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Background: Survival rates for patients after starting hemodialysis (HD) remain low, and cardiovascular events remain the most common cause of death. However, few reports have investigated risk models that include electrocardiogram (ECG) findings. The present study aimed to develop a novel risk model including ECG findings for predicting all-cause death in patients undergoing HD. Methods: We enrolled 454 patients undergoing HD at 4 facilities from April 2008 to March 2021. Multivariate Cox regression analysis was performed to identify predictive factors, which were used to create a nomogram. We calculated the area under the curve (AUC) and used calibration plots to evaluate the risk model. Bootstrapping was also performed to evaluate the relationship between predicted and observed probabilities. Results: During the 3-year follow-up period, 98 (21.5%) patients died. Age (P< 0.001), serum albumin level (P= 0.03), history of stroke prior to HD initiation (P= 0.001), atrial fibrillation (P= 0.01), and corrected QT interval (P= 0.005) were identified as independent predictors of all-cause death. The predictive model was constructed using all these parameters with good discrimination of all-cause death, showing an AUC of 0.83 with 80.1% sensitivity and 75.6% specificity. The AUC based on the tenfold cross-validation was 0.82, with 78.2% sensitivity and 75.1% specificity, suggesting a good model. Conclusion: This novel risk model can effectively stratify high-risk patients and predict 3-year all-cause mortality in patients undergoing HD. We anticipated that this risk model might contribute to identify high-risk cases earlier and provide safer prescriptions and treatments for individual patients. Graphical abstract:

Acetone gas in exhaled breath and skin gas is produced when fatty acids are used as an energy source in the body. The selective and sensitive continuous measurement of acetone gas would be useful for the early screening of diabetes mellitus, a condition characterized by increased fatty acid metabolism. In particular, there is a growing need for acetone gas sensors that enable the wearable measurement of trace concentrations of acetone gas emitted through the skin. In this study, we improved the sensor’s sensitivity by optimizing the fluorescence measurement system and flow cell of a previously developed biofluorometric acetone gas sensor (bio-sniffer) using secondary alcohol dehydrogenase. To evaluate the performance of the improved acetone bio-sniffer, we constructed a dilution system to prepare acetone gas at subparts per billion by volume (ppbv) levels and verified its accuracy using gas chromatography–mass spectrometry. As a result, the dilution system was able to prepare 0.1 ppbv of acetone gas with a coefficient of variation of 5%. The improved acetone bio-sniffer demonstrated quantitative characteristics in the concentration range of 0.5–1000 ppbv, with a lower limit of quantification that was 40 times better than that of the conventional acetone bio-sniffer. In the future, this system is expected to be used for continuous measurement of acetone gas released through the skin.

Abstract: Spider silk is an archetypal biopolymer material with extreme tensile properties arising from its complex hierarchical assembly. While recent advances in sequencing have yielded abundant insights, relatively little is known concerning post-translational modifications (PTMs) in spider silk. Here, we probe the PTM landscape of dragline silk from the Jorō spider (Trichonephila clavata) using a combination of mass spectroscopy and solid-state nuclear magnetic resonance (NMR). The results reveal a wide array of potential modifications, including hydroxyproline, phosphorylation, and dityrosine cross-links, encompassing the different spidroin constituents. Notably, the MaSp3 repetitive region displayed numerous PTMs, whereas MaSp1 and MaSp2 variants showed distinct phosphorylation patterns in its terminal domains. The N-terminal domain (NTD) phosphorylation sites were found predominantly at the dimer interface, suggesting a modulatory function with respect to its pH-driven dimerization function, a hypothesis supported by studies using phosphomimetic NTD mutants. Possible roles of phosphoserine in limiting β-sheet formation, and hydroxyproline in disrupting β-turns are also discussed. Impact statement: Spider silk is an archetypal biomaterial that can outperform our most sophisticated artificial fibers. The secret to its mechanical properties lies in its complex hierarchical structure—encompassing the nano- to macroscales—that forms through a process of molecular self-assembly of the constituent spidroin proteins. While recent advances in "biomateriomics” have given us tremendous insights into the sequence–function relationships that determine spider silk behavior, the picture is still far from complete. One area that has received little attention is posttranslational modifications (PTMs). PTMs are ubiquitous biological phenomena that are crucial for providing dynamic control of the proteome, and effectively expand the structural and functional design space of proteins beyond that provided by the canonical amino acids. Here, we undertook a comprehensive analysis of PTMs from spider dragline silk fiber, which revealed numerous potential sites for a wide array of modifications. The results provide a fascinating window into additional layers of complexity underlying the mechanical behavior of spider silk, and suggest further avenues for creating novel, dynamically tunable, bioinspired materials. Graphical abstract:

The safety and feasibility of using staged flow diverter (FD) for ruptured cerebral aneurysms, in which coil embolization is performed in the acute phase and FD is deployed in the subacute phase, has recently been reported. This strategy requires assuming the rupture point and performing coil embolization. Although vessel wall magnetic resonance imaging (VW-MRI) has been reported to be useful in predicting the rupture point of aneurysms, its use with staged FD has not yet been reported. We report the first case of staged FD with preoperative contrast-enhanced VW-MRI to predict the rupture point for partially thrombosed vertebral artery dissecting large aneurysm involving posterior inferior cerebellar artery (PICA) origin. This approach achieved a very good outcome, not only completely occluding the aneurysm, but also reconstructing the parent artery while maintaining the patency of the PICA.

A circular patch antenna-coupled quantum well optical modulator for 1550 nm is proposed for the incident millimeter-wave polarization angle-independent phase modulation. The core layer of the modulator is composed of a multiple five-layer asymmetric coupled quantum well structure. The design and theoretical millimeter wave reception characteristics of circular and rectangular patch antennas with a gap structure are theoretically discussed for comparison. The circular antenna with an outer radius of 330 μm and a gap radius of 310 μm is designed. The optical phase modulators with both types of antennas are fabricated, and their modulation characteristics in the 60 GHz millimeter wave band are demonstrated and compared. The phase modulation independent of the incident millimeter-wave polarization angle is successfully realized. The CSR of 55.0 dB (3.56 mrad of phase shift) is obtained when irradiated with 60 GHz millimeter waves. The phase shift of 3.0 to 3.6 mrad is obtained at any polarization angle of the radio waves at an incident power density of 4.4 W/m2.

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Metabolic abnormalities play a pivotal role in various pathological conditions, necessitating the quantification of specific metabolites for diagnosis. While mass spectrometry remains the primary method for metabolite measurement, its limited throughput underscores the need for biosensors capable of rapid detection. Previously, we reported that pillar[6]arene with 12 carboxylate groups (P6AC) forms host–guest complexes with 1-methylnicotinamide (1-MNA), which is produced in vivo by nicotinamide N-methyltransferase (NNMT). P6AC acts as a biosensor by measuring the fluorescence quenching caused by photoinduced electron transfer upon 1-MNA binding. However, the low sensitivity of P6AC makes it impractical for detecting 1-MNA in unpurified biological samples. In this study, we found that P6A with 12 sulfonate groups (P6AS) is a specific and potent supramolecular host for 1-MNA interactions even in biological samples. The 1-MNA binding affinity of P6AS in water was found to be (5.68 ± 1.02) × 106M–1, which is approximately 700-fold higher than that of P6AC. Moreover, the 1-MNA detection limit of P6AS was determined to be 2.84 × 10–7M, which is substantially lower than that of P6AC. Direct addition of P6AS to culture medium was sufficient to quantify 1-MNA produced by cancer cells. Furthermore, this sensor was able to specifically detect 1-MNA even in unpurified human urine. P6AS therefore enables rapid and high-throughput quantification of 1-MNA, and further improvement of our strategy will contribute to the establishment of high-throughput screening of NNMT inhibitors, diagnosis of liver diseases, and imaging of human cancer cells in vivo.

The role of the kidney as an excretory organ for exogenous and endogenous compounds is well recognized, but there is a wealth of data demonstrating that the kidney has significant metabolizing capacity for a variety of exogenous and endogenous compounds that in some cases surpass the liver. The induction of drug-metabolizing enzymes by some chemicals can cause drug–drug interactions and intraindividual variability in drug clearance. In this study, we evaluated the expression and induction of cytochrome P450 (P450) and UDP-glucuronosyltransferase (UGT) isoforms in 3D-cultured primary human renal proximal tubule epithelial cells (RPTEC) to elucidate their utility as models of renal drug metabolism. CYP2B6, CYP2E1, CYP3A4, CYP3A5, and all detected UGTs (UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7) mRNA levels in 3D-RPTEC were significantly higher than those in 2D-RPTEC and HK-2 cells and were close to the levels in the human kidney cortex. CYP1B1 and CYP2J2 mRNA levels in 3D-RPTEC were comparable to those in 2D-RPTEC, HK-2 cells, and the human kidney cortex. Midazolam 1’-hydroxylation, trifluoperazine N-glucuronidation, serotonin O-glucuronidation, propofol O-glucuronidation, and morphine 3-glucuronidation in the 3D-RPTEC were significantly higher than the 2D-RPTEC and comparable to those in the HepaRG cells, although bupropion, ebastine, and calcitriol hydroxylations were not different between the 2D- and 3D-RPTEC. Treatment with ligands of the aryl hydrocarbon receptor and farnesoid X receptor induced CYP1A1 and UGT2B4 expression, respectively, in 3D-RPTEC compared with 2D-RPTEC. We provided information on the expression, activity, and induction abilities of P450s and UGTs in 3D-RPTEC as an in vitro human renal metabolism model.

Icing interventions on the injured skeletal muscle affect the macrophage-related regenerative events and muscle repair. However, despite its importance for the practice in sport medicine, the influence of different icing protocols on muscle regeneration remains unclear. Here, using a rodent model of mild muscle injury with necrosis in a small fraction of myofibers, the injured animals were allocated to four groups: non-icing control (Con) and a single treatment (Ice-1), three treatments (Ice-3), or nine treatments (Ice-9) with a 30-min icing each time within two days following injury. Muscle regeneration was compared between the groups on post-injury days 1, 3, 5, and 7. The results showed that compared with the Con group, muscle regeneration was faster in the Ice-9 group (but not in the Ice-1 and Ice-3 groups), as indicated by more rapid accumulation of satellite cells within the regenerating area and enlarged size of regenerating myofibers (p<0.05, respectively). There was also less macrophage accumulation (p<0.05) and a trend toward early removal of necrotic myofibers in the damaged/regenerating area in the Ice-9 group (p=0.0535). These results demonstrate that in the case of mild muscle damage, more frequent icing treatment is more effective to stimulate muscle regeneration.

Human-borne acetone is a potent marker of lipid metabolism. Here, an enzyme immobilization method for secondary alcohol dehydrogenase (S-ADH), which is suitable for highly sensitive and selective biosensing of acetone, was developed, and then its applicability was demonstrated for spatiotemporal imaging of concentration distribution. After various investigations, S-ADH-immobilized meshes could be prepared with less than 5% variation by cross-linking S-ADH with glutaraldehyde on a cotton mesh at 40 °C for 15 min. Furthermore, high activity was obtained by adjusting the concentration of the coenzyme nicotinamide adenine dinucleotide (NADH) solution added to the S-ADH-immobilized mesh to 500 μM and the solvent to a potassium phosphate buffer solution at pH 6.5. The gas imaging system using the S-ADH-immobilized mesh was able to image the decrease in NADH fluorescence (ex 340 nm, fl 490 nm) caused by the catalytic reaction of S-ADH and the acetone distribution in the concentration range of 0.1–10 ppm-v, including the breath concentration of healthy people at rest. The exhaled breath of two healthy subjects at 6 h of fasting was quantified as 377 and 673 ppb-v, which were consistent with the values quantified by gas chromatography–mass spectrometry.

Background: Appropriate exploratory efficacy data from Phase I trials are vital for subsequent phases. Owing to the uniqueness of brain tumors (BTs), use of different strategies to evaluate efficacy is warranted. We studied exploratory efficacy evaluation in Phase I trials involving BTs. Methods: Using Clarivate’s Cortellis™, 42 Phase I trials of BT interventions conducted from 2020 to 2022 were analyzed for efficacy endpoints, which were set as primary endpoints (PEs) or secondary endpoints (SEs). Additionally, these metrics were compared in two subgroups: trials including only BTs (Group-A) and those including BTs among mixed solid tumors (Group-B). Results: Selected studies included a median of 1.5 PEs (range, 1–6) and 5 SEs (range, 0–19). Efficacy endpoints were included as PEs and SEs in 2 (5%) and 31 (78%) trials, respectively. Among the latter 31 trials that included 94 efficacy endpoints, 24, 22, 20, 9, and 8 reflected overall response rate (ORR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and disease control rate (DCR), respectively. ORR for BT was determined using various methods; however, the Response Evaluation Criteria in Solid Tumors (RECIST) was used less frequently in Group-A than in Group-B (p= 0.0039). Conclusions: Recent Phase I trials included efficacy endpoints as SEs, with ORR, PFS, or OS included in ~ 50% trials and DOR or DCR in ~ 25%. No established criteria exist for imaging evaluation of BTs. Phase I trials involving mixed solid tumor cohorts revealed challenges in designing methods to assess the exploratory efficacy of BTs.

Because exacerbation of severe asthma decreases patients’ quality of life, this study aimed to identify predictive factors for asthma exacerbation.

This study investigated the suitability of surface modification for a long-range surface plasmon (LRSP) aptasensor using two different hydrogels, aiming at real-time monitoring of vancomycin (VCM) in undiluted serum and blood. Three different layer structures were formed on a gold surface of LRSP sensor chip using poly[2-methacryloyloxyethyl phosphorylcholine (MPC)-co-N-methacryloyl-(L)-tyrosinemethylester (MAT)] (PMM) and poly[MPC-co-2-ethylhexyl methacrylate (EHMA)-co-MAT] (PMEM). The peptide aptamer for VCM was immobilized in PMM and PMEM via MAT. Among four differently prepared sensor chips, the LRSP hydrogel aptasensor with PMM, referred to as the PMM hydrogel, exhibited the highest sensor output and superior antifouling properties. Following the optimization of the PMM hydrogel preparation conditions, the shelf life of the PMM hydrogel was determined to exceed 2 weeks, and the same sensor chip could be used for 102 days without significant performance deterioration. The PMM hydrogel was then applied for VCM measurement in undiluted serum in vitro, where it demonstrated a limit of detection of 0.098 μM and a dynamic range of 0.18–100 μM, covering the therapeutic range. Additionally, the PMM hydrogel enabled the continuous measurement of various VCM concentrations in serum without rinsing and showed a concentration-dependent output in undiluted blood. These findings underscore the potential of the PMM hydrogel for real-time and direct monitoring of VCM in body fluids.

The on‐tree counting of chestnut fruit (bur) is essential for yield estimation and monitoring of fruit load as well as tree health, which is important in determining the management strategy for orchards, markets, and tree health monitoring. However, the practice is still conducted by manual count or farmers’ intuition. Precise and effective counting method is yet to be established. This study attempted to count chestnut fruits with the object detection algorithm, You Only Look Once (YOLO), using the RGB imagery collected with an unmanned aerial vehicle (UAV). The model trained with 500 images (7866 burs labeled with bounding boxes) in YOLO version 4 (v4) could count the number of burs with a R2value of 0.98 and a root mean square error of 6.3 (8.3% of the mean) relative to the manual count in the data set for each whole tree (n= 53). The R2of linear regression between the number of burs obtained with the YOLOv4 model and the total yield was 0.76, with a standard error of 1.08 kg tree−1(26.4% of coefficient of variation), which was equivalent to the in situ burs count by an expert technician. In addition, the number of burs counted with the YOLOv4 model after the adjustment of trunk circumference was negatively correlated with nut weight. Overall, the study revealed that YOLO algorithm coupled with UAV‐based RGB imagery is a precise and efficient method for on‐tree burs detection, which could be used as an indicator of yield and fruit load. This report aims to develop high‐throughput method for detection of on‐tree chestnut fruits.YOLO algorithm coupled with UAV‐based RGB imagery could detect chestnut fruits precisely and efficiently.The burs estimated by the algorithm could be an indicator of yield and fruit load.

Cysteine (Cys) and its oxidized form, cystine (Cys2), play crucial roles in biological systems and have considerable applications in cell culture. However, Cys in cell culture media is easily oxidized to Cys2, leading to solubility issues. Traditional analytical methods struggle to maintain the oxidation states of Cys and Cys2 during analysis, posing a significant challenge to accurately measuring and controlling these compounds. To effectively control the Cys and Cys2 levels, a rapid and accurate analytical method is required. Here, we screened derivatizing reagents that can react with Cys even under acidic conditions to realize a novel analytical method for simultaneously determining Cys and Cys2 levels. Diethyl 2-methylenemalonate (EMM) was found to possess the desired traits. EMM, characterized by its dual electron-withdrawing attributes, allowed for a rapid reaction with Cys under acidic conditions, preserving intact information for understanding the functions of target compounds. Combined with LC–MS/MS and an internal standard, this method provided high analytical accuracy in a short analytical time of 9 min. Using the developed method, the rapid oxidation of Cys in cell culture media was observed with the headspace of the storage container considerably influencing Cys oxidation and Cys2 precipitation rates. The developed method enabled the direct and simplified analysis of Cys behavior in practical media samples and could be used in formulating new media compositions, ensuring quality assurance, and real-time analysis of Cys and Cys2 in cell culture supernatants. This novel approach holds the potential to further enhance the media performance by enabling the timely optimal addition of Cys.

A stereoscopic imaging or holography is a useful technology for a 3D display. These 3D imaging technologies can reconstruct floating volumetric spatial images fly off a displaying screen or a hologram. However a floating and popping up area of reconstructing 3D images is narrow, and the area is restricted between viewing positions and the display or hologram. If you want to make the lengths of popping ups fly off the displaying or holographic screen long, it is necessary to prepare a gigantic displaying unit with the large screen. But such an argument is nonsense even if we can realize such a stupid idea with costing a huge amount of money. To solve these problems, the authors have been starting researches for developing optical unit systems composed of virtual lenses, mirrors or diffusing screens which are virtually arranged and floating in the air. In this paper, the authors describe an aerial reflection screen using soapy water or thin films for aero signage which is floating in the air and enables to make images invisible from back.

Nuts are nutrient‐dense foods rich in unsaturated fatty acids, protein, dietary fiber, vitamins, and minerals. The present prebirth cohort study examined the association between maternal nut intake during pregnancy and the risk of childhood behavioral problems in 5‐year‐old Japanese children. Study subjects were 1199 mother–child pairs. Dietary intake was assessed using a diet history questionnaire. Emotional problems, conduct problems, hyperactivity problems, peer problems, and low prosocial behavior were assessed using the parent‐reported version of the Strengths and Difficulties Questionnaire. Adjustments were made for a priori‐selected nondietary confounders and potentially related dietary factors. Compared with mothers who had not eaten nuts during pregnancy, mothers who had eaten nuts had a significantly reduced risk of peer problems in children; the adjusted odds ratio was 0.64 (95% confidence interval: 0.42–0.97). There were no measurable associations between maternal consumption of nuts during pregnancy and the risk of childhood emotional problems, conduct problems, hyperactivity problems, and low prosocial behavior. Maternal consumption of nuts during pregnancy may be associated with a decreased risk of peer problems in 5‐year‐old children. Maternal diet during pregnancy is associated with child development.Nuts are nutrient‐dense foods. However, the number of epidemiological investigations examining the association between maternal nut intake during pregnancy and the risk of childhood behavioral problems is very limited. Maternal diet during pregnancy is associated with child development. Nuts are nutrient‐dense foods. However, the number of epidemiological investigations examining the association between maternal nut intake during pregnancy and the risk of childhood behavioral problems is very limited. In the current study, nut consumption was associated with a decreased risk of peer problems in children.Further investigation of the potential benefits of nut consumption during pregnancy on child behavior is warranted. In the current study, nut consumption was associated with a decreased risk of peer problems in children. Further investigation of the potential benefits of nut consumption during pregnancy on child behavior is warranted.

To clarify the evolutionary history of the Lilium maculatum–L. pensylvanicumcomplex in Japan and to improve the circumscription of its component taxa, we conducted phylogenetic analyses based on chloroplast and nuclear internal and external transcribed spacer (ITS, ETS) DNA sequences, a genome‐wide analysis of single‐nucleotide polymorphisms (SNPs) using multiplexed ISSR genotyping by sequencing (MIG‐seq), and morphological observations. Topological differences between the chloroplast and nuclear ITS + ETS phylogenies indicate that ancient hybridization or incomplete lineage sorting were involved in the origin of “maculatum”, but the relatively long length of relevant branches indicates that incomplete lineage sorting is implausible. The results of STRUCTURE analysis (K= 3, the highest delta Kvalue) using MIG‐seq indicate that “maculatum” has already developed its own cluster and can be considered a species (L. maculatum) that originated through the hybridization of L. pacificum(sp. nov.) and L. pensylvanicum. MIG‐seq Neighbor‐Net and STRUCTURE analyses (K= 3), as well as chloroplast DNA phylogeny, reveal that populations in disjunct limestone areas (L. maculatumvar. bukosanense) originated via the hybridization of L. maculatumand L. pacificum, whereas populations in the Sado‐Tobishima Islands (L. maculatumvar. sadoense, var. nov.) originated via hybridization between L. maculatumand L. pensylvanicum. These taxa appear to be more or less genetically isolated from other populations based on the STRUCTURE analysis (K= 5), although we do not know whether this isolation resulted from geographic distance or reproductive barriers. Based on available MIG‐seq and morphological data, respectively, we consider the two hybrid‐origin populations to be independent varieties. Furthermore, the morphology of seaside populations of L. maculatumin East Tohoku District appears to have deviated slightly from that of mountain populations (L. maculatumf. monticola); as such, coastal populations merit recognition as a form of L. maculatum(L. maculatumf. spontaneum, comb. & stat. nov.). Other seaside populations of L. maculatumin the West Tohoku District appear to have originated from populations of L. pacificum, but have been successively taken over by L. maculatumthrough introgression, and have consequently evolved into a form of L. maculatum(L. maculatumf. maculatum). In addition, we found putative extant hybrid populations of L. maculatum × L. pensylvanicum. We recognize three species, two varieties, two forms, and one hybrid in the L. maculatum–L. pensylvanicumcomplex in Japan.