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Increased fear of falling (FOF) increases the risk of falling and is an important issue for living an independent life.　Patients undergoing hemodialysis (HD) frequently fall, and this may be attributed to increased FOF due to common fall risk factors as well as severe chronic kidney disease and HD-related factors.　The purpose of this narrative review was to summarize the current knowledge on the mechanisms of increased FOF leading to falls in patients undergoing HD.　Patients undergoing HD have enhanced FOF compared to community elderly people.　Furthermore, an increase in FOF is correlated with a decrease in physical activity and physical function.　It has been reported that FOF in patients undergoing HD may be associated with past and future falls, and the risk of falling increases sharply when FOF exceeds a certain threshold.　Increased FOF may serve as a fundamental mechanism leading to increased fall risk by interacting with physical inactivity and physical frailty, affecting lower limb muscle activity during walking.　Further research is needed to clarify the relationship between increased FOF and falls in patients undergoing HD.　Regular clinical assessment of FOF is critical for identifying fall risk in patients undergoing HD.

The aim of the present study was to determine the effectiveness of combined exercise and nutrition interventions on physical function and quality of life (QOL) in patients with acute leukemia or malignant lymphoma (ML) during inpatient chemotherapy. The study was a randomized controlled trial where patients with acute leukemia or ML who were receiving inpatient chemotherapy and exercise therapy were divided into an intervention group (IG) and a control group (CG). Both groups underwent resistance training and aerobic exercise. The patients in the IG were instructed to take nutritional supplements twice a day. Assessment items were muscle strength (handgrip strength and knee extension strength), 6-min walking test, skeletal muscle mass, QOL, nutritional status, and fatigue. Two-way analysis of variance showed a significant interaction for bilateral handgrip strength and knee extension strength. No significant interactions were found for the other items. The results of the present study showed improved muscle strength in the IG compared to the CG, indicating the effectiveness of combined exercise and nutrition interventions during inpatient chemotherapy in patients with acute leukemia or ML.

The original 100.3 Mb reference genome for Caenorhabditis elegans , generated from the wild-type laboratory strain N2, has been crucial for analysis of C. elegans since 1998 and has been considered complete since 2005. Unexpectedly, this long-standing reference was shown to be incomplete in 2019 by a genome assembly from the N2-derived strain VC2010. Moreover, genetically divergent versions of N2 have arisen over decades of research and hindered reproducibility of C. elegans genetics and genomics. Here we provide a 106.4 Mb gap-free, telomere-to-telomere genome assembly of C. elegans , generated from CGC1, an isogenic derivative of the N2 strain. We used improved long-read sequencing and manual assembly of 43 recalcitrant genomic regions to overcome deficiencies of prior N2 and VC2010 assemblies, and to assemble tandem repeat loci including a 772-kb sequence for the 45S rRNA genes. While many differences from earlier assemblies came from repeat regions, unique additions to the genome were also found. Of 19,972 protein-coding genes in the N2 assembly, 19,790 (99.1%) encode products that are unchanged in the CGC1 assembly. The CGC1 assembly also may encode 183 new protein-coding and 163 new ncRNA genes. CGC1 thus provides both a completely defined reference genome and corresponding isogenic wild-type strain for C. elegans , allowing unique opportunities for model and systems biology.

Objectives: Hemorrhagic events are a rare but potentially fatal complication in patients with polycythemia vera (PV)., Methods: We analyzed the characteristics of hemorrhagic events in 267 patients with PV., Results: A median follow-up of 4.8 years revealed that 23 (8.6%) hemorrhagic events occurred. Significantly more hemorrhagic events occurred in younger patients aged below 60 years (n = 72) than in older patients aged 60 years or above (n = 191) (n = 12 [16.7%] vs. n = 11 [5.8%], respectively, P  = 0.012). In univariate analysis among the younger patients, white blood cell (WBC) count ≥ 15 × 10 9 /L (hazard ratio [HR] = 7.746, 95% confidence interval [CI] 2.082-28.830, P  = 0.002), palpable splenomegaly (HR = 5.629, 95% CI 1.193-26.550, P  = 0.029), and JAK2 V617F allele burden ≥ 80% (HR = 22.850, 95% CI 2.885-181.00, P  = 0.003) were associated with an increased risk of hemorrhagic events. In multivariate analysis, JAK2 V617F allele burden ≥ 80% (HR = 9.394, 95% CI 1.046-84.380, P  = 0.046) was a significant risk factor., Conclusions: There is an increased risk of hemorrhagic events after diagnosis in younger PV patients with a high JAK2 V617F allele burden, high WBC count or palpable splenomegaly. It is important to consider treatment options that aim to avoid hemorrhagic events by reducing the JAK2 V617F allele burden in younger PV patients.

Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic nervous system dysfunction and cerebellar ataxia or parkinsonism. Recently, expanded GAA repeats (≥250 repeat units) in intron 1 of FGF14 have been shown to be responsible for spinocerebellar ataxia type 27B (SCA27B), a late-onset ataxia with an autosomal dominant inheritance. Patients with SCA27B may also exhibit autonomic nervous system dysfunction, potentially overlapping with the clinical presentations of MSA patients. In this study, to explore the possible involvement of expanded GAA repeats in MSA, we investigated the frequencies of expanded GAA repeats in FGF14 in 548 patients with MSA, 476 patients with undiagnosed ataxia, and 455 healthy individuals. To fully characterize the structures of the expanded GAA repeats, long-range PCR products suggesting the expansion of GAA repeats were further analyzed using a long-read sequencer. Of the 548 Japanese MSA patients, we identified one MSA patient (0.2%) carrying an expanded repeat with (GAA) ≥250 . Among the 476 individuals with undiagnosed ataxia, (GAA) ≥250 was observed in six (1.3%); this frequency was higher than that in healthy individuals (0.2%). The clinical characteristics of the MSA patient with (GAA) ≥250 were consistent with those of MSA, but not with SCA27B. Further research is warranted to explore the possibility of the potential association of expanded GAA repeats in FGF14 with MSA., Competing Interests: Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: Written informed consent was obtained from all the patients. This study was approved by the institutional review board of the University of Tokyo and participating institutions., (© 2024. The Author(s).)

Background: By 2060, the global burden of dementia, particularly Alzheimer's disease (AD), is expected to increase significantly, necessitating effective palliative care strategies. Dysphagia, a common condition among people with dementia, leads to malnutrition, aspiration pneumonia, and a reduced quality of life., Objective: This study aimed to identify oral health management factors that could predict a decline in swallowing function in older adults with AD., Methods: Data from the Akita-Omorimachi study, which included 63 adults diagnosed with AD, were analysed. Swallowing function was assessed using the modified water-swallowing test (MWST) at baseline and after 1 year., Results: The results indicated that 25.4% of participants exhibited a decline in swallowing function, as indicated by a decrease from the highest MWST score of 5 at baseline to a lower score at follow-up. Poisson regression analysis revealed that refusal of oral care (incidence rate ratio (IRR): 7.28), tongue coating (IRR: 4.21), and unclear articulation of /ka/ (IRR: 5.79) were significant predictors of swallowing function decline. The participants with these indicators had a higher risk of developing dysphagia., Conclusions: These findings suggest that factors related to specific oral health problems may predict poor swallowing function in older adults with AD. Moreover, implementing targeted oral care interventions, including person-centered care and regular tongue cleaning, may improve the outcomes in this vulnerable population. Despite the limitations of this study, including a small sample size, the results underscore the importance of comprehensive oral health management in preventing dysphagia-related complications., (© 2024 John Wiley & Sons Ltd.)

Background: This systematic review and meta-analysis aimed to investigate the association between health-related quality of life (HRQOL) as measured with the Short Form 36 Health Survey (SF-36) or Short Form 12 Health Survey (SF-12) and mortality risk in patients with diverse types of cancer., Methods: A literature search was conducted using CINAHL, PubMed/MEDLINE, and Scopus databases to collect articles published before December 2022. Of these, observational studies that examined the association between HRQOL and mortality risk in patients with various cancer types were extracted. A subgroup analysis with a focus on the timing when HRQOL assessment was performed., Results: Nineteen studies were included in the final analysis. Through overall analysis of the timing of HRQOL measurements, most domains were found to be significantly associated with the mortality risk, irrespective of the timing of assessment, but HRQOL assessed in pre-treatment and palliative phases had particularly strong association., Conclusions: In the present review, the physical functioning domain of HRQOL was found to be associated with mortality risk in a diverse group of cancer patients. This suggests the need for supportive care to improve HRQOL in cancer patients., Competing Interests: Declarations. Conflict of interest: The authors declare that there is no conflict of interest., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

CREB3L1, a gene encoding the endoplasmic reticulum stress transducer, is specifically overexpressed in platelet RNA from patients with myeloproliferative neoplasms (MPNs). However, the pathophysiological roles of CREB3L1 overexpression remain unclear. In the present study, we aimed to study CREB3L1 messenger RNA (mRNA) expression in the red blood cells (RBCs) of patients with MPN and its role in erythrocytosis. Elevated expression of CREB3L1 was exclusively observed in the RBCs of patients with polycythemia vera (PV) harboring JAK2 exon 12 mutations, but not in those harboring JAK2 V617F mutation or control subjects. In erythropoiesis, CREB3L1 expression was sharply induced in erythroblasts of bone marrow cells collected from patients with JAK2 exon 12 mutation. This was also evident when erythropoiesis was induced in vitro using hematopoietic stem and progenitor cells (HSPCs) with JAK2 exon 12 mutation. Interestingly, overexpression of CREB3L1 in RBCs was observed in patients with reactive erythrocytosis whose serum erythropoietin (EPO) levels exceeded 100 mIU/mL. Elevated CREB3L1 expression was also observed in the erythroblasts of a patient with acute erythroid leukemia. EPO-dependent induction of CREB3L1 was evident in erythroblasts differentiated from HSPCs in vitro, regardless of driver mutation status or MPN pathogenesis. These data strongly suggest that CREB3L1 overexpression in RBCs is associated with hyperactivation of the EPO receptor and its downstream molecule, JAK2. Short hairpin RNA (shRNA) knockdown of CREB3L1 expression in HSPCs blocked erythroblast formation in vitro. These results suggest that CREB3L1 is required for erythropoiesis in the presence of JAK2 exon 12 mutation or high level of EPO, possibly by antagonizing cellular stress., Competing Interests: Conflict of Interest Disclosure M Araki and MI are employees of Meiji Seika Pharma. M Ando has received honoraria and research funding from Chugai Pharmaceutical, Sumitomo Pharma, Kyowa Kirin, and AbbVie; honoraria from Novartis Pharma, AstraZeneca, and Astellas Pharma; and research funding from Century Therapeutics and Daiichi Sankyo. NK has received a salary from PharmaEssentia Japan where he is a board member; acted as a consultant for Torii Pharmaceutical; received honoraria from Novartis Pharma, Takeda Pharmaceutical, and Nippon Shinyaku; received research funding from Kyowa Kirin, Bayer Yakuhin, Daiichi Sankyo, Takeda Pharmaceutical, PharmaEssentia, and Taiho Pharmaceutical; and endowed chair funded by PharmaEssentia Japan and Meiji Seika Pharma. All other authors have no declarations., (Copyright © 2024 International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)

Study Design: Retrospective cohort study., Objective: To investigate the incidence of and risk factors for segmental motor paralysis after anterior cervical spine surgery., Summary of Background Data: Segmental motor paralysis is a potential complication following both anterior and posterior cervical decompression procedures; however, previous studies investigating risk factors for segmental motor paralysis after anterior cervical spine surgery were limited by small sample sizes. Consequently, the exact pathogenesis and risk factors for this complication remain poorly understood, highlighting the need for larger-scale investigations focused exclusively on anterior cervical spine surgeries., Methods: We retrospectively reviewed the clinico-demographic and operative factors and postoperative outcomes of 1,428 patients undergoing anterior cervical spine surgery at three spine centers in Japan. Postoperative segmental motor paralysis was defined as deterioration of upper extremity muscle strength by ≥1 grade; recovery was defined as a return to preoperative muscle strength levels. Univariate and multivariate analyses were performed to identify risk factors., Results: Ninety-nine patients (6.9%) developed segmental motor paralysis, mostly involving the C5 segment (81.8%), the incidence being highest in patients with ossification of the posterior longitudinal ligament (OPLL) and those undergoing anterior cervical corpectomy and fusion or hybrid fusion (discectomy + corpectomy). Older age, male sex, higher body mass index, OPLL, and cervical corpectomy were independent risk factors for paralysis, with these patients having significantly worse clinical outcomes at 1 year postoperatively. Most patients (74/99, 79.6%) regained preoperative muscle strength levels an final follow up., Conclusion: This study identified important clinico-demographic and operative risk factors for segmental motor paralysis after anterior cervical spine surgery. Patients undergoing corpectomy, with or without OPLL, were found to be at particularly high risk. While most patients recover well, worse outcomes with segmental motor paralysis highlight the importance of preventing this complication, particularly for OPLL patients and corpectomy procedures., Level of Evidence: III., Competing Interests: Conflicts of interest: All authors have no conflict of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Recently developed rapid real-time reverse transcription PCR (RT-PCR) systems adopting microfluidic thermal cycling technology are ideal for point-of-care (POC) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because the RNA extraction step before real-time RT-PCR is rate-limiting, a direct RNA extraction method (direct method) that adopts chemical viral lysis and eliminates RNA purification steps is preferable for rapid real-time RT-PCR. In the direct method, selecting the transport medium is essential because it may be introduced into subsequent real-time RT-PCR steps, but might inhibit PCR. However, the influence of transport medium on the combination of the direct method and rapid real-time RT-PCR has been yet unstudied. In the present study, we examined the influence of various transport mediums when combining the direct method and rapid real-time RT-PCR of GeneSoC ® (GeneSoC ® RT-PCR), the recently developed compact PCR system that adapts novel microfluidic thermal cycling technology., Methods: To explore the influence of the transport medium on the GeneSoC ® RT-PCR, the concordance of the RNA extraction and direct method was evaluated in the clinical samples collected in viral transport medium (VTM) or eSwab ® . The sensitivity of GeneSoC ® RT-PCR combined with the direct method was assessed using spiked samples in generic (H 2 O and PBS) or commercially available transport media (VTM and eSwab ® ). Analytical sensitivity was examined using clinical specimens collected from the VTM and eSwab ® . The inhibitory effect of PCR inhibitors on clinical specimens was assessed using clinical samples diluted 1,000 times., Results: While only 1 copy/reaction of RNA was detected in H 2 O and eSwab ® of the spiked samples, a minimum of 5 copies/reaction was detected in PBS (-) and VTM. Among the clinical specimens tested using the direct method, the detection of viral RNA was unstable in the samples containing less than 100 copies/reaction viral RNA in VTM, whereas less than 10 copies/reaction viral RNA were detected in eSwab ® . The positive, negative, and overall concordance between the RNA extraction and the direct method was 84%, 100%, and 85%, respectively, in eSwab ® samples, whereas the values were 35%, 100%, and 38%, respectively, in VTM samples. When the clinical samples were diluted 1,000 times, GeneSoC ® RT-PCR could detect as low as 1.15 copies/reaction RNA using direct method, and the sensitivity was comparable to that of RNA extraction., Conclusion: The combination of the direct method and microfluidic rapid PCR machine GeneSoC ® has a high sensitivity for detecting SARS-CoV-2 RNA in clinical samples with eSwab ® transport medium., Competing Interests: Conflict of interest: This study was partly funded and provided the study materials (chips and kits) by Kyorin Pharmaceutical Co., Ltd., (©2024 Tottori University Medical Press.)

We investigated the influence of sarcopenia on treatment outcomes in elderly patients receiving medical therapy for lower urinary tract symptoms (LUTS). We included male patients with LUTS aged ≥ 75 years who had not changed their medication for 1 year. Current conditions were estimated using IPSS, overactive bladder symptoms score (OABSS), and screening tool for sarcopenia (SARC-F). We also evaluated prostatic volume (PV), serum testosterone level, grip strength, and nutrition status. SARC-F score of ≧4 was defined as sarcopenia. We included 59 patients in this study, including 16 patients (27.1%) with sarcopenia. The mean grip strength was significantly lower in the sarcopenia group than the non-sarcopenia group (25.5 vs. 30 kg, p < 0.01). IPSS total score, voiding symptom score of IPSS, and IPSS-QOL were significantly higher in the sarcopenia group than the non-sarcopenia group. The non-sarcopenia group had significantly larger PV (40 vs. 20 ml, p < 0.01) and higher testosterone levels (497.5 vs. 369 ng/ml, p = 0.03) compared with the sarcopenia group, whereas the percentage of patients taking dutasteride tended to be higher in the non-sarcopenia group than the sarcopenia group (58.1% vs. 31.3%, p = 0.07). Moderate and severe LUTS (IPSS total ≥ 8) persisted in 34 patients (57.6%) after medical treatment. Multivariate analysis showed that only SARC-F was a significant factor affecting the IPSS total ≥ 8 despite medical treatment for 1 year (OR 1.67, 95%CI: 1.13-2.46, p = 0.01). Sarcopenia defined by using SARC-F is a significant factor for unsatisfactory medical treatment of LUTS in elderly men aged ≥ 75 years., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Adult spinal deformity (ASD) has a significant impact on trunk balance and quality of life in the elderly. Postoperative rod fractures pose significant challenges, but the mechanisms of their occurrence are underexplored compared to other complications such as proximal junctional kyphosis. This study investigated factors associated with rod fracture in patients with ASD., Methods: A retrospective single-center study analyzed 110 adult patients who underwent spinal deformity correction between 2012 and 2020. Comparative analysis and univariate and multivariate Cox regression analyses were employed to identify factors associated with rod fracture., Results: In this study, rod fracture occurred in 14.5% of patients. The rod fracture group exhibited a larger change in lumbar lordosis (LL), a higher proportion of patients with pre-operatively existing (pre-existing) vertebral fractures, and a greater percentage of patients with a rod diameter of 6 mm or less compared to the non-rod fracture group. Univariate Cox regression analysis revealed that rod fracture was associated with pre-existing vertebral fracture, LL change, preoperative sagittal vertical axis, and preoperative pelvic tilt. Multivariate Cox regression analysis identified pre-existing vertebral fractures and the amount of LL change as independent factors associated with rod fractures., Conclusion: Pre-existing vertebral fractures and the magnitude of lumbar lordosis correction are independent risk factors for rod fracture following ASD surgery. Surgeons should consider these factors during preoperative planning to reduce the risk of postoperative rod fracture., Level of Evidence: IV., (© 2024. The Author(s), under exclusive licence to Scoliosis Research Society.)

Objective: Detrusor underactivity (DU) is a common cause of lower urinary tract symptoms (LUTS). To date, no consensus has been reached on the urodynamic criteria for defining DU. We previously proposed the area under the curve of the Watts factor (WF-AUC) as a new parameter for diagnosing DU. By comparing previously reported five criteria for DU and WF-AUC, we analyzed whether the WF-AUC could assess detrusor contraction in women with LUTS., Methods: Using urodynamic data of consecutive 77 women with LUTS, first, we classified DU based on previously reported five criteria. Second, we assessed the potential correlation between multiple parameters and WF-AUC. Third, receiver operating characteristic curve analysis was performed to determine the cutoff value of WF-AUC for diagnosing DU based on previously reported five criteria. Fourth, a linear regression analysis was conducted and compared using multiple criteria and female bladder outlet obstruction index (BOOIf)., Results: WF-AUC was positively correlated with the maximum values of WF, bladder contractility index (BCI), and projected isovolumetric pressure 1 (PIP1) with correlation coefficients of 0.63, 0.57, and 0.34, respectively. AUC for diagnosing DU based on previously reported five criteria ranging from 0.773 to 0.896 with different cutoff values of AUC-WF. The Spearman's correlation test revealed that BOOIf was significantly correlated with BCI, but not W max , PIP1 and WF-AUC., Conclusions: This study demonstrated the non-inferiority of the WF-AUC compared to previously reported criteria for defining DU. Depending on the cutoff value, the WF-AUC could appropriately evaluate women with DU, regardless of the presence of BOO., (© 2024 The Japanese Urological Association.)

Purpose: This systematic review and meta-analysis aimed to examine the impact of global quality of life (QOL) on mortality risk in patients with cancer, considering cancer type and timepoint of QOL assessment., Methods: A systematic search was conducted using Cumulated Index to Nursing and Allied Health Literature, PubMed/MEDLINE, and Scopus databases from inception to December 2022. Observational studies that assessed QOL and examined mortality risk in patients with cancer were extracted. Subgroup analyses were performed for cancer types and timepoints of QOL assessment., Results: Overall, global QOL was significantly associated with mortality risk (hazard ratio: 1.06, 95% confidence interval: 1.05-1.07; p < 0.00001). A subgroup analysis based on cancer type demonstrated that lung, head and neck, breast, esophagus, colon, prostate, hematologic, liver, gynecologic, stomach, brain, bladder, bone and soft tissue, and mixed type cancers were significantly associated with mortality risk; however, melanoma and pancreatic cancer were not significantly associated with mortality risk. Additionally, global QOL was associated with mortality risk at all timepoints (pretreatment, posttreatment, and palliative phase); pretreatment QOL had the largest impact, followed by posttreatment QOL., Conclusion: These findings provide evidence that QOL is associated with mortality risk in patients with cancer at any timepoint. These results indicate the importance of evaluating the QOL and supportive interventions to improve QOL in any phase., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Silole- and phosphole-containing polycyclic aromatic compounds have attracted significant attention in the field of organic functional materials. The structure of the aromatic units has great impact on the photophysical properties of the resulting silole- and phosphole-containing polycyclic aromatic compounds. Here, dibenzo-fused naphtho[2,3- b :6,7- b ']disilole (NDS) and naphtho[2,3- b :6,7- b ']diphosphole (NDP), where a naphthalene unit is arranged between two silole and phosphole units, respectively, were designed and synthesized. The solid-state structures of them were confirmed by X-ray crystallographic analysis. The photophysical properties were evaluated by UV-vis absorption and photoluminescence spectroscopies and compared with those of their related compounds, such as dibenzo-fused silolo[3,2- b ]silole and benzo[1,2- b :4,5- b ']disilole, ever reported. The longest wavelength absorption band of a series of silole-fused compounds was found to be red-shifted in the order benzo[1,2- b :4,5- b ']disilole < NDS < silolo[3,2- b ]silole derivatives. For a series of phosphole-fused compounds, π-extension from phospholo[3,2- b ]phosphole to NDP derivatives induces the lower absorption coefficient of the longest wavelength absorption band and the red-shift of the second longest wavelength absorption band. Both NDS and NDP exhibit much lower fluorescence quantum yields than their related compounds.

Objectives: Japanese children have been shown to exhibit decreased masticatory function; however, limited evidence is available regarding the efficacy of certain food items in improving this issue. Therefore, this study examined the effects of chewing hard gummy candy on the masticatory function of Japanese children aged 6-12 years., Methods: The study included 26 participants (10 boys and 16 girls; mean age ± standard error = 9.3 ± 0.3 years) who were asked to chew hard gummy candy twice daily for 4 weeks at home. The lip-closing force, occlusal force, and masticatory performance of the participants were recorded before commencement (T1), 4 weeks after commencement (T2), and 4 weeks after completion (T3) of the training. Statistical analyses were performed using the Wilcoxon rank-sum test or the Wilcoxon signed-rank test with Bonferroni correction., Results: No significant differences in masticatory function by gender and age groups (defined based on mean age at T1) were observed at T1. The lip-closing and right occlusal forces increased significantly after 4 weeks of exercise, and the effects persisted for another 4 weeks after completion. The masticatory performance also improved after training, although these effects did not persist and deteriorated substantially 4 weeks after completion of the training., Conclusions: Habitual mastication training using hard gummy candy markedly enhances masticatory function (e.g., lip-closing force, occlusal force, and masticatory performance) in Japanese children., Competing Interests: Declaration of competing interest All authors are required to disclose any COI within the period of 12 months prior to the submission of any manuscript in the subject matter of which any company, entity, or organization has an interest.The corresponding author is required to complete this form with information from all the authors listed in the manuscript., (Copyright © 2024. Published by Elsevier B.V.)

Background: Tooth loss significantly impacts oral function and overall health deterioration. Dental caries and periodontal disease are major contributors to tooth loss, emphasizing the critical need to prevent these conditions. Genetic studies have played a crucial role in deepening our understanding of the underlying mechanisms of these diseases. While large-scale genome-wide association studies (GWAS) on dental caries and periodontal disease have been conducted extensively, research focusing on Asian populations remains limited. Given substantial genetic and lifestyle variations across ethnicities, conducting studies across diverse populations is imperative. This study aimed to uncover new insights into the genetic mechanisms of these diseases, contributing to broader knowledge and potential targeted interventions., Methods: We conducted a GWAS using genome data from 45,525 Japanese individuals, assessing their self-reported history of dental caries and periodontal disease. Additionally, we performed a meta-analysis by integrating our results with those from a previous large-scale GWAS predominantly involving European populations., Results: While no new loci associated with periodontal disease were identified, we discovered two novel loci associated with dental caries. The lead variants of these loci were intron variant rs10974056 in GLIS3 and intron variant rs4801882 in SIGLEC5., Conclusion: Our study findings are anticipated to advance understanding of the underlying mechanisms of dental caries and periodontal disease. Thes insights may inform better management strategies for patients affected by these conditions., (© 2024. The Author(s).)

We herein report a novel de novo KCNH5 variant in a patient with refractory epileptic encephalopathy. The patient exhibited seizures at 1 year and 7 months old, which gradually worsened, leading to a bedridden status. Brain magnetic resonance imaging (MRI) showed cerebral atrophy and cerebellar hypoplasia. A trio whole-exome sequence analysis identified a de novo heterozygous c.640A>C, p.Lys214Gln variant in KCNH5 that was predicted to be deleterious. Recent studies have linked KCNH5 to various epileptic encephalopathies, with many patients showing normal MRI findings. The present case expands the clinical spectrum of the disease, as it is characterized by severe neurological prognosis, cerebral atrophy, and cerebellar hypoplasia.

Objective: This study aimed to identify risk factors for postoperative proximal junctional kyphosis (PJK) with vertebral fracture in adult spinal deformity (ASD) patients. We performed a survival analysis considering various factors, including osteoporosis., Methods: This single-center retrospective study included 101 ASD patients (mean age: 67.2 years, mean follow-up: 8.1 years). We included patients aged ≥50 years with abnormal radiographic variables undergoing corrective long spinal fusion. The main outcome measure was PJK with vertebral fracture, analyzed based on patient data, radiographic measurements, sagittal parameters, bone mineral density, and osteoporosis medication., Results: PJK occurred in 37.6% of patients, with vertebral fracture type 2 accounting for 65% of these cases. Kaplan-Meier analysis indicated a median PJK-free survival time of 60.7 months. Existing vertebral fracture (grade 1 or higher or grade 2 or higher) was a significant risk factor for PJK with vertebral fracture, with hazard ratios of 4.58 and 5.61, respectively. The onset time of PJK with vertebral fracture was 1.5 months postoperatively, with 44% of these cases occurring within 1 month and 64% within 2 months., Conclusions: PJK with vertebral fracture affected 25% of ASD patients, emphasizing the importance of osteoporosis evaluation. Existing vertebral fracture emerged as a significant independent risk factor, surpassing bone mineral density. This study provides valuable insights for spine surgeons, highlighting the need to provide osteoporosis treatment and emphasize potential postoperative complications during discussions with patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We report a case of retroperitoneal abscess mimicking a malignant retroperitoneal tumor. A 77-yearold woman was referred to our hospital because of retroperitoneal tumor without any symptoms. The tumor was located just behind the inferior vena cava, and the tumor size was about 38 mm. The tumor showed no abnormal findings in positron emission tomography (PET) and 123I-MIBG scintigraphy. We considered the tumor as benign tumor or retroperitoneal cyst. Follow-up computed tomography (CT) 6 months after the first visit to our department showed no change in the tumor. However, 3months later, she presented with fever, general fatigue and back pain. CT scan at that time showed that the tumor had enlarged to about 70 mm, and the tumor seemed to have invaded into the inferior vena cava. Thrombus into the inferior vena cava was also found. These findings were suggestive of malignancy, so we decided to remove the tumor. During the operation, the tumor was removed together with the inferior vena cava and right kidney because of severe adhesion. The pathological diagnosis was retroperitoneal abscess. Retroperitoneal abscess is caused by various reasons including diabetes mellitus, steroid use, inflammatory disease of gastrointestinal tract and retroperitoneal organs. Although the etiology was unknown in the present case, acute infection of the preexisting retroperitoneal cyst was a possible cause.

Sarcopenia is prevalent among 11-25% of adult cancer survivors, depending on the cancer type, although the available data on post-treatment survivors in Japan are limited. If cancer patients develop cachexia, they may experience sustained weight loss as a result, ultimately leading to sarcopenia. Conversely, some patients experience post-treatment weight gain, resulting in sarcopenic obesity. Both sarcopenia and obesity elevate the risk of cardiovascular diseases and mortality; therefore, the importance of sarcopenia prevention and management is undeniable. The Guidelines for Exercise for Cancer Survivors recommend continued physical activity. Recent studies have reported the effectiveness of multimodal interventions, combining pharmacological, nutritional, and exercise approaches, necessitating multidisciplinary care for post-treatment sarcopenia. Innovative health interventions using mobile devices have also gained attention. However, studies on sarcopenia in post-treatment cancer survivors, especially those regarding exercise interventions, remain scarce in Japan, primarily due to limited insurance coverage for such post-treatment interventions and workforce challenges. It is clear that some cancer survivors have sarcopenia, which can lead to worse survival and secondary illness. While the benefits of exercise are clear, a comprehensive approach to sarcopenia is a further challenge for the future.

Background: Although posterior decompression with fusion (PDF) are effective for treating thoracic myelopathy, surgical treatment has a high risk of various complications. There is currently no information available on the perioperative complications in thoracic ossification of the longitudinal ligament (T-OPLL) and thoracic ossification of the ligamentum flavum (T-OLF). We evaluate the perioperative complication rate and cost between T-OPLL and T-OLF for patients underwent PDF., Methods: Patients undergoing PDF for T-OPLL and T-OLF from 2012 to 2018 were detected in Japanese nationwide inpatient database. One-to-one propensity score matching between T-OPLL and T-OLF was performed based on patient characteristics and preoperative comorbidities. We examined systemic and local complication rate, reoperation rate, length of hospital stays, costs, discharge destination, and mortality after matching., Results: In a total of 2,660 patients, 828 pairs of T-OPLL and T-OLF patients were included after matching. The incidence of systemic complications did not differ significantly between the T-OPLL and OLF groups. However, local complications were more frequently occurred in T-OPLL than in T-OLF groups (11.4% vs. 7.7% P = 0.012). Transfusion rates was also significantly higher in the T-OPLL group (14.1% vs. 9.4%, P = 0.003). T-OPLL group had longer hospital stay (42.2 days vs. 36.2 days, P = 0.004) and higher medical costs (USD 32,805 vs. USD 25,134, P < 0.001). In both T-OPLL and T-OLF, the occurrence of perioperative complications led to longer hospital stay and higher medical costs. While fewer patients in T-OPLL were discharged home (51.6% vs. 65.1%, P < 0.001), patients were transferred to other hospitals more frequently (47.5% vs. 33.5%, P = 0.001)., Conclusion: This research identified the perioperative complications of T-OPLL and T-OLF in PDF using a large national database, which revealed that the incidence of local complications was higher in the T-OPLL patients. Perioperative complications resulted in longer hospital stays and higher medical costs., (© 2024. The Author(s).)

Background: Both cancer diagnosis/treatment modality and surgical technique for the spine have been developed recently. Nationwide trends in the surgical treatment for metastatic spinal tumors have not been reported in the last decades. This study aimed to examine recent trends in the surgical treatment for spinal metastasis and in-hospital patient outcomes using nationwide administrative hospital discharge data., Methods: The Diagnosis Procedure Combination database from 2012 to 2020 was used to extract data from patients who underwent surgical procedures for spinal metastasis with the number of non-metastatic spinal surgery at the institutions that have performed metastatic spine surgeries at least one case in the same year. Trends in the surgical treatment for spinal metastasis, patients' demographics, and in-hospital mortality/outcomes were investigated., Results: This study analyzed 10,321 eligible patients with spinal metastasis. The surgical treatment for spinal metastasis increased 1.68 times from 2012 to 2020, especially in fusion surgery, whereas the proportion of metastatic spinal surgery retained with a slight increase in the 2%s. Distributions of the primary site did not change, whereas age was getting older. In-hospital mortality and length of stay decreased over time (9.9-6.8%, p < 0.001; 37-30 days, p < 0.001). Postoperative complication and unfavorable ambulatory retained stable and slightly decreased, respectively., Conclusion: During the last decade, surgical treatment for spinal metastasis, especially fusion surgery, has increased in Japan. In-hospital mortality and length of stay decreased. Recent advances in cancer treatment and surgical techniques might influence this trend., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Purpose: To identify risk factors, including FRAX (a tool for assessing osteoporosis) scores, for development of proximal junctional kyphosis (PJK), defined as Type 2 in the Yagi-Boachie classification (bone failure), with vertebral fracture (VF) after surgery for symptomatic adult spinal deformity., Methods: This was a retrospective, single institution study of 127 adults who had undergone corrective long spinal fusion of six or more spinal segments for spinal deformity and been followed up for at least 2 years. The main outcome was postoperative development of PJK with VF. Possible predictors of this outcome studied included age at surgery, BMI, selected radiographic measurements, bone mineral density, and 10-year probability of major osteoporotic fracture (MOF) as determined by FRAX. We also analyzed use of medications for osteoporosis. Associations between the selected variables and PJK with VF were assessed by the Mann-Whitney, Fishers exact, and Wilcoxon signed-rank tests, and Kaplan-Meier analysis, as indicated., Results: Forty patients (31.5%) developed PJK with VF postoperatively,73% of them within 6 months of surgery. Statistical analysis of the selected variables found that only a preoperative estimate by FRAX of a > 15% risk of MOF within 10 years, pelvic tilt > 30° at first standing postoperatively and lower instrumented level (fusion terminating at the pelvis) were significantly associated with development of PJK with VF., Conclusion: Preoperative assessment of severity of osteoporosis using FRAX provides an accurate estimate of risk of postoperative PJK with VF after surgery for adult spinal deformity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This systematic review and meta-analysis investigated the impact of quality of life (QoL) on mortality risk in patients with esophageal cancer. A literature search was conducted using the CINAHL, PubMed/MEDLINE, and Scopus databases for articles published from inception to December 2022. Observational studies that examined the association between QoL and mortality risk in patients with esophageal cancer were included. Subgroup analyses were performed for time points of QoL assessment and for types of treatment. Seven studies were included in the final analysis. Overall, global QoL was significantly associated with mortality risk (hazard ratio 1.02, 95% confidence interval 1.01-1.04; p < 0.00004). Among the QoL subscales of QoL, physical, emotional, role, cognitive, and social QoL were significantly associated with mortality risk. A subgroup analysis by timepoints of QoL assessment demonstrated that pre- and posttreatment global and physical, pretreatment role, and posttreatment cognitive QoL were significantly associated with mortality risk. Moreover, another subgroup analysis by types of treatment demonstrated that the role QoL in patients with surgery, and the global, physical, role, and social QoL in those with other treatments were significantly associated with mortality risk. These findings indicate that the assessment of QoL in patients with esophageal cancer before and after treatment not only provides information on patients' condition at the time of treatment but may also serve as an outcome for predicting life expectancy. Therefore, it is important to conduct regular QoL assessments and take a proactive approach to improve QoL based on the results of these assessments., (© 2024. The Author(s), under exclusive licence to The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: Patients with breast cancer present with various problems that have an adverse effect on the quality of life (QOL). However, the association between the QOL and mortality among patients with breast cancer remains controversial. Therefore, this systematic review and meta-analysis aimed to determine whether QOL impacts prognosis in patients with breast cancer., Methods: The databases of CINAHL, Scopus, and PubMed databases were searched to retrieve observational studies that assessed the QOL and mortality risk in patients with breast cancer published before December 2022., Results: Among the 119,061 articles retrieved, six observational studies were included in the meta-analysis. Physical QOL (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 1.01-1.07, p = 0.003), emotional QOL (HR: 1.01, 95% CI: 1.00-1.03, p = 0.05), and role QOL (HR: 1.01, 95% CI: 1.00-1.01, p = 0.007) showed significant associations with mortality risk. In contrast, global QOL, cognitive QOL, and social QOL showed no associations with mortality risk. Subgroup analysis performed according to treatment time points revealed that the post-treatment physical QOL was associated with mortality risk., Conclusions: Physical QOL, emotional QOL, and role QOL are associated with mortality risk in patients with breast cancer. Furthermore, post-treatment physical QOL showed a more significant association with prolonged survival than pre-treatment physical QOL., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Background: There are cases of superficial siderosis (SS) with spinal ventral fluid-filled collection in the spinal canal. In our previous study, the balanced steady-state free precession sequence magnetic resonance imaging is useful in identifying the location of dural defects. However, because of its narrow scan area and long scan time, it cannot easily detect the defect location in some patients with small dural defect. In this study, we applied 4-dimensional (4D) dynamic computed tomography (CT) imaging, including time-axis imaging, to myelography using the latest CT imaging equipment, which can perform short-time continuous imaging, to identify the dural defect site., Methods: Twenty SS patients with ventral fluid-filled collection in the spinal canal (9 males, 11 females; mean age 61.6 years) underwent 4D dynamic CT myelography. A 192-row helical CT (SOMATOM Force, SIEMENS, Munich, Germany) with high-speed scanning capability was used to obtain 9-11 scans per minute at low dose while passing contrast medium into the subarachnoid space. Then, contrast leakage sites were identified., Results: The contrast leakage sites could be identified in all 20 cases: C7/Th1, 2 cases; Th1/2, 5 cases; Th2/3, 9 cases; Th3/4, 1 case; Th5/6, 1 case; Th7/8, 1 case; and Th8/9, 1 case. Eighteen cases underwent surgical operation, and actual dural defects were confirmed at the contrast leakage sites. The mean ± standard deviation of leakage time from contrast agent injection was 19.0 ± 9.2 s., Conclusions: The 4D dynamic CT myelography can be used to reliably identify the location of spinal fluid leakage. In SS cases, dural defects could be visualized in an average of 19 seconds., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objective: Rehabilitation therapy plays an important role in treating physical and functional impairments observed in individuals undergoing hematopoietic stem cell transplants (HSCT). This study assessed the rehabilitation practices implemented in the HSCT population internationally., Materials and Methods: A 48-question online survey comprising questions soliciting information regarding patient characteristics, therapy details (timing, indication, and administering providers), outcome measures, and precautions were developed by an international group of cancer rehabilitation physicians. As reported by European registries, surveys were administered to personnel providing care to patients receiving HSCT at cancer centers, which comprised the top 10% of HSCT volume. In addition, emails were sent to National Medical Societies and registries in the Latin America, Asia, and Pacific regions., Results: Forty-three institutions from 18 countries responded to the survey. Half of the centers provided referrals for rehabilitation therapy at the time of admission. Referrals were provided for functional decline (84.5%), risk of falls (53.3%), and discharge planning (42.2%). Rehabilitation therapies were administered by physical therapists (93.0%), occupational therapists (34.9%), therapy aides (14.0%), and speech-language pathologists (11.6%). Approximately 95% of the surveyed centers used objective functional measures such as sit-to-stand (46.5%), grip strength (46.5%), and 6-min walk/gait speed (both 34.9%). The blood counts were monitored to determine the appropriateness of the therapy modalities., Conclusion: Rehabilitation practices varied internationally; however, most centers provided skilled therapy during hospitalization for HSCT, utilized objective and patient-reported outcomes, and monitored blood counts to determine the safety of administering therapy., (Copyright © 2024 Hematology/Oncology and Stem Cell Therapy.)

algebraic concepts such as category are considered cornerstones on which logical consistency relies in any sophisticated study of natural phenomena. However, to the best of our knowledge, in molecular/genetic biology, their application is still severely limited because they capture neither the dynamics nor provide a visual form. The Petri net (PN) has often been used to illustrate visually parallel, asynchronous dynamic events in small data systems. A prototypal hybrid model combining both category theory and extended PNs may instead be indispensable for that purpose. This hybrid model incorporates 1) token-like elements of a group, 2) object-like places of a category, 3) square poles (rather than pentagon poles) that enable unique identifications of single-strand DNA sequences from the shape of its polygonal line, 4) creation/annihilation morphisms that generate/erase tokens, 5) Cartesian products 'Z5×Z2×…' that enable conversions between DNA and RNA sequences, 6) somatic recombinations (VDJ recombinations) for antibodies displayed concretely in category-theoretic form, 7) 'identity protein Δ' translated from a triplet of identity bases 'EEE' as an advanced concept from our previous display of the canonical central dogma, 8) illustrations of an incidence-matrix-like matrix A that includes operators as coordinates, and 9) basic topics concerning the canonical central dogma being displayed concretely using concepts of conventional category theory such as 'adjoint', 'adjoint functor', 'natural transformation', 'Yoneda's lemma' and 'Kan extension'. These ideas provide more advanced tools that expand our previous model concerning nucleic-acid-base sequences. Despite the nascent nature of our methodology, our hybrid model has potential in a variety of applications, illustrated using molecular/genetic sequences, in particular providing a simple dynamic/visual representation. With further improvements, this approach may prove effective in reducing the need for large data-storing systems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sawamura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Low physical function can be effectively improved via intradialytic exercise. However, the association between the effects of intradialytic exercise on physical function and malnutrition severity has not been studied extensively. This study aimed to investigate the impact of nutritional status severity on physical function in patients undergoing hemodialysis with low physical function to whom intradialytic exercise was prescribed., Methods: The participants were patients with decreased mobility [walking speed < 1.0 m/s and/or Short Physical Performance Battery (SPPB) < 12] who had been undergoing hemodialysis thrice a week for 6 months and performing intradialytic exercise program. Patients were divided into groups based on the Geriatric Nutritional Risk Index (GNRI) [Non-malnutrition group (GNRI > 98), Gentle/slim malnutrition group (GNRI ≤ 98, GNRI ≥ 92), Mild malnutrition group (GNRI < 92, GNRI ≥ 82), Severe malnutrition group (GNRI < 82)]. The primary outcomes were Grip strength, isometric knee extension strength (IKES), SPPB, and 10-m walking speed measured at baseline and at 6 months. Statistical analyses were performed using a linear mixed-effects model with the intention-to-treat analysis, including within-group analysis and between-group comparison., Results: A total of 805 participants were included in the study. Within-group comparisons showed significantly improved IKES, 10-m walking speed, and SPPB improved, except in the Severe malnutrition group. Grip strength significantly improved in the Gentle/slim and mild malnutrition groups. Between-group comparison with controls showed that the improvement in Grip strength was significantly bigger in the Gentle/slim malnutrition group [0.98 (0.15 to 1.82) kg] than in the non-malnutrition group. However, IKES in the Severe malnutrition group [- 5.14 (- 9.18 to - 1.10) %] less significantly improve than that in the non-malnutrition group. No significant differences were found in the other indices., Conclusion: In patients with severe malnutrition, the changes in IKES scores resulting from Intradialytic exercise were significantly smaller than those observed in non-malnourished patients. Therefore, it is necessary to initiate suitable nutritional and exercise therapy based on the severity of malnutrition., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Dominance heritability in complex traits has received increasing recognition. However, most polygenic score (PGS) approaches do not incorporate non-additive effects. Here, we present GenoBoost, a flexible PGS modeling framework capable of considering both additive and non-additive effects, specifically focusing on genetic dominance. Building on statistical boosting theory, we derive provably optimal GenoBoost scores and provide its efficient implementation for analyzing large-scale cohorts. We benchmark it against seven commonly used PGS methods and demonstrate its competitive predictive performance. GenoBoost is ranked the best for four traits and second-best for three traits among twelve tested disease outcomes in UK Biobank. We reveal that GenoBoost improves prediction for autoimmune diseases by incorporating non-additive effects localized in the MHC locus and, more broadly, works best in less polygenic traits. We further demonstrate that GenoBoost can infer the mode of genetic inheritance without requiring prior knowledge. For example, GenoBoost finds non-zero genetic dominance effects for 602 of 900 selected genetic variants, resulting in 2.5% improvements in predicting psoriasis cases. Lastly, we show that GenoBoost can prioritize genetic loci with genetic dominance not previously reported in the GWAS catalog. Our results highlight the increased accuracy and biological insights from incorporating non-additive effects in PGS models., (© 2024. The Author(s).)

Amyand's hernia is a rare type of inguinal hernia characterized by the presence of the vermiform appendix within the hernia sac. It was named after Claudius Amyand who performed the world's first successful appendectomy on an 11-year-old boy with a right inguinal hernia in 1735 and discovered a herniated appendix during surgery. This condition warrants urgent surgical treatment, with the type of surgical intervention depending on the appendix's condition. However, the nonspecific clinical presentation often complicates the preoperative diagnosis, emphasizing the critical role of imaging in surgical planning. Herein, we present the case of a 74-year-old male who presented with fever, inguinal swelling, and discomfort. Clinical suspicion of inguinal and scrotal inflammation prompted us to perform a prompt CT scan. This radiological evaluation led to a preoperative diagnosis of a Type 3 Amyand's hernia. This case highlights the significance of CT scans in the accurate and timely diagnosis of Amyand's hernia. Distinguishing between various types of Amyand's hernia is pivotal as it profoundly influences surgical decision-making and postoperative outcomes. By sharing this case, we contribute to current knowledge about Amyand's hernia, increase clinical awareness of the condition, and emphasize the crucial role of imaging in its management., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Acute myocardial infarction (AMI) is associated with a decline in renal function. This study aimed to investigate the impact of engaging in moderate to vigorous intensity physical activity (MVPA) for more than 30 min per day on changes in renal function during the first 3 months after AMI onset. A prospective, observational study was conducted, enrolling 87 patients (75 men; average age, 65.2 ± 12.5 years) who had experienced AMI. The cystatin C-based estimated glomerular filtration rate (eGFRcys) was collected at and 3 months after discharge. Daily MVPA was measured using triaxial accelerometers at a threshold of 3.0 Metabolic equivalent of the task for 3 months. Generalized estimating equations (GEE) were applied to evaluate the longitudinal association between the number of days per week of MVPA for 30 min or more and within-patient changes in eGFRcys. The patients were categorized into three groups based on their MVPA engagement days: 0 days (n = 20), 1-2 days (n = 14), and 3-7 days (n = 53) groups. After adjusting for potential confounding variables, GEE analysis revealed that the eGFRcys slope over 3 months was significantly higher in the 3-7 days group than in 0 days group (B = 2.9, (95% confidence interval: 1.5-4.2), p < 0.001). Similar results were obtained when MVPA time thresholds were set to 40 and 60 min. These findings suggest a significant positive effect of engaging in MVPA for 30 min or more for 3-7 days per week in the improvement of renal function after AMI onset., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Introduction: Patients with chronic kidney disease (CKD) are susceptible to frailty because of a range of nutrition-related factors. While protein restriction is commonly advised to preserve kidney function in patients with CKD, insufficient protein intake could potentially exacerbate frailty risk. This study aimed to elucidate the relationship between frailty and protein intake in patients with CKD., Methods: This cross-sectional study enrolled patients with CKD stage 3-5. Frailty and prefrailty were assessed using the Japanese version of the Cardiovascular Health Study (J-CHS) criteria. To estimate dietary protein intake, Maroni's formula based on 24-h urine collection was used. The potential association between frailty/pre-frailty and protein intake was investigated using a logistic regression analysis., Results: Ninety-seven individuals with CKD were included in the study, with a median age of 73.0 years (interquartile range: 67.0, 82.0). Among them, 34 were women (35.1%), and the estimated glomerular filtration rate (eGFR) was 36.3 mL/min/1.73 m 2 (interquartile range: 26.9, 44.1). Frailty and pre-frailty were identified in 13.4% and 55.7% of participants, respectively. Comparing the groups, protein intake in the frailty/pre-frailty group (0.83 g/kgBW/day [0.72, 0.93]) was lower than that in the robust group (0.89 g/kgBW/day [0.84, 1.19], p = 0.002). Upon logistic regression analysis, protein intake exhibited an independent association with frailty/pre-frailty (odds ratio: 0.72, 95% confidence interval: 0.59-0.89, p = 0.003)., Conclusion: Reduced protein intake in patients with CKD is associated with frailty and pre-frailty. It is advisable to ensure that patients with CKD who are at risk of frailty consume an adequate amount of protein., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Study Design: Retrospective cohort study., Objectives: To compare the frequency of complications and outcomes between patients with ossification of the posterior longitudinal ligament (OPLL) of the cervical spine and those with cervical spondylotic myelopathy (CSM) who underwent anterior surgery., Summary of Background Data: Anterior cervical spine surgery for OPLL is an effective surgical procedure; however, it is complex and technically demanding compared with the procedure for CSM. Few reports have compared postoperative complications and clinical outcomes after anterior surgeries between the 2 pathologies., Methods: Among 1434 patients who underwent anterior cervical spine surgery at 3 spine centers within the same spine research group from January 2011 to March 2021, 333 patients with OPLL and 488 patients with CSM were retrospectively evaluated. Demographics, postoperative complications, and outcomes were reviewed by analyzing medical records. In-hospital and postdischarge postoperative complications were investigated. Postoperative outcomes were evaluated 1 year after the surgery using the Japanese Orthopaedic Association score., Results: Patients with OPLL had more comorbid diabetes mellitus preoperatively than patients with CSM ( P <0.001). Anterior cervical corpectomies were more often performed in patients with OPLL than in those with CSM (73.3% and 14.5%). In-hospital complications, such as reoperation, cerebrospinal fluid leak, C5 palsy, graft complications, hoarseness, and upper airway complications, occurred significantly more often in patients with OPLL. Complications after discharge, such as complications of the graft bone/cage and hoarseness, were significantly more common in patients with OPLL. The recovery rate of the Japanese Orthopaedic Association score 1 year postoperatively was similar between patients with OPLL and those with CSM., Conclusion: The present study demonstrated that complications, both in-hospital and after discharge following anterior spine surgery, occurred more frequently in patients with OPLL than in those with CSM., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Although many studies have explored the correlation between quality of life and survival, none have reported this relationship for specific cancers assessed at distinct time points. This meta-analysis aimed to investigate the impact of pretreatment Global Quality of Life (QOL) and functioning QOL, including physical, social, role, emotional, and cognitive QOLs, on mortality risk in patients with lung cancer., Methods: A literature search was conducted across the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and PubMed databases for articles published between their inception and December 2022. Subsequently, 11 studies were selected based on predefined eligibility criteria to investigate the relationship between pretreatment QOLs and mortality risk in patients with lung cancer., Results: Pretreatment global, physical, social, role, and emotional QOLs were significantly associated with mortality risk as follows: Global QOL (hazard ratio [HR] = 1.08 95% confidence interval [CI] = 1.03-1.13); Physical QOL (HR = 1.04 95% CI = 1.02-1.05); Social QOL (HR = 1.02 95% CI = 1.01-1.03; Role QOL (HR = 1.01 95% CI = 1.01-1.02); Emotional QOL (HR = 1.01 95% CI = 1.00-1.03)., Conclusions: These findings underscore the importance of early QOL assessment after diagnosis as well as early provision of physical, social, and psychological support accommodating each patient's demands., Trial Registration: The International Prospective Register of Systematic Reviews registration number CRD42023398206, Registered on February 20, 2023., (© 2024. The Author(s).)

Pesticides are widely used to improve crop productivity by eliminating weeds and pests. Conventional pesticide development involves synthesizing compounds, testing their activities, and studying their effects on the ecosystem. However, as pesticide discovery has an extremely low success rate, many compounds must be synthesized and tested. To overcome the high human, financial, and time costs of this process, machine learning is attracting increasing attention. In this study, we used machine learning for the molecular design of novel seed compounds for herbicides and insecticides. Classification models were constructed by using compounds that had been tested as herbicides and insecticides, and an inverse analysis of the constructed models was conducted. In the molecular design of herbicides, we proposed 186 new samples as herbicides using ensemble learning and a method for expressing explanatory variables that consider the relationships among eight weed species. For the molecular design of insecticides, we used undersampling and ensemble learning for the analysis of unbalanced data. Based on approximately 340,000 compounds, 12 potential insecticides were proposed, of which 2 exhibited actual activity when tested. These results demonstrate the potential of the developed machine-learning method for rapidly identifying novel herbicides and insecticides., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Purpose: Exercise therapy is a crucial intervention for improving health-related quality of life (HRQOL) in patients undergoing haemodialysis. However, factors that improve HRQOL by improving physical function and dialysis-related symptoms remain unknown. This study aimed to examine the physical function parameters and dialysis-related symptoms that improve HRQOL following intradialytic exercise., Methods: This multicentre cohort study included 596 patients who participated in an intradialytic exercise program three times per week for a period of 6 months, which comprised of stretching and resistance training. EuroQol 5 dimensions 5-level (EQ5D-5L), grip strength, isometric knee extension strength, 10-m walking speed, Short Physical Performance Battery (SPPB), and improvement in dialysis-related symptoms were measured at the baseline and post-intervention. A linear mixed model was used to analyse the effects of improved physical function and dialysis-related symptoms on improvements in EQ5D-5L., Results: As a physical function index affecting ΔEQ5D-5L, only SPPB showed a significant increase in ΔEQ5D-5L compared with the non-improved group [difference in ΔEQ5D-5L, 0.05 (0.004 to 0.092) point; p < 0.05]). In addition, dialysis-related symptoms with Improved physical conditions [difference in ΔEQ5D-5L, 0.07 (0.02 to 0.13) point] and an Extended walking distance [difference in ΔEQ5D-5L was 0.07 (0.01 to 0.12) point] significantly influenced ΔEQ5D-5L (p < 0.05, both)., Conclusions: The improvements observed in the SPPB scores and self-percieved physical fitness and ambulation range, attributable to intradialytic exercise, may potentially improve HRQOL., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: Amyotrophic lateral sclerosis (ALS) is a devastating, incurable neurodegenerative disease. A subset of ALS patients manifests with early-onset and complex clinical phenotypes. We aimed to elucidate the genetic basis of these cases to enhance our understanding of disease etiology and facilitate the development of targeted therapies., Methods: Our research commenced with an in-depth genetic and biochemical investigation of two specific families, each with a member diagnosed with early-onset ALS (onset age of <40 years). This involved whole-exome sequencing, trio analysis, protein structure analysis, and sphingolipid measurements. Subsequently, we expanded our analysis to 62 probands with early-onset ALS and further included 440 patients with adult-onset ALS and 1163 healthy controls to assess the prevalence of identified genetic variants., Results: We identified heterozygous variants in the serine palmitoyltransferase long chain base subunit 2 (SPTLC2) gene in patients with early-onset ALS. These variants, located in a region closely adjacent to ORMDL3, bear similarities to SPTLC1 variants previously implicated in early-onset ALS. Patients with ALS carrying these SPTLC2 variants displayed elevated plasma ceramide levels, indicative of increased serine palmitoyltransferase (SPT) activity leading to sphingolipid overproduction., Interpretation: Our study revealed novel SPTLC2 variants in patients with early-onset ALS exhibiting frontotemporal dementia. The combination of genetic evidence and the observed elevation in plasma ceramide levels establishes a crucial link between dysregulated sphingolipid metabolism and ALS pathogenesis. These findings expand our understanding of ALS's genetic diversity and highlight the distinct roles of gene defects within SPT subunits in its development., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Oral function evaluation in older adults with dementia is important for determining appropriate and practical dietary support plans; however, it can be challenging due to their difficulties in comprehending instructions and cooperating during assessments. The feasibility of oral function evaluation has not been well studied. This cross-sectional study aimed to determine the feasibility of oral function evaluation in older adults with Alzheimer's disease (AD) according to Functional Assessment Staging of Alzheimer's Disease (FAST) stages. In total, 428 older adults with AD (45 men and 383 women; mean age: 87.2 ± 6.2 years) were included. Multilevel logistic regression models were used to examine the prevalence of participants who were unable to perform oral function evaluations, including oral diadochokinesis (ODK), repeated saliva swallow test (RSST), and modified water swallow test (MWST). In comparison to the reference category (combined FAST stage 1-3), FAST stage 7 was associated with the infeasibility of ODK (adjusted odds ratio, 95% confidence interval = 26.7, 4.2-168.6), RSST (5.9, 2.2-16.1), and MWST (8.7, 1.6-48.5, respectively). Oral function evaluation is difficult in older adults with severe AD. Simpler and more practical swallowing function assessments and indicators that can be routinely observed are required.

Myeloid cells, which originate from hematopoietic stem/progenitor cells (HSPCs), play a crucial role in mitigating infections. This study aimed to explore the impact of mesenchymal stem/stromal cells (MSCs) on the differentiation of HSPCs and progenitors through the C-C motif chemokine CCL2/CCR2 signaling pathway. Murine MSCs, identified as PDGFRα + Sca-1 + cells (PαS cells), were found to secrete CCL2, particularly in response to lipopolysaccharide stimulation. MSC-secreted CCL2 promoted the differentiation of granulocyte/macrophage progenitors into the myeloid lineage. MSC-derived CCL2 plays an important role in the early phase of myeloid cell differentiation in vivo. Single-cell RNA sequencing analysis confirmed that CCL2-mediated cell fate determination was also observed in human bone marrow cells. These findings provide valuable insights for investigating the in vivo effects of MSC transplantation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the efficacy and safety of mirabegron and vibegron in female OAB patients., Methods: We conducted a multicenter, prospective, randomized crossover study of female patients with OAB. The patients were assigned to Group MV (mirabegron for 8 weeks, followed by vibegron for 8 weeks) or group VM (vibegron for 8 weeks, followed by mirabegron for 8 weeks). The primary endpoint was the change in OABSS from baseline, and the secondary endpoint was the change in FVC parameters. After completion of the study, each patient was asked which drug was preferable., Results: A total of 83 patients were enrolled (40 and 43 in groups MV and VM, respectively). At 8th and 16th week, 33 and 29 in Group MV and 34 and 27 in Group VM continued to receive the treatment. The change in PVR was not significantly different between treatment with mirabegron and vibegron. The changes in OABSS, nighttime frequency, mean, and maximum voided volume were similar between mirabegron and vibegron. The mean change in the daytime frequency was greater in the vibegron than in the mirabegron. Of the 56 patients, 15 (27%) and 30 (53%) preferred mirabegron and vibegron, respectively. The remaining 11 patients (20%) showed no preference. The change in the urgency incontinence score during vibegron was better in patients who preferred vibegron to mirabegron., Conclusion: The efficacies of mirabegron and vibegron in female patients was similar. The patients' preference for vibegron could depend on the efficacy of vibegron for urgency incontinence., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We present three cases of bilateral metachronous testicular tumors. The patient in case 1 had a history of left orchiectomy for undescended testis at the age of 19. The pathological findings revealed germ cell neoplasia in situ. Twenty-four years later (age＝43), he was diagnosed with right testicular tumor with lymph node and lung metastasis (stage IIIc). Right orchiectomy was performed, and the pathological finding showed nonseminomatous germ cell tumor. He underwent chemotherapy, followed by lymph node dissection and lung metastasectomy. The patient in case 2 had a history of left orchiectomy for testicular tumor at the age of 41. The pathological finding of the left testis revealed seminoma (stage IA). Nineteen years later (age＝60), he was diagnosed with right testicular tumor and underwent right orchiectomy. Herein, the pathological finding showed seminoma (stage IA). The patient in case 3 had a history of right orchiectomy for testicular tumor at the age of 25. The pathological findings revealed seminoma (stage IS), and he underwent adjuvant radiation of the para-aortic field without subsequent recurrence. Fourteen years later (age＝39), he was diagnosed with left testicular tumor and underwent left orchiectomy. The pathological finding revealed seminoma (stage IB). The patient underwent adjuvant carboplatin monotherapy to prevent recurrence. Due to the long interval between the occurrence of bilateral metachronous testicular tumors (mean＝19 years ; three cases), long-term observation is necessary to detect the possible occurrence of contralateral testicular tumors. Contralateral testicular biopsy might be considered at the time of orchiectomy for unilateral testicular tumor if associated with testicular atrophy and/or a history of undescended testis.

Abstract: Hematopoietic stem cell transplants play an important role in the treatment of cancer, particularly hematologic malignancies. These patients can encounter functional impairments unique to hematopoietic stem cell transplant, including deconditioning, cancer-related fatigue, steroid myopathy, graft versus host disease, and capillary leak syndrome. Medical fragility and increased risk of infection may make rehabilitation challenging on the acute care and postacute care settings. Patients admitted to acute inpatient rehabilitation experience a high rate of transfer to the primary acute service and high rate of mortality after transfer back. Physical medicine and rehabilitation physicians can use a number of strategies to mitigate these patients' risk of medical complications including evidence-based predictive models to assist with postacute rehabilitation triage, physiatry-led consult-based rehabilitation, and oncology hospitalist comanagement on inpatient rehabilitation., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)