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Mothers of school-aged children ages 3 to 17 years with developmental disabilities (DDs) commonly report sleep problems in their children associated with impaired maternal sleep. However, existing research relies heavily on mothers' self-reported sleep. This study aimed to determine the feasibility of objectively measuring child and mother sleep-wake patterns using actigraphy and videosomnography. This was an observational pilot study. Mothers wore actigraphy watches and video-recorded their child's sleep for 7 nights. Mothers also completed a 7-day sleep diary and questionnaires on sleep quality, depressive symptoms, stress, and child sleep problems. Ten mothers (32-49 years) and ten children with DDs (8-12 years) completed this study. Half of the children were boys with autism spectrum disorders. We successfully recruited 77% of eligible mothers for the study during the pandemic. Eight mothers successfully wore the actigraphy, and nine successfully video-recorded their child's sleep. Mothers rated their participation positively and considered the data collection protocol acceptable. While mothers' sleep patterns from actigraphy were mostly within recommendations, self-reported sleep quality was poor. Child's sleep estimates from videosomnography showed children slept substantially less than recommended sleep hours. Mothers also reported a high frequency of child sleep problems. Consistent with this pattern, mothers also endorsed elevated stress and depression. The use of actigraphy and videosomnography is feasible. Objective sleep measurement for mothers' and children's sleep is needed with self-report to measure multidimensional aspects of sleep and discrepancies between objective and self-report sleep measures. Future studies can use multi-methods sleep measures and work toward interventions that can improve family sleep and reduce mothers' stress and depression.

Although poor health has been reported in parents of children with autism spectrum disorder (ASD), most studies excluded fathers and focused on mental health. We combined 2016-2019 data from the National Surveys of Children's Health to determine child and parent characteristics that predict poor mental and physical health in fathers (n = 818) and mothers (n = 2111) of children with ASD. For fathers of children with ASD, higher parenting stress was significantly associated with greater odds of poor physical health, whereas racial and ethnic minorities and living at 400% above the federal poverty were significantly associated with lower odds of poor mental health. For mothers of children with ASD, greater child sleep problems were significantly associated with greater odds of poor physical health, and two-parent household living 400% above the poverty line was significantly associated with reported lower odds of poor mental health. Continued efforts to reduce parenting stress and improve child sleep problems, along with expanding existing services and coverages of ASD services, especially for low-income families, may help reduce the burden on these families, preventing adverse future health outcomes in this population.

The linear dependence of age, period, and birth cohort is a challenge for the analysis of social change. With either repeated cross-sectional data or conventional panel data, raw change cannot be decomposed into over-time differences that are attributable to the effects of common experiences of alternative birth cohorts, features of the periods under observation, and the cumulation of lifecourse aging. This article proposes a rolling panel model for cohort, period, and aging effects, suggested by and tuned to the treble panel data collected for the General Social Survey from 2006 through 2014. While the model does not offer a general solution for the identification of the classical age-period-cohort accounting model, it yields warranted interpretations under plausible assumptions that are reasonable for many outcomes of interest. In particular, if aging effects can be assumed to be invariant over the course of an observation interval, and if separate panel samples of the full age distribution overlap within the same observation interval, then period and aging effects can be parameterized and interpreted separately, adjusted for cohort differences that pulse through the same observation interval. The estimated cohort effects during the observation interval are then interpretable as effects during the observation interval of entangled period and cumulated aging differences from before the observation interval.

The so-called “Corona Blue” decline in mental health after the COVID-19 outbreak. This study examines how COVID-19 risk perception affects mental health via urban space usage in Seoul, Korea, and Shanghai, China. It uniquely explores direct PR-MH and OS-MH effects, along with indirect effects mediated by pandemic-driven changes in urban space utilization. Results reveal that visits to urban destinations and open spaces mediate the relationship between perceived risk and MH, with differing significance levels between the two cities. In Seoul, disruptions in daily life negatively affected mental health through decreased interactions with urban destinations and outdoor spaces, with a statistically significant impact on stress through urban destinations. This suggests that maintaining access to and engagement with these spaces is crucial for mental health during crises. Conversely, Shanghai showed indirect effects predominantly through perceptions of safety, which significantly influenced anxiety levels through urban destinations, but did not manifest similarly through interactions with outdoor spaces. Caution in interpretation is necessary for better generation, but the outcomes of this study underscore the importance of considering cultural, historical, and political contexts in understanding the varying impacts of future pandemic policies on mental health.

Abstract We demonstrate that the contextuality of measurement selection can enhance the precision of quantum metrology with a simple linear optical experiment. Contextuality is a nonclassical property known as a resource for various quantum information processing tasks. Recent studies show that contextuality by anomalous weak values can be utilized to enhance metrological precision, unraveling the role of contextuality in quantum metrology. Our contextual quantum metrology (coQM) scheme can elevate the precision of the optical polarimetry as much as 6 times the precision limit given by the Quantum Fisher Information. We achieve the contextuality-enabled enhancement with two mutually complementary measurements, whereas, in the conventional method, some optimal measurements to achieve the precision limit are either theoretically challenging to find or experimentally infeasible to realize. These results highlight that the contextuality of measurement selection is applicable in practice for quantum metrology.

We identified a novel mouse plasmacytoid dendritic cell (pDC) lineage derived from the common lymphoid progenitors (CLPs) that is dependent on expression of Bcl11a. These CLP-derived pDCs, which we refer to as ‘B-pDCs’, have a unique gene expression profile that includes hallmark B cell genes, normally not expressed in conventional pDCs. Despite expressing most classical pDC markers such as SIGLEC-H and PDCA1, B-pDCs lack IFN-α secretion, exhibiting a distinct inflammatory profile. Functionally, B-pDCs induce T cell proliferation more robustly than canonical pDCs following Toll-like receptor 9 (TLR9) engagement. B-pDCs, along with another homogeneous subpopulation of myeloid-derived pDCs, display elevated levels of the cell surface receptor tyrosine kinase AXL, mirroring human AXL+ transitional DCs in function and transcriptional profile. Murine B-pDCs therefore represent a phenotypically and functionally distinct CLP-derived DC lineage specialized in T cell activation and previously not described in mice.

Objectives While older adults showed higher mortality during COVID-19 pandemic, protective behaviours (knowledge regarding coping with COVID-19 symptoms and preventive behaviours) were highlighted to be important to prevent the spread of infection. This study aimed to identify individual and community-level variables influencing deficient knowledge regarding coping with COVID-19 and not-practicing COVID-19 of older adults during the pandemic.Design This is a secondary analysis of a cross-sectional study using the 2020 Korea Community Health Survey (KCHS).Setting 255 community public health centres nationwide, South Korea.Methods and analysis Using 2020 KCHS data, multilevel logistic regression analysis was conducted on 55 005 adults aged 65 years or older.Results Older adults who reside alone, as opposed to with their spouse and who lack the support of another individual exhibited insufficient COVID-19 coping-related knowledge (OR: 1.142, p

Abstract This observational study aimed to compare the glottic view between video and direct laryngoscopy for tracheal intubation in the surgical position for thyroid surgery with intraoperative neuromonitoring. Patients scheduled for elective thyroid surgery with intraoperative neuromonitoring were enrolled. After the induction of anesthesia, patients were positioned in the thyroid surgical posture with a standard inclined pillow under their head and back. An investigator assessed the glottic view using the percentage of glottic opening (POGO) scale and the modified Cormack–Lehane grade in direct laryngoscopy and then video laryngoscopy sequentially while using the same McGRATH™ MAC video laryngoscope at once, with or without external laryngeal manipulation, at the surgical position. A total of thirty-nine patients were participated in this study. Without external laryngeal manipulation, the POGO scale significantly improved during video laryngoscopy compared to direct laryngoscopy in the thyroid surgical position (60.0 ± 38.2% vs. 22.4 ± 23.8%; mean difference (MD) 37.6%, 95% confidence interval (CI) = [29.1, 46.0], P

Background: Fcγ-receptor (FcγR)-independent enhancement of SARS-CoV-2 infection mediated by N-terminal domain (NTD)-binding monoclonal antibodies (mAbs) has been observed in vitro, but the functional significance of these antibodies in vivo is less clear. Methods: We characterized 1,213 SARS-CoV-2 spike (S)-binding mAbs derived from COVID-19 convalescent patients for binding specificity to the SARS-CoV-2 S protein, VH germ-line usage, and affinity maturation. Infection enhancement in a vesicular stomatitis virus (VSV)-SARS-CoV-2 S pseudovirus (PV) assay was characterized in respiratory and intestinal epithelial cell lines, and against SARS-CoV-2 variants of concern (VOC). Proteomic deconvolution of the serum antibody repertoire was used to determine functional attributes of secreted NTD-binding mAbs. Results: We identified 72/1213 (5.9%) mAbs that enhanced SARS-CoV-2 infection in a PV assay. The majority (68%) of these mAbs recognized the NTD, were identified in patients with mild and severe disease, and persisted for at least 5 months post-infection. Infection enhancement by NTD-binding mAbs was not observed in intestinal and respiratory epithelial cell lines and was diminished or lost against SARS-CoV-2 VOC. Proteomic deconvolution of the serum antibody repertoire from 2 of the convalescent patients identified, for the first time, NTD-binding, infection-enhancing mAbs among the circulating immunoglobulins directly isolated from serum. Functional analysis of these mAbs demonstrated robust activation of FcγRIIIa associated with antibody binding to recombinant S proteins. Conclusions: Functionally active NTD-specific mAbs arise frequently during natural infection and can last as major serum clonotypes during convalescence. These antibodies display functional attributes that include FcγR activation, and may be selected against by mutations in NTD associated with SARS-CoV-2 VOC.

Abstract Although Li‐metal has been revisited as the most attractive anode in building high‐energy‐density batteries owing to its superiority, such as ultimate theoretical capacity and lowest working voltage, notorious Li dendrite growth has plagued its practical uses. Since dendritic Li electroplating is mostly caused by poor Li+ transport and inferior stability of solid‐electrolyte interphase (SEI), an innovative reframing of the electrolyte is crucial to the success of Li‐metal anodes (LMAs). This review presents a new class of electrolytes, nano‐colloidal electrolytes (NCEs), providing a new avenue for next‐generation Li‐metal batteries (LMBs). Without searching for new salts/solvents or their compositional tuning, NCEs exploiting multi‐functional nanoparticles dispersed in liquid electrolytes can promote Li+ transport and reinforce the SEI of liquid electrolytes that are solely used. This review discusses various types of nanoparticles and their key roles in demonstrating excellent suppression of Li dendrite growth and enhancing the cycling stability of LMBs. Unraveling the underlying design principles of NCEs offers practical solutions for stabilizing LMAs, paving the way for developing intelligent battery systems.

Abstract Antipsychotic (AP)-naive first-episode psychosis (FEP) patients display early dysglycemia, including insulin resistance and prediabetes. Metabolic dysregulation may therefore be intrinsic to psychosis spectrum disorders (PSDs), independent of the metabolic effects of APs. However, the potential biological pathways that overlap between PSDs and dysglycemic states remain to be identified. Using meta-analytic approaches of transcriptomic datasets, we investigated whether AP-naive FEP patients share overlapping gene expression signatures with non-psychiatrically ill early dysglycemia individuals. We meta-analyzed peripheral transcriptomic datasets of AP-naive FEP patients and non-psychiatrically ill early dysglycemia subjects to identify common gene expression signatures. Common signatures underwent pathway enrichment analysis and were then used to identify potential new pharmacological compounds via Integrative Library of Integrated Network-Based Cellular Signatures (iLINCS). Our search results yielded 5 AP-naive FEP studies and 4 early dysglycemia studies which met inclusion criteria. We discovered that AP-naive FEP and non-psychiatrically ill subjects exhibiting early dysglycemia shared 221 common signatures, which were enriched for pathways related to endoplasmic reticulum stress and abnormal brain energetics. Nine FDA-approved drugs were identified as potential drug treatments, of which the antidiabetic metformin, the first-line treatment for type 2 diabetes, has evidence to attenuate metabolic dysfunction in PSDs. Taken together, our findings support shared gene expression changes and biological pathways associating PSDs with dysglycemic disorders. These data suggest that the pathobiology of PSDs overlaps and potentially contributes to dysglycemia. Finally, we find that metformin may be a potential treatment for early metabolic dysfunction intrinsic to PSDs.

Background: 4-carvomenthenol[4-methyl-1-(1-methylethyl)-3-cyclohexen-1-ol] is a main component of Origanum vulgare L., Zanthoxylum piperitum (L.) DC., and other plants. It has been reported to exhibit anti-inflammatory, antibacterial, and anti-tumor effects. Furthermore, it is necessary to conduct a toxicity test on 4-carvomenthenol to ensure its safety. Methods: This study included 5-week-old Institute of Cancer Research mice that were categorized into 3 treatment groups (12, 25, and 50 mg/kg 4-carvomenthenol dose levels) and a control group (10% dimethyl sulfoxide, 40% polyethylene glycol 300, 5% Tween 80, and 45% normal saline injection of the final volume), with 5 male mice and 5 female mice per group. All groups were observed for clinical symptoms and body weight in a period of 14 days and were subjected to gross necropsy after euthanasia. Results: No deaths were recorded. No test substance-related clinical signs in the female mice of the 12 mg/kg dose group were observed. Abnormal gait was observed in 1 male from day 1 to day 3 in the 12 mg/kg dose group; 1−3 males from day 1 to day 7 and 1−5 females from day 1 to day 15 in the 25 mg/kg dose group; and 2−5 males and 2–5 females from day 1 to day 15 in the 50 mg/kg dose group. No test substance-related effect on the body weight and necropsy findings was observed. Conclusion: The results of this study suggested that the lethal dose of 4-carvomenthenol could be greater than 50 mg/kg. However, further research is needed, especially repeated-dose toxicity studies, to confirm the efficacy and safety of 4-carvomenthenol.

Abstract Background Despite a well-known relation between smoking tobacco and the tuberculosis epidemic, the factors associated with smoking cessation in tuberculosis patients are unclear. This study aims to examine the cascade of smoking cessation and the factors associated with persistent smoking among tuberculosis patients. Methods We conducted a prospective cohort study enrolling adult patients with pulmonary tuberculosis between 2016 and 2019 in the Republic of Korea. We examined the smoking status at baseline, followed the current smokers, re-examined their smoking status after 6 months of anti-tuberculosis treatment, and identified the factors associated with persistent smoking. Results Of the 419 enrolled patients, 109 (26.0%) were current smokers at baseline. Of the 79 current smokers who completed the 6-month survey, 24 (30.4%) succeeded in quitting smoking after 6 months of treatment. The adjusted odds ratio for persistent smoking was 6.57 (95% confidence interval [CI], 1.76–27.83) for drinking and 0.15 (95% CI, 0.03–0.68) for diabetes comorbidity. Conclusion Drinking alcohol and diabetes comorbidity were important factors in smoking cessation. Only one third of the tuberculosis patients in our study cohort succeeded in quitting smoking during the 6-month treatment period. More aggressive interventions for smoking cessation should be adopted within the national anti-tuberculosis program.

Abstract The presynaptic release apparatus can be specialized to enable specific synaptic functions. Habituation is the diminishing of a physiological response to a frequently repeated stimulus and in Aplysia, habituation to touch is mediated by a decrease in transmitter release from the sensory neurons that respond to touch even after modest rates of action potential firing. This synaptic depression is not common among Aplysia synaptic connections suggesting the presence of a release apparatus specialized for this depression. We found that specific splice forms of ApCaV2, the calcium channel required for transmitter release, are preferentially used in sensory neurons, consistent with a specialized release apparatus. However, we were not able to find a specific ApCaV2 splice uniquely required for synaptic depression. The C-terminus of ApCaV2 alpha1 subunit retains conserved binding to Aplysia rab-3 interacting molecule (ApRIM) and ApRIM-binding protein (ApRBP) and the C-terminus is required for full synaptic expression of ApCaV2. We also identified a splice form of ApRIM that did not interact with the ApCav2 alpha 1 subunit, but it was not preferentially used in sensory neurons.

Background and Objectives: Retrograde intrarenal surgery (RIRS) is a minimally invasive technique for nephrolithiasis. RIRS is performed via a monitor screen displaying a magnified surgical site. Respiration can affect the stability of the surgical view during RIRS because the kidneys are close to the diaphragm. The purpose of this trial is to compare the effect of anesthesia type on the stability of the surgical view during RIRS between spinal anesthesia and general anesthesia. Materials and Methods: Patients were allocated to the general anesthesia group or spinal anesthesia group. During surgery, movement of the surgical field displayed on the monitor screen was graded by the first assistant on a 10-grade numeric rating scale (0–10). Next, it was also graded by the main surgeon. After surgery, we evaluated the discomfort with the anesthesia method for all patients. Results: Thirty-four patients were allocated to the general anesthesia group and 32 patients to the spinal anesthesia group. The average values of the two surgeons for surgical field oscillation grade showed vision on the monitor screen was more stable in the general anesthesia group than the spinal anesthesia group (3.3 ± 1.6 vs. 5.0 ± 1.6, p < 0.001). The degrees of the inconvenience of the surgery did not differ between the groups (0.7 ± 1.8 vs. 1.6 ± 2.6, p = 0.114), even though more patients reported inconvenience with a grade of 3 or more in the spinal anesthesia group (8.8% vs. 28.1%, p = 0.042). Conclusions: In terms of the visualization of the surgical site, general anesthesia might provide a more stable surgical view during RIRS compared to spinal anesthesia without increasing inconvenience induced by the type of anesthesia.

Metabolic dysfunction is commonly observed in schizophrenia spectrum disorders (SSDs). The causes of metabolic comorbidity in SSDs are complex and include intrinsic or biological factors linked to the disorder, which are compounded by antipsychotic (AP) medications. The exact mechanisms underlying SSD pathophysiology and AP-induced metabolic dysfunction are unknown, but dysregulated lipid metabolism may play a role. Lipidomics, which detects lipid metabolites in a biological sample, represents an analytical tool to examine lipid metabolism. This systematic review aims to determine peripheral lipid signatures that are dysregulated among individuals with SSDs (1) with minimal exposure to APs and (2) during AP treatment. To accomplish this goal, we searched MEDLINE, Embase, and PsychINFO databases in February 2024 to identify all full-text articles written in English where the authors conducted lipidomics in SSDs. Lipid signatures reported to significantly differ in SSDs compared to controls or in relation to AP treatment and the direction of dysregulation were extracted as outcomes. We identified 46 studies that met our inclusion criteria. Most of the lipid metabolites that significantly differed in minimally AP-treated patients vs. controls comprised glycerophospholipids, which were mostly downregulated. In the AP-treated group vs. controls, the significantly different metabolites were primarily fatty acyls, which were dysregulated in conflicting directions between studies. In the pre-to-post AP-treated patients, the most impacted metabolites were glycerophospholipids and fatty acyls, which were found to be primarily upregulated and conflicting, respectively. These lipid metabolites may contribute to SSD pathophysiology and metabolic dysfunction through various mechanisms, including the modulation of inflammation, cellular membrane permeability, and metabolic signaling pathways.

We report an extensive high-sensitivity search for axion dark matter above 1 GHz at the Center for Axion and Precision Physics Research (CAPP). The cavity resonant search, exploiting the coupling between axions and photons, explored the frequency (mass) range of 1.025 GHz (4.24 μeV) to 1.185 GHz (4.91 μeV). We have introduced a number of innovations in this field, demonstrating the practical approach of optimizing all the relevant parameters of axion haloscopes, extending presently available technology. The CAPP 12 T magnet with an aperture of 320 mm made of Nb_{3}Sn and NbTi superconductors surrounding a 37 l ultralight-weight copper cavity is expected to convert Dine-Fischler-Srednicki-Zhitnitsky axions into approximately 10^{2} microwave photons per second. A powerful dilution refrigerator, capable of keeping the core system below 40 mK, combined with quantum-noise-limited readout electronics, achieved a total system noise of about 200 mK or below, which corresponds to a background of roughly 4×10^{3} photons per second within the axion bandwidth. The combination of all those improvements provides unprecedented search performance, imposing the most stringent exclusion limits on axion-photon coupling in this frequency range to date. These results also suggest an experimental capability suitable for highly sensitive searches for axion dark matter above 1 GHz.

This study aims to unveil the complexity of introducing and sustaining instructional improvement at a school site by documenting successes and challenges encountered by a research-practice partnership among university researchers, school and district leaders, and a mathematics coordinator from the county office of education. The study answers two questions: How did a research-practice partnership attend to teachers' voices and craft coherence around a school's mathematics teaching improvement goals? What characterised the complexity of sustaining the improvement efforts? Data included meeting fieldnotes, teacher survey responses, and transcripts of interviews with teachers, school and district leaders, and the county coordinator. Qualitative thematic analyses revealed several ways in which the team attended to teacher voices and crafted coherence dynamically through interactions supported by tools and activities aimed at surfacing complexity and creating a shared vision. Points of convergence included a focus on adult learning and collaboration. Analyses also unveiled challenges, including the emotional work entailed in instructional change and the necessity to buffer the school from conflicting external demands. Conclusions highlight the importance of deliberate negotiation of tensions and crafting of coherence so that stakeholders can more easily build a shared vision for high-quality classroom teaching and high-quality teacher learning.

Summary: Ribosome profiling is a sequencing technique that provides a global picture of translation across a genome. Here, we present iRibo, a software program for integrating any number of ribosome profiling samples to obtain sensitive inference of annotated or unannotated translated open reading frames. We describe the process of using iRibo to generate a species’ translatome from a set of ribosome profiling samples using S. cerevisiae as an example.For complete details on the use and execution of this protocol, please refer to Wacholder et al. (2023).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Dopamine is a hormone that is released by the adrenal gland and influences motor control and motivation. Dopamine is known to have 5 receptors which are D1, D2, D3, D4 and D5, which are further categorized into 2 families: D1 family and D2 family. The D1 family is known to play a role in motivation and motor control whereas the D2 family is known to affect attention and sleep. THC, a type of cannabinoid, can lead to feelings of euphoria, anxiety, fear, distrust, or panic. THC is known to affect dopamine in regions such as the anterior cingulate cortex (ACC), and plays a role in fundamental cognitive processes. Although there is a vast amount of research between the relationship of THC on dopamine, there continues to be limited research in relation to THC on dopamine receptors. The D1 receptor plays a role in several essential functions, such as memory, attention, impulse control, regulation of renal function, and locomotion. Accordingly, this review is intended to summarize the relationship between THC and D1 receptors, highlighting key gaps in the literature and avenues for future research.

A high-fiber diet is widely recognized for its positive effects on the gut microbiome. However, the specific impact of a high-fiber diet on the gut microbiome and bowel habits of patients with colon cancer remains poorly understood. In this study, we aimed to assess the effects of a modified microbiota-accessible carbohydrate (mMAC) diet on gut microbiota composition and clinical symptoms in colon cancer patients who underwent surgical resection. To achieve this, we enrolled 40 patients in two groups: those who received adjuvant chemotherapy and those who did not. Fecal samples were collected before and after dietary interventions for microbial and metabolite analyses. Each group was randomized in a 1: 1 ratio to follow either a 3-week conventional diet followed by a 3-week mMAC diet, or the reverse sequence. Although there were no significant differences in the microbial diversity data before and after the mMAC diet in both the non-chemotherapy and chemotherapy groups, distinct differences in gut microbial composition were revealed after the mMAC diet. Specifically, the abundance of Prevotella, which is associated with high-fiber diets, was further elevated with increased concentrations of acetate and propionate after the mMAC diet. Additionally, patients who experienced improved diarrhea and constipation after the mMAC diet exhibited an enrichment of beneficial bacteria and notable changes in metabolites. In conclusion, this study provides valuable insights into the potential benefits of the mMAC diet, specifically its impact on the gut microbiome and clinical symptoms in postoperative colorectal cancer (CRC) patients. These findings emphasize the potential role of a high-fiber diet in influencing the gut microbiome, and the clinical symptoms warrant further investigation.

Abstract Psoriasis is a skin disease that causes lesions of various sizes across the body and can persist for years with cyclic deterioration and improvement. During treatment, and a multiple-severity disease, with irregular severity within the observation area may be found. The current psoriasis evaluation is based on the subjective evaluation criteria of the clinician using the psoriasis area and severity index (PASI). We proposed a novel psoriasis evaluation method that detects representative regions as evaluation criteria, and extracts severity features to improve the evaluation performance of various types of psoriasis, including multiple-severity diseases. We generated multiple-severity disease images using CutMix and proposed a hierarchical multi-scale deformable attention module (MS-DAM) that can adaptively detect representative regions of irregular and complex patterns in multiple-severity disease analyses. EfficientNet B1 with MS-DAM exhibited the best classification performance with an F1-score of 0.93. Compared with the performance of the six existing self-attention methods, the proposed MS-DAM showed more than 5% higher accuracy than that of multiscale channel attention module (MS-CAM). Using the gradient-weighted activation mapping method, we confirmed that the proposed method works at par with human visual perception. We performed a more objective, effective, and accurate analysis of psoriasis severity using the proposed method.

Malicious reverse engineering of software has served as a valuable technique for attackers to infringe upon and steal intellectual property. We can employ obfuscation techniques to protect against such attackers as useful tools to safeguard software. Applying obfuscation techniques to source code can prevent malicious attackers from reverse engineering a program. However, the ambiguity surrounding the protective efficacy of these source code obfuscation tools and techniques presents challenges for users in evaluating and comparing the varying degrees of protection provided. This paper addresses these issues and presents a methodology to quantify the effect of source code obfuscation. Our proposed method is based on three main types of data: (1) the control flow graph, (2) the program path, and (3) the performance overhead added to the process—all of which are derived from a program analysis conducted by human experts and automated tools. For the first time, we have implemented a tool that can quantitatively evaluate the quality of obfuscation techniques. Then, to validate the effectiveness of the implemented framework, we conducted experiments using four widely recognized commercial and open-source obfuscation tools. Our experimental findings, based on quantitative values related to obfuscation techniques, demonstrate that our proposed framework effectively assesses obfuscation quality.

AbstractSpecies in the genus Trametes (Basidiomycota, Polyporales) have been used in natural medicine for a long time. Many studies reported that mycelia or fruiting bodies of Trametes spp. exhibited effects of antioxidant, anti-inflammatory, anticancer, and antimicrobial activities. However, comparative analysis in this genus is scarce due to limitation of morphological identification and the sample number. In this study, the 19 strains of seven Trametes species were chosen to generate a five-gene-based phylogeny with the 31 global references. In addition, 39 culture extracts were prepared for 13 strains to test for anticancer and antibacterial activities. Strong anticancer activities were found in several extracts from T. hirsuta and T. suaveolens. Anticancer activities of T. suaveolens, T. cf. junipericola and T. trogii were first described here. The antibacterial ability of T. versicolor and T. hirsuta extracts has been confirmed. The antibacterial activities of T. suaveolens have been reported at the first time in this study. These results suggest an efficient application of the genus Trametes as the drug resources especially for anticancer agents.

Abstract Objective Self‐limited infantile epilepsy (SeLIE) has distinctive clinical features, and the PRRT2 gene is known to be a considerable genetic cause. There have been a few studies on PRRT2‐positive SeLIE only, and anti‐seizure medications are often required due to frequent seizures at initial seizure onset. This study aimed to provide clinical information for the early recognition of patients with PRRT2‐positive SeLIE and to propose effective anti‐seizure medications for seizure control. Methods We retrospectively reviewed 36 patients diagnosed with SeLIE with genetically confirmed pathogenic variants of PRRT2. In addition, six atypical cases with neonatal‐onset seizures and unremitting after 3 years of age were included to understand the expanded clinical spectrum of PRRT2‐related epilepsy. We analyzed the initial presentation, clinical course, and seizure control response to anti‐seizure medications. Results Patients with PRRT2‐related epilepsy had characteristic seizure semiology at the initial presentation, including all afebrile, clustered (n = 23, 63.9%), short‐duration (n = 33, 91.7%), and bilateral tonic–clonic seizures (n = 26, 72.2%). Genetic analysis revealed that c. 649dupC was the most common variant, and six patients had a 16p11.2 microdeletion containing the PRRT2 gene. One‐third of the patients were sporadic cases without a family history of epilepsy or paroxysmal movement disorders. In the 33 patients treated with anti‐seizure medications, sodium channel blockers, such as carbamazepine, were the most effective in seizure control. Significance Our results delineated the clinical characteristics of PRRT2‐positive SeLIE, differentiating it from other genetic infantile epilepsies and discovered the effective anti‐seizure medications for initial clustered seizure control. If afebrile bilateral tonic–clonic seizures develop in a normally developed infant as a clustered pattern, PRRT2‐positive SeLIE should be considered as a possible diagnosis, and sodium channel blockers should be administered as the first medication for seizure control.

PurposeTo represent 24-2 visual field (VF) losses of individual patients using a hybrid approach of archetypal analysis (AA) and fuzzy c-means (FCM) clustering.MethodsIn this multicenter retrospective study, we classified characteristic patterns of 24-2 VF using AA and decomposed them with FCM clustering. We predicted the change in mean deviation (MD) through supervised machine learning from decomposition coefficient change. In addition, we compared the areas under the receiver operating characteristic curves (AUCs) of the decomposition coefficient slopes to detect VF progression using three criteria: MD slope, Visual Field Index slope, and pointwise linear regression analysis.ResultsWe identified 16 characteristic patterns (archetypes or ATs) of 24-2 VF from 132,938 VFs of 18,033 participants using AA. The hybrid approach using FCM revealed a lower mean squared error and greater correlation coefficient than the AA single approach for predicting MD change (all P ≤ 0.001). Three of 16 AUCs of the FCM decomposition coefficient slopes outperformed the AA decomposition coefficient slopes in detecting VF progression for all three criteria (AT5, superior altitudinal defect; AT10, double arcuate defect; AT13, total loss) (all P ≤ 0.028).ConclusionA hybrid approach combining AA and FCM to analyze 24-2 VF can visualize VF tests in characteristic patterns and enhance detection of VF progression with lossless decomposition.

The color conversion efficiency of phosphor films can be significantly improved by producing them in the shape of photonic crystals (PhCs). When light with photonic band‐edge wavelengths is incident on a PhCs phosphor film, the excitation photons are resonantly absorbed, enhancing the emission intensity. This study develops three‐dimensional PhC phosphor films based on self‐assembled inverse opal structures. PhC phosphors are constructed using a silk fibroin polymer and red organic fluorescent dyes (λpeak ≈ 610 nm) doped into it. The photonic structures are designed using electromagnetic wave simulations and photonic band structure analyses. The fabricated PhC phosphor films are integrated with blue micro‐light‐emitting diode (micro‐LED) chips (λpeak ≈ 452 nm), resulting in a color conversion efficiency increase of more than 1.5 times that of bulk phosphor films. Additionally, experiments are performed using various micro‐LED chips with a size of less than 100 μm. Overall, the results of this study demonstrate the potential of PhC phosphor films in future micro‐LED‐based devices and applications, including displays and communication systems.

BackgroundNitrous oxide has shown potentially as an efficacious intervention for treatment-resistant depression, yet there remains insufficient evidence pertaining to repeated administration of nitrous oxide over time and active placebo-controlled studies with optimal blinding. Thus, we aim to examine the feasibility and preliminary efficacy of a six-week follow up study examining the effects of a 4 week course of weekly administered nitrous oxide as compared to the active placebo, midazolam.MethodsIn this randomized, active placebo-controlled, pilot trial, 40 participants with treatment-resistant depression will receive either inhaled nitrous oxide (1 hour at 50% concentration) plus intravenous saline (100mL) or inhaled oxygen (1 hour at 50% concentration) plus intravenous midazolam (0.02 mg/kg in 100mL, up to 2mg) once per week, for 4 consecutive weeks. Participants will be followed up for 6 weeks starting from the first treatment visit. Primary feasibility outcomes include recruitment rate, withdrawal rate, adherence, missing data, and adverse events. The primary exploratory clinical outcome is change in Montgomery-Åsberg Depression Rating Scale (MADRS) score at day 42 of the study. Other exploratory clinical outcomes include remission (defined as MADRS score DiscussionThis pilot study will provide valuable information regarding the feasibility and preliminary efficacy of repeated nitrous oxide administration over time for treatment-resistant depression. If feasible, this study will inform the design of a future definitive trial of nitrous oxide as an efficacious and fast-acting treatment for treatment-resistant depression.Trial registrationClinicalTrials.gov NCT04957368. Registered on July 12, 2021.

IntroductionNusinersen is the first drug approved for spinal muscular atrophy (SMA) treatment. In this study, we aimed to evaluate the long-term safety and efficacy of nusinersen, assess the therapeutic effects based on the treatment initiation timing and baseline motor function, and explore the perception of functional improvement from either parents or patients, utilizing 3-year nationwide follow-up data in South Korea.MethodsWe enrolled patients with SMA who were treated with nusinersen under the National Health Insurance coverage, with complete motor score records available and a minimum treatment duration of 6 months. To evaluate the motor function of patients, the Hammersmith Infant Neurological Examination-2 (HINE-2) was used for type 1 and the Expanded Hammersmith Functional Motor Scale (HFMSE) was used for types 2 and 3 patients. A significant improvement was defined as a HINE-2 score gain ≥5 for patients with type 1 and an HFMSE score ≥ 3 for patients with types 2 and 3 SMA. Effects of treatment timing were assessed. Patients with type 2 were further categorized based on baseline motor scores for outcome analysis. We also analyzed a second dataset from five tertiary hospitals with the information on parents/patients-reported impressions of improvement.ResultsThe study comprised 137 patients, with 21, 103, and 13 patients representing type 1, 2, and 3 SMA, respectively. At the 3-year follow-up, the analysis encompassed 7 patients with type 1, 12 patients with type 2, and none with type 3. Nearly half of all enrolled patients across SMA types (42.8, 59.2 and 46.2%, respectively) reached the 2-year follow-up for analysis. Patients with type 1 SMA exhibited gradual motor function improvement over 1-, 2-, and 3-year follow-ups (16, 9, and 7 patients, respectively). Patients with type 2 SMA demonstrated improvement over 1-, 2-, and 3-year follow-ups (96, 61 and 12 patients, respectively). Early treatment from symptom onset resulted in better outcomes for patients with type 1 and 2 SMA. In the second dataset, 90.7% of 108 patients reported subjective improvement at the 1-year follow-up.ConclusionNusinersen treatment for types 1–3 SMA is safe and effective in long-term follow-up. Early treatment initiation was a significant factor affecting long-term motor outcome.

With the increasing popularity of battery‐powered mobility, ensuring the safety and reliability of Li‐ion batteries (LIBs) has become critical for manufacturers. Despite advanced manufacturing processes for large‐scale Li‐ion cells, “latent defects” still unintentionally appear, due to imbalanced battery design, invisible faults, and extreme operating conditions. These defects cause performance degradation and can even lead to battery fires. Hence, early detection of latent defects, along with understanding the influence of cell parameters and operating conditions on battery failure scenarios, is crucial. For straightforward investigations and interpretations, noninvasive and in operando battery imaging techniques and methods have been proposed using X‐rays, neutrons, and ultrasound, as these can penetrate active and component materials and cell packaging. Moreover, magnetic‐field‐guided visualization of the current distribution pattern in cells under a current load has been proposed to identify invisible defects. This review thoroughly examines various imaging techniques for internal batteries, from the atomic and molecular levels in electrode materials and interfaces to macroscale battery systems. By assessing qualitative case studies and newly discovered phenomena, this review provides valuable insights into state‐of‐the‐art noninvasive battery imaging and its potential to improve the safety and reliability of LIB technology.

In an optical system with multiple lens groups and increased zoom magnification levels, achieving a smooth zoom locus is increasingly difficult. Traditional methods for calculating zoom loci often involve complex and time-consuming formulas. Consequently, we utilized the Padé approximation in optical design software to compute the zoom locus analytically, irrespective of the number of zoom positions (nodes). The initial data were used to assign orders to rational function polynomials, facilitating Padé approximation. If the image surface extended beyond the depth of focus (DOF), a node was added, with adjustments made until it fell within the DOF range. Furthermore, Padé approximation was performed to prevent singularities. The loci of all lens groups in the optical system can be expressed in a rational function format. Specifically, the numerator and denominator polynomial degrees were 20° and 1°, respectively, with their sum being the total number of nodes. In addition, we calculated the zoom locus by increasing the numerator sequence to minimize the occurrence of the singularity and added the node automatically to enable zoom locus calculation in all optical systems. Accordingly, we could make fast calculations, unlike conventional methods, using complex and time-consuming simultaneous equations. Therefore, we could express the locus of the compensated group in the form of a smooth function, as presently shown.

Herein, we describe the case of a 43-month-old girl who presented with clinical manifestations of dyskinetic cerebral palsy (CP), classified as the Gross Motor Function Classification System (GMFCS) V. The patient had no family history of neurological or perinatal disorders. Despite early rehabilitation, serial assessments using the Gross Motor Function Measure (GMFM) showed no significant improvements in gross motor function. Brain magnetic resonance imaging showed nonspecific findings that could not account for developmental delay or dystonia. Whole-genome sequencing identified a heterozygous NM_002074.5(GNB1):c.239T>C (p.Ile80Thr) mutation in guanine nucleotide-binding protein beta 1 (GNB1) gene. Considering this case and previous studies, genetic testing for the etiology of dyskinetic CP is recommended for children without relevant or with nonspecific brain lesions.

Summary: Background: Identifying novel epigenetic signatures associated with serum immunoglobulin E (IgE) may improve our understanding of molecular mechanisms underlying asthma and IgE-mediated diseases. Methods: We performed an epigenome-wide association study using whole blood from Framingham Heart Study (FHS; n = 3,471, 46% females) participants and validated results using the Childhood Asthma Management Program (CAMP; n = 674, 39% females) and the Genetic Epidemiology of Asthma in Costa Rica Study (CRA; n = 787, 41% females). Using the closest gene to each IgE-associated CpG, we highlighted biologically plausible pathways underlying IgE regulation and analyzed the transcription patterns linked to IgE-associated CpGs (expression quantitative trait methylation loci; eQTMs). Using prior UK Biobank summary data from genome-wide association studies of asthma and allergy, we performed Mendelian randomization (MR) for causal inference testing using the IgE-associated CpGs from FHS with methylation quantitative trait loci (mQTLs) as instrumental variables. Findings: We identified 490 statistically significant differentially methylated CpGs associated with IgE in FHS, of which 193 (39.3%) replicated in CAMP and CRA (FDR < 0.05). Gene ontology analysis revealed enrichment in pathways related to transcription factor binding, asthma, and other immunological processes. eQTM analysis identified 124 cis-eQTMs for 106 expressed genes (FDR < 0.05). MR in combination with drug-target analysis revealed CTSB and USP20 as putatively causal regulators of IgE levels (Bonferroni adjusted P

This study proposes a new application of AcciMap, a tool initially created within safety science. AcciMap assists designers by identifying and anticipating systemic conditions that have contributed to prior failures and may influence the implementation of new design interventions. For validation, we applied AcciMap to analyze factors contributing to child abuse cases in South Korea. This process identified potential facilitators and barriers related to the implementation of a child abuse assessment checklist developed by the research team. We found that AcciMap enables designers to apply systems thinking to complex problems. It allows the consideration of potential implementation issues for new design interventions across multiple levels, helping designers understand and anticipate the complex systemic structures affecting their intervention. By exploring how AcciMap can be used for in-depth sociotechnical system analysis, this study contributes to advancing our understanding of systemic design.

Abstract Introduction SB4 is the first approved biosimilar of etanercept, a biologic tumor necrosis factor inhibitor, to treat various autoimmune diseases including axial spondylarthritis (axSpA), rheumatoid arthritis (RA), psoriatic arthritis (PsA), and plaque psoriasis (PsO). This post-marketing surveillance (PMS) study of SB4 investigated safety and effectiveness in routine clinical practice and is part of the drug approval process in Korea. Methods This prospective, multi-center, open-label, observational, phase IV PMS study was designed to enroll patients with axSpA, RA, PsA, and PsO in Korea from September 2015 to September 2019. Both etanercept-naïve patients or patients switched from reference etanercept were included. SB4 was administered weekly via subcutaneous injections using pre-filled syringes. Safety was assessed by the incidence of adverse events (AEs), adverse drug reactions (ADRs) and serious adverse events (SAE). Effectiveness was assessed by the change from baseline of investigator-rated Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in patients with ankylosing spondylitis (AS) and disease activity score-28 (DAS28) in patients with RA. Results Among 316 enrolled patients, 314 were included in the safety analysis (176 with AS and 138 with RA). The overall incidence of AEs, ADRs and serious AEs were 17.8, 9.9, and 1.3%, respectively. Most AEs were mild (66.7%) or moderate (31.1%) and not related to SB4 (58.9%). Most common AEs were injection site pruritus (1.9%) and injection site rash (1.3%). At week 24, mean disease activity scores significantly decreased compared to baseline in naïve patients with AS and RA (BASDAI 2.7 vs. 6.2, p