Exploring the Effects of Whole Food-Based Dragon Fruit on Metabolic Disorders in High-Fat Diet-Induced Mice.

SCOPE: Metabolic syndrome (MetS) significantly contributes to premature mortality, with obesity being a major risk factor. Dragon fruit, cultivated globally, exhibits bioactivity in preventing obesity-related diseases. Traditional studies using organic solvents for extraction do not align with actual consumption patterns. METHOD AND RESULTS: This study evaluates whole red dragon fruit's effectiveness in ameliorating metabolic disorders using a high-fat diet-induced obesity model in mice for 20 weeks. The experimental groups include the supernatant (RS), precipitate (RP), and pomace (PO) of red dragon fruit juice, compared to the supernatant of white dragon fruit juice (WS). The study finds that dragon fruit extracts reduced adipose tissue weight, body fat percentage, pro-inflammatory cytokines, and improved blood lipid profiles. RP is the most effective, reducing body weight by 4.33 g, improving lipid metabolism and glucose homeostasis, and altering gut microbiota to enhance beneficial bacteria and short-chain fatty acids. RP's efficacy in preventing MetS and obesity is attributed to its bioactive components. CONCLUSION: These findings advocate for using whole fruits in developing functional products, amplifying the agricultural economic value of red dragon fruit.

The role of genetic testing in adult patients with unexplained epilepsy.

OBJECTIVE: Genetic causes are often overlooked in patients with epilepsy of unknown etiology, particularly in adults. We aimed to evaluate clinical features of genetic epilepsy and the utility of genetic testing. METHODS: We retrospectively screened consecutive unrelated adult epilepsy patients at an epilepsy clinic from April 2022 to May 2023. Patients with unknown etiology or special brain lesions were classified as unexplained epilepsy. In them, patients with young-onset seizures or family history of seizures who were recommended for and ultimately underwent genetic testing using either panel next-generation sequencing (NGS) or whole-exome sequencing (WES) were enrolled. A definite or probable genetic diagnosis was established through genotype-phenotype correlation. We compared the demographic characteristics between genetic epilepsy and other etiologies. RESULTS: Of the 374 adult epilepsy patients, 258 were classified as unexplained epilepsy, 129 were suspected of having genetic epilepsy due to young-onset seizures or a positive family history, 33 underwent genetic testing; 13 harbored variants classified as pathogenic, and 6 reached a definite genetic diagnosis, resulting in a yield of 18%. Among the 27 patients without a definite genetic diagnosis, 7 had a nongenetic structural etiology. Patients with genetic etiology exhibited greater multisystem involvement particularly multiple structural anomalies and early childhood-onset seizures, but wasn't directly correlated with young-onset seizures or a positive family history. The diagnostic yield was comparable between panel NGS and WES. SIGNIFICANCE: In adult patients with unexplained epilepsy, genetic epilepsy is more associated with multisystem involvement and multiple structural anomalies but not family history of seizures or young-onset seizures.

Rationally designed febuxostat-based hydroxamic acid and its pH-Responsive nanoformulation elicits anti-tumor activity.

Attempts to furnish antitumor structural templates that can prevent the occurrence of drug-induced hyperuricemia spurred us to generate xanthine oxidase inhibitor-based hydroxamic acids and anilides. Specifically, the design strategy involved the insertion of febuxostat (xanthine oxidase inhibitor) as a surface recognition part of the HDAC inhibitor pharmacophore model. Investigation outcomes revealed that hydroxamic acid 4 elicited remarkable antileukemic effects mediated via HDAC isoform inhibition. Delightfully, the adduct retained xanthine oxidase inhibitory activity, though xanthine oxidase inhibition was not the underlying mechanism of its cell growth inhibitory effects. Also, compound 4 demonstrated significant in-vivo anti-hyperuricemic (PO-induced hyperuricemia model) and antitumor activity in an HL-60 xenograft mice model. Compound 4 was conjugated with poly (ethylene glycol) poly(aspartic acid) block copolymer to furnish pH-responsive nanoparticles (NPs) in pursuit of circumventing its cytotoxicity towards the normal cell lines. SEM analysis revealed that NPs had uniform size distributions, while TEM analysis ascertained the spherical shape of NPs, indicating their ability to undergo self-assembly. HDAC inhibitor 4 was liberated from the matrix due to the polymeric nanoformulation's pH-responsiveness, and the NPs demonstrated selective cancer cell targeting ability.

The flavonoid hydroxygenkwanin reduces inflammation and neointimal formation.

Abnormal vascular smooth muscle cell (VSMC) proliferation and migration play crucial roles in neointimal hyperplasia and restenosis progression in response to stimulation with various inflammatory cytokines, such as platelet-derived growth factor-BB (PDGF-BB) and tumour necrosis factor-α (TNF-α). Hydroxygenkwanin (HGK) exerts remarkable anti-inflammatory, antitumour, antiproliferative and antimigratory effects. The aim of the study was to elucidate the therapeutic effect and regulatory mechanism of HGK on neointimal hyperplasia. The results showed that HGK inhibited the abnormal proliferation, migration, and inflammation of PDGF-BB- or TNF-α-treated VSMCs through regulation of the PDK1/AKT/mTOR pathway. In addition, HGK promoted circulating endothelial progenitor cell (EPC) chemotaxis. In an in vivo assay, HGK dramatically enhanced re-endothelization and reduced neointimal hyperplasia after femoral artery denudation with a guide wire in mice. These results suggest that HGK can serve as a therapeutic target drug or a functional food supplement for the treatment of restenosis.

Optimal positions of clear aligner attachments to achieve lower canine tipping and bodily movement using finite element analysis.

Background/purpose: Clear aligners are popular orthodontic tools because of their relatively aesthetic appearance and convenience of use. Nevertheless, bodily tooth movements still present challenges. This study evaluated various configurations of attachments placed on the mandibular canine in terms of the efficiency of canine bodily movement and correction of tipping. Materials and methods: A finite element model of the mandible was constructed to investigate the effects of various attachment configurations on the overall bodily movement and undesirable tipping of a mandibular canine. Canine movements were categorized into four types, namely tipping and bodily movements in the mesial and distal directions. The size and shape of the attachments were fixed, but their placement and orientation were varied. Five and seven attachment configurations were evaluated for their influence on tipping and bodily movements, respectively. Results: Attachment configuration significantly influenced mandibular canine tipping. The mesial occlusal-distal cervical and mesial occlusal-mesial cervical configurations had notable effects on mesial tipping, and the mesial occlusal-mesial cervical configuration excelled in distal tipping by increasing strain by 33.1%. The mesial occlusal-mesial cervical attachment configuration consistently had superior efficiency in facilitating both mesial and distal bodily movements of the canine. Conclusion: The mesial occlusal-mesial cervical attachment configuration excelled in all four types of canine movement. Irrespective of the attachment configuration, canines tend to move overall with slight tipping due to skeletal resistance and their center of rotation. The attachment configuration is crucial to the success of clear aligner treatment and must be carefully considered in clinical practice.

Trajectories of hepatic steatosis and incidence of cardiovascular disease over a 29-year follow-up.

AIM: To examine the dynamic change in hepatic steatosis status during repeated assessments over time, and its potential impact on the risk of developing cardiovascular disease (CVD). METHODS: We assessed trajectories of hepatic steatosis and other metabolic disorders in 3134 middle-aged adults undergoing longitudinal assessment of ultrasonography during a pre-baseline period (1993-2009) in a population-based cohort study of liver health. Subsequently, we determined the association of hepatic steatosis trajectories with the incidence of CVD among 2185 CVD-free individuals, followed until 2021. Metabolic risk factors and cardiovascular events (including coronary heart disease and stroke) were determined through medical examination and linkage with nationwide health databases. RESULTS: We identified three discrete trajectories of hepatic steatosis according to changing pattern over time through group-based trajectory modeling: "stable, non-steatosis" (n = 1298), "intermittent" (n = 921), and "persistent steatosis" (n = 915). During the pre-baseline period, hepatic steatosis trajectories were associated with trajectories of developing diabetes and hypertension, and persistent steatosis (vs. other trajectories) was associated with higher risks and rapidly progressive disease patterns. At a median 13.6 years of follow-up, 629 CVD events occurred. A persistent (vs. non-steatosis: HR 1.44, 95% CI 1.17-1.76), but not intermittent, steatosis pattern predicted the future risk of CVD, after adjustment for age, sex, smoking, and obesity. This association was independent of genetic background, and remained after accounting for pre-baseline body-mass index, other cardiometabolic risk factors, Framingham risk score, medications, and hepatic fibrosis score. CONCLUSIONS: The persistence of hepatic steatosis is associated with trajectories of metabolic disorder development and increased risk of CVD. These data have important implications for practice and further research.

CURE: A deep learning framework pre-trained on large-scale patient data for treatment effect estimation.

Treatment effect estimation (TEE) aims to identify the causal effects of treatments on important outcomes. Current machine-learning-based methods, mainly trained on labeled data for specific treatments or outcomes, can be sub-optimal with limited labeled data. In this article, we propose a new pre-training and fine-tuning framework, CURE (causal treatment effect estimation), for TEE from observational data. CURE is pre-trained on large-scale unlabeled patient data to learn representative contextual patient representations and fine-tuned on labeled patient data for TEE. We present a new sequence encoding approach for longitudinal patient data embedding both structure and time. Evaluated on four downstream TEE tasks, CURE outperforms the state-of-the-art methods, marking a 7% increase in area under the precision-recall curve and an 8% rise in the influence-function-based precision of estimating heterogeneous effects. Validation with four randomized clinical trials confirms its efficacy in producing trial conclusions, highlighting CURE's capacity to supplement traditional clinical trials.

Network properties determine neural network performance.

Machine learning influences numerous aspects of modern society, empowers new technologies, from Alphago to ChatGPT, and increasingly materializes in consumer products such as smartphones and self-driving cars. Despite the vital role and broad applications of artificial neural networks, we lack systematic approaches, such as network science, to understand their underlying mechanism. The difficulty is rooted in many possible model configurations, each with different hyper-parameters and weighted architectures determined by noisy data. We bridge the gap by developing a mathematical framework that maps the neural network's performance to the network characters of the line graph governed by the edge dynamics of stochastic gradient descent differential equations. This framework enables us to derive a neural capacitance metric to universally capture a model's generalization capability on a downstream task and predict model performance using only early training results. The numerical results on 17 pre-trained ImageNet models across five benchmark datasets and one NAS benchmark indicate that our neural capacitance metric is a powerful indicator for model selection based only on early training results and is more efficient than state-of-the-art methods.

Modulatory Effects of Lactobacillus paracasei-Fermented Turmeric on Metabolic Dysregulation and Gut Microbiota in High-Fat Diet-Induced Obesity in Mice.

Turmeric, derived from Curcuma longa, and Lactobacillus paracasei, a lactic acid bacteria, have been studied for their potential antiobesity effects. To date, the antiobesity effects of turmeric fermented with L. paracasei have not been sufficiently investigated. This study was conducted via oral administration of 5% L. paracasei-fermented (FT) and unfermented turmeric (UT) in diet over 16 weeks using high-fat diet (HFD)-induced obese C57BL/6J mice. Results showed that the curcuminoid content of turmeric decreased following fermentation. Furthermore, FT significantly suppressed weight gain and liver and visceral adipose tissue weight and reduced plasma metabolic parameters in both the UT and FT experimental groups. The effects of FT were more noticeable than those of the unfermented form. Moreover, FT downregulated the expression of adipogenesis, lipogenesis, and inflammatory-related protein, but upregulated liver ß-oxidation protein SIRT 1, PPARα, and PGC-1α in perigonadal adipose tissue. Additionally, FT ameliorated insulin resistance by activating insulin receptor pathway protein expressions in visceral adipose tissues. FT also modulated gut microbiota composition, particularly in two beneficial bacteria, Akkermansia muciniphila and Desulfovibrio, as well as two short-chain fatty acid-producing bacteria: Muribaculum intestinale and Deltaproteobacteria. Our findings indicate that the modulation effect of FT may be an important pathway for its antiobesity mechanisms.

Lactobacillus rhamnosus 069 and Lactobacillus brevis 031: Unraveling Strain-Specific Pathways for Modulating Lipid Metabolism and Attenuating High-Fat-Diet-Induced Obesity in Mice.

Obesity is a global health crisis, marked by excessive fat in tissues that function as immune organs, linked to microbiota dysregulation and adipose inflammation. Investigating the effects of Lactobacillus rhamnosus SG069 (LR069) and Lactobacillus brevis SG031 (LB031) on obesity and lipid metabolism, this research highlights adipose tissue's critical immune-metabolic role and the probiotics' potential against diet-induced obesity. Mice fed a high-fat diet were treated with either LR069 or LB031 for 12 weeks. Administration of LB031 boosted lipid metabolism, indicated by higher AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, and increased the M2/M1 macrophage ratio, indicating LB031's anti-inflammatory effect. Meanwhile, LR069 administration not only led to significant weight loss by enhancing lipolysis which evidenced by increased phosphorylation of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) but also elevated Akkermansia and fecal acetic acid levels, showing the gut microbiota's pivotal role in its antiobesity effects. LR069 and LB031 exhibit distinct effects on lipid metabolism and obesity, underscoring their potential for precise interventions. This research elucidates the unique impacts of these strains on metabolic health and highlights the intricate relationship between gut microbiota and obesity, advancing our knowledge of probiotics' therapeutic potential.

Structural Variances in Curcumin Degradants: Impact on Obesity in Mice.

Some thermal degradants of curcuminoids have demonstrated moderate health benefits in previous studies. Feruloyl acetone (FER), recently identified as a thermal degradant of curcumin, has been previously associated with anticancer and antioxidative effects, yet its other capabilities remain unexplored. Moreover, earlier reports suggest that methoxy groups on the aromatic ring may influence the functionality of the curcuminoids. To address these gaps, an animal study was conducted to investigate the antiobesity effects of both FER and its demethoxy counterpart (DFER) on mice subjected to a high-fat diet. The results demonstrated the significant prevention of weight gain and enlargement of the liver and various adipose tissues by both samples. Furthermore, these supplements exhibited a lipid regulatory effect in the liver through the adiponectin/AMPK/SIRT1 pathway, promoted thermogenesis via AMPK/PGC-1α activation, and positively influenced gut-microbial-produced short-chain fatty acid (SCFA) levels. Notably, DFER demonstrated superior overall efficacy in combating obesity, while FER displayed a significant effect in modulating inflammatory responses. It is considered that SCFA may be responsible for the distinct effects of FER and DFER in the animal study. Future studies are anticipated to delve into the efficacy of curcuminoid degradants, encompassing toxicity and pharmacokinetic evaluations.

Study on Anti-Inflammatory Effects of and Muscle Recovery Associated with Transdermal Delivery of Chaenomeles speciosa Extracts Using Supersonic Atomizer on Rat Model.

Repetitive motion or exercise is associated with oxidative stress and muscle inflammation, which can lead to declining grip strength and muscle damage. Oleanolic acid and ursolic acid have anti-inflammatory and antioxidant properties and can be extracted from Chaenomeles speciosa through ultrasonic sonication. We investigated the association between grip strength declines and muscle damage induced by lambda carrageenan (LC) injection and exercise exposure in rats. We also assessed the reparative effects of transdermal pretreatment and post-treatment with C. speciosa extracts (CSEs) by using a supersonic atomizer. The half-maximal inhibitory concentration (IC50) of CSEs for cells was 10.5 mg/mL. CSEs significantly reduced the generation of reactive oxygen species and inflammatory factors (interleukin [IL]-6 and IL-1ß) in in vitro cell tests. Rats subjected to LC injection and 6 weeks of exercise exhibited significantly increased inflammatory cytokine levels (IL-1ß, TNF-α, and IL-6). Hematoxylin and eosin staining revealed inflammatory cell infiltration and evident muscle damage in the gastrocnemius muscle, which exhibited splitting and the appearance of the endomysium and perimysium. The treated rats' grip strength significantly declined. Following treatment with CSEs, the damaged muscles exhibited decreased IL-1ß, TNF-α, and IL-6 levels and normal morphologies. Moreover, grip strength significantly recovered. Pretreatment with CSEs yielded an immediate and significant increase in grip strength, with an increase of 180% and 165% occurring in the rats exposed to LC injection and exercise within the initial 12 h period, respectively, compared with the control group. Pretreatment with CSEs delivered transdermally using a supersonic atomizer may have applications in sports medicine and training or competitions.

Evaluating the link between immune characteristics and attention deficit hyperactivity disorder through a bi-directional Mendelian randomization study.

Context: Despite the recognition of attention deficit hyperactivity disorder (ADHD) as a multifaceted neurodevelopmental disorder, its core causes are still ambiguous. The objective of this study was to explore if the traits of circulating immune cells contribute causally to susceptibility to ADHD. Methods: By employing a unified GWAS summary data covering 731 immune traits from the GWAS Catalog (accession numbers from GCST0001391 to GCST0002121), our analysis focused on the flow cytometry of lymphocyte clusters, encompassing 3,757 Sardinians, to identify genetically expected immune cells. Furthermore, we obtained summarized GWAS statistics from the Psychiatric Genomics Consortium to evaluate the genetic forecasting of ADHD. The studies employed ADHD2019 (20,183 cases and 35,191 controls from the 2019 GWAS ADHD dataset) and ADHD2022 (38,691 cases and 275,986 controls from the 2022 GWAS ADHD dataset). Through the examination of genome-wide association signals, we identified shared genetic variances between circulating immune cells and ADHD, employing the comprehensive ADHD2022 dataset. We primarily utilized inverse variance weighted (IVW) and weighted median methods in our Mendelian randomization research and sensitivity assessments to evaluate diversity and pleiotropy. Results: After adjusting for false discovery rate (FDR), three distinct immunophenotypes were identified as associated with the risk of ADHD: CD33 in Im MDSC (OR=1.03, CI: 1.01~1.04, P=3.04×10-5, PFDR =0.015), CD8br NKT %T cell (OR=1.08, 95%CI: 1.04~1.12, P=9.33×10-5, PFDR =0.023), and CD8br NKT %lymphocyte (OR=1.08, 95%CI: 1.03~1.12, P=3.59×10-4, PFDR =0.066). Furthermore, ADHD showed no statistical effects on immunophenotypes. It's worth noting that 20 phenotypes exist where ADHD's appearance could diminish 85% of immune cells, including FSC-A in myeloid DC (ß= -0.278, 95% CI: 0.616~0.931, P=0.008), CD3 in CD45RA- CD4+ (ß= -0.233, 95% CI: 0.654~0.960, P=0.017), CD62L- monocyte AC (ß=0.227, 95% CI: 0.038~1.518, P=0.019), CD33 in CD33br HLA DR+ CD14dim (ß= -0.331, 95% CI: 0.543~0.950, P=0.020), and CD25 in CD39+ resting Treg (ß=0.226, 95% CI: 1.522, P=0.022), and FSC-A in monocytes (ß= -0.255, 95% CI: 0.621~0.967, P=0.234), among others. Conclusion: Studies indicate that the immune system's response influences the emergence of ADHD. The findings greatly improve our understanding of the interplay between immune responses and ADHD risk, aiding in the development of treatment strategies from an immunological perspective.

Clinicopathological features and cancer transcriptomic profiling of poorly cohesive gastric carcinoma subtypes.

Gastric poorly cohesive carcinoma (PCC) manifests with a diffuse pattern and diverse tumor cell morphologies, often indicating a more unfavorable prognosis. Recent consensus has reclassified PCC based on the proportion of signet-ring cells (SRCs) in tumors for research purposes. The two most distinct subtypes, poorly cohesive carcinoma not otherwise specified (PCC-NOS) and signet-ring cell carcinoma (SRCC), are characterized by less than 10% and more than 90% SRCs, respectively. However, research comparing the clinicopathological and transcriptomic differences between these subtypes remains limited. In this study, we conducted a comparative analysis of clinicopathological features in 55 advanced-stage PCCs, consisting of 43 PCC-NOS and 12 SRCC cases. Subsequently, 12 PCC-NOS and 5 SRCC cases were randomly selected for initial cancer-related gene expression profiling and pathway enrichment analysis using the GeoMx digital spatial profiler, followed by validation in a separate validation group comprising 16 PCC-NOS and 6 SRCC cases. These transcriptomic findings were then correlated with tumor morphology and clinicopathological data. PCC-NOS cases exhibited larger tumor size, a higher prevalence of pathological N3 disease, and a worse 1-year progression-free survival rate compared to SRCC cases. Clustering of PCC-NOS and SRCC was successfully achieved using the GeoMx Cancer Transcriptome Atlas. Among all studied genes, only MMP7 showed differential expression, with its overexpression significantly associated with the PCC-NOS subtype, increased perineural invasion, and earlier disease progression. Pathway analysis revealed significantly enriched pathways in PCC-NOS related to vesicle-mediated transport, adaptive immune systems, oncogenic signaling, and extracellular matrix organization, while SRCC displayed significant enrichment in pathways associated with respiratory electron transport and the cell cycle. In conclusion, this study compares and correlates clinicopathological features and transcriptomic data between PCC-NOS and SRCC at advanced stages, employing the latest consensus classification and a novel platform for analysis.

Risk of Keratitis and Keratopathy in Hidradenitis Suppurativa Patients: A Global Federated Health Network Analysis.

BACKGROUND/AIM: Hidradenitis suppurativa (HS) is linked to immune dysregulation and systemic inflammation. While previous studies indicate a higher prevalence of ocular manifestations in HS, the specific risk of keratopathy and keratitis remains unclear. The primary aim of this study was to assess the risk of keratitis and keratopathy in individuals with HS. PATIENTS AND METHODS: In this retrospective cohort study conducted with data from the TriNetX database, 53,716 patients with HS were matched to an equivalent number of non-HS controls using propensity score matching. The study covered the period from January 1st, 2005, to December 31st, 2017. Hazard ratios and their respective 95% confidence intervals (CIs), were computed to evaluate the occurrences of keratitis and keratopathy over a 5-year duration in patients with HS, compared to non-HS controls. RESULTS: HS was associated with a 1.52 times higher risk of keratitis over a 5-year period (95%CI=1.24-1.86) and a 1.47 times higher risk of keratopathy (95%CI=1.18-1.84). These risks remained consistent in sensitivity analyses. The elevated risk of keratitis was observed across both sexes. However, the risk of keratopathy was significantly higher in women with HS (HR=1.61, 95%CI=1.24-2.10) and individuals aged 18-64 years (HR=1.32, 95%CI=1.04-1.68). CONCLUSION: HS was linked to an elevated risk of both keratitis and keratopathy over a 5-year period. Ophthalmologic manifestations are recommended to be considered in HS standard care.

Additive Blending Effects on PEDOT:PSS Composite Films for Wearable Organic Electrochemical Transistors.

Organic electrochemical transistors (OECTs) employing conductive polymers (CPs) have gained remarkable prominence and have undergone extensive advancements in wearable and implantable bioelectronic applications in recent years. Among the diverse arrays of CPs, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is a common choice for the active-layer channel in p-type OECTs, showing a remarkably high transconductance for the high amplification of signals in biosensing applications. This investigation focuses on the novel engineering of PEDOT:PSS composite materials by seamlessly integrating several additives, namely, dimethyl sulfoxide (DMSO), (3-glycidyloxypropyl)trimethoxysilane (GOPS), and a nonionic fluorosurfactant (NIFS), to fine-tune their electrical conductivity, self-healing capability, and stretchability. To elucidate the intricate influences of the DMSO, GOPS, and NIFS additives on the formation of PEDOT:PSS composite films, theoretical calculations were performed, encompassing the solubility parameters and surface energies of the constituent components of the NIFS, PEDOT, PSS, and PSS-GOPS polymers. Furthermore, we conducted a comprehensive array of material analyses, which reveal the intricacies of the phase separation phenomenon and its interaction with the materials' characteristics. Our research identified the optimal composition for the PEDOT:PSS composite films, characterized by outstanding self-healing and stretchable capabilities. This composition has proven to be highly effective for constructing an active-layer channel in the form of OECT-based biosensors fabricated onto polydimethylsiloxane substrates for detecting dopamine. Overall, these findings represent significant progress in the application of PEDOT:PSS composite films in wearable bioelectronics and pave the way for the development of state-of-the-art biosensing technologies.

The effect of a bone-preserving board game program on the knowledge, attitudes and preventive behaviors of osteoporosis in older adults.

Osteoporosis predisposes to fractures, which affect the quality of life and can be life-threatening. However, the knowledge, attitudes and preventive behaviors of osteoporosis in older adults are insufficient. The aim of this paper was to develop and test the effect of a bone-preserving board game program among older adults. A convenience sample of 85 older adults recruited from two community activity centers in southern Taiwan were assigned to either an experimental group or a control group. The experimental group played a bone-preserving board game for 4 weeks, and the control group participated in routine community center activities. The generalized estimating equation showed significantly larger improvements in knowledge, attitudes, and preventive behaviors in the experimental group than in the control group. Board games designed for older adults can support public health education and help prevent osteoporosis. Our results provide a reference for educators, clinical practitioners and researchers.

Deep-learning model to improve histological grading and predict upstaging of atypical ductal hyperplasia / ductal carcinoma in situ on breast biopsy.

AIMS: Risk stratification of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS), diagnosed using breast biopsy, has great clinical significance. Clinical trials are currently exploring the possibility of active surveillance for low-risk lesions, whereas axillary lymph node staging may be considered during surgical planning for high-risk lesions. We aimed to develop a machine-learning algorithm based on whole-slide images of breast biopsy specimens and clinical information to predict the risk of upstaging to invasive breast cancer after wide excision. METHODS AND RESULTS: Patients diagnosed with ADH/DCIS on breast biopsy were included in this study, comprising 592 (740 slides) and 141 (198 slides) patients in the development and independent testing cohorts, respectively. Histological grading of the lesions was independently evaluated by two pathologists. Clinical information, including biopsy method, lesion size, and Breast Imaging Reporting and Data System (BI-RADS) classification of ultrasound and mammograms, were collected. Deep DCIS consisted of three deep neural networks to evaluate nuclear grade, necrosis, and stromal reactivity. Deep DCIS output comprised five parameters: total patches, lesion extent, Deep Grade, Deep Necrosis, and Deep Stroma. Deep DCIS highly correlated with the pathologists' evaluations of both slide- and patient-level labels. All five parameters of Deep DCIS were significantly associated with upstaging to invasive carcinoma in subsequent wide excisional specimens. Using multivariate logistic regression, Deep DCIS predicted upstaging to invasive carcinoma with an area under the curve (AUC) of 0.81, outperforming pathologists' evaluation (AUC, 0.71 and 0.69). After including clinical and hormone receptor status information, performance further improved (AUC, 0.87). This combined model retained its predictive power in two subgroup analyses: the first subgroup included unequivocal DCIS (excluding cases of ADH and DCIS suspicious for microinvasion) (AUC, 0.83), while the second excluded cases of high-grade DCIS (AUC, 0.81). The model was validated in an independent testing cohort (AUC, 0.81). CONCLUSION: This study demonstrated that deep-learning models can refine histological evaluation of ADH and DCIS on breast biopsies, which may help guide future treatment planning.

Purple Napiergrass (Pennisetum purpureum Schumach) Hot Water Extracts Ameliorate High-Fat Diet-Induced Obesity and Metabolic Disorders in Mice.

Purple Pennisetum (Pennisetum purpureum Schumach), a hybrid between Taihucao No. 2 and the local wild species of purple Pennisetum, has dark red stems and leaves due to its anthocyanin content. This study explores the potential of purple napiergrass extracts (PNE) in alleviating obesity and metabolic disorders induced by a high-fat diet in mice, where 50% of the caloric content is derived from fat. Mice were orally administered low-dose or high-dose PNE alongside a high-fat diet. Experimental findings indicate that PNE attenuated weight gain, reduced liver, and adipose tissue weight, and lowered blood cholesterol, triglyceride, low-density lipoprotein, and blood sugar levels. Stained sections showed that PNE inhibited lipid accumulation and fat hypertrophy in the liver. Immunoblotting analysis suggested that PNE improved the inflammatory response associated with obesity, dyslipidemia, and hyperglycemia induced by a high-fat diet. Furthermore, PNE potentially functions as a PPAR-γ agonist, increasing the adiponectin (ADIPOQ) concentration and suppressing inflammatory factors, while elevating the anti-inflammatory factor interleukin-10 (IL-10) in the liver. PNE-treated mice showed enhanced activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and AMP-activated protein kinase (AMPK) pathways and increased fatty acid oxidation and liver lipolysis. In conclusion, this study elucidated the mechanisms underlying the anti-inflammatory, PI3K/Akt, and AMPK pathways in a high-fat diet-induced obesity model. These findings highlight the potential of PNE in reducing weight, inhibiting inflammation, and improving blood sugar and lipid levels, showing the potential for addressing obesity-related metabolic disorders in humans.