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Abstract Aim Many studies have revealed the benefits of robotic surgery for rectal cancer; however, real‐world data are insufficient. This study aimed to compare the short‐term outcomes and perioperative costs of laparoscopic and robotic surgery for rectal cancer using a real‐world database. Methods The data of patients who underwent laparoscopic or robotic surgery for rectal cancer between January 2018 and January 2021 from a nationwide Japanese inpatient database provided by Medical Data Vision Co., Ltd. were analyzed. We performed propensity score matching (PSM) analysis to compare the in‐hospital mortality, morbidity, readmission rate, reoperation rate, length of postoperative stay, and medical costs between the two groups. Results We performed PSM analysis on 18 952 eligible patients. After PSM, 1396 patients in the laparoscopic group and 1396 in the robotic group were compared. The robotic group had a lower surgical site infection rate (2.9% vs. 1.5%, p = 0.010), lower respiratory failure rate (1.3% vs. 0.6%, p = 0.049), and higher operative medical costs (1 291 371 vs. 1 312 462 JPY, p = 0.013). The total medical costs of the two groups were comparable (1 862 439 vs. 1 895 822 JPY, p = 0.051). Conclusions PSM analysis revealed that robotic surgery was associated with better outcomes than laparoscopic surgery in terms of surgical site infection and respiratory failure rates. The operative medical costs of robotic surgery were significantly higher than those of laparoscopic surgery. However, there was no significant difference in the total medical costs between robotic and laparoscopic surgery for rectal cancer.

Neuroaxonal dystrophy (NAD) is a neurodegenerative disease characterized by spheroid (swollen axon) formation in the nervous system. In the present study, we focused on a newly established autosomal recessive mutant strain of F344-kk/kk rats with hind limb gait abnormalities and ataxia from a young age. Histopathologically, a number of axonal spheroids were observed throughout the central nervous system, including the spinal cord (mainly in the dorsal cord), brain stem, and cerebellum in F344-kk/kk rats. Transmission electron microscopic observation of the spinal cord revealed accumulation of electron-dense bodies, degenerated abnormal mitochondria, as well as membranous or tubular structures in the axonal spheroids. Based on these neuropathological findings, F344-kk/kk rats were diagnosed with NAD. By a positional cloning approach, we identified a missense mutation (V95E) in the Hspa8 (heat shock protein family A (Hsp70) member 8) gene located on chromosome 8 of the F344-kk/kk rat genome. Furthermore, we developed the Hspa8 knock-in (KI) rats with the V95E mutation using the CRISPR-Cas system. Homozygous Hspa8-KI rats exhibited ataxia and axonal spheroids similar to those of F344-kk/kk rats. The V95E mutant HSC70 protein exhibited the significant but modest decrease in the maximum hydrolysis rate of ATPase when stimulated by co-chaperons DnaJB4 and BAG1 in vitro, which suggests the functional deficit in the V95E HSC70. Together, our findings provide the first evidence that the genetic alteration of the Hspa8 gene caused NAD in mammals.

Resulta difícil entender por qué en el Perú, una actividad productiva característica y en líneas generales tan exitosa a nivel macroeconómico como lo es la agricultura está subdividida en un subsector altamente productivo -agroexportador, que posiciona sus productos en los mercados más exigentes a nivel global- y una agricultura de familiar que mantiene a su actor principal, el agricultor tradicional, en un estado de subsistencia. Este último parece haberse estancado en el tiempo, conservando una matriz productiva centrada en cultivos transitorios de baja rentabilidad, sin acceso a tecnología o a asistencia técnica que le permita incrementar su competitividad, autonomía y poder de negociación, este fortalecimiento de capacidades les permitiría afrontar de una mejor manera las perturbaciones de mercado como la inflación postpandemia o la crisis de fertilizantes, dichas situaciones adversas no están delimitadas a una región o país por el contrario se encuentran generalizadas debido a la presión por la demanda mundial de alimentos por lo que es propicia la presente oportunidad para explorar cómo es que se aborda la temática de la innovación, el incremento de la productividad y la evolución del sector agrícola alrededor del mundo desde la perspectiva académica a través del análisis bibliométrico y el análisis estructural.

Intracellular potassium ion (K+) concentration is higher than extracellular K+ concentration. Some cells maintain intracellular potassium levels by taking up extracellular potassium. However, investigating these details requires techniques to measure intracellular potassium concentrations. We established a method to easily measure intracellular potassium concentrations using a simpler electrode. The LAQUAtwin K-11 was capable of linearly quantifying potassium concentrations and was not affected by cellular constituents other than nucleic acids; however, it did not tolerate low temperatures. Interference caused by a high concentration of nucleic acids was eliminated by the addition of cations. It was also suggested that the concentration of nucleic acids in the cell suspension was not sufficiently high to interfere with the measurements. Intracellular potassium concentrations increased and decreased in response to extracellular potassium concentrations. Exposure to valinomycin did not decrease the potassium concentration, suggesting that re-uptake of the potassium released outside the cells occurred immediately. Additionally, potassium concentrations could be measured in the brain tissue homogenates using the device. This measurement method can track the relative changes in potassium concentration in cells under various conditions and in tissues of various disease models.

This study investigates whether the present bias influences the payment behavior of credit card holders in Japan. We hypothesize that credit card holders with present bias prefer to delay bill payment, even at the cost of accepting interest charges. To test this hypothesis, we utilize a dataset comprising 128,032 observations from a leading securities company. Our analysis reveals that a significant number of respondents indeed delayed credit card bill payments, suggesting a potential association with present bias behavior. Probit regression models further confirm the link between impatience, impulsivity, and credit card payment behavior. Specifically, impatience and impulsivity exhibit a positive association with credit card payments, indicating that impatient and impulsive credit card users are more likely to postpone payment, even when interest charges are incurred. The implications of this study extend to both credit card users and issuers, highlighting the influential role of impulsivity in the timely payment of bills.

Objectives: To compare the characteristics and prognosis of patients with nontuberculous mycobacterial (NTM) pulmonary disease (PD) with pleuroparenchymal fibroelastosis (PPFE) with those of patients with nodular/bronchiectatic (NB) and fibrocavitary (FC) NTM-PD. Methods: This multicenter, retrospective, observational study enrolled 32 patients with NTM-PPFE (median age: 70.5 years, 15 females) from six institutions in Japan from January 2003 to December 2018. Their clinical characteristics and response to therapy were compared with age- and sex-matched cohorts of patients with noncavitary NB and cavitary NB/FC NTM-PD. Results: Patients with NTM-PPFE had a lower body mass index and a higher standard NTM-PD therapy initiation rate than patients with other NTM-PD types. Sputum culture conversion rates were comparable between groups; however, patients with NTM-PPFE had a higher incidence of treatment-related adverse events, including optic neuropathy associated with high-dose ethambutol therapy, lower percent predicted forced vital capacity values, higher serum Krebs von den Lungen-6 (KL-6) levels, and poorer treatment outcomes than the other groups. Cox regression revealed that NTM-PPFE was an independent risk factor for death/pneumothorax (adjusted hazard ratio: 35.3, 95% confidence interval: 3.90-4692). Conclusion: NTM-PPFE is a unique NTM-PD phenotype with a poorer prognosis than the NB and FC phenotypes.

Objectives: In patients with stable ischemic heart disease, there is no evidence for the effect of revascularization treatment timing on the need for repeat procedures. We aimed to determine if repeat revascularizations differed among patients who received coronary artery bypass graft surgery after the time recommended by physicians compared with those who had timely percutaneous coronary intervention. Methods: We identified 25,520 British Columbia residents 60 years or older who underwent first-time nonemergency revascularization for angiographically proven, stable left main or multivessel ischemic heart disease between January 1, 2001, and December 31, 2016. We estimated unadjusted and adjusted cumulative incidence functions for repeat revascularization, in the presence of death as a competing risk, after index revascularization or last staged percutaneous coronary intervention for patients undergoing delayed coronary artery bypass grafting compared with timely percutaneous coronary intervention. Results: After adjustment with inverse probability of treatment weights, at 3 years, patients who underwent delayed coronary artery bypass grafting had a statistically significant lower cumulative incidence of a repeat revascularization compared with patients who received timely percutaneous coronary intervention (4.84% delayed coronary artery bypass grafting, 12.32% timely percutaneous coronary intervention; subdistribution hazard ratio, 0.16, 95% CI, 0.04-0.65). Conclusions: Patients who undergo delayed coronary artery bypass grafting have a lower cumulative incidence of repeat revascularization than patients who undergo timely percutaneous coronary intervention. Patients who want to wait to receive coronary artery bypass grafting will see the benefit of lower repeat revascularization over percutaneous coronary intervention unaffected by a delay in treatment.

IntroductionSpinal cord injury (SCI) leads to severe disabilities and remains a significant social and economic challenge. Despite advances in medical research, there are still no effective treatments for SCI. Human amnion-derived mesenchymal stem cells (hAMSCs) have shown potential due to their anti-inflammatory and neuroprotective effects. This study evaluates the therapeutic potential of intravenously administered hAMSCs in SCI models.MethodsThree days after induction of SCI with forceps calibrated with a 0.2 mm gap, hAMSCs or vehicle were administered intravenously. Up to 4 weeks of SCI induction, motor function was assessed by scores on the Basso Mouse Locomotor Scale (BMS) and the Basso-Beattie-Bresnahan Scale (BBB), and sensory function by hindlimb withdrawal reflex using von Frey filaments. Six weeks after SCI induction, gait function was assessed using three-dimensional motion analysis. Immunohistochemistry, polymerase chain reaction (PCR), flow cytometry, and ELISA assay were performed to clarify the mechanisms of functional improvement.ResultsThe hAMSC treatment significantly improved sensory response and gait function. In the SCI site, immunohistochemistry showed a reduction in Iba1-positive cells and PCR revealed decreased TNFα and increased BDNF levels in the hAMSC-treated group. In assessing the systemic inflammatory response, hAMSC treatment reduced monocytic bone marrow-derived suppressor cells (M-MDSCs) and Ly6C-positive inflammatory macrophages in the bone marrow by flow cytometry and serum NO levels by ELISA assay.DiscussionThis study demonstrates the therapeutic potential of the hAMSC in SCI, with improvements in gait and sensory functions and reduced inflammation both locally and systemically. The findings support further investigation of the hAMSC as a potential treatment for SCI, focusing on their ability to modulate inflammation and promote neuroprotection.

The importance of non-financial capital in firm valuation has been increasing. Non-financial capital comprises intellectual, human, social, relational, natural, and manufactured capital. This study proposes a clustered corporate value model to identify financial and non-financial factors influencing firm value. We cluster a group of companies and build a principal component regression model for each cluster, using the Bayesian Information Criterion for evaluation, with financial and non-financial factors as explanatory variables. We also considered the time lag in the impact of financial and non-financial factors on corporate value. In other words, we consider the impact of financial and non-financial factors on corporate value over multiple years, not just a single year. We propose an algorithm that identifies clusters and constructs a regression model for each, optimizing the combination of cluster divisions and explanatory variables using adjusted R-squared as the evaluation criterion. The cluster-specific corporate value model shows higher explanatory power than the industry-specific cluster-based corporate value model for the electrical, chemical, food, construction, and service industries.

Abstract A 12‐year‐old male domestic cat with multiple subcutaneous mast cell tumours (MCTs) presented with a 2‐week history of pruritus and raw/bleeding skin from self‐trauma at Kagoshima University Veterinary Teaching Hospital. Polymerase chain reaction (PCR) and histopathological analyses revealed intertumoral heterogeneity among tumour locations based on the mutation status of KIT. In addition, the expression pattern of KIT was characterized. After failed treatment with vinblastine (2.0–2.2 mg/m2, intravenous administration, two doses in total) or nimustine (25 mg/m2, intravenous administration, two doses in total), toceranib (2.2–2.6 mg/kg, orally administered, every other day) was administered to treat recurrent MCTs harbouring the KIT exon eight internal tandem duplication mutation, achieving a complete response. However, toceranib resistance developed 2 months after treatment initiation. Subsequent PCR analysis was conducted to identify the mutational status of KIT in each MCT and to detect the presence of secondary mutations associated with the acquisition of toceranib resistance. Secondary KIT mutations (c.998G>C and c.2383G>C), which were not initially detected in tumour cells at diagnosis, were identified after the development of resistance to toceranib. This indicates that the tumour cells in feline MCTs in the same case have diverse characteristics. Our findings encourage further investigation into the development of therapeutic strategies for feline MCTs, particularly focusing on the heterogeneous nature of KIT/KIT and overcoming acquired resistance to toceranib.

We have recently shown delayed increases in GABAB receptor (GABABR) subunit protein levels in the hippocampal dentate gyrus (DG), but not in the pyramidal CA1 and CA3 regions, at 15–30 days after the systemic single administration of trimethyltin (TMT) in mice. An attempt was thus made to determine whether the delayed increases return to the control levels found in naive mice afterward. In the DG on hippocampal slices obtained at 90 days after the administration, however, marked increases were still seen in protein levels of both GABABR1 and GABABR2 subunits without significant changes in calbindin and glial fibrillary acidic protein (GFAP) levels on immunoblotting analysis. Fluoro-Jade B staining clearly revealed the absence of degenerated neurons from the DG at 90 days after the administration. Although co-localization was invariably detected between GABABR2 subunit and GFAP in the DG at 30 days on immunohistochemical analysis, GABABR2-positive cells did not merge well with GFAP-positive cells in the DG at 90 days. These results suggest that both GABABR1 and GABABR2 subunits would be tardily and sustainably up-regulated by cells other than neurons and astrocytes in the murine DG at 90 days after a systemic single injection of TMT.

Cardiomyopathies are major causes of heart failure. Chagas disease (CD) is caused by the parasite Trypanosoma cruzi, and it is endemic in Central and South America. Thirty percent of cases evolve into chronic chagas cardiomyopathy (CCC), which has worse prognosis as compared with other cardiomyopathies. In vivo bioenergetic analysis and ex vivo proteomic analysis of myocardial tissues highlighted worse mitochondrial dysfunction in CCC, and previous studies identified nuclear-encoded mitochondrial gene variants segregating with CCC. Here, we assessed the role of the mitochondrial genome through mtDNA copy number variations and mtDNA haplotyping and sequencing from heart or blood tissues of severe, moderate CCC and asymptomatic/indeterminate Chagas disease as well as healthy controls as an attempt to help decipher mitochondrial-intrinsic genetic involvement in Chagas disease development. We have found that the mtDNA copy number was significantly lower in CCC than in heart tissue from healthy individuals, while blood mtDNA content was similar among asymptomatic Chagas disease, moderate, and severe CCC patients. An MtDNA haplogrouping study has indicated that African haplogroups were over represented in the Chagas subject groups in comparison with healthy Brazilian individuals. The European lineage is associated with protection against cardiomyopathy and the macro haplogroup H is associated with increased risk towards CCC. Using mitochondria DNA sequencing, 84 mtDNA-encoded protein sequence pathogenic variants were associated with CCC. Among them, two variants were associated to left ventricular non-compaction and two to hypertrophic cardiomyopathy. The finding that mitochondrial protein-coding SNPs and mitochondrial haplogroups associate with risk of evolving to CCC is consistent with a key role of mitochondrial DNA in the development of chronic chagas disease cardiomyopathy.

Purpose: Following total hip arthroplasty (THA), anxiety about dislocation often limits patient's quality of life. However, the factors that cause anxiety about dislocation remain unclear. This study was an investigation of whether limited range of motion (ROM) at the hip before surgery is associated with anxiety about dislocation after THA. Methods: A retrospective cohort study was performed using questionnaires and medical records. Questionnaires were mailed to 796 female patients who underwent THA at our hospital between April 2015 and August 2020. The questionnaire was to be self-administered and asked participants to select their level of anxiety about dislocation during activities of daily living from the following answer choices: non-anxious, anxious, and extremely anxious. Hip ROM was measured within 3 days before surgery. The association between anxiety about dislocation and hip ROM was evaluated using logistic regression analysis after adjusting for potentially relevant factors. Results: In total, 513 (64.4%) patients responded to the questionnaire and were included in the analysis. Those patients who reporting feeling extremely anxious about dislocation after THA had limited hip flexion ROM. This association was independent of surgical approach and postoperative follow-up duration. A ROM of less than 80° during hip flexion was used to identify those respondents who reported extreme anxiety about dislocation. Conclusion: The results of this study suggest that patients with a limited hip flexion ROM before THA may be extremely anxious about dislocation after THA.

Abstract Cardiac sarcoidosis (CS) is the scarring of heart muscles by autoimmunity, leading to heart abnormalities and patients with sarcoidosis with cardiac involvements have poor prognoses. Due to the small number of patients, it is difficult to stratify all patients of CS by human leukocyte antigen (HLA) analysis. We focused on the structure of antigen-recognizing pockets in heterodimeric HLA-class II, in addition to DNA sequences, and extracted high-affinity combinations of antigenic epitopes from candidate autoantigen proteins and HLA. Four HLA heterodimer-haplotypes (DQA1*05:03/05:05/05:06/05:08-DQB1*03:01) were identified in 10 of 68 cases. Nine of the 10 patients had low left ventricular ejection fraction (

Panic selling causes long-term losses and hinders investors’ return to the market. It has been explained using prospect theory aspects such as loss and regret aversion. Additionally, overconfidence and overreaction contribute to the disposition effect, leading investors to sell stocks prematurely. However, the framing effect, another disposition effect attribute, has been underexplored in the context of panic selling. This study investigates how the framing effect influences panic selling, particularly during market crises, when investors perceive information differently, depending on its positive or negative framing. Utilizing data from a collaborative survey, we examine Japanese investors’ behavior during the COVID-19 market crisis. Negative framing is negatively associated with complete or partial sale of securities, whereas positive framing has the opposite effect. During market crises, investors presented with negative framing are less likely to panic sell, whereas those presented with positive framing are more prone to it. Other significant factors include gender; men tend to engage more in panic selling. Conversely, higher education, financial literacy, and greater household income and assets are associated with a reduced likelihood of panic selling. These findings underscore the critical role of framing in investor behavior during market crises, providing new insights into the mechanisms underlying panic selling.

Abstract Purpose Several studies investigated endometrial patterns, with respect to pregnancy rates following the transfer of embryos but did not distinguish between single‐ and multiple‐blastocyst procedures. We clarified how the endometrial pattern imaged to transfer a frozen embryo is associated with pregnancy outcomes in single‐blastocyst frozen‐embryo transfer (sbFET). Methods Patients ≤35 years who underwent sbFET on the hormone replacement protocol. We analyzed endometrial patterns’ associations with pregnancy outcomes in relation to blastocyst grade and pregnancy‐related factors. Results Of the 1383 cycles, 483 were Lf, 840 were partial‐Lf, and 60 were non‐Lf. Leaf pattern (Lf): central echogenic line present and continuous. Overall, decreasing distinctness of the central echogenic line was associated with significantly lower rates of clinical pregnancy (Lf: 70.4%; partial‐Lf: 58.1%; non‐Lf: 28.3%) and live birth (56.3%, 45.5%, and 15.0%) and a higher miscarriage rate (20.0%, 21.7%, and 47.1%). Logistic regressions showed pregnancy and live birth to be significantly more likely and miscarriage less likely in Lf than non‐Lf: OR (95% CI): 6.07 (3.24–11.37), 7.43 (3.47–15.39), and 0.20 (0.07–0.57). Conclusions Non‐Lf presentation was associated with lower rates of pregnancy and live birth, suggesting it signals unsuitable conditions for embryo transfer. We provide information on the pregnancy outcomes of sbFET for endometrial patterns.

Post-translational modifications (PTMs) are protein modifications that occur after protein biosynthesis, playing a crucial role in regulating protein function. They are involved in the functional expression of G-protein-coupled receptors (GPCRs), as well as intracellular and secretory protein signaling. Here, we aimed to investigate the PTMs of the apelin receptor (APLNR), a GPCR and their potential influence on the receptor's function. In an in vitro experiment using HEK cells, we only observed glycosylation as a PTM of the APLNR and ineffective receptor signaling by the agonist, (Pyr1)-apelin-13. In contrast, when analyzing mouse spinal cord, we detected glycosylation and other PTMs, excluding isopeptidation. This suggests that additional PTMs are involved in the functional expression of the APLNR in vitro. In summary, these findings suggest that the APLNR in vivo requires multiple PTMs for functional expression. To comprehensively understand the pharmacological effects of the APLNR, it is essential to establish an in vitro system that adequately replicates the receptor's PTM profile. Nonetheless, it is crucial to overcome the challenge of heat-sensitive proteolysis in APLNR studies. By elucidating the regulation of PTMs, further research has the potential to advance the analysis and pharmacological studies of both the apelin/APLNR system and GPCR signal modulation.

Abstract Background Ventriculoperitoneal (VP) shunt placement is commonly performed to treat hydrocephalus and complications are not uncommon. We report here a case of generalized peritonitis caused by migration of the abdominal end of a VP shunt catheter into the bowel after multiple VP shunt revisions over 30 years. Laparoscopic surgery was successfully performed for the peritonitis and the VP shunt system subsequently reconstructed without complications. Case presentation The patient was a 49-year-old woman who had a VP shunt placed for obstructive hydrocephalus at the age of 13 years. The shunt system required seven revisions because of various malfunctions, including two occasions where a nonfunctioning shunt catheter was left inside the abdomen for safety reasons. Approximately 1 year after the seventh revision, she developed abdominal pain and fever. Abdominal computed tomography suggested that the shunt catheter had migrated into the small intestine and caused an intra-abdominal abscess. We performed emergency exploratory laparoscopy, which revealed perforation of the small intestine by the tip of a nonfunctioning shunt catheter. A growing abscess was found around the perforated intestinal wall, causing bacterial ascites. After the functioning shunt catheter was pulled out from the abdomen, the nonfunctioning catheter that had perforated the intestinal wall was removed. The functioning shunt catheter was then connected to the cerebrospinal fluid drainage system to manage her severe hydrocephalus. Finally, the contaminated abdominal cavity was copiously irrigated with saline solution and a peritoneal drain placed. Twenty-five days later, she underwent another VP shunt surgery in which a VP shunt catheter was placed. She was discharged 45 days after the surgery for peritonitis without complications. Conclusion In cases of peritonitis with a history of VP shunt placement, perforation by a VP shunt catheter is possible, though rare. A delay in treatment could lead to a potentially fatal complication, such as septic shock. Laparoscopic surgery enabled a faster, more hygienic, and minimally invasive operation for managing this rare but serious complication of VP shunt placement.

Neuroaxonal dystrophy (NAD) is a neurodegenerative disease characterized by spheroid (swollen axon) formation in the nervous system. In the present study, we focused on a newly established autosomal recessive mutant strain of F344-kk/kk rats with hind limb gait abnormalities and ataxia from a young age. Histopathologically, a number of axonal spheroids were observed throughout the central nervous system, including the spinal cord (mainly in the dorsal cord), brain stem, and cerebellum in F344-kk/kk rats. Transmission electron microscopic observation of the spinal cord revealed accumulation of electron-dense bodies, degenerated abnormal mitochondria, as well as membranous or tubular structures in the axonal spheroids. Based on these neuropathological findings, F344-kk/kk rats were diagnosed with NAD. By a positional cloning approach, we identified a missense mutation (V95E) in the Hspa8 (heat shock protein family A (Hsp70) member 8) gene located on chromosome 8 of the F344-kk/kk rat genome. Furthermore, we developed the Hspa8 knock-in (KI) rats with the V95E mutation using the CRISPR-Cas system. Homozygous Hspa8-KI rats exhibited ataxia and axonal spheroids similar to those of F344-kk/kk rats. The V95E mutant HSC70 protein exhibited the significant but modest decrease in the maximum hydrolysis rate of ATPase when stimulated by co-chaperons DnaJB4 and BAG1 in vitro, which suggests the functional deficit in the V95E HSC70. Together, our findings provide the first evidence that the genetic alteration of the Hspa8 gene caused NAD in mammals.