Adoption of mobile dementia prevention services for middle-aged and older adults: applying the theory of coping strategies for dementia risks.

The prevalence of dementia is increasing due to the aging population, leading to significant investments in information technology-based dementia care solutions such as mobile dementia prevention services (MDPS). These services aim to facilitate early diagnosis and prevent cognitive decline, with the ultimate goal of reducing medical costs. This study examines how aging individuals perceive and evaluate MDPS and how these perceptions influence their adoption intentions. Drawing from a coping perspective, we analyze the impact of susceptibility and severity dimensions in dementia risk perception on the perceived usefulness and self-incongruence in MDPS adoption. Focusing on middle-aged and older adults aged 55 and above, the study reveals significant but contrasting effects of susceptibility and severity. Perceived susceptibility of dementia is associated with emotion-focused coping, positively influencing self-incongruence with MDPS. Perceived severity of dementia is linked to problem-focused coping, negatively impacting self-incongruence but positively influencing the perceived usefulness of MDPS, promoting adoption. These findings provide insights into promoting MDPS by considering dementia risk perceptions and contribute to the development of effective dementia-related strategies for aging individuals.

CT synthesis with deep learning for MR-only radiotherapy planning: a review.

MR-only radiotherapy planning is beneficial from the perspective of both time and safety since it uses synthetic CT for radiotherapy dose calculation instead of real CT scans. To elevate the accuracy of treatment planning and apply the results in practice, various methods have been adopted, among which deep learning models for image-to-image translation have shown good performance by retaining domain-invariant structures while changing domain-specific details. In this paper, we present an overview of diverse deep learning approaches to MR-to-CT synthesis, divided into four classes: convolutional neural networks, generative adversarial networks, transformer models, and diffusion models. By comparing each model and analyzing the general approaches applied to this task, the potential of these models and ways to improve the current methods can be can be evaluated.

Effect of catalyst and oxidant concentrations in a TEMPO oxidation system on the production of cellulose nanofibers.

In traditional TEMPO oxidation systems, the high cost of TEMPO catalysts has been a significant barrier to the industrialization of oxidized CNF. From an economic perspective, presenting the characteristics of various CNFs produced with the oxidation systems with reduced catalyst usage could facilitate the industrial application of CNF across a wide range of fields. In this study, it was demonstrated that reducing the amount of TEMPO catalyst used (from 0.1 to 0.05 mmol g-1) in a conventional oxidation system increased the carboxylate content by approximately 6.3%. Furthermore, the activation of hydroxyl amine TEMPO, which is generated after the oxidation reaction of cellulose, was enhanced by adjusting the dosage of the inexpensive oxidant NaClO, leading to a 20% improvement in carboxylate content. This suggests that controlling the amount of NaClO as an oxidant can be a key parameter in adjusting the dosage of TEMPO to achieve the targeted degree of surface substitution. Results from the dispersion stability, UV-transmittance, and morphological properties of TEMPO-oxidized CNF using microfluidizing treatment showed that high carboxylate content plays a crucial role in producing high-purity CNF suspensions, which are small, uniform, and free from microfibers. Additionally, by varying the number of mechanical treatments applied to the oxidized cellulose, various types of CNF suspensions with different mean widths were obtained. We expect that these findings offer meaningful insights to end-users seeking a breakthrough in the performance limitations of final applications using cellulose nanomaterials.

A potent pan-sarbecovirus neutralizing antibody resilient to epitope diversification.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing coronavirus mAbs that are sufficiently potent for clinical development and retain activity despite viral evolution remain elusive. We identified a human mAb, designated VIR-7229, which targets the viral receptor-binding motif (RBM) with unprecedented cross-reactivity to all sarbecovirus clades, including non-ACE2-utilizing bat sarbecoviruses, while potently neutralizing SARS-CoV-2 variants since 2019, including the recent EG.5, BA.2.86, and JN.1. VIR-7229 tolerates extraordinary epitope variability, partly attributed to its high binding affinity, receptor molecular mimicry, and interactions with RBM backbone atoms. Consequently, VIR-7229 features a high barrier for selection of escape mutants, which are rare and associated with reduced viral fitness, underscoring its potential to be resilient to future viral evolution. VIR-7229 is a strong candidate to become a next-generation medicine.

Prevalence of medication overload among older people with HIV: a MedSafer study.

BACKGROUND: Older people with HIV (PWH) are at risk of polypharmacy (taking multiple medications). Most medications may be necessary and indicated to manage HIV (e.g., antiretroviral therapy [ART]) and HIV-associated comorbidities. However, some are potentially inappropriate medications (PIMs), defined as causing greater harm than benefit, which leads to medication overload. The objective of this study was to characterize polypharmacy (taking multiple medications) and medication overload (prescription of ≥ 1 PIMs) among older PWH. METHODS: This retrospective study included older PWH (aged ≥ 50 years old) attending the tertiary care HIV clinic at the McGill University Health Centre (Montreal, Canada), from June 2022-June 2023. Patient characteristics, medications, and select laboratory values (e.g., CD4 count, hemoglobin A1C) were entered into the MedSafer software identifying PIMs and classifying them according to risk of adverse drug event. We measured the prevalence of polypharmacy (≥ 5 medications prescribed, both including and excluding ART) and medication overload (≥ 1 PIMs). Multivariable logistic regression identified factors associated with medication overload. RESULTS: The study included 100 patients, with a median age of 59 years (IQR = 54-63; range 50-82); 42% female. Polypharmacy affected 89% of patients when including antiretroviral therapy (ART) and 60% when excluding ART. Medication overload was present in 58% of patients, and 37.4% of identified PIMs were classified as high-risk. Polypharmacy was the sole predictor of medication overload. CONCLUSION: Older PWH are at significant risk of medication overload and receiving higher risk PIMs. Deprescribing PIMs in this population could improve medication appropriateness while reducing the risk of ADEs.

Two psammobiont species of Anomalohalacarus (Acari, Halacaridae) from South Korea.

Background: The genus Anomalohalacarus Newell, 1949, which is known to occur exclusively inhabiting sand, has not been previously reported from Korea. During a recent survey of the meiofauna from several intertidal sandy beaches in South Korea, we found both sexes of two psammobiont halacarids, Anomalohalacarusangustus sp. nov. and A.biformis Abé, 1996. New information: Both species are similar to each other in sharing an undivided posterior dorsal plate, three and two setae on the anterior and posterior epimeral plates, respectively, three bipectinate setae on tibia IV, and four ventral setae on tarsus I. However, A.angustus sp. nov. is distinguished from A.biformis by the absence of areolae posteriorly on the anterior dorsal plate, a much more slender posterior dorsal plate, a pair of subgenital setae on the genital foramen in females, and seven branched perigenital setae on the genitoanal plate in males. The feature of branched perigenital setae in males is reported for the first time in the genus Anomalohalacarus. The Korean specimens of A.biformis agree well with the original description from Japan, except for the number of ventral bipectinate setae on tibia II. This study presents (re)descriptions of both species with detailed illustrations and provides a dichotomous key to Anomalohalacarus species, including the new species, based on morphological characters. The genus Anomalohalacarus is reported for the first time in South Korea.

Efficacy of weekly versus daily cholecalciferol for repleting serum vitamin D (25(OH)D) deficiency: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND/RATIONALE: Weekly cholecalciferol can replace daily supplementation to reduce pill burden in patients with complex medication regimens and hypovitaminosis D, but evidence supporting this switch is unclear. OBJECTIVE: We aimed to determine whether weekly cholecalciferol was superior to daily cholecalciferol to replete patients with hypovitaminosis D. METHODS: We conducted a systematic review of randomized controlled trials involving participants with baseline hypovitaminosis D (<30 ng/ml) comparing weekly versus daily cholecalciferol dosing and where serum cholecalciferol was measured within 120 days of starting treatment. We searched MEDLINE, CINAHL and EMBASE from inception to 7 May 2024. A random-effects meta-analysis evaluated the odds ratio for repletion of serum vitamin D levels. FINDINGS: Eight trials involving 542 patients were included in the analysis. Weekly and daily cholecalciferol were not significantly different in correcting hypovitaminosis D (OR = 1.5, 95% CI = 0.3-6.9, p = 0.6, favouring weekly dosing, I2 = 85.3%). A sensitivity analysis excluding otherwise healthy patients had similar findings (OR = 0.8, 95% CI = 0.3-2.1, p = 0.6). Most studies were at risk of bias; the different doses being compared increased the heterogeneity. CONCLUSIONS: Limited direct evidence supports a switch from daily to weekly cholecalciferol dosing; however, weekly supplementation was not demonstrably worse at repleting levels and decreased a patient's daily pill burden.

Selection bias obfuscates the discovery of fast radio burst sources.

Fast radio bursts (FRBs) are a newly discovered class of extragalactic radio transients characterized by their high energy and short duration (from microseconds to milliseconds)1. The physical origin of these FRBs remains unknown and is a subject of ongoing research, with magnetars emerging as leading candidates2,3. Previous studies have used various methodologies to address the problem of FRB origin, including demographic analyses of FRB host galaxies and their local environments4-6, assessments of FRB rate evolution with redshift7-9 and searches for proposed multi-messenger FRB counterparts10. However, these studies are susceptible to substantial biases stemming from unaccounted radio and optical selection effects. Here we present empirical evidence for a substantial selection bias against detecting FRBs in galaxies with large inclination angles (edge-on) using a sample of hosts identified for FRBs discovered by untargeted surveys. This inclination-related bias probably leads to a significant underestimation (by about a factor of two) of the FRB rates reported in the literature and disfavours globular clusters as the dominant origin of FRB sources, as previously speculated6. These conclusions have important implications for FRB progenitor models and targeted FRB follow-up strategies. We further investigate the impact of this bias on the relative rate of FRBs in different host environments. Our analysis suggests that scattering in FRB hosts is probably responsible for the observed bias11,12. However, a larger sample of localized FRBs is required to robustly quantify the contribution of scattering to the inclination-related selection bias.

Pediatric Early Warning Scores Before Rapid Response Poorly Predict Intensive Care Unit Transfers.

BACKGROUND: The Pediatric Early Warning Score (PEWS) is a clinical tool used to identify children at risk for clinical deterioration, but its utility remains debated, particularly in high-resource settings. Our objective with this study was to assess the predictive performance of the PEWS for unplanned PICU transfers after pediatric rapid response team (RRT) activation. METHODS: A retrospective cohort study at a tertiary care academic children's hospital included all hospitalized patients up to 21 years old who had RRT activations between August 2021 and July 2022. Demographic and clinical data, the primary reason for RRT activation, and the modified Brighton PEWS were collected. The primary outcome was PICU transfer following RRT activation, and the secondary outcome was rapid escalation of care within 4 hours after RRT activation. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) were calculated at multiple PEWS thresholds. RESULTS: Of 297 RRT activations in 244 patients, 183 (63%) resulted in a PICU transfer, 75% of which were due to respiratory concerns. The PEWS was recorded in 89% of RRT activations within the preceding 4 hours. There was no significant difference in the PEWS between patients with or without PICU transfer or rapid escalation of care. The sensitivity, specificity, and AUROC of PEWS for predicting PICU transfer or rapid escalation of care were low (AUROC 0.495-0.613). CONCLUSIONS: PEWS within 4 hours before RRT activation was a poor predictor of PICU transfer or rapid escalation care. Further work is needed to develop a more sensitive and specific tool.

Two-stage deep learning framework for occlusal crown depth image generation.

The generation of depth images of occlusal dental crowns is complicated by the need for customization in each case. To decrease the workload of skilled dental technicians, various computer vision models have been used to generate realistic occlusal crown depth images with definite crown surface structures that can ultimately be reconstructed to three-dimensional crowns and directly used in patient treatment. However, it has remained difficult to generate images of the structure of dental crowns in a fluid position using computer vision models. In this paper, we propose a two-stage model for generating depth images of occlusal crowns in diverse positions. The model is divided into two parts: segmentation and inpainting to obtain both shape and surface structure accuracy. The segmentation network focuses on the position and size of the crowns, which allows the model to adapt to diverse targets. The inpainting network based on a GAN generates curved structures of the crown surfaces based on the target jaw image and a binary mask made by the segmentation network. The performance of the model is evaluated via quantitative metrics for the area detection and pixel-value metrics. Compared to the baseline model, the proposed method reduced the MSE score from 0.007001 to 0.002618 and increased DICE score from 0.9333 to 0.9648. It indicates that the model showed better performance in terms of the binary mask from the addition of the segmentation network and the internal structure through the use of inpainting networks. Also, the results demonstrated an improved ability of the proposed model to restore realistic details compared to other models.

A Multi-bit ECRAM-Based Analog Neuromorphic System with High-Precision Current Readout Achieving 97.3% Inference Accuracy.

This article proposes an analog neuromorphic system that enhances symmetry, linearity, and endurance by using a high-precision current readout circuit for multi-bit nonvolatile electro-chemical random-access memory (ECRAM). For on-chip training and inference, the system uses activation modules and matrix processing units to manage analog update/read paths and perform precise output sensing with feedback-based current scaling on the ECRAM array. The 250nm CMOS neuromorphic chip was tested with a 32 x 32 ECRAM synaptic array, achieving linear and symmetric updates and accurate read operations. The proposed circuit system updates the 32 x 32 ECRAM across 100 levels, maintaining consistent synaptic weights, and operates with an output error rate of up to 2.59% per column. It consumes 5.9 mW of power excluding the ECRAM array and achieves 97.3% inference accuracy on the MNIST dataset, close to the software-confirmed 97.78%, with only the final layer (64 x 10) mapped to the ECRAM.

Differences in Depressive Symptom Profile by Age Group in Koreans With Major Depressive Disorder: Results From Nationwide General Population Surveys.

OBJECTIVE: This study investigated to what extent a range of depressive symptoms was differentially present depending on age group in Korean population. METHODS: Data was pooled from five nationally representative surveys in which 29,418 respondents aged at least 18 years were interviewed face-to-face using the Korean version of the Composite International Diagnostic Interview. A total of 691 (2.1%) respondents were found to have had at least 1 episode of major depressive disorder (MDD) within the last 12 months. Logistic regression analysis was conducted to identify the association between age groups (18-39 years, 40-59 years, and 60 years or older) and 26 depressive symptoms among the respondents with MDD. RESULTS: Associations were observed between somatic symptoms-including insomnia, awakening 2 h earlier-and cognitive symptoms such as feelings of guilt, thoughts of death, and suicidal ideation with the older age group. Whereas, atypical depressive symptoms such as increased appetite, weight gain, and hypersomnia were associated with the younger age group. When adjusted for sociodemographic factors, symptoms such as depressed mood, awakening 2 h earlier, and feeling guilty in the older age group, and hypersomnia, psychomotor retardation, and worse in the morning in the younger age group still remained statistically significant. Furthermore, fatigue and decreased libido were newly associated with the younger age group. CONCLUSION: The findings of this study revealed distinct patterns of symptomatology in MDD based on age groups. These differences should be considered owing to their potential relevance to treatment response and prognosis in the clinical setting.

Molecular basis of convergent evolution of ACE2 receptor utilization among HKU5 coronaviruses.

DPP4 was considered a canonical receptor for merbecoviruses until the recent discovery of African bat-borne MERS-related coronaviruses using ACE2. The extent and diversity with which merbecoviruses engage ACE2 and their receptor species tropism remain unknown. Here, we reveal that HKU5 enters host cells utilizing Pipistrellus abramus (P.abr) and several non-bat mammalian ACE2s through a binding mode distinct from that of any other known ACE2-using coronaviruses. These results show that several merbecovirus clades independently evolved ACE2 utilization, which appears to be a broadly shared property among these pathogens, through an extraordinary diversity of ACE2 recognition modes. We show that MERS-CoV and HKU5 have markedly distinct antigenicity, due to extensive genetic divergence, and identified several HKU5 inhibitors, including two clinical compounds. Our findings profoundly alter our understanding of coronavirus evolution and pave the way for developing countermeasures against viruses poised for human emergence.

All-in-one wearable drug efficacy assessment systems for bulbar muscle function using amyotrophic lateral sclerosis animal models.

Preclinical studies are crucial for developing amyotrophic lateral sclerosis drugs. Current FDA-approved drugs have been created by monitoring limb muscle function and histological analysis of amyotrophic lateral sclerosis model animals. Drug candidates for this disease have yet to be tested for bulbar-onset type due to the limitations of traditional preclinical tools: excessive animal use and discrete detection of disease progress. Here, our study introduces an all-in-one, wireless, integrated wearable system for facilitating continuous drug efficacy assessment of dysphagia-related muscles in animals during natural eating behaviors. By incorporating a kirigami-based strain-isolation mechanism, this device mounted on the skin of animals mitigates electromyography signal contamination caused by unpredictable animal movements. Our findings indicate this system, measuring the progression of motor neuron denervation, offers high precision in monitoring drug effects on dysphagia-responsible bulbar muscles. This study paves the way for more humane and efficient approaches to developing treatment solutions for degenerative neuromuscular diseases.

Computationally designed mRNA-launched protein nanoparticle vaccines.

Both protein nanoparticle and mRNA vaccines were clinically de-risked during the COVID-19 pandemic1-6. These vaccine modalities have complementary strengths: antigen display on protein nanoparticles can enhance the magnitude, quality, and durability of antibody responses7-10, while mRNA vaccines can be rapidly manufactured11 and elicit antigen-specific CD4 and CD8 T cells12,13. Here we leverage a computationally designed icosahedral protein nanoparticle that was redesigned for optimal secretion from eukaryotic cells14 to develop an mRNA-launched nanoparticle vaccine for SARS-CoV-2. The nanoparticle, which displays 60 copies of a stabilized variant of the Wuhan-Hu-1 Spike receptor binding domain (RBD)15, formed monodisperse, antigenically intact assemblies upon secretion from transfected cells. An mRNA vaccine encoding the secreted RBD nanoparticle elicited 5- to 28-fold higher levels of neutralizing antibodies than an mRNA vaccine encoding membrane-anchored Spike, induced higher levels of CD8 T cells than the same immunogen when delivered as an adjuvanted protein nanoparticle, and protected mice from vaccine-matched and -mismatched SARS-CoV-2 challenge. Our data establish that delivering protein nanoparticle immunogens via mRNA vaccines can combine the benefits of each modality and, more broadly, highlight the utility of computational protein design in genetic immunization strategies.

A pan-variant miniprotein inhibitor protects against SARS-CoV-2 variants.

The continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has compromised neutralizing antibody responses elicited by prior infection or vaccination and abolished the utility of most monoclonal antibody therapeutics. We previously described a computationally-designed, homotrimeric miniprotein inhibitor, designated TRI2-2, that protects mice against pre-Omicron SARS-CoV-2 variants. Here, we show that TRI2-2 exhibits pan neutralization of variants that evolved during the 4.5 years since the emergence of SARS-CoV-2 and protects mice against BQ.1.1, XBB.1.5 and BA.2.86 challenge when administered post-exposure by an intranasal route. The resistance of TRI2-2 to viral escape and its direct delivery to the upper airways rationalize a path toward clinical advancement.

Computed Tomography of Contemporary Occupational Lung Disease: A Pictorial Review.

Occupational lung disease remains one of the most common work-related illnesses and accounts for most deaths from occupational illness. Occupational lung diseases often have delayed manifestation over decades and nonspecific clinical presentations, making it challenging for clinicians to promptly identify the disease and implement preventive measures. Radiologists play a crucial role in identifying and diagnosing occupational lung diseases, allowing for removal of the exposure and early medical intervention. In this review, we share our clinical and radiologic approach to diagnosing occupational lung disease and its subtypes. A collection of sample cases of occupational lung diseases commonly encountered in the modern era at a large Canadian university hospital is included to facilitate understanding. This review will provide radiologists with valuable insights into recognizing and diagnosing occupational lung diseases.

Double-bar technique for the correction of asymmetric pectus excavatum.

Background: Minimally invasive repair of pectus excavatum (MIRPE) improves clinical outcomes and chest wall morphology. However, asymmetry in patients with pectus excavatum (PE) remains as an important issue, even after surgery. Here, we evaluated the benefit of double-bar technique in achieving a symmetric chest wall. Methods: This retrospective study included 79 patients with PE who underwent MIRPE between 2017 and 2021. The patients were divided into the double- or non-double-bar groups. Asymmetric degree (AD) and sternal rotation angle (SRA) were used to assess the severity of asymmetry based on computed tomography (CT) images. The primary outcome was the change in radiologic parameters. Secondary outcomes were clinical results, including hospital stay, pain scores, and complication rates. Subgroup analysis of patients with preoperative asymmetric PE was performed. Results: Patients in the double-bar group (n=23) were younger than those in the non-double-bar group (n=56). Additionally, the double-bar group exhibited lower pain scores and shorter hospital stay. Based on radiological assessments, the double-bar group demonstrated a greater decrease in AD without compromising improvement in the Haller index (HI). The benefit of the double-bar technique was more obvious among patients with asymmetry with a preoperative AD >5%, resulting in a significant reduction in AD. In this subgroup, a better correction of sternal rotation was observed. Conclusions: The double-bar technique may be a promising option for correcting asymmetry in patients with PE. Simplified AD and SRA radiologic assessments can be used to evaluate improvements in chest wall configuration.

Insights from Li and Zn systems for advancing Mg and Ca metal batteries.

The inherent limitations of lithium (Li)-ion batteries have sparked interest in exploring alternative technologies, especially those relying on metallic anodes: monovalent Li and divalent zinc (Zn), magnesium (Mg), and calcium (Ca) metals. In particular, Mg and Ca metal batteries offer significant advantages based on the natural abundance of their raw materials and high energy-storage capabilities resulting from the bivalency of the carrier ions. Yet, these battery systems are far from commercialization, and the lack of reliable electrolytes constitutes a primary concern. The formation of ion-insulating passivation layers on these metallic anodes and their inferior desolvation kinetics have long been recognized as formidable hurdles in the way of optimizing the electrolyte composition. These impediments call for innovative strategies in electrolyte engineering and an extensive analysis of the resulting solid-electrolyte-interphase (SEI) layer. In this review, we introduce recent pioneering studies of divalent Mg and Ca metal batteries that have been concerned with these issues. This review particularly focuses on drawing an analogy with Li and Zn metal batteries in terms of the relative advancement and by benchmarking against the strategies developed for these analogous systems. The areas of interest include a fundamental understanding of the thermodynamics and evolution of the morphology of metallic anodes, a correlation between the electrolyte and SEI compositions, state-of-the-art electrolyte strategies to realize reversible (de)plating of Mg and Ca, and new perspectives on the SEI properties and their relevance to corrosion and the calendar life. We finally encourage researchers in the community to delve into these emerging areas by linking with successful stories in the analogous systems, but identifying distinct aspects of Mg and Ca batteries that still require attention.

TIPRL Regulates Stemness and Survival in Lung Cancer Stem Cells through CaMKK2-CaMK4-CREB Feedback Loop Activation.

Frequent recurrence and metastasis caused by cancer stem cells (CSCs) are major challenges in lung cancer treatment. Therefore, identifying and characterizing specific CSC targets are crucial for the success of prospective targeted therapies. In this study, it is found that upregulated TOR Signaling Pathway Regulator-Like (TIPRL) in lung CSCs causes sustained activation of the calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) signaling pathway by binding to CaMKK2, thereby maintaining stemness and survival. CaMKK2-mediated activation of CaM kinase 4 (CaMK4) leads to phosphorylation of cAMP response element-binding protein (CREB) at Ser129 and Ser133, which is necessary for its maximum activation and the downstream constitutive expression of its target genes (Bcl2 and HMG20A). TIPRL depletion sensitizes lung CSCs to afatinib-induced cell death and reduces distal metastasis of lung cancer in vivo. It is determined that CREB activates the transcription of TIPRL in lung CSCs. The positive feedback loop consisting of CREB and TIPRL induces the sustained activation of the CaMKK2-CaMK4-CREB axis as a driving force and upregulates the expression of stemness- and survival-related genes, promoting tumorigenesis in patients with lung cancer. Thus, TIPRL and the CaMKK2 signaling axis may be promising targets for overcoming drug resistance and reducing metastasis in lung cancer.