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Variants in KIF1A are associated with hereditary spastic paraplegia (SPG30), which can manifest in both pure and complex forms. We describe a Japanese family with a novel KIF1A variant presenting with a complex form of SPG30. Patient 1, a 69-year-old woman, experienced progressive gait disturbance due to spastic paraparesis and cerebellar atrophy, and intellectual disability. Patient 2, the daughter of Patient 1, exhibited similar symptoms with more severe dysarthria. Patients 1 and 2 shared a heterozygous c.173 C > G (p.Ser58Trp) variant in the motor domain of KIF1A (NM_001244008.2), which is classified as likely pathogenic. This family highlights the role of autosomal dominant inheritance in a complex form of SPG30, expanding the understanding of its genetic basis and clinical presentation. [ABSTRACT FROM AUTHOR]

An exact parallel algorithm of dynamic mode decomposition (DMD) with Hankel matrices for large-scale flow data is proposed. The proposed algorithm enables the DMD and the Hankel DMD for large-scale data obtained by high-fidelity flow simulations, such as large-eddy simulations or direct numerical simulations using more than a billion grid points, on parallel computations without any approximations. The proposed algorithm completes the computations of the DMD by utilizing block matrices of X T X ∈ R k × k (where X ∈ R n × k is a large data matrix obtained by high-fidelity simulations, the number of snapshot data is n ≳ 10 9 , and the number of snapshots is k ≲ O (10 3) ) without any approximations: for example, the singular value decomposition of X is replaced by the eigenvalue decomposition of X T X . Then, the computation of X T X is parallelized by utilizing the domain decomposition often used in flow simulations, which reduces the memory consumption for each parallel process and wall-clock time in the DMD by a factor approximately equal to the number of parallel processes. The parallel computation with communication is performed only for X T X , allowing for high parallel efficiency under massively parallel computations. Furthermore, the proposed exact parallel algorithm is extended to the Hankel DMD without any additional parallel computations, realizing the Hankel DMD of large-scale data collected by over a billion grid points with comparable cost and memory to the DMD without Hankel matrices. Moreover, this study shows that the Hankel DMD, which has been employed to enrich information and augment rank, is advantageous for large-scale high-dimensional data collected by high-fidelity simulations in data reconstruction and predictions of future states (while prior studies have reported such advantages for low-dimensional data). Several numerical experiments using large-scale data, including laminar and turbulent flows around a cylinder and transonic buffeting flow around a full aircraft configuration, demonstrate that (i) the proposed exact parallel algorithm reproduces the existing non-parallelized Hankel DMD, (ii) the Hankel DMD for large-scale data consisting of over a billion grid points is feasible by using the proposed exact parallel algorithm with high parallel efficiency on more than 6 thousand CPU cores, and (iii) the Hankel DMD has advantages for high-dimensional data such as n ≳ 10 9 . [ABSTRACT FROM AUTHOR]

The Oyashio region east of northern Japan has experienced frequent marine heatwaves (MHWs) since 2010, and in the summer and fall of 2022, sea surface temperature hit a record high as of that year. This study examined the impact of the 2022/23 MHW on dissolved oxygen (DO) by analyzing observations from a vessel and biogeochemical Argo floats. It was found that warm saline water from the Kuroshio Current intruded at ~ 42°N in July. DO anomalies from the climatology above a depth of 200 m were negatively correlated with the temperature anomalies at the same depth, while the opposite was true for deeper depths. In the density coordinate, DO and temperature anomalies exhibited a strong negative correlation when the potential density (σθ) was less than ~ 27.0 kg m−3. Thus, it was demonstrated that subsurface DO anomalies could be statistically predicted from temperature and salinity fields using this relationship. Notably, DO anomalies could be divided into components related to isopycnal mixing and density-surface heaving. This decomposition revealed a dynamical process, whereby the intrusion of the Kuroshio water, which is lighter than the Oyashio water, pushed down the density surfaces, causing oxygenation. Meanwhile, isopycnal mixing tended to mitigate the increase of DO concentration since DO concentration was smaller in the south than in the north on an isopycnal surface of σθ < 27.0 kg m−3. This study clarified that, during the 2022/23 MHW, deoxygenation occurred near the surface owing the warming, whereas the DO concentration increased in the subsurface layer. [ABSTRACT FROM AUTHOR]

Purpose: Remote ischemic periconditioning (RIPC) has demonstrated cardioprotective effects and improved clinical outcomes as an adjunct to emergent percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI). However, whether RIPC affects the cardiac sympathetic nerve activity in patients with STEMI remains unclear. This study investigated the effects of RIPC on cardiac sympathetic nerve activity in patients with STEMI. Methods: We prospectively assigned patients with STEMI who underwent emergent PCI to receive RIPC or no procedure (control group) upon arrival at the cardiac catheterization laboratory. The primary endpoint was cardiac sympathetic nerve activity assessed through the washout rate (WR) in cardiac 123I-metaiodobenzylguanidine (123I-MIBG) imaging. Results: Patients in the RIPC (n = 62) and control (n = 60) groups had similar demographic and clinical characteristics at baseline. Multivariable linear regression models revealed that the culprit lesion of the left anterior descending artery and hemoglobin level were significantly and independently associated with WR at discharge. WRs of the groups differed insignificantly at discharge. However, the RIPC group (n = 49) showed significantly lower WR than the control group (n = 47) at 1 year after discharge (p = 0.027). In the single-photon emission computed tomography analysis at 1 year after discharge, the RIPC group demonstrated significantly higher late uptake (p = 0.021) and lower WR (p = 0.013) in the nonculprit lesion, with a non-significant decrease in WR for the culprit lesion. Conclusion: RIPC can suppress augmented cardiac sympathetic nerve activity in patients with STEMI, particularly in nonculprit lesions. [ABSTRACT FROM AUTHOR]

Reduced function or hypomorphic variants in recombination-activating genes (RAG) 1 or 2 result in a broad clinical phenotype including common variable immunodeficiency (CVID) and even adult-onset disease. Milder RAG variants are less characterized. Here we describe the longitudinal course of a milder combined RAG deficiency in 3 of 7 siblings sharing the same RAG2 mutations over a 50-year study. Whole-genome and repertoire sequencing, bacteriophage immunizations, and deep immunophenotyping were used to compare affected and unaffected family members. The clinical phenotype of three affected siblings with hypomorphic RAG deficiency ranged from combined immunodeficiency and early mortality to a late-onset CID with hyper-IgM phenotype. T cells were remarkably similar across affected siblings, yet CDR3 skewing and regulatory T cell defects were not observed. B cell analysis showed elevated unswitched CD27+ and CD21low cells as well as features of an autoreactive antibody repertoire and presence of secreted autoantibodies, yet no clinical autoimmunity was present. Most striking was an expanded polyclonal marginal zone-like B cell population (IgM+IgD+CD27+) utilizing the self-reactive unmutated VH4-34 receptor demonstrating that hypomorphic RAG deficiency can promote expansion of self-reactive B cells. This process, however, was not sufficient to trigger clinical autoimmunity. Utilizing multiple approaches, we functionally measured the specific RAG2 variant effects and assessed how selection and secondary triggers altered the BCR repertoire and immunophenotype overtime. Overall, we demonstrate a broad disease spectrum in siblings with identical hypomorphic RAG deficiency, highlighting that phenotypic divergence can result from expansion of IgM + memory B cells. [ABSTRACT FROM AUTHOR]

Background: Intermittent hypoxia, a consequence of sleep-disordered breathing (SDB), may contribute to an increased risk of cognitive decline. However, the association between SDB and cognition remains highly variable. Methods: Fifty-two community-dwelling healthy older adults (28 women) were recruited. All participants underwent neuropsychiatric evaluations, simultaneous ambulatory polysomnography (PSG), and near-infrared spectroscopy (NIRS) recordings. We quantified the average coherence between oxy-Hb and SpO2 signals during SDB events to determine whether it could predict cognitive outcomes in healthy older adults, where higher coherence indicates reduced protection against systemic hypoxia. Results: The mean (SD) coherence of oxy-Hb and SpO2 was 0.16 (0.07). Linear regression analysis showed a significant association between mean coherence and worse Stroop Color Word Test scores (t=-0.304, p =.004). In contrast, oxy-Hb reduction alone and conventional SDB parameters did not show a significant association with cognition. Conclusion: This is the first report to demonstrate an association between a novel parameter of brain-systemic oxygenation coherence in SDB and cognition in older adults. A higher coherence rate of cortical oxy-Hb and systemic SpO2 during SDB may reflect a loss of compensatory mechanisms against systemic hypoxia and could help stratify older adults with a higher risk for cognitive decline. [ABSTRACT FROM AUTHOR]

Aim: Oral health is important in patients with diabetes. While health literacy may promote preventive dental visits, the evidence is sparse among them. Additionally, because education is indicated as a determinant of health literacy, none clarified whether health literacy can mitigate educational inequalities in healthcare-seeking behaviors. We examined combined associations of education and health literacy with preventive dental visits in patients with diabetes. Methods: We used cross-sectional data from the Japan COVID-19 and Society Internet Survey (JACSIS) in 2020. We included 1441 patients reporting to have diabetes currently. Educational level was self-reported. Health literacy was measured using the validated scale. Preventive dental visits in the past 12 months were self-reported. We estimated multivariable-adjusted prevalence ratio (PR) for preventive dental visits. Results: 54% of the participants had preventive dental visits; 35% had high health literacy. Overall, high health literacy was significantly associated with preventive dental visits. Being more educated and/or having high health literacy were associated with an increased prevalence of preventive dental visits (P for trend < 0.001). Compared with less education and low health literacy group, adjusted PRs (95% confidence intervals) of preventive dental visits were 1.10 (0.93, 1.31) for less education and high health literacy group, 1.14 (1.00, 1.30) for more education and low health literacy group, and 1.29 (1.13, 1.48) for more education and high health literacy group. Conclusions: The present data suggest that health literacy may help promote preventive dental visits and do not deny the possibility that health literacy can mitigate educational inequalities in patients with diabetes. [ABSTRACT FROM AUTHOR]

Cellulose nanofibrils (CNFs) are a promising new material derived from biomass, known for their lightweight, high strength, and low thermal expansion properties. However, concerns have been raised about their potential health impact due to their fibrous and ultrafine nature. This study aimed to evaluate the effects of different types of CNFs on rat alveolar macrophages (NR8383). The CNFs tested included TEMPO-oxidized CNFs (CNF1), phosphorylated CNFs (CNF2), mechanically fibrillated CNFs from softwood bleached kraft pulp (CNF3), CNFs derived from citrus peels (CNF4), and two size fractions (coarse and ultrafine) of softwood bleached kraft pulp obtained by aqueous counter collision processing (CNF5 and CNF6). The findings showed no significant production of reactive oxygen species in any of the CNF exposure groups. However, exposure to CNF1, CNF2, and CNF3 led to increased mitochondrial dehydrogenase activity, elevated pro-inflammatory cytokine production, and upregulation of inflammation-related genes. These effects were less pronounced in the CNF4, CNF5, and CNF6 groups. Cellular uptake of CNFs was observed across all groups, and the response to CNF exposure differed from the response to microcrystalline cellulose, which was used as a reference material. No clear correlation was found between the observed effects and the presence of biological contaminants, such as bacteria and endotoxins, in the CNF dispersions. These findings suggest that CNFs may either activate macrophages or demonstrate biocompatibility rather than cytotoxicity. The impact and biocompatibility of CNFs on alveolar macrophages appear to be influenced by various factors, including the source of the CNF raw material, the manufacturing process, physicochemical properties, and biological characteristics of the CNF dispersion. This study provides valuable insights into the potential inhalation effects of CNFs. [ABSTRACT FROM AUTHOR]

Global warming directly and indirectly affects the biology and ecology of aquatic insects. Chironomids are ubiquitous on the earth and are suitable for systematic analysis of the warming effect on insects. Here, we measured the survival rate for the fourth-instar larvae of seven Chironomus species at different temperatures. The mid-temperature for survival after 1-h temperature exposure to Chironomus sulfurosus larvae was the highest (43 °C) among seven Chironomus species. In addition, 14.5% of C. sulfurosus larvae survived at 40 °C from the first to the fourth instar for 14 days, whereas larvae of the other three species with relatively high thermal tolerance in the 1-h exposure test could not. These results indicate that only C. sulfurosus larvae are tolerant of 40 °C. We examined the expression levels of specific genes encoding four heat shock proteins and one heat shock protein cognate in C. sulfurosus larvae at various temperatures using quantitative real-time PCR. The expression levels of genes for hsc70, hsp67, hsp60, hsp27, and hsp23 genes were higher at 40 °C than those at 35 °C, at which 97% of larvae survived for 14 days. Therefore, in conjunction with the present phylogenetic analysis, the thermal tolerance of C. sulfurosus is associated with the up-regulated hsp and hsc genes, which may underlie a mechanism for the organism's response to high temperatures. [ABSTRACT FROM AUTHOR]

Background: Palbociclib is a cell-cycle targeted small molecule agent used as one of the standards of care in combination with endocrine therapy for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Although several gene alterations such as loss of Rb gene and amplification of p16 gene are known to be conventional resistance mechanisms to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, the comprehensive landscape of resistance is not yet fully elucidated. The purpose of this study is to identify the novel resistant genes to the CDK4/6 inhibitors in HR-positive HER2-negative breast cancer. Methods: The whole genome knockout screen using CRISPR/Cas9 genome editing was conducted in MCF7 to identify resistant genes to palbociclib. The candidate genes for resistance were selected by NGS analysis and GSEA analysis and validated by cell viability assay and mouse xenograft models. Results: We identified eight genes including RET, TIRAP, GNRH1, SEMA3F, SEMA5A, GATA4, NOD1, SSTR1 as candidate genes from the whole genome knockout screen. Among those, knockdown of SEMA3F by siRNA significantly and consistently increased the cell viability in the presence of CDK4/6 inhibitors in vitro and in vivo. Furthermore, the level of p-Rb was maintained in the palbociclib treated SEMA3F-downregulated cells, indicating that the resistance is driven by increased activity of cyclin kinases. Conclusion: Our observation provided the first evidence of SEMA3F as a regulator of sensitivity to CDK4/6 inhibitors in breast cancer. The detailed mechanisms of resistance deserve further functional studies to develop the better strategy to overcome resistance in CDK4/6 inhibitors. [ABSTRACT FROM AUTHOR]

The target of this study is a norm-conservative scheme for the Ostrovsky equation, as its mathematical analysis has not been addressed. First, the existence and uniqueness of its numerical solutions are demonstrated. Subsequently, a convergence estimate in the two-norm is established. This, in turn, implies a convergence in the first-order Sobolev space using a supplementary sup-norm boundedness argument. Finally, this conservative scheme can be implemented in a differential form, which is considerably better than the integral form in terms of computational cost-effectiveness. [ABSTRACT FROM AUTHOR]

Furihata and Matsuo proposed in 2010 an energy-conserving scheme for the Zakharov equations, as an application of the discrete variational derivative method (DVDM). This scheme is distinguished from conventional methods (in particular the one devised by Glassey (Math Comput 58(197):83–102, 1992)) in that the invariants are consistent with respect to time, but it has not been sufficiently studied both theoretically and numerically. In this study, we theoretically prove the solvability under the loosest possible assumptions. We also prove the convergence of this DVDM scheme by improving the argument by Glassey. Furthermore, we perform intensive numerical experiments for comparing the above two schemes. It is found that the DVDM scheme is superior in terms of accuracy, but since it is fully-implicit, the linearly-implicit Glassey scheme is better for practical efficiency. In addition, we proposed a way to choose a solution for the first step that would allow Glassey's scheme to work more efficiently. [ABSTRACT FROM AUTHOR]

Gradient Langevin dynamics and a variety of its variants have attracted increasing attention owing to their convergence towards the global optimal solution, initially in the unconstrained convex framework while recently even in convex constrained non-convex problems. In the present work, we extend those frameworks to non-convex problems on a non-convex feasible region with a global optimization algorithm built upon reflected gradient Langevin dynamics and derive its convergence rates. By effectively making use of its reflection at the boundary in combination with the probabilistic representation for the Poisson equation with the Neumann boundary condition, we present promising convergence rates, particularly faster than the existing one for convex constrained non-convex problems. [ABSTRACT FROM AUTHOR]

Purpose: Periosteal chondrosarcoma (PCS) is the rarest subtype of chondrosarcoma and is recognized as a low-grade malignant tumour, reported to have an 88% ten year overall survival rate. The relationship between surgical margins and clinical outcome is inconsistent; some authors claim that PCS can be successfully treated with marginal resection and others report more local recurrence and distant metastasis with marginal compared to wide resection. This study was intended to report the treatment and prognosis of localized PCS patients from the Japanese National Bone and Soft Tissue Tumor Registry database and to perform a systematic review of the literature to determine the relationship between surgical margins and rates of local recurrence, distant metastasis, and mortality. Methods: Twenty-three patients with pathologically-diagnosed PCS between 2006 and 2022 from the Japanese National Bone and Soft Tissue Tumor Registry database were retrospectively analyzed. Of the 105 studies found through a systematic search using Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases, nine studies were ultimately included. Results: The local recurrence rate after R0 resection was 2.5% (3/118 patients) and after R1 resection was 33.3% (11/33 patients) (p < 0.001). The distant metastasis rate in the R0 resection group was 5.9% (7/118 patients) and in the R1 resection group was 27.3% (9/33 patients) (p = 0.010). Mortality following R0 resection was 4.2% (5/118 patients) but after R1 resection was 18.2% (6/33 patients) (p = 0.040). Conclusion: Wide resection may be necessary for localized PCS to prevent local recurrence and distant metastasis and improve survival. [ABSTRACT FROM AUTHOR]

Permanent preservation of genetic resources may be indispensable for the future of humanity. This requires liquid nitrogen, as is the case for preserving animal sperm. However, this technique is expensive and poses a risk of irrecoverable sample loss on non-replenishment of liquid nitrogen in case of natural disasters. In this study, we demonstrate that lyophilization may be used as a reliable method for long-term preservation of mouse sperm at room temperature. Sperm from four mouse strains were freeze-dried and stored in a non-temperature controlled room for 5–6 years. Although the ability of the stored sperm to activate oocytes had diminished slightly, healthy offspring were obtained by artificially activating the oocytes after sperm injection. Moreover, the birth rate did not decrease even after ≤ 6 years of storage. Furthermore, owing to its low cost, safety, and ease of storage at any location, we believe that this method could be a major mode of preserving mammalian genetic resources in the future. [ABSTRACT FROM AUTHOR]

Purpose: This multi-institutional observational study aimed to assess the incidence, severity, and impact of radiotherapy-related late toxicities of the cervical skin and soft tissue in head and neck cancer patients. We also explored patient interest in fat grafting as a potential treatment for skin and soft tissue sequelae. Methods: This study was conducted across 19 institutions in Japan. The study involved head and neck cancer patients who received ≥ 60 Gy of cervical radiotherapy concomitant with a history of neck dissection and were free of cancer recurrence ≥ 3 years after the final treatment. Consenting outpatients completed a self-administered questionnaire to collect data on symptom severity and the attending outpatient physicians reported data on demographics and treatments in a case report form. Results: A total of 222 patients were enrolled. The incidence proportion of late cervical skin and soft tissue toxicities was 96%, with 32% of patients reporting their symptoms as severe, and 69% of patients reporting an impact on quality of life (QOL). An interest in or consideration of fat grafting was reported by 34% of patients, with a greater desire among those with severe symptoms. Conclusion: This study elucidated the incidence, severity, and life impact of late toxicities affecting the cervical skin and soft tissue after radiotherapy for head and neck cancer. These late toxicities were highly prevalent and significantly impacted QOL. There is a substantial demand for new treatments, such as fat grafting, to address these complications and enhance the QOL for survivors of head and neck cancer. [ABSTRACT FROM AUTHOR]

Background: Recurrent cases of spontaneous spinal epidural hematoma are rare, and there are no reports of spontaneous resolution and recurrence in toddlers. Case presentation: We present a case of a toddler with a cervical spontaneous spinal epidural hematoma, characterized by three episodes of sudden-onset transient torticollis with subsequent natural recovery. The patient was referred to our hospital after the second episode, during which symptoms were already improving. Conservative management without surgery was chosen, leading to spontaneous resolution. During the third episode, the symptoms were mild, and observation was again selected, resulting in natural improvement. Post-resolution magnetic resonance imaging revealed an extradural cyst, suggesting that the hemorrhage had occurred within the cyst. Conclusion: Recurrent cases of cervical spontaneous epidural hematomas often resolve with conservative treatment, particularly in cases with mild myelopathy. Our case suggests a possible association between a spinal cystic structure and hemorrhage within the spinal canal. Conservative management may be appropriate in cases of spontaneous epidural hematomas with mild or improving symptoms to avoid the risk of postoperative kyphosis. [ABSTRACT FROM AUTHOR]

Chondrosarcoma (CS) is a malignant tumor that produces cartilaginous matrix and is the second most common primary bone sarcoma. CS encompasses a range of histological subtypes, with high-grade conventional central CS being particularly rare, occurring at a rate of 1.81 cases per 1 million person-years. Complete surgical resection is the standard curative treatment for this subtype, as radiation therapy and chemotherapy have proven ineffective. High-grade conventional central CS is highly metastatic and prone to recurrence, resulting in a poor prognosis. Therefore, effective multidisciplinary treatment strategies are urgently needed. Patient-derived cell lines offer promising tools for exploring new therapeutic approaches. However, only two cell lines of high-grade CSs are currently available in public cell banks. In this study, we aimed to establish a novel cell line for high-grade conventional central CS. We successfully developed the NCC-CS1-C1 cell line using surgically resected tumor tissues from a patient with conventional central grade 3 CS. This cell line harbored an IDH1 mutation (p.R132S), commonly found in 50% of CS cases, and exhibited complex copy number variants. A high-throughput screening of 221 anti-cancer drugs identified five candidates—bortezomib, carfilzomib, doxorubicin, panobinostat, and romidepsin—that demonstrated low IC50 values, indicating potential efficacy in treating CS. These findings suggest that NCC-CS1-C1 is a valuable tool for both preclinical and basic research on high-grade conventional central CS. [ABSTRACT FROM AUTHOR]

Giant cell tumor of bone (GCTB) is a rare osteolytic tumor composed of mononuclear stromal cells, macrophages, and osteoclast-like giant cells. While generally benign, GCTB has a high risk of local recurrence and can occasionally undergo malignant transformation or metastasis, posing significant clinical challenges. The primary treatment is complete surgical resection; however, effective management strategies for recurrent or advanced GCTB remain elusive, underscoring the need for further preclinical research. This study reports the establishment of a novel cell line, NCC-GCTB10-C1, derived from a recurrent GCTB lesion. NCC-GCTB10-C1 retains the characteristic H3-3A G34W mutation, which is central to the tumor’s pathogenesis, and demonstrates significant growth potential, spheroid formation capability, and invasive properties. Extensive drug screening of NCC-GCTB10-C1, along with nine previously established GCTB cell lines, revealed a distinct drug response profile, with the cell line showing resistance to many previously effective agents. However, doxorubicin, foretinib, and ceritinib were identified as promising therapeutic candidates due to their low IC50 values in NCC-GCTB10-C1. The establishment of NCC-GCTB10-C1 offers a critical resource for further research into GCTB, especially in the context of recurrent disease, and holds potential for the development of more effective treatment strategies. [ABSTRACT FROM AUTHOR]

Giant cell tumor of bone (GCTB) is a rare bone tumor that is genetically characterized by a unique mutation in the H3-3A gene. Curative surgical resection is the standard treatment. Unfortunately, a considerable proportion of patients with GCTB have local recurrence and pulmonary metastasis after surgical treatment, and current chemotherapy treatments have shown non-effective. Considering the heterogeneity of the disease, patient-derived cancer models established from multiple cases are required. Therefore, we aimed to establish novel GCTB cell lines for use in preclinical studies. In this study, we successfully established two GCTB cell lines, NCC-GCTB14-C1 and NCC-GCTB15-C1. Both cell lines retained the genetic characteristics of the original tumors, constantly proliferated, and exhibited migratory activity. These cells formed spheroids with morphologically variable phenotypes. We found that they were compatible with chemosensitivity assays, and drug screening using these cell lines led to the identification of potential therapeutic candidates for GCTB. Therefore, NCC-GCTB14-C1 and NCC-GCTB15-C1 may be useful for elucidating the pathogenesis of and developing novel treatments for GCTB. [ABSTRACT FROM AUTHOR]

B-type natriuretic peptide (BNP) levels accurately reflect the degree of cardiac overload in heart failure. Considering cardiac morphology and intracardiac pressure, including the left ventricular end-systolic volume index (LVESVI) and left ventricular end-diastolic volume index (LVEDVI), is essential for cardiac overload assessment. These indexes influence plasma BNP levels, and high heart rate is likely associated with cardiac morphology. However, the direct relationship between high heart rate and plasma BNP levels remains unknown. In this study, we simultaneously measured various hemodynamic parameters and plasma BNP levels during cardiac catheterization in 5,429 inpatients with sinus rhythm at our hospital. Furthermore, we examined how heart rate is associated with cardiac morphology, intracardiac pressure, and plasma BNP levels via regression analysis and structure equation modeling (SEM). Univariate regression analysis revealed a significant positive correlation between heart rate and log BNP. The path model with SEM revealed significant positive relations of heart rate and LVESVI with left ventricular end-diastolic pressure, in addition to a significant negative relation of heart rate and LVEDVI with log BNP. Collectively, these findings suggest no positive relation (rather, a negative relation) between heart rate and log BNP and that high heart rate is indirectly associated with increased plasma BNP levels by altering cardiac morphology and intracardiac pressure. [ABSTRACT FROM AUTHOR]

The interaction of tumor cells and their microenvironment is thought to be a key factor in tumor development. We present spatial RNA profiles obtained from 30 lung adenocarcinoma patients at the non-invasive and later invasive stages. We use spatial transcriptome sequencing data in conjunction with in situ RNA profiling to conduct higher resolution analyses. The detailed examination of each case, as well as the subsequent computational analyses based on the observed diverse profiles, reveals that significant changes in the phenotypic appearances of tumor cells are frequently associated with changes in immune cell features. The phenomenon coincides with the induction of a series of cellular expression programs that enable tumor cells to transform and break through the immune cell barrier, allowing them to progress further. The study shows how lung tumors develop through interaction in their microenvironments. The role of immune-tumor cell interactions in lung adenocarcinoma (LUAD) development remains to be explored. Here, spatial transcriptomics and in situ RNA profiling of samples from 30 LUAD patients reveals changes in the phenotypic properties of tumors cells associated with changes in immune cell features. [ABSTRACT FROM AUTHOR]

Background: Radical cystectomy in women generally includes the removal of the uterus, ovaries, and anterior vaginal wall, but the criteria for reproductive organ sparing are not clear. Methods: A total of 2674 patients with bladder cancer were retrospectively reviewed, having undergone cystectomy at this nationwide multicenter from January 2013 to December 2019. We evaluated the incidence of malignancy in reproductive organs in a cohort of 417 women and analyzed the clinicopathological features of reproductive organ involvement. Recurrence-free survival and overall survival were reported using Kaplan–Meier survival curves. Results: Median follow-up was 36.9 months. Of the 417 patients with urothelial carcinoma of the bladder, 325 underwent hysterectomy, and 92 had a spared uterus and anterior wall of the vagina. Twenty-nine (8.9%) patients exhibited reproductive organ involvement; this consisted of 22 (6.8%) uteri, 16 (4.9%) vaginas, and two (0.6%) ovaries. Incidental primary reproductive malignancies were found in only two (0.6%) patients. Recurrence-free survival and overall survival were significantly shorter in patients with reproductive organ involvement than in those without. Patients with reproductive organ involvement were more likely to have tumors with ≥ cT3 or sub-localization at the posterior/trigone/bladder neck. Conclusions: The risk of reproductive organ involvement cannot be ignored in women undergoing radical cystectomy for urothelial carcinoma of the bladder, therefore, the eligibility criteria for reproductive organ preservation should be considered carefully. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the incidence and risk factors of lower extremity pain and/or numbness after laparoscopic colorectal surgery and robot-assisted laparoscopic radical prostatectomy in the lithotomy position combined with the Trendelenburg position. The relationship between creatine kinase (CK) levels and lower extremity pain and/or numbness was also investigated. Methods: We retrospectively reviewed adult patients who underwent laparoscopic colorectal surgery and robot-assisted laparoscopic radical prostatectomy in the lithotomy position combined with the Trendelenburg position between May 2015 and April 2020. Logistic regression analysis was used to identify risk factors of lower extremity pain and/or numbness. Preoperative and postoperative CK levels were compared in patients with and those without lower extremity pain and/or numbness. Results: Among 940 patients, 1.9% experienced lower extremity pain and/or numbness postoperatively. The incidences of lower extremity pain and/or numbness after laparoscopic colorectal surgery and after robot-assisted laparoscopic radical prostatectomy were 1.7% and 2.1%, respectively. Multivariate logistic regression analysis revealed that only duration of surgery > 4 h (odds ratio = 3.144, 95% CI: 1.102–8.969, p = 0.032) was a significant predictor of lower extremity pain and/or numbness. Postoperative median CK level in patients with lower extremity pain and/or numbness was significantly higher than that in patients without lower extremity pain and/or numbness. Conclusion: The incidence of lower extremity pain and/or numbness after laparoscopic colorectal surgery was comparable to that after robot-assisted laparoscopic radical prostatectomy. Prolonged duration of surgery contributed to lower extremity pain and/or numbness. Significantly elevated CK levels in patients with lower extremity pain and/or numbness suggest the involvement of muscle injury in these symptoms. [ABSTRACT FROM AUTHOR]

Background: There have been few reports of a totally extraperitoneal approach for laparoscopic lateral lymph node dissection (LLND) for patients with metachronous lateral pelvic lymph node metastases following surgery for rectal cancer. Therefore, this study reports the short-term outcomes of LLND via an extraperitoneal approach. Methods: A total of 10 patients underwent LLND through a laparoscopic extraperitoneal approach in our hospital since October 2018. Patients with suspected resectable lateral lymph node recurrence after surgery for rectal cancer on computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography CT (PET-CT) were selected for this procedure. Results: Nine of the 10 cases were completed using this procedure, but one case was converted to an intraperitoneal approach. The median operative time was 231 min, and the median estimated blood loss was 10 ml. There was one case of wound infection, but no other postoperative complications were seen. In one patient, no metastases were found in the retrieved lymph nodes. Conclusion: The short-term outcomes of LLND through a laparoscopic extraperitoneal approach were acceptable. Because this procedure can be performed without violating the peritoneum, it is less invasive than the conventional intraperitoneal approach and is useful for metachronous lateral pelvic lymph node metastases. [ABSTRACT FROM AUTHOR]

Drug repositioning of approved drugs offers advantages over de novo drug development for a rare type of cancer. To efficiently identify on-target drugs from clinically successful kinase inhibitors in cancer drug repositioning, drug screening and molecular profiling of cell lines are essential to exclude off-targets. We developed a pharmacoproteogenomic approach to identify on-target kinase inhibitors, combining molecular profiling of genomic features and kinase activity, and drug screening of patient-derived cell lines. This study examined eight patient-derived giant cell tumor of the bone (GCTB) cell lines, all of which harbored a signature mutation of H3-3A but otherwise without recurrent copy number variants and mutations. Kinase activity profiles of 100 tyrosine kinases with a three-dimensional substrate peptide array revealed that nine kinases were highly activated. Pharmacological screening of 60 clinically used kinase inhibitors found that nine drugs directed at 29 kinases strongly suppressed cell viability. We regarded ABL1, EGFR, and LCK as on-target kinases; among the two corresponding on-target kinase inhibitors, osimertinib and ponatinib emerged as on-target drugs whose target kinases were significantly activated. The remaining 26 kinases and seven kinase inhibitors were excluded as off-targets. Our pharmacoproteomic approach enabled the identification of on-target kinase inhibitors that are useful for drug repositioning. [ABSTRACT FROM AUTHOR]

Hypertension causes aortic wall thickening until the original wall stress is restored. We hypothesized that this regulation involves stress fiber (SF) tension transmission to the nucleus in smooth muscle cells (SMCs) and investigated the strain in the SF direction as a condition required for this transmission. Thoracic aortas from Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHRs) were examined. SFs in aortic SMCs were fluorescently labeled and observed under a confocal microscope while stretched along the circumferential (θ) axis. Three conditions were studied: WKY physiological (WKYphys; blood pressure changes from diastolic to systolic for WKY), high-strain state (WKYhigh; diastolic to hypertensive level for WKY simulating initial hypertension), and SHR physiological (SHRphys; diastolic to systolic for SHR simulating after wall-thickening). SF strain and direction were measured. The SF inclination angle from the θ axis was 18° ± 3° in WKYphys, 13° ± 2° in WKYhigh, and 20° ± 1° in SHRphys. SF strain was 0.01 ± 0.02 in WKYphys, 0.20 ± 0.04 in WKYhigh, and 0.02 ± 0.02 SHRphys. SF strain was minimal in WKYphys, significantly increased in WKYhigh, and reduced to approximately zero in SHRphys. These findings support SFs function as mechanosensors in response to hypertension. [ABSTRACT FROM AUTHOR]

Background: Accurate identification and characterization of lymph nodes (LNs) are essential in cancer staging and treatment planning. While artificial intelligence (AI) has shown potential in detecting lymphadenopathy on contrast-enhanced CT scans, its performance on non-contrast (plain) CT scans remains less explored. This retrospective study aimed to assess the efficacy of AI for segmenting LNs on plain CT in patients with lung or gastrointestinal cancer. Eligible cases were selected based on plain CT scans with 5 mm slice thickness, showing mediastinal or hilar LNs with a short-axis diameter of ≥ 10 mm. A total of 144 patients (105 men, 39 women; mean age, 76 years) were included, comprising 342 LNs. A commercially available deep learning AI software was used for segmentation, with the ground-truth defined by two radiologists' consensus on LNs measuring ≥ 10 mm. Results: The AI software showed a sensitivity of 83.9%, with no statistically significant difference between mediastinal and hilar LNs (p = 0.84). The false-positive rate was 0.465 per patient. The Dice coefficient was 0.908, and there was no statistically significant difference between the mediastinum and hilum (p = 0.19). The sensitivity decreased in larger LNs, showing an inverse correlation (r = −0.122, p < 0.01). Conclusions: This study demonstrated the robustness of the AI software in the segmentation of LNs in the mediastinum and hilum on plain CT scans. [ABSTRACT FROM AUTHOR]

Serum leucine-rich alpha-2 glycoprotein (LRG) can monitor disease activities during biologics treatment in patients with inflammatory bowel disease (IBD). It is unclear whether the pretreatment serum LRG level can predict clinical effectiveness including serum trough levels of ustekinumab in patients with IBD. This multicenter prospective cohort study included 184 patients (Crohn's disease, 104; ulcerative colitis, 80) who received ustekinumab (n = 119) or anti-tumor necrosis factor (n = 65) between January 2019 and March 2023. Multivariate logistic regression analysis revealed serum LRG level at week 0 (0w-LRG, odds ratio 0.12, 95% confidence interval 0.02–0.68) as one of significant factors for clinical remission at week 8. We divided patients into the low- and the high-LRG groups by the median 0w-LRG (18.2 µg/mL) and compared the effectiveness. In patients who received ustekinumab, the proportion of clinical remission at week 8 was significantly different between in the low- (76.9%) and in the high-LRG group (59.3%, P = 0.038), and median serum trough level at week 8 was significantly different between in the low- (10.9 µg/mL, interquartile range 6.7–13.4) and the high-LRG group (5.3 µg/mL, interquartile range 2.4–8.3, P < 0.001). The 0w-LRG can predict the effectiveness including serum trough levels of ustekinumab during induction treatment for patients with IBD. [ABSTRACT FROM AUTHOR]

Recent studies have proposed the contribution of aseismic slip (AS) to earthquake swarms. We investigated the role of AS in earthquake swarms that occurred in 2009, 2015, and 2019 at the Hakone volcano, central Japan, through highly resolved hypocenter distribution analysis, geodetic observation analysis, and identification of similar earthquakes. We observed diffusion-like migration of hypocenters during these swarms. The hydraulic diffusivity varied among the swarms, indicating differing dynamics. The 2015 swarm exhibited rapid hypocenter migration and significant crustal deformation, as revealed by the temporal sequences of tiltmeters near the swarm region. Right-lateral shear dislocation on fault planes could explain the crustal deformation observed in 2015, indicating that AS released approximately 90% of the moment. However, the 2009 swarm lacked evidence of significant AS contribution, indicating that the primary mechanism was fluid pressure diffusion. The substantial contribution of AS to the 2015 swarm might be attributed to increased fluid pressure due to the intrusion of hydrothermal fluid into the shallow part beneath the volcano during volcanic unrest. Our findings imply that the temporal and spatial patterns of seismicity can provide valuable insights into the underlying mechanics of earthquake swarms. [ABSTRACT FROM AUTHOR]

The integrative multi-kingdom interaction of the gut microbiome in ulcerative colitis (UC) and Crohn's disease (CD) remains underinvestigated. Here, we perform shotgun metagenomic sequencing of feces from patients with UC and CD, and healthy controls in the Japanese 4D cohort, profiling bacterial taxa, gene functions, and antibacterial genes, bacteriophages, and fungi. External metagenomic datasets from the US, Spain, the Netherlands, and China were analyzed to validate our multi-biome findings. We found that Enterococcus faecium and Bifidobacterium spp. were enriched in both diseases. Enriched Escherichia coli was characteristic of CD and was linked to numerous antibiotic resistance genes involved in efflux pumps and adherent-invasive Escherichia coli virulence factors. Virome changes correlated with shifts in the bacteriome, including increased abundances of phages encoding pathogenic genes. Saccharomyces paradoxus and Saccharomyces cerevisiae were enriched in UC and CD, respectively. Saccharomyces cerevisiae and Escherichia coli had negative associations with short-chain fatty acid (SCFA)-producing bacteria in CD. Multi-biome signatures and their interactions in UC and CD showed high similarities between Japan and other countries. Since bacteria, phages, and fungi formed multiple hubs of intra- or trans-kingdom networks with SCFA producers and pathobionts in UC and CD, an approach targeting the interaction network may hold therapeutic promise. Here, the authors perform a multi-biome analysis in ulcerative colitis and Crohn's disease patients from the Japanese 4D cohort, identifying intra- and trans-kingdom interactions including bacteria, phages, and fungi, providing potential candidate therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Colonoscopy is widely performed. However, reports of colonoscopic incarceration within inguinal hernias are rare. Incarceration during colonoscopy is a critical condition, and attempting forced reduction may exacerbate complications; therefore, a careful approach is required. Here, we present a case of colonoscopic incarceration of a left inguinal hernia that was successfully reduced under fluoroscopic guidance, followed by elective endoscopic surgery. Case presentation: A 74-year-old man presented for colonoscopy at a primary care clinic and was referred to our hospital for the incarceration of the colonoscope within the inguinal hernia. On arrival, the colonoscope remained in situ through the anus. Laboratory tests and imaging studies confirmed the absence of perforation. Manual pressure was applied under fluoroscopic guidance to successfully reduce the hernia and allow for scope extraction. No evidence of perforation was revealed in the follow-up fluoroscopic examination using a gastrografin enema. Six weeks later, the patient underwent definitive surgery for total extraperitoneal hernia repair. Conclusions: A complication of colonoscopy is the incarceration of the colonoscope within the inguinal hernia, particularly in older men. Therefore, inquiring about the patient's history of inguinal hernia, particularly those accompanied by scrotal swelling, besides assessing the surgical history before performing a colonoscopy, is critical. Furthermore, recent trends include attempts at incarceration reduction under fluoroscopic guidance, with emergency surgery reserved for irreducible cases. [ABSTRACT FROM AUTHOR]

The ability to detect threats quickly is crucial for survival. Primates, including humans, have been shown to identify snakes quickly and accurately due to their evolutionary history. However, it is unclear which visual features humans and primates detect as threat targets. Several studies have suggested that snake scales possess potent visual features. My previous study demonstrated that removing snake scales through digital image processing reduces attention directed toward snakes. Here, I conducted a visual search task using luminance- and contrast-adjusted photographs of snakes and salamanders in monkeys that had never seen these real reptiles and amphibians. This study demonstrates that the presence or absence of snake scales is responsible for the rapid detection of target animals. The monkeys quickly detected one snake photograph from the eight salamander photographs than vice versa. However, when the same salamanders were clothed with snake scales using image processing, the difference in detection speed between snakes and salamanders disappeared. These results are consistent with the snake-detection theory that snakes were a strong selective pressure favoring modifications in the primate visual system that allow them to detect snakes more quickly or reliably. This strongly suggests that primates' snake detection depends on the snake-scale shapes, which are both snake-specific and common to all snakes. [ABSTRACT FROM AUTHOR]

Background: Lipolysis-stimulated lipoprotein receptor (LSR), a lipid receptor, is associated with cancer progression. However, detailed effects on intracellular metabolism are unclear. We aimed to elucidate the mechanism of LSR-mediated lipid metabolism in gastric cancer. Methods: We investigated lipid metabolic changes induced by lipoprotein administration in gastric cancer cells and evaluated the significance of LSR expression and lipid droplets formation in gastric cancer patients. The efficacy of inhibiting β-oxidation in gastric cancer cells was also examined in vitro and vivo. Results: In gastric cancer cells, LSR promoted cellular uptake of lipoprotein and cell proliferation. Furthermore, the inhibition of LSR in gastric cancer cells expressing high levels of LSR counteracted both effects. Immunohistochemical analysis of human gastric cancer tissues showed that the increase in lipid droplets via LSR is a factor that influences prognosis. Lipidomics analysis of LSR-high-expressing gastric cancer cells revealed an increase in β-oxidation. Based on these results, we used etomoxir, a β-oxidation inhibitor, and found that it inhibited cell proliferation as well as the suppression of LSR. Similarly, in a mouse xenograft model of LSR-highly expressing gastric cancer cells, the tumor growth effect of high-fat diet feeding was counteracted by etomoxir, consistent with the Ki-67 labeling index. Conclusions: We demonstrated that lipids are taken up into gastric cancer cells via LSR and cause an increase in β-oxidation, resulting in the promotion of cancer progression. Controlling LSR-mediated lipid metabolism may be a novel therapeutic strategy for gastric cancer. [ABSTRACT FROM AUTHOR]

High clouds play an important role in climate variations by shading the sun and contributing to the greenhouse effect. It has been suggested that these variations are strongly controlled by atmospheric circulations; however, the relationship between high clouds and circulations in global simulations has been confirmed only for a limited number of general circulation models (GCMs). Increasing our understanding of this relationship requires a more complete dataset of state-of-the-art GCMs. This study quantifies the relationship between high clouds and circulations by spatial and temporal correlation using data from 28 atmospheric GCMs along with a global nonhydrostatic model, a new-type of GCM, and reveals a robust and strong relationship in most models. This study also finds that the sensitivity, which is defined as the slope of the relationship between high clouds and mass fluxes of circulations, is highly model-dependent. This suggests that a similar change of circulations does not guarantee that of high clouds, which could be one reason for the complexity in projecting high-cloud changes due to warming. Moreover, this study confirms in both observation and models that the relationship with circulations is stronger for medium-thickness and thick high clouds than for thin clouds. Furthermore, the relationship between high clouds and circulations is more convincing in near-equatorial regions between 15°S–15°N, the ascending branch of the Hadley circulation, where deep convection is especially active. [ABSTRACT FROM AUTHOR]

Myxofibrosarcoma (MFS), an aggressive soft tissue sarcoma, presents a significant challenge because of its high recurrence rate, distal metastasis, and complex genetic background. Although surgical resection is the standard treatment for MFS, the outcomes are unsatisfactory and effective non-surgical treatment strategies, including drug therapy, are urgently warranted. MFS is a rare tumor that requires comprehensive preclinical research to develop promising drug therapies; however, only two MFS cell lines are publicly available worldwide. The present study reports two novel patient-derived MFS cell lines, NCC-MFS7-C1 and NCC-MFS8-C1. These cell lines have been extensively characterized for their genetic profile, proliferation, spheroid-forming capacity, and invasive behavior, confirming that they retain MFS hallmarks. Furthermore, we conducted comprehensive drug screening against these cell lines and six others previously established in our laboratory to identify potential therapeutic candidates for MFS. Among the screened agents, actinomycin D, bortezomib, and romidepsin demonstrated considerable antiproliferative effects that were superior to those of doxorubicin, a standard drug, highlighting their potential as novel drugs. In conclusion, NCC-MFS7-C1 and NCC-MFS8-C1 are valuable research resources that contribute to the understanding of the pathogenesis and development of novel therapies for MFS. [ABSTRACT FROM AUTHOR]

Synovial sarcoma (SS) is identified as a sarcoma with monomorphic blue spindle cells that display variable epithelial differentiation and is characterized by the SS18::SSX fusion gene. SS accounts for approximately 5–10% of all soft tissue sarcomas, making it a relatively common type within this group of tumors. Since SS is generally sensitive to chemotherapy, the standard treatment for SS includes extensive surgical resection, complemented by neoadjuvant chemotherapy with several approved anticancer drugs. However, in advanced and metastatic cases, the efficacy of these drugs is limited, resulting in poor prognoses. This underscores the need for innovative therapeutic strategies. Patient-derived cancer cell lines are essential tools for basic and preclinical research, yet only four SS cell lines are publicly available. To facilitate the studies of SS, we have developed a novel SS cell line, named NCC-SS6-C1, derived from surgically excised tumor tissue of an SS patient. NCC-SS6-C1 cells preserve the SS18::SSX1 fusion gene, consistent with the genetic characteristics of the original tumor. The cells exhibit continuous proliferation, invasiveness, and the ability to form spheroids. Additionally, we confirmed that this cell line was useful for evaluating the efficacy of anticancer drugs. Our results suggest that NCC-SS6-C1 is a useful tool for basic and pre-clinical studies of SS. [ABSTRACT FROM AUTHOR]

Ice nucleating particles (INPs) affect the cloud radiative budget in the rapidly warming Arctic by changing the cloud liquid/ice phase balance. Dust emitted in the Arctic (Arctic dust) has been suggested to be a major contributor to INPs in the Arctic lower troposphere. However, how Arctic dust and its impacts on ice nucleation change with Arctic warming has not been explored. Here we find that the simulated dust emission flux in the Arctic (>60°N) in global model simulations increases by 20% from 1981–1990 to 2011–2020. This increase weakens the sensitivity of ice nucleation in Arctic lower tropospheric clouds to warming by 40% compared to the case without considering Arctic dust emission increases. Our results demonstrate a better understanding of the counterbalancing feedbacks of Arctic dust (i.e., increasing emissions and decreasing ice nucleation efficiency) is needed for more accurate estimates of changes in ice nucleation in the rapidly changing Arctic climate. [ABSTRACT FROM AUTHOR]

It is established that neurogenesis of dentate gyrus is increased after ischemic insult, although the regulatory mechanisms have not yet been elucidated. In this study, we focused on Ezh2 which suppresses gene expression through catalyzing trimethylation of lysine 27 of histone 3. Male gerbils were injected with adeno-associated virus (AAV) carrying shRNA targeting to Ezh2 into right dentate gyrus 2 weeks prior to forebrain ischemia. One week after ischemia, animals were injected with thymidine analogue to label proliferating cells. Three weeks after ischemia, animals were killed for histological analysis. AAV-mediated knockdown of Ezh2 significantly decreased the ischemia-induced increment of proliferating cells, and the proliferated cells after ischemia showed significantly longer migration from subgranular zone (SGZ), compared to the control group. Furthermore, the number of neural stem cells in SGZ significantly decreased after ischemia with Ezh2 knockdown group. Of note, Ezh2 knockdown did not affect the number of proliferating cells or the migration from SGZ in the non-ischemic condition. Our data showed that, specifically after ischemia, Ezh2 knockdown shifted the balance between self-renewal and differentiation toward differentiation in adult dentate gyrus. [ABSTRACT FROM AUTHOR]

Prostate cancer (PC) is common among men and has become a significant societal issue. Localized PC has a good prognosis with appropriate treatment. Prostatectomy, particularly robot-assisted radical prostatectomy (RARP), has become a common treatment since the da Vinci prostatectomy was approved by the FDA in 2001. The current study aimed to assess the learning curve for RARP, focusing on anastomosis time, using the cumulative sum (CUSUM) method. Data were collected from Nagoya City University Hospital between May 2011 and December 2018 and included 469 surgeries performed by experienced surgeons. Our findings indicated that, on average, 11 patients were required to complete the initial phase and 24 patients were required to complete the consolidation phase of anastomosis. Additionally, for complete resection of pT2c cases, 16 cases were required for the initial phase and 27 cases were required for the consolidation phase. The CUSUM method proved useful for visualizing trends in surgical proficiency, although the study noted potential confounding biases and limitations in evaluating surgical proficiency based solely on surgical time or positive surgical margins. [ABSTRACT FROM AUTHOR]

Background: Capicua transcriptional repressor-double homeobox 4 sarcoma (CDS) is a rare and aggressive malignant soft tissue tumor that typically arises within the soft tissues. We report an exceptionally rare case of a gastric CDS successfully resected despite its extensive invasion into surrounding organs. Case presentation: A 48-year-old male presented with a progressively enlarging abdominal mass. Upper gastrointestinal endoscopy revealed a large ulcerative tumor on the posterior gastric wall. Biopsy results initially suggested a neuroendocrine cell carcinoma. Contrast-enhanced computed tomography showed a 20 cm tumor protruding from the posterior stomach wall, directly invading the pancreas and colon. We performed a multivisceral resection (stomach, pancreatic tail, spleen, and transverse colon) achieving an R0 resection. Pathological examination of the permanent specimen revealed small round cells with high nuclear-to-cytoplasmic ratios. Immunohistochemical staining confirmed the diagnosis of CDS. The patient recovered well and was discharged on postoperative day 33. Conclusions: This case report describes the first detailed account of a surgically resected aggressive CDS originating from the stomach. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is often diagnosed at advanced stages, and early-stage diagnosis of pancreatic cancer is difficult because of nonspecific symptoms and lack of available biomarkers. Methods: We performed comprehensive serum miRNA sequencing of 212 pancreatic cancer patient samples from 14 hospitals and 213 non-cancerous healthy control samples. We randomly classified the pancreatic cancer and control samples into two cohorts: a training cohort (N = 185) and a validation cohort (N = 240). We created ensemble models that combined automated machine learning with 100 highly expressed miRNAs and their combination with CA19-9 and validated the performance of the models in the independent validation cohort. Results: The diagnostic model with the combination of the 100 highly expressed miRNAs and CA19-9 could discriminate pancreatic cancer from non-cancer healthy control with high accuracy (area under the curve (AUC), 0.99; sensitivity, 90%; specificity, 98%). We validated high diagnostic accuracy in an independent asymptomatic early-stage (stage 0-I) pancreatic cancer cohort (AUC:0.97; sensitivity, 67%; specificity, 98%). Conclusions: We demonstrate that the 100 highly expressed miRNAs and their combination with CA19-9 could be biomarkers for the specific and early detection of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Allogeneic bone grafts are used to treat bone defects in orthopedic surgery, but the osteogenic potential of artificial bones remains a challenge. In this study, we developed a β-tricalcium phosphate (β-TCP) formulation containing MgO, ZnO, SrO, and SiO2 and compared its bone-forming ability with that of β-TCP without biological elements. We prepared β-TCP discs with 60% porosity containing 1.0 wt% of these biological elements. β-TCP scaffolds were loaded with bone marrow-derived mesenchymal stem cells (BMSC) from 7-week-old male rats and cultured for 2 weeks. ALP activity and mRNA expression of osteogenic markers were evaluated. In addition, scaffolds were implanted subcutaneously in rats and analyzed after 7 weeks. In vitro, the MgO group showed lower Ca concentrations and higher osteogenic marker expression compared to controls. In vivo, the MgO group showed higher ALP activity compared to controls, and RT-qPCR analysis showed significant expression of BMP2 and VEGF. Histopathology, fluorescent immunostaining, and micro-CT also showed relatively better bone formation in the MgO group. β-TCP with MgO may enhance bone morphology in vitro and in vivo and improve the prognosis of patients with substantial and refractory bone defects. [ABSTRACT FROM AUTHOR]

Background: Anal fistula cancer is rare and definitive treatment has not yet been established. Laparoscopic abdominoperineal resection is generally the first choice of treatment if the cancer is determined to be resectable. However, complicated anal fistula cancer often requires extensive resection. Using a myocutaneous flap for reconstruction after resection in such cases, radical resection can be performed regardless of the size of the anal fistula cancer. Case presentation: We report two cases in which we performed laparoscopic abdominoperineal resection with extensive buttock resection and myocutaneous flap reconstruction for widespread anal fistula cancer. One of the cases was reconstruction with a posterior thigh flap, the other was with a bilateral expanded gluteus maximus flap. Both cases were anal fistula cancers that developed from complicated anal fistulas. Conclusions: If the size of anal fistula cancer is large and extended buttock resection is necessary, radical resection of anal fistula cancer is possible using myocutaneous flap for reconstruction after extended abdominoperineal resection. [ABSTRACT FROM AUTHOR]

In this study, we aim to conduct real-time sensing of indoor dust concentration distribution to mitigate the airborne transmission of coronaviruses. Airborne infection, facilitated by viruses present in particulate matter, emphasizes the importance of monitoring dust concentration as an indicator of virus spread. Our approach involves the implementation of a time-synchronized wireless sensor network for real-time sensing of dust concentration distribution. The time-synchronized wireless sensor network relies on a proposed time-synchronization algorithm, ensuring a time error of less than ± 1.27 ms. This precision enables the measurement of even fast-moving dust particles. To validate the feasibility of the wireless time-synchronized sensor network, we utilized a dust ejector (air cannon) and positioned time-synchronized sensors in a row. Dust particles released from the ejector passed through each time-synchronized sensor terminal. Simultaneously, a video recording (60 frames) was conducted, and the measured times of the time-synchronized sensor terminals were compared with the lap times of the video. The results of this comparison revealed identical lap times between the time-synchronized sensor data and the video, affirming the successful operation of the time-synchronized wireless distributed sensor node as designed. [ABSTRACT FROM AUTHOR]

Flowering phenology of alpine plant communities is determined by the interaction between abiotic and biological factors. Bees and flies are major pollinators in alpine ecosystems. The abundance of bumble bees consistently increases with seasonal progress reflecting the colony development cycle, while fly abundance fluctuates unpredictably. Responding to the seasonal dynamics of pollinators, flowering phenology of alpine communities is expected to vary between bee-visited and fly-visited plants within and among regions. We compared the relationship between flower-visitor composition and flowering phenology across geographic regions: fly-dominated New Zealand alpine, subtropical Taiwan alpine, mid-latitudinal alpines in central and northern Japan, and high-elevation Mongolian grassland. Thermal gradient was a fundamental factor regulating flower patterns across regions, and clear seasonality at higher latitudes created diverse flower patterns within communities. Floral abundance of fly-visited plants was less predictable with large variation, whereas that of bee-visited plants showed consistent patterns across regions reflecting the seasonality of bee activity. In New Zealand, most plants were linked to syrphid and/or non-syrphid flies. The network structures of the East Asian alpines were commonly constituted by syrphid flies, non-syrphid flies, and bumble bees, and these groups had specific niche width. In the Mongolian grassland, many insect groups formed diverse networks with small niche overlap. Overall, bumble bees are suggested to be a driver of diverse flowering phenology in alpine ecosystems. In contrast, flies may not be a powerful driver of flowering phenology. Pollination networks between bumble bees and alpine plants are expected to be sensitive to climate change. [ABSTRACT FROM AUTHOR]

Background: Comprehensive genomic profiling (CGP) can aid the discovery of clinically useful, candidate antitumor agents; however, the variant annotations sometimes differ among the various types of CGP tests as well as the public database. The aim of this study is to clarify the genomic landscape of evaluating detected variants in patients with a malignant solid tumor. Methods: The present, cross-sectional study used data from 57,084 patients with a malignant solid tumor who underwent CGP at the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) between June 1, 2019 and August 18, 2023. The pathogenicity of the variants was annotated using public databases. Results: As a result of re-annotation of the detected variants, 20.1% were pathogenic and 1.4% were benign. The mean number of pathogenic variants was 4.30 (95% confidence interval: 4.27–4.32) per patient. Of the entire cohort, 5.7% had no pathogenic variant. The co-occurrence of the genes depended on the tumor type. Germline findings were detected in 6.2%, 8.8%, and 15.8% of the patients using a tumor/normal panel, tumor-only panel, and liquid panel, respectively, with the most common gene being BRCA2 followed by TP53 and BRCA1. Conclusions: The detected variants should be re-annotated because several benign variants or variants of unknown significance were included in the CGP, and the genomic landscape derived from these results will help researchers and physicians interpret the results of CGP tests. The method of extracting presumptive, germline, pathogenic variants from patients using a tumor-only panel or circulating tumor DNA panel requires improvement. [ABSTRACT FROM AUTHOR]

Background: Ureteral injury occurs in 0.3–1.5% of colorectal cancer surgeries. Devices to visualize the ureteral course and avoid ureteral injury are required for minimally invasive surgery (MIS). The NIRC™ fluorescent ureteral catheter (FUC) is a versatile ureteral visualization device currently available in Japan that can be used in combination with a variety of laparoscopic and robotic systems. In this study, we examined the outcomes of high-risk patients who underwent colorectal cancer surgery with FUC insertion. Methods: One hundred forty-one patients who underwent MIS for colorectal cancer and colorectal cancer recurrence at our institute between January 2021 and May 2024 underwent preoperative FUC insertion because of the high risk of ureteral injury and surgical difficulty. For these patients, patient background data and short-term outcomes were examined. The results are expressed as the median and interquartile range. Results: Age, 70 [60–78]; M:F(n), 84:57; BMI, 22.1 [19.7–24.7]; T4 (TNM classification), 52 cases (36.9%); preoperative intestinal obstruction, 45 cases (31.9%); abscess formation, 30 cases (21%); surgical history, 70 cases (50%); recurrent cancer, 14 cases (9.9%); preoperative chemo-radiotherapy, 28 cases (19.9%); time required for FUC insertion, 12 [9–19] minutes; operation time, 412 [309–552] minutes; blood loss, 10 [5–30] ml; open conversion, 0 cases; postoperative hospitalization, 12 [9–17.5]; circumferential resection margins < 1 mm (rectal surgery), 4/87 cases (4.6%); comorbidities, 0 ureteral injury, 1 urethral injury during FUC insertion (0.7%) and 16 CD Grade 3 or higher cases (11%). Conclusions: FUC may improve the safety of MIS and reduce blood loss in addition to preventing ureteral injury and is expected to have oncological advantages for ensuring the margin of the tumor without fear of ureteral injury. However, the time required for and complications associated with FUC are challenging. New methods for less invasive and easier ureteral visualization may be needed. [ABSTRACT FROM AUTHOR]