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Abstract Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by germline variants in the APC gene, leading to the development of numerous colorectal polyps and significantly increases the risk of colorectal cancer. A diagnosis is typically made using colonoscopy, and genetic testing can assist in patient surveillance and carrier identification. Recent advances include the use of whole-genome array comparative genomic hybridization (a-CGH), which provides better resolution of genetic imbalances. We aimed to explore the specific features of FAP patients with whole APC gene deletions using high-resolution a-CGH and to compare patient characteristics. Two polyposis patients with whole APC deletions were identified, and the lost genetic sizes ranged from 0.3–1.1 Mb. Nervous abnormalities were a characteristic symptom in a patient with a 1.1 Mb loss. A patient with an approximately 0.3 Mb loss, which included the entire APC gene, presented a polyposis phenotype without intellectual disability. The comparison of genetic losses, with or without intellectual disability, revealed 7 genetic changes. Consequently, EPB41L4A is a candidate gene associated with the neurogenic phenotype.

Abstract The possibility that risks interact with spatial information (such as the SNARC effect) has been explored but studies did not demonstrate a consistent left-to-right representation of risks. This is probably due to the perception of risk being different in each individual experience. The present study aimed to clarify the spatial characteristics of acute deterioration risks perceived from illnesses. Registered nurses and general students participated in the present experiment. They were instructed to judge, by pressing one of the left/right response buttons, whether the risk of a given target (illness name) presented on a computer screen was higher or lower compared to that of a standard stimulus. Reaction times to the target were measured. No spatial-risk association was observed in the comprehensive analysis, but further inspection revealed that approximately half of the participants have a left-to-right representation and the other half have a right-to-left representation. Moreover, participants’ responses appeared to be faster when the target was representationally farther away from the standard stimulus (i.e., distance effect). These findings therefore suggest a spatially aligned magnitude representation of acute deterioration risk (i.e., mental risk line) but this horizontal risk orientation is likely to be dichotomous depending on the individuals and/or given situations.

Background: The prognostic significance of liver dysfunction in COVID-19 patients remains unclear. In this study, we investigated the association between liver function test results and severe disease progression in COVID-19 patients. Methods: This retrospective study included consecutive Japanese COVID-19 patients admitted between February 2020 and July 2021. Predictive variables for severe disease progression were identified by multivariate logistic regression analysis. Severe disease-free survival was estimated with the Kaplan–Meier method and Cox regression analysis. Aspartate aminotransferase (AST) was divided into three grades: grade 1, AST < 30 U/L; grade 2, 30 U/L ≤ AST < 60 U/L; and grade 3, AST > 60 U/L. Results: Among 604 symptomatic patients, 141 (23.3%) developed severe disease at a median of 2 days postadmission. The median hospital stay was 10 days, and 43 patients (7.1%) died during hospitalization. Multivariate regression analysis revealed that hypertension, decreased lymphocyte count, and elevated LDH, CRP, and AST levels (grade 2 and grade 3 relative to grade 1) were the significant predictive variables. Severe disease-free survival time was significantly different between the different AST grades (hazard ratio (HR): grade 2 vs. grade 1, 4.07 (95% confidential interval (CI): 2.06–8.03); grade 3 vs. grade 1, 7.66 (95% CI: 3.89–15.1)). Conclusions: The AST level at admission was an independent risk factor for severe disease in hospitalized Japanese patients with COVID-19.

Abstract Background: Sea anemones are well known to contain multiple peptide toxins. However, of more than 1100 species of sea anemones distributed worldwide, only a little over 50 have been studied for peptide toxins. Therefore, innumerable unique and novel peptide toxins remain to be discovered in unstudied sea anemones. Methods: Isolation of peptide toxins in the sea anemone Heteractis aurora was attempted by gel filtration and reverse-phase high performance liquid chromatography, using the toxicity to crabs as an index. The amino acid sequences of the isolated four toxins (Hau I-IV) and their precursors were determined using a combination of protein sequencing and cDNA cloning. Results: Hau I and IV were potently lethal to crabs, whereas Hau II and III were only paralytic. The precursor proteins of the four toxins were commonly composed of a signal peptide, a propart, and the remaining region including a mature peptide. Interestingly, four and two copies of the mature peptide were present in the precursor proteins of Hau II and III, respectively. Homology searches revealed that Hau I (30 amino acid residues) is a novel peptide toxin, although it has the same cysteine pattern CXXC-C-C as the boundless β-hairpin (BBH) family. Hau II (27 amino acid residues) and III (28 amino acid residues) were homologous with the BBH family, whereas Hau IV (49 amino acid residues) was a new member of the well-known type 1 sodium channel toxin family. Conclusion: This study showed that a novel class of toxin (Hau I), two BBH family toxins (Hau II and III), and a type 1 sodium channel toxin (Hau IV) are present in the toxin of the sea anemone H. aurora.

Abstract Background Previous systematic reviews suggest that nurse-led interventions improve short-term blood pressure (BP) control for people with hypertension. However, the long-term effects, adverse events, and appropriate target BP level are unclear. This study aimed to evaluate the long-term efficacy and safety of nurse-led interventions. Methods We conducted a systematic review and meta-analysis. We searched the Cochrane Central Register of Controlled Trials, PubMed, and CINAHL, as well as three Japanese article databases, as relevant randomized controlled trials from the oldest possible to March 2021. This search was conducted on 17 April 2021. We did an update search on 17 October 2023. We included studies on adults aged 18 years or older with hypertension. The treatments of interest were community-based nurse-led BP control interventions in addition to primary physician-provided care as usual. The comparator was usual care only. Primary outcomes were long-term achievement of BP control goals and serious adverse events (range: 27 weeks to 3 years). Secondary outcomes were short-term achievement of BP control goals and serious adverse events (range: 4 to 26 weeks), change of systolic and diastolic BP from baseline, medication adherence, incidence of hypertensive complications, and total mortality. Results We included 35 studies. Nurse-led interventions improved long-term BP control (RR 1.10, 95%CI 1.03 to 1.18). However, no significant differences were found in the short-term effects of nurse-led intervention compared to usual care about BP targets. Little information on serious adverse events was available. There was no difference in mortality at both terms between the two groups. Establishing the appropriate target BP from the extant trials was impossible. Conclusions Nurse-led interventions may be more effective than usual care for achieving BP control at long-term follow-up. It is important to continue lifestyle modification for people with hypertension. We must pay attention to adverse events, and more studies examining appropriate BP targets are needed. Nurse-led care represents an important complement to primary physician-led usual care.

ABSTRACT Purpose: Amid rising health awareness, natural products which has milder effects than medical drugs are becoming popular. However, only few systems can quantitatively assess their impact on living organisms. Therefore, we developed a deep-learning system to automate the counting of cells in a gerbil model, aiming to assess a natural product’s effectiveness against ischemia. Methods: The image acquired from paraffin blocks containing gerbil brains was analyzed by a deep-learning model (fine-tuned Detectron2). Results: The counting system achieved a 79%-positive predictive value and 85%-sensitivity when visual judgment by an expert was used as ground truth. Conclusions: Our system evaluated hydrogen water’s potential against ischemia and found it potentially useful, which is consistent with expert assessment. Due to natural product’s milder effects, large data sets are needed for evaluation, making manual measurement labor-intensive. Hence, our system offers a promising new approach for evaluating natural products.

Abstract A young patient diagnosed with advanced colon cancer and liver metastasis was found to have familial adenomatous polyposis (FAP) through comprehensive genomic analysis. Whole-genome array comparative genomic hybridization (aCGH) revealed germline deletions at chromosome 5q22.1-22.2 encompassing the entire APC gene. The patient and her son exhibited mild intellectual disability without developmental delay. This case highlights the need for further exploration of the characteristics associated with whole APC deletions. aCGH is a valuable tool for studying FAP and provides a detailed analysis of large deletions.

The glomerular filtration barrier (GFB), composed of endothelial cells, glomerular basement membrane, and podocytes, is a unique structure for filtering blood while detaining plasma proteins according to size and charge selectivity. Structurally, the fenestrated endothelial cells, which align the capillary loops, are in close proximity to mesangial cells. Podocytes are connected by specialized intercellular junctions known as slit diaphragms and are separated from the endothelial compartment by the glomerular basement membrane. Podocyte-endothelial cell communication or crosstalk is required for the development and maintenance of an efficient filtration process in physiological conditions. In pathological situations, communication also has an essential role in promoting or delaying disease progression. Podocytes and endothelial cells can secrete signaling molecules, which act as crosstalk effectors and, through binding to their target receptors, can trigger bidirectional paracrine or autocrine signal transduction. Moreover, the emerging evidence of extracellular vesicles derived from various cell types engaging in cell communication has also been reported. In this review, we summarize the principal pathways involved in the development and maintenance of the GFB and the progression of kidney disease, particularly in kidney transplantation.

Simultaneous and cooperative muscle activation results in involuntary posture stabilization in vertebrates. However, the mechanism through which more muscles than joints contribute to this stabilization remains unclear. We developed a computational human body model with 949 muscle action lines and 22 joints and examined muscle activation patterns for stabilizing right upper or lower extremity motions at a neutral body posture (NBP) under gravity using actor–critic reinforcement learning (ACRL). Two feedback control models (FCM), muscle length change (FCM–ML) and joint angle differences, were applied to ACRL with a normalized Gaussian network (ACRL–NGN) or deep deterministic policy gradient. Our findings indicate that among the six control methods, ACRL–NGN with FCM–ML, utilizing solely antagonistic feedback control of muscle length change without relying on synergy pattern control or categorizing muscles as flexors, extensors, agonists, or synergists, achieved the most efficient involuntary NBP stabilization. This finding suggests that vertebrate muscles are fundamentally controlled without categorization of muscles for targeted joint motion and are involuntarily controlled to achieve the NBP, which is the most comfortable posture under gravity. Thus, ACRL–NGN with FCM–ML is suitable for controlling humanoid muscles and enables the development of a comfortable seat design.

IntroductionThe dysregulation of cell fate toward osteoprecursor cells associated with most GNAS-based disorders may lead to episodic de novo extraskeletal or ectopic bone formation in subcutaneous tissues. The bony lesion distribution suggests the involvement of abnormal differentiation of mesenchymal stem cells (MSCs) and/or more committed precursor cells. Data from transgenic mice support the concept that GNAS is a crucial factor in regulating lineage switching between osteoblasts (OBs) and adipocyte fates. The mosaic nature of heterotopic bone lesions suggests that GNAS genetic defects provide a sensitized background for ectopic osteodifferentiation, but the underlying molecular mechanism remains largely unknown.MethodsThe effect of GNAS silencing in the presence and/or absence of osteoblastic stimuli was evaluated in the human L88/5 MSC line during osteodifferentiation. A comparison of the data obtained with data coming from a bony lesion from a GNAS-mutated patient was also provided.ResultsOur study adds some dowels to the current fragmented notions about the role of GNAS during osteoblastic differentiation, such as the premature transition of immature OBs into osteocytes and the characterization of the differences in the deposed bone matrix.ConclusionWe demonstrated that our cell model partially replicates the in vivo behavior results, resulting in an applicable human model to elucidate the pathophysiology of ectopic bone formation in GNAS-based disorders.

The virulence of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), depends on the expression of toxins and virulence factors controlled by the quorum-sensing (QS) system, encoded on the virulence accessory gene regulator (agr) locus. The aim of this study was to identify a phytochemical that inhibits Agr-QS function and to elucidate its mechanism. We screened 577 compounds and identified physalin H, physalin B, and isophysalin B—–phytochemicals belonging to physalins found in plants of the Solanaceae family—–as novel Agr-QS modulators. Biological analyses and in vitro protein–DNA binding assays suggested that these physalins suppress gene expression related to the Agr-QS system by inhibiting binding of the key response regulator AgrA to the agr promoters, reducing the function of hemolytic toxins downstream of these genes in MRSA. Furthermore, although physalin F suppressed gene expression in the Agr-QS system, its anti-hemolytic activity was lower than that of physalins H, B, and isophysalin B. Conversely, five physalins isolated from the same plant with the ability to suppress Agr-QS did not reduce bacterial Agr-QS activity but inhibited AgrA binding to DNA in vitro. A docking simulation revealed that physalin interacts with the DNA-binding site of AgrA in three docking states. The carbonyl oxygens at C-1 and C-18 of physalins, which can suppress Agr-QS, were directed to residues N201 and R198 of AgrA, respectively, whereas these carbonyl oxygens of physalins, without Agr-QS suppression activity, were oriented in different directions. Next, 100-ns molecular dynamics simulations revealed that the hydrogen bond formed between the carbonyl oxygen at C-15 of physalins and L186 of AgrA functions as an anchor, sustaining the interaction between the carbonyl oxygen at C-1 of physalins and N201 of AgrA. Thus, these results suggest that physalin H, physalin B, and isophysalin B inhibit the interaction of AgrA with the agr promoters by binding to the DNA-binding site of AgrA, suppressing the Agr-QS function of S. aureus. Physalins that suppress the Agr-QS function are proposed as potential lead compounds in the anti-virulence strategy for MRSA infections.

In hydrated soft biological tissues experiencing edema, which is typically associated with various disorders, excessive fluid accumulates and is encapsulated by impermeable membranes. In certain cases of edema, an indentation induced by pressure persists even after the load is removed. The depth and duration of this indentation are used to assess the treatment response. This study presents a mixture theory-based approach to analyzing the edematous condition. The finite element analysis formulation was grounded in mixture theory, with the solid displacement, pore water pressure, and fluid relative velocity as the unknown variables. To ensure tangential fluid flow at the surface of tissues with complex shapes, we transformed the coordinates of the fluid velocity vector at each time step and node, allowing for the incorporation of the transmembrane component of fluid flow as a Dirichlet boundary condition. Using this proposed method, we successfully replicated the distinct behavior of pitting edema, which is characterized by a prolonged recovery time from indentation. Consequently, the proposed method offers valuable insights into the finite element analysis of the edematous condition in biological tissues.

Crinum asiaticum L. (Amaryllidaceae) is a perennial bulbous herb, locally utilized for possessing multifaceted pharmacological properties including anticancer, immune-stimulating, analgesic, antiviral, antimalarial, antibacterial and antifungal, in addition to its popularity as an aesthetic plant. Separation of MeOH extract of C. asiaticum leaves yielded three known compounds as cycloneolitsol (1), hippeastrine (2) and β-sitosterol (3). Among these, compounds 1 and 2 were subjected to the cytotoxic assay and found that they induced mild effect against HCT116, Huh7 and DU145 cell lines with the IC50 values from 73.76 to 132.53 μM. When tested for TRAIL-resistance abrogating activity, 1 (100 μM) along with TRAIL (100 ng/mL) showed moderate activity in AGS cells producing 25 % more inhibition than the agent alone. Whereas 2 (20 and 30 μM) in combination with TRAIL (100 ng/mL) exhibited strong activity in abrogating TRAIL-resistance and caused 34 % and 36 % more inhibition in AGS cells, respectively. The in-silico studies of compound 2 revealed high docking hits with the TRAIL-associated anti-apoptotic proteins which give a justification for the regulatory interactions to induce such abrogating activity. It is still recommended to conduct further investigations to understand their exact molecular mechanism.

The phenomenon of lithic miniaturization during the Late Pleistocene at times coincided with increased artifact standardization and cutting edge efficiency-likely reflecting the use of small, sharp artifacts as interchangeable inserts for composite cutting tools and hunting weapons. During Marine Isotope Stage 2, Upper Paleolithic toolmakers in northern East Asia specifically used pressure techniques to make small, highly standardized lithic artifacts called microblades. However, little is currently known about how microblades affected the cutting edge efficiency of the toolkits they were a part of. We applied three methods of analyzing cutting edge efficiency to two Upper Paleolithic assemblages recently excavated from Tolbor-17, Mongolia, that document the periods before and after the introduction of microblade technology to the Tolbor Valley. A model incorporating allometric relationships between blank cutting edge length and mass suggests no difference in efficiency between the two periods, while two more conventional approaches both indicate a significant increase. The potential for improved cutting edge efficiency is only observed when the microblade sample is artificially inflated via simulation. Our results highlight challenges related to detecting and interpreting archaeological differences in cutting edge efficiency at the assemblage level.

Abstract Figurative depictions in art first occur ca. 50,000 years ago in Europe, Africa, and Southeast Asia. Considered by most as an advanced form of symbolic behavior, they are restricted to our species. Here, we report a piece of ornament interpreted as a phallus-like representation. It was found in a 42,000 ca.-year-old Upper Paleolithic archaeological layer at the open-air archaeological site of Tolbor-21, in Mongolia. Mineralogical, microscopic, and rugosimetric analyses points toward the allochthonous origin of the pendant and a complex functional history. Three-dimensional phallic pendants are unknown in the Paleolithic record, and this discovery predates the earliest known sexed anthropomorphic representation. It attests that hunter-gatherer communities used sex anatomical attributes as symbols at a very early stage of their dispersal in the region. The pendant was produced during a period that overlaps with age estimates for early introgression events between Homo sapiens and Denisovans, and in a region where such encounters are plausible.

Abstract Slow rocking chairs can easily put people to sleep, while violent shaking, such as during earthquakes, may lead to rapid awakening. However, the influence of external body vibrations on arousal remains unclear. Herein, a computational model of a locus coeruleus (LC)-norepinephrine (NE) system and cardio-respiratory system were used to show that respiratory entrainment of the LC modulates arousal levels, which is an adaptation to avoid physical risks from external vibration. External vibrations of sinusoidal waves with different frequencies ranging from 0.1 to 20 [Hz] were applied to the LC based on the results of previous studies. We found that respiratory entrainment of the LC decreased the breathing rate (BR) and heart rate (HR) to maintain the HR within its normal range. Furthermore, 1:1 phase locking enhanced arousal level while phase-amplitude coupling decreased it for larger vibration stimuli. These findings suggest that respiratory entrainment of the LC might automatically modulate cardio-respiratory system homeostasis and arousal levels for performance readiness (fight/flight or freeze) to avoid physical risks from larger external vibrations.

Abstract Aim The current study compared the postoperative quality of life (QOL) between the esophagogastrostomy method (PGEG) and double tract method (PGDT) after proximal gastrectomy using the Postgastretomy Syndrome Assessment Scale (PGSAS)‐45. Methods Among the 2364 patients who received the PGSAS‐45 questionnaire, 300 PGEG and 172 PGDT cases responded. The main outcomes measures (MOMs) consisted of seven subscales (SS) covering symptoms, meals (amount and quality), ability to work, dissatisfaction with daily life, physical and mental component summary of the 8‐Item Short Form Health Survey (SF‐8), and change in body weight, and were compared between PGEG and PGDT. Results Overall, PGDT promoted significantly better constipation SS scores (p

Abstract Idiopathic pulmonary fibrosis (IPF) is a severe and progressive chronic fibrosing interstitial lung disease with causes that have remained unclear to date. Development of effective treatments will require elucidation of the detailed pathogenetic mechanisms of IPF at both the molecular and cellular levels. With a biomedical corpus that includes IPF-related entities and events, text-mining systems can efficiently extract such mechanism-related information from huge amounts of literature on the disease. A novel corpus consisting of 150 abstracts with 9297 entities intended for training a text-mining system was constructed to clarify IPF-related pathogenetic mechanisms. For this corpus, entity information was annotated, as were relation and event information. To construct IPF-related networks, we also conducted entity normalization with IDs assigned to entities. Thereby, we extracted the same entities, which are expressed differently. Moreover, IPF-related events have been defined in this corpus, in contrast to existing corpora. This corpus will be useful to extract IPF-related information from scientific texts. Because many entities and events are related to lung diseases, this freely available corpus can also be used to extract information related to other lung diseases such as lung cancer and interstitial pneumonia caused by COVID-19.

ABSTRACT USA300, a major Panton–Valentine leukocidin (PVL)-producing methicillin-resistant Staphylococcus aureus (MRSA) clone associated with skin and soft tissue infections (SSTIs), carries a type IV staphylococcal cassette chromosome mec (SCCmec) element. Recently, a USA300 variant, ΨUSA300, with a 12-bp deletion of ccrB2 in the SCCmec element, was identified in Japan by Takadama et al. (15). To understand the current status of PVL-positive MRSA in the community, a nationwide surveillance of MRSA isolated from outpatients at dermatology departments was conducted. This study included 1,619 outpatients who visited dermatology departments at 22 healthcare facilities in 11 prefectures in Japan between 2018 and 2021; S. aureus were isolated from these outpatients. Molecular epidemiological analysis was performed using PCR, SCCmec and spa typing, pulsed-field gel electrophoresis, multilocus sequence typing, and antimicrobial susceptibility testing. A total of 980 S. aureus were isolated, 293 of which were identified as MRSA. Among MRSA isolates, PVL genes were detected in 18 of 63 (28.6%) in 2018, 34 of 85 (40.0%) in 2019, 29 of 65 (44.6%) in 2020, and 40 in 80 (50.0%) in 2021. Among the PVL-positive MRSA, 16 of 121 (13.2%) and 94 of 121 (77.7%) isolates were identified as USA300 and ΨUSA300, respectively. ΨUSA300 strains were collected from six prefectures in Japan: Kagawa, Osaka, Tokyo, Kanagawa, Fukushima, and Saitama. ΨUSA300 was isolated more frequently than USA300 from patients with deep-seated SSTIs (P < 0.05). Our findings showed that PVL-positive MRSA isolates were significantly increased in the Japanese community. Furthermore, the USA300 variant ΨUSA300 has emerged as the predominant PVL-positive MRSA clone across the Kanto, Kinki, and Shikoku regions of Japan, and this variant may possess a greater propensity to cause deep-seated SSTIs than in USA300. IMPORTANCE USA300 is an MRSA clone producing PVL, a toxin associated with SSTIs. ΨUSA300 is a USA300 variant recently identified in Japan by Takadama et al. (15). Here, we found that the prevalence rate of PVL-positive MRSA in S. aureus was elevated in the Japanese community, and ΨUSA300 accounted for most of them. ΨUSA300 strains have been isolated from several areas in Japan and were associated with deep-seated SSTIs. This study highlighted the emerging threat posed by ΨUSA300 in Japan.

A transformable wheel designed in this study is proposed to meet the increasingly complex travel requirements of people because it is urgent to provide a smooth and barrier-free travel scheme in complex and changeable urban land. The transformable wheel, with 10 pivoting-head parts, allows vehicles with the wheels to surmount low-height obstacles that deliberately complicates the terrain such as blind roads, small steps, bumps and door sills, and to achieve low-consumption travel. In this study, we demonstrate that the transformable wheels improve its performance by nearly 30% under the road conditions of low-height obstacles and is especially suitable for carts and suitcases passing through low-height obstacles such as blind lanes and low stairs.

Abstract Background The emerging concepts of fetal-like reprogramming following tissue injury have been well recognized as an important cue for resolving regenerative mechanisms of intestinal epithelium during inflammation. We previously revealed that the remodeling of mesenchyme with collagen fibril induces YAP/TAZ-dependent fate conversion of intestinal/colonic epithelial cells covering the wound bed towards fetal-like progenitors. To fully elucidate the mechanisms underlying the link between extracellular matrix (ECM) remodeling of mesenchyme and fetal-like reprogramming of epithelial cells, it is critical to understand how collagen type I influence the phenotype of epithelial cells. In this study, we utilize collagen sphere, which is the epithelial organoids cultured in purified collagen type I, to understand the mechanisms of the inflammatory associated reprogramming. Resolving the entire landscape of regulatory networks of the collagen sphere is useful to dissect the reprogrammed signature of the intestinal epithelium. Methods We performed microarray, RNA-seq, and ATAC-seq analyses of the murine collagen sphere in comparison with Matrigel organoid and fetal enterosphere (FEnS). We subsequently cultured human colon epithelium in collagen type I and performed RNA-seq analysis. The enriched genes were validated by gene expression comparison between published gene sets and immunofluorescence in pathological specimens of ulcerative colitis (UC). Results The murine collagen sphere was confirmed to have inflammatory and regenerative signatures from RNA-seq analysis. ATAC-seq analysis confirmed that the YAP/TAZ-TEAD axis plays a central role in the induction of the distinctive signature. Among them, TAZ has implied its relevant role in the process of reprogramming and the ATAC-based motif analysis demonstrated not only Tead proteins, but also Fra1 and Runx2, which are highly enriched in the collagen sphere. Additionally, the human collagen sphere also showed a highly significant enrichment of both inflammatory and fetal-like signatures. Immunofluorescence staining confirmed that the representative genes in the human collagen sphere were highly expressed in the inflammatory region of ulcerative colitis. Conclusions Collagen type I showed a significant influence in the acquisition of the reprogrammed inflammatory signature in both mice and humans. Dissection of the cell fate conversion and its mechanisms shown in this study can enhance our understanding of how the epithelial signature of inflammation is influenced by the ECM niche.

Abstract Recently, direct oral anticoagulants (DOACs) have been widely used as antithrombotic agents to replace warfarin, but their clinical impact in patients with gastrointestinal bleeding is unclear. We compared the effects of warfarin and DOACs on the outcomes of patients with colonic diverticular bleeding. The patients were divided into warfarin and DOAC groups. We compared the clinical outcomes and the effect of the DOAC dosing and examined any readmissions due to colonic diverticular bleeding within 1 year. A total of 95 events (warfarin group: n = 43 and DOAC group: n = 52) were included. Compared with the warfarin group, the DOAC group was significantly older, had a lower rate of concomitant antiplatelet agents, and a shorter hospital stay, but no significant differences were found in the other clinical outcomes. Thirty-seven patients (71.2%) in the DOAC group had appropriate dosing, whereas 15 patients (28.9%) had an inappropriate dose. The patients with overdose or contraindications had significantly lower minimum hemoglobin levels. In the univariate analysis, prior hospitalization for colonic diverticular bleeding was a significant predictor of readmission. Compared with warfarin, patients with colonic diverticular bleeding treated with DOACs were older and had shorter hospital stays, and the inappropriate use of DOACs may worsen outcomes.

In the super-aged society, the social role of nursing care industries is increasing. Many workers in the industries have the low back pain. Countermeasures to prevent it in the field of nursing care are urgent issues. One of the causes of the low back pain is known as an increase in lumbar intervertebral pressure. However, it is very difficult to measure the lumbar intervertebral pressure in a non-invasive manner. The goal of this research is to develop a human body finite element (FE) model to estimate physical burden such as the low back pain. In this paper, we investigated the validity of model prediction such as muscle activity and intervertebral disc pressures in a half-crouching position, which is a common posture causing the low back pain. An experiment using a human adult male volunteer was conducted to compare with the prediction results. The participant kept a half-crouching position while holding a box with his both hands. Activity of 16 superficial muscles was measured in three conditions of 0.6 kg, 9.2 kg, and 18.0 kg as the weight of the box. Under three conditions similar to the experiment, the muscle activity and intervertebral disc pressures when holding a box in a half-crouching posture were calculated using the human body FE model. The trend of change in the calculated muscle activation levels for each box weight generally showed good agreement with the experimental data. Predicted results of intervertebral disc pressures from the third lumbar to the fifth lumbar spine vertebra generally agreed with test data obtained from the literature. Muscle activity and distributions of intradiscal pressures, muscle contractile forces, and tensile strains of muscle and tendon changed according to the weight of the box. These results demonstrated that this model has the possibility of evaluating physical burden when holding a box.

Abstract Aim Total gastrectomy results in the complete loss of gastric function and the development of severe postgastrectomy syndrome. During the jejunal pouch procedure following total gastrectomies, a substitute stomach is created to alleviate the effects of postgastrectomy syndrome. However, the procedure's effectiveness remains controversial. This study aimed to explore the effect of jejunal pouch creation after total gastrectomy on postoperative quality of life. Methods A nationwide multi‐institutional cross‐sectional study, the Postgastrectomy Syndrome Assessment study NEXT, used the Postgastrectomy Syndrome Assessment Scale‐45 questionnaire to explore the optimal gastrectomy procedure for cancer located in the upper third of the stomach or around the esophagogastric junction. The questionnaire consists of 45 items consolidated into 19 main outcome measures relating to postgastrectomy symptoms, amount of food ingested, quality of ingestion, ability for working, level of satisfaction for daily life, and the physical and mental component summary of the 8‐Item Short Form Health Survey. Eligible completed questionnaires were retrieved from 1909 patients. Of these, the data were analyzed for 1020 patients who underwent total gastrectomy and 93 patients who underwent jejunal pouch creation after total gastrectomy. Results Postoperative quality of life was compared between patients with and without pouches. The analysis revealed that patients with pouches, particularly oral pouches, experienced substantially improved postoperative quality of life than those without, even after adjusting for several clinical factors using multiple regression analyses. Conclusion The results suggest that total gastrectomy with jejunal pouch creation, particularly oral pouches, may significantly improve postoperative quality of life.

Abstract Aim To identify whether the coronavirus disease 2019 (COVID‐19) pandemic affects the operational efficiency of emergency medical services (EMS) and the survival rate of out‐of‐hospital cardiac arrest (OHCA) in prehospital settings. Methods We conducted a population‐based cohort study in Kobe, Japan, between March 1, 2020, and September 31, 2022. In study 1, the operational efficiency of EMS, such as the total out‐of‐service time for ambulances, the daily occupancy rate of EMS, and response time, was compared between the pandemic and nonpandemic periods. In study 2, the impacts of the changes in EMS operational efficiency were investigated among patients with OHCA, with 1‐month survival as the primary outcome and return of spontaneous circulation, 24‐h survival, 1‐week survival, and favorable neurological outcomes as the secondary outcomes. Logistic regression analysis was conducted to identify the factors associated with survival among patients with OHCA. Results The total out‐of‐service time, occupancy rate, and response time significantly increased during the pandemic period (p

Abstract Background and Aim Obesity is a well‐known risk factor for the development and severity of acute pancreatitis (AP), but the relationship between the abdominal visceral fat area (VFA) and mortality is unclear. We evaluated the effect of the VFA on mortality in severe AP (SAP). Methods This retrospective, single‐center cohort study examined 119 consecutive patients with SAP from April 2009 to March 2019. The VFA at the umbilical level was assessed using computed tomography. The primary endpoint was to evaluate whether visceral obesity affects mortality in SAP. Results The median age was 63 years, and 66% of participants were male. Nine patients (7.5%) died during their hospital stay. The median body mass index (BMI) was 22.2 kg/m2, and six obese patients had a BMI of over 30 kg/m2 (5%). The median waist circumference and VFA were 85.5 cm and 112 cm2, respectively. Sixty‐eight (57.1%) patients had a VFA over 100 cm2. The prognostic factor score based on the Japanese guidelines for AP management (cutoff value [COV], 4; area under the curve [AUC] = 0.869) and age [COV, 72; AUC = 0.780]) showed moderate accuracy for predicting mortality, followed by the VFA (COV, 167 cm2; AUC = 0.679). Univariate logistic analysis, but not multivariate analysis, showed that an increased VFA was associated with a significantly higher odds ratio (OR) for predicting mortality (OR: 4.38, P = 0.0406). The survival times of SAP patients with and without an increased VFA of 167 cm2 were not significantly different. Conclusions Visceral obesity did not have a significant impact on predicting mortality in patients with SAP.

This paper proposes a hardware accelerator design for motorcycle detection based on deep learning. We designed the training parameters by K-means algorithm and created the motorcycle dataset from Thailand's urban scene. Due to the rapid evolution of deep learning and the need for high-performance, low-power, and scalable models for application platforms, we designed the YOLOv2 accelerator architecture on the PYNQ platforms by using five optimization methods, including loop unrolling/pipeline, loop tiling, data quantization, memory ping-pong, and multi-channel data transmission. The proposed training parameters can increase the accuracy from the original 76.8% to 89.45%. The hardware experimental results obtained 14.10 GOP/s (100MHz) and 25.98 GOP/s (150MHz) on the PYNQ (ZYNQ 7020). The performance of the acceleration platform that we designed is 6.32 times faster than that of the CPU (i7), and the energy consumption is 1/26 of the CPU. In addition, the hardware accelerated deep learning applications have in recent years improved a lot in accuracy and calculation speed.

The definition of homelessness and the policies responding to it differ from society to society, as does understanding a state of being "homeless", all of which are socially constructed. Because in Japan today homelessness is perceived only as a situation of sleeping on the street, the prevalence is perceived as low. However, this definition is narrow compared to what, for example, FEANTSA has proposed in Europe. Therefore, Japanese policy and policy makers need to shift to be congruent with international standards. To begin this shift we need to understand how the "narrow" perception of homelessness in Japan has been constructed. Therefore, in this paper a historical review is provided starting on the premise of the "loss of home" of Japanese society after World War II, the rapid increase of "visible homelessness" since the 1990s, the enactment of formal homelessness law, and rising "visible homelessness". More recently there is also expanded interest in "invisible homelessness" due to current homelessness research. The issue of lack of a public housing allowance and limited public housing is explored connected to an absence of housing policy. Finally, the Covid-19 pandemic has increased anxiety about the loss of homes and there is a need to shift homelessness measures into housing policy.

IntroductionHigh serum levels of fibroblast growth factor 23 (FGF23) characterize chronic kidney disease (CKD) since its early stages and have been suggested to contribute to inflammation and cardiovascular disease. However, the mechanisms linking FGF23 with these pathological conditions remain still incompletely defined. The alpha-2-HS-glycoprotein (AHSG), a liver-produced anti-inflammatory cytokine, is highly modulated by inflammation itself, also through the TNFα/NFκB signaling pathway. In our previous study, we found that FGF23 modulates the production of AHSG in the liver in a bimodal way, with stimulation and inhibition at moderately and highly increased FGF23 concentrations, respectively.MethodsThe present study, aiming to gain further insights into this bimodal behavior, was performed in hepatocyte human cells line (HepG2), using the following methods: immunochemistry, western blot, chromatin immunoprecipitation, fluorescence in situ hybridization (FISH), qRT-PCR, and gene SANGER sequencing.ResultsWe found that FGF23 at 400 pg/ml activates nuclear translocation of NFκB, possibly increasing AHSG transcription. At variance, at 1,200 pg/ml, FGF23 inactivates NFκB through the activation of two specific NFκB inhibitors (IκBα and NKIRAS2) and induces its detachment from the AHSG promoter, reducing AHSG transcription.ConclusionThese results add another piece to the puzzle of FGF23 involvement in the multifold interactions between CKD, inflammation, and cardiovascular disease, suggesting the involvement of the NFκB pathway, which might represent a potential therapeutic target in CKD.

Irinotecan (CTP-11) is one of the standard therapies for colorectal cancer (CRC). CTP-11 is enzymatically converted to the hydrophobic 7-ethyl-10-hydroxycamptothecin (SN38), a one hundred-fold more active metabolite. Conjugation of hydrophobic anticancer drugs to nanomaterials is a strategy to improve their solubility, efficacy, and selectivity. Carbon dots (CDs) have garnered interest for their small sizes (

The purpose of this study was to examine and compare Mongolians (118 men and 252 women) and Japanese (158 men and 201 women) university students’ awareness related to their occupation and their motivations for entering university. The survey focused on the vocational motives, university performance/experiences, and motivations for entering university. The analyses showed that although Mongolian and Japanese students have similar occupational views, there are some cultural differences that can be mainly identified with the recent historic developments and social changes both the nations experienced (e.g socialistic era in Mongolia).

Abstract The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

A 69-year-old man presented with jaundice and appetite loss. Blood analyses showed elevated aminotransferase levels, hyperbilirubinemia, positivity for antinuclear antibody, elevated immunoglobulin (Ig) G4 levels, and negativity for hepatitis virus markers. Additionally, computed tomography revealed a focal enlargement of the pancreatic body and enhancement of the peripheral bile ducts. Liver biopsy showed interface hepatitis, supporting a clinical diagnosis of autoimmune hepatitis (AIH). Immunohistochemistry revealed that IgG4-bearing plasma cells accounted for more than 60% of the IgG-bearing plasma cells in the portal area. Then, we started oral prednisolone therapy. After tapering, serum transaminase levels became elevated again, and we had to adjust the dose. Azathioprine maintenance therapy was necessary to prevent relapse. We herein report a case of IgG4-hepatopathy with a clinical course similar to that of AIH with acute onset.

In leukemia, a distinct subpopulation of cancer-initiating cells called leukemia stem cells (LSCs) is believed to drive population expansion and tumor growth. Failing to eliminate LSCs may result in disease relapse regardless of the amount of non-LSCs destroyed. The first step in targeting and eliminating LSCs is to identify and characterize them. Acute precursor B lymphoblastic leukemia (B-ALL) cells derived from patients were incubated with fluorescent glucose analog 2-(N-(7-Nitrobenz-2-oxa-1, 3-diazol-4-yl) Amino)-2-Deoxyglucose (NBDG) and sorted based on NBDG uptake. Cell subpopulations defined by glucose uptake were then serially transplanted into mice and evaluated for leukemia initiating capacity. Gene expression profiles of these cells were characterized using RNA-Sequencing (RNA-Seq). A distinct population of NBDG-low cells was identified in patient B-ALL samples. These cells are a small population (1.92% of the entire leukemia population), have lower HLA expression, and are smaller in size (4.0 to 7.0 μm) than the rest of the leukemia population. All mice transplanted with NBDG-low cells developed leukemia between 5 and 14 weeks, while those transplanted with NBDG-high cells did not develop leukemia (p ≤ 0.0001-0.002). Serial transplantation of the NBDG-low mouse model resulted in successful leukemia development. NBDG-medium (NBDG-med) populations also developed leukemia. Interestingly, comprehensive molecular characterization of NBDG-low and NBDG-med cells from patient-derived xenograft (PDX) models using RNA-Seq revealed a distinct profile of 2,162 differentially-expressed transcripts (DETs) (p

Summary: Background: In double-blind randomized controlled trials (RCTs) of antidepressants, blinding can be broken due to the apparent side effects, and unsuccessful blinding can lead to overestimation of effect sizes. New generation antidepressants with less severe side effects may be less susceptible to broken blinding. However, successfulness of blinding in new generation antidepressant trials and its influence on trial effect size estimates remain unclear. Methods: Extending a previous systematic review assessing blinding successfulness in psychiatric trials (2000-2010), we searched PubMed/Medline for double-blinded antidepressant RCTs (2010-2020) for trials assessing blinding success. Our primary outcome was the degree of blinding successfulness, measured as kappa statistics between guesses and true allocations. We used random-effects meta-analysis to synthesize studies. We used meta-regression and Pearson's r to examine the relationship between blinding success and effect sizes. This study is registered with PROSPERO (CRD42021249973). Findings: Among 154 eligible studies, 11 (7·1%) contained information on blinding assessment between 2010 and 2020. Five studies were added from the previous review, and altogether nine of the 16 studies provided usable data. Agreement in individual studies ranged from κ=-0·14 to 0·38. The summary agreement between guesses and the truth was 0·21 (95% CI: 0·14 to 0·28) among patients and 0·17 (95% CI: 0·05 to 0·30) among assessors. Blinding success was not associated with effect size (patients: r = 0·37, p = 0·32; assessors: r = 0·28; p = 0·72). Meta-regression also failed to find a significant relationship between blinding success and depression effect sizes (β=0·06, p = 0·09). Interpretation: Less than 10% of the antidepressant RCTs reported blinding assessment. The results in new generation antidepressant trials indicated that patients and assessors were unlikely to be able to judge treatment allocation. There was little evidence that the extent of unblinding biased the effect size estimates of new generation antidepressants. Funding: None.

BackgroundThe number of mobile health (mHealth) apps continues to rise each year. Widespread use of the Mobile App Rating Scale (MARS) has allowed objective and multidimensional evaluation of the quality of these apps. However, no Japanese version of MARS has been made available to date. ObjectiveThe purposes of this study were (1) to develop a Japanese version of MARS and (2) to assess the translated version’s reliability and validity in evaluating mHealth apps. MethodsTo develop the Japanese version of MARS, cross-cultural adaptation was used using a universalist approach. A total of 50 mental health apps were evaluated by 2 independent raters. Internal consistency and interrater reliability were then calculated. Convergent and divergent validity were assessed using multitrait scaling analysis and concurrent validity. ResultsAfter cross-cultural adaptation, all 23 items from the original MARS were included in the Japanese version. Following translation, back-translation, and review by the author of the original MARS, a Japanese version of MARS was finalized. Internal consistency was acceptable by all subscales of objective and subjective quality (Cronbach α=.78-.89). Interrater reliability was deemed acceptable, with the intraclass correlation coefficient (ICC) ranging from 0.61 to 0.79 for all subscales, except for “functionality,” which had an ICC of 0.40. Convergent/divergent validity and concurrent validity were also considered acceptable. The rate of missing responses was high in several items in the “information” subscale. ConclusionsA Japanese version of MARS was developed and shown to be reliable and valid to a degree that was comparable to the original MARS. This Japanese version of MARS can be used as a standard to evaluate the quality and credibility of mHealth apps.

Abstract Lindbladione (1) is a neural stem cell differentiation activator isolated from Lindbladia tubulina by our group. Hes1 dimerization inhibitory activity of lindbladione (1) was discovered using our original fluorescent Hes1 dimer microplate assay. We also found that lindbladione (1) accelerates the differentiation of neural stem cells. We conducted the first total synthesis of lindbladione (1) via Heck reaction of 1-hexene-3-one 7 with iodinated naphthoquinone 12, which was provided by Friedel–Crafts acylation followed by Claisen condensation, in the presence of Pd (II) acetate. Careful deprotection of the benzyl groups of 13 successively provided lindbladione (1). Synthesized lindbladione (1) exhibited potent Hes1 dimer inhibition (IC50 of 2.7 μM) in our previously developed fluorescent Hes1 dimer microplate assay. Synthesized lindbladione (1) also accelerated the differentiation of C17.2 mouse neural stem cells into neurons dose dependently, increasing the number of neurons by 59% (2.5 μM) and 112% (10 μM) compared to the control. These activities are comparable to those of naturally occurring lindbladione (1) isolated from L. tublina.

Abstract Background and Aim Although hemodialysis (HD) is a strong risk factor for postendoscopic sphincterotomy (ES) bleeding, additional risk factors in HD patients remain unclear. There is no model for predicting post‐ES bleeding risk in HD patients. Therefore, we conducted a retrospective multicenter study to reveal these risk factors and develop a predictive model of post‐ES bleeding in HD patients. Methods We retrospectively reviewed the medical records of HD patients who underwent ES at eight hospitals between January 2006 and December 2016, with post‐ES bleeding as the main outcome measure. Univariate analyses were performed to extract possible risk factors for post‐ES bleeding. Factors that were clinically important and statistically significant in our univariate analyses were then included in our logistic regression analysis for the development of a multivariate predictive model of post‐ES bleeding. This predictive model was visualized using a predictive nomogram. Results Post‐ES bleeding occurred in 20 (16.3%) of 123 HD patients. Based on clinically important factors and the results of our univariate analyses, platelet count, prothrombin time (international normalized ratio), and HD duration were included in our predictive model of post‐ES bleeding. Receiver operating characteristic analysis found that this model had an area under the curve of 0.715 (95% confidence interval, 0.609–0.822). We developed a predictive nomogram based on these results. Conclusions We demonstrated that post‐ES bleeding is more common in HD patients than in the general population and succeeded in constructing a predictive model that can effectively identify HD patients at risk of post‐ES bleeding.

Novel coronavirus (SARS-Coronavirus-2:SARS-CoV-2) which emerged in Wuhan, China, has spread to multiple countries rapidly. We report the first case of meningitis associated with SARS-CoV-2 who was brought in by ambulance due to a convulsion accompanied by unconsciousness. He had never been to any foreign countries. He felt generalized fatigue and fever (day 1). He saw doctors nearby twice (day 2 and 5) and was prescribed Laninamivir and antipyretic agents, His family visited his home and found that he was unconsciousness and lying on the floor in his vomit. He was immediately transported to this hospital by ambulance (day 9). Under emergency transport, he had transient generalized seizures that lasted about a minute. He had obvious neck stiffness. The specific SARS-CoV-2 RNA was not detected in the nasopharyngeal swab but was detected in a CSF. Anti- HSV 1 and varicella-zoster IgM antibodies were not detected in serum samples. A brain MRI showed hyperintensity along the wall of right lateral ventricle and hyperintense signal changes in the right mesial temporal lobe and hippocampus, suggesting the possibility of SARS-CoV-2 meningitis. This case warns the physicians of patients who have CNS symptoms.

BackgroundCurrent guidelines do not clarify whether older patients with advanced chronic kidney disease (CKD) may benefit of low protein (LP) diet if they are at risk of malnutrition. We compared the effects of normocalorie/normoprotein (NP) and normocalorie/LP diet on nutritional status and metabolic complications related to the progression of kidney damage in these patients.MethodsThis pilot study had an open-label randomized-controlled design (ClinicalTrials.gov Id: NCT05015647). Thirty-five patients were treated for 6 months with two different diets (LP = 17) and (NP = 18). Malnutrition was assessed by the Malnutrition Inflammation Score and International Society of Renal Nutrition and Metabolism criteria. Renal function was assessed by creatinine and cystatin-C-based estimated glomerular filtration rate (eGFR).ResultsAt the end of the study, Malnutrition Inflammation Score was improved in both LP and NP groups (respectively: 3 ± 3 vs. 6 ± 1.5, p = 0.020 and 3 ± 2.5 vs. 6 ± 2, p = 0.012), prevalence of protein energy wasting syndrome decreased only in LP. LP group had higher eGFRcys-C (17 ± 6 vs. 12 ± 4 ml/min/1.73 m2; p < 0.05), lower serum urea (105 ± 65 vs. 138 ± 30 mg/dl; p < 0.05) and lower parathormone (68 ± 10 vs. 99 ± 61 ng/L; p < 0.05) than NP. Serum and urinary phosphorous did not change while fibroblast growth factor 23 (FGF23)-intact and FGF23 c-terminal increased in both groups [FGF23-intact in LP: 70 (48; 98) vs. 126 (90; 410) pg/ml, p < 0.01 and in NP: 86 (57; 194) vs. 143 (119; 186) pg/ml, p < 0.01; FGF23 c-terminal in LP: 77 (30.3; 112) vs. 111 (63; 384) RU/ml, p < 0.01 and in NP: 142 (56.6; 175) vs. 157 (76.7; 281) RU/ml, p < 0.01].ConclusionsLP diet has a favorable impact on nutritional status as much as NP diet with possible greater benefits on the progression of kidney disease and some of its metabolic complications.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT05015647, identifier: NCT05015647.

Late Pleistocene hunter-gatherers in East Asia adopted pottery, yet the ability to reconstruct circulation, mobility, and exchange has been hampered, in part, due to problematic regional geochronology. The driving forces behind pottery adoption is unclear. The purpose of this study is to test our results of the first systematic petrographic pottery sourcing from the pre-Younger Dryas by utilizing neutron activation analysis. We examine samples from the Sankauyama I site on Tanegashima Island, southern Japan, dating to the Incipient Jomon, ca. 14,000/13,500–12,800 cal BP, with a well-defined geochronology. Our NAA results corroborate with the petrographic study suggesting that pottery was mainly produced in-situ, but some vessels were transported long distances from another island. Changing from high mobility, sedentary Incipient Jomon foragers made pottery, occasionally investing in long-distance ceramic vessel transportation and exchange likely involving ocean crossing. This may be associated with a risk-buffering strategy in the context of rising sea levels and isolation of Tanegashima.

Introduction: Previous studies have reported the effectiveness of inflammatory bowel disease (IBD) self-management. However, it is unclear which types of self-management interventions are effective. We conducted a systematic literature review to clarify the status and efficacy of self-management interventions for IBD. Methods: Searches were performed in databases including Embase, Medline, and Cochrane Library. Randomized, controlled studies of interventions in adult human participants with IBD involving a self-management component published in English from 2000 to 2020 were included. Studies were stratified based on study design, baseline demographic characteristics, methodological quality, and how outcomes were measured and analyzed for statistically significant improvements in outcomes, such as psychological health, quality of life, and healthcare resource usage. Results: Among 50 studies included, 31 considered patients with IBD and 14 and 5 focused on patients with ulcerative colitis and Crohn’s disease, respectively. Improvements in an outcome were reported in 33 (66%) studies. Most of the interventions that significantly improved an outcome index were based on symptom management and many of these were also delivered in combination with provision of information. We also note that among effective interventions, many were conducted with individualized and patient-participatory activities, and multidisciplinary healthcare practitioners were responsible for delivery of the interventions. Conclusion: Ongoing interventions that focus on symptom management with provision of information may support self-management behavior in patients with IBD. A participatory intervention targeting individuals was suggested to be an effective intervention method.

Autophagy is a fundamental process involved in regulating cellular homeostasis. Autophagy has been classically discovered as a cellular process that degrades cytoplasmic components non-selectively to produce energy. Over the past few decades, this process has been shown to work in energy production, as well as in the reduction of excessive proteins, damaged organelles, and membrane trafficking. It contributes to many human diseases, such as neurodegenerative diseases, carcinogenesis, diabetes mellitus, development, longevity, and reproduction. In this review, we provide important information for interpreting results related to autophagic experiments and present the role of autophagy in this field.

This paper presents an approach to the estimation of a window shape for increasing the adaptability of glass façade-cleaning robots to different buildings. For this approach, a window scanning robot equipped with a 2D laser range scanner installed perpendicularly to a window surface is developed for the testbed, and a method for the window shape estimation is proposed, which consists of the robot’s pose estimation with an extended Kalman filter (EKF) and the loop closure based on the robot’s pose estimated. The effectiveness of the proposed approach is demonstrated through an experiment that is carried out on a window placed on a floor. The experimental results show that the window scanning robot can acquire a window shape, moving on a window surface, and the proposed approach is effective in increasing the accuracy of the window shape estimation.

Given the abundant computational resources and the huge amount of data of compound–protein interactions (CPIs), constructing appropriate datasets for learning and evaluating prediction models for CPIs is not always easy. For this study, we have developed a web server to facilitate the development and evaluation of prediction models by providing an appropriate dataset according to the task. Our web server provides an environment and dataset that aid model developers and evaluators in obtaining a suitable dataset for both proteins and compounds, in addition to attributes necessary for deep learning. With the web server interface, users can customize the CPI dataset derived from ChEMBL by setting positive and negative thresholds to be adjusted according to the user’s definitions. We have also implemented a function for graphic display of the distribution of activity values in the dataset as a histogram to set appropriate thresholds for positive and negative examples. These functions enable effective development and evaluation of models. Furthermore, users can prepare their task-specific datasets by selecting a set of target proteins based on various criteria such as Pfam families, ChEMBL’s classification, and sequence similarities. The accuracy and efficiency of in silico screening and drug design using machine learning including deep learning can therefore be improved by facilitating access to an appropriate dataset prepared using our web server (https://binds.lifematics.work/).

How do athletes represent actions from their sport? How are these representations structured and which knowledge is shared among experts in the same discipline? To address these questions, the event segmentation task was used. Experts in Taekwondo and novices indicated how they would subjectively split videos of Taekwondo form sequences into meaningful units. In previous research, this procedure was shown to unveil the structure of internal action representations and to be affected by sensorimotor knowledge. Without specific instructions on the grain size of segmentation, experts tended to integrate over longer episodes which resulted in a lower number of single units. Moreover, in accordance with studies in figure-skating and basketball, we expected higher agreement among experts on where to place segmentation marks, i.e., boundaries. In line with this hypothesis, significantly more overlap of boundaries was found within the expert group as compared to the control group. This was observed even though the interindividual differences in the selected grain size were huge and expertise had no systematic influence here. The absence of obvious goals or objects to structure Taekwondo forms underlines the importance of shared expert knowledge. Further, experts might have benefited from sensorimotor skills which allowed to simulate the observed actions more precisely. Both aspects may explain stronger agreement among experts even in unfamiliar Taekwondo forms. These interpretations are descriptively supported by the participants’ statements about features which guided segmentation and by an overlap of the group’s agreed boundaries with those of an experienced referee. The study shows that action segmentation can be used to provide insights into structure and content of action representations specific to experts. The mechanisms underlying shared knowledge among Taekwondoists and among experts in general are discussed on the background of current theoretic frameworks.

Eighteen compounds, including fourteen flavonoids (1–14), one steroid (15), two fatty acids (16,17), and one nitrogen-containing compound (18), were isolated from the methanol extract of the whole Blumea lacera plant collected in Thailand. Compounds 1–11 and 15–17 exhibited tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance-overcoming activity. Among them, bonanzin (2) and cirsilineol (7) had particularly strong TRAIL resistance-overcoming activity, where the IC50 values against the human gastric adenocarcinoma cell line AGS in the presence of TRAIL (100 ng/mL) were 10.7 μM and 5.9 μM, respectively.

Abstract Preterm premature rupture of membranes and massive genital bleeding in the second trimester are serious obstetrical problems in pregnancy after trachelectomy. We had managed a twin post‐trachelectomy pregnancy by multiple strategies, and two healthy infants were delivered at 32+5 weeks, although the optimum management for such patients is unknown.