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Abstract Objective Dementia is a significant medical and social issue in most developed countries. Practical tools for predicting the progression of degenerative dementia are highly valuable. Machine learning (ML) methods facilitate the construction of effective models using real-world data, which may include missing values and various integrated datasets. Method This retrospective study analyzed data from 679 patients diagnosed with degenerative dementia at Fu Jen Catholic University Hospital, who were evaluated by neurologists, psychologists and followed for over two years. Predictive variables were categorized into demographic (D), clinical dementia rating (CDR), mini-mental state examination (MMSE), and laboratory data value (LV) groups. These categories were further integrated into three subgroups (D-CDR, D-CDR-MMSE, and D-CDR-MMSE-LV). We utilized the extreme gradient boosting (XGB) model to rank the importance of variables and identify the most effective feature combination via a step-wise approach. Result The D-CDR-MMSE-LV model combination showed robust performance with an excellent area under the receiver operating characteristic curve (AUC) and the highest sensitivity value (84.66). Employing both demographic and neuropsychiatric variables, our prediction model achieved an AUC of 83.74. By incorporating additional clinical information from laboratory data and applying our proposed feature selection strategy, we constructed a model based on eight variables that achieved an AUC of 85.12 using the XGB technique. Conclusion We established a machine-learning model to monitor the progression of dementia using a limited, real-world clinical dataset. The XGB technique identified eight critical variables across our integrated datasets, potentially providing clinicians with valuable guidance.

Abstract The renal lymphatic system is critical for maintaining kidney homeostasis and regulating the immune response inside the kidney. In various kidney pathological situations, the renal lymphatic network experiences lymphangiogenesis, which is defined as the creation of new lymphatic vessels. Kidney lymphangiogenesis controls immunological response inside the kidney by controlling lymphatic flow, immune cell trafficking, and immune cell regulation. Ongoing study reveals lymphangiogenesis’s different architecture and functions in numerous tissues and organs. New research suggests that lymphangiogenesis in kidney disorders may regulate the renal immune response in various ways. The flexibility of lymphatic endothelial cells (LECs) improves the kidney’s immunological regulatory function of lymphangiogenesis. Furthermore, current research has shown disparate findings regarding its impact on distinct renal diseases, resulting in contradictory outcomes even within the same kidney condition. The fundamental causes of the various effects of lymphangiogenesis on renal disorders remain unknown. In this thorough review, we explore the dual impacts of renal lymphangiogenesis on several kidney pathologies, with a particular emphasis on existing empirical data and new developments in understanding its immunological regulatory function in kidney disease. An improved understanding of the immunological regulatory function of lymphangiogenesis in kidney diseases might help design novel medicines targeting lymphatics to treat kidney pathologies.

Abstract Over the past few decades, the expanded applications of in-vivo confocal microscopy (IVCM) have greatly enhanced the knowledge of a variety of conjunctival diseases. IVCM allows non-invasively detailed observation of tarsal, palpebral and bulbar conjunctiva, from the superficial to the substantia propria at the cellular level. IVCM has been shown as a powerful tool for the assessment of morphological changes in both physiological and pathological conditions. High-resolution images of different cellular phenotypes, together with quantifiable results, open new insights into understanding the mechanisms of conjunctival diseases, as well as provide valuable and longitudinal information for the diagnosis and therapeutic evaluation. This review aims to provide an overview of the current knowledge on the applications of IVCM on conjunctival disorders, including aging changes, dry eye-related morphological changes, glaucoma and glaucoma surgery-related morphological changes, conjunctival neoplasm, pterygium, allergic conjunctivitis, trachomatous scarring, and the conjunctiva-associated lymphoid tissue (CALT) changes. In this review, we highlight the key findings of previous studies and discusses the current limitations and challenges of IVCM in assessing the structural characteristics of the conjunctiva. Furthermore, we consider possible future directions for unlocking the full potential of IVCM applications. The insights presented here will contribute to a more comprehensive understanding of the applications of IVCM in conjunctival diseases.

Hyperuricemia (HUA), defined by elevated serum uric acid levels, is well-established in its association with systemic conditions like gout and cardiovascular diseases. Recently, however, emerging research has revealed a potential connection between HUA and ocular disorders, particularly epiretinal pathologies. This review investigates the pathophysiological mechanisms linking HUA to epiretinal conditions, including epiretinal membrane formation, macular edema, and retinal vascular diseases. By thoroughly analyzing current literature, this review seeks to deepen the understanding of the relationship between HUA and epiretinal disorders, with the aim of informing new therapeutic strategies and enhancing patient outcomes.

Abstract A new population of peripheral helper T (Tph) cells has been identified and contributed to various autoimmune diseases. Tph cells can secrete interleukin-21 (IL-21), interferon (IFN) and C-X-C motif chemokine ligand 13 (CXCL13) to moderate renal disease. Moreover, Tph cells can congregate in huge numbers and immerse within inflamed tissue. Compared to Tfh cells, Tph cells express high programmed cell death protein 1 (PD-1), major histocompatibility complex II (MHC-II), C-C chemokine receptor 2 (CCR2) and C-C chemokine receptor 5 (CCR5) but often lack expression of the chemokine receptor C-X-C chemokine receptor 5 (CXCR5). They display features distinct from other T cells, which are uniquely poised to promote responses and antibody production of B cells within pathologically inflamed non-lymphoid tissues and a key feature of Tph cells. In this review, we summarize recent findings on the role of Tph cells in chronic kidney disease, acute kidney injury, kidney transplantation and various renal diseases.

Abstract Aims Sex differences in long‐term post‐discharge clinical outcomes in Asian patients hospitalized for acute decompensated heart failure (HF) persist despite the world‐wide implementation of guideline‐directed medical therapy for decades. The present study aims to elucidate the puzzling dilemma and to depict the directions of solution. Methods and results Between 2011 and 2020, a total of 12 428 patients (6518 men and 5910 women, mean age 73.50 ± 14.85) hospitalized for acute decompensated HF were retrospectively enrolled from a university HF cohort. Compared with men, women hospitalized for acute decompensated HF were older in age (76.40 ± 13.43 vs. 71.20 ± 15.67 years old, P 50%) than men (P 50%) and HF with mildly reduced EF (40%–50%), but not in HF with reduced EF (

Abstract Background Fibroblast growth factor 19 (FGF19) is an enterohepatic hormone the synthesis of which is stimulated by bile acid activation of the nuclear farnesoid X receptor (FXR) in ileal enterocytes. Increased production of FGF19 downregulates hepatocyte bile acid synthesis and gluconeogenesis, while concurrently upregulating hepatocyte glycogenesis and gallbladder (GB) filling. The physiologic impact of this regulatory cycle is illustrated in cholecystectomized humans, in whom the disturbed meal‐related flux of GB bile decreases serum FGF19 concentrations. Objective Determine if serum FGF19 concentrations are lower in dogs with clinical GB mucoceles (GBMs) than in control dogs. Animals Seven dogs with GBM diagnosed using abdominal ultrasonography, biochemical markers, and GB histopathology. Forty‐two control dogs without gastrointestinal or hepatobiliary disorders also were evaluated. Health status of controls was assessed by physical examination and diagnostic hematologic and biochemical test results. Methods Prospective cross‐sectional study to compare fasting plasma or serum FGF19 concentrations between groups. Concentrations of FGF19 were quantified by a commercially available FGF19 ELISA. Results Concentrations of FGF19 were significantly lower in dogs with clinical GBM (median, 14.0 pg/mL; range, 12.8‐67.2) than in control dogs (median, 145.3 pg/mL; range, 36.5‐285.1). Conclusions and Clinical Importance In dogs, GBM is associated with significantly decreased serum FGF19 concentrations. We speculate that this finding reflects compromised GB contraction and decreased enterohepatic circulation of bile flow. Subnormal FGF19 concentrations may influence bile acid synthesis and hepatic metabolism.

Fibrinogen–fibrin degradation products (DR-70) are derived from tumor cells or metastases. Our previous study reported the diagnostic values in dogs with tumors, but no research has yet to be conducted to establish DR-70 as a prognostic marker. Herein, we investigated changes in DR-70 concentrations and disease courses in dogs with tumors. Overall survival time (OST) analysis was performed in 195 dogs with tumors, stratified with a recommended cut-off (1.514 µg/mL). Continual DR-70 measurements were performed during the medical interventions of 27 dogs with neoplasms. Clinical conditions and medical records were retrospectively reviewed. According to a cut-off value, dogs with plasma DR-70 concentrations above 1.514 µg/mL had shorter survival rates than those with concentrations below this threshold. In cases with complete or partial remission in response to treatment, the DR-70 concentration was decreased compared with that at the first visit, whereas it was increased in patients with disease progression. Our study suggested that changes in DR-70 concentration can be used as a prognostic biomarker for canine neoplasms. Furthermore, increased plasma DR-70 levels might be associated with shorter survival, and DR-70 concentrations may reflect responses to medical intervention.

Diagnostic markers for myasthenia gravis (MG) are limited; thus, innovative approaches are required for supportive diagnosis and personalized care. Gut microbes are associated with MG pathogenesis; however, few studies have adopted machine learning (ML) to identify the associations among MG, gut microbiota, and metabolites. In this study, we developed an explainable ML model to predict biomarkers for MG diagnosis. We enrolled 19 MG patients and 10 non-MG individuals. Stool samples were collected and microbiome assessment was performed using 16S rRNA sequencing. Untargeted metabolic profiling was conducted to identify fecal amplicon significant variants (ASVs) and metabolites. We developed an explainable ML model in which the top ASVs and metabolites are combined to identify the best predictive performance. This model uses the SHapley Additive exPlanations method to generate both global and personalized explanations. Fecal microbe–metabolite composition differed significantly between groups. The key bacterial families were Lachnospiraceae and Ruminococcaceae, and the top three features were Lachnospiraceae, inosine, and methylhistidine. An ML model trained with the top 1 % ASVs and top 15 % metabolites combined outperformed all other models. Personalized explanations revealed different patterns of microbe–metabolite contributions in patients with MG. The integration of the microbiota-metabolite features and the development of an explainable ML framework can accurately identify MG and provide personalized explanations, revealing the associations between gut microbiota, metabolites, and MG. An online calculator employing this algorithm was developed that provides a streamlined interface for MG diagnosis screening and conducting personalized evaluations.

Background: Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH). Methods: PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-μg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1–3 months. Results: Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-μg mRNA-1273, 467 (32.8%) 50-μg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count 200 copies/mL (aOR, 0.27; 95% CI, 0.09–0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68–5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10–0.41; reference, 100-μg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine). Conclusions: PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-μg mRNA-1273 could generate a higher antibody response than with 50-μg mRNA-1273 and BNT162b2 vaccine.

Abstract Evolution of SARS-CoV-2 variants emphasizes the need for multivalent vaccines capable of simultaneously targeting multiple strains. SCTV01E is a tetravalent COVID-19 vaccine derived from the spike protein of SARS-CoV-2 variants Alpha, Beta, Delta, and Omicron BA.1. In this double-blinded placebo-controlled pivotal efficacy trial (NCT05308576), the primary endpoint was vaccine efficacy (VE) against COVID-19 seven days post-vaccination in individuals without recent infection. Other endpoints included evaluating safety, immunogenicity, and the VE against all SARS-CoV-2 infections in individuals meeting the study criteria. Between December 26, 2022, and January 15, 2023, 9,223 individuals were randomized at a 1:1 ratio to receive SCTV01E or a placebo. SCTV01E showed a VE of 69.4% (95% CI: 50.6, 81.0) 7 days post-vaccination, with 75 cases in the placebo group and 23 in the SCTV01E group for the primary endpoint. VEs were 79.7% (95% CI: 51.0, 91.6) and 82.4% (95% CI: 57.9, 92.6), respectively, for preventing symptomatic infection and all SARS-CoV-2 infections 14 days post-vaccination. SCTV01E elicited a 25.0-fold higher neutralizing antibody response against Omicron BA.5 28 days post-vaccination compared to placebo. Reactogenicity was generally mild and transient, with no reported vaccine-related SAE, adverse events of special interest (AESI), or deaths. The trial aligned with the shift from dominant variants BA.5 and BF.7 to XBB, suggesting SCTV01E as a potential vaccine alternative effective against present and future variants.

Abstract Diabetic corneal neuropathy (DCN) is a common diabetic ocular complication with limited treatment options. In this study, we investigated the effects of topical and oral fenofibrate, a peroxisome proliferator-activated receptor-α agonist, on the amelioration of DCN using diabetic mice (n = 120). Ocular surface assessments, corneal nerve and cell imaging analysis, tear proteomics and its associated biological pathways, immuno-histochemistry and western blot on PPARα expression, were studied before and 12 weeks after treatment. At 12 weeks, PPARα expression markedly restored after topical and oral fenofibrate. Topical fenofibrate significantly improved corneal nerve fibre density (CNFD) and tortuosity coefficient. Likewise, oral fenofibrate significantly improved CNFD. Both topical and oral forms significantly improved corneal sensitivity. Additionally, topical and oral fenofibrate significantly alleviated diabetic keratopathy, with fenofibrate eye drops demonstrating earlier therapeutic effects. Both topical and oral fenofibrate significantly increased corneal β-III tubulin expression. Topical fenofibrate reduced neuroinflammation by significantly increasing the levels of nerve growth factor and substance P. It also significantly increased β-III-tubulin and reduced CDC42 mRNA expression in trigeminal ganglions. Proteomic analysis showed that neurotrophin signalling and anti-inflammation reactions were significantly up-regulated after fenofibrate treatment, whether applied topically or orally. This study concluded that both topical and oral fenofibrate ameliorate DCN, while topical fenofibrate significantly reduces neuroinflammation.

Abstract Does social media alleviate or exacerbate loneliness? Past research has shown mixed results regarding the relationship between social media usage and loneliness among younger and older adults. Unlike younger individuals, older adults may decrease their loneliness through social media interactions. Additionally, previous research has indicated that the link between social media use and loneliness can vary depending on one’s shy tendency. Therefore, this study aims to explore the relationship between individuals’ social media use and loneliness while considering age and shyness tendency as moderating variables. The study employed a questionnaire survey conducted through convenience sampling, resulting in 234 valid responses from participants in Northern Taiwan. Among them, 113 were college students (aged 18 to 25, average age 19.40), and 121 were older adults (aged 50 to 82, average age 60.81). Using hierarchical regression analysis, results indicated that (1) age moderates the relationship between personal social media use and loneliness. Minimal differences were observed among younger individuals, but among older adults, increased social media usage time was associated with a significant reduction in loneliness. (2) Shyness tendency moderate the relationship between personal social media use and loneliness. Individuals with higher shyness tendency experience an increase in loneliness as their social media usage time lengthens.

Rheumatoid arthritis (RA) is a well-known autoimmune disorder associated with joint pain, swelling, cartilage and bone degradation, as well as deformity. In cellular and animal model investigations, extracts from Antrodia cinnamomea, a traditional medicinal fungus used in Taiwan, demonstrate anti-inflammatory properties. The 25(S) ergostane stereo-isomer of antcin K, known as 25S-antcin K, was previously isolated from A. cinnamomea and was found to exhibit a more potent effect than antcin K. In the current study, we examined the anti-RA effects of 25S-antcin K. 25S-antcin K abolishes IL-1β-induced promotion of TNF-α, CCL2, and VEGF arthritic factors production by inhibiting AMPK, Akt, and p38 pathways and enhancing miR-374b expression. Importantly, administration of 25S-antcin K also antagonizes collagen-induced arthritis-induced RA symptoms, such as inflammation, cartilage degradation, and bone erosion in vivo. These results provide a novel avenue, suggesting that 25S-antcin K is a potential candidate for developing RA therapy agents.

Ferroptosis is a recently identified form of cell death characterized by lipid peroxidation and elevated iron levels. It is closely associated with hematologic malignancies, including leukemia, multiple myeloma (MM), and myelodysplastic syndromes (MDS). Research indicates that ferroptosis could represent a novel therapeutic target for these hematologic malignancies. Furthermore, traditional Chinese medicine (TCM) has been shown to modulate hematologic malignancies through the ferroptosis pathway. This paper aims to elucidate the mechanisms underlying ferroptosis and summarize the current research advancements regarding ferroptosis in hematologic malignancies, as well as the role of traditional Chinese medicine in the prevention and treatment of ferroptosis, with the goal of enhancing treatment efficacy.

Cemented soft rock is prone to softening when exposed to water, and its mechanical properties deteriorate rapidly, which is an important reason to induce the instability and failure of engineering soft rock mass. The softening mechanism of soft rock is essentially the deterioration of microstructure caused by the change of water-rock interface. Considering the general characteristics of soft rock, the microstructural evolution characteristics and element loss over varying immersion time are then compared and analyzed. The Interfacial Cemented Bonding (ICB) structure is proposed to describe the evolution of water-rock interface. Based on the diffusion theory, the theoretical equation describing the evolution of water-rock interface is derived and compared with the experimental results. The meso-softening damage factor (MSDF) of soft rock is proposed and introduced into a numerical method to establish a strength degradation discrete element method (SD-DEM) model. The results show that the softening process of soft rock is accompanied by the shedding and suspension of particles and the dissolution of soluble substances. Besides, the softening of soft rock has obvious nonlinear dynamic characteristics. The fitting degree between the theoretical values and the experimental results is relatively high, which verifies the reliability and rationality of the dissolution-diffusion interfacial softening model. The numerical results are in good agreement with the experimental ones. This study provides a new idea for understanding the mechanism of water-induced softening characteristics and strength degradation of soft rock.

Objectives: To determine the associated pathogen during the 2023 conjunctivitis outbreak in Vietnam Methods: RNA-sequencing was used to identify pathogens before and during the outbreak. Results: 24 patients with infectious conjunctivitis between March and October 2023 from Hai Yen Vision Institute in Vietnam were swabbed. Coxsackievirus A24v was the most common pathogen identified. Phylogenetic analysis of these strains demonstrates similarities to the Coxsackievirus identified in the 2022 India outbreak. Human adenovirus D was also circulating. Ocular findings of tearing, purulence, and itching were common in this outbreak. Conclusions: Multiple viruses can co-circulate during conjunctivitis outbreaks. Hemorrhagic conjunctivitis, commonly associated with coxsackievirus conjunctivitis, was not a common clinical sign in this outbreak. Repeat genetic surveillance, with the notable inclusion of RNA virus detection strategies, is important for outbreak detection.

Abstract Background Luffa (Luffa spp.) is an economically important crop of the Cucurbitaceae family, commonly known as sponge gourd or vegetable gourd. It is an annual cross-pollinated crop primarily found in the subtropical and tropical regions of Asia, Australia, Africa, and the Americas. Luffa serves not only as a vegetable but also exhibits medicinal properties, including anti-inflammatory, antidiabetic, and anticancer effects. Moreover, the fiber derived from luffa finds extensive applications in various fields such as biotechnology and construction. However, luffa Fusarium wilt poses a severe threat to its production, and existing control methods have proven ineffective in terms of cost-effectiveness and environmental considerations. Therefore, there is an urgent need to develop luffa varieties resistant to Fusarium wilt. Single-plant GWAS (sp-GWAS) has been demonstrated as a promising tool for the rapid and efficient identification of quantitative trait loci (QTLs) associated with target traits, as well as closely linked molecular markers. Results In this study, a collection of 97 individuals from 73 luffa accessions including two major luffa species underwent single-plant GWAS to investigate luffa Fusarium wilt resistance. Utilizing the double digest restriction site associated DNA (ddRAD) method, a total of 8,919 high-quality single nucleotide polymorphisms (SNPs) were identified. The analysis revealed the potential for Fusarium wilt resistance in accessions from both luffa species. There are 6 QTLs identified from 3 traits, including the area under the disease progress curve (AUDPC), a putative disease-resistant QTL, was identified on the second chromosome of luffa. Within the region of linkage disequilibrium, a candidate gene homologous to LOC111009722, which encodes peroxidase 40 and is associated with disease resistance in Cucumis melo, was identified. Furthermore, to validate the applicability of the marker associated with resistance from sp-GWAS, an additional set of 21 individual luffa plants were tested, exhibiting 93.75% accuracy in detecting susceptible of luffa species L. aegyptiaca Mill. Conclusion In summary, these findings give a hint of genome position that may contribute to luffa wild resistance to Fusarium and can be utilized in the future luffa wilt resistant breeding programs aimed at developing wilt-resistant varieties by using the susceptible-linked SNP marker.

青銀世代對數位遊戲的使用動機具差異性，而數位遊戲的開發或設計往往無法為所有年齡層量身定做，例如長者對於規則太複雜、時間太緊湊的遊戲設計有負面的認知，但年輕人反而追求遊戲的效率。此外，過去探討不同世代數位遊戲設計及功能評估的研究，大多為受試者自陳、觀察和訪談方法蒐集主動意識層面的資料，較少透過語意聯想這類的結果探究。 據此，本研究欲以數位遊戲認知的語意聯想測驗（Word Association Test, WAT）蒐集多元的資料以探討世代間之異同。本研究以便利取樣招募178位不同年齡層的對象，包含年輕人組73位（女性占78%，年齡介於15-27歲）、中高齡者組50位（女性占80%，年齡介於46-64歲）和高齡者組55位（女性占65%，年齡介於65-92歲）。參與者被邀請以紙筆方式進行測驗，並須回答當提到數位遊戲時，他們會想到什麼詞彙，參與者最多可填答12個詞彙。研究結果共測得962個詞彙，年輕人組、中高齡者組以及高齡者組分別測得640、180以及142個詞彙，後以本研究建構之數位遊戲聯想編碼架構歸納資料。三組參與者的聯想詞彙在不同編碼類目中的分布各有異同，包含：在數位遊戲使用的負面動機中，年輕人組較傾向聯想與心理有害相關之內容，中高齡者與高齡者組則較會聯想到與生理有害相關的部分；在正面動機的部分，年輕人組與中高齡者組較傾向聯想到娛樂性，高齡者組則是聯想到有用性；三組樣本皆出現的重複詞彙有：「動腦」、「有趣」、「打發時間」與「沉迷」。本研究期能啟發數位遊戲相關學術與實務工作者，在未來重視不同世代對數位遊戲的認知異同，且積極扭轉各世代對於玩數位遊戲後所產生的負面印象。 Introduction Digital technologies have driven innovation and changes in information dissemination, consumption, entertainment, and social welfare. The ability to use this innovation is often based on age, with younger generations significantly more comfortable than are older generations. This “digital divide” poses a challenge to societies such as Taiwan’s, where the National Development Council estimated that 14% of the population was above the age of 65 years in 2018 and estimated that this number would reach 20% by 2025, making Taiwan a superaged society. In such superaged societies, scholars suggest, digital technologies can be used to promote social welfare and the mental and physical health of older individuals. Digital gaming, which has the potential to bridge the gap between users of different generations, is a helpful tool for promoting the well-being of young and old alike. The perception of digital games among users of different generations may influence their motivation for playing games and their overall attitude to digital gaming. To collect diverse data from various age groups, this study employed the Word Association Test (WAT) to determine participants’ underlying cognition and emotions. Thus, the aim of this study was to investigate differences in cognitive perceptions and approach-avoidance conflict of digital games among users of different generations. The stimulus word “digital games” was used in the WAT to investigate the cognitive perceptions of different age groups regarding digital games. The study began by considering the applications of digital gaming and then reflected on the differences in the perception of digital games between young-adult, middle-aged, and older groups. Subsequently, the intergroup similarities and differences in perceptions of digital gaming were evaluated.. Method Convenience sampling was employed to recruit participants from different generations and living in Taipei, Taiwan. The young-adult participants included college students, graduate students, nearby residents, and high school students from a certain campus. The older-adult participants were recruited from neighborhoods, community centers, and locations near the aforementioned college. After invalid samples (those without age information) were excluded, 178 valid samples remained. To capture inter-age-group differences in cognitive perceptions of digital games, the participants were divided into three groups: the young-adults group, middle-aged and older-adults group, and advanced age group. The age classifications for the two older groups followed the age categories of the Ministry of Labor in Taiwan: 45 years and above and 65 years and above, respectively. The young-adults group comprised 73 participants [22% male, age of 15-27 years, mean (SD) = 20.18 (2.24)], the middle-aged and older-adults group comprised 50 participants [20% male, age of 46-64 years, mean (SD) = 59.40 (4.45)], and the advanced age group comprised 55 participants [35% male, age of 65-92 years, mean (SD) = 70.69 (4.94)]. The primary research method employed in this study was content analysis of associations with digital game vocabulary. The objective was to systematically categorize and describe data in accordance with predetermined coding categories to obtain structured and quantifiable information about content. Through the literature review conducted for this study, three coding themes were identified in cognitive perceptions of digital games: (1) neutral, (2) positive, and (3) negative game perceptions. The study’s WAT was conducted in paper-and-pencil format, and the aim was not to measure how many words the participants could provide within a set time frame. Instead, the participants were encouraged to answer with as many words as possible. The WAT was concluded when the participants indicated they could not think of any more words or when they had provided 12 words. Finally, the participants’ responses were transcribed verbatim, and the number of words provided by each participant and the summarized themes were calculated. Results The distribution of vocabulary in the three participant groups for neutral, positive, and negative game perceptions revealed that the young-adults group and the middle-aged and older-adults group gave the highest number of responses that were coded as positive game perceptions, whereas the advanced age group gave the most responses coded as neutral game perceptions. This indicated that the younger individuals may have had more positive perceptions of digital games than the older individuals did. In the coding theme of neutral game perceptions, the types of words most commonly provided by the young-adults group were those relating to game types; the three most commonly used words were competitive, simulation, and interaction. The types of words most commonly provided by the middle-aged and older-adults group were those relating to game titles, with the three most widely used words being “Mahjong,” “Candy Crush,” and “Su doku”. The types of words most commonly provided by the advanced age group were also those relating to game titles; the three most often recurring words were “Happy Farm,” “Candy Crush,” and playing cards. Interestingly, “Candy Crush” was a common word for both the middle-aged and older-adults group and the advanced age group, suggesting that this digital game is commonly played by middle-aged and older individuals in Taiwan but not by young adults. No other words were shared by the three groups in this coding theme. In the coding theme of positive game perceptions, the types of words most commonly provided by the young-adults group were those relating to entertainment, with the three most commonly used words being stress relief, fun, and happiness. The middle-aged and older-adults group gave similar responses to the young-adults group; their two most frequently used terms were fun and stress relief. The types of words most commonly provided by advanced age group were coded as utility, with the most often used terms being brain exercise, passing time, preventing dementia, and learning. Three terms were common to the three groups: passing time, brain exercise, and fun, indicating that the different age groups had similar positive perceptions of playing digital games. In the coding theme of negative game perceptions, the types of words most commonly provided by the young-adults group were those relating to psychological harm, with the most common term being addiction. The types of words most commonly provided by the middle-aged and older-adults group and the advanced age group were related to physical harm, with the often used term being eye discomfort. Notably, addiction was common to all three groups, suggesting that individuals from all generations perceive digital games as addictive. However, the middle-aged and older-adults group appeared to worry more that digital games were harmful to their eyes than that they were addictive. Conclusion This study examined and coded responses regarding perceptions of digital gaming of individuals in three distinct age groups and discovered specific differences between the groups’ responses.

Abstract Background To describe the diagnostic performance of a deep learning (DL) algorithm in detecting Fuchs endothelial corneal dystrophy (FECD) based on specular microscopy (SM) and to reliably detect widefield peripheral SM images with an endothelial cell density (ECD) > 1000 cells/mm2. Methods Five hundred and forty-seven subjects had SM imaging performed for the central cornea endothelium. One hundred and seventy-three images had FECD, while 602 images had other diagnoses. Using fivefold cross-validation on the dataset containing 775 central SM images combined with ECD, coefficient of variation (CV) and hexagonal endothelial cell ratio (HEX), the first DL model was trained to discriminate FECD from other images and was further tested on an external set of 180 images. In eyes with FECD, a separate DL model was trained with 753 central/paracentral SM images to detect SM with ECD > 1000 cells/mm2 and tested on 557 peripheral SM images. Area under curve (AUC), sensitivity and specificity were evaluated. Results The first model achieved an AUC of 0.96 with 0.91 sensitivity and 0.91 specificity in detecting FECD from other images. With an external validation set, the model achieved an AUC of 0.77, with a sensitivity of 0.69 and specificity of 0.68 in differentiating FECD from other diagnoses. The second model achieved an AUC of 0.88 with 0.79 sensitivity and 0.78 specificity in detecting peripheral SM images with ECD > 1000 cells/mm2. Conclusions Our pilot study developed a DL model that could reliably detect FECD from other SM images and identify widefield SM images with ECD > 1000 cells/mm2 in eyes with FECD. This could be the foundation for future DL models to track progression of eyes with FECD and identify candidates suitable for therapies such as Descemet stripping only.

In this paper, modal properties of the seated human body were identified from measured transmissibilities to the head, chest, lumbar spine L3, pelvis, hips and thighs with single-axis translational vibration; how they were affected by vibration direction and magnitude was quantitatively compared for the first time. To this end, eight subjects were exposed to fore-aft, lateral and vertical single-axis vibrations with three magnitudes at 0.4, 0.8 and 1.2 m/s 2 r.m.s., respectively. Three and five vibration modes were identified with fore-aft vibration and with vertical vibration in the sagittal plane, respectively, while three modes identified with lateral vibration were in the coronal plane. As the vibration magnitude increased from 0.4 to 1.2 m/s 2 r.m.s., the modal frequencies of the modes at 1.2, 2.2, 2.9 and 6.2 Hz, which contained the pitch, lateral movements, fore-aft movements and vertical movements of the upper body, respectively, were reduced to 1.0, 1.8, 2.3 and 5.8 Hz significantly, and the damping ratios of the modes identified at 0.8, 5.2 and 10.9 Hz were changed. High similarity was observed between the modal shapes identified with different vibration magnitudes.

Background As the burden and distribution of calcification within chronic total occlusion (CTO) lesions can be diverse, its effect on CTO recanalization using multiple devices and techniques is debatable. This study investigated the role of calcification in wiring-based intraplaque tracking techniques for CTO recanalization.Methods A modified J-CTO score without counting calcification was used to analyze the procedures of 458 consecutive patients who underwent CTO interventions. Failed guidewire crossing and intraplaque tracking were considered procedural failures. Recanalization time details were analyzed for successful procedures.Results In patients with calcified CTO, the rate of procedural success only significantly declined to be lower than that of noncalcified CTO when the modified J-CTO score was ≥3 (77% vs. 94%, p = 0.008). In 422 patients with successful procedures, the presence of calcification was irrelevant to guidewire crossing time, but was accompanied with longer time from guidewire cross to final angiogram when the modified J-CTO score was 1–2 (53 ± 35 vs. 35 ± 17 [noncalcified] min, p 60 min (OR = 4.8, 95% CI = 2.2–10.2) in successfully recanalized lesions with modified J-CTO score 1–2.Conclusions Using intraplaque guidewire tracking, calcification was unfavorable for very difficult CTO lesions, and caused prolongation of angioplasty time for lesions with moderate complexity. This suggested that the role of calcification in the J-CTO score could be altered when different recanalization techniques were applied for CTO interventions.

ABSTRACTObjective To investigate efficacy and prognostic factors in the treatment of adult newly-diagnosed acute myeloid leukemia (AML) with or without allogeneic hematopoietic stem cell transplantation (Allo-HSCT).Methods We retrospectively analyzed 668 patients with newly-diagnosed AML (non-M3 type) in the Department of Hematology at Shanghai Changhai Hospital from January 2012 to December 2021. Based on different induction chemotherapy regimens, patients were categorized into an IA (idarubicin, IDA + cytarabine, Ara-C) (3 + 7, regimen) group (n = 303) and a DA (daunorubicin, DNR + cytarabine, Ara-C) (3 + 7, regimen) group (n = 365) with or without allo-HSCT. Minimal residual disease (MRD), complete response (CR), overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse effects (AE) were analyzed and compared. Characteristics significantly associated with overall or progression-free survival (OS or PFS) upon univariate analysis were subsequently included in a Cox proportional hazard model.Results This study used data from 668 AML patients. After induction therapy, the CR rate in the IA group was 70.63% and ORR was 79.87%, which were significantly higher than those in the DA group (with a CR rate of 56.99% and an ORR of 70.14%) (P = 0.0002 and P = 0.0035, respectively). There were no significant differences in drug safety between the two chemotherapy regimens used in IA and DA (P > 0.05). The recurrence rate was lower in patients with an MRD

AbstractObjective The association between nutritional status and prognosis of idiopathic pulmonary fibrosis (IPF) remains unclear. This systematic review and meta-analysis aimed to explore the effect of body mass index (BMI) and weight loss on the prognosis of IPF patients.Methods We accumulated studies on IPF, BMI, and weight loss from databases including PubMed, Embase, Web of science, Scopus, Ovid and Cochrane Library up to 4 August 2023. Using Cox proportional hazard regression model for subgroup analysis, hazard ratio (HR) and 95% confidence intervals (CI) for BMI in relation to mortality, acute exacerbation (AE), and hospitalization in IPF patients were calculated, and HR, odds ratio (OR), and 95% CI for weight loss corresponding to IPF patient mortality were assessed. Sensitivity analysis was peformed by eliminating every study one by one, and publication bias was judged by Egger’s test and trim-and-fill method.Results A total of 34 eligible studies involving 18,343 IPF patients were included in the meta-analysis. The pooled results by univariate Cox regression analysis showed that baseline BMI was a predictive factor for IPF mortality (HR = 0.93, 95%CI = [0.91, 0.94]). Furthermore, the results by the multivariable regression model indicated that baseline BMI was an independent risk factor for predicting IPF mortality (HR = 0.94, 95%CI = [0.91, 0.98]). Weight loss was identified as a risk factor for IPF mortality (HR = 2.74, 95% CI = [2.12, 3.54]; OR = 4.51, 95% CI = [1.72, 11.82]) and there was no predictive value of BMI for acute exacerbation (HR = 1.00, 95% CI= [0.93, 1.07]) or hospitalization (HR = 0.95, 95% CI = [0.89, 1.02]).Conclusion Low baseline BMI and weight loss in the course of IPF may indicate a high risk of mortality in patients with IPF, so it is meaningful to monitor and manage the nutritional status of IPF patients, and early intervention should be conducted for low BMI and weight loss.

BackgroundSodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP4i) are important second-line treatments for patients with type 2 diabetes mellitus (T2DM). Patients taking SGLT2i have favorable cardiovascular outcomes via various mechanisms, including autonomic nervous system (ANS) modulation. This study aimed to use neuro-electrocardiography (neuECG) to test the effects of SGLT2i or DPP4i on the ANS.MethodsPatients with T2DM, who did not reach target hemoglobin (Hb)A1C levels despite metformin treatment, were enrolled. SGLT2i or DPP4i were prescribed randomly unless a compelling indication was present. NeuECG and heart rate were recorded for 10 min before and after a 3-month treatment. The patients were treated according to standard practice and the obtained data for skin sympathetic nerve activity (SKNA) and ANS entropy were analyzed offline.ResultsWe enrolled 96 patients, of which 49 received SGLT2i and 47 received DPP4i. The baseline parameters were similar between the groups. No adverse event was seen during the study period. In the burst analysis of SKNA at baseline, all parameters were similar. After the 3-month treatment, the firing frequency was higher in SGLT2i group (0.104 ± 0.045 vs 0.083 ± 0.033 burst/min, p < 0.05), with increased long firing duration (7.34 ± 3.66 vs 5.906 ± 2.921, p < 0.05) in 3-s aSKNA scale; the other parameters did not show any significant change. By symbolic entropy, the most complex patterns (Rank 3) were found to be significantly higher in SGLT2i-treated patients than in DDP4i-treated group (0.084 ± 0.028 vs 0.07 ± 0.024, p = 0.01) and the direction of change in Rank 3, after SGLT2i treatment, was opposite to that observed in the DDP4i group (0.012 ± 0.036 vs. −0.005 ± 0.037, p = 0.024). Our findings demonstrated the favorable autonomic modulation by SGLTi and the detrimental effects of DPP4i on ANS.ConclusionWe demonstrated the autonomic modulation by SGLTi and DPP4i using SKNA in patients with DM, which might provide insights into the favorable outcomes of SGLT2i. Furthermore, we refined the analytical methods of neuECG, which uses SKNA to evaluate autonomic function.

Abstract Acute asthma exacerbation refers to the progressive deterioration of asthma symptoms that is always triggered by virus infection represented by respiratory syncytial virus (RSV). After RSV infection, exaggerated Th2‐mediated pulmonary inflammation is the critical pathological response of asthmatic patients with acute exacerbation. Significantly, airway epithelial cells, being the primary targets of RSV infection, play a crucial role in controlling the pulmonary inflammatory response by releasing airway epithelial cell‐derived exosomes (AEC‐Exos), which potentially influence the development of asthma. However, the specific role of AEC‐Exos in acute asthma exacerbation after RSV infection remains obscure. The purpose of this study was to determine the distinct function of AEC‐Exos in exacerbating acute asthma following RSV infection. Blockade of exosomes by GW reduce the enhanced pulmonary inflammation significantly. Specifically, the enhanced Th2 inflammation was induced by AEC‐Exos thorough transportation of hsa‐miR‐155‐5p–Sirtuin 1 (SIRT1) pathway during acute asthma exacerbation. Targeted inhibition of hsa‐miR‐155‐5p blocks the exaggerated Th2 inflammation effectively in mice with acute asthma exacerbation. In summary, our study showed that during acute asthma exacerbation after RSV infection, AEC‐Exos promote the enhanced Th2 inflammation through transportation of increased hsa‐miR‐155‐5p, which was mediated partly through SIRT1‐mediated pathway. hsa‐miR‐155‐5p is a potential biomarker for early prediction of acute asthma exacerbation.

BackgroundVasculogenic Mimicry (VM) can reduce the efficacy of anti-angiogenesis and promote distant metastasis in hepatocellular carcinoma (HCC). Our previous studies have found that Celastrus orbiculatus extract (COE) can inhibit the VM formation in HCC by reducing EphA2 expression. However the underlying mechanism related to EphA2 in VM formation is unclear.PurposeThis study aimed to confirm that EphA2 is one of the potential targets of COE, and to explore the effect of EphA2 in VM formation in hypoxia context in HCC.MethodsTCM Systems Pharmacology database and proteomics analysis were used to explore the key targets of COE in HCC treatment. CD31-PAS double staining and VE-CAD staining were used to indicate vasculogenic mimicry. The localization of EphA2 and VE-CAD was examined through fluorescent microscopy. CCK8 assay, cell invasion assay, and tube formation assay were used to indicate the formation of VM under hypoxic conditions. The regulatory relationship of EphA2 upstream and downstream molecules were evaluated through COIP and Western Blot. The nude mouse xenograft tumor models were used to observe the VM formation after knocking down or overexpressing EphA2.ResultsEphA2 is identified to the target of COE, and the driving gene of HCC. In HCC surgical specimens, EphA2 expression is closely associated with the VM formation of HCC. COE-regulated EphA2 is involved in hypoxia-induced VM formation in HCC cells in vitro. EphA2 is regulated by HIF directly or indirectly by C-MYC. Overexpression of EphA2 can promote the VM formation of HCC in nude mice, while knocking down EphA2 can inhibit the VM formation.ConclusionEphA2, as a target of COE, plays a crucial regulatory role in the formation of vasculogenic mimicry in HCC, involving upstream HIF/MYC transcriptional promotion and downstream PI3K/FAK/VE-CAD expression regulation.

The cornea is an avascular tissue in the eye that has multiple functions in the eye to maintain clear vision which can significantly impair one’s vision when subjected to damage. Peroxisome proliferator-activated receptors (PPARs), a family of nuclear receptor proteins comprising three different peroxisome proliferator-activated receptor (PPAR) isoforms, namely, PPAR alpha (α), PPAR gamma (γ), and PPAR delta (δ), have emerged as potential therapeutic targets for treating corneal diseases. In this review, we summarised the current literature on the therapeutic effects of PPAR agents on corneal diseases. We discussed the role of PPARs in the modulation of corneal wound healing, suppression of corneal inflammation, neovascularisation, fibrosis, stimulation of corneal nerve regeneration, and amelioration of dry eye by inhibiting oxidative stress within the cornea. We also discussed the underlying mechanisms of these therapeutic effects. Future clinical trials are warranted to further attest to the clinical therapeutic efficacy.

Rice, a critical staple on a global scale, faces escalating challenges in yield preservation due to the rising prevalence of abiotic and biotic stressors, exacerbated by frequent climatic fluctuations in recent years. Moreover, the scorching climate prevalent in the rice-growing regions of South China poses obstacles to the cultivation of good-quality, heavy-grain varieties. Addressing this dilemma requires the development of resilient varieties capable of withstanding multiple stress factors. To achieve this objective, our study employed the broad-spectrum blast-resistant line Digu, the brown planthopper (BPH)-resistant line ASD7, and the heavy-grain backbone restorer lines Fuhui838 (FH838) and Shuhui527 (SH527) as parental materials for hybridization and multiple crossings. The incorporation of molecular markers facilitated the rapid pyramiding of six target genes (Pi5, Pita, Pid2, Pid3, Bph2, and Wxb). Through a comprehensive evaluation encompassing blast resistance, BPH resistance, cold tolerance, grain appearance, and quality, alongside agronomic trait selection, a promising restorer line, Guihui5501 (GH5501), was successfully developed. It demonstrated broad-spectrum resistance to blast, exhibiting a resistance frequency of 77.33% against 75 artificially inoculated isolates, moderate resistance to BPH (3.78 grade), strong cold tolerance during the seedling stage (1.80 grade), and characteristics of heavy grains (1,000-grain weight reaching 35.64 g) with good grain quality. The primary rice quality parameters for GH5501, with the exception of alkali spreading value, either met or exceeded the second-grade national standard for premium edible rice varieties, signifying a significant advancement in the production of good-quality heavy-grain varieties in the southern rice-growing regions. Utilizing GH5501, a hybrid combination named Nayou5501, characterized by high yield, good quality, and resistance to multiple stresses, was bred and received approval as a rice variety in Guangxi in 2021. Furthermore, genomic analysis with gene chips revealed that GH5501 possessed an additional 20 exceptional alleles, such as NRT1.1B for efficient nitrogen utilization, SKC1 for salt tolerance, and STV11 for resistance to rice stripe virus. Consequently, the restorer line GH5501 could serve as a valuable resource for the subsequent breeding of high-yielding, good-quality, and stress-tolerant hybrid rice varieties.

Background: Interstitial lung disease (ILD) treatment is a critical unmet need. Selenium is an essential trace element for human life and an antioxidant that activates glutathione, but the gap between its necessity and its toxicity is small and requires special attention. Whether selenium can be used in the treatment of ILD remains unclear. Methods: We investigated the prophylactic and therapeutic effects of selenite, a selenium derivative, in ILD using a murine model of bleomycin-induced idiopathic pulmonary fibrosis (IPF). We further elucidated the underlying mechanism using in vitro cell models and examined their relevance in human tissue specimens. The therapeutic effect of selenite in bleomycin-administered mice was assessed by respiratory function and histochemical changes. Selenite-induced apoptosis and reactive oxygen species (ROS) production in murine lung fibroblasts were measured. Results: Selenite, administered 1 day (inflammation phase) or 8 days (fibrotic phase) after bleomycin, prevented and treated deterioration of lung function and pulmonary fibrosis in mice. Mechanistically, selenite inhibited the proliferation and induced apoptosis of murine lung fibroblasts after bleomycin treatment both in vitro and in vivo. In addition, selenite upregulated glutathione reductase (GR) and thioredoxin reductase (TrxR) in murine lung fibroblasts, but not in lung epithelial cells, upon bleomycin treatment. GR and TrxR inhibition eliminates the therapeutic effects of selenite. Furthermore, we found that GR and TrxR were upregulated in the human lung fibroblasts of IPF patient samples. Conclusions: Selenite induces ROS production and apoptosis in murine lung fibroblasts through GR and TrxR upregulation, thereby providing a therapeutic effect in bleomycin-induced IPF.

Abstract Artificial intelligence (AI) models have shown great accuracy in health screening. However, for real-world implementation, high accuracy may not guarantee cost-effectiveness. Improving AI’s sensitivity finds more high-risk patients but may raise medical costs while increasing specificity reduces unnecessary referrals but may weaken detection capability. To evaluate the trade-off between AI model performance and the long-running cost-effectiveness, we conducted a cost-effectiveness analysis in a nationwide diabetic retinopathy (DR) screening program in China, comprising 251,535 participants with diabetes over 30 years. We tested a validated AI model in 1100 different diagnostic performances (presented as sensitivity/specificity pairs) and modeled annual screening scenarios. The status quo was defined as the scenario with the most accurate AI performance. The incremental cost-effectiveness ratio (ICER) was calculated for other scenarios against the status quo as cost-effectiveness metrics. Compared to the status quo (sensitivity/specificity: 93.3%/87.7%), six scenarios were cost-saving and seven were cost-effective. To achieve cost-saving or cost-effective, the AI model should reach a minimum sensitivity of 88.2% and specificity of 80.4%. The most cost-effective AI model exhibited higher sensitivity (96.3%) and lower specificity (80.4%) than the status quo. In settings with higher DR prevalence and willingness-to-pay levels, the AI needed higher sensitivity for optimal cost-effectiveness. Urban regions and younger patient groups also required higher sensitivity in AI-based screening. In real-world DR screening, the most accurate AI model may not be the most cost-effective. Cost-effectiveness should be independently evaluated, which is most likely to be affected by the AI’s sensitivity.

Background: Renal interstitial fibrosis is the pathophysiological basis of type 2 diabetes mellitus (T2DM). Exercise appears to improve kidney interstitial fibrosis in T2DM, in which silent information regulator factor 2-related enzyme 1 (Sirt1) is a critical regulator. However, the role of Sirt1 in mediating exercise on renal tissue as well as its mechanism remains unknown. Methods: T2DM mouse models were created using a high-fat diet mixed with streptozotocin, followed by 8 weeks of treadmill exercise and niacinamide (Sirt1 inhibitor) intervention. Kits for detecting biochemical indices of renal function were used. The pathological appearance and severity of renal tissue were examined using hematoxylin and eosin, Masson and immunohistochemical staining. The mRNA and protein expression of relevant signaling pathway factors were determined to use real-time reverse transcriptase-polymerase chain reaction and western blotting. Results: T2DM can promote renal interstitial fibrosis, increase kidney index, serum creatinine, blood urea nitrogen and 24 h urinary total protein and cause pathological changes in renal tissue and affect renal function. After 8 weeks of exercise intervention, the biochemical indicators in the kidney of T2DM mice were decreased, Sirt1 expression was increased, the expression of TGF-β1, Smad3, collagen type I (COL1) and collagen type III (COL3) were decreased, and the renal interstitial fibrosis, renal tissue structural lesions and renal function were improved. However, after the nicotinamide intervention, renal interstitial fibrosis of T2DM mice was aggravated, and the improvement effect of exercise on renal interstitial fibrosis of T2DM mice was abolished. Conclusion: The upregulation of Sirt1 expression by exercise can inhibit the transforming growth factor β1/Smad3 pathway, thereby inhibiting the expression and deposition of COL1 and COL3 in renal interstitium, thereby improving renal interstitial fibrosis in T2DM.

[Objective] In water-rich rock stratum regions, preventing confined aquifer inrush accidents is a key focus and challenge in the design and construction of deep foundation pit projects. Accurately and effectively determining the critical thickness of foundation pit bottom plate is crucial in preventing confined aquifer inrush accidents. Therefore, it is necessary to conduct stability study on foundation pit bottom plate inrush damage problem in confined aquifer. [Method] Based on the nonlinear Mohr-Coulomb failure criterion and considering the influence of various strength parameters and the heterogeneity characteristics of soil layers, a mechanical analysis model for foundation pit bottom plate inrush damage is established. Using the limit equilibrium method, a safety factor calculation formula for bottom plate inrush stability considering the inherent strength of soil layers is proposed. The calculation method for inrush damage in the current technical specifications for foundation pit support is modified. Taking the foundation pit of a utility tunnel project in soft soil layers in Jinan as example, the effectiveness of the proposed modified calculation formula for pit bottom plate inrush stability is validated. Additionally, variations in the safety factor of bottom plate inrush stability under the influence of different soil strength parameters, impermeable layer thickness, and confined water pressure are analyzed. [Result & Conclusion] With the increase in soil cohesion, heterogeneity constant, density, and impermeable layer thickness, the safety factor of pit bottom plate inrush stability continuously increases. Conversely, as the soil nonlinear coefficient, confined water pressure, and foundation pit width increase, the safety factor of pit bottom plate inrush stability continuously decreases. The calculated values of the inrush safety factors considering the influence of soil inherent strength parameters, are generally greater than the values obtained using the current calculation method in the technical specifications for foundation support. The verification using the proposed modified inrush stability calculation formula is more economical.

Abstract Kidney disease is a progressive and irreversible condition in which immunity is a contributing factor that endangers human health. It is widely acknowledged that macrophages play a significant role in developing and causing numerous kidney diseases. The increasing focus on the mechanism by which macrophages express apoptosis inhibitor of macrophages (AIM) in renal diseases has been observed. AIM is an apoptosis inhibitor that stops different things that cause apoptosis from working. This keeps AIM-bound cell types alive. Notably, the maintenance of immune cell viability regulates immunity. As our investigation progressed, we concluded that AIM has two sides when it comes to renal diseases. AIM can modulate renal phagocytosis, expedite the elimination of renal tubular cell fragments, and mitigate tissue injury. AIM can additionally exacerbate the development of renal fibrosis and kidney disease by prolonging inflammation. IgA nephropathy (IgAN) may also worsen faster if more protein is in the urine. This is because IgA and immunoglobulin M are found together and expressed. In the review, we provide a comprehensive overview of prior research and concentrate on the impacts of AIM on diverse subcategories of nephropathies. We discovered that AIM is closely associated with renal diseases by playing a positive or negative role in the onset, progression, or cure of kidney disease. AIM is thus a potentially effective therapeutic target for kidney diseases.

Abstract Background The aging population has caused assistive technology (AT) to receive attention. Thus, ensuring accurate user comprehension of AT has become increasingly crucial, and more specialized education for students in relevant fields is necessary. The goal of this study was to explore the learning outcomes in the context of AT for older adults and individuals with disabilities through the use of VR experiential learning. Methods A parallel-group design was used. Sixty third-year university students studying gerontology and long-term-care-related subjects in Taiwan were enrolled, with the experimental (VR) and control (two-dimensional [2D] video) groups each comprising 30 participants. Both groups received the same 15-minute lecture. Subsequently, the experimental group received experiential learning through a VR intervention, whereas the control group watched a 2D video to learn. The students’ knowledge of AT was assessed using a pretest and posttest. Additionally, their skills in evaluation of residential environments were assessed using the Residential Environment Assessment (REA) Form for Older Adults. All data analyses were performed with SPSS version 22. Results In the posttest conducted after the intervention, the experimental group exhibited a significant 20.67 point improvement (p

Magnetorheological (MR) dampers have significantly advanced automotive suspension systems by providing adaptable damping characteristics in response to varying road conditions and driving dynamics. This review offers a comprehensive analysis of the evolution and integration of MR dampers in semi-active suspension systems. Semi-active systems present an optimal balance by integrating the simplicity inherent in passive systems with the adaptability characteristic of active systems, while mitigating the substantial energy consumption. The fundamental principles of MR technology, the design of MR dampers, and the diverse control strategies employed to optimize suspension performance were examined. The classical, modern, and intelligent control methods, along with the related research, were emphasized. Based on the above-mentioned methods, the benefits of MR semi-active control were highlighted, while the challenges and future research directions in MR damper technology were also addressed. Through a synthesis of recent research findings and practical applications, this paper underscores the advancements in MR-based semi-active suspension systems and their promising prospects in the automotive industry.

Given the challenges of aging populations, both in Taiwan and globally, issues related to older consumers need more attention. According to surveys in Taiwan, food is one of the most important consumer products for older adults. In recent years, functional foods have become popular, often using health claims as a promotional tool. Therefore, this study has investigated food product packaging in common retail channels in Taiwan by conducting a content analysis of all items with health claims (160 samples). This study specifically compared products related to aging and those unrelated to aging. The results revealed that more than half the participants with health claims did not provide specific descriptions of their health effects. Furthermore, products related to aging often included health terms and claims to supplement with specific nutrients in their health claims. This study has aimed to offer recommendations for educating older consumers, regulating health claims in food advertising, promoting an age-friendly consumer environment, and consumer protection.

On 15 January 2022, a massive underwater volcano erupted in the Tonga region, releasing a significant amount of volcanic ash and gases into the atmosphere. The United States Geological Survey (USGS) estimated the seismic source to have a surface wave magnitude (Ms) of 5.8. This eruption was observed from space, and the resulting atmospheric shockwave swept across the Pacific Ocean. Reports from various locations worldwide indicated rapid fluctuations in air pressure following this event. Taiwan, situated in the western Pacific, approximately 8,500 km from the eruption source, observed significant changes. During this volcanic eruption, both rapid air pressure changes and several significant changes in the Earth’s physical parameters were observed in Taiwan. The Tonga eruption is a unique event, and comprehensive observations provide an opportunity to explore and explain the mechanisms behind this extreme event. Data from ground surface air pressure gauges, coastal tide gauges, underwater pressure gauges, infrasound sensors, digital microphones, and seismometers were collected. These data were analyzed to identify their origin and explain their interactions. The results of this study first present the detailed propagation characteristics of air pressure waves in the Taiwan region and verify the occurrence of a specific tsunami phenomenon caused by the atmospheric disturbance from the Tonga eruption. It follows a distinct mechanism, explaining its arrival time and wave height distribution around Taiwan, which is different from conventional tsunamis of tectonic origins, which are formed by rapid changes in water caused by earthquakes or underwater landslides.

Background: Demographics of pulmonary hypertension (PH) has changed a lot over the past forty years. Several recent registries noted an increase in mean age of PH but only a few of them investigated the characteristics of elderly patients. Thus, we aimed to analyze the characteristics of PH in such a population in this study. Methods: This multicenter study enrolled patients diagnosed with PH in group 1, 3, 4, and 5 consecutively from January 1, 2019 to December 31, 2020. A total of 490 patients was included, and patients were divided into three groups by age (≤45 years, 45–65 years, and >65 years). Results: The mean age of PH patients diagnosed with PH was 55.3 ± 16.3 years of age. There was higher proportion of elderly patients classified as group 3 PH (≤45: 1.3, 45–65: 4.5, >65: 8.1 %; p = 0.0206) and group 4 PH (≤45: 8.4, 45–65: 14.5, >65: 31.6 %; p 65, mean difference, 77.8 m [95% confidence interval (CI), 2.1–153.6 m]), lower mean pulmonary arterial pressure (mPAP) (≤45 vs. >65, mean difference, 10.8 mmHg [95% CI, 6.37–15.2 mmHg]), and higher pulmonary arterial wedge pressure (PAWP) (≤45 vs. 45–65, mean difference, −2.1 mmHg [95% CI, −3.9 to −0.3 mmHg]) compared to young patients. Elderly patients had a poorer exercise capacity despite lower mPAP level compared to young population, but they received combination therapy less frequently compared to young patients (triple therapy in group 1 PH, ≤45: 16.7, 45–65: 11.3, >65: 3.8 %; p = 0.0005). Age older than 65 years was an independent predictor of high mortality for PH patients. Conclusions: Elderly PH patients possess unique hemodynamic profiles and epidemiologic patterns. They had higher PAWP, lower mPAP, and received combination therapy less frequently. Moreover, ageing is a predictor of high mortality for PH patients. Exercise capacity-hemodynamics mismatch and inadequate treatment are noteworthy in the approach of elderly population with PH.

The proximal convoluted tubule (PCT) of the kidney is a crucial functional segment responsible for reabsorption, secretion, and the maintenance of electrolyte and water balance within the renal tubule. However, there is a lack of a well-defined endogenous transgenic line for studying PCT morphogenesis. By analyzing single-cell transcriptome data from the adult zebrafish kidney, we have identified the expression of odd-skipped-related 2 (osr2, which encodes an odd-skipped zinc-finger transcription factor) in the PCT. To gain insight into the role of osr2 in PCT morphogenesis, we have generated a transgenic zebrafish line Tg(osr2:EGFP), expressing enhanced green fluorescent protein (EGFP). The EGFP expression pattern closely mirrors that of endogenous Osr2, faithfully recapitulating its native expression profile. During kidney development, we can use EGFP to track PCT development, which is also preserved in adult zebrafish. Additionally, osr2:EGFP-labeled zebrafish PCT fragments displayed short lengths with infrequent overlap, rendering them conducive for nephrons counting. The generation of Tg(osr2:EGFP) transgenic line is accompanied by simultaneous disruption of osr2 activity. Importantly, our findings demonstrate that osr2 inactivation had no discernible impact on the development and regeneration of Tg(osr2:EGFP) zebrafish nephrons. Overall, the establishment of this transgenic zebrafish line offers a valuable tool for both genetic and chemical analysis of PCT.

Methamphetamine is a highly abused psychostimulant that substantially impacts public health. Prenatal and postnatal methamphetamine exposure alters gene expression, brain development, and behavior in the offspring, although the underlying mechanisms are not fully defined. To assess these adverse outcomes in the offspring, we employed a mouse model of prenatal and postnatal methamphetamine exposure. Juvenile offspring were behaviorally assessed on the open field, novel object recognition, Y-maze, and forced swim tests. In addition, RNA sequencing was used to explore potential alterations in prefrontal cortical gene expression. We found that methamphetamine-exposed mice exhibited decreased locomotor activity and impaired cognitive performance. In addition, differential expression of genes involved in neurotransmission, synaptic plasticity, and neuroinflammation were found with notable changes in dopaminergic signaling pathways. These data suggest potential neural and molecular mechanisms underlying methamphetamine-exposed behavioral changes. The altered expression of genes involved in dopaminergic signaling and synaptic plasticity highlights potential targets for therapeutic interventions for substance abuse disorders and related psychiatric complications.

Abstract Non–small cell lung cancer (NSCLC) is associated with a poor survival rate, even for patients with early-stage cancer. Identifying patients with pathological N0 NSCLC who may benefit from adjuvant chemotherapy treatment after surgery is essential. We conducted a retrospective cohort study used data from the Surveillance, Epidemiology, and End Results database and included 26,380 patients with pathological N0 NSCLC after surgery between January 2018, and December 2019. Among 26,380 patients, 24,273 patients received surgery alone and the other 2107 patients received surgery plus adjuvant chemotherapy. After 1:1 propensity score matching, both groups contained 2107 patients. Adjuvant chemotherapy did not show significantly better 24-month survival in T2aN0 NSCLC patients (83.41% vs. 82.91%, p = 0.067), although it did for T2bN0 patients (86.36% vs. 81.70%, p = 0.028). Poorly-differentiated NSCLC remained a high-risk factor for pT2N0, and adjuvant chemotherapy provided better 24-month survival after matching (86.36% vs. 81.70%, p = 0.029). In conclusion, when treating pN0 NSCLC, adjuvant chemotherapy had a beneficial effect when the tumor size was larger than 4 cm. The effect when the tumor size was between 3 and 4 cm was not remarkable. Poorly-differentiated NSCLC was a high-risk factor in the pT2N0 stage.

Abstract Organ regeneration necessitates precise coordination of accelerators and brakes to restore organ function. However, the mechanisms underlying this intricate molecular crosstalk remain elusive. In this study, the level of proenkephalin-A (PENK-A), expressed by renal proximal tubular epithelial cells, decreases significantly with the loss of renal proximal tubules and increased at the termination phase of zebrafish kidney regeneration. Notably, this change contrasts with the role of hydrogen peroxide (H2O2), which acts as an accelerator in kidney regeneration. Through experiments with penka mutants and pharmaceutical treatments, we demonstrate that PENK-A inhibits H2O2 production in a dose-dependent manner, suggesting its involvement in regulating the rate and termination of regeneration. Furthermore, H2O2 influences the expression of tcf21, a vital factor in the formation of renal progenitor cell aggregates, by remodeling H3K4me3 in renal cells. Overall, our findings highlight the regulatory role of PENK-A as a brake in kidney regeneration.

Abstract Background Equid alphaherpesvirus 1 (EHV-1) is a global viral pathogen of domestic equids which causes reproductive, respiratory and neurological disease. Few isolates acquired from naturally infected USA-based hosts have been fully sequenced and analyzed to date. An ORF 30 (DNA polymerase) variant (A2254G) has previously been associated with neurological disease in host animals. The purpose of this study was to perform phylogenomic analysis of EHV-1 isolates acquired from USA-based hosts and compare these isolates to previously sequenced global isolates. Methods EHV-1 was isolated from 23 naturally infected USA-based equids (6 different states, 15 disease outbreaks) with reproductive (22/23) or neurological disease (1/23). Following virus isolation, EHV-1 DNA was extracted for sequencing using Illumina MiSeq. Following reference-based assembly, whole viral genomes were annotated and assessed. Previously sequenced EHV-1 isolates (n = 114) obtained from global host equids were included in phylogenomic analyses. Results The overall average genomic distance was 0.0828% (SE 0.004%) for the 23 newly sequenced USA isolates and 0.0705% (SE 0.003%) when all 137 isolates were included. Clade structure was predominantly based on geographic origin. Numerous nucleotide substitutions (mean [range], 179 [114–297] synonymous and 81 [38–120] non-synonymous substitutions per isolate) were identified throughout the genome of the newly sequenced USA isolates. The previously described ORF 30 A2254G substitution (associated with neurological disease) was found in only one isolate obtained from a host with non-neurological clinical signs (reproductive disease), six additional, unique, non-synonymous ORF 30 substitutions were detected in 22/23 USA isolates. Evidence of recombination was present in most (22/23) of the newly sequenced USA isolates. Conclusions Overall, the genomes of the 23 newly sequenced EHV-1 isolates obtained from USA-based hosts were broadly similar to global isolates. The previously described ORF 30 A2254G neurological substitution was infrequently detected in the newly sequenced USA isolates, most of which were obtained from host animals with reproductive disease. Recombination was likely to be partially responsible for genomic diversity in the newly sequenced USA isolates.

Thermal barrier coating (TBC) materials can improve energy conversion efficiency and reduce fossil fuel use. Herein, novel rare earth tantalates RETaO4, as promising candidates for TBCs, were reassembled into multi-component solid solutions with a monoclinic structure to further depress thermal conductivity via an entropy strategy. The formation mechanisms of oxygen vacancy defects, dislocations, and ferroelastic domains associated with the thermal conductivity are demonstrated by aberration-corrected scanning transmission electron microscopy. Compared to single-RE RETaO4 and 8YSZ, the intrinsic thermal conductivity of (5RE1/5)TaO4 was decreased by 35%–47% and 57%–69% at 1200 ℃, respectively, which is likely attributed to multi-scale phonon scattering from Umklapp phonon–phonon, point defects, domain structures, and dislocations. r¯RE3+/rTa5+ and low-temperature thermal conductivity are negatively correlated, as are the ratio of elastic modulus to thermal conductivity (E/κ) and high-temperature thermal conductivity. Meanwhile, the high defects’ concentration and lattice distortion in high-entropy ceramics enhance the scattering of transverse-wave phonons and reduce the transverse-wave sound velocity, leading to a decrease in the thermal conductivity and Young’s modulus. In addition, 5HEC-1 has ultra-low thermal conductivity, moderate thermal expansion coefficients, and high hardness among three five-component high-entropy samples. Thus, 5HEC-1 with superior thermal barrier and mechanical properties can be used as promising thermal insulating materials.