly less acidic in patients with cholesteatoma and those carrying wet earwax genotypes (ABCC11 538G/G or 538G/A) than in the controls and those carrying the dry earwax genotype (ABCC11 538A/A), respectively. Furthermore, earwax pH was significantly positively correlated with high preoperative cholesteatoma stages in the patients with cholesteatoma., Conclusion: Our results show that the less acidic earwax pH was significantly related to the development and progression of acquired middle ear cholesteatoma. The less acidic earwax pH may play an important role in the mechanism underlying the association between acquired middle ear cholesteatoma and the ABCC11 gene at site 538., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Objectives: We developed the deep neural network (DNN) model to automatically measure hallux valgus angle (HVA) and intermetatarsal angle (IMA) on foot radiographs. The objective is to assess the accuracy of the model by comparing to the manual measurement of foot and ankle surgeons., Materials and Methods: A DNN was developed to predict the bone axes of the first proximal phalanx and all metatarsals from the first to the fifth in foot radiographs. The dataset used for model development consisted of 1798 radiographs collected from a population-based cohort and patients at our foot and ankle clinic. The retrospective validation cohort comprised of 92 radiographs obtained from 92 consecutive patients visiting our foot and ankle clinic. The mean absolute error (MAE) between automatic measurements by the model and the median of manual measurements by three foot and ankle surgeons was compared to 3° using one-tailed t-test and was also compared to the inter-rater difference in manual measurements among the three surgeons using two-tailed paired t-test., Results: The MAE for HVA was 1.3° (upper limit of 95% CI 1.6°), and this was significantly smaller than the inter-rater difference of 2.0 ± 0.2° among the surgeons, demonstrating the superior accuracy of the model. In contrast, the MAE for IMA was 0.8° (upper limit of 95% CI 1.0°) that showed no significant difference from the inter-rater difference of 1.0 ± 0.1° among the surgeons., Conclusion: Our model demonstrated the ability to measure the HVA and IMA with an accuracy comparable to that of specialists., (© 2024. The Author(s).)

This study aimed to investigate the association of combination of birth weight and current body mass index (BMI) with the risk of hypertension in adulthood. This cross-sectional study used data from the Tohoku Medical Megabank Community-based Cohort Study conducted in Japan. A total of 10,688 subjects aged ≥20 years were eligible. We calculated the least square (LS) means of systolic blood pressure (SBP) and trend tests were performed to evaluate the linear relationships between birth weight categories and SBP. We also used a multivariate logistic regression analysis to assess the risk of hypertension associated with the combination of birth weight and current BMI. There was a statistically inverse association between birth weight and SBP in the 20-64 age group, but no significant association in the ≥65 age group. Low birth weight (LBW) with normal BMI group had a higher risk of hypertension than the normal or high birth weight groups with normal BMI. Furthermore, the group with LBW and BMI ≥25.0 kg/m 2 was the highest risk for hypertension (adjusted odds ratio: 2.73; 95% CI, 2.04-3.65) compared to the reference group (birth weight 2500-3499 g and BMI 18.5-24.9 kg/m 2 ). There was a significant association between LBW and subsequent risk of hypertension. In addition, participants with lower birth weights had a higher risk of hypertension than those with higher birth weights. However, even in participants with a lower birth weight, the risk of hypertension could be reduced when they maintained an optimal BMI., (© 2024. The Author(s).)

Introduction: Fluorine 18-fluoro-glucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) is commonly used for the staging of head and neck cancer. This study aimed to evaluate the correlation between 18 F-FDG PET/CT, haematological parameters and prognosis in patients with advanced head and neck cancer., Methods: This was a single-institutional retrospective study of 83 patients with advanced head and neck squamous cell carcinoma (HNSCC) who underwent 18 F-FDG PET/CT imaging before initial treatment between 2014 and 2018. 18 F-FDG PET/CT after treatment was performed in 57 patients. The prognostic parameters of the pre- and post-treatment maximum standardised uptake value (SUV max ), metabolic tumour volume (MTV), total lesion glycolysis (TLG) of primary tumours and haematological parameters were analysed to evaluate the association between overall survival (OS) and progression-free survival (PFS)., Results: Pre-MTV, pre-TLG and post-SUV max were significantly associated with poor OS and PFS (p < 0.05). Haematological parameters, including pretreatment neutrophil/lymphocyte ratio and C-reactive protein/albumin ratio, were associated with 18 F-FDG PET/CT parameters. In multivariate analysis, post-SUV max was an independent prognostic factor for OS and PFS., Conclusion: A correlation between PET/CT metabolic and haematological parameters was observed. The volume and intensity of 18 F-FDG uptake region, in addition to haematological parameters, are feasible markers for predicting the progression of HNSCC in daily practice. Further, post-SUV max could be an independent parameter for predicting poor survival., (© 2024 John Wiley & Sons Ltd.)

Background: Identifying accurate prognostic factors is crucial for postoperative management of early gastric cancer (EGC) patients. Skeletal muscle quality (SMQ), defined by muscle density on computed tomography (CT) images, has been proposed as a novel prognostic factor. This study compared the prognostic significance of SMQ changes with the well-established factor of body weight (BW) loss in the postoperative EGC setting., Methods: This single-center retrospective study included 297 postoperative EGC patients (median age 69 years, 68.4% male) who had preoperative and 1-year-postoperative gastrectomy CT images. SMQ was defined as the modified intramuscular adipose tissue content (mIMAC = skeletal muscle density-subcutaneous fat density on CT images) and the change as ΔmIMAC. Log-rank test, Kaplan-Meier survival, and Cox proportional hazards regression analyses were used to assess the associations between prognosis and either ΔmIMAC or BW change (ΔBW). Prognosis prediction by ΔmIMAC and ΔBW was compared by using the area under the curve (AUC) of the receiver operating characteristic curve., Results: ΔmIMAC was significantly associated with prognosis (log-rank test; P = 0.037), but ΔBW was not (P = 0.243). Prognosis was significantly poorer in the severely decreased mIMAC group than in the preserved group (multivariate Cox proportional hazards regression analysis; P = 0.030) but was unaffected by BW changes (P = 0.697). The AUC indicated a higher prognostic value for ΔmIMAC than ΔBW (ΔmIMAC: AUC = 0.697, ΔBW: AUC = 0.542)., Conclusions: One-year post-gastrectomy SMQ changes may be better prognostic EGC predictors than BW changes., (© 2024. Society of Surgical Oncology.)

Purpose: While comprehensive research exists on the mutation of the DNA repair gene BRCA1, limited information is available regarding the clinical significance of BRCA1 gene expression. Given that cancer cell proliferation is aggrevated by DNA repair, we hypothesized that high BRCA1 gene expression breast cancer (BC) might be linked with aggressive tumor biology and poor clinical outcomes., Methods: The cohorts: The Cancer Genome Atlas (TCGA, n = 1069), METABRIC (n = 1903), and SCAN-B (n = 3273) were utilzed to obtain data of 6245 BC patients., Results: BC patients without BRCA1 mutation exhibited higher BRCA1 expression, which was associated with DNA repair functionality. However, no such correlation was observed with BRCA2 expression. The association of high BRCA1 expression with cancer cell proliferation was evidenced by significant enrichment of cell proliferation-related gene sets, higher histological grade, and proliferation score. Furthermore, increased levels of homologous recombination deficiency, intratumoral heterogeneity, and altered fractions were associated with high BRCA1 expression. Moreover, BC with high BRCA1 expression exhibited reduced infiltration of dendritic cells and CD8 T-cells, while showing increased infiltration of Th1 cells. Surprisingly, BRCA1 expression was not associated with the survival of BC irrespective of the subtypes. Conversely, BC with low BRCA1 expression enriched cancer aggravating pathway gene sets, such as Cancer Stem Cell-related signaling (NOTCH and HEDGEHOG), Angiogenesis, Epithelial-Mesenchymal Transition, Inflammatory Response, and TGF-beta signaling., Conclusion: Despite being linked to heightened proliferation of cancer cells and unassertive phenotype, BRCA1 expression did not show any association with survival in BC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Recent studies have demonstrated that ultraviolet B (UVB) irradiation impacts both skin and hepatic functions. In this study, we investigated the effects of UVB irradiation on cholesterol metabolism in the liver. Hairless mice were exposed to UVB (1.6 J/cm 2 ) irradiation. Dorsal skin and liver samples were collected 24 h after exposure. Total RNA was extracted from the skin and liver tissues, and used for DNA microarray analysis and real-time polymerase chain reaction (PCR). Hepatic mRNA expression of Cyp7a1 revealed a 4.4-fold decrease in the UVB (+) group compared to that in the UVB (-) group. No differences were observed in the expression of the other genes related to cholesterol metabolism. Additionally, the level of hepatic total cholesterol in the UVB (+) group was significantly higher than in the UVB (-) group. These findings suggest that acute UVB irradiation increases total cholesterol levels and decreases Cyp7a1 expression in the liver., (© 2024 AOCS.)

Purpose: CD133, a cancer stem cells (CSC) marker, has been reported to be associated with treatment resistance and worse survival in triple-negative breast cancer (BC). However, the clinical relevance of CD133 expression in ER-positive/HER2-negative (ER + /HER2-) BC, the most abundant subtype, remains unknown., Methods: The BC cohorts from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1904) and The Cancer Genome Atlas (TCGA, n = 1065) were used to obtain biological variables and gene expression data., Results: Epithelial cells were the exclusive source of CD133 gene expression in a bulk BC. CD133-high ER + /HER2- BC was associated with CD24, NOTCH1, DLL1, and ALDH1A1 gene expressions, as well as with WNT/β-Catenin, Hedgehog, and Notch signaling pathways, all characteristic for CSC. Consistent with a CSC phenotype, CD133-low BC was enriched with gene sets related to cell proliferation, such as G2M Checkpoint, MYC Targets V1, E2F Targets, and Ki67 gene expression. CD133-low BC was also linked with enrichment of genes related to DNA repair, such as BRCA1, E2F1, E2F4, CDK1/2. On the other hand, CD133-high tumors had proinflammatory microenvironment, higher activity of immune cells, and higher expression of genes related to inflammation and immune response. Finally, CD133-high tumors had better pathological complete response after neoadjuvant chemotherapy in GSE25066 cohort and better disease-free survival and overall survival in both TCGA and METABRIC cohorts., Conclusion: CD133-high ER + /HER2- BC was associated with CSC phenotype such as less cell proliferation and DNA repair, but also with enhanced inflammation, better response to neoadjuvant chemotherapy and better prognosis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Multiple biliary tumors rarely develop in patients without underlying chronic hepatobiliary disease. Those lesions are regarded as multifocal neoplasms if there is no interconnecting dysplasia. This study aimed to determine whether 2 separate tumors in the biliary tract represent true multifocal independent tumorigenesis or intraluminal implantation of a single neoplasm. Two separate biliary tumors without intervening dysplasia were identified in 9 cases: biliary intraductal papillary neoplasm (IPNB; n=5) and extrahepatic cholangiocarcinoma (n=4). The 2 tumors were histologically similar in all cases. In 5 metachronous cases, the second tumor developed 2 to 13 years after the complete resection of the first tumor. In 4 synchronous cases, 2 separate neoplasms were identified in a surgical specimen. The metachronous presentation was more common in IPNB cases, whereas the synchronous development was more frequent in cholangiocarcinoma cases. The second tumors in 4 metachronous cases (4/5; 80%) and smaller lesions in all synchronous cases (4/4; 100%) were located in a lower part of the biliary. Immunophenotypes of cytokeratins and mucin core proteins were almost identical between the 2 lesions. Next-generation sequencing also confirmed that the 2 neoplasms shared gene mutations involving KRAS , GNAS , APC , BRAF , CTNNB1 , SMAD4 , TP53 , or ARID1A in all cases. In conclusion, multiple biliary tumors without underlying chronic biliary disease are most likely due to intraductal implantation of a single neoplasm. Thick mucinous bile in IPNB and increasing use of trans-ampullary biliary interventions may contribute to this unique form of tumor extension., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Changes in stent graft (SG) orientation after frozen elephant trunk (FET) treatment for aortic arch aneurysms are not well understood. This study investigated changes in SG orientation and their effects on aortic events after FET for aortic arch aneurysms., Methods: This study included 57 patients with true aneurysms who underwent elective total arch replacement using FET between 2016 and 2023. Postoperative SG angle, descending aortic (DA) diameter at the end of the SG, and the DA angle were measured retrospectively by using enhanced computed tomography (CT)., Results: Median patient age was 74 years. The median stent size was 33 mm, and the stent length was 12 cm (range, 23-37 mm and 6-15 cm). Enhanced CT showed that all the patients had completely thrombosed aneurysms after the procedure. Aortic events (dissection or type Ib leaks) were observed in four patients during the follow-up period. The diameter of the DA at the end of the SG and the DA angle increased in recent periods (P=0.04 and P=0.01, respectively). The SG angle changed to an obtuse angle in the recent periods (P<0.0001). The probability of postoperative aortic events did not correlate with changes in SG orientation but with the ratio of recent postoperative descending diameter to preoperative descending diameter (P=0.04)., Conclusions: The descending aorta into which the SG was inserted showed flattening and widening movements owing to the spiring back force. One of the factors related to aortic events was dilation of the postoperative DA due to oversizing of the SG., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1169/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Background: Lung cancer remains the primary cause of cancer-related mortality globally, treated using immune checkpoint inhibitors (ICIs), which are introducing new therapeutic potential and complexities, including severe immune-related adverse events (irAEs) and rare fistula formation. The interaction between coronavirus disease 2019 (COVID-19) and ICIs further complicates treatment outcomes, occasionally leading to spontaneous tumor regression, suggesting potential immune response modulation by COVID-19. This report elucidates a unique case of non-small cell lung cancer (NSCLC) managed with these challenges, highlighting the delicate balance required for modern oncological care., Case Description: A 44-year-old male patient with stage IIIC NSCLC, no driver mutations such as those in epidermal growth-factor receptor ( EGFR ) or anaplastic lymphoma kinase ( ALK ) genes, and a tumor proportion score of <1% experienced multiple complications after ICI plus chemotherapy. The treatment regimen comprised durvalumab, tremelimumab, carboplatin, and nab-paclitaxel. The patient experienced multiple complications including: (I) esophageal mediastinal fistula; (II) severe irAEs such as grade 3 colitis; (III) COVID-19 and Candida albicans infections; (IV) cytokine release syndrome; and (V) myocarditis. Treatment interventions included high-dose steroids, antifungal therapy, mechanical support in the intensive care unit, and hemodialysis. The patient showed remarkable tumor regression and recovery from acute adverse events with eventual tumor resolution and closure of the esophageal mediastinal fistula. Tumor cells were positive for angiotensin-converting enzyme 2, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have infected tumor cells and caused an antitumor effect as an oncolytic virus., Conclusions: Clinicians should be aware that COVID-19 might be associated with the development of severe irAEs and unexpectedly enhanced antitumor effects. The findings also suggest new fields of study regarding the interaction between viral infection and tumor immune response, which may inform future therapeutic approaches., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-444/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Background & Aims: This study aimed to clarify the association between physical activity (PA) and physical functions, including both muscle quantity and quality of ankle plantar flexor muscles in patients with knee osteoarthritis (OA)., Methods: A retrospective cohort study was conducted with ninety-two patients with knee OA. PA, leg muscle cross-sectional area (CSA), knee strength, passive knee angle, and knee pain of the affected side were assessed. PA was assessed by the 2011 Knee Society scoring system. CSA of the quadriceps and ankle plantar flexor muscles on the affected side was measured using a computed tomography image. Based on muscle attenuation assessed with Hounsfield units (HU), the muscle quality of targeted muscle was divided into 4 groups as follows: fat tissue (-190 to -30 HU), very low-density muscle (-29 to -1 HU), low-density muscle (0 to 34 HU), and normal-density muscle (NDM, 35 to 100 HU). The CSA was obtained for each of the 4 groups. Univariate and multivariate linear regression analyses were performed to determine the factors associated with PA., Results: The regression analysis revealed that higher PA was independently associated with the NDM CSA of ankle plantar flexor (β = 0.51), higher knee extension strength (β = 0.28), and milder knee pain (β = -0.29) after adjustment with age, sex, height, weight, and body mass index., Conclusion: The present study suggested that NDM CSA of ankle plantar flexor in addition to knee function is one of the factors determining the PA in patients with knee OA., Competing Interests: Declaration of competing interest Some authors (SM, SK, KN) have a financial relationship with Kyocera and Zimmer-Biomet unrelated to this study., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: The management of chronic thromboembolic pulmonary hypertension (CTEPH) has advanced significantly in recent years, thereby improving patient prognosis. However, the impact of cancer on the outcomes of patients with CTEPH under current treatment remains unclear. This study aimed to investigate the prevalence of cancer in patients with CTEPH and determine how comorbid cancer affects their prognosis and clinical course., Methods: Data from an ongoing Japanese prospective cohort study were analyzed. Prevalence and primary cancer sites were evaluated. The association of a history of cancer with a composite endpoint, including all-cause death, lung transplantation, and worsening of CTEPH, as well as venous thromboembolism and bleeding events, was assessed., Results: Of the 1,270 patients in the cohort, 134 (10.6%) had a history of cancer, with the most common primary sites being the breast in women and the prostate in men. The incidence of composite outcome and all-cause death was higher in those with a history of cancer (p < 0.001, log-rank test). In the Cox proportional hazard model, age- and sex-adjusted hazard ratios for the composite outcome and all-cause death were 2.69 (95% confidence interval, 1.48-4.89, p = 0.001) and 4.25 (95% confidence interval, 1.98-9.10, p < 0.001), respectively, for patients with a history of cancer. No significant differences in venous thromboembolism and bleeding events were observed between patients with and those without a history of cancer., Conclusions: A history of cancer, with a prevalence of 10.6%, is an independent risk factor for mortality in patients with CTEPH undergoing the currently recommended treatment., Competing Interests: Disclosure statement Tsujino I. reports personal fees from Janssen Pharmaceutical and Nippon Shinyaku and affiliation with the division supported by endowments from Nippon Shinyaku, Nippon Boehringer Ingelheim, Mochida Pharmaceutical, Kaneka, Takeyama, and the Medical System Network outside the submitted work. Hosokawa K. reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, and Pfizer outside the submitted work. Taniguchi Y. reported grants from Janssen Pharmaceutical and Nippon Shinyaku and personal fees from Janssen Pharmaceutical and Nippon Shinyaku outside the submitted work. Inami T. reports personal fees from Janssen Pharmaceutical and Bayer Yakuhin outside the submitted work. Yamashita J. reports a grant from Abbott Vascular Japan and personal fees from Kaneka Medix, Boston Scientific Japan, Nihon Kohden, Philips Japan, Janssen Pharmaceutical, and Bayer Yakuhin outside the submitted work. Ogino H. reports consulting fees from Terumo, Japan Lifeline, and Century Medical, outside the submitted work. Ikeda N. reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, Daiichi Sankyo, and Bristol-Myers Squibb outside the submitted work. Yaoita N. reports personal fees from Bayer Yakuhin and Konica Minolta outside the submitted work. Shimokawahara H. reports a grant from Bayer Yakuhin and personal fees from Actelion Pharmaceuticals Japan, Bayer Yakuhin, and Nippon Shinyaku, outside the submitted work. Tanabe N. reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, and Nippon Shinyaku outside the submitted work. Kubota K. reports personal fees from Janssen Pharmaceutical and Nippon Shinyaku outside the submitted work. Ogihara Y. reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, and Daiichi Sankyo and grants from Bayer Yakuhin and Daiichi Sankyo outside the submitted work. Kawakami T. reports personal fees from Kaneka Medix, Abbott Medical Japan., and ACIST Japan outside the submitted work. Tamura Y. reports grants from Bayer Yakuhin, Nippon Shinyaku, and Mochida Pharmaceutical and personal fees from Bayer Yakuhin, Nippon Shinyaku, Daiichi Sankyo, and Janssen Pharmaceutical outside the submitted work. Abe K. reports a grant from Konica Minolta and Daiichi Sankyo outside the submitted work. Nakamura J., Masaki K., Funakoshi K., Adachi S., Hatano M, Shigeta A., Horimoto K., Dohi Y., and Tatsumi K. report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims/introduction: This study aimed to investigate the risk factors for diabetic retinopathy (DR) and diabetic kidney disease (DKD) in Japanese patients with diabetes mellitus (DM). Identifying these factors could provide insights into the shared and distinct mechanisms contributing to these complications in the diabetic population., Materials and Methods: We conducted a retrospective analysis using the J-DREAMS (Japan Diabetes compREhensive database project based on an Advanced electronic Medical record System) database, which is directly linked to electronic medical records. The study included Japanese people aged 18 years and older with diabetes, who were registered at a referral center between December 1, 2015, and March 31, 2021, and had simultaneous measurements of serum creatinine and hemoglobin A1c (HbA1c). The presence or absence of DR and DKD was determined for 8,794 and 8,770 patients, respectively. Multivariable logistic regression analyses were used to identify risk factors, considering patient characteristics, comorbid conditions, and laboratory data as explanatory variables., Results: Common risk factors for both DR and DKD included hypertension, anemia, diabetic neuropathy, cerebrovascular disease, chronic heart failure, low serum albumin levels, and elevated HbA1c. The contributions of age, duration of DM, and body mass index (BMI) differed between the DR and DKD groups., Conclusions: In addition to poor glycemic control and hypertension, anemia, low serum albumin, cerebrovascular disease, and heart failure were identified as independent common risk factors for DR and DKD, suggesting the existence of cardio-renal anemia syndrome in patients with DM., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

The effect of inhibiting retrogradation and changes in chain length distribution by AG and BE, which are texture-modifying enzymes, has been clarified. To ascertain in which part of the rice grain retrogradation occurs and which enzymes is most effective, the degree of retrogradation in each part of the rice grain was measured from the surface to the core of the same rice grain using a synchrotron radiation X-ray beam with a beam size of 100 μm. Retrogradation was effectively suppressed at all measurement sites by enzyme addition, although the effect of enzymes was greater at the surface. Rice grain sections were stained with iodine and eosin. A starch layer that does not easily form a complex with iodine was observed inside the protein layer at the surface of cooked rice. A starch layer with a long molecular chain that forms complexes with iodine was observed inside the rice grain., 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 Ltd.. All rights reserved.)

Background: Polydoctoring can increase the risk of care fragmentation among patients with multimorbidity, but its impact on health outcomes remains unclear., Aim: To determine the effects of polydoctoring, as measured by the regularly visited facilities (RVF) indicator, on patient outcomes among older individuals with multimorbidity., Design & Setting: Data from the ongoing prospective cohort study, Kawasaki Aging and Wellbeing Project (KAWP), was utilised in this study. Among the 1026 KAWP participants aged 85-89 years, those with two or more chronic conditions were enrolled in this study., Method: Care fragmentation and polydoctoring was evaluated using the RVF, which is a new indicator that measures the number of medical facilities consistently involved in a patient's care. Based on RVF, mortality was analysed using the Cox proportional hazards model, with adjustments for age, sex, frailty, and number of comorbidities., Results: A significant reduction in mortality rates was observed in participants with an RVF of ≥3 and 2-4 comorbidities (hazard ratio [HR] 0.43, 95% confidence interval [CI] = 0.18 to 0.99, P value = 0.048). However, no significant difference in mortality based on RVF was observed for those with ≥5 comorbidities. Notably, individuals with ≥5 comorbidities and an RVF of 0 had a significantly higher HR for death (HR 2.68, 95% CI = 1.05 to 6.84, P value = 0.039)., Conclusion: In older patients with multimorbidity, polydoctoring may reduce mortality in patients with ≤4 coexisting conditions, but it does not significantly impact mortality in those with ≥5 conditions. These findings provide insights for healthcare decision making in managing older patients with multimorbidity., (Copyright © 2024, The Authors.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming a major health problem worldwide. Liver regeneration is crucial for restoring liver function, and is regulated by extraordinary complex process, involving numerous factors under both physiologic and pathologic conditions. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid synthesized by sphingosine kinase 1 (SphK1), plays an important role in liver function through S1P receptors (S1PRs)-expressing cells. In this study, we investigated the effect of lipid overload on hepatocyte proliferation in a mouse hepatic steatosis model induced by feeding a methionine- and choline-deficient (MCD) diet. After 50% partial hepatectomy (PHx), liver tissues were sampled at various timepoints and then analyzed by immunohistochemistry, oil Red-O staining, quantitative-polymerase chain reaction (qPCR), and flow cytometry. In mice fed the MCD-diet, significantly exacerbated hepatic steatosis and accelerated liver regeneration were observed. After PHx, hepatocyte proliferation peaked at 48 and 36 hr in the liver of chow- and MCD-diet fed mice, respectively. By contrast, increased expression of S1PR2 was observed in hepatic neutrophils and macrophages of MCD-diet fed mice. Flow cytometry and qPCR experiments demonstrated that levels of HGF and FGF2 released by neutrophils and macrophages were significantly higher in MCD-diet fed mice. In conclusion, hepatic lipid overload recruits Kupffer cells and neutrophils that release HGF and FGF2 via SphK1/S1PR2 activation to accelerate hepatocyte proliferation., Competing Interests: VWe have no conflict of interest to declare., (2024 The Japan Society of Histochemistry and Cytochemistry.)

Background: Occupational health, grounded in occupational medicine, aims to enhance the well-being and labor productivity of the working population. Within this realm, there has been growing concern over the increasing instances of labor loss due to diminished physical capacity and the rise in musculoskeletal disorders. Chronic pain is also associated with musculoskeletal disorders. Another pressing issue related to chronic musculoskeletal pain was needed assistance services are underutilized, is referred to as a "service gap". Understanding trends based on age and affected regions of the body is indispensable for developing strategies to address chronic musculoskeletal pain in workers. This study aimed to elucidate age-specific trends in the prevalence and number of pain sites in chronic musculoskeletal pain as well as the patterns of treatment during chronic musculoskeletal pain, categorized by age and affected site., Methods: This study was conducted in December 2022 in contract to Cross Marketing Inc. The survey began on December 12, 2022 and ended on December 15, 2022. An online survey was administered to 1,946 participants (973 women and 973 men), and responses were collected, ensuring a roughly equal distribution of samples among men and women across six age groups ranging from their 20 to 70 s. The survey inquired about the presence of chronic pain in each of the eight body parts and the adoption of five different treatments when experiencing pain. Statistical analysis was performed using the chi-square test, with the measurement data categorized by age group and body part., Results: The results indicated a significantly higher prevalence of chronic pain at three or more sites among individuals in their 30 s: the prevalence of pain at each of the eight body sites varied with age. Approximately half of the participants did not engage in specific treatments during episodes of chronic pain. The presence or absence of treatment showed no significant differences according to affected site or age group. This study revealed age- and body part-related relationships with chronic musculoskeletal pain in middle-aged patients and highlighted healthcare service gaps in its management in Japan., Competing Interests: The authors declare that they have no competing interests. None of the authors are employees of Cross Marketing, Inc. Yasumasa Oka is an employee of the Kanazawa Orthopedic and Sports Medicine Clinic. Noriyuki Kida is an employee of the Kyoto Institute of Technology. Michio Wachi and Takumi Jiroumaru is an employee of the Bukkyo University., (© 2024 Oka et al.)

Objective: To evaluate comorbidities in Japanese testicular cancer (TC) survivors in a multi-institutional, cross-sectional study., Methods: This study enrolled TC survivors who visited any of the eight high-volume institutions in Japan from 2018 to 2019. After obtaining informed consent, participants answered questionnaires about their comorbidities. We analyzed the impact of treatment on comorbidities rate in TC survivors., Results: A total of 509 TC survivors responded to the comorbidity questionnaires. Median age at the time of response was 43 years (IQR 35-51 years) and median follow-up period after treatment was 5.1 years (IQR 2.1-9.2 years). TC survivors were divided according to the number of cycles of chemotherapy into the following groups: None (n = 153); 1-2 cycles (n = 34); 3-4 cycles (n = 234); or ≥5 cycles (n = 88). The prevalence of kidney disease increased significantly with increasing number of cycles of chemotherapy (p < 0.05). The relative risk of cardiovascular disease in the groups with three or more cycles was 2.6 compared to the group without chemotherapy., Conclusion: The present study showed that the prevalence of kidney disease in TC survivors was increased with increasing number of cycles of chemotherapy., (© 2024 The Japanese Urological Association.)

The rare physical property of negative thermal expansion (NTE) is intriguing because materials with a large NTE over a wide temperature range can serve as high-performance thermal expansion compensators. However, the applications of NTE are hindered by the fact that most of the available NTE materials show small magnitudes of NTE, and/or NTE occurs only in a narrow temperature range. Herein, for the first time, we investigated the effect of anion substitution instead of general Pb/Ti-site substitutions on the thermal expansion properties of a typical ferroelectric NTE material, PbTiO 3 . Intriguingly, the substitution of S for O in PbTiO 3 further increases the tetragonality of PbTiO 3 . Consequently, an unusually enhanced NTE with an average volumetric coefficient of thermal expansion of  V = -2.50 × 10 -5 K -1 was achieved over a wide temperature range (300-790 K), which is in contrast to that of pristine PbTiO 3 (  V = -1.99 × 10 -5 K -1 , RT-763 K). The intensified NTE is attributed to the enhanced hybridization between Pb/Ti and O/S atoms by the substitution of S, as evidenced by our theoretical investigations. We therefore demonstrate a new technique for introducing mixed anions to achieve a large NTE over a wide temperature range in PbTiO 3 -based ferroelectrics.

Objective: To investigate the recovery processes of pusher behavior (PB) and unilateral spatial neglect (USN) based on the severity of PB and USN, and to determine the relationship between activities of daily living (ADL) independence levels., Design: This retrospective study aimed to examine the temporal changes and their association with ADL independence levels based on the severity of PB and USN., Setting: Recovery ward of Moriyama Neurological Center Hospital between March 2017 and October 2022., Participants: We included all patients with cerebrovascular disease admitted to the recovery ward of Moriyama Neurological Center Hospital between March 2017 and October 2022. A total of 174 patients with PB and USN were classified into 4 groups as follows: severe PB and severe USN (Group A), severe PB and mild USN (Group B), mild PB and severe USN (Group C), and mild PB and mild USN (Group D)., Interventions: Not applicable., Main Outcome Measures: Kaplan-Meier survival analysis was used to determine whether the time to recovery from PB or USN (SCP: ≤1.75 points; Catherine Bergego Scale: 0 points) differed between groups. In addition, group differences in functional independence measure (FIM) scores and efficiencies were examined., Results: There were significant differences among Groups A and B, and Groups A and C, as determined by the log-rank test (P<.05), and recovery was prolonged when both PB and USN were severely impaired. Similarly, FIM scores and efficiencies were lower in Group A (P<.05). When PB and USN were severely impaired, ADL was adversely affected, and the recovery process was prolonged. In addition, when 1 of the 2 symptoms was severe and the other was mild, each recovery course tended to show improvement, suggesting that they exerted a mutual influence on each other., Conclusions: These findings indicate that severity classification may help to determine functional prognosis in patients with PB and USN., (Copyright © 2024 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

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.

Background: The efficacy of balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic disease (CTEPD) without pulmonary hypertension (PH) remains unknown. Exercise PH (Ex-PH) is associated with impaired exercise capacity, even when pulmonary hemodynamics are normal at rest. We hypothesized that patients with Ex-PH could be the candidates for BPA. This study aimed to determine the prevalence and clinical profiles of Ex-PH and the effect of BPA on oxygenation and Ex-PH in patients with CTEPD and mean pulmonary arterial pressure (mPAP) ≤ 20 mmHg., Methods: We retrospectively reviewed 23 patients (median age 65 years) with CTEPD and mPAP ≤20 mmHg at rest who underwent cardiopulmonary exercise testing with right heart catheterization. Patients were divided into two groups: Ex-PH, defined by an mPAP/ cardiac output (CO) slope (mPAP/CO slope) > 3.0, and non-Ex-PH., Results: Overall, 12 and 11 patients were identified as Ex-PH and non-Ex-PH groups, respectively. There were no significant differences in clinical parameters, including hemodynamics at rest, and blood gas analysis between Ex-PH and non-Ex-PH groups. Among 9 patients with Ex-PH, BPA improved World Health Organization-functional class and PaO 2 at rest and was associated with a decrease in the mPAP/CO slope. All 3 patients discontinued LTOT after BPA. There were no significant complications during each BPA session., Conclusions: Ex-PH was common among patients with CTEPD without PH. BPA could improve symptoms, oxygenation, and exercising hemodynamics in patients with CTEPD and Ex-PH., Competing Interests: Declaration of Competing Interest: We have nothing to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Patients with cardiac sarcoidosis (CS) are at an increased risk of fatal ventricular arrhythmic events (FVAE). However, the predictive value of 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) in assessing the risk of FVAE in patients with CS remains uncertain., Methods: We included data from 121 patients with CS (39 men and 82 women; mean age: 59.5 years) who underwent FDG-PET imaging between March 2008 and November 2020, with follow-ups completed in July 2023. Of these, 82 patients had available cardiac magnetic resonance imaging data, including late gadolinium enhancement (LGE). FDG-PET images were analysed using a polar-map model to determine the regional mean percentage uptake relative to the maximal cardiac 18 F-FDG uptake in each of the 17 segments defined by the American Heart Association., Results: Patients experiencing FVAE after FDG-PET (n = 43) showed lower percent uptake in the basal inferoseptal segment compared to those who did not (n = 78) (41.8 ± 15.2 % vs. 54.4 ± 13.8 %, P < 0.001). Patients with a basal inferoseptal percent uptake below the median had a lower FVAE-free survival rate than those with a higher percent uptake (58.1 % vs. 78 % at 5 years, P = 0.007), which was consistent in patients with LGE in the same regions with reduced 18 F-FDG uptake. A Cox hazard model indicated that the FVAE risk decreased with a hazard ratio of 0.862 (95 % CI 0.770-0.964) for every 5 % increase in basal inferoseptal percent uptake (P = 0.009)., Conclusion: Reduced 18 F-FDG uptake in the basal interventricular septum, including the inferoseptal segment, may be a valuable predictor of future FVAE in patients with CS., Competing Interests: Declaration of competing interest S. Yasuda has received grant support from Takeda Pharmaceutical, Abbott, and Boston Scientific and lecture fees from Daiichi Sankyo and Bristol Myers Squibb. The other authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: This study evaluated the endoscopic management and clinical outcomes of patients with colonic diverticular bleeding (CDB) during the coronavirus disease 2019 (COVID-19) pandemic., Methods: A total of 388 hospitalized patients diagnosed with CDB at two hospitals during (April 2020-March 2023) and before (April 2017-March 2020) the pandemic were enrolled in the study. We performed one-to-one propensity score matching (PSM) on the participants. We analyzed endoscopic management and clinical outcomes before and during the pandemic using a total of 264 patients matched in a PSM analysis., Results: A total of 213 (1.3%) and 172 (1.2%) colonoscopies were performed before and during the pandemic, respectively in patients with CDB (P = 0.70). After PSM, the number of early colonoscopies (63.6% vs. 76.5%, P = 0.03) and colonoscopies performed outside regular working hours (23.8% vs. 47.7%, P < 0.01) was significantly lower during the pandemic than before it. A univariate logistic regression analysis revealed that the risks of rebleeding within 30 days (odds ratio [OR]: 0.81, P = 0.42) and composite outcome (OR: 0.90, P = 0.69) were not increased during the pandemic., Conclusions: During the pandemic, the number of early colonoscopies and colonoscopies performed outside regular working hours decreased; however, this decrease did not influence rebleeding and composite outcome in patients with CDB., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2024 The Japan Society of Coloproctology.)

Objective: Rupture of cerebral aneurysms has a poor prognosis, and growing aneurysms are prone to rupture. Although the number of coil embolization procedures is increasing worldwide, they are more prone to recurrence than clipping surgeries. However, there is still no drug that prevents aneurysm growth or recanalization after coil embolization. The authors have previously focused on the role of hemodynamics in cerebral aneurysm development and reported that inhibition of the P2X4 purinoceptor, by which vascular endothelial cells sense blood flow, reduced the induction and growth of aneurysms in an animal model. In this study, the authors investigated the effects of paroxetine, a P2X4 inhibitor also used as an antidepressant, on aneurysm growth and recanalization after endovascular coiling., Methods: Using the J-ASPECT Study registry, the largest comprehensive reimbursement database system for acute stroke inpatient care in Japan, the authors searched for patients incidentally taking paroxetine who were registered in the decade 2010-2019 with an unruptured cerebral aneurysm or who underwent aneurysm coiling. They calculated the growth incidence and growth rate by the person-year method and the odds ratio for recanalization within 1 year after coiling and statistically compared to controls., Results: Seventy-eight stroke facilities participated, and 275 patients were identified as potentially eligible. Thirty-seven patients with unruptured aneurysms and 38 after coil embolization met all eligibility criteria. They were compared with 396 control cases of unruptured aneurysms and 308 coil-placement controls. Multivariate analysis showed that paroxetine significantly reduced the incidence of aneurysm growth (number of cases with growth/person/year; incidence rate ratio [IRR] 0.24, 95% CI 0.05-0.66; p = 0.003) and the growth rate (total increase in maximum diameter in millimeters/person/year; IRR 0.57, 95% CI 0.28-0.98; p = 0.04). Paroxetine also significantly reduced the odds of recanalization in the year after coiling (OR 0.21, 95% CI 0.05-0.95; p = 0.04). The authors then performed propensity score matching to reduce bias due to imbalances in patient characteristics between the two groups; the outcome confirmed that paroxetine significantly reduced aneurysm growth incidence (IRR 0.02, 95% CI 0.008-0.05; p < 0.0001) and growth rate (IRR 0.03, 95% CI 0.01-0.06; p < 0.0001) and the 1-year recanalization (OR 0.18, 95% CI 0.03-0.99; p = 0.04)., Conclusions: This observational cohort study suggests that P2X4 inhibitors such as paroxetine may be clinically applicable as prophylaxis against aneurysm rupture and postoperative recanalization.