Changes in skeletal muscle function during chemotherapy and related factors in patients with acute leukemia.

INTRODUCTION: Skeletal muscle function is an important prognostically relevant indicator in patients with acute leukemia (AL), but skeletal dysfunction during chemotherapy is not well understood. This study aimed to investigate the factors that influence changes in skeletal muscle function from before the start of chemotherapy to before allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: This was a retrospective cohort study that included 90 patients with AL who underwent chemotherapy before transplantation to perform allo-HSCT (men, 67.3%; median age, 53 years). The outcome measure was defined as changes in skeletal muscle function from before chemotherapy to before allo-HSCT, and was assessed by measuring the psoas muscle index (PMI) as skeletal muscle quantity and computed tomography values (CTV) as skeletal muscle quality using a computed tomography scanner. We examined the differences in PMI and CTV before chemotherapy and allo-HSCT, and the factors associated with changes in PMI. RESULT: The mean PMI for before chemotherapy and allo-HSCT were 4.6 ± 1.4 cm2/m2 and 4.0 ± 1.3 cm2/m2 and significant differences were observed (p < 0.001). However, the mean CTV before chemotherapy and allo-HSCT were 47.3 ± 4.5 HU and 47.4 ± 5.0 HU, respectively, and no significant differences were found (p = 0.798). In stepwise multiple regression analysis, age and sex were identified as factors related to changes in PMI (age, p = 0.019; sex, p = 0.001). CONCLUSION: We found that skeletal muscle quantity decreased during chemotherapy in patients with AL and was influenced by male sex and older age. TRIAL REGISTRATION NUMBER:   TRIAL REGISTRATION NUMBER: 34-096(11,243). Date of registration: September 11, 2023.

Association between changes in nutritional status and ability to perform activities of daily living in older patients with heart failure: A stratified analysis by frailty status.

OBJECTIVES: We aimed to determine the association between changes in nutritional status and the activities of daily living (ADL) at discharge, considering frailty status of older patients with heart failure (HF). METHODS: This study included 491 older inpatients with HF categorized into the following groups based on their clinical frailty scale (CFS) scores: low, intermediate, and high. Changes in nutritional status were assessed using the Controlling Nutritional Status score at admission and discharge. The outcome variable was Barthel Index (BI) at discharge. RESULTS: Multivariate logistic regression analysis indicated an association between improvement in nutritional status and high BI at discharge in both the low and intermediate CFS groups (odds ratio [OR], 2.18 [95% confidence interval, 1.04-4.58]), (OR, 2.45 [1.21-4.95]), respectively. CONCLUSIONS: Improvement in the ADL at discharge in older patients with HF was associated with improved nutritional status during hospitalization in the low and intermediate CFS groups.

Quantum annealing and computation: challenges and perspectives.

In the introductory article of this theme issue, we provide an overview of quantum annealing and computation with a very brief summary of the individual contributions to this issue made by experts as well as a few young researchers. We hope the readers will get the touch of the excitement as well as the perspectives in this unusually active field and important developments there. This article is part of the theme issue 'Quantum annealing and computation: challenges and perspectives'.

Development and validation of ischemic heart disease and stroke prognostic models using large-scale real-world data from Japan.

BACKGROUND: Previous cardiovascular risk prediction models in Japan have utilized prospective cohort studies with concise data. As the health information including health check-up records and administrative claims becomes digitalized and publicly available, application of large datasets based on such real-world data can achieve prediction accuracy and support social implementation of cardiovascular disease risk prediction models in preventive and clinical practice. In this study, classical regression and machine learning methods were explored to develop ischemic heart disease (IHD) and stroke prognostic models using real-world data. METHODS: IQVIA Japan Claims Database was searched to include 691,160 individuals (predominantly corporate employees and their families working in secondary and tertiary industries) with at least one annual health check-up record during the identification period (April 2013-December 2018). The primary outcome of the study was the first recorded IHD or stroke event. Predictors were annual health check-up records at the index year-month, comprising demographic characteristics, laboratory tests, and questionnaire features. Four prediction models (Cox, Elnet-Cox, XGBoost, and Ensemble) were assessed in the present study to develop a cardiovascular disease risk prediction model for Japan. RESULTS: The analysis cohort consisted of 572,971 invididuals. All prediction models showed similarly good performance. The Harrell's C-index was close to 0.9 for all IHD models, and above 0.7 for stroke models. In IHD models, age, sex, high-density lipoprotein, low-density lipoprotein, cholesterol, and systolic blood pressure had higher importance, while in stroke models systolic blood pressure and age had higher importance. CONCLUSION: Our study analyzed classical regression and machine learning algorithms to develop cardiovascular disease risk prediction models for IHD and stroke in Japan that can be applied to practical use in a large population with predictive accuracy.

Towards optimization of photonic-crystal surface-emitting lasers via quantum annealing.

Photonic-crystal surface-emitting lasers (PCSELs), which utilize a two-dimensional (2D) optical resonance inside a photonic crystal for lasing, feature various outstanding functionalities such as single-mode high-power operation and arbitrary control of beam polarizations. Although most of the previous designs of PCSELs employ spatially uniform photonic crystals, it is expected that lasing performance can be further improved if it becomes possible to optimize the spatial distribution of photonic crystals. In this paper, we investigate the structural optimization of PCSELs via quantum annealing towards high-power, narrow-beam-divergence operation with linear polarization. The optimization of PCSELs is performed by the iteration of the following three steps: (1) time-dependent 3D coupled-wave analysis of lasing performance, (2) formulation of the lasing performance via a factorization machine, and (3) selection of optimal solution(s) via quantum annealing. By using this approach, we discover an advanced PCSEL with a non-uniform spatial distribution of the band-edge frequency and injection current, which simultaneously enables higher output power, a narrower divergence angle, and a higher linear polarization ratio than conventional uniform PCSELs. Our results potentially indicate the universal applicability of quantum annealing, which has been mainly applied to specific types of discrete optimization problems so far, for various physics and engineering problems in the field of smart manufacturing.

Genetic analysis of Japanese patients with small bowel adenocarcinoma using next-generation sequencing.

BACKGROUND: Small bowel adenocarcinomas (SBAs) are rare and there is little comprehensive data on SBA genomic alterations for Asian patients. This study aimed to profile genomic alterations of SBA in Japanese patients using targeted next-generation sequencing (NGS). METHODS: We examined 22 surgical resections from patients with primary SBA. SBA genomic alterations were analyzed by NGS. Mismatch repair (MMR) status was determined by immunohistochemical analysis. Mucin phenotypes were classified as gastric (G), intestinal (I), gastrointestinal (GI), and null (N) types on MUC2, MUC5AC, MUC6, and CD10 immunostaining. RESULTS: The most common genomic alterations found in SBA tumors were TP53 (n = 16), followed by KRAS (n = 6), APC (n = 5), PIK3CA (n = 4), CTNNB1 (n = 3), KIT (n = 2), BRAF (n = 2), CDKN2A (n = 2), and PTEN (n = 2). Deficient MMR tumors were observed in 6 out of 22 patients. Tumor mucin phenotypes included 2 in G-type, 12 in I-type, 3 in GI-type, and 5 in N-type. APC and CTNNB1 mutations were not found in G-type and GI-type tumors. KRAS mutations were found in all tumor types except for G-type tumors. TP53 mutations were found in all tumor types. Although no single gene mutation was associated with overall survival (OS), we found that KRAS mutations were associated with significant worse OS in patients with proficient MMR tumors. CONCLUSIONS: SBA genomic alterations in Japanese patients do not differ significantly from those reports in Western countries. Tumor localization, mucin phenotype, and MMR status all appear to impact SBA gene mutations.

What is the optimal nutritional assessment tool for predicting decline in the activity of daily living among older patients with heart failure?

The clinical importance of nutritional management in activities of daily living (ADL) among older inpatients with heart failure (HF) is greatly increasing. We determined the optimal nutritional assessment tool that can predict ADL decline among older inpatients with HF. We prospectively investigated 91 inpatients aged ≥ 65 years with HF in an acute hospital. We measured their nutritional status at admission using nutrition indices: the controlling nutritional status (CONUT), the geriatric nutritional risk index, the prognostic nutritional index, and the mini nutritional assessment. Logistic regression analysis was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the relationships between the malnutrition status assessed by each nutritional index category and the ADL decline measured by the Barthel index (BI) in the univariate and multivariate analyses. Among the participants, 28.6% (n = 26; median age 81.5 years; 69.2% men) of the participants were included in the Reduced BI group and 71.4% (n = 65; median age 79.0 years; 67.7% men) in the Maintained BI group. The Reduced BI group showed a significantly higher CONUT value than the Maintained BI group, but there were no significant differences in other nutritional indices. In the multivariate logistic regression analysis, a higher CONUT score was associated with a significantly elevated risk of Reduced BI (adjusted OR 0.24; 95%CI 0.08-0.75; p = 0.014). We found that CONUT is an appropriate nutritional assessment tool for predicting ADL decline among older inpatients with HF in the early phase of hospitalization.

Relationship between Sarcopenia and Swallowing Capacity in Community-Dwelling Older Women.

BACKGROUND: Swallowing disorders are a serious health concern among older adults. Previous studies reported that sarcopenia may affect swallowing disorders; however, whether sarcopenia is related to the capacity to swallow (measured according to swallowing speed) in community-dwelling older adults is unclear. OBJECTIVES: The aim of this study was to investigate the relationship between sarcopenia and swallowing capacity in community-dwelling older women. METHODS: This cross-sectional observational study was conducted among community-dwelling older women in Japan. The inclusion criteria were as follows: women aged ≥65 years, with the ability to walk independently, and without dysphagia. The exclusion criterion was a history of stroke or Parkinson's disease that directly caused dysphagia. The participants were divided into a sarcopenia and a healthy group based on the criteria of the Asian Working Group for Sarcopenia 2019. We measured swallowing speed (mL/s) as the swallowing capacity by conducting a 100-mL water-swallowing test. To assess the relationship between sarcopenia and swallowing capacity, we performed a multiple regression analysis. RESULTS: Two-hundred and sixty participants were enrolled in the study. Their mean age was 82.3 ± 6.9 years, and 61 (23.5%) of them displayed sarcopenia. The mean swallowing speed was 11.5 ± 4.9 mL/s, and 17 women (6.5%) exhibited choking or a wet-hoarse voice. Multiple regression analysis revealed that sarcopenia was related to the swallowing capacity after adjusting for age, the Mini-Mental State Examination, and the number of comorbidities (ß = -0.20, 95% CI -3.78 to -0.86, p = 0.002). CONCLUSIONS: We found that sarcopenia was related to the swallowing capacity in older women in this study. Future research should clarify whether a similar relationship exists in older men as well as the effect of sarcopenia on the swallowing capacity in older adults over a period of time.

Retrieval of Retained Capsule Endoscopy at Small Bowel Stricture by Double-Balloon Endoscopy Significantly Decreases Surgical Treatment.

GOALS: The aim is to elucidate the efficacy and safety of double-balloon endoscopy (DBE) for small bowel capsule endoscopy (SBCE) retrieval from small bowel stricture and to follow the outcome of the stricture where the SBCE was entrapped. BACKGROUND: The retention of SBCE is a serious adverse event and most retained capsules are retrieved by surgery. There is still no report analyzing the follow-up of patients with stricture after retrieval of entrapped SBCEs by DBE. METHODS: This study was designed a retrospective cohort study. Subjects were 12 consecutive patients with small bowel stricture where retrieval of entrapped SBCE was attempted using DBE. Success rate of the SBCE retrieval by DBE, surgical rate of the small bowel stricture, adverse events of DBE, and outcomes in the follow-up period were evaluated. RESULTS: Diagnoses were Crohn's disease, nonsteroidal anti-inflammatory drugs-induced enteropathy, ischemic enteritis, and carcinoma in 8, 2, 1, and 1 patients, respectively. SBCE was successfully retrieved in 11 of the 12 patients (92%). No adverse events were encountered in all endoscopic procedures such as retrieval of SBCEs and dilation of the strictures. Nine of the 12 patients (75%) did not undergo surgical treatment for the stricture where SBCE was entrapped through the follow-up period (mean, 1675±847 d). CONCLUSIONS: Retrieval of SBCEs using DBE was safe, had a high success rate, and was useful to evaluate the need for surgery. Seventy-five percent of patients with small bowel stricture where the SBCE was entrapped did not require surgery through approximately 5 years.

Double-balloon endoscopy is safe and effective for the diagnosis and treatment of small-bowel disorders: prospective multicenter study carried out by expert and non-expert endoscopists in Japan.

BACKGROUND AND AIM: Double-balloon endoscopy (DBE) has enabled direct, detailed examination of the entire small bowel with interventional capabilities. Although its usefulness is recognized, efficacy and safety have not been extensively evaluated by prospective multicenter studies. To evaluate the efficacy and safety of DBE carried out by expert and non-expert endoscopists, a prospective, multicenter study was conducted in five university hospitals and a general hospital in Japan. METHODS: A total of 120 patients who underwent 179 procedures were enrolled in the study. Experts carried out 129 procedures and non-experts carried out 50 procedures. Primary and secondary end points were evaluation of safety, the rate of achievement of procedural objectives, namely, identification of a new lesion, detailed examination to establish a therapeutic strategy, or exclusion of significant lesions by total enteroscopy, and rate of successful examination of the entire small bowel and evaluation of safety. RESULTS: Overall rate of achievement of procedural objectives was 82.5% (99/120). Overall success rate for examination of the entire small bowel was 70.8% (34/48). Incidence of adverse events was 1.1% (a mucosal injury and an episode of pyrexia in two of 179 examinations). No severe adverse events were encountered. There were no significant differences in any of the outcome measures comparing expert and non-expert operators. CONCLUSIONS: DBE is effective and safe for patients with suspected small bowel diseases, and can be safely carried out even by a non-expert under the supervision of an expert, following a simple training program.

Localization of phosphorylated ErbB1-4 and heregulin in colorectal cancer.

BACKGROUND: The ErbB family consists of four proteins including (EGFR)/ErbB1, ErbB2, ErbB3, and ErbB4, and plays a crucial role in the promotion of multiple tumorigenic processes. In addition to the traditional pathways of EGFR signaling, EGFR translocates to the nucleus and acts as a transcription factor in the proliferation of cancer cells. Heregulin is known as both an ErbB3 and an ErbB4 ligand. This study aimed to investigate the expression of heregulin and its relevant EGFR family members as well as their phosphorylated forms in human colorectal cancer (CRC) tissues and to determine the relationship between their expression and clinicopathological factors including patient prognosis. METHODS: We analyzed the effects of exogenous heregulin on ErbB2, ErbB3 and ErbB4 phosphorylation in Caco-2, DLD-1, and HCT 116 colon cancer cell lines by western blot analysis. We examined 155 surgical resections from colorectomy patients. Cellular localization of ErbB1-4, their phosphorylated forms and heregulin protein was analyzed in CRC surgical resections by immunohistochemical analysis. Immunohistochemical results were compared with clinicopathological factors and patient prognosis. RESULTS: Phosphorylated ErbB2 (pErbB2) and phosphorylated ErbB3 (pErbB3) were detected in both nuclear and cytosolic fractions of Caco-2 and DLD-1 cells stimulated by exogenous heregulin. Whereas, phosphorylated ErbB4 (pErbB4) was detected only in cytosolic fractions of HCT 116 cells stimulated by exogenous heregulin. Phosphorylated EGFR (pEGFR) immunoreactivity was observed in the cytoplasm and nuclei of cancer cells, whereas the pattern of EGFR staining was membranous and cytoplasmic. Subcellular localization of pErbB2, cytoplasmic, membranous, or nuclear, varied among cases. pErbB3 immunoreactivity was exclusively observed in the nuclei of cancer cells. pErbB4 immunoreactivity was observed in the cell membrane of cancer cells. Statistically, heregulin immunoreactivity correlated with pErbB2 and pErbB4 expression. In multivariate analysis for disease free survival, lymph node status, pErbB3 and pErbB4 expression retained independent prognostic significance. In multivariate analysis for overall survival, lymph node status, pEGFR and pErbB4 retained independent prognostic significance. CONCLUSIONS: ErbB2 and ErbB3 phosphorylated by heregulin localized in the nucleus of CRC cells. Phosphorylated ErbB1-4 and heregulin contribute to poorer patient prognosis in CRC. This heregulin-ErbB family member autocrine loop may be a candidate for targeted treatment of CRC.

Novel real number representations in Ising machines and performance evaluation: Combinatorial random number sum and constant division.

Quantum annealing machines are next-generation computers for solving combinatorial optimization problems. Although physical simulations are one of the most promising applications of quantum annealing machines, a method how to embed the target problem into the machines has not been developed except for certain simple examples. In this study, we focus on a method of representing real numbers using binary variables, or quantum bits. One of the most important problems for conducting physical simulation by quantum annealing machines is how to represent the real number with quantum bits. The variables in physical simulations are often represented by real numbers but real numbers must be represented by a combination of binary variables in quantum annealing, such as quadratic unconstrained binary optimization (QUBO). Conventionally, real numbers have been represented by assigning each digit of their binary number representation to a binary variable. Considering the classical annealing point of view, we noticed that when real numbers are represented in binary numbers, there are numbers that can only be reached by inverting several bits simultaneously under the restriction of not increasing a given Hamiltonian, which makes the optimization very difficult. In this work, we propose three new types of real number representation and compared these representations under the problem of solving linear equations. As a result, we found experimentally that the accuracy of the solution varies significantly depending on how the real numbers are represented. We also found that the most appropriate representation depends on the size and difficulty of the problem to be solved and that these differences show a consistent trend for two annealing solvers. Finally, we explain the reasons for these differences using simple models, the minimum required number of simultaneous bit flips, one-way probabilistic bit-flip energy minimization, and simulation of ideal quantum annealing machine.

Inhibition of glutamine metabolism increases sensitivity to plasma-activated medium-induced cytotoxicity.

Non-thermal atmospheric pressure plasma (NTP), an ionized gas containing electrons, ions, radicals, and photons, has various biological effects, including wound healing and anticancer effects. Plasma-activated medium (PAM), which is prepared by irradiating medium with NTP, preferentially kills cancer cells. Large amounts of reactive oxygen species (ROS) and reactive nitrogen species (RNS) included in PAM are closely related to its anticancer effects. The precise mechanism of PAM-induced cytotoxicity is not fully understood; however, PAM exposure has been reported to reduce cellular energy metabolism. Glutamine (Gln) is an important amino acid as an energy source in cancer cells. Gln is converted to glutamate by glutaminase (GLS), and is utilized to synthesize ATP and glutathione (GSH). Expression levels of GLS have been shown to be higher in certain types of cancers. In this study, we examined the effects of GLS inhibition on PAM cytotoxicity using breast cancer MDA-MB-231 cells. Pretreatment with BPTES, a glutaminase 1 (GLS1) inhibitor, dose-dependently enhanced PAM-induced cell death. PAM-induced ROS production and γ-H2AX formation, a DNA damage marker, were increased in cells pretreated with BPTES compared with PAM alone. BPTES pretreatment enhanced a PAM-induced decrease in intracellular GSH, indicating the possibility that BPTES reduces the antioxidant capacity of MDA-MB-231 cells. In addition, BPTES pretreatment enhanced PAM-induced loss of the mitochondrial membrane potential and reduction of ATP production. Moreover, GLS1 knockdown promoted PAM-induced cell death. Taken together, the combination of GLS1 inhibitors such as BPTES is considered to be useful for enhancing the cytotoxic effects of PAM against cancer cells.

Development of optimization method for truss structure by quantum annealing.

In this study, we developed a new method of topology optimization for truss structures by quantum annealing. To perform quantum annealing analysis with real variables, representation of real numbers as a sum of random number combinations is employed. The nodal displacement is expressed with binary variables. The Hamiltonian H is formulated on the basis of the elastic strain energy and position energy of a truss structure. It is confirmed that truss deformation analysis is possible by quantum annealing. For the analysis of the optimization method for the truss structure, the cross-sectional area of the truss is expressed with binary variables. The iterative calculation for the changes in displacement and cross-sectional area leads to the optimal structure under the prescribed boundary conditions.

The impact of changes in physical activity on functional recovery for older inpatients in post-acute rehabilitation units.

PURPOSE: The effect of increased physical activity duration on functional recovery in older inpatients in subacute settings is not well established. This study aimed to investigate the relationship between physical activity and functional recovery in older patients receiving post-acute and subacute care. METHODS: We analyzed cohort data of hospitalized older patients (age ≥ 65 years) in the post-acute rehabilitation units. The main outcome was functional independence measure (FIM) gain. Physical activity was measured using a triaxial accelerometer. Changes in sedentary behavior and total physical activity time from admission to discharge were measured as changes in each physical activity time. Logistic regression analysis was performed to examine the relationship between changes in physical activity and FIM gain. RESULTS: A total of 210 patients were eligible for analysis. The mean age of the study patients was 83.6 ± 7.2 years, and 63.8% (n = 134) were female. According to the multivariate regression analysis, changes in sedentary behavior time were significantly associated with high recovery of FIM gain (odds ratio [OR] 0.996, 95% confidence interval [CI]: 0.993-1.000; p = 0.026), and changes in total physical activity time also showed a similar association (OR 1.006, 95% CI 1.000-1.011; p = 0.041). CONCLUSION: Decreased sedentary behavior time and increased total physical activity time were significantly associated with high functional recovery in post-acute rehabilitation units. These results suggest that interventions for physical activity duration may be effective in improving activities of daily living in older post-acute and subacute patients.

Characteristics of falls in Japanese community-dwelling older adults.

OBJECTIVE: Understanding the characteristics of falls among older adults is necessary to prevent them. These characteristics include questions such as when (month and time), where (places), who (age), what (injury), why (trigger), and how (direction) the falls occur. The objective of this study was to identify the characteristics of falls in individuals aged 65-74 years (young-old), 75-84 years (old-old), and ≥85 years (oldest-old). METHODS: We conducted an observational mail survey among community-dwelling older adults in Japan and collected detailed information on the incidence of falls over the past 3 years. The month, time, location, trigger, direction, and resulting trauma of each fall were analyzed and compared across the different age groups (young-old, old-old, and oldest-old). RESULTS: A total of 1695 falls among 1074 community-dwelling older adults were analyzed in this study. Falls were frequent during May and October as well as during the winter season from December to February, especially between 10:00 a.m. and 11:00 a.m. These fall characteristics were consistent across all the age groups. There was a higher incidence of outdoor falls among relatively young older adults, which were typically caused by tripping or slipping. However, as one progresses with age, there is a higher incidence of falls indoors, typically due to loss of balance or leg entrapment. Approximately 60% of older fallers experience some form of injury due to falls, with fractures considered the most serious, occurring in ≈10% of all falls. CONCLUSION: We clarified the characteristics of falls including the "when, where, who, what, why, and how" of the fall. A future challenge is to use this valuable information to develop effective fall prevention programs for older populations worldwide. Geriatr Gerontol Int 2024; ••: ••-••.

Effect of Early Rehabilitation Services After Discharge on Social Activity Among Chronic Stroke Survivors: A Multicenter Prospective Study.

BACKGROUND: Social inactivity after a stroke leads to adverse outcomes, making social activity after discharge important for chronic stroke survivors. This study aimed to investigate the effects of early rehabilitation services after discharge on social activity among chronic stroke survivors. METHODS: The participants were prospectively recruited from 3 convalescent hospitals. Receipt of early rehabilitation services after discharge for chronic stroke survivors was defined as the utilization of day care or home-based rehabilitation services by the Japanese long-term care insurance system. Social activity was assessed using the Frenchay Activities Index (FAI) premorbid and at 3, 6, and 12 months after discharge. In this study, the outcome was defined as the change in the FAI score from 3 to 12 months after discharge. Multivariate regression analysis was performed to examine the effect of access to rehabilitation on changes in FAI. RESULTS: Ninety stroke survivors (age 67.2±11.6 years, 52 male) were enrolled. The FAI showed improvements by 27.4% and 1.4% from 3 to 12 months after discharge in the rehabilitation and nonrehabilitation groups, respectively. Multivariate regression analysis showed that access to rehabilitation after discharge was positively associated with the FAI change from 3 to 12 months after discharge (B=30.3, ß=0.38, 95% confidence interval=11.13-49.47, P=0.002). CONCLUSIONS: Early rehabilitation services after discharge were significantly associated with increased social activity.

Relationship between progressive improvement in gait ability one year after discharge and skeletal muscle characteristics of stroke survivors.

BACKGROUND: The clinical importance of skeletal muscle characteristics for improving gait ability of stroke survivors is increasing. We aimed to examine the association between muscle quantity and quality at discharge and changes in gait independence at the time of 1 year after discharge in patients with stroke. METHODS: This prospective observational study included 100 patients with stroke who were admitted to a convalescent rehabilitation ward. We defined muscle quantity and quality operationally as muscle thickness and echo intensity observed in ultrasonography images, respectively, and measured quadriceps muscle on the paretic and non-paretic sides at the time of discharge. The outcome measured in our study was changes in gait independence 1 year after discharge, as assessed by the Functional Independence Measure gait assessment tool score. RESULTS: Among the study participants, 23 (23.0 %) were assessed to have reduced gait independence, while 77 (77.0 %) were evaluated to have improved or maintained gait independence. Our multivariate logistic regression analysis revealed that only muscle quantity on the paretic side was significantly associated with an improvement or maintenance of gait independence (odds ratios 3.32; 95 % confidence interval 1.01-10.95; p = 0.049). CONCLUSIONS: Our findings revealed that an improvement in gait independence 1 year after discharge was influenced by quadriceps muscle quantity on the paretic side at the time of discharge in patients with subacute stroke. This finding highlights the importance of lower limb muscle quantity on the paretic side as a clinically significant factor that influences the improvement in gait ability after hospital discharge.

Relationship Between Immunophenotypes, Genetic Profiles, and Clinicopathologic Characteristics in Small Bowel Adenocarcinoma.

Small bowel adenocarcinoma (SBA) is rare, and scant data exist regarding its molecular and clinicopathologic characteristics. This study aimed to clarify the correlation between immunophenotypes, DNA mismatch repair status, genomic profiling, and clinicopathologic characteristics in patients with SBA. We examined 68 surgical resections from patients with primary SBA for immunohistochemical analyses of CK7, CK20, CD10, CDX2, MUC1, MUC2, MUC4, MUC5AC, and MUC6 expression as well as mismatch repair status. Genomic profiling was performed on 30 cases using targeted next-generation sequencing. Tumor mucin phenotypes were classified as gastric, intestinal, gastrointestinal, or null based on MUC2, MUC5AC, MUC6, and CD10 immunostaining. The expression of these proteins was categorized into 3 classifications according to their relationship to: (1) tumor location: CK7/CK20, MUC4, and MUC6; (2) histologic type: mucinous adenocarcinoma was positive for MUC2 and negative for MUC6; and (3) TNM stage: CD10 was downregulated, whereas MUC1 was upregulated in advanced TNM stages. CDX2 was a specific marker for SBA generally expressed in the small intestine. MUC1 and MUC4 expression was significantly associated with worse prognosis. MUC2 expression correlated with better prognosis, except for mucinous adenocarcinoma. Although the difference was not statistically significant, gastric-type tumors were more frequently located in the duodenum and were absent in the ileum. APC and CTNNB1 mutations were not found in the gastric-type tumors. The SBA immunophenotype correlated with tumor location, biological behavior, and genomic alterations. Our results suggest that the molecular pathway involved in carcinogenesis of gastric-type SBA differs from that of intestinal-type SBA.

Cell density-dependent nuclear accumulation of ELK3 is involved in suppression of PAI-1 expression.

Cell-cell contact regulates the proliferation and differentiation of non-transformed cells, e.g., NIH/3T3 cells show growth arrest at high cell density. However, only a few reports described the dynamic behavior of transcription factors involved in this process. In this study, we showed that the mRNA levels of plasminogen activator inhibitor type 1 (PAI-1) decreased drastically at high cell density, and that ELK3, a member of the Ets transcription factor family, repressed PAI-1 expression. We also demonstrated that while ELK3 was distributed evenly throughout the cell at low cell density, it accumulated in the nucleus at high cell density, and that binding of DNA by ELK3 at the A domain facilitated its nuclear accumulation. Furthermore, we found that ETS1, a PAI-1 activator, occupied the ELK3-binding site within the PAI-1 promoter at low cell density, while it was released at high cell density. These results suggest that at high cell density, the switching of binding of transcription factors from ETS1 to ELK3 occurs at a specific binding site of the PAI-1 promoter, leading to the cell-density dependent suppression of PAI-1 expression.