Influence of preoperative embolisation on resection of brain arteriovenous malformations: cohort study.

PURPOSE: Preoperative endovascular embolisation is a widely used adjunct for the surgical treatment of brain arteriovenous malformations (AVMs). However, whether this improves completeness of AVM resection is unknown, as previous analyses have not adjusted for potential confounding factors. We aimed to determine if preoperative endovascular embolisation was associated with increased rate of complete AVM resection at first surgery, following adjustment for Spetzler-Martin grade items. METHODS: We identified a cohort of all patients undergoing first ever AVM resection in a specialist neurosciences unit in the NHS Lothian Health Board region of Scotland between June 2004 and June 2022. Data was prospectively extracted from medical records. Our primary outcome was completeness of AVM resection. We determined the odds of complete AVM resection using binomial logistic regression with adjustment for Spetzler-Martin grading system items: maximum nidus diameter, eloquence of adjacent brain and the presence of deep venous drainage. RESULTS: 88 patients (median age 40y [IQR 19-53], 55% male) underwent AVM resection. 34/88 (39%) patients underwent preoperative embolisation and complete resection was achieved at first surgery in 74/88 (84%). Preoperative embolisation was associated with increased adjusted odds of complete AVM resection (adjusted odds ratio [aOR] 8.6 [95% confidence interval (95% CI) 1.7-67.7]; p = 0.017). The presence of deep venous drainage was associated with reduced chance of complete AVM resection (aOR 0.18 [95% CI 0.04-0.63]; p = 0.009). CONCLUSIONS: Preoperative embolisation is associated with improved chances of complete AVM resection following adjustment for Spetzler-Martin grade, and should therefore be considered when planning surgical resection of AVMs.

Ambient printing of native oxides for ultrathin transparent flexible circuit boards.

Metal oxide films are essential in most electronic devices, yet they are typically deposited at elevated temperatures by using slow, vacuum-based processes. We printed native oxide films over large areas at ambient conditions by moving a molten metal meniscus across a target substrate. The oxide gently separates from the metal through fluid instabilities that occur in the meniscus, leading to uniform films free of liquid residue. The printed oxide has a metallic interlayer that renders the films highly conductive. The metallic character of the printed films promotes wetting of trace amounts of evaporated gold that would otherwise form disconnected islands on conventional oxide surfaces. The resulting ultrathin (<10 nanometers) conductors can be patterned into flexible circuits that are transparent, mechanically robust, and electrically stable, even at elevated temperatures.

Adaptive ambiguity-aware weighting for multi-label recognition with limited annotations.

In multi-label recognition, effectively addressing the challenge of partial labels is crucial for reducing annotation costs and enhancing model generalization. Existing methods exhibit limitations by relying on unrealistic simulations with uniformly dropped labels, overlooking how ambiguous instances and instance-level factors impacts label ambiguity in real-world datasets. To address this deficiency, our paper introduces a realistic partial label setting grounded in instance ambiguity, complemented by Reliable Ambiguity-Aware Instance Weighting (R-AAIW)-a strategy that utilizes importance weighting to adapt dynamically to the inherent ambiguity of multi-label instances. The strategy leverages an ambiguity score to prioritize learning from clearer instances. As proficiency of the model improves, the weights are dynamically modulated to gradually shift focus towards more ambiguous instances. By employing an adaptive re-weighting method that adjusts to the complexity of each instance, our approach not only enhances the model's capability to detect subtle variations among labels but also ensures comprehensive learning without excluding difficult instances. Extensive experimentation across various benchmarks highlights our approach's superiority over existing methods, showcasing its ability to provide a more accurate and adaptable framework for multi-label recognition tasks.

Diagnostic value of a deep learning-based hyoid bone tracking model for aspiration in patients with post-stroke dysphagia.

Objective: Hyoid bone movement is potentially related to aspiration risk in post-stroke dysphagia (PSD) patients but is difficult to assess quantitatively. This study aimed to measure the distance of hyoid bone movement more efficiently and accurately using a deep learning model and determine the clinical usefulness of the model in PSD patients. Methods: This study included 85 patients with PSD within 6 months from onset. Patients were grouped into an aspiration group (n = 35) and a non-aspiration group (n = 50) according to the results of a videofluoroscopic swallowing study. Hyoid bone movement was tracked using a deep learning model constructed with the BiFPN-U-Net(T) architecture. The maximum distance of hyoid bone movement was measured horizontally (H max), vertically (V max), and diagonally (D max). Results: Compared with the non-aspiration group, the aspiration group showed significant decreases in hyoid bone movement in all directions. The area under the curve of V max was highest at 0.715 with a sensitivity of 0.680 and specificity of 0.743. The V max cutoff value for predicting aspiration risk was 1.61 cm. The success of oral feeding at the time of discharge was significantly more frequent when hyoid movement was equal to or larger than the cutoff value although no significant relationship was found between hyoid movement and other clinical characteristics. Conclusion: Hyoid bone movement of PSD patients can be measured quantitatively and efficiently using a deep learning model. Deep learning model-based analysis of hyoid bone movement seems to be useful for predicting aspiration risk and the possibility of resuming oral feeding.

Long-term (10-year) monitoring of transposon-mediated transgenic cattle.

The production of transgenic animals using non-viral methods has raised questions regarding their long-term health and genomic stability. In this study, we evaluated these aspects in transgenic cattle over ten years, using transposon-mediated gene transfer. Our longitudinal analysis included a comprehensive health assessment and whole-genome DNA resequencing. We found no significant alterations in physiological parameters or health complications in transposon-mediated transgenic cattle that exceeded 10 years of age. Genomic analysis revealed that the rates of somatic mutations and copy number variations in transgenic cattle were comparable to those in non-transgenic cattle. Furthermore, structural variants were infrequent, suggesting that transposon-mediated gene insertion did not compromise genomic integrity. These findings highlight the viability of transposon systems for generating transgenic livestock, potentially expanding their applications in agriculture and biotechnology. This study contributes significantly to our understanding of the long-term implications of transgenesis in large animals and supports the safety and stability of this method.

Improving monitoring network design to detect leaks at hazardous facilities: Lessons from a CO2 storage site.

Exploring the challenges posed by uncertainties in numerical modeling for hazardous material storage, this study introduces methodologies to improve monitoring networks for detecting subsurface leakages. The proposed approaches were applied to the Korea CO2 Storage Environmental Management (K-COSEM) test site, undergoing calibration, validation and uncertainty analysis through hydraulic and controlled-CO2 release tests. The calibration phase involved inter-well tracer and multi-well pumping tests, leveraging the Parameter ESTimation (PEST) model to determine the aquifer flow and solute transport properties of the K-COSEM site. To tackle uncertainties with limited observation data, we adopted Latin Hypercube simulation. Our uncertainty analysis confirmed model accuracy in simulating observed CO2 breakthrough curves. We also explored a probabilistic method to identify the environmental change point (EnCP) through correlation analysis with the distance from the CO2 injection well, revealing a linear trend and pinpointed potential preferential flow pathways by assessing detection probabilities. Evaluating CO2 detection capabilities was crucial for optimizing monitoring well placement, highlighting strategic well selection based on detection probabilities. This study advances managing uncertainties in hydrogeological modeling, underscoring the importance of sophisticated models in designing monitoring networks for hazardous leak detection in complex subsurface conditions.

RIPK3 causes mitochondrial dysfunction and albuminuria in diabetic podocytopathy through PGAM5-Drp1 signaling.

BACKGROUND: Receptor-interacting protein kinase (RIPK)3 is an essential molecule for necroptosis and its role in kidney fibrosis has been investigated using various kidney injury models. However, the relevance and the underlying mechanisms of RIPK3 to podocyte injury in albuminuric diabetic kidney disease (DKD) remain unclear. Here, we investigated the role of RIPK3 in glomerular injury of DKD. METHODS: We analyzed RIPK3 expression levels in the kidneys of patients with biopsy-proven DKD and animal models of DKD. Additionally, to confirm the clinical significance of circulating RIPK3, RIPK3 was measured by ELISA in plasma obtained from a prospective observational cohort of patients with type 2 diabetes, and estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), which are indicators of renal function, were followed up during the observation period. To investigate the role of RIPK3 in glomerular damage in DKD, we induced a DKD model using a high-fat diet in Ripk3 knockout and wild-type mice. To assess whether mitochondrial dysfunction and albuminuria in DKD take a Ripk3-dependent pathway, we used single-cell RNA sequencing of kidney cortex and immortalized podocytes treated with high glucose or overexpressing RIPK3. RESULTS: RIPK3 expression was increased in podocytes of diabetic glomeruli with increased albuminuria and decreased podocyte numbers. Plasma RIPK3 levels were significantly elevated in albuminuric diabetic patients than in non-diabetic controls (p = 0.002) and non-albuminuric diabetic patients (p = 0.046). The participants in the highest tertile of plasma RIPK3 had a higher incidence of renal progression (hazard ratio [HR] 2.29 [1.05-4.98]) and incident chronic kidney disease (HR 4.08 [1.10-15.13]). Ripk3 knockout improved albuminuria, podocyte loss, and renal ultrastructure in DKD mice. Increased mitochondrial fragmentation, upregulated mitochondrial fission-related proteins such as phosphoglycerate mutase family member 5 (PGAM5) and dynamin-related protein 1 (Drp1), and mitochondrial ROS were decreased in podocytes of Ripk3 knockout DKD mice. In cultured podocytes, RIPK3 inhibition attenuated mitochondrial fission and mitochondrial dysfunction by decreasing p-mixed lineage kinase domain-like protein (MLKL), PGAM5, and p-Drp1 S616 and mitochondrial translocation of Drp1. CONCLUSIONS: The study demonstrates that RIPK3 reflects deterioration of renal function of DKD. In addition, RIPK3 induces diabetic podocytopathy by regulating mitochondrial fission via PGAM5-Drp1 signaling through MLKL. Inhibition of RIPK3 might be a promising therapeutic option for treating DKD.

Development of a fit-for-purpose multi-marker panel for early diagnosis of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) suffers from lack of an effective diagnostic method, which hampers improvement in patient survival. Carbohydrate antigen 19-9 (CA19-9) is the only FDA-approved blood biomarker for PDAC, yet its clinical utility is limited due to suboptimal performance. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a burgeoning technology in clinical proteomics for discovery, verification, and validation of novel biomarkers. A plethora of protein biomarker candidates for PDAC have been identified using LC-MS, yet few has successfully transitioned into clinical practice. This translational standstill is owed partly to insufficient considerations of practical needs and perspectives of clinical implementation during biomarker development pipelines, such as demonstrating analytical robustness of proposed biomarkers which is critical for transitioning from research-grade to clinical-grade assays. Moreover, throughput and cost-effectiveness of proposed assays ought to be considered concomitantly from early phases of the biomarker pipelines for enhancing widespread adoption in clinical settings. Here, we developed a fit-for-purpose multi-marker panel for PDAC diagnosis by consolidating analytically robust biomarkers as well as employing a relatively simple LC-MS protocol. In discovery phase, we comprehensively surveyed putative PDAC biomarkers from both in-house data and prior studies. In verification phase, we developed a multiple-reaction monitoring (MRM)-MS-based proteomic assay using surrogate peptides that passed stringent analytical validation tests. We adopted a high-throughput protocol including short gradient (<10 min) and simple sample preparation (no depletion or enrichment steps). Additionally, we developed our assay using serum samples, which are usually the preferred biospecimen in clinical settings. We developed predictive models based on our final panel of 12 protein biomarkers combined with CA19-9, which showed improved diagnostic performance compared to using CA19-9 alone in discriminating PDAC from non-PDAC controls including healthy individuals and patients with benign pancreatic diseases. A large-scale clinical validation is underway to demonstrate the clinical validity of our novel panel.

Decreased Sirtuin 4 Levels Promote Cellular Proliferation and Invasion in Papillary Thyroid Carcinoma.

OBJECTIVE: This study examined the effect of Sirtuin 4 (Sirt4), a NAD+-dependent deacetylase, on the proliferation and progression of papillary thyroid carcinoma (PTC). METHODS: Data from The Cancer Genome Atlas (TCGA) were analyzed to identify Sirt4 expression in thyroid cancer. Subsequently, the correlation between Sirt4 expression and clinical characteristics was examined in 205 PTC tissue samples. In vitro assays using three human thyroid cancer cell lines (B-CPAP, TPC-1, and SNU-790) were conducted to assess the effects of regulated Sirt4 expression on cell growth, apoptosis, invasion, and migration. Furthermore, in vivo experiments were performed in a xenograft mouse model. RESULTS: GEO and TCGA data indicated that Sirt4 expression is lower in thyroid cancer and Sirt4 downregulation is associated with poor overall survival. In our PTC tissues, positive Sirt4 expression was associated with decreased extracapsular extension. In in vitro experiments using three human thyroid cancer cell lines, overexpression of Sirt4 decreased cell survival, clonogenic potential, and invasion and migratory capabilities, as well as inducing apoptosis and increasing reactive oxygen species levels. Sirt4 overexpression upregulated E-cadherin and downregulated N-cadherin, suggesting its potential involvement in the regulation of epithelial-mesenchymal transition. These findings were confirmed in vivo using a xenograft mouse model. CONCLUSION: This study provides novel insight into the potential contribution of Sirt4 to regulation of the pathological progression of PTC. The data suggest that Sirt4 plays a tumor-suppressive role in PTC by inhibiting growth, survival, and invasive potential. Future research should investigate the molecular mechanisms underlying these effects of Sirt4.

Association of remnant cholesterol with risk of dementia: a nationwide population-based cohort study in South Korea.

BACKGROUND: The association between remnant cholesterol (remnant-C) and cardiovascular disease risk is well established, but its association with dementia remains unclear. We aimed to examine this association using a large-scale population dataset. METHODS: We did a nationwide, population-based cohort study in which we identified participants aged 40 years and older who underwent the national health examination in 2009 from South Korea's National Health Insurance Service. We excluded people who were younger than 40 years and those with a triglyceride concentration of 400 mg/dL or higher due to concerns regarding the accuracy of calculated low-density lipoprotein cholesterol concentration in individuals with extremely high triglyceride concentrations. People who were previously diagnosed with dementia before the index date, and those who had any missing variables were also excluded. To minimise the influence of possible reverse causation, we excluded individuals who had developed any type of dementia within 1 year of the baseline measurements. We calculated hazard ratios (HRs) for all-cause dementia, Alzheimer's disease, and vascular dementia in each quartile of remnant-C using the Cox proportional hazards model adjusted for age, sex, body-mass index, estimated glomerular filtration rate, income level, smoking status, alcohol consumption, regular exercise, diabetes, hypertension, statin and fibrate use, and total cholesterol concentrations. We also did subgroup analyses to investigate the association between remnant-C and the risk of dementia stratified by age, sex, obesity, glycaemic status (normoglycaemia, impaired fasting glucose, new-onset type 2 diabetes, type 2 diabetes with a duration of less than 5 years, and type 2 diabetes with a duration of 5 years or more), hypertension, chronic kidney disease, and dyslipidaemia, using likelihood ratio tests. FINDINGS: 4 234 415 individuals who underwent the national health examination in 2009 were deemed eligible for inclusion. We excluded 1 612 819 individuals on the basis of age, triglyceride concentration, missing variables, or having dementia at baseline. We identified 2 621 596 participants aged 40 years and older (1 305 556 men and 1 316 040 women) who underwent the national health examination and followed them up until the date of any incident of dementia or the end of the study period of Dec 31, 2020. During a median follow-up of 10·3 years (IQR 10·1-10·6), 146 991 (5·6%) participants developed all-cause dementia, 117 739 (4·5%) developed Alzheimer's disease, and 14 536 (0·6%) developed vascular dementia. The risk of dementia increased progressively with higher remnant-C concentrations. Compared with the lowest quartile of remnant-C (quartile 1), HRs in the highest quartile (quartile 4) were 1·11 (95% CI 1·09-1·13) for all-cause dementia, 1·11 (1·08-1·13) for Alzheimer's disease, and 1·15 (1·09-1·21) for vascular dementia. Subgroup analyses revealed that the risk of dementia associated with high remnant-C concentrations was higher in middle-aged people aged 40-59 years than in older people. The risk of dementia associated with high concentrations of remnant-C was notably more pronounced in individuals with diabetes compared with those without diabetes, and the risk increased steeply with a longer duration of diabetes. INTERPRETATION: Results showed that higher remnant-C concentrations were independently associated with increased risks of all-cause dementia, Alzheimer's disease, and vascular dementia. More research is needed to determine the mechanisms underlying this finding. Monitoring and managing higher concentrations of remnant-C might have important implications for reducing the risk of dementia. FUNDING: None.

Income dynamics and risk of colorectal cancer in individuals with type 2 diabetes: a nationwide population-based cohort study.

BACKGROUND: Individuals with type 2 diabetes (T2D) have increased colorectal cancer (CRC) risk, but it is unknown whether income dynamics are associated with CRC risk in these individuals. We examined whether persistent low- or high-income and income changes are associated with CRC risk in non-elderly adults with T2D. METHODS: Using nationally representative data from the Korean Health Insurance Service database, 1,909,492 adults aged 30 to 64 years with T2D and no history of cancer were included between 2009 and 2012 (median follow-up of 7.8 years). We determined income levels based on health insurance premiums and assessed annual income quartiles for the baseline year and the four preceding years. Hazard ratios(HRs) and 95% confidence intervals(CIs) were estimated after adjusting for sociodemographic factors, CRC risk factors, and diabetes duration and treatment. RESULTS: Persistent low income (i.e., lowest income quartile) was associated with increased CRC risk (HRn=5years vs. n=0years 1.11, 95% CI 1.04-1.18; P for trend=0.004). Income declines (i.e., a decrease≥25% in income quantile) were also associated with increased CRC risk (HR≥2 vs. 0 declines 1.10, 95% CI 1.05-1.16; p for trend=0.001). In contrast, persistent high income (i.e., highest income quartile) was associated with decreased CRC risk (HRn=5years vs. n=0years 0.81, 95% CI 0.73-0.89; p for trend<0.0001), which was more pronounced for rectal cancer (HR 0.64, 95% CI 0.53-0.78) and distal colon cancer (HR 0.70, 95% CI 0.57-0.86). CONCLUSIONS: Our findings underscore the need for increased public policy awareness of the association between income dynamics and CRC risk in adults with T2D.

Exploring the potential of black fungus, Auricularia auricula, as a feed additive in African catfish, Clarias gariepinus, farming.

This study explores the beneficial effects of Auricularia auricula (AA) as a feed additive in promoting growth, digestive enzyme activities, antioxidative responses, heat tolerance, and disease resistance against Edwardsiella tarda in African catfish (Clarias gariepinus) farming. The application of feed additives is a hot topic in recent aquaculture studies aimed at promoting the growth and health of aquaculture species. After 8 weeks of feeding trial, the results of the present study revealed that fish-fed AA diets performed significantly better (p < 0.05) compared to the control group in growth performances, including final weight, weight gain, and specific growth rate. The highest performances were observed in the fish-fed AA at 3 and 4 %. A similar trend was also observed in the values of feed conversion ratio, hepatosomatic index, and visceral somatic index, with the lowest values (p < 0.05) in the fish-fed AA at 3 and 4 %. AA diets enhanced the activities of all tested digestive enzymes (amylase, protease, and lipase) significantly (p < 0.05), with the highest activities in the fish-fed AA at 3 and 4 %. Meanwhile, fish-fed AA diets exhibited significantly higher (p < 0.05) catalase, superoxide dismutase, and glutathione peroxidase activities both before and after heat stress, with the highest activities in the fish that received AA at 3 and 4 %. Furthermore, AA diets stimulated disease resistance in African catfish, with the fish-fed AA at 4 % performing the highest cumulative survival rate (73.3 ± 5.77 %) post-infection with E. tarda in African catfish. The findings of the current study suggest that AA has huge potential as a feed additive in African catfish farming.

A phase 4 randomized active-controlled clinical study to compare the efficacy and safety of sustained-release pregabalin with immediate-release pregabalin in type 2 diabetic patients with peripheral neuropathic pain.

AIMS: The objective of this study was to demonstrate that sustained-release (SR) pregabalin is non-inferior to immediate-release (IR) pregabalin in attenuating diabetic peripheral neuropathic (DPN) pain along with patient satisfaction and compliance. METHODS: This was an 8-week, randomized, active-controlled, open-label, phase 4 study. Eligible subjects who had been on IR pregabalin for 4 weeks were randomized to 1:1 ratio to either continue with twice-daily IR pregabalin (75 mg), or to switch to once-daily SR pregabalin (150 mg). Primary efficacy endpoint was the change in visual analogue scale (VAS) scores after 8 weeks of treatment compared to baseline in both SR and IR pregabalin groups. RESULTS: Among 130 randomized subjects, 125 patients were included in full analysis set. For the change in VAS pain score, the least squares (LS) mean were -17.95 (SR pregabalin) and -18.74 (IR pregabalin) and the LS mean difference between both groups was 0.79, with the upper limit of the 95 % confidence interval [-5.99, 7.58] below the pre-specified non-inferiority margin of 9.2 mm. CONCLUSIONS: This study demonstrates that the new once-daily SR pregabalin formulation is not different to the twice-daily IR pregabalin in alleviating DPN pain, indicating its potential as a promising treatment for DPN pain with a comparable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05624853.

Iteratively Calibratable Network for Reliable EEG-Based Robotic Arm Control.

Robotic arms are increasingly being utilized in shared workspaces, which necessitates the accurate interpretation of human intentions for both efficiency and safety. Electroencephalogram (EEG) signals, commonly employed to measure brain activity, offer a direct communication channel between humans and robotic arms. However, the ambiguous and unstable characteristics of EEG signals, coupled with their widespread distribution, make it challenging to collect sufficient data and hinder the calibration performance for new signals, thereby reducing the reliability of EEG-based applications. To address these issues, this study proposes an iteratively calibratable network aimed at enhancing the reliability and efficiency of EEG-based robotic arm control systems. The proposed method integrates feature inputs with network expansion techniques. This integration allows a network trained on an extensive initial dataset to adapt effectively to new users during calibration. Additionally, our approach combines motor imagery and speech imagery datasets to increase not only its intuitiveness but also the number of command classes. The evaluation is conducted in a pseudo-online manner, with a robotic arm operating in real-time to collect data, which is then analyzed offline. The evaluation results demonstrated that the proposed method outperformed the comparison group in 10 sessions and demonstrated competitive results when the two paradigms were combined. Therefore, it was confirmed that the network can be calibrated and personalized using only the new data from new users.

Complete genome sequences of two tombusvirus-like viruses identified in Echinacea purpurea seeds.

Echinacea is an herbaceous plant originating from North America that is cultivated for gardening and landscaping because of its showy flowers. Using high-throughput sequencing, we identified two viral contigs from echinacea seeds that were related to the family Tombusviridae. These two viruses were similar to oat chlorotic stunt virus (OCSV) and other unassigned tombusviruses; therefore, we tentatively named them Echinacea-associated tombusviruses 1 and 2 (EaTV1 and EaTV2, respectively). The EaTVs represent putative readthrough sites and have no poly(A) tails, aligning with the common features of family Tombusviridae. The EaTVs are included in a monophyletic group of OCSV and several unassigned tombusviruses. Because OCSV is the only member of Avenavirus to date, EaTVs are tentative members of Avenavirus, or they are close sister species to OCSV with several unassigned tombusviruses. RNA-dependent RNA polymerases and coat proteins were well conserved among EaTVs and unassigned tombusviruses; however, their similarities were not correlated, implying divergent and complex evolution.

Spatial detection and consequences of nonrenal calcitriol production as assessed by targeted mass spectrometry imaging.

The immune benefits of vitamin D3 supplementation beyond calcium and phosphate maintenance are highly clinically debated. Kidney expression of CYP27B1 is the source of endocrine, circulating 1,25(OH)2D3 (active form of vitamin D) that maintains serum calcium and phosphate. 1,25(OH)2D3 may also be made by the CYP27B1 enzyme in nonrenal cells, like immune cells, in a process driven by cellular availability of 25(OH)D3 and inflammation. Due to the endocrine nature of 1,25(OH)2D3 in circulation, it is difficult to discern between these 2 sources. We recently created a regulatory deletion model of Cyp27b1 (M1/M21-DIKO) where mice have normal inflammatory-regulated Cyp27b1 expression in nonrenal tissues (unlike global Cyp27b1-KO) but no expression within the kidney. Here, utilizing on-tissue chemical derivatization and matrix assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI), we investigated the distribution of 1,25(OH)2D3 and 25(OH)D3 in the kidney, liver, spleen, and thymus. MALDI-MSI demonstrated increased 1,25(OH)2D3 in nonrenal tissues such as the spleen after vitamin D3 supplementation in M1/M21-DIKO mice. Additionally, from this, we found increased Il4 and decreased Tnfa in the spleen after vitamin D3 supplementation. Taken together, these data demonstrate nonrenal production of 1,25(OH)2D3 in vivo and provide a consequence of vitamin D3 supplementation and nonrenal 1,25(OH)2D3 production in cytokine changes.

High remnant-cholesterol levels increase the risk for end-stage renal disease: a nationwide, population-based, cohort study.

BACKGROUND: The effect of remnant-cholesterol (remnant-C) on incident end-stage renal disease (ESRD) has not been studied longitudinally. This retrospective cohort study evaluated the association between remnant-C and the development of ESRD in a nationwide Korean cohort. METHODS: Participants in a National Health Insurance Service health examination (n = 3,856,985) were followed up until the onset of ESRD. The median duration of follow-up was 10.3 years. The Martin-Hopkins equation was used to determine low-density lipoprotein cholesterol (LDL-C) levels from directly measured triglyceride, high-density lipoprotein cholesterol (HDL-C), and total cholesterol levels. Remnant-C levels were determined by subtracting HDL-C and LDL-C from total cholesterol. The risk for incident ESRD was calculated for each quartile of remnant-C, adjusting for conventional risk factors such as baseline renal function, comorbidities, and total cholesterol levels. RESULTS: ESRD developed in 11,073 (0.29%) participants. The risk for ESRD exhibited a gradual increase according to higher levels of remnant-C, with a 61% increased risk in the highest quartile than in the lowest (hazard ratio [HR] 1.61 [95% confidence interval (CI) 1.50-1.72]). The elevated risk for ESRD in the highest quartile versus the lowest quartile was more prominent in younger than in older subjects (20-29 years, HR 4.07 [95% CI 2.85-5.83]; 30-39 years, HR 2.39 [95% CI 1.83-3.13]; ≥ 70 years, HR 1.32 [95% CI 1.16-1.51]). In addition, the increased risk for ESRD related to higher remnant-C levels was greater in females than in males. CONCLUSIONS: Independent of conventional risk factors, remnant-C levels were positively associated with incident ESRD, particularly in younger populations and adult females. Reducing remnant-C levels may be a novel preventive strategy against ESRD.

Mitigating Trunk Compensatory Movements in Post-Stroke Survivors through Visual Feedback during Robotic-Assisted Arm Reaching Exercises.

Trunk compensatory movements frequently manifest during robotic-assisted arm reaching exercises for upper limb rehabilitation following a stroke, potentially impeding functional recovery. These aberrant movements are prevalent among stroke survivors and can hinder their progress in rehabilitation, making it crucial to address this issue. This study evaluated the efficacy of visual feedback, facilitated by an RGB-D camera, in reducing trunk compensation. In total, 17 able-bodied individuals and 18 stroke survivors performed reaching tasks under unrestricted trunk conditions and visual feedback conditions. In the visual feedback modalities, the target position was synchronized with trunk movement at ratios where the target moved at the same speed, double, and triple the trunk's motion speed, providing real-time feedback to the participants. Notably, trunk compensatory movements were significantly diminished when the target moved at the same speed and double the trunk's motion speed. Furthermore, these conditions exhibited an increase in the task completion time and perceived exertion among stroke survivors. This outcome suggests that visual feedback effectively heightened the task difficulty, thereby discouraging unnecessary trunk motion. The findings underscore the pivotal role of customized visual feedback in correcting aberrant upper limb movements among stroke survivors, potentially contributing to the advancement of robotic-assisted rehabilitation strategies. These insights advocate for the integration of visual feedback into rehabilitation exercises, highlighting its potential to foster more effective recovery pathways for post-stroke individuals by minimizing undesired compensatory motions.

Electromagnetic Interference Shielding Properties of Highly Flexible Poly(styrene-co-butyl acrylate)/PEDOT:PSS Films Fabricated by Latex Technology.

As the use of stretchable electronic devices increases, the importance of flexible electromagnetic interference (EMI) shielding films is emerging. In this study, a highly flexible shielding film was fabricated using poly(styrene-co-butyl acrylate) (p(St-co-BA)) latex as a matrix and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) as a conductive filler, and then the mechanical properties and EMI shielding performance of the film were examined. Styrene and butyl acrylate were copolymerized to lower the high glass transition temperature and increase the ductility of brittle polystyrene. The latex blending technique was used to produce a shielding film in which the aqueous filler dispersion was uniformly dispersed in the emulsion polymerized resin. To determine the phase change in the copolymer matrix with temperature, the storage modulus was measured, and a time-temperature superposition master curve was constructed. The drying temperature of water-based copolymer resin suitable for film fabrication was set based on this curve. The glass transition temperature and flexibility of the blends were determined by evaluating the thermomechanical analysis and tensile tests. The EMI shielding effectiveness (SE) of the films was analyzed at frequencies from 50 MHz to 1.5 GHz, covering the VHF and UHF ranges. As the filler content increased, the SE of the blend film increased, but the elongation increased until a certain content and then decreased. The optimal content of PEDOT:PSS that satisfied both the ductility and shielding performance of the film was found to be 10 wt%. In this case, the elongation at break reached 300%, and the SE of a 1.6 mm thick film was about 35 dB. The film developed in this study can be used as an EMI shielding material that requires high flexibility.

Behavior of Extracranial-to-Intracranial Extended Arterial Dissections of the Vertebral Artery.

BACKGROUND: Vertebral artery dissections (VADs) may extend from the extracranial to the intracranial vasculature (e+iVAD). We evaluated how the characteristics of e+iVAD differed from those of intracranial VAD (iVAD). METHODS AND RESULTS: From 2002 to 2019, among consecutive patients with cervicocephalic dissection, those with iVAD and e+iVAD were included, and their clinical characteristics were compared. In patients with unruptured dissections, a composite clinical outcome of subsequent ischemic events, subsequent hemorrhagic stroke, or mortality was evaluated. High-resolution magnetic resonance images were analyzed to evaluate intracranial remodeling index. Among 347 patients, 51 (14.7%) had e+iVAD and 296 (85.3%) had iVAD. The hemorrhagic presentation occurred solely in iVAD (0.0% versus 19.3%), whereas e+iVAD exhibited higher ischemic presentation (84.3% versus 27.4%; P<0.001). e+iVAD predominantly presented steno-occlusive morphology (88.2% versus 27.7%) compared with dilatation patterns (11.8% versus 72.3%; P<0.001) of iVAD. The ischemic presentation was significantly associated with e+iVAD (iVAD as a reference; adjusted odds ratio, 3.97 [95% CI, 1.67-9.45]; P=0.002]). Patients with unruptured VAD showed no differences in the rate of composite clinical outcome between the groups (log-rank, P=0.996). e+iVAD had a lower intracranial remodeling index (1.4±0.3 versus 1.6±0.4; P<0.032) and a shorter distance from dural entry to the maximal dissecting segment (6.9±8.4 versus 15.7±7.4; P<0.001). CONCLUSIONS: e+iVAD is associated with lower rates of hemorrhages and higher rates of ischemia than iVAD at the time of admission. This may be explained by a lower intracranial remodeling index and less deep intrusion of the dissecting segment into the intracranial space.