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Transition state theory (TST) provides a framework to estimate the rate of chemical reactions. Despite its great success with many reaction systems, the underlying assumptions such as local equilibrium and nonrecrossing do not necessarily hold in all cases. Although dynamical systems theory can provide the mathematical foundation of reaction tubes existing in phase space that enables us to predict the fate of reactions free from the assumptions of TST, numerical demonstrations for large systems have been yet one of the challenges. Here, we propose a dimensionality reduction algorithm to demonstrate structures in phase space (called reactive islands) that predict reactivity in systems with many degrees of freedom. The core of this method is the application of supervised principal component analysis, where a coordinate transformation is performed to preserve the dynamical information on reactivity (i.e., to which potential basin the system moves from a region of interest) as much as possible. The reactive island structures are expected to be reflected in the transformed, low-dimensional phase space. As an illustrative example, the algorithm is scrutinized using a modified Hénon–Heiles Hamiltonian system extended to many degrees of freedom, which has three channels leading to three different products from one stable potential basin. It is shown that our algorithm can predict the reactivity in the transformed, low-dimensional coordinate system better than a naïve coordinate system and that the reactivity distribution in the transformed low-dimensional space is considered to reflect the underlying reactive islands. [ABSTRACT FROM AUTHOR]

Asset price bubbles are situations where asset prices exceed the fundamental values defined by the present value of dividends. This paper presents a conceptually new perspective: the necessity of bubbles. We establish the bubble necessity theorem in a plausible general class of economic models: with faster long-run economic growth (G) than dividend growth (G d) and counterfactual long-run autarky interest rate (R) below dividend growth, all equilibria are bubbly with nonnegligible bubble sizes relative to the economy. This bubble necessity condition naturally arises in economies with sufficiently strong savings motives and multiple factors or sectors with uneven productivity growth. [ABSTRACT FROM AUTHOR]

Background Although randomized clinical trials (RCTs) demonstrated short-term benefits of endovascular therapy (EVT) for acute ischemic stroke (AIS) with a large ischemic region, little is known about the long-term cost-effectiveness or its difference by the extent of the ischemic areas. We aimed to assess the cost-effectiveness of EVT for AIS involving a large ischemic region from the perspective of Japanese health insurance payers, and analyze it using the Alberta Stroke Program Early CT Score (ASPECTS). Methods The Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism-Japan Large Ischemic Core Trial (RESCUE-Japan LIMIT) was a RCT enrolling AIS patients with ASPECTS of 3-5 initially determined by the treating neurologist primarily using MRI. The hypothetical cohort and treatment efficacy were derived from the RESCUE-Japan LIMIT. Costs were calculated using the national health insurance tariff. We stratified the cohort into two subgroups based on ASPECTS of ≤3 and 4-5 as determined by the imaging committee, because heterogeneity was observed in treatment efficacy. EVT was considered cost-effective if the incremental cost-effectiveness ratio (ICER) was below the willingness-topay of 5 000 000 Japanese yen (JPY)/quality-adjusted life year (QALY). Results EVT was cost-effective among the RESCUE-Japan LIMIT population (ICER 4 826 911 JPY/QALY). The ICER among those with ASPECTS of ≤3 and 4-5 was 19 396 253 and 561 582 JPY/QALY, respectively. Conclusion EVT was cost-effective for patients with AIS involving a large ischemic region with ASPECTS of 3-5 initially determined by the treating neurologist in Japan. However, the ICER was over 5 000 000 JPY/QALY among those with an ASPECTS of ≤3 as determined by the imaging committee. [ABSTRACT FROM AUTHOR]

Blastomycosis is a fungal disease caused by inhalation of Blastomyces spores from the environment that can result in severe pulmonary illness and high hospitalization rates. In early March 2023, Public Health Delta and Menominee Counties (Michigan) reported a cluster of blastomycosis cases among paper mill workers to the Michigan Department of Health and Human Services (MDHHS). MDHHS subsequently notified CDC. On March 17, paper mill management requested a health hazard evaluation (HHE) from CDC's National Institute for Occupational Safety and Health (NIOSH) to investigate potential workplace exposures to Blastomyces and recommend prevention and control measures at the mill. The workplace epidemiologic investigation combined a NIOSH HHE medical survey consisting of a questionnaire on work and health with Blastomyces urine antigen testing of specimens obtained from workers to assist in case finding, with additional case information from MDHHS blastomycosis surveillance data. Assessment of 645 mill workers identified 162 cases of blastomycosis with illness onset during November 1, 2022--May 15, 2023, with the weekly case count peaking at 21 cases in early March 2023. HHE environmental sampling in and around the mill did not identify the source of workers' Blastomyces exposure in the mill. This outbreak was the largest documented blastomycosis outbreak in the United States, and the first associated with a paper mill or an industrial setting. A coordinated public health response facilitated swift prevention measures with recommendations focused on reducing workers' exposure to Blastomyces, including hazard communication, respiratory protection, mill cleaning, and ventilation system improvements. [ABSTRACT FROM AUTHOR]

During the anaerobic digestion (AD) of food waste, the deliberate secession of substrate rapidly increases the microbial cell population, which can reach a maximum in 2–3 d. During short-term resting (STR), an increase in free NH3 due to an increase in pH is a key inhibitor of cell proliferation; therefore, cell growth would be further promoted if free NH3 was reduced. To explore adopting an STR technique to increase microbial cells in the AD of organic waste, we attempted to reduce free NH3 by controlling the pH in the reactors. Two semi-continuously treated reactors were fed with food waste at a loading rate of 3.0 g-VS/L/d for 40 days and then the feeding was stopped in both reactors until day 47. One of the reactors was maintained at pH 7.37 ± 0.03, whereas pH was not controlled in the other. During STR, the cell density in the pH-controlled condition reached a maximum of 7.48 × 1010 cells/mL, which was twice as high as that before STR, and 1.7-times higher than that in the non-pH-controlled condition. These results demonstrated that mitigating NH3 using pH can affect cell proliferation during STR. [ABSTRACT FROM AUTHOR]

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of the motor system. Pathogenic variants in SPTLC1, encoding a subunit of serine palmitoyltransferase, cause hereditary sensory and autonomic neuropathy type 1 (HSAN1), and have recently been associated with juvenile ALS. SPTLC1 variants associated with ALS cause elevated levels of sphinganines and ceramides. Reports on ALS associated with SPTLC1 remain limited. This study aimed to investigate the frequency of SPTLC1 variants in ALS and relevant clinical characteristics. Methods: We analyzed whole-exome and whole-genome sequence data from 40 probands with familial ALS and 413 patients with sporadic ALS without previously identified causative variants. Reverse transcription polymerase chain reaction (RT-PCR) analysis and droplet digital PCR (ddPCR) were used to assess splicing and mosaicism, respectively. Plasma sphingolipid levels were quantified to analyze biochemical consequences. Results: The heterozygous c.58G>A, p.Ala20Thr variant was identified in a 21-year-old Japanese female patient presenting with symmetric weakness which slowly progressed over 15 years. RT-PCR analysis showed no splice defects. Plasma sphingolipid levels in the patient were significantly increased compared to her asymptomatic parents. ddPCR revealed that the asymptomatic father harbored a mosaic variant with 17% relative mutant allele abundance in peripheral blood leukocytes. Conclusions: We identified a pathogenic c.58G>A, p.Ala20Thr SPTLC1 variant in a patient with juvenile ALS, likely inherited from an asymptomatic parent with mosaicism. Lipid analysis results are consistent with previous findings on SPTLC1-associated ALS. Further studies are necessary to determine the clinical effect of mosaic variants of SPTLC1. [ABSTRACT FROM AUTHOR]

A monoanionic bidentate [PN]‐type ligand based on dibenzophosphole was synthesized, and its coordination properties toward titanium and zirconium were investigated. The complexes [PN]M (NR2)3 (M = Ti, R = Me; M = Zr, R = Et) were synthesized through the reaction of 4‐(1H‐pyrrole‐2‐yl)dibenzophosphole, [PN]H, with three equivalents of Ti (NMe2)4 or Zr (NEt2)4. Both titanium and zirconium complexes featuring the [PN] ligand were characterized by NMR and elemental analysis. Single‐crystal X‐ray crystallography unveiled the solid‐state structure of [PN]Zr (NEt2)3, with the pyrrolido group coordinated to the zirconium center in the η1‐mode. Ethylene polymerization at 0.4 MPa using these complexes and dried modified methylaluminoxane (dMMAO) as a cocatalyst yielded linear polyethylene (PE) with a melting point of 128°C–136°C; the polymerization activity reached up to 64 kg/mol (Zr)·h·bar at 70°C. [ABSTRACT FROM AUTHOR]

Comprehending the resilience of regional hydroclimate in response to CO2 removal is essential for guiding future mitigation and adaptation strategies. Using an ensemble of model simulations forced by idealized CO2 ramp-up followed by ramp-down, here we show that the winter precipitation over the Northeastern Pacific and Western North America (NPWNA) is irreversible even if global warming is reversed back to 2 °C level. This asymmetric change features a tripolar pattern and is tied to Aleutian Low intensification, which is driven by both zonal and meridional gradients of sea surface temperature (SST) anomalies in the tropical central-eastern Pacific. Distinct from the zonal SST gradient—explained by different timescales of surface and subsurface warming and ocean dynamical processes, amplified through the Bjerknes feedback—the meridional SST gradient originates from the southward shift of the intertropical convergence zone, maintained by the wind-evaporation-SST feedback. Our findings suggest that the regional hydrological risks over the NPWNA induced by CO2 ramp-up cannot be fully eliminated by CO2 removal even if the global warming level is restored back. [ABSTRACT FROM AUTHOR]

Comprehending the resilience of regional hydroclimate in response to CO2 removal is essential for guiding future mitigation and adaptation strategies. Using an ensemble of model simulations forced by idealized CO2 ramp-up followed by ramp-down, here we show that the winter precipitation over the Northeastern Pacific and Western North America (NPWNA) is irreversible even if global warming is reversed back to 2 °C level. This asymmetric change features a tripolar pattern and is tied to Aleutian Low intensification, which is driven by both zonal and meridional gradients of sea surface temperature (SST) anomalies in the tropical central-eastern Pacific. Distinct from the zonal SST gradient—explained by different timescales of surface and subsurface warming and ocean dynamical processes, amplified through the Bjerknes feedback—the meridional SST gradient originates from the southward shift of the intertropical convergence zone, maintained by the wind-evaporation-SST feedback. Our findings suggest that the regional hydrological risks over the NPWNA induced by CO2 ramp-up cannot be fully eliminated by CO2 removal even if the global warming level is restored back. [ABSTRACT FROM AUTHOR]

Since therapeutic options are limited the utilization of prebiotics is suggested to prevent food allergies (FAs). Using an experimental peach allergy model we explored the effect of dietary fiber pectin, a high-methoxyl heteropolysaccharide, on the manifestation of FA. CBA/J mice were sensitized, subsequently orally boosted and provoked with peach peel extract. For dietary intervention, mice were fed a pectin containing diet before (primary-preventive) or after (secondary-preventive) sensitization. Non-treated allergic and sham-treated mice were fed a diet containing 20% cellulose. Fecal microbiota, humoral and intestinal immune cell responses were analyzed. Pectin remarkably affected the gut microbiota composition and diversity, promoting mainly the growth of Bacteroides. The frequency of mast cells, macrophages, and CD3+T cells in the lamina propria of the small intestine was reduced, whereas the frequency of B cells and CD4+T cell subpopulation was enhanced. Pectin intervention in the primary-preventive stetting significantly triggered serum IgA levels, whereas production of IgE and mMCPT-1 was reduced. Remarkably, in both settings peach allergen-specific IgG1/IgG2a ratio and specific IgE were significantly reduced to baseline. The data suggest, that dietary supplementation of pectin in both intervention approaches can diminish inflammatory responses and signs of allergic immune responses, accompanied by alteration of the gut microbiota composition. [ABSTRACT FROM AUTHOR]

Recent studies focusing on neural activity captured by neuroimaging modalities have provided various metrics for elucidating the functional networks and dynamics of the entire brain. Functional magnetic resonance imaging (fMRI) can depict spatiotemporal functional neural networks and dynamic characteristics due to its excellent spatial resolution. However, its temporal resolution is limited. Neuroimaging modalities such as electroencephalography (EEG) and magnetoencephalography (MEG), which have higher temporal resolutions, are utilized for multi-temporal scale and multi-frequency-band analyzes. With this advantage, numerous EEG/MEG-bases studies have revealed the frequency-band specific functional networks involving dynamic functional connectivity and multiple temporal-scale time-series patterns of neural activity. In addition to analyzing neural data, the examination of behavioral data can unveil additional aspects of brain activity through unimodal and multimodal data analyzes performed using appropriate integration techniques. Among the behavioral data assessments, pupillometry can provide comprehensive spatial-temporal-specific features of neural activity. In this perspective, we summarize the recent progress in the development of metrics for analyzing neural data obtained from neuroimaging modalities such as fMRI, EEG, and MEG, as well as behavioral data, with a special focus on pupillometry data. First, we review the typical metrics of neural activity, emphasizing functional connectivity, complexity, dynamic functional connectivity, and dynamic state transitions of whole-brain activity. Second, we examine the metrics related to the time-series data of pupillary diameters and discuss the possibility of multimodal metrics that combine neural and pupillometry data. Finally, we discuss future perspectives on these multiple and multimodal metrics. [ABSTRACT FROM AUTHOR]

During morphogenesis, epithelial sheets undergo sequential folding to form three-dimensional organ structures. The resulting folds are often irreversible, ensuring that morphogenesis progresses in one direction. However, the mechanism establishing folding irreversibility remains unclear. Here, we report a mechanical property of epithelia that determines folding irreversibility. Using a mechanical assay, we demonstrate that long-term, high-curvature folding induces plastic, irreversible deformations, while short-term or low-curvature folding results in an elastic, shape-restoring response. This elastic-plastic transition occurs in a switch-like manner, with critical thresholds in folding curvature and duration. The transition is induced by F-actin accumulating into a bracket-like structure across the fold, triggered by cells sensing deformations via mechanosensitive signaling pathways, including TRPC 3/6-mediated calcium influx and ligand-independent EGFR activation. These results demonstrate that cells control epithelial folding irreversibility by detecting folding characteristics and adaptively switching between elastic and plastic responses, providing mechanical insight into the directionality of morphogenesis. During morphogenesis, epithelial folding is irreversible, ensuring that the process proceeds in one direction. Here, the authors report that, given sufficient curvature or duration of a fold, these cells can form an actin "bracket" that holds the fold in place. [ABSTRACT FROM AUTHOR]

Maintaining the high-temperature and pressure conditions required for sustained nuclear fusion is challenging due to the turbulent transport that naturally occurs in the plasma. Developing reliable models for turbulent transport is essential for progress in fusion research and development. This study proposes multi-fidelity modeling for the improved accuracy of regression models for turbulent transport in magnetic fusion plasma. Multi-fidelity modeling combines low-fidelity data, which have low accuracy but many data points, with high-fidelity data, which are highly accurate but have few data points or small parameter ranges, to enhance the overall predictive accuracy of a model. We used a multi-fidelity information fusion technique, Nonlinear AutoRegressive Gaussian Process regression (NARGP), to solve the regression problems associated with turbulent transport in plasma. We applied NARGP to (i) merge the low-resolution and high-resolution simulation results, (ii) apply regression of turbulence diffusivity to the experimental dataset using linear analyses, and (iii) adapt the quasi-linear transport model to nonlinear simulation results of a particular discharge. We demonstrated that NARGP improved the prediction accuracy of the plasma turbulent transport model. NARGP offers a robust and versatile method for integrating multi-fidelity data, and its broad applicability may contribute to optimizing fusion reactor design and operation. [ABSTRACT FROM AUTHOR]

Background: Fetal monitoring in low-resource settings is often inadequate. A mobile cardiotocograph fetal monitoring device is a digital innovation that could ensure the safety of pregnant women at high risk and their fetuses through early detection and management of fetal distress. Research is scarce on factors that affect the implementation of fetal heart monitoring using the mobile cardiotocograph device in low-resource settings, including Tanzania. This study aimed to explore the barriers and facilitators of fetal monitoring with a mobile cardiotocograph device in Tanzania. Methods: We adopted an exploratory qualitative study to analyze the barriers and facilitators of fetal monitoring using the mobile cardiotocograph device in primary healthcare facilities. Seventeen face-to-face in-depth interviews with healthcare providers and seven focus group discussions with women were conducted. Braun and Clarke's thematic analysis guided the data analysis. It included the following steps: familiarizing with data, generating initial codes, searching for themes, reviewing themes, defining and naming themes, and producing the report. Results: Three themes emerged as barriers: individual-related ones, including inadequate knowledge and skills to use mobile cardiotocograph devices, institutional barriers attributed to limited referral infrastructures and staff shortage, and community-related barriers, such as myths and misconceptions that limit antenatal care checkups. Individual factors, including motives and desires of healthcare providers and community trust in the healthcare system, support systems related to training and mentorship opportunities for healthcare providers, and the availability of community-based health programs in the respective areas, were revealed as facilitators of mobile cardiotocograph devices. Conclusion: Implementing iCTG in primary healthcare facilities is affected by several factors, from individual to institutional level. Providing user-friendly procedure manuals and training on the functions of the iCTG device and cardiotocograph interpretations could serve as potential solutions to improve the competence and confidence of healthcare providers. Moreover, the availability of supportive infrastructure, adequate human resources for health, and community sensitization were good points to start with when addressing institutional and community barriers. Nevertheless, multistakeholder engagement during the design and implementation of fetal monitoring using a mobile cardiotocograph device is warranted. [ABSTRACT FROM AUTHOR]

Purpose: Bleeding complication is a critical risk factor for outcomes of acute heart failure patients requiring mechanical circulatory support (MCS), including percutaneous catheter-type heart pumps (Impella). The Japanese registry for Percutaneous Ventricular Assist Device (J-PVAD) is an ongoing, large-scale, real-world registry to characterize Japanese patients requiring Impella. Here we analyzed bleeding complication profiles in patients who received Impella. Methods: All consecutive Japanese patients who received Impella from October 2017 to January 2020 were enrolled. The 30-day survival and bleeding complications were analyzed. Results: A total of 1344 patients were included: 653 patients received Impella alone, 685 patients received a combination of veno-arterial extracorporeal membrane oxygenation and Impella (ECPELLA), and 6 patients had failed Impella delivery. Overall 30-day survival was 67.0%, with Impella alone at 81.9% and ECPELLA at 52.7%. Overall bleeding/hematoma adverse events with a relation or not-excluded relation to Impella was 6.92%. Among them, the rates of hematoma and bleeding from medical device access sites were 1.41% and 4.09%, respectively. There was no difference between etiologies for these events. Conclusion: This study represents the first 3-year survival and the safety profile focused on bleeding adverse events from the J-PVAD registry. The results show that the real-world frequency of bleeding adverse events for patients who received Impella was an expected range from previous reports, and future real-world studies should aim to expand this data set to improve outcomes and adverse events. [ABSTRACT FROM AUTHOR]

Understanding the interaction between macrophages and biomaterials is important for the creation of new biomaterials and the development of technologies to control macrophage function. Since macrophages are strongly adhesive, caution is required when performing in vitro evaluations. Similarly, when THP-1 cells, macrophage precursor cells, are differentiated into macrophages using phorbol-12-myristate-13-acetate (PMA), it becomes difficult to detach them from the adherent substrate, which has been a problem on investigation of immunological responses to biomaterials. In this study, the interaction of THP-1 cell-differentiated macrophages with biomaterials was analyzed based on a new method of seeding THP-1 cells. THP-1 cells were cultured in static and rotation culture without and with PMA. In undifferentiated THP-1 cells, there was no change in cellular function between static and rotation cultures. In rotation culture with PMA, THP-1 cells differentiated and formed macrophage aggregates. IL-1β and MRC1 expression in macrophage aggregates was examined after differentiation and M1/M2 polarization. Macrophage aggregates in rotation culture tended to be polarized toward M2 macrophages compared with those in static culture. In the evaluation of the responses of macrophage aggregates to several kinds of polymeric materials, macrophage aggregates showed different changes in MRC1 expression over time at 30, 50, and 70 rpm. Rotation speed of 30 rpm was considered most appropriate condition in that it gave stable results with the same trend as obtained with static culture. The use of macrophage aggregates obtained by rotational culture is expected to provide new insights into the evaluation of inflammatory properties of biomaterials. [ABSTRACT FROM AUTHOR]

Our recently created RNA-sequence-based microRNA (miRNA) expression signature in breast cancer clinical specimens revealed that some miR-30 family members were significantly downregulated in cancer tissues. Based on TCGA database analyses, we observed that among the miR-30 family members, miR-30a-3p (the passenger strand derived from pre-miR-30a) was significantly downregulated in breast cancer (BC) clinical specimens, and its low expression predicted worse prognoses. Ectopic expression assays showed that miR-30a-3p transfected cancer cells (MDA-MB-157 and MDA-MB-231) had their aggressive phenotypes significantly suppressed, e.g., their proliferation, migration, and invasion abilities. These data indicated that miR-30a-3p acted as a tumor-suppressive miRNA in BC cells. Our subsequent search for miR-30a-3p controlled molecular networks in BC cells yielded a total of 189 genes. Notably, among those 189 genes, cell-cycle-related genes (ANLN, MKI67, CCNB1, NCAPG, ZWINT, E2F7, PDS5A, RIF1, BIRC5, MAD2L1, CACUL1, KIF23, UBE2S, EML4, SEPT10, CLTC, and PCNP) were enriched according to a GeneCodis 4 database analysis. Moreover, the overexpression of four genes (ANLN, CCNB1, BIRC5, and KIF23) significantly predicted worse prognoses for patients with BC according to TCGA analyses. Finally, our assays demonstrated that the overexpression of ANLN had cancer-promoting functions in BC cells. The involvement of miR-30a-3p (the passenger strand) in BC molecular pathogenesis is a new concept in cancer research, and the outcomes of our study strongly indicate the importance of analyzing passenger strands of miRNAs in BC cells. [ABSTRACT FROM AUTHOR]

We investigated a blastomycosis cluster among humans and canines in a neighborhood in Wisconsin, United States. We conducted interviews and collected serum specimens for Blastomyces antibody testing by enzyme immunoassay. Although no definitive exposure was identified, evidence supports potential exposures from the riverbank, riverside trails or yards, or construction dust. [ABSTRACT FROM AUTHOR]

Background: The pathological mechanism of the gastrointestinal forms of food allergies is less understood in comparison to other clinical phenotypes, such as asthma and anaphylaxis Importantly, high‐IgE levels are a poor prognostic factor in gastrointestinal allergies. Methods: This study investigated how high‐IgE levels influence the development of intestinal inflammation and the metabolome in allergic enteritis (AE), using IgE knock‐in (IgEki) mice expressing high levels of IgE. In addition, correlation of the altered metabolome with gut microbiome was analysed. Results: Ovalbumin‐sensitized and egg‐white diet‐fed (OVA/EW) BALB/c WT mice developed moderate AE, whereas OVA/EW IgEki mice induced more aggravated intestinal inflammation with enhanced eosinophil accumulation. Untargeted metabolomics detected the increased levels of N‐tau‐methylhistamine and 2,3‐butanediol, and reduced levels of butyric acid in faeces and/or sera of OVA/EW IgEki mice, which was accompanied with reduced Clostridium and increased Lactobacillus at the genus level. Non‐sensitized and egg‐white diet‐fed (NC/EW) WT mice did not exhibit any signs of AE, whereas NC/EW IgEki mice developed marginal degrees of AE. Compared to NC/EW WT mice, enhanced levels of lysophospholipids, sphinganine and sphingosine were detected in serum and faecal samples of NC/EW IgEki mice. In addition, several associations of altered metabolome with gut microbiome—for example Akkermansia with lysophosphatidylserine—were detected. Conclusions: Our results suggest that high‐IgE levels alter intestinal and systemic levels of endogenous and microbiota‐associated metabolites in experimental AE. This study contributes to deepening the knowledge of molecular mechanisms for the development of AE and provides clues to advance diagnostic and therapeutic strategies of allergic diseases. [ABSTRACT FROM AUTHOR]

The microwave free-space technique is an important method to characterize material properties in the scientific fields and actual applications. A microstrip patch antenna is a good radiating element to construct a compact, low-cost free-space setup. It is necessary to clarify the effects of different properties of radiating patch antenna. In this study, microwave attenuation and phase shift are measured with patch antennas with different radiated microwave power and gain. Both the experimental results of attenuation and phase shift show that a high gain of the radiating elements is helpful to measure the microwave parameters in the free-space method accurately, while improving radiating power has less effect. [ABSTRACT FROM AUTHOR]

Formalin-fixed paraffin-embedded (FFPE) tissue samples are important for genomic analysis of thyroid carcinomas, particularly for various molecularly targeted therapies. Therefore, this study developed and validated a technique for preparing FFPE tissue samples that preserves nucleic acid quality, which is fundamental for precise genomic analysis, more effectively than conventional methods. We analyzed surgically resected thyroid gland tumors, lymph node metastases, and separately fixed tumor samples to optimize formalin fixation and assess the influence of specimen type and preparation methods on nucleic acid quality. We assessed several quality indicators, including the DNA integrity number, cycle threshold ratio, RNA integrity number, and DV200. Separately fixed tumor samples consistently exhibited higher DNA and RNA quality than conventionally processed samples. Additionally, lymph node metastases often exhibit nucleic acid quality matching or exceeding that of thyroid gland tumors, highlighting their potential reliability for genomic analysis. These findings suggest the utility of various specimen types for the comprehensive genetic profiling of thyroid carcinomas. In conclusion, this study demonstrated that preparing separately fixed tumor samples is an effective method for preserving DNA and RNA quality for genomic analyses. Biopsy punches enable specimen collection at various facilities, including those without the ability to handle frozen specimens. This contributes to the development of a method for obtaining high-quality pathological samples that can be widely used in general medical practice. Moreover, lymph node metastases often exhibit nucleic acid quality equal to or superior to that of thyroid gland tumors, highlighting their potential as acceptable sources for genomic analyses. [ABSTRACT FROM AUTHOR]

The article in the Journal of Neurology discusses a case of argyrophilic grain disease (AGD) initially diagnosed as Parkinson's disease. AGD is a tauopathy that can lead to cognitive decline, with specific neuropathological features such as argyrophilic grains and astrocytic changes. The case study describes an 89-year-old woman with parkinsonian symptoms who later developed dementia, leading to a diagnosis of PD with dementia. Postmortem examination confirmed AGD as the underlying pathology, highlighting the importance of considering AGD in cases of parkinsonism without dementia in older individuals. [Extracted from the article]

Constrained geometry complexes (CGCs) are homogeneous olefin polymerization catalysts that have been improved because of their considerably high activity and their copolymerization abilities for ethylene with α‐olefins. The ancillary ligands in CGCs comprise bridged 6π‐electron moieties (e.g., cyclopentadienyl (Cp) and fluorenyl) and amide donors. In this study, we investigated the effect of changing the 6π‐electron moieties to a diphenylmethyl moiety (Ph2C) on the polymerization activity of [Me2Si(Ph2C)(tBuN)]ZrCl2(thf) (thf = tetrahydrofuran). We synthesized [Me2Si(Ph2C)(tBuN)]ZrCl2(thf) and characterized it via 1H nuclear magnetic resonance analysis and single‐crystal X‐ray crystallography. Ethylene polymerization at 2 MPa using a catalyst of the [Me2Si(Ph2C)(tBuN)]ZrCl2(thf) and modified methylaluminoxane (MMAO) as a cocatalyst yielded a linear polyethylene (PE) with a high melting point (124°C–134°C); moreover, the polymerization activity of the catalyst was found to be up to 445 g (PE) mmol (Zr)−1 h−1. The polymerization of styrene using the zirconium complex and MAOs did not proceed, but the polymerization of 1,3‐butadiene produced a small amount of polybutadiene with ~60% cis‐1,4‐structure. These results indicate that non‐Cp‐type CGCs, which can be defined as metal complexes bearing an ancillary ligand in which non‐Cp moieties (benzyl moiety in this study) and an amido group are bridged by an organic linker, can become a new family of homogeneous olefin polymerization catalysts. [ABSTRACT FROM AUTHOR]

The document discusses a case of a septuagenarian man with adult T-cell leukemia-lymphoma (ATL) and neurolymphomatosis, successfully managed with valemetostat. ATL is a rare and aggressive malignancy linked to HTLV-1, with neurological complications like CNS involvement and neurolymphomatosis. Treatment typically involves chemotherapy, but valemetostat, a novel inhibitor, showed promise in this case. The patient experienced improvements with valemetostat, but adverse reactions led to discontinuation and eventual demise. The study highlights the potential of valemetostat in treating ATL with neurological complications, emphasizing the need for further research in this area. [Extracted from the article]

Bitter taste perception is crucial for animal survival. By detecting potentially harmful substances, such as plant secondary metabolites, as bitter, animals can avoid ingesting toxic compounds. In vertebrates, this function is mediated by taste receptors type 2 (T2Rs), a family of G protein-coupled receptors (GPCRs) expressed on taste buds. Given their vital roles, T2Rs have undergone significant selective pressures throughout vertebrate evolution, leading to frequent gene duplications and deletions, functional changes, and intrapopulation differentiation across various lineages. Recent advancements in genomic and functional research have uncovered the repertoires and functions of bitter taste receptors in a wide range of vertebrate species, shedding light on their evolution in relation to dietary habits and other ecological factors. This review summarizes recent research on bitter taste receptors and explores the mechanisms driving the diversity of these receptors from the perspective of vertebrate ecology and evolution. [ABSTRACT FROM AUTHOR]

In today's information-driven society, the amount of generated and processed data is constantly increasing, requiring continuous advancements and refinements of memory components. With global digitalization, there is an urgent need for data storage devices meeting specific criteria: they should be energyefficient and compact, possess high capacity, and rapid information read/write rates, while being sustainable and made of recyclable materials. In this context, metal--organic frameworks (MOFs) could become efficient alternative materials for memory device creation due to their simple synthesis, scalability, and low energy consumption. The fabrication process for MOF-based memory elements is straightforward and efficient. Here we propose MOFs (HKUST-1) synthesis using an innovative approach based on droplet microfluidics that allows MOFs synthesis in 32 s, which can be used for further fabrication of memory elements. After revealing optimized experimental synthesis conditions by numerical simulation of droplet formation in a channel of a microfluidic chip, we obtain HKUST-1 microcrystals of various crystallinities and sizes by adjusting the reaction temperature and flow rates. We conduct a thorough structural and optical investigation of the resulting HKUST-1 microcrystals, which we further deposit on a conductive platform to form a memristive element. The memory device made from MOF microcrystals developed using droplet microfluidics demonstrates a higher ON/OFF ratio and faster fabrication compared to conventionally synthesized MOFs. [ABSTRACT FROM AUTHOR]

The control of the microstructures of polymer materials derived from diene‐based monomers is crucial, and various synthetic methods, including anionic, radical, and coordination polymerization reactions, have been extensively explored. Here, we demonstrated the coordination polymerization of 2‐phenyl[3]dendralenes (P3D) as a diene monomer. The polymerization process using monocyclopentadienyltitanium trichloride (CpTiCl3) as a catalyst and modified methylaluminoxane (MMAO) as a cocatalyst (CpTiCl3/MMAO) yielded polymers with an exclusive 4,6‐structure that is distinct from those produced by anionic polymerization. Furthermore, the copolymerization of P3D with isoprene and styrene proceeded randomly. [ABSTRACT FROM AUTHOR]

Morphogens, locally produced signaling molecules, form a concentration gradient to guide tissue patterning. Tissue patterns emerge as a collaboration between morphogen diffusion and responsive cell behaviors, but the mechanisms through which diffusing morphogens define precise spatial patterns amidst biological fluctuations remain unclear. To investigate how cells respond to diffusing proteins to generate tissue patterns, we develop SYMPLE3D, a 3D culture platform. By engineering gene expression responsive to artificial morphogens, we observe that coupling morphogen signals with cadherin-based adhesion is sufficient to convert a morphogen gradient into distinct tissue domains. Morphogen-induced cadherins gather activated cells into a single domain, removing ectopically activated cells. In addition, we reveal a switch-like induction of cadherin-mediated compaction and cell mixing, homogenizing activated cells within the morphogen gradient to form a uniformly activated domain with a sharp boundary. These findings highlight the cooperation between morphogen gradients and cell adhesion in robust tissue patterning and introduce a novel method for tissue engineering to develop new tissue domains in organoids. Synopsis: A synthetic biology approach termed SYMPLE3D demonstrates that cell adhesion output in response to diffusible proteins can convert a signaling gradient into binarized tissue domains with a sharp boundary. The SYMPLE3D system allows to explore which cellular responses to secreted proteins can robustly generate multicellular patterns. Interlocking of morphogen gradient and cadherin induces a robust pattern of distinct tissue domains with a sharp boundary. Morphogen-induced cadherin gathers receiver cells to remove ectopically-activated cells within a signaling gradient. A switch-like property of cadherin function causes cell mixing inside a morphogen gradient, generating a uniformly-activated tissue domain. A synthetic biology approach termed SYMPLE3D demonstrates that cell adhesion output in response to diffusible proteins can convert a signaling gradient into binarized tissue domains with a sharp boundary. [ABSTRACT FROM AUTHOR]

Flow experience is one of the most ambitious targets of any user interface designer. However, it has remained elusive to evaluate how well user interfaces give rise to flow experience outside conducting invasive self-reporting-based questionnaires, which remove the users from the flow experience and can't be massively applied. At the same time, otherwise, well-built systems do track the behaviour of users on the interface, and therefore, user behaviour data could act as a reliable proxy for assessing the experience of users. Currently, there is little empirical research or data about which indices of user behaviours might correspond with having a flow experience as well as the different psychological constituents of the flow experience. Therefore, facing the challenge of using users' behaviour data to model users' experience, we investigated the associations between users' behaviour data (e.g. mouse clicks, activity time in the system, and average response time) and their self-reported flow experience by using data mining (i.e. associations rules) analysing data from 204 subjects. Results demonstrate that the speed of users' actions negatively affects the flow experience antecedents while also positively affecting the loss of self-consciousness. Our study advances the literature, providing insights to identify users' flow experience through behaviour data. [ABSTRACT FROM AUTHOR]

Context The relationship between the genomic profile and prognosis of advanced thyroid carcinoma requiring drug therapy has not been reported. Objective To evaluate the treatment period and overall survival time for each genetic alteration in advanced thyroid carcinoma that requires drug therapy. Methods We conducted a retrospective observational study using a national database in Japan, which included 552 cases of thyroid carcinoma out of 53 543 patients in the database. Results The database included anaplastic thyroid carcinoma (23.6%), poorly differentiated thyroid carcinoma (10.0%), and differentiated thyroid carcinoma (66.4%). The most common genetic abnormalities were TERT promoter (66.3%), BRAF (56.7%), and TP53 (32.2%). The typical driver genes were BRAF V600E (55.0%), RAS (18.5%), RET fusion (4.7%), NTRK fusion (1.6%), and ALK fusion (0.4%). The most common regimen was lenvatinib, and the time to treatment failure was not different despite the presence of BRAF or RAS mutations. In differentiated thyroid carcinoma and poorly differentiated thyroid carcinoma, TP53 alterations independently predicted worse overall survival (hazard ratio = 2.205, 95% confidence interval: 1.135-4.283). In anaplastic thyroid carcinoma, no genetic alterations were associated with overall survival. Conclusion Genetic abnormalities with treatment options were found in 62.7% of advanced thyroid carcinomas. TP53 abnormality was an independent poor prognostic factor for overall survival in differentiated thyroid carcinoma. The time to treatment failure for lenvatinib was not different based on genetic profile. [ABSTRACT FROM AUTHOR]

Background: Although acute hepatitis caused by varicella zoster virus mostly develops in immunocompromised patients, hyperacute liver failure is very rare. To our knowledge, there are no previous reports on liver transplant patients. Methods: We report the first case of fatal hyperacute liver failure due to varicella zoster virus immediately after living‐donor liver transplantation without cutaneous lesions and review the literature. Result: The present case exhibited rapid development and progression of acute liver failure from postoperative days 11–13, despite being seropositive for varicella zoster virus but unvaccinated and on immunosuppression before transplantation. Especially in solid organ transplantation, only six cases of severe acute liver failure that included hepatic encephalopathy and/or impaired consciousness and sudden extremely high (> 4000 U/L) serum aspartate aminotransferase levels have been reported in heart, lung, and kidney transplant patients. Conclusions: Early diagnosis of hyperacute liver failure due to varicella zoster virus is challenging because the disease progresses rapidly and skin lesions are absent. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer is characterized by aggressive peritoneal dissemination. Neutrophils are mobilized to peritoneal cavity in some patients with ovarian cancer dissemination; however, its pathological significance remains unknown. This study aimed to investigate the role of neutrophil extracellular traps (NETs) in ovarian cancer dissemination. We conducted a retrospective analysis of clinical data and samples from 340 patients with ovarian cancer who underwent primary surgery between 2007 and 2016 at the Osaka University Hospital. In vitro, NETs formation was induced by stimulating human peripheral neutrophils. The human ovarian cancer cell line, OVCAR8, was cocultured with NETs. For an ovarian cancer dissemination mouse model, we performed an intraperitoneal injection of OVCAR8 cells into nude mice. The association between NETs and peritoneal dissemination was explored, and model mice were treated with the PAD4 inhibitor GSK484 to assess antitumor efficacy. Neutrophilia (neutrophil count >7000/mm3) correlated with shorter survival, advanced peritoneal dissemination, elevated granulocyte colony-stimulating factor (G-CSF) levels, increased neutrophil count in ascites, and augmented NETs foci in peritoneal dissemination sites. In vitro assays revealed that G-CSF stimulated neutrophils to form NETs, promoting cancer cell adhesion. In vivo investigations revealed that G-CSF–producing tumor-bearing mice had accelerated peritoneal dissemination and poor prognosis. NETs formation was pathologically observed at the peritoneal dissemination sites. Inhibition of NETs formation by GSK484 significantly delayed peritoneal dissemination in vivo. In conclusion, G-CSF was associated with intra-abdominal NETs formation and increased peritoneal dissemination. NETs represent potential therapeutic targets for ovarian cancer, particularly in patients with neutrophilia. [ABSTRACT FROM AUTHOR]

In this study, the adsorptive behavior of zirconium metal–organic frameworks (Zr-MOFs) was investigated for the adsorption of alkali and alkaline earth metal ions from multi-element aqueous solutions. Zr-MOFs exhibit high water stability, notable surface area, and a significant pore volume, all of which contribute to their enhanced adsorption capacity. Three Zr-MOFs, namely bare UiO-66, amine-functionalized NH2-UiO-66, and carboxyl-functionalized UiO-66-(COOH)2, were tested for the adsorption of alkali and alkaline earth metal ions. Among the 3 MOFs that were tested, only the carboxyl group-functionalized Zr-MOF showed significant adsorption capacity toward divalent metal ions. Further, a thorough investigation was conducted to understand how the pH, initial concentration of the solution, and Zr-MOF dosage impact the adsorption properties of UiO-66-(COOH)2. At the natural pH (6.5) of the solution, UiO-66-(COOH)2 exhibited a superior adsorption capacity toward Sr2+ (15.3 mg g−1) and Ca2+ (7.9 mg g−1), which was attributable to the stronger electrostatic attraction of these ions relative to monovalent ions. The kinetic study results indicated that the preferred mechanism of adsorption was chemisorption for divalent metal ions. Additionally, the adsorption behavior of UiO-66-(COOH)2 for 24 elements was evaluated and the MOF showed significant adsorption of Sr2+ and Ca2+ alongside other divalent and trivalent metal ions. The experimental findings of the present study suggest that carboxylic-functionalized Zr-MOF holds significant potential toward the preparation of suitable sorbents for the extraction of higher-valence metal ions. [ABSTRACT FROM AUTHOR]

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

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

Widely present in Japan's deep subterranean formations, pre-Neogene sedimentary rocks offer an option for high-level radioactive waste (HLW) deep geological disposal due to their favorable properties. However, their barrier properties necessitate further investigation. This research examines the characteristics of pre-Neogene sedimentary rocks, focusing on two rock types: the melange type with a distinct block-in-matrix structure and the sandstone-dominant coherent type. Their ability and mechanism to sorb Cs+ and Eu3+ are assessed, and the differences between the two types are compared. The influence of inorganic carbon in groundwater and the role of clay minerals, such as illite, in the sorption of these metal ions, are highlighted. This investigation lays the groundwork for future studies on migration behaviors of radionuclides, essential for ensuring the long-term safety of HLW geological disposal. [ABSTRACT FROM AUTHOR]

Loss-of-function (LoF) variants in the TANK binding kinase 1 (TBK1) gene are implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. In this study, we present the first familial cases of ALS and parkinsonism associated with a novel TBK1 variant. We describe two siblings: one diagnosed with classical ALS and the other with a unique syndrome overlapping ALS and parkinsonism. Comprehensive clinical and imaging evaluations supported these diagnoses. Genetic analysis through whole-genome sequencing revealed a previously unknown heterozygous splice site variant in TBK1. Functional assessments demonstrated that this splice site variant leads to abnormal splicing and subsequent degradation of the mutated TBK1 allele by nonsense-mediated decay, confirming its pathogenic impact. Our findings suggest a broader involvement of TBK1 in neurodegenerative diseases and underscore the need for further research into TBK1's role, advocating for screening for TBK1 variants in similar familial cases. [ABSTRACT FROM AUTHOR]

This study aimed to determine the characteristics of accelerations and angular velocities obtained by an inertial measurement unit (IMU) attached to a cane between older people with and without physical frailty. Community-dwelling older people walked at a comfortable speed using a cane with a built-in IMU. Physical frailty was assessed using exercise-related items extracted from the Kihon Check List. The efficacy of five machine learning models in distinguishing older people with physical frailty was investigated. This study included 48 older people, of which 24 were frail and 24 were not. Compared with the non-frail participants, the older people with physical frailty had a small root mean square value in the vertical and anteroposterior directions and angular velocity in the anteroposterior direction (p < 0.001, r = 0.36; p < 0.001, r = 0.29; p < 0.001, r = 0.30, respectively) and a large mean power frequency value in the vertical direction (p = 0.042, r = 0.18). The decision tree model could most effectively classify physical frailty, with an accuracy, F1 score, and area under the curve of 78.6%, 91.8%, and 0.81, respectively. The characteristics of IMU-attached cane usage by older adults with physical frailty can be utilized to effectively evaluate and determine physical frailty in their usual environments. [ABSTRACT FROM AUTHOR]

Purpose: To describe Light Adjustable Lens (RxSight, Inc) (LAL) visual and refractive outcomes in a Japanese patient population with and without prior refractive surgery. Methods: In this retrospective chart review of patients with cataract in a private eye clinic, 34 eyes from 21 patients underwent cataract surgery with LAL implantation. Eyes underwent light treatment to adjust the patients' refraction after implantation to meet individual visual goals. Standard visual and refractive outcomes were collected. Contrast sensitivity (to assess quality of vision), clinical defocus and vergence curves (to assess range of vision), and patient satisfaction were also collected. Results: The mean prediction error of the light adjustment was −0.04 ± −0.48. Thirty-one eyes (91%) and 33 eyes (97%) were within ±0.25 and ±0.50 diopters (D) of manifest spherical equivalent target, respectively. Thirty-two eyes (94%) had residual refractive cylinder of 0.50 D or less. The full depth of focus was 3.68 D. Monocular contrast sensitivity shows frequencies equivalent to a normal population aged 50 to 60 years. The mean satisfaction score was 8.8 (scale: 1 to 10). There were no adverse events and no eyes lost corrected distance visual acuity from the light treatment. Conclusions: LALs in cataract refractive surgery hold great promise, including for the Japanese population, which have unique ocular biometrics. By providing a safe procedure and the ability for postoperative adjustments, the LAL provided a tailored approach to vision correction, ultimately improving patient outcomes and satisfaction. [J Refract Surg. 2024;40(11):e854–e862.] [ABSTRACT FROM AUTHOR]

Introduction: Hybrid dialysis is widely used in Japan. Although previous reports have shown the beneficial effects of hybrid dialysis, little is known about the daily change in peritoneal ultrafiltration volume in hybrid dialysis. Methods: A multicenter, cross‐sectional study was conducted in 25 patients with hybrid dialysis. The primary outcome measure was the change in peritoneal ultrafiltration volume between after HD and before HD, according to PD prescription and PD holiday. The secondary outcome measure was the correlation between the difference in ultrafiltration volume and each factor. Results: The total ultrafiltration volume and the ultrafiltration volume of glucose dialysate after HD increased from 970 ± 408 to 1151 ± 480 (p < 0.01) and from 576 ± 392 to 750 ± 517 (p < 0.01), respectively, compared with before HD. In contrast, the ultrafiltration volume of icodextrin dialysate did not change (from 470 ± 204 to 494 ± 242, p = 0.40). The difference in total ultrafiltration volume was correlated with the difference in glucose dialysate ultrafiltration volume and hybrid duration, but not with the difference in icodextrin dialysate ultrafiltration volume and peritoneal dialysis duration. Conclusion: This study showed that the peritoneal ultrafiltration volume for glucose dialysate increased after HD compared with before HD in patients with hybrid dialysis, whereas that for icodextrin dialysate did not change. [ABSTRACT FROM AUTHOR]

Introduction: Carney's triad is a rare syndrome characterized by the co-occurrence of gastric gastrointestinal stromal tumor (GIST), pulmonary chondroma, and extra-adrenal paraganglioma. We present a case of a young woman with GISTs associated with this triad. Case presentation: A 28-year-old woman was identified with multiple gastric tumors and a right lung nodule during a routine health check-up. CT scans and upper gastrointestinal endoscopy revealed a 50 mm mass on the lesser curvature of the stomach, along with two additional gastric lesions and a 20 mm nodule in the right lung. The patient had a history of right middle lobectomy at the age of 19 for pulmonary chondroma. During surgery, enlarged lymph nodes were observed, indicating metastasis, which necessitated a total gastrectomy with radical (D2) lymph node dissection. Pathological examination confirmed seven GISTs, with immunohistochemical staining positive for KIT (+), DOG1 (+), and negative for SDHB (−). The postoperative course was uneventful, and the patient was discharged on the seventh postoperative day. Despite opting out of adjuvant imatinib therapy, she remains disease-free 2 years postoperatively. Conclusions: This case underscores the necessity of total gastrectomy with lymph node dissection due to the high incidence of metastasis in GISTs associated with Carney's triad. Further research is required to determine the optimal extent of lymph node dissection in such cases. [ABSTRACT FROM AUTHOR]

The article "The repressed life of adult female patients with mild ADHD" published in Frontiers in Psychiatry discusses the overlooked characteristics of adult females with mild ADHD, focusing on their daily struggles and psychopathological phenotypes. It highlights the challenges faced by these individuals in the workplace, their tendency to camouflage their symptoms, and the prevalence of comorbidities such as anxiety disorders. The article also addresses the cultural differences in symptom manifestation and the impact of ADHD on social activities. The authors emphasize the need for a better understanding of these individuals to prevent underdiagnosis or misdiagnosis. [Extracted from the article]

Background: Scheie syndrome, an attenuated subtype of mucopolysaccharidosis type I, is a rare storage disease that causes progressive glycosaminoglycans (GAGs) accumulation. Cardiovascular disorders determine the prognosis, and cardiac valve abnormalities are the most common cause. The patients are usually young so mechanical valve replacement is often performed, but because of the features of this disease, the surgical treatment is very risky. Recently, transcatheter aortic valve implantation (TAVI) has been reported as an alternative choice for aortic stenosis, but optimal choice is still unclear. Here, we introduce a patient that underwent TAVI and refer to the histological finding of a biological valve extracted in relation to GAGs accumulation. Case presentation: A 54-year-old woman with Scheie syndrome underwent valve surgeries three times throughout her whole life. At age 41, she received a mitral valve replacement with a mechanical valve for mitral stenosis. She promptly developed severe diastolic dysfunction and low output syndrome after the release of aortic clamping, thus requiring temporary mechanical circulatory support4. At age 51, she suffered from heart failure due to severe aortic stenosis and underwent TAVI because conventional aortic valve replacement (AVR) was deemed too risky. Three years later, her heart failure relapsed, and an echocardiogram unexpectedly revealed thickened bioprosthetic valve leaflets and a significant pressure gradient across the valve, consistent with early structural valve deterioration. AVR was performed via median sternotomy with a mechanical valve. As with the first operation, she presented refractory heart failure requiring mechanical circulatory support and was meticulously managed. However, she steadily showed worsening of multiple organ systems and died 9 days after the operation. Pathological autopsy and histological examination revealed accumulation of tissue with GAGs on the leaflets of the bioprosthetic valve of TAVI, which may have been the cause of early structural valve deterioration. Conclusion: For patients with Scheie syndrome, a biological valve can be compromised by the accumulation of GAGs, thereby causing early SVD. These findings may support valve selection for these high-risk patients. [ABSTRACT FROM AUTHOR]