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In the manufacturing of optical products, precise adjustments are made to maintain the optical axis alignment of optical components, which are then securely positioned using adhesives. To achieve positional accuracy at the micron level, it is essential to comprehend the deformation of the adhesive joint over time during processing. This study focuses on investigating the displacement of optical components resulting from the deformation of a cationic photopolymerized epoxy adhesive, which cures under ultraviolet (UV) radiation. First, the conversion of the adhesive was formulated based on a curing reaction model. This conversion can be divided into three stages: the initial reaction during UV irradiation, the subsequent dark reaction, and the reaction induced by heating. Moreover, formulations were developed to describe changes in curing shrinkage, thermal expansion, and viscoelasticity in relation to the conversion. These equations, governing the adhesive properties, were then used to perform finite element method (FEM) simulations to analyze the position of the optical component. Experimental tests on adhesively bonded components were conducted under conditions identical to those employed in the simulation. Throughout the curing process of the adhesive, the optical component was continuously imaged using a coherence-scanning interferometer, enabling the quantification of its displacement from the acquired images. The results of the FEM simulation and experimental analysis exhibited a consistent trend, indicating the effectiveness of the modeling and simulation methods employed in this study. The majority of the displacement of the optical component occurred over several hours during the dark reaction stage, rather than during UV irradiation. Notably, the movement of the optical component was not limited solely to the thickness direction of the adhesive layer because of curing shrinkage but also extends to the in-plane direction because of the non-uniform distribution of the UV irradiation intensity. [ABSTRACT FROM AUTHOR]

In this study, the relationship between the energy release rate (G1C), crack propagation rate (da/dN), and the fracture morphology of specimens with deteriorated adhesives after moisture absorption were investigated through the double cantilever beam (DCB) method. The specimens were prepared using a thermosetting epoxy adhesive based on compound carboxyl-terminated butadiene–nitrile rubber and Al 6061-T6 adherends. To accelerate the deterioration of the adhesives, open-faced specimens were immersed in water at 63°C at varying durations. Prior to the assembly of the DCB specimens, the adherends were either treated using acidic solutions or sand blasted. Consequently, the effect of the moisture deterioration of adhesive and the surface treatment performed on the adherend on the fracture morphology was studied. Furthermore, the relationship between G1C and da/dN was systematically investigated. At a constant crack opening speed, the failure mode changed from cohesive to interfacial fracture, and then reverted back cohesive fracture as the deterioration of the specimens progressed due to increasing immersion time. Interfacial fracture was not observed for the specimens with sandblasted adherends. Lastly, a decrease in da/dN was not observed even with increasing G1C values of the immersed specimens because interfacial fracture was easy to occur when the cyclic strains were applied. [ABSTRACT FROM AUTHOR]

Double lap joints were prepared using epoxy adhesive and aluminum plates, and their high-temperature strength properties were studied. Tensile, thermal aging, creep, and cyclic fatigue tests were performed to systematically investigate the effects of the aging temperature, testing temperature, stress waveform, and stress ratio on the strength and fracture morphology of the double lap joints. When the specimen was exposed to 135°C, the strength decreased significantly. Also, the relationship between the test temperature and shear strength could be expressed using an equation obtained from thermal activation theory. Additionally, in the fatigue test at room temperature, the strength of the specimen subjected to constant stress was higher than that of the specimen subjected to cyclic strain. The effect of creep deformation increased in the creep test at high temperatures, and therefore, the strength decreased significantly. [ABSTRACT FROM AUTHOR]

Optical components are often adjusted to maintain their alignment along the optical axis. They are fixed at their optimal positions particularly using ultraviolet (UV) ray-curable adhesives. To achieve a micron-level positional accuracy, it is necessary to understand adhesive shrinkage while curing and the resulting deformation of the adhesive joint. However, it is challenging to perform a quantitative evaluation of the cure shrinkage and mechanical properties of adhesives given the process complexity and strong dependence on curing conditions. Therefore, this study clarified the effects of various curing conditions on the curing extent of an adhesive under UV curing for positioning and heat curing as a post-curing process. The cure shrinkage, coefficient of thermal expansion, and viscoelastic properties of the adhesive were also measured. Each material property could be defined as a function of the curing extent to predict the changes in the properties under different curing conditions. The adhesive curing process was divided into three stages: adhesive gelation under UV irradiation, fast reaction stage under heating, and slow reaction stage under heating. The adhesive state changed from viscous to viscoelastic to elastic as it cured, and this process proceeded in the aforementioned three stages. Three different formulae were fitted corresponding to each stage, with good agreement with the experimental measurements. [ABSTRACT FROM AUTHOR]

The effect of cyclic moisture-absorption/desorption on adhesive strength was investigated using water at 23°C. Bulk plates and open face lap joints were prepared using epoxy adhesive, and their weight transition and shear strength were measured. The diffusion coefficient of the absorption process increased with the number of cycles and reached a constant value. In contrast, the diffusion coefficient of the desorption process was not affected by the number of cycles. As a part of the calcium carbonate disappeared from the surface, the weight of the bulk plates was reduced, and this weight reduction was irreversible. However, the strength of the lap joint was not significantly damaged by moisture absorption at 23°C. [ABSTRACT FROM AUTHOR]

The effect of strain rate on the mechanical properties of two epoxy adhesives was investigated by conducting experiments on dumbbell-shaped specimens prepared from the adhesives. The tensile rate was changed stepwise from 5.2 × 10–5 to 1.2 × 106 mm/min, and the yield stress, Young's modulus, elongation, and tensile strength were evaluated. The yield stress and tensile strength showed a clear dependence on the strain rate. The results from this study allowed us to propose a procedure for predicting the creep strength and high-rate impact strength from the results of a simple tensile test. [ABSTRACT FROM AUTHOR]

The application of primer is one of the most widely used pre-treatments to improve adhesion. However, few studies on the adhesive mechanism have investigated the effect of the organic solvent used for the primer on the improving of adhesion strength. In this study, attenuated total reflection infrared spectroscopy was performed to evaluate the interphases of multiple primers with different organic solvents for dilution. The main conclusion of this work is that the interphase thickness depends on the relative permittivity and viscosity of the organic solvent used for the primer. [ABSTRACT FROM AUTHOR]

Adhesive properties are often affected by water. In this study, to clarify the water-resistant properties of a thermosetting epoxy adhesive containing dicyandiamide (DICY) and carboxyl-terminated butadiene acrylonitrile rubber (CTBN), immersion tests of open-faced specimens and bulk specimens in water were performed, and the changes in the properties were investigated in terms of chemistry and mechanical strength. After immersing the open-faced specimens in water, the mechanical strengths were evaluated by two different methods: interfacial cutting method and secondary bonding method. Using both methods, a decrease in strength with immersion time was obtained, and the tendencies of the strength change were found to be very similar for the different evaluation methods. Chemical changes were also evaluated by infrared spectroscopy. Through periodical measurements of the infrared spectra of a fully-cured bulk adhesive specimen during water immersion, the chemical degradation of the epoxy adhesive containing DICY and CTBN was investigated, revealing an association with the change in mechanical strength in which hydrolysis of the cyano groups in DICY and CTBN led to a decrease in strength. Strength recovery experiments were also conducted by drying the specimens after water immersion, determining that the mechanical recovery strength changed with water temperature and immersion time. [ABSTRACT FROM AUTHOR]

Background and Aims: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of cardiovascular events independently of glycemic control. However, the possibility that SGLT2 inhibitors improve vascular restenosis is unknown. The aim of this study was to examine whether dapagliflozin could prevent neointima thickening following balloon injury and, if so, to determine the underlying mechanisms., Methods: Saline, dapagliflozin (1.5 mg/kg/day), or losartan (30 mg/kg/day) was administered orally for five weeks to male Wistar rats. Balloon injury of the left carotid artery was performed a week after starting the treatment and rats were sacrificed 4 weeks later. The extent of neointima was assessed by histomorphometric and immunofluorescence staining analyses. Vascular reactivity was assessed on injured and non-injured carotid artery rings, changes of target factors by immunofluorescence, RT-qPCR, and histochemistry., Results: Dapagliflozin and losartan treatments reduced neointima thickening by 32 % and 27 %, respectively. Blunted contractile responses to phenylephrine and relaxations to acetylcholine and down-regulation of eNOS were observed in the injured arteries. RT-qPCR investigations indicated an increased in gene expression of inflammatory (IL-1beta, VCAM-1), oxidative (p47phox, p22phox) and fibrotic (TGF-beta1) markers in the injured carotid. While these changes were not affected by dapagliflozin, increased levels of AT1R and NTPDase1 (CD39) and decreased levels of ENPP1 were observed in the restenotic carotid artery of the dapagliflozin group., Conclusions: Dapagliflozin effectively reduced neointimal thickening. The present data suggest that dapagliflozin prevents restenosis through interfering with angiotensin and/or extracellular nucleotides signaling. SGLT2 represents potential new target for limiting vascular restenosis., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In this study, we used near-infrared spectroscopy to measure the moisture penetration in epoxy adhesives and investigated the difference in the diffusion coefficients between the bulk and the adhesive layer. Moisture diffusion was evaluated under 100% RH and water immersion conditions. First, the effects of the curing agents and additives on moisture diffusion in the bulk were gravimetrically evaluated using epoxy-coated quartz glass plates. Different diffusion behaviors were observed depending on the curing agent used. The presence of additives resulted in higher diffusion coefficients, whereas the overall moisture content was low. Next, the moisture distribution in the adhesive layer was visualized using a specimen sandwiched between the quartz glass plates, and the diffusion coefficient of the adhesive layer was calculated. The diffusion coefficient in the adhesive layer was larger than that in the bulk. For adhesives cured with hydrophobic diamine, the diffusion coefficient within the adhesive layer increased by approximately 1.5 times compared with that in the bulk, regardless of the exposure environment. The adhesive, composed of a resin, Dicyandiamide, and additives, showed a 2-fold increase in the diffusion coefficient under high-humidity exposure conditions but no significant change under the water immersion condition. Therefore, these results suggest that, for an accurate analysis of moisture distribution, it is important to measure the diffusion coefficient of the adhesive layer directly rather than using the diffusion coefficient of the material itself.

Background and Objectives: There is no disease-modifying treatment of corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), 2 disorders characterized by their striking phenotypic, and, in CBS, pathologic heterogeneity. Seed amplification assays (SAAs) could enable the detection of neuropathologic processes, such as α-synuclein (αSyn) copathology, that affect the success of future disease-modifying treatment strategies. The primary objective was to assess possible αSyn copathology in CBS and PSP, as detected in CSF using an αSyn SAA (αSyn-SAA). Secondary objectives were to evaluate the association of αSyn-SAA positivity with other biomarkers including of Alzheimer disease (AD), and with clinical presentation. We hypothesized that αSyn-SAA positivity would be detectable in CBS and PSP and that it would be associated with AD biomarker positivity and β-amyloid (Aβ) 42 levels, neurodegeneration as assessed by neurofilament light chain (NfL) levels, and symptoms associated with synucleinopathies., Methods: This cross-sectional observational study included patients clinically diagnosed with CBS and PSP who underwent a lumbar puncture between 2012 and 2021 (Toronto Western Hospital, Canada). CSF was tested for αSyn-SAA positivity, AD biomarkers, and NfL levels. Clinical data were derived from medical records., Results: We tested the CSF of 40 patients with CBS (19 female patients, 65.9 ± 8.6 years) and 28 with PSP (13 female patients, 72.5 ± 8.7 years old), mostly White (n = 50) or Asian (n = 14). αSyn-SAA positivity was observed in 35.9% patients with CBS and 28.6% with PSP. In young-onset, but not late-onset patients, αSyn-SAA positivity and AD positivity were associated (odds ratio [OR] 8.8, 95% CI 1.2-82.6, p < 0.05). A multivariable linear regression analysis showed a significant interaction of αSyn-SAA status by age at onset on CSF Aβ42 levels (β = 0.3 ± 0.1, p < 0.05). Indeed, age at onset was positively related to Aβ42 levels only in αSyn-SAA-positive patients, as shown by slope comparison. A logistic regression analysis also suggested that REM sleep behavior disorder was associated with αSyn-SAA positivity (OR 60.2, 95% CI 5.2-1,965.8; p < 0.01)., Discussion: We detected a frequency of αSyn-SAA positivity in CBS and PSP in line with pathologic studies, highlighting the usefulness of SAAs for in vivo detection of otherwise undetectable neuropathologic processes. Our results also suggest that AD status (specifically low Aβ42) and older age at onset may contribute to αSyn-SAA positivity. This opens new perspectives for the stratification of patients in clinical trials.

Background: The timely management of rapidly evolving epidemiological scenarios caused by disease outbreaks is crucial to prevent devastating consequences. However, delayed laboratory diagnostics can hamper swift health policy and epidemic response, especially in remote regions such as the western Brazilian Amazon. The aim of the article is to analyze the impact of the COVID-19 pandemic on the volume and characteristics of emergency medical services (EMS) in Manaus, focusing on how the pandemic affected sensitive indicators such as response time and the use of advanced life support ambulances. Additionally, the study seeks to understand how changes in prehospital EMS patterns, triggered by the pandemic, could be utilized as health surveillance tools, enabling a more rapid response in epidemic scenarios., Methods: This retrospective, descriptive study included data from the SAMU (Serviço de Atendimento Móvel de Urgência) medical records between January and June 2020., Results: A total of 45,581 calls resulted in mobile units being dispatched during this period. These patients were predominantly male (28,227, 61.9%), with a median age of 47 years (IQR 30-67). The median response time significantly increased during the pandemic, reaching a median of 45.9 min (IQR 30.6-67.7) ( p < 0.001). EMS calls were reduced for trauma patients and increased for other medical emergencies, especially respiratory conditions, concomitantly to an escalation in the number of deaths caused by SARS and COVID-19 ( p < 0.001). The employment of advanced life support ambulances was higher during the pandemic phase ( p = 0.0007)., Conclusion: The COVID-19 pandemic resulted in a temporary disorder in the volume and reason for EMS calls in Manaus. Consequently, sensitive indicators like the response time and the employment of advanced life support ambulances were negatively affected. Sudden prehospital EMS pattern changes could play an important role in health surveillance systems, allowing for earlier establishment of countermeasures in epidemics. The impact of the COVID-19 pandemic on prehospital EMS and its role in health surveillance should be further explored.

During the fertilization of fish eggs, the hardening of the egg envelope is mediated by transglutaminase (hTGase). After fertilization, TGase undergoes processing. We isolated hTGase from extracts of unfertilized and water-activated rainbow trout eggs. Rainbow trout hTGase (Rt-hTGase) appeared as an 80 kDa protein, and its processed form was 55 kDa. Their N-terminal amino acid sequences were nearly identical, suggesting processing in the C-terminal region. The specific activities were not significantly different, indicating that C-terminal processing does not activate the enzyme itself. We cloned the cDNA by reverse transcription polymerase chain reaction (RT-PCR) using degenerate primers followed by RACE-PCR. The deduced amino acid sequence of the cDNA was similar to that of factor XIII subunit A (FXIIIA). Molecular phylogenetic and gene syntenic analyses clearly showed that hTGase was produced by duplication of FXIIIA during the evolution to Teleostei. The 55 kDa processed form of Rt-hTGase is predominantly composed of an enzyme domain predicted from the amino acid sequence of the cDNA. It is hypothesized that the C-terminal domain of Rt-hTGase binds to egg envelope proteins, and that processing allows the enzyme to move freely within the egg envelope, increasing substrate-enzyme interaction and thereby accelerating hardening., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To verify if data obtained in the prehospital evaluation of patients with severe acute respiratory syndrome (SARS) during the initial response to the COVID-19 pandemic is associated with clinical outcomes: mechanical ventilation, hospital discharge, and death. This is a retrospective analysis involving secondary data from the Emergency Medical Service (EMS) records and the Health Surveillance Information System of patients assisted by the EMS in Manaus, from January to June 2020, the period of the first peak of COVID-19 cases. The combination of the two databases yielded a total of 1.190 patients, who received a first EMS response and were later admitted to hospital with SARS and had data on clinical outcomes of interest available. Patients were predominantly male (754, 63.4%), with a median age of 66 (IQR: 54.0-78.0) years. SARS illness before medical assistance was associated to need for invasive mechanical ventilation (IMV, p < 0.001). Lower pre-hospital SpO 2 was associated to death (p = 0.025). Death was more common among patients with respiratory support needs, especially in the invasive ventilation group (262/287; 91.3%) (p < 0.001). In addition, IMV was more common among elderly individuals (p < 0.001). Patients admitted to ICU had a greater chance of dying when compared to non-ICU admitted patients (p < 0.001), and closely related to IMV (p < 0.001). Patients in ICU were also older (p = 0.003) and had longer hospital stay (p < 0.001). Mortality was associated with mechanical ventilation (p < 0.001), ICU admission (p < 0.001), and older age (p < 0.001). Patients who died had a shorter length of both ICU and total hospital stay (p < 0.001). Prehospital EMS may provide feasible and early recognition of critical patients with SARS in strained healthcare systems, such as in low-resource settings and pandemics., (© 2024. The Author(s).)

Competing Interests: None.

Background: Disability in ambulation has a critical impact on activities of daily living in patients with multiple sclerosis (MS). The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a self-reported instrument developed to assess the impact of MS on walking. The scale's 12 items assess various aspects of walking-related tasks during the past 2 weeks. MSWS-12 has been used in multiple clinical studies and translated into several languages. In the present study, we translated the MSWS-12 into Japanese and evaluated its psychometric properties in a cross-sectional study., Methods: The original English MSWS-12 version 2 (v2) was translated into Japanese through a standard procedure. Sixty consecutive Japanese MS patients completed the newly prepared Japanese MSWS-12v2 questionnaire and repeated the test 14 days later. Physical disability was assessed by the Expanded Disability Status Scale (EDSS), Timed 25-foot Walk (T25FW), and 9-hole Peg Test (9HPT). Cognitive performance was evaluated using the Processing Speed Test (PST). Fatigue and health-related quality of life were assessed using the Japanese versions of the Fatigue Severity Scale (FSS) and the Functional Assessment of MS (FAMS)., Results: The mean age of the patients was 42.5 years, with median disease duration of 10 years, and median EDSS of 2.0 (range 0, 6.5). Forty-seven patients (78.3 %) had relapsing-remitting, 9 (15.0 %) had secondary-progressive, and 4 (6.7 %) had primary-progressive phenotypes. The median score of the MSWS-12v2 was 5.95 (interquartile range 0, 50.6). Twenty-seven patients (45 %) scored the lowest possible score (0 points), while one (1.7 %) scored the highest possible score (100 points). Cronbach's alpha was 0.98 (95 % confidence interval [CI] 0.97, 0.98), and the test-retest intraclass correlation was 0.95 (95%CI 0.94, 0.96). MSWS-12v2 score was strongly correlated with EDSS (Spearman's ρ = 0.73 [95%CI 0.58, 0.83]), T25FW (ρ = 0.70 [95%CI 0.55, 0.81]), and total FAMS score (ρ = -0.80 [95%CI -0.88, -0.69]), and moderately correlated with 9HPT (ρ = 0.65 [95%CI 0.47, 0.77] for the dominant hand; ρ = 0.62 [95%CI 0.43, 0.75] for the non-dominant hand), PST (ρ = -0.65 [95%CI -0.78, -0.47]), and FSS (ρ = 0.68 [95%CI 0.52, 0.80]). Among the subcomponents of FAMS, the mobility subcomponent showed the most robust correlation with MSWS-12v2 score (ρ = -0.91 [95%CI -0.94, -0.81]). In patients with minimal or no objective disability (EDSS < 3.0, n = 40), only the mobility subcomponent of FAMS was strongly correlated with MSWS-12v2 score (ρ = -0.76 [95% CI -0.87, -0.58]). In contrast, correlations of MSWS-12v2 score with EDSS and T25FW were weak in this subgroup (ρ = 0.28 [95%CI -0.03, 0.55] for EDSS; ρ = 0.25 [95%CI -0.06, 0.52] for T25FW). Response patterns for the single items showed that 32.5 % of the patients with EDSS below 3.0 reported having problems with balance, followed by climbing stairs and standing while doing things (both 25 %)., Conclusion: The Japanese version of the MSWS-12v2 developed in this study is reliable, valid, and helpful for screening walking disability in Japanese MS patients, including those with minimal objective disability., Competing Interests: Declaration of competing interest Yusei Miyazaki has received travel and speaker honoraria from Alexion Pharma, Biogen Japan, Chugai Pharmaceutical Company, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, and Teijin Pharma. Masaaki Niino has received travel and speaker honoraria from Alexion Pharma, Biogen Japan, Chugai Pharmaceutical Company, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, and Takeda Pharmaceutical Company. Naoya Minami has received travel and speaker honoraria from Argenx Japan. The other authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The long-term consequences of concussions may include pathological neurodegeneration as seen in Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). Tau-PET showed promise as a method to detect tau pathology of CTE, but more studies are needed OBJECTIVE: This study aimed (1) to assess the association of imaging evidence of tau pathology with brain volumes in retired athletes and (2) to examine the relationship between tau-PET and neuropsychological functioning., Methods: Former contact sport athletes were recruited through the Canadian Football League Alumni Association or the Canadian Concussion Centre clinic. Athletes completed MRI, [ 18 F]flortaucipir tau-PET, and a neuropsychological battery. Memory composite was created by averaging the Rey Auditory Verbal Learning Test and Rey Visual Design Learning Test z-scores. Grey matter (GM) volumes were age/intracranial volume corrected using normal control MRIs. Tau-PET % positivity in GM was calculated as the number of positive voxels (≥ 1.3 standardized uptake value ratio (SUVR)/total voxels)., Results: 47 retired contact sport athletes negative for AD (age:51 ± 14; concussions/athlete:15 ± 2) and 54 normal controls (age:50 ± 13) were included. Tau-PET positive voxels had significantly lower GM volumes, compared to tau-PET negative voxels (- 0.37 ± 0.41 vs. - 0.31 ± 0.37, paired p = .006). There was a significant relationship between GM tau-PET % positivity and memory composite score (r =  - .366, p = .02), controlled for age, PET scanner, and PET scan duration. There was no relationship between tau-PET measures and concussion number, or years of sport played., Conclusion: A higher tau-PET signal was associated with reduced GM volumes and lower memory scores. Tau-PET may be useful for identifying those at risk for neurodegeneration., (© 2024. The Author(s).)

Objectives: The risk of postoperative bleeding is high after gastric endoscopic submucosal dissection (ESD) in patients continuously treated with antithrombotic agents (ATAs). The effectiveness of endoscopic hand suturing (EHS) on bleeding after gastric ESD was investigated in patients at high risk of delayed bleeding., Methods: Patients with neoplasms ≤2 cm who underwent gastric ESD and continued to receive perioperative ATAs were enrolled in this multicenter phase II study. The mucosal defect was closed with EHS after removing the lesion. Postoperative bleeding rate was assessed for 3-4 postoperative weeks as a primary outcome measure. The technical success of EHS and adverse events were also assessed. Based on expected and threshold postoperative bleeding rates of 10% and 25%, respectively, we aimed to include 48 patients in the study., Results: A total of 49 patients were enrolled in the study, and 43 patients were finally registered as the per-protocol set. The postoperative bleeding rate was 7.0% (3/43 patients; the upper limit of one-sided 95% confidence interval [CI], 17.1% and 97.5% CI, 19.1%). The upper limits of the CI were below the threshold value (25%), and the postoperative bleeding rate was below the expected value (10%). The technical EHS success rate, closure maintenance rate on postoperative day 3, and postoperative subclinical bleeding rate were 100%, 83%, and 2%, respectively. No severe adverse events related to EHS were observed., Conclusions: Endoscopic hand suturing may prevent postoperative bleeding in patients undergoing gastric ESD while being treated continuously with ATAs (UMIN000038140)., (© 2024 Japan Gastroenterological Endoscopy Society.)

Chiral molecular assemblies have attracted considerable attention because of their interesting physical properties, such as spin-selective electron transport. Cation-anion salts of three azolium cations, imidazolium ( HIm + ), triazolium ( HTrz + ), and thiazolium ( HThz + ), in combination with a chiral camphorsulfonate (1 S - CS - ) and their racemic compounds ( rac - CS - ) were prepared and compared in terms of phase transitions, crystal structures, dynamics of constituent molecules, dielectric responses, and proton conductivities. The cation-anion crystals containing HIm + showed no significant difference in proton conductivity between the homochiral and racemic crystals, whereas the HTrz + -containing crystals showed higher proton conductivity and lower activation energy in the homochiral form than in the racemic form. A two-dimensional hydrogen-bonding network consisting of HTrz + and -SO 3 - groups and similar in-plane rotational motion was observed in both crystals; however, the HTrz + cation in the homochiral crystal exhibited the rotational motion modulated with translational motion, whereas the HTrz + cation in the racemic crystal exhibited almost steady in-plane rotational motion. The different motional degrees of freedom were confirmed by crystal structure analyses and temperature- and frequency-dependent dielectric constants. In contrast, steady in-plane rotational motion with the thermally activated fluctuating motion of CS - was observed both in homochiral and racemic crystals containing HIm + , which averaged the motional space of protons resulting in similar dielectric responses and proton conductivities. The control of motional degrees of freedom in homochiral crystals affects the proton conductivity and is useful for the design of molecular proton conductors.

Surface-enhanced Raman scattering (SERS) is an attractive technique in molecular detection with high sensitivity and label-free characteristics. However, its use in protein detection is limited by the large volume of proteins, hindering its approach to the narrow spaces of hotspots. In this study, we fabricated a Au nanoTriangle plate Array on Gel (AuTAG) as an SERS substrate by attaching a Au nanoTriangle plate (AuNT) arrangement on a thermoresponsive hydrogel surface. The AuTAG acts as an actively tunable plasmonic device, on which the interparticle distance is altered by controlling temperature via changes in hydrogel volume. Further, we designed a Gel Filter Trapping (GFT) method as an active protein delivery strategy based on the characteristics of hydrogels, which can absorb water and separate biopolymers through their three-dimensional (3D) polymer networks. On the AuTAGs, fabricated with AuNTs modified with charged surface ligands to prevent the nonspecific adsorption of analytes to particles, the GFT method helped the delivery of proteins to hotspot areas on the AuNT arrangement. This combination of a AuTAG substrate and the GFT method enables ultrahigh sensitivity for protein detection by SERS up to a single-molecule level as well as a wide quantification concentration range of 6 orders due to their geometric advantages.

Late-onset Alzheimer's disease (LOAD) is the most common form of Alzheimer's disease (AD). However, modeling sporadic LOAD that endogenously captures hallmark neuronal pathologies such as amyloid-β (Aβ) deposition, tau tangles, and neuronal loss remains an unmet need. We demonstrate that neurons generated by microRNA (miRNA)-based direct reprogramming of fibroblasts from individuals affected by autosomal dominant AD (ADAD) and LOAD in a three-dimensional environment effectively recapitulate key neuropathological features of AD. Reprogrammed LOAD neurons exhibit Aβ-dependent neurodegeneration, and treatment with β- or γ-secretase inhibitors before (but not subsequent to) Aβ deposit formation mitigated neuronal death. Moreover inhibiting age-associated retrotransposable elements in LOAD neurons reduced both Aβ deposition and neurodegeneration. Our study underscores the efficacy of modeling late-onset neuropathology of LOAD through high-efficiency miRNA-based neuronal reprogramming.

Background: Good accuracy for the clinical diagnosis of frontotemporal lobar degeneration (FTLD) by specialists in an early onset dementia clinic has been reported., Objective: To assess the diagnostic accuracy of FTLD in an entire population, without restrictions related to patient age or diagnosing physician., Methods: Volumes of the "Annual of the Pathological Autopsy Cases in Japan," with reports of 130,105 autopsies throughout Japan from 2007 to 2016, were descriptively analyzed., Results: There were 219 patients with clinical and/or pathological diagnoses of FTLD. The sensitivity and specificity were 24.5% and 76.9%, respectively. Age at death for pathologically confirmed patients was 76.3 ± 11.6 years (mean ± standard deviation). Overlooked patients died significantly older than patients with an accurate clinical diagnosis., Conclusions: Clinical diagnoses of FTLD had low sensitivity. Furthermore, the age at death of pathologically confirmed patients suggests that FTLD affects a wide age range and is not restricted to presenile individuals., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The quality and bias of annotations by annotators (e.g., radiologists) affect the performance changes in computer-aided detection (CAD) software using machine learning. We hypothesized that the difference in the years of experience in image interpretation among radiologists contributes to annotation variability. In this study, we focused on how the performance of CAD software changes with retraining by incorporating cases annotated by radiologists with varying experience., Methods: We used two types of CAD software for lung nodule detection in chest computed tomography images and cerebral aneurysm detection in magnetic resonance angiography images. Twelve radiologists with different years of experience independently annotated the lesions, and the performance changes were investigated by repeating the retraining of the CAD software twice, with the addition of cases annotated by each radiologist. Additionally, we investigated the effects of retraining using integrated annotations from multiple radiologists., Results: The performance of the CAD software after retraining differed among annotating radiologists. In some cases, the performance was degraded compared to that of the initial software. Retraining using integrated annotations showed different performance trends depending on the target CAD software, notably in cerebral aneurysm detection, where the performance decreased compared to using annotations from a single radiologist., Conclusions: Although the performance of the CAD software after retraining varied among the annotating radiologists, no direct correlation with their experience was found. The performance trends differed according to the type of CAD software used when integrated annotations from multiple radiologists were used., (© 2024. The Author(s).)

Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease with uncertain genetic predisposition in most sporadic cases. The spatial architecture of cell types and gene expression are the basis of cell-cell interactions, biological function and disease pathology, but are not well investigated in the human motor cortex, a key ALS-relevant brain region. Recent studies indicated single nucleus transcriptomic features of motor neuron vulnerability in ALS motor cortex. However, the brain regional vulnerability of ALS-associated genes and the genetic link between region-specific genes and ALS risk remain largely unclear. Here, we developed an entropy-weighted differential gene expression matrix-based tool (SpatialE) to identify the spatial enrichment of gene sets in spatial transcriptomics. We benchmarked SpatialE against another enrichment tool (multimodal intersection analysis) using spatial transcriptomics data from both human and mouse brain tissues. To investigate regional vulnerability, we analysed three human motor cortex and two dorsolateral prefrontal cortex tissues for spatial enrichment of ALS-associated genes. We also used Cell2location to estimate the abundance of cell types in ALS-related cortex layers. To dissect the link of regionally expressed genes and ALS risk, we performed burden analyses of rare loss-of-function variants detected by whole-genome sequencing in ALS patients and controls, then analysed differential gene expression in the TargetALS RNA-sequencing dataset. SpatialE showed more accurate and specific spatial enrichment of regional cell type markers than multimodal intersection analysis in both mouse brain and human dorsolateral prefrontal cortex. Spatial transcriptomic analyses of human motor cortex showed heterogeneous cell types and spatial gene expression profiles. We found that 260 manually curated ALS-associated genes are significantly enriched in layer 5 of the motor cortex, with abundant expression of upper motor neurons and layer 5 excitatory neurons. Burden analyses of rare loss-of-function variants in Layer 5-associated genes nominated NOMO1 as a novel ALS-associated gene in a combined sample set of 6814 ALS patients and 3324 controls (P = 0.029). Gene expression analyses in CNS tissues revealed downregulation of NOMO1 in ALS, which is consistent with a loss-of-function disease mechanism. In conclusion, our integrated spatial transcriptomics and genomic analyses identified regional brain vulnerability in ALS and the association of a layer 5 gene (NOMO1) with ALS risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Symptom scales for achalasia after per-oral endoscopic myotomy (POEM) are lacking. This study aimed to propose a new scale based on the conventional Eckardt score (c-ES) and evaluate persistent symptoms that impair patients' quality of life (QOL) post-POEM., Methods: Dysphagia, regurgitation, and chest pain frequencies were assessed using a 6-point scale modified-ES (m-ES) after POEM, with "occasional" symptoms on the c-ES further subdivided into three-period categories on m-ES. Symptom severity was further evaluated using a 5-point scale ranging from 1 to 5 points, with a score ≥ 3 points defined as persistent symptoms impairing QOL. We analyzed the correlation between the m-ES and severity score, diagnostic performance of the m-ES for persistent symptoms, and overlaps between each residual symptom., Results: Overall, 536 patients (median follow-up period, 2.9 years) post-POEM were included in this multicenter study. Significant correlations were observed between the m-ES and severity scores for dysphagia (r = 0.67, p < 0.01), regurgitation (r = 0.73, p < 0.01), and chest pain (r = 0.85, p < 0.01). Twenty-six patients (4.9%) had persistent symptoms post-POEM, and 23 of them had m-ES-specific symptom frequency ≥ once a month, which was determined as the optimal frequency threshold for screening persistent symptoms. The total m-ES predicted persistent symptoms more accurately than the total c-ES (area under the curve: 0.95 vs. 0.79, p < 0.01). Furthermore, dysphagia and chest pain were the major residual symptoms post-POEM covering 91.4% of regurgitation., Conclusions: The new post-POEM scale successfully evaluated the QOL-based patient symptom severities. Our study implied the possibility of a simpler scale using residual dysphagia and chest pain., (© 2024. Japanese Society of Gastroenterology.)

Objective: Despite being a less-invasive procedure, esophagectomy can cause severe infectious complications, such as pneumonia and anastomotic leakage. Herein, we aimed to clarify the inflammatory characteristics of pneumonia/anastomotic leakage after esophagectomy by assessing the difference between the postoperative trends of serum C-reactive protein (CRP) and procalcitonin (PCT) levels in patients with pneumonia/anastomotic leakage using the values on the consecutive postoperative day (POD)., Methods: This study included 439 patients who underwent minimally invasive esophagectomy. Serum CRP and PCT levels were measured on PODs 1-7, 10, and 14. Pneumonia and anastomotic leakage were defined as Clavien-Dindo grades ≥ 2., Results: Pneumonia and anastomotic leakage occurred in 96 and 51 patients, respectively. The CRP and PCT levels peaked on POD 3 (11.6 ± 6.8 mg/dL) and POD 2 (0.69 ± 2.9 ng/mL), respectively. Between PODs 3 and 14, CRP levels were significantly higher in patients with pneumonia and anastomotic leakage than in those without complications (P < 0.001). Between PODs 3 and 14, PCT levels were significantly higher in patients with pneumonia; however, on most PODs, there were no significant differences in PCT levels between patients with and without anastomotic leakage., Conclusion: Inflammatory reactions caused by pneumonia may be more intense than those caused by anastomotic leakage after esophagectomy. Postoperative trends in serum CRP and PCT levels may vary depending on the complication type. Pneumonia and anastomotic leakage after esophagectomy can be potentially distinguished by the postoperative trend of PCT values before detailed examinations, such as computed tomography and endoscopy., (© 2024. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Background Postoperative chylothorax is a rare but life-threatening complication of esophagectomy. However, due to its rarity, researching the risk factors and selecting appropriate treatment options has been limited. Methods This study included 727 patients with esophageal cancer who underwent minimally invasive esophagectomy at our hospital. To detect the risk factors for chylothorax, we divided the patients into two groups, with and without postoperative chylothorax. We then compared patient characteristics, tumor-specific variables, and operative details. Subsequently, we analyzed the peri-treatment characteristics and outcomes for the three distinct treatment options we had chosen: surgery, conversion (the group that finally underwent surgery after unsuccessful conservative treatment), and conservative. Results Of the 727 patients, 18 (2.5%) developed a chylothorax. The mean BMI was lower (20.3 vs. 21.9, p=0.057), and more cases of thoracic duct resection were found in the chylothorax group (33.3% vs. 6.2%, p=0.001), with statistical significance. Multivariate analysis identified thoracic duct resection as a risk factor (adjusted odds ratio, 6.83). The drainage volume two days after chylothorax was higher in the surgery group, although the difference was not statistically significant (surgery group, 1,405 ml vs. conversion group, 260 ml vs. conservative group, 310 ml; p=0.073). The surgery group had the shortest median postoperative hospital days among these groups (21.5 as compared to 102 and 25.0 days in the conversion and conservative groups, respectively; p<0.001). None of the patients died during their hospital stays. Conclusion Thoracic duct resection during the initial minimally invasive esophagectomy was an independent risk factor for chylothorax. If drainage volume does not decrease on the second day, early surgery may lead to earlier discharge., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of the Graduate School of Medicine, Tohoku University issued approval 2019-1-429. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tsuchitani et al.)

The Human Glycome Atlas (HGA) Project was launched in April 2023, spearheaded by three Japanese institutes: the Tokai National Higher Education and Research System, the National Institutes of Natural Sciences, and Soka University. This was the first time that a field in the life sciences was adopted by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) for a Large-scale Academic Frontiers Promotion Project. This project aims to construct a knowledgebase of human glycans and glycoproteins as a standard for the human glycome. A high-throughput pipeline for comprehensively analyzing 20,000 blood samples in its first five years is planned, at which time an access-controlled version of a human glycomics knowledgebase, called TOHSA, will be released. By the end of the final tenth year, TOHSA will provide a central resource linking human glycan data with other omics data including disease-related information., (© The Author(s) 2024. Published by Oxford University Press.)