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Abstract BackgroundControlling saturated fat and cholesterol intake is important for the prevention of cardiovascular diseases. Although the use of mobile diet-tracking apps has been increasing, the reliability of nutrition apps in tracking saturated fats and cholesterol across different nations remains underexplored. ObjectiveThis study aimed to examine the reliability and consistency of nutrition apps focusing on saturated fat and cholesterol intake across different national contexts. The study focused on 3 key concerns: data omission, inconsistency (variability) of saturated fat and cholesterol values within an app, and the reliability of commercial apps across different national contexts. MethodsNutrient data from 4 consumer-grade apps (COFIT, MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!) and an academic app (Formosa FoodApp) were compared against 2 national reference databases (US Department of Agriculture [USDA]–Food and Nutrient Database for Dietary Studies [FNDDS] and Taiwan Food Composition Database [FCD]). Percentages of missing nutrients were recorded, and coefficients of variation were used to compute data inconsistencies. One-way ANOVAs were used to examine differences among apps, and paired 2-tailed t ResultsAcross the 5 apps, 836 food codes from 42 items were analyzed. Four apps, including COFIT, MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!, significantly underestimated saturated fats, with errors ranging from −13.8% to −40.3% (all PP< ConclusionsThe findings reveal substantial inaccuracies and inconsistencies in diet-tracking apps’ reporting of saturated fats and cholesterol. These issues raise concerns for the effectiveness of using consumer-grade nutrition apps in cardiovascular disease prevention across different national contexts and within the apps themselves.

The relationship between a performer’s conscious involvement or investment in movement control and monitoring and the ability to inhibit the movement is still unclear. We conducted three experiments to investigate whether a higher inclination for conscious movement investment benefits the inhibition of a simple keypress response. In all experiments, the inclination for conscious movement investment was measured with the Movement-Specific Reinvestment Scale. In Experiment 1, participants performed the go/no-go task and conscious investment was manipulated by directing conscious attention either to the finger movement (i.e., internal focus) or to the resulting motion of the key (i.e., external focus). The results showed that neither the participants’ inclination for conscious movement investment, nor the direction of conscious attention affected inhibition performance. In Experiment 2, participants performed the stop-signal task, which is more attention demanding than the go/no-go task. The results showed that participants with a high or low inclination for conscious movement investment did not differ in inhibition performance. In Experiment 3 an ego-depletion procedure was included that limits resources for conscious movement investment. Before and after this ego-depletion procedure, participants performed the stop-signal task. The results showed that participants with a high inclination for conscious movement investment slowed down inhibition when they felt mentally depleted, while no slowing down of inhibition was found among participants who felt less depleted and/or had a low inclination for conscious movement investment. Together, the study provides evidence that increased conscious movement investment is beneficial for movement inhibition. Yet, these effects only emerge against the dynamic background of interacting individual (e.g., inclination for conscious movement investment, available attentional resources) and task constraints (e.g., task difficulty).

Aims: We compared the efficacy, fidelity, acceptability, and feasibility of a creative movement (CM) intervention for children with autism spectrum disorder (ASD), delivered face-to-face (F2F) or through telehealth (TH). Methods: Fifteen children with ASD received the CM intervention F2F or through TH. Motor assessments were used to evaluate effects of F2F and TH interventions on children's motor skills, while video coding was used to assess affect, socially directed verbalization, interpersonal synchrony, and motor coordination during training. Stakeholder feedback and training fidelity data on the intervention were also collected. Results: Children in both subgroups showed similar baseline performance and training-related improvements in motor skills, positive/interested affect, socially directed verbalization, interpersonal synchrony, and dual/multilimb coordination. Parents in the TH subgroup considered the intervention feasible and acceptable; however, they reported greater effort to supervise and redirect their child's attention compared to the F2F subgroup. Trainers for the TH subgroup reported more communication difficulties, technological issues, and longer session lengths, but found greater parental involvement compared to the F2F subgroup. Conclusions: CM interventions are consistent, acceptable, feasible, and effective in improving social, behavioral-affective, and motor skills of children with ASD, regardless of the method of delivery. Clinicians should make efforts to reduce communication/technological issues and parental burden when delivering CM interventions through TH. ClinicalTrials.Gov Study ID-NCT04258254.

Abstract Declines in oral consumption and swallowing function are common reasons which may elevate the risk of malnutrition in the older adults. This study aimed to provide valuable information and contribute to the existing body of knowledge in this field as well as highlight the importance of a comprehensive assessment of oral health, swallowing function, and nutritional status in long-term care residents. This was a cross-sectional study. Thirty-nine participants were recruited from a nursing home. The comprehensive assessment was evaluated in participants, including oral health (Oral Health Assessment Tool (OHAT)), swallowing function (Functional Oral Intake Scale (FOIS) and Eating Assessment Tool (EAT)-10), and nutritional status (Mini Nutritional Assessment-Short Form (MNA-SF). The average age of participants was 80.4 ± 11.7 years, and 46% of these older adults were found to be at the risk of malnutrition. There was a negative correlation between the OHAT and MNA-SF scores. In addition, subjects with poor oral health (OHAT score = 5~8), oral consumption of a modified diet (FOIS score = 4~6), and reduced swallowing function (EAT-10 score ≥ 3) were more likely to be at risk of malnutrition. A comprehensive evaluation of oral health and swallowing function was closely connected with the nutritional status of older nursing home dwellers.

Abstract Background Malignant ascites is prevalent in advanced‐stage ovarian cancer and may facilitate identification of the drivers of muscle loss. This study aimed to evaluate the association of ascites with changes in systemic inflammation and muscle after treatment of advanced‐stage ovarian cancer. Methods We evaluated 307 patients with advanced‐stage (III/IVA) ovarian cancer who underwent primary debulking surgery and adjuvant platinum‐based chemotherapy between 2010 and 2019. The changes in skeletal muscle index (SMI) and radiodensity (SMD) were measured using pre‐surgery and post‐chemotherapy portal‐venous phase contrast‐enhanced computed tomography scans at L3. Systemic inflammation was measured using albumin levels, prognostic nutritional index (PNI), neutrophil‐lymphocyte ratio (NLR), and platelet‐lymphocyte ratio (PLR). Primary endpoint was the changes in SMI and SMD after treatment. Linear regression analysis was used to test associations between muscle change and other covariates. Mediation analysis was used to determine the mediator. Results The median (range) age was 53 (23–83) years. The median duration (range) of follow‐up was 5.2 (1.1–11.3) years. Overall, 187 (60.9%) patients had ascites. The changes in muscle and systemic inflammatory markers after treatment were significantly different between patients with and without ascites (SMI: −3.9% vs. 2.2%, P

Abstract Background Skeletal muscle loss during treatment is associated with poor survival outcomes in patients with ovarian cancer. Although changes in muscle mass can be assessed on computed tomography (CT) scans, this labour‐intensive process can impair its utility in clinical practice. This study aimed to develop a machine learning (ML) model to predict muscle loss based on clinical data and to interpret the ML model by applying SHapley Additive exPlanations (SHAP) method. Methods This study included the data of 617 patients with ovarian cancer who underwent primary debulking surgery and platinum‐based chemotherapy at a tertiary centre between 2010 and 2019. The cohort data were split into training and test sets based on the treatment time. External validation was performed using 140 patients from a different tertiary centre. The skeletal muscle index (SMI) was measured from pre‐ and post‐treatment CT scans, and a decrease in SMI ≥ 5% was defined as muscle loss. We evaluated five ML models to predict muscle loss, and their performance was determined using the area under the receiver operating characteristic curve (AUC) and F1 score. The features for analysis included demographic and disease‐specific characteristics and relative changes in body mass index (BMI), albumin, neutrophil‐to‐lymphocyte ratio (NLR), and platelet‐to‐lymphocyte ratio (PLR). The SHAP method was applied to determine the importance of the features and interpret the ML models. Results The median (inter‐quartile range) age of the cohort was 52 (46–59) years. After treatment, 204 patients (33.1%) experienced muscle loss in the training and test datasets, while 44 (31.4%) patients experienced muscle loss in the external validation dataset. Among the five evaluated ML models, the random forest model achieved the highest AUC (0.856, 95% confidence interval: 0.854–0.859) and F1 score (0.726, 95% confidence interval: 0.722–0.730). In the external validation, the random forest model outperformed all ML models with an AUC of 0.874 and an F1 score of 0.741. The results of the SHAP method showed that the albumin change, BMI change, malignant ascites, NLR change, and PLR change were the most important factors in muscle loss. At the patient level, SHAP force plots demonstrated insightful interpretation of our random forest model to predict muscle loss. Conclusions Explainable ML model was developed using clinical data to identify patients experiencing muscle loss after treatment and provide information of feature contribution. Using the SHAP method, clinicians may better understand the contributors to muscle loss and target interventions to counteract muscle loss.

To assess the effects of hydroxysafflor yellow A (HSYA) on ultraviolet A (UVA)-induced damage in HaCaT keratinocytes. HaCaT keratinocytes were UVA-irradiated, and the effects of HSYA on cell viability, reactive oxygen species (ROS) generation, lipid peroxidation, and messenger (m)RNA expression were measured. mRNA expressions of matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, and cyclooxygenase (COX)-2 were determined by a real-time polymerase chain reaction (RT-PCR). UVA exposure led to a decrease in cell viability and an increase in ROS generation in HaCaT keratinocytes. HSYA effectively increased the viability of HaCaT keratinocytes after UVA exposure and protected them from UVA-induced oxidative stress. Moreover, HSYA inhibited expressions of MMP-1, MMP-2, MMP-9, and COX-2 by HaCaT keratinocytes with UVA-induced photodamage. Our results suggest that HSYA can act as a free radical scavenger when keratinocytes are photodamaged. HSYA has the potential to be a skin-protective ingredient against UVA-induced photodamage.

The molecular and genetic mechanisms underlying left atrial (LA) enlargement and atrial fibrosis following right ventricular (RV) dependent pacing remain unclear. Our objective was to investigate genetic expressions in the LA of pigs subjected to RV pacing for atrioventricular block (AVB), as well as to identify the differential gene expressions affected by biventricular (BiV) pacing. We established an AVB pig model and divided the subjects into three groups: a sham control group, an RV pacing group, and a BiV pacing group. Differential expression genes (DEGs) analyses conducted through next-generation sequencing (NGS) and enrichment analyses were employed to identify genes with altered expression in the LA myocardium. The RV pacing group showed a significant increase in extracellular fibrosis in the LA myocardium compared to the control group. NGS analysis revealed suppressed expression of the sirtuin signaling pathway in the RV pacing group. Among the DEGs within this pathway, GADD45G was found to be downregulated in the RV pacing group and upregulated in the BiV pacing group. Remarkably, the BiV pacing group exhibited elevated levels of GADD45G protein. In our study, we observed significant downregulation of SIRT1 and GADD45G genes, which are associated with the sirtuin signaling pathway, in the LA myocardium of the RV pacing group when compared to the control group. Moreover, these genes, which were downregulated in the RV pacing group, displayed a noteworthy upregulation in the BiV pacing group when compared to the RV pacing group.

Di(2-ethylhexyl) phthalate (DEHP) is a worldwide common plasticizer. Nevertheless, DEHP is easily leached out to the environment due to the lack of covalent bonds with plastic. High dose of DEHP exposure is often observed in hemodialysis patients because of the continual usage of plastic medical devices. Although the liver is the major organ that catabolizes DEHP, the impact of long-term DEHP exposure on the sensitivity of liver cancer to chemotherapy remains unclear. In this study, we established long-term DEHP-exposed hepatocellular carcinoma (HCC) cells and two NOD/SCID mice models to investigate the effects and the underlying mechanisms of long-term DEHP exposure on chemosensitivity of HCC. The results showed long-term DEHP exposure potentially increased epithelial-mesenchymal transition (EMT) in HCC cells. Next generation sequencing showed that long-term DEHP exposure increased cell adhesion/migratory related genes expression and blunted sorafenib treatment induced genes alterations. Long-term exposure to DEHP reduced the sensitivity of HCC cells to sorafenib-induced anti-migratory effect by enhancing the EMT transcription factors (slug, twist, and ZEB1) and mesenchymal protein (vimentin) expression. In NOD/SCID mice model, we showed that long-term DEHP-exposed HCC cells exhibited higher growth rate. Regarding the anti-HCC effects of sorafenib, subcutaneous HuH7 tumor grew slowly in sorafenib-treated mice. Nonetheless, the anti-tumor growth effect of sorafenib was not observed in long-term DEHP-exposed mice. Higher mesenchymal markers and proliferating cell nuclear antigen (PCNA) expression were found in sorafenib-treated long-term DEHP-exposed mice. In conclusion, long-term DEHP exposure promoted migratory activity in HCC cells and decreased sorafenib sensitivity in tumor-bearing mice.

DNA vaccines for infectious diseases and cancer have been explored for years. To date, only one DNA vaccine (ZyCoV-D) has been authorized for emergency use in India. DNA vaccines are inexpensive and long-term thermostable, however, limited by the low efficiency of intracellular delivery. The recent success of mRNA/lipid nanoparticle (LNP) technology in the coronavirus disease 2019 (COVID-19) pandemic has opened a new application for nucleic acid-based vaccines. Here, we report that plasmid encoding a trimeric spike protein with LNP delivery (pTS/LNP), similar to those in Moderna’s COVID-19 vaccine, induced more effective humoral responses than naked pTS or pTS delivered via electroporation. Compared with TSmRNA/LNP, pTS/LNP immunization induced a comparable level of neutralizing antibody titers and significant T helper 1-biased immunity in mice; it also prolonged the maintenance of higher antigen-specific IgG and neutralizing antibody titers in hamsters. Importantly, pTS/LNP immunization exhibits enhanced cross-neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and protects hamsters from the challenge of SARS-CoV-2 (Wuhan strain and the Omicron BA.1 variant). This study indicates that pDNA/LNPs as a promising platform could be a next-generation vaccine technology.

Background Metabolic disorder is noted for pacing‐induced cardiomyopathy. The benefits of His bundle pacing over right ventricular (RV) pacing in preventing pacing‐induced cardiomyopathy from a metabolic perspective are yet to be fully understood. Method and Results Three pig groups were established for this study: sham control, RV pacing (RV pacing for 6 months), and His pacing (RV pacing for 6 months, followed by His bundle pacing for 3 months). Complete atrioventricular block was created in the last 2 groups. Left ventricular function and dyssynchrony were assessed via echocardiography, while proteins linked to metabolism, endoplasmic reticulum stress, and inflammation in left ventricular myocardium were examined. The RV pacing group had significantly more left ventricular mechanical dyssynchrony compared with the other groups. The RV pacing group exhibited triglyceride and diacylglycerol accumulation in cardiomyocytes and higher expression of binding immunoglobulin protein and tumor necrosis factor‐α than the other groups. Additionally, the expression of CD36 was activated, while the expression of hormone‐sensitive lipase was downregulated in the RV pacing group compared with the His pacing and sham control groups. Furthermore, the expressions of GLUT4 and pyruvate dehydrogenase were higher in the RV pacing group than the sham control and His pacing groups. Notably, the abnormal fatty acid and glucose metabolic pathways in the left ventricular myocardium during RV pacing could be corrected by His bundle pacing. Conclusions His bundle pacing can mitigate the abnormal metabolism disorders, endoplasmic reticulum stress, and inflammation induced during RV pacing and may contribute to the superiority of conduction system pacing over RV pacing in reducing heart failure hospitalization.

Abstract Background Cones are essential for color recognition, high resolution, and central vision; therefore cone death causes blindness. Understanding the pathophysiology of each cell type in the retina is key to developing therapies for retinal diseases. However, studying the biology of cone cells in the rod-dominant mammalian retina is particularly challenging. In this study, we used a bacterial artificial chromosome (BAC) recombineering method to knock in the “CreERT2” sequence into the Gnat2 and Arr3 genes, respectively and generated three novel inducible CreERT2 mice with different cone cell specificities. Results These models (Gnat2 CreERT2 , Arr3 T2ACreERT2 , and Arr3 P2ACreERT2 ) express temporally controllable Cre recombinase that achieves conditional alleles in cone photoreceptors. Cre-LoxP recombination can be induced as early as postnatal day (PD) two upon tamoxifen injection at varying efficiencies, ranging from 10 to 15% in Gnat2 CreERT2 , 40% in Arr3 T2ACreERT2 , and 100% in Arr3 P2ACreERT2 . Notably, knocking in the P2A-CreERT2 cassette does not affect cone cell morphology and functionality. Most cone-phototransduction enzymes, including Opsins, CNGA3, etc. are not altered except for a reduction in the Arr3 transcript. Conclusions The Arr3 P2ACreERT2 mouse, an inducible cone-specific Cre driver, is a valuable line in studying cone cell biology, function, as well as its relationship with rod and other retinal cells. Moreover, the Cre activity can be induced by delivering tamoxifen intragastrically as early as PD2, which will be useful for studying retinal development or in rapid degenerative mouse models.

Estrogen deficiency increases the secretion of inflammatory mediators and can lead to obesity. Consequently, estrogen deficiency can cause metabolic syndrome, particularly insulin resistance during menopause. Both fish oil and perilla oil contain n-3 fatty acids, which may regulate several inflammatory cytokines. Additionally, adjusting the dietary n-3:n-6 fatty-acid ratio to 1:2 may help treat or prevent chronic diseases. Therefore, we investigated the effect of anti-inflammatory and insulin-signaling pathways, not solely in relation to the (n-3:n-6 fatty-acid ratio at 1:2), but also considering the origin of n-3 fatty acids found in fish oil and perilla oil, in a mouse model of estrogen deficiency induced by ovariectomy and obesity induced by a high-fat diet (HFD). Female C57BL/6J mice were divided into five groups: sham mice on a normal diet; ovariectomized (OVX) mice on a normal diet (OC); OVX mice on a HFD plus lard oil (OL), fish oil (OF), or perilla oil (OP). The dietary n-3:n-6 ratio in the OF and OP groups was adjusted to 1:2. The results showed OF group exhibited significantly lower abdominal adipose tissue weight, fewer liver lipid droplets, and smaller uterine adipocytes, compared with the OL group. Compared with the OL group, the OF and OP groups exhibited higher oral glucose tolerance and lower serum alanine aminotransferase activity, triacylglycerol levels, and total cholesterol levels. Hepatic JAK2, STAT3, and SOCS3 mRNA expression and p–NF–κB p65 and IL-6 levels were significantly lower in the OF and OP groups than in the OL group. Only the OF group exhibited an increase in PI3K and Akt mRNA expression, decrease in GLUT2 mRNA expression, and considerable elevation of p-Akt. Both fish and perilla oil reduced inflammatory signaling markers. However, only fish oil improved insulin signaling (PI3K, Akt, and GLUT2). Our data suggest that fish oil can alleviate insulin signaling through activating the PI3K-Akt-GLUT2 cascade signaling pathway.

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a predominantly drug-induced disease, with a mortality rate of 15–20%, that engages the expertise of multiple disciplines: dermatology, allergy, immunology, clinical pharmacology, burn surgery, ophthalmology, urogynecology, and psychiatry. SJS/TEN has an incidence of 1–5/million persons per year in the United States, with even higher rates globally. One of the challenges of SJS/TEN has been developing the research infrastructure and coordination to answer questions capable of transforming clinical care and leading to improved patient outcomes. SJS/TEN 2021, the third research meeting of its kind, was held as a virtual meeting on August 28–29, 2021. The meeting brought together 428 international scientists, in addition to a community of 140 SJS/TEN survivors and family members. The goal of the meeting was to brainstorm strategies to support the continued growth of an international SJS/TEN research network, bridging science and the community. The community workshop section of the meeting focused on eight primary themes: mental health, eye care, SJS/TEN in children, non-drug induced SJS/TEN, long-term health complications, new advances in mechanisms and basic science, managing long-term scarring, considerations for skin of color, and COVID-19 vaccines. The meeting featured several important updates and identified areas of unmet research and clinical need that will be highlighted in this white paper.

Abstract Motor execution, observation, and imagery are important skills used in motor learning and rehabilitation. The neural mechanisms underlying these cognitive-motor processes are still poorly understood. We used a simultaneous recording of functional near-infrared spectroscopy (fNIRS) and electroencephalogram (EEG) to elucidate the differences in neural activity across three conditions requiring these processes. Additionally, we used a new method called structured sparse multiset Canonical Correlation Analysis (ssmCCA) to fuse the fNIRS and EEG data and determine the brain regions of neural activity consistently detected by both modalities. Unimodal analyses revealed differentiated activation between conditions; however, the activated regions did not fully overlap across the two modalities (fNIRS: left angular gyrus, right supramarginal gyrus, as well as right superior and inferior parietal lobes; EEG: bilateral central, right frontal, and parietal). These discrepancies might be because fNIRS and EEG detect different signals. Using fused fNIRS-EEG data, we consistently found activation over the left inferior parietal lobe, superior marginal gyrus, and post-central gyrus during all three conditions, suggesting that our multimodal approach identifies a shared neural region associated with the Action Observation Network (AON). This study highlights the strengths of using the multimodal fNIRS-EEG fusion technique for studying AON. Neural researchers should consider using the multimodal approach to validate their findings.