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Limited experimental research has been conducted on organic Rankine cycle (ORC) systems that use wet working fluids. Therefore, the present study examined how the performance of an ORC system that uses a wet working fluid (R134a) was affected by the superheat degree ratio (SDR) under various scroll rotation speeds. The SDR is the dimensionless ratio between superheat degree and evaporation temperature at a given heat source temperature. Experimental results indicated that at scroll rotation speeds of 900, 1350, and 1800 rpm, the maximum output power of the aforementioned system was 1103, 1464, and 1537 W, respectively, with SDRs of 0.49, 0.49, and 0.54, respectively. The maximum net efficiencies at these speeds were 5.87%, 5.91%, and 5.32%, respectively, which occurred at SDRs of 0.61, 0.49, and 0.48, respectively. This level of system performance was attributable to the high enthalpy at the expander inlet and the high mass flow rate at the high evaporation pressure under an SDR of approximately 0.5. Although increasing the SDR did not enhance the scroll expander's isentropic efficiency, this efficiency decreased considerably when the SDR fell below 0.2. These findings emphasize the importance of optimizing the SDR of ORC systems to improve their performance. [ABSTRACT FROM AUTHOR]

Aims: The PIONEER‐HF and PARAGLIDE‐HF trials aimed to determine the efficacy and safety of the in‐hospital initiation of sacubitril/valsartan in patients hospitalized for AHF. However, whether the inclusion and exclusion criteria of the trials apply to patients encountered in real‐world routine care is unclear. This study aimed to investigate the applicability of the PIONEER‐HF and PARAGLIDE‐HF trials to real‐world AHF patients. Methods and results: We identified 28 293 AHF hospitalized patients between August 2008 to August 2017 from the Chang Gung Research Database and classified them into four groups based on left ventricular ejection fraction (LVEF) and trial criteria. Cox proportional hazards models were used to compare the risk of HF hospitalization and cardiovascular (CV) death. We defined PIONEER‐HF eligible (n = 3683) and non‐eligible (n = 3502) patients with an LVEF ≤40%, and PARAGLIDE‐HF eligible (n = 5191) and non‐eligible (n = 5832) patients with an LVEF >40%. Over a mean follow‐up of 3.5 years, the PIONEER‐HF non‐eligible and eligible groups exhibited similar rates of HF hospitalization and CV death (41.1% vs. 41.8%, adjusted hazard ratio [aHR]: 0.95; 95% CI: 0.88–1.04). No significant difference was found in the composite outcome between PARAGLIDE‐HF non‐eligible and eligible groups (36.7% vs. 38.6%; aHR: 0.97; 95% CI: 0.90–1.04). Conclusions: Using trial criteria, only 31.3% of AHF patients were eligible for sacubitril–valsartan. Yet, non‐eligible patients demonstrated similar outcomes to eligible patients, indicating a need for further evaluation of sacubitril–valsartan benefits in non‐eligible AHF patients. [ABSTRACT FROM AUTHOR]

This article presents an AR HUD using micro LED technology for enhanced brightness and image quality. It utilizes micro LED's high brightness to merge AR images seamlessly with external views and employs Nature 3D technology to improve the HUD's 3D depth, significantly boosting vehicle safety. [ABSTRACT FROM AUTHOR]

Licochalcone A (LicA), a natural compound extracted from licorice root, has been shown to exert a variety of anticancer activities. Whether LicA has such effects on endometrial cancer (EMC) is unclear. This study aims to investigate the antitumor effects of LicA on EMC. Our results show that LicA significantly reduced the viability and induced apoptosis of EMC cells and EMC‐7 cells from EMC patients. LicA was also found to induce endoplasmic reticulum (ER) stress, leading to increased expression of ER‐related proteins (GRP78/PERK/IRE1α/CHOP) in EMC cell lines. Suppression of GRP78 expression in human EMC cells treated with LicA significantly attenuated the effects of LicA, resulting in reduced ER‐stress mediated cell apoptosis and decreased expression of ER‐ and apoptosis‐related proteins. Our findings demonstrate that LicA induces apoptosis in EMC cells through the GRP78‐mediated ER‐stress pathway, emphasizing the potential of LicA as an anticancer therapy for EMC. [ABSTRACT FROM AUTHOR]

Background: For R/M HNSCC, the differences in prognosis and treatment options between distant metastasis (DM) and locoregional recurrence, especially in the DM group, remain unclear. Methods: From the Taiwan Head Neck Society registry database, patients who were diagnosed with R/M HNSCC and received cetuximab‐based frontline therapy were collected for analysis. Results: Among the enrolled patients, 59.3% (491/827) belonged to the DM group. The DM group had less primary site of oral cavity, less betel nut chewing, higher lactate dehydrogenase (LDH) levels, and higher LDH/albumin ratio compared with the non‐DM group. For the patients with primary site of oral cavity and current smokers, DM coexisted with poorer outcomes. In the DM group, EXTREME‐like regimen was more suitable for older patients, those with elevated LDH, and those with higher LDH/albumin ratio than TPExtreme‐like regimen. Conclusion: DM coexisted with poorer prognosis in certain groups. LDH‐associated biomarkers may aid treatment options for DM patients. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions Oral and esophageal cancers are globally prevalent, especially in East Asia. Over half of head and neck cancer patients developing second primary esophageal cancer (SPEC) were initially diagnosed with oral cavity cancer (OCC). This study assessed the cost‐effectiveness of universal endoscopic screening for early SPEC prevention in newly diagnosed OCC patients at different stages.This study employed Markov cohort models to evaluate the cost‐effectiveness of endoscopic SPEC screening post‐OCC diagnosis (stages 0 to IV) between screened and non‐screened groups. Four surveillance frequencies were assessed: (i) one time, (ii) annual for 3 years, (iii) annual for 10 years, and (iv) annual for life. A hypothetical cohort of 100 000 cases across stages was compared for costs and quality‐adjusted life‐years (QALYs), discounted annually at 3%.All four screening strategies were beneficial for all OCC stages, especially for early‐stage patients, resulting in higher QALYs. Lifetime/annual screening from the payer's perspective proved most favorable, with incremental QALYs of 1.23 at stage 0 and 0.06 at stage IV. Incremental costs for this strategy ranged from NTD 121 331 (USD 4044) at stage 0 to NTD 13 032 (USD 434) at stage IV. Both incremental costs and incremental cost‐effectiveness ratio (ICER) values indicated cost savings from a societal perspective. The ICER values ranged from NTD −626 440 (USD −20 881) at stage 0 and NTD −475 021 (USD −15 834) at stage IV.Overall, our study provided cost‐effectiveness evidences to understanding the cost‐effectiveness of endoscopic screening in OCC patients, particularly emphasizing the benefits of early and consistent screening. [ABSTRACT FROM AUTHOR]

Recent work has indicated that atmospheric radiative heating reduces the kinetic energy of large‐scale eddies in the midlatitudes. However, a physical mechanism that connects radiation to the midlatitude eddy kinetic energy is still uncertain. Using a high‐resolution general circulation model we perform an experiment in which the radiative cooling profile at each model time step is overwritten with the climatological mean, computed from a control simulation. This approach separates the mean and transient effects of radiative heating on the extratropical circulation. We find that, when radiative heating is fixed, the globally‐averaged eddy kinetic energy is enhanced by ∼6%. We show that thermal radiation dampens temperature anomalies near the surface and tropopause in low‐pressure systems, destroying eddy available potential energy and eddy kinetic energy. We identify this as a possible mechanism by which atmospheric radiative heating weakens midlatitude cyclones. Plain Language Summary: The atmosphere can be differentially heated through the absorption of visible and infrared radiation by water vapor and clouds. This process of radiative heating is thought to promote the formation of tropical cyclones, but its impact on midlatitude cyclones—storms characterized by the passage of warm and cold fronts—is less clear. Here we show that, unlike tropical cyclones, radiative heating weakens midlatitude storms. We argue that radiative cooling in the warm sector, and radiative heating in the cold sector of midlatitude cyclones, reduces the temperature gradient which is critical for the development of these weather systems. This study underscores an essential difference between tropical and midlatitude storms: in the tropics, temperature gradients are small, but at higher latitudes, temperature gradients are the drivers of storm formation. Key Points: When radiative interactions are suppressed, the global‐mean eddy kinetic energy increases by ∼6%Radiative cooling coincident with positive temperature anomalies destroys eddy available potential energy and eddy kinetic energyThe energetic perspective provides a useful way to understand the effect of radiative heating on the general circulation [ABSTRACT FROM AUTHOR]

Background and Aims: We aimed to explore the risk factors associated with virological and clinical relapse, as well as their impact on overall mortality, in hepatitis B virus (HBV)‐infected patients receiving nucleos(t)ide analogues (NUCs) therapy prior to chemotherapy initiation. Methods: From 2010 to 2020, we conducted a prospective cohort study involving patients with HBV infection undergoing cytotoxic chemotherapy. We utilized the Kaplan–Meier method and Cox proportional hazard regression models to assess risk factors. Results: We observed that TDF or TAF (HR: 2.16, 95% CI 1.06–4.41; p =.034), anthracycline (HR: 1.73, 95% CI 1.10–2.73; p =.018), baseline HBV DNA (HR: 1.55, 95% CI 1.33–1.81; p <.001) and end‐of‐treatment HBsAg titre >100 IU/mL (HR: 7.81, 95% CI 1.94–31.51; p =.004) were associated with increased risk of virological relapse. Additionally, TDF or TAF (HR: 4.91, 95% CI 1.45–16.64; p =.011), baseline HBV DNA (HR: 1.48, 95% CI 1.10–1.99; p =.009) and end‐of‐treatment HBsAg titre >100 IU/mL (HR: 6.09, 95% CI.95–38.87; p =.056) were associated with increased risk of clinical relapse. Furthermore, we found that virological relapse (HR: 3.32, 95% CI 1.33–8.32; p =.010) and clinical relapse (HR: 3.59, 95% CI 1.47–8.80; p =.005) significantly correlated with all‐cause mortality in HBV patients receiving cytotoxic chemotherapy with prophylactic NUCs therapy. Conclusions: The risk of virological and clinical relapse was linked to baseline HBV DNA, end‐of‐treatment HBsAg levels and TDF or TAF for prophylaxis; additionally, experiencing relapse heightens the risk of all‐cause mortality. Further research is warranted to explore potential strategies for preventing virological and clinical relapse in high‐risk patients. [ABSTRACT FROM AUTHOR]

The most effective drug, doxorubicin (DOX), is widely used worldwide for clinical application as an anticancer drug. DOX‐induced cytotoxicity is characterized by mitochondrial dysfunction. There is no alternative treatment against DOX‐induced cardiac damage despite intensive research in the present decades. Ohwia caudata has emerged as a potential herbal remedy that prevents from DOX‐induced cytotoxicity owing to its pharmacological action of sustaining mitochondrial dynamics by attenuating oxidative stress and inducing cellular longevity. However, its underlying mechanisms are unknown. The novel treatment provided here depends on new evidence from DOX‐treated H9c2 cells, which significantly enhanced insulin‐like growth factor (IGF) II receptor (IGF‐IIR) pathways that activated calcineurin and phosphorylated dynamin‐related protein 1 (p‐Drp1) at ser616 (p‐Drp1[ser616]); cells undergo apoptosis due to these factors, which translocate to mitochondria and disrupt their function and integrity, and in terms of herbal medicine treatment, which significantly blocked these phenomena. Thus, our findings indicate that maintaining integrity of mitochondria is an essential element in lowering DOX‐induced cytotoxicity, which further emphasizes that our herbal medicine can successfully block IGF‐IIR pathways and could potentially act as an alternative mechanism in terms of cardioprotective against doxorubicin. [ABSTRACT FROM AUTHOR]

Three carbazole‐substituted anthracene 2CbzAn, 26CbzAn, and 246CbzAn have been developed. The introduction of these carbazole substituents could generate more triplet states with energy levels close to 2× E(T1) that could successfully facilitate the triplet‐triplet annihilation upconversion (TTA‐UC) process to achieve high upconversion quantum yield (UCQY). This observation aligns with the Adachi theory about TTA‐UC mechanisms. In organic light‐emitting diode (OLED) device investigation, in a non‐doped state show an external quantum efficiency (EQEmax) of 5.82% with exceptional pure‐blue emission (CIEy of 0.101), and the DPaNIF doped DMPPP/26CbzAn bilayer structure reaches an impressive EQEmax of 11.12%. [ABSTRACT FROM AUTHOR]

Lately, carbazole‐based self‐assembled monolayers (SAMs) are widely employed as effective hole‐selective layers (HSLs) in inverted perovskite solar cells (PSCs). Nevertheless, these SAMs tend to aggregate in solvents due to their amphiphilic nature, hindering the formation of a monolayer on the ITO substrate and impeding effective passivation of deep defects in the perovskites. In this study, a series of new SAMs including DPA‐B‐PY, CBZ‐B‐PY, POZ‐B‐PY, POZ‐PY, POZ‐T‐PY, and POZ‐BT‐PY are synthesized, which are employed as interfacial repairers and coated atop CNph SAM to form a robust CNph SAM@pseudo‐planar monolayer as HSL in efficient inverted PSCs. The CNph SAM@pseudo‐planar monolayer strategy enables a well‐aligned interface with perovskites, synergistically promoting perovskite crystal growth, improving charge extraction/transport, and minimizing nonradiative interfacial recombination loss. As a result, the POZ‐BT‐PY‐modified PSC realizes an impressively enhanced solar efficiency of up to 24.45% together with a fill factor of 82.63%. Furthermore, a wide bandgap PSC achieving over 19% efficiency. Upon treatment with the CNph SAM@pseudo‐planar monolayer, also demonstrates a non‐fullerene organic photovoltaics (OPVs) based on the PM6:BTP‐eC9 blend, which achieves an efficiency of 17.07%. Importantly, these modified PSCs and OPVs all show remarkably improved stability under various testing conditions compared to their control counterparts. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusion The first step in computed tomography (CT) reconstruction is to estimate attenuation pathlength. Usually, this is done with a logarithm transformation, which is the direct solution to the Beer‐Lambert Law. At low signals, however, the logarithm estimator is biased. Bias arises both from the curvature of the logarithm and from the possibility of detecting zero counts, so a data substitution strategy may be employed to avoid the singularity of the logarithm. Recent progress has been made by Li et al. [IEEE Trans Med Img 42:6, 2023] to modify the logarithm estimator to eliminate curvature bias, but the optimal strategy for mitigating bias from the singularity remains unknown.The purpose of this study was to use numerical techniques to construct unbiased attenuation pathlength estimators that are alternatives to the logarithm estimator, and to study the uniqueness and optimality of possible solutions, assuming a photon counting detector.Formally, an attenuation pathlength estimator is a mapping from integer detector counts to real pathlength values. We constrain our focus to only the small signal inputs that are problematic for the logarithm estimator, which we define as inputs of <100 counts, and we consider estimators that use only a single input and that are not informed by adjacent measurements (e.g., adaptive smoothing). The set of all possible pathlength estimators can then be represented as points in a 100‐dimensional vector space. Within this vector space, we use optimization to select the estimator that (1) minimizes mean squared error and (2) is unbiased. We define “unbiased” as satisfying the numerical condition that the maximum bias be less than 0.001 across a continuum of 1000 object thicknesses that span the desired operating range. Because the objective function is convex and the constraints are affine, optimization is tractable and guaranteed to converge to the global minimum. We further examine the nullspace of the constraint matrix to understand the uniqueness of possible solutions, and we compare the results to the Cramér‐Rao bound of the variance.We first show that an unbiased attenuation pathlength estimator does not exist if very low mean detector signals (equivalently, very thick objects) are permitted. It is necessary to select a minimum mean detector signal for which unbiased behavior is desired. If we select two counts, the optimal estimator is similar to Li's estimator. If we select one count, the optimal estimator becomes non‐monotonic. The oscillations cause the unbiased estimator to be noise amplifying. The nullspace of the constraint matrix is high‐dimensional, so that unbiased solutions are not unique. The Cramér‐Rao bound of the variance matches well with the expected I−0.5${{I}^{ - 0.5}}$ scaling law and cannot be attained.If arbitrarily thick objects are permitted, an unbiased attenuation pathlength estimator does not exist. If the maximum thickness is restricted, an unbiased estimator exists but is not unique. An optimal estimator can be selected that minimizes variance, but a bias‐variance tradeoff exists where a larger domain of unbiased behavior requires increased variance. [ABSTRACT FROM AUTHOR]

Oral submucous fibrosis (OSF) is a precancerous condition in the oral cavity, which is closely related to the myofibroblast conversion of buccal mucosal fibroblasts (BMFs) after chronic consumption of areca nut. Emerging evidence suggests pyroptosis, a form of programmed cell death that is mediated by inflammasome, is implicated in persistent myofibroblast activation and fibrosis. Besides, numerous studies have demonstrated the effects of non‐coding RNAs on pyroptosis and myofibroblast activities. Herein, we aimed to target key long non‐coding RNA PVT1 with natural compound, carvacrol, to alleviate pyroptosis and myofibroblast activation in OSF. We first identified PVT1 was downregulated in the carvacrol‐treated fBMFs and then demonstrated that myofibroblast features and expression of pyroptosis makers were all reduced in response to carvacrol treatment. Subsequently, we analysed the expression of PVT1 and found that PVT1 was aberrantly upregulated in OSF specimens and positively correlated with several fibrosis markers. After revealing the suppressive effects of carvacrol on myofibroblast characterisitcs and pyroptosis were mediated by repression of PVT1, we then explored the potential mechanisms. Our data showed that PVT1 may serve as a sponge of microRNA(miR)‐20a to mitigate the myofibroblast activation and pyroptosis. Altogether, these findings indicated that the anti‐fibrosis effects of carvacrol merit consideration and may be due to the attenuation of pyroptosis and myofibroblast activation by targeting the PVT1/miR‐20a axis. [ABSTRACT FROM AUTHOR]

This study utilized a large‐scale representative sample to explore the prevalence of sexting and its associated factors among adolescents in Taiwan. A total of 12,954 students in grade 5–12 countrywide were randomly selected to answer the sexting module of an online survey. 13.7% of the respondents reported having ever received sexts on cellphone, and 2.0% had sent sexts to others. The prevalence was higher among older adolescents. Gender differences were also found, in which female students were more likely to receive sexts (15.8% vs. 11.7%), while male students were at higher risk of sending sexts to others (2.9% vs. 1.1%). A series of hierarchical logistic regression were further performed to examine the associations between potential factors and receiving/sending sexts as the outcome variables. Age, gender, and time spending on texting were significantly associated with receiving and ending sexts. Online respect was found positively associated with receiving sexts but negatively associated with sending them. Privacy awareness was found not significantly associated with sexting. As the first national survey on this growing issue in Taiwan, the results of the present study highlighted the existence of sexting among local youth. Practice and policy implications were discussed. [ABSTRACT FROM AUTHOR]

Highlights Bulk molding compound (BMC) manufactured using fiber reinforced polymers (FRPs) has attracted extensive attention and is widely used because of its capability to fabricate structures with complex shapes. This study investigated the effects of aging on the mechanical properties of BMC composites made using an epoxy matrix and discontinuous carbon fibers of varying lengths. Tensile, compressive, and flexural tests were conducted. The results showed that longer fibers did not necessarily increase the moduli and strengths of BMC composites due to stress concentrations resulting from the curling and entanglement of the longer fibers. When aged, BMC composites using shorter carbon fibers exhibited more significant reductions in moduli and strengths due to higher void contents, resulting in more severe matrix epoxy degradation. When comparing epoxy and BMC, BMC experienced greater reductions in moduli and strengths even though carbon fiber, a type of artificial fiber, should be less affected by aging. This is because aging not only degraded the matrix epoxy but also affected the adhesion between the fibers and the matrix, leading to a larger displacement of the fibers, resulting in a more severe reduction in the mechanical properties of the BMC composites. BMC composites were manufactured using epoxy and discontinuous carbon fibers. Longer fibers did not necessarily increase strengths due to entanglement. BMC using shorter fibers had more voids and hence degraded more severely. BMC showed greater strength reductions than epoxy due to matrix degradation. Degradation of matrix epoxy affected the adhesion between fibers and matrix. [ABSTRACT FROM AUTHOR]

Transition metal dichalcogenides (TMDs) have garnered attention as potential catalysts for water splitting owing to their unique structures, diverse electronic properties, and composition from earth‐abundant elements. While certain TMD catalysts, notably MoS2, have shown promising activity for hydrogen evolution reactions (HER), achieving performance comparable to traditional platinum catalysts remains a challenge. While significant effort has been invested into understanding the effect of TMD's structural properties, such as defectiveness and crystalline phases, recent work has emphasized the role of extrinsic factors on HER. This review summarizes the current understanding of the impact of commonly overlooked electrocatalytic effects that exhibit an enhanced importance in TMD‐based HER. By combining recent advances in theoretical modeling and experimental work, we review the dominating effects of extrinsic factors including electronic resistance, interfacial barriers, surface roughness, oxidation, and valence impurities. Our work aims to provide insights into optimizing TMDs as highly efficient catalysts for HER, facilitating future advancements in hydrogen generation technology. [ABSTRACT FROM AUTHOR]

The primary function of the skin is to form a mechanical, permeability, antimicrobial, and ultraviolet radiation barrier, which is essential for maintaining physiological homeostasis. Our previous studies demonstrated that cutaneous pigmentation could promote skin barrier function in addition to providing anti‐ultraviolet irradiation defense. The present study aimed to develop a new regimen that enhances skin barrier function by regulating skin pigmentation using low‐concentration imiquimod. Results showed that topical application of low‐concentration imiquimod effectively induced skin hyperpigmentation in the dorsal skin and external ear of mice without inducing inflammatory cell infiltration. An in vitro study also revealed that low‐concentration imiquimod did not induce any cytotoxic effects on melanoma cells but triggered excessive melanin synthesis. In coculture systems, low‐concentration imiquimod was noted to increase tyrosinase activity in a broader cellular context, revealing the potential role of neighboring cells in melanin production. The next‐generation sequencing result indicated that PKCη and Dnm3 might regulate melanin synthesis and release during imiquimod treatment. Overall, our study presents new insights into the regulation of melanin production by low‐concentration imiquimod, both in a mice model and cultured cells. Furthermore, our study highlights the potential benefits of imiquimod in promoting melanin synthesis without causing skin disruptions or inducing inflammation, validating its potential to serve as a method for enhancing skin barrier functions by regulating the epidermal melanization reaction. [ABSTRACT FROM AUTHOR]

The association between influenza infection and thromboembolism (TE) events, including cardiovascular events, cerebrovascular events, pulmonary embolism, and deep vein thrombosis, is supported by compelling evidence. However, there is a disparity in the risk factors that impact the outcomes of severe influenza‐complicated TE in intensive care unit (ICU) patients. The objective of this study was to evaluate the outcomes of severe influenza‐complicated TE in ICU patients and identify any associated risk factors. Methods: A retrospective cohort study was conducted, recruiting consecutive patients with TE events admitted to the ICU between December 2015 through December 2018 at our institution in Taiwan. The study included a group of 108 patients with severe influenza and a control group of 192 patients with severe community‐acquired pneumonia. Associations between complicated TE, length of ICU stay, and 90‐day mortality were evaluated using logistic regression analysis, and risk factors were identified using univariate and multivariate generalized linear regression analyses. Results: TE event prevalence was significantly higher in ICU patients with severe influenza than in ICU patients with severe CAP (21.3% vs. 5.7%, respectively; p < 0.05). Patients with severe influenza who developed TE experienced a significant increase in the ratio of mechanical ventilation use, length of mechanical ventilation use, ICU stay, and 90‐day mortality when compared to patients without TE (all p < 0.05). The comparison of severe CAP patients with and without TE revealed no significant differences (p > 0.05). The development of thromboembolic events in patients with severe influenza or severe noninfluenza CAP is linked to influenza infection and hypertension (p < 0.05). Furthermore, complicated TE and the severity of the APACHE II score are risk factors for 90‐day mortality in ICU patients with severe influenza (p < 0.05). Conclusions: Patients with severe influenza and complicated TE are more likely to have an extended ICU stay and 90‐day mortality than patients with severe CAP. The risk is significantly higher for patients with a higher APACHE II score. The results of this study may aid in defining better strategies for early recognition and prevention of severe influenza‐complicated TE. [ABSTRACT FROM AUTHOR]

Dual antiplatelet therapy (DAPT) with ticagrelor or adjusted‐dose prasugrel has been used for acute coronary syndrome (ACS). However, few studies have directly compared these two drugs. In this study, we compared the real‐world applications and outcomes of these two drugs in patients with ACS who had undergone percutaneous coronary intervention (PCI). This retrospective cohort study was conducted using the data of eligible patients with ACS who had undergone PCI at Chang Gung Memorial Hospital System between June 2019 and December 2021. The primary efficacy‐related outcome was the occurrence of major adverse cardiovascular events (MACEs), and the primary safety‐related outcome was major bleeding. Inverse probability of treatment weighting based on propensity score was performed to reduce confounding effects. The study included 2,636 patients; of them, 429 received prasugrel and 2,207 received ticagrelor. No significant between‐group difference was observed in the risk of MACE (13.1 vs. 13.1 events per 100 person‐years, respectively, hazard ratio (HR): 1.01, 95% confidence interval (CI): 0.71–1.43). Both groups exhibited similar rates of major bleeding (3.9 vs. 4.1 events per 100 person‐years, respectively, subdistribution HR: 0.96, 95% CI: 0.68–1.35). In real‐world settings, adjusted‐dose prasugrel and ticagrelor exhibit comparable safety and efficacy profiles in East Asian patients with ACS after PCI. Our findings offer valuable insights for future clinical decision making and patient management strategies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Youth violence, victimization, and bullying are pervasive in schools across the United States and are detrimental for learning and healthy development. K‐12 school safety is an increasingly urgent issue to research and understand from multiple perspectives. Physical and psychological safety in school is linked to better student and school outcomes and is fundamental to fostering well‐being and prosocial behavior. METHODS: Despite research demonstrating positive outcomes associated with school safety, there is no comprehensive conceptual model in the literature that considers precursors, strategies, mechanisms, and outcomes of school safety together. The current paper presents an equity‐centered comprehensive model of school safety, which is intended as a holistic representation of the multiple factors and pathways that contribute to school safety and positive youth development. RESULTS: This model can guide research and practice through an equity‐centered and comprehensive approach. This model can enable practitioners, researchers, and policymakers to make informed decisions and reach consensus regarding planning and decisions related to reducing violence and establishing supportive school environments. CONCLUSION: Our model suggests that a comprehensive approach can ensure the safety and well‐being of students and staff. By thinking ecologically, schools, communities, and stakeholders can ensure that all aspects of the school context are included in school safety. [ABSTRACT FROM AUTHOR]

Objectives: To investigate community health centers' (CHCs) health literacy. Design: A cross‐sectional study. Sample: A total of 374 CHCs were surveyed and 258 CHCs responded, with an effective questionnaire response rate of 69.0%. Measurements: Data were collected by using a self‐developed health literacy assessment tool to survey CHCs' health literacy throughout Taiwan from January to December 2019. Results: The item of organizational health literacy (OHL) with the highest proportion of CHCs not implementing them was "Design of easy‐to‐use computer applications and new media" (47.3% not yet achieved), followed by "Involving target audiences in document and service development" (34.9% not yet achieved). CHCs located in northern Taiwan had higher health literacy achievement scores than those in other regions, and those in urban areas had higher health literacy achievement scores than those in general and remote areas. Conclusions: This study identified items with poor implementation of OHL and found regional differences in health literacy among CHCs. The findings can inform the development of targeted interventions to improve health literacy in underperforming CHCs and guide policymakers in allocating resources to regions and areas in need of. [ABSTRACT FROM AUTHOR]

Next‐generation phenotyping (NGP) can be used to compute the similarity of dysmorphic patients to known syndromic diseases. So far, the technology has been evaluated in variant prioritization and classification, providing evidence for pathogenicity if the phenotype matched with other patients with a confirmed molecular diagnosis. In a Nigerian cohort of individuals with facial dysmorphism, we used the NGP tool GestaltMatcher to screen portraits prior to genetic testing and subjected individuals with high similarity scores to exome sequencing (ES). Here, we report on two individuals with global developmental delay, pulmonary artery stenosis, and genital and limb malformations for whom GestaltMatcher yielded Cornelia de Lange syndrome (CdLS) as the top hit. ES revealed a known pathogenic nonsense variant, NM_133433.4: c.598C>T; p.(Gln200*), as well as a novel frameshift variant c.7948dup; p.(Ile2650Asnfs*11) in NIPBL. Our results suggest that NGP can be used as a screening tool and thresholds could be defined for achieving high diagnostic yields in ES. Training the artificial intelligence (AI) with additional cases of the same ethnicity might further increase the positive predictive value of GestaltMatcher. [ABSTRACT FROM AUTHOR]

The food industry is a significant contributor to carbon emissions, impacting carbon footprint (CF), specifically during the heat drying process. Conventional heat drying processes need high energy and diminish the nutritional value and sensory quality of food. Therefore, this study aimed to investigate the integration of artificial intelligence (AI) in food processing to enhance quality and reduce CF, with a focus on heat drying, a high energy‐consuming method, and offer a promising avenue for the industry to be consistent with sustainable development goals. Our finding shows that AI can maintain food quality, including nutritional and sensory properties of dried products. It determines the optimal drying temperature for improving energy efficiency, yield, and life cycle cost. In addition, dataset training is one of the key challenges in AI applications for food drying. AI needs a vast and high‐quality dataset that directly impacts the performance and capabilities of AI models to optimize and automate food drying. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Methods Results Conclusion We retrospectively studied young patients with head and neck squamous cell carcinoma (HNSCC) to identify factors associated with disease‐specific survival (DSS).Patient and tumor characteristics of patients aged ≤45 who received treatments for non‐metastatic HNSCC were collected to identify factors associated with DSS. Proportional hazards regression was applied separately for surgical and non‐surgical patients.230 patients were included. Surgical and non‐surgical patients had similar DSS. Higher pathologic stages, positive margins, perineural invasion (PNI), extranodal extension and negative HPV status were associated with worse DSS for surgical patients and negative HPV status for non‐surgical patients. In the multivariate analysis, pathologic stages, positive margins, and PNI were associated with worse DSS in surgical patients.Pathologic stages, positive margins, and PNI are independently associated with worse DSS in young surgical HNSCC patients. PNI is a uniquely strong prognostic factor for young patients. [ABSTRACT FROM AUTHOR]

A cost‐effective chemical prelithiation solution, which consists of Li+, polyaromatic hydrocarbon (PAH), and solvent, is developed for a model hard carbon (HC) electrode. Naphthalene and methyl‐substituted naphthalene PAHs, namely 2‐methylnaphthalene and 1‐methylnaphthalene, are first compared. Grafting an electron‐donating methyl group onto the benzene ring can decrease electron affinity and thus reduce the redox potential, which is validated by density functional theory calculations. Ethylene glycol dimethyl ether (G1), diethylene glycol dimethyl ether, and triethylene glycol dimethyl ether solvents are then compared. The G1 solution has the highest conductivity and least steric hindrance, and thus the 1‐methylnaphthalene/G1 solution shows superior prelithiation capability. In addition, the effects of the interaction time between Li+ and 1‐methylnaphthalene in G1 solvent on the electrochemical properties of a prelithiated HC electrode are investigated. Nuclear magnetic resonance data confirm that 10‐h aging is needed to achieve a stable solution coordination state and thus optimal prelithiation efficacy. It is also found that appropriate prelithiation creates a more Li+‐conducing and robust solid‐electrolyte interphase, improving the rate capability and cycling stability of the HC electrode. [ABSTRACT FROM AUTHOR]

Age, ethnic background and genetic components have been identified as the established risks for prostate cancer (PCa). Pentraxin 3 (PTX3), originally identified as a pattern‐recognition molecule for defence against infectious agents, has multiple functions in tissue repair and in the regulation of cancer‐associated inflammation. In this study, we sought to investigate the impact of PTX3 gene variants on the development of PCa. Genotypes of four common single‐nucleotide polymorphisms (SNPs) of PTX3 gene, including rs1840680, rs2305619, rs3816527 and rs2120243, were profiled among 705 PCa patients and 705 ethnicity‐matched controls. In this study, we found that patients who carry at least one minor allele (C) of rs3816527 (AC and CC) tended to develop advanced forms of diseases (clinical large T stage, OR, 1.593, p = 0.032; pathologically‐confirmed nodal spread, OR, 1.987, p = 0.011; metastatic tumour, OR, 3.896, p = 0.032) as compared with those homologous for the major allele (AA). Further stratification analysis showed that such association of rs3816527 with lymphatic and distal metastasis of PCa was accentuated in the younger age group (≤65 at diagnosis) but not seen in the older age group (>65 at diagnosis), suggesting an age‐specific effect of PTX3 variants. Prediction of PTX3 protein structure implied that polymorphism may alter the quaternary organization and oligomerization of PTX3 protein. Moreover, our gene silencing experiments and survey of public datasets revealed that elevation of PTX3 levels in PCa was required for cell migration and associated with tumour metastasis. Our results highlight an association of PTX3 rs3816527 with the progression of PCa. [ABSTRACT FROM AUTHOR]

Pyrocurzerenone is a natural compound found in Curcuma zedoaria and Chloranthus serratus. However, the anticancer effect of pyrocurzerenone in oral cancer remains unclear. Using the MTT assay, wound healing assay, transwell assay and western blot analysis, we investigated the impact of pyrocurzerenone on antimetastatic activity, as well as the critical signalling pathways that underlie the processes of oral cancer cell lines SCC‐9, SCC‐1 and SAS in this work. Our findings suggested that pyrocurzerenone inhibits cell migration and invasion ability in oral cancer cell lines. Furthermore, phosphorylation of ERK1/2 had significant inhibitory effects in SCC‐9 and SCC‐1 cell lines. Combining ERK1/2 inhibitors with pyrocurzerenone decreased the migration and invasion activity of SCC‐9 and SCC‐1 cell lines. We also found that the expressed level of cathepsin S decreased under pyrocurzerenone treatment. This study showed that pyrocurzerenone reduced ERK1/2 expression of the proteins and cathepsin S, suggesting that it could be a valuable treatment to inhibit human oral cancer cell metastasis. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cell therapy, a developing approach in cancer immunotherapy, involves isolating NK cells from peripheral blood. However, due to their limited number and activity, it is essential to significantly expand these primary NK cells and enhance their cytotoxicity. In this study, we investigated how Raddeanin A potentiate NK activity using KHYG‐1 cells. The results indicated that Raddeanin A increased the expression levels of cytolytic molecules such as perforin, granzymes A and granzymes B, granulysin and FasL in KHYG‐1 cells. Raddeanin A treatment increased CREB phosphorylation, p65 phosphorylation, NFAT1 and acetyl‐histone H3 expression. Raddeanin A elevated caspase 3 and PARP cleavage, increased t‐Bid expression, promoting apoptosis in K562 cells. Furthermore, it reduced the expression of HMGB2, SET and Ape1, impairing the DNA repair process and causing K562 cells to die caspase‐independently. Additionally, Raddeanin A increased ERK, p38 and JNK phosphorylation at the molecular level, which increased granzyme B production in KHYG‐1 cells. Raddeanin A treatment increased Ras, Raf phosphorylation, MEK phosphorylation, NKG2D, NKp44 and NKp30 expression in KHYG‐1 cells. Collectively, our data indicate that Raddeanin A enhances the cytotoxic activity of NK cells against different cancer cells. [ABSTRACT FROM AUTHOR]

Meningioma is the most common type of primary brain tumor. Surgical resection followed by surveillance is the first‐line treatment for the majority of symptomatic meningiomas; however, recent advances in molecular sequencing, DNA methylation, proteomics, and single‐cell sequencing provide insights into further characterizing this heterogeneous group of tumors with a wide range of prognoses. A subset of these tumors are highly aggressive and cause severe morbidity and mortality. Therefore, identifying those individuals with a poor prognosis and intervening are critical. This review aims to help readers interpret the molecular profiling of meningiomas to identify patients with worse prognoses and guide the management and strategy for surveillance. In light of recent advances in the molecular profiling of meningiomas, this review provides practical guidance for incorporating genomic, methylomic, and proteomic information about meningiomas into management decisions. [ABSTRACT FROM AUTHOR]

In this study, we investigate the effect of terminal benzene derivatives in triphenylamine‐based oxime esters on their photoreactivity. Five novel oxime esters (Miko series) that containing different benzene derivatives as terminal groups, were synthesized. The electronic properties of the substituents on the benzene ring range from electron‐donating to electron‐withdrawing. Specifically, a methoxy benzene for Miko‐MOB, tert‐butyl benezene for Miko‐t‐Bu, chloro benzene for Miko‐CB, trifluoromethyl benzene for Miko‐TFM, and nitro benzene for Miko‐NB. Additionally, a compound with benzene only as the terminal substituent (TP‐1) was selected for comparision. All the new compounds exhibited higher molar extinction coefficients than TP‐1. Additionally, the steady‐state photolysis and electron spin resonance (ESR) properties would decrease from the electron‐donating substitutes to electron‐withdrawing substitutes. Finally, these oxime esters are utilized in Type I photoinitiating systems for the free radical polymerization of trimethylolpropane triacrylate (TMPTA) under UV or LED@405 nm light irradiation conditions. Among all formulations, Miko‐MOB demonstrated the highest double bond conversion efficiency under both UV and LED@405 nm light irradiation. Thus, terminal benzene derivatives in oxime esters play an important role in tuning the optical and photochemical reaction performance, offering significant value for the design strategy of such photoinitiators. [ABSTRACT FROM AUTHOR]

Background: To elucidate the role of balloon Eustachian tuboplasty (BET) in the management of chronic rhinosinusitis with obstructive Eustachian tube dysfunction (ETD), we evaluated the results of endoscopic sinus surgery (ESS) with and without BET in patients with chronic rhinosinusitis with obstructive ETD. Methods: This randomized controlled trial conducted in a single‐institution tertiary care center setting included 50 patients diagnosed with primary chronic rhinosinusitis and obstructive ETD between July 2018 and June 2022. Twenty‐five patients were prospectively enrolled for combined ESS/BET. The control group (25 patients) underwent ESS alone. Outcome measurements of the Sinonasal Outcome Test 22, modified Lund–Kennedy score, Eustachian Tube Dysfunction Questionnaire‐7 (ETDQ‐7), and serial Eustachian tube function test results were analyzed 3 months postoperatively. Results: The improvement (12.60 ± 6.50) in the ETDQ‐7 score in the BET group was significantly higher than that in the control group (6.60 ± 5.58). The ratio of improvement in the ETDQ‐7 score was also significantly higher in the BET than in the control group (92% vs. 68%, p = 0.034). Logistic regression analysis showed that performing BET (odds ratio [OR]: 5.41, 95% confidence interval [CI]: 1.02–28.79, p = 0.048) and a low post‐modified Lund–Kennedy score (OR: 0.15, 95% CI: 0.04–0.54, p = 0.004) were significantly associated with ETDQ‐7 score improvement. Conclusion: Combined BET/ESS could decrease otologic symptoms and improve Eustachian tube function. BET may be an appropriate adjunctive procedure for treating chronic rhinosinusitis with obstructive ETD. [ABSTRACT FROM AUTHOR]

Bladder cancer poses a significant challenge to chemotherapy due to its resistance to cisplatin, especially at advanced stages. Understanding the mechanisms behind cisplatin resistance is crucial for improving cancer therapy. The enzyme glutathione S‐transferase omega class 1 (GSTO1) is known to be involved in cisplatin resistance in colon cancer. This study focused on its role in cisplatin resistance in bladder cancer. Our analysis of protein expression in bladder cancer cells stimulated by secretions from tumor‐associated macrophages (TAMs) showed a significant increase in GSTO1. This prompted further investigation into the role of GSTO1 in bladder cancer. We found a strong correlation between GSTO1 expression and cisplatin resistance. Mechanistically, GSTO1 triggered the release of large extracellular vesicles (EVs) that promoted cisplatin efflux, thereby reducing cisplatin–DNA adduct formation and enhancing cisplatin resistance. Inhibition of EV release effectively counteracted the cisplatin resistance associated with GSTO1. In conclusion, GSTO1‐mediated EV release may contribute to cisplatin resistance caused by TAMs in bladder cancer. Strategies to target GSTO1 could potentially improve the efficacy of cisplatin in treating bladder cancer. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Epithelial‐myoepithelial carcinoma of the breast is an extremely rare biphasic tumor. This report documents the first case of epithelial‐myoepithelial carcinoma presenting in the location of a previously treated ductal carcinoma in order to increase the awareness of this entity as a potential differential for recurrent breast lesions. Epithelial‐myoepithelial carcinoma of the breast is an exceedingly rare biphasic tumor, seldom documented in medical literature. This report describes the first known case of this entity at the site of a previously treated neoplasm in a 75‐year‐old female with a history of high‐grade ductal carcinoma in situ who presented with a new breast mass. Imaging demonstrated an oval shaped mass with microlobulated borders and hypoechoic echogenicity on ultrasound. Following multidisciplinary discussion, she underwent a mastectomy, revealing epithelial‐myoepithelial carcinoma with metaplastic squamous cell carcinoma. The patient began chemotherapy but discontinued due to poor tolerance and neurological complications. Generally, prognosis for epithelial‐myoepithelial carcinoma (World Health Organization Classification of Breast Tumors 2019, 8562/3) is highly variable, with limited available data suggesting that epithelial‐myoepithelial carcinoma may follow a course similar to that of breast adenocarcinomas with both hematogenous and lymphatic spread. Treatment typically involves curative excision, though the role of axillary lymph node sampling remains under discussion. This case underscores the need for vigilance in post‐treatment surveillance for breast cancer and highlights the importance of recognizing this entity in recurrent breast pathology. [ABSTRACT FROM AUTHOR]

Background: Deep‐learning‐based image reconstruction and noise reduction methods (DLIR) have been increasingly deployed in clinical CT. Accurate image quality assessment of these methods is challenging as the performance measured using physical phantoms may not represent the true performance of DLIR in patients since DLIR is trained mostly on patient images. Purpose: In this work, we aim to develop a patient‐data‐based virtual imaging trial framework and, as a first application, use it to measure the spatial resolution properties of a DLIR method. Methods: The patient‐data‐based virtual imaging trial framework consists of five steps: (1) insertion of lesions into projection domain data using the acquisition geometry of the patient exam to simulate different lesion characteristics; (2) insertion of noise into projection domain data using a realistic photon statistical model of the CT system to simulate different dose levels; (3) creation of DLIR‐processed images from projection or image data; (4) creation of ensembles of DLIR‐processed patient images from a large number of noise and lesion realizations; and (5) evaluation of image quality using ensemble DLIR images. This framework was applied to measure the spatial resolution of a ResNet based deep convolutional neural network (DCNN) trained on patient images. Lesions in a cylindrical shape and different contrast levels (−500, −100, −50, −20, −10 HU) were inserted to the lower right lobe of the liver in a patient case. Multiple dose levels were simulated (50%, 25%, 12.5%). Each lesion and dose condition had 600 noise realizations. Multiple reconstruction and denoising methods were used on all the noise realizations, including the original filtered‐backprojection (FBP), iterative reconstruction (IR), and the DCNN method with three different strength setting (DCNN‐weak, DCNN‐medium, and DCNN‐strong). Mean lesion signal was calculated by performing ensemble averaging of all the noise realizations for each lesion and dose condition and then subtracting the lesion‐present images from the lesion absent images. Modulation transfer functions (MTFs) both in‐plane and along the z‐axis were calculated based on the mean lesion signals. The standard deviations of MTFs at each condition were estimated with bootstrapping: randomly sampling (with replacement) all the DLIR/FBP/IR images from the ensemble data (600 samples) at each condition. The impact of varying lesion contrast, dose levels, and denoising strengths were evaluated. Statistical analysis with paired t‐test was used to compare the z‐axis and in‐plane spatial resolution of five algorithms for five different contrasts and three dose levels. Results: The in‐plane and z‐axis spatial resolution degradation of DCNN becomes more severe as the contrast or radiation dose decreased, or DCNN denoising strength increased. In comparison with FBP, a 59.5% and 4.1% reduction of in‐plane and z‐axis MTF (in terms of spatial frequencies at 50% MTF), respectively, was observed at low contrast (−10 HU) for DCNN with the highest denoising strength at 25% routine dose level. When the dose level reduces from 50% to 12.5% of routine dose, the in‐plane and z‐axis MTFs reduces from 92.1% to 76.3%, and from 98.9% to 95.5%, respectively, at contrast of −100 HU, using FBP as the reference. For most conditions of contrasts and dose levels, significant differences were found among the five algorithms, with the following relationship in both in‐plane and cross‐plane spatial resolution: FBP > DCNN‐Weak > IR > DCNN‐Medium > DCNN‐Strong. The spatial resolution difference among algorithms decreases at higher contrast or dose levels. Conclusions: A patient‐data‐based virtual imaging trial framework was developed and applied to measuring the spatial resolution properties of a DCNN noise reduction method at different contrast and dose levels using real patient data. As with other non‐linear image reconstruction and post‐processing techniques, the evaluated DCNN method degraded the in‐plane and z‐axis spatial resolution at lower contrast levels, lower radiation dose, and higher denoising strength. [ABSTRACT FROM AUTHOR]

Proliferative vitreoretinopathy (PVR) is a visual‐threatening disease, which cause from the migration of retinal pigment epithelium (RPE). Tricetin, a family of flavonoids, can inhibit the metastasis of several cancers. Herein, we aim to evaluate the possible effect of tricetin on inhibiting ARPE‐19 cells migration. The Boyden chamber assay, wound healing assay, RNA sequencing, and Western blot analysis were applied in our experiment. The results revealed that tricetin inhibited the cell migration abilities of ARPE‐19 cells. Moreover, using RNA sequencing technology, we revealed that tricetin repressed bone morphogenetic protein‐6 (BMP‐6) gene expressions in ARPE‐19 cells. Overexpression of BMP‐6 resulted in significant restoration of cell migration capabilities of tricetin‐treated ARPE‐19 cells. Furthermore, tricetin suppressed the phosphorylation of the p38 signaling pathway. Moreover, blocking the p38 pathway also inhibits BMP‐6 expression and migration in the ARPE‐19 cells. In conclusion, this study revealed that tricetin inhibits the ARPE‐19 cell migration mainly via the suppression of BMP‐6 expression and p38 signaling pathway. [ABSTRACT FROM AUTHOR]

Background: To identify genotypes associated with neovascular age‐related macular degeneration (nAMD) and investigate the associations between genotype variations and anti‐vascular endothelial growth factor (VEGF) treatment response. Methods: This observational, retrospective, case series study enrolled patients diagnosed with nAMD who received anti‐VEGF treatment in National Taiwan University Hospital with at least one‐year follow‐up between 2012 and 2020. A genome‐wide association study (GWAS) was conducted on enrolled patients and controls. Correlations between the genotypes identified from GWAS and the treatment response of functional/anatomical biomarkers, including visual acuity (VA), presence of intraretinal or subretinal fluid (SRF), serous or fibrovascular pigmented epithelium detachment (PED), and disruption of the ellipsoid zone (EZ), were analysed. Results: In total, 182 patients with nAMD and 1748 controls were enrolled. GWAS revealed 16 single nucleotide polymorphisms (SNPs) as risk loci for nAMD, including seven loci in CFH and ARMS2/HTRA1 and nine novel loci, including rs117517872 and rs79835234(COPB2‐DT), rs7525578(RAP1A), rs2123738(LOC105376755), rs1374879(CNTN3), rs3812692(SAR1A), rs117501587(PRKCA), rs9965945(CNDP1), and rs189769231(MATK). Our study revealed rs800292(CFH), rs11200638(HTRA1), and rs2123738(LOC105376755) correlated with poor treatment response in VA (P = 0.005), SRF (P = 0.044), and fibrovascular PED (P = 0.007), respectively. Rs9965945(CNDP1) was correlated with poor response in disruption of EZ (P = 0.046) and serous PED (P = 0.049). Conclusions: Among the 16 SNPs found in the GWAS, four loci—CFH, ARMS2/HTRA1, and two novel loci—were correlated with the susceptibility of nAMD and anatomical/functional responses after anti‐VEGF treatment. [ABSTRACT FROM AUTHOR]

Background: While surgery remains the primary treatment for oral squamous cell carcinoma (OCSCC), induction chemotherapy (IC) can be used as a bridging or neoadjuvant therapy. This nationwide study in Taiwan examines the survival outcomes of OCSCC patients who received IC before surgery. Methods: We analyzed data from 29,891 patients with OCSCC. Of these, 29,058 initially underwent surgery (OP group), whereas 833 received IC before surgery (IC + OP group). A propensity score (PS)‐matched analysis (4, 1 ratio, 3260 vs. 815 patients) was performed considering tumor subsite, sex, age, Charlson comorbidity index, clinical T1–T4b tumors, clinical N0–3 disease, and clinical stage I–IV. Results: In the PS‐matched cohort, the 5‐year disease‐specific survival (DSS) and overall survival (OS) rates were 65% and 57%, respectively. When comparing the OP and IC + OP groups, the 5‐year DSS rates were 66% and 62%, respectively (p = 0.1162). Additionally, the 5‐year OS rates were 57% and 56%, respectively (p = 0.9917). No significant intergroup differences in survival were observed for specific subgroups with cT4a tumors, cT4b tumors, cN3 disease, pT4b tumors, and pN3 disease. However, for patients with pT4a tumors, the OP group demonstrated superior 5‐year outcomes compared to the IC + OP group, with a DSS of 62% versus 52% (p = 0.0006) and an OS of 53% versus 44% (p = 0.0060). Notably, patients with cT2–3, cN1, and c‐Stage II disease in the IC + OP group were significantly more likely to achieve pT0–1 status (p < 0.05). Conclusions: Following PS matching, the IC + OP group generally exhibited similar prognosis to the OP group. However, for pT4a tumors, the OP group showed superior 5‐year outcomes. While IC may not universally improve survival, it could be advantageous for patients who respond positively to the treatment. [ABSTRACT FROM AUTHOR]

Vulnerable atherosclerotic plaque rupture, the leading cause of fatal atherothrombotic events, is associated with an increased risk of mortality worldwide. Peroxisome proliferator–activated receptor delta (PPARδ) has been shown to modulate vascular smooth muscle cell (SMC) phenotypic switching, and, hence, atherosclerotic plaque stability. Melatonin reportedly plays a beneficial role in cardiovascular diseases; however, the mechanisms underlying improvements in atherosclerotic plaque vulnerability remain unknown. In this study, we assessed the role of melatonin in regulating SMC phenotypic switching and its consequential contribution to the amelioration of atherosclerotic plaque vulnerability and explored the mechanisms underlying this process. We analyzed features of atherosclerotic plaque vulnerability and markers of SMC phenotypic transition in high‐cholesterol diet (HCD)–fed apolipoprotein E knockout (ApoE−/−) mice and human aortic SMCs (HASMCs). Melatonin reduced atherosclerotic plaque size and necrotic core area while enhancing collagen content, fibrous cap thickness, and smooth muscle alpha‐actin positive cell coverage on the plaque cap, which are all known phenotypic characteristics of vulnerable plaques. In atherosclerotic lesions, melatonin significantly decreased the synthetic SMC phenotype and KLF4 expression and increased the expression of PPARδ, but not PPARα and PPARγ, in HCD‐fed ApoE−/− mice. These results were subsequently confirmed in the melatonin‐treated HASMCs. Further analysis using PPARδ silencing and immunoprecipitation assays revealed that PPARδ plays a role in the melatonin‐induced SMC phenotype switching from synthetic to contractile. Collectively, we provided the first evidence that melatonin mediates its protective effect against plaque destabilization by enhancing PPARδ‐mediated SMC phenotypic switching, thereby indicating the potential of melatonin in treating atherosclerosis. [ABSTRACT FROM AUTHOR]

Sepsis causes systemic inflammatory responses and acute lung injury (ALI). Despite modern treatments, sepsis‐related ALI mortality remains high. Aqueous extract of Descuraniae Semen (AEDS) exerts anti‐endoplasmic reticulum (ER) stress, antioxidant and anti‐inflammatory effects. AEDS alleviates inflammation and oedema in ALI. Sodium‐potassium‐chloride co‐transporter isoform 1 (NKCC1) is essential for regulating alveolar fluid and is important in ALI. The NKCC1 activity is regulated by upstream with‐no‐lysine kinase‐4 (WNK4) and STE20/SPS1‐related proline/alanine‐rich kinase (SPAK). This study aimed to investigate the effects of AEDS on lipopolysaccharide (LPS)‐induced ALI model in A549 cells, considering the regulation of ER stress, WNK4‐SPAK‐NKCC1 cascades, inflammation and apoptosis. Cell viability was investigated by the CCK‐8 assay. The expressions of the proteins were assessed by immunoblotting analysis assays. The levels of pro‐inflammatory cytokines were determined by ELISA. The expression of cytoplasmic Ca2+ in A549 cells was determined using Fluo‐4 AM. AEDS attenuates LPS‐induced inflammation, which is associated with increased pro‐inflammatory cytokine expression and activation of the WNK4‐SPAK‐NKCC1 pathway. AEDS inhibits the WNK4‐SPAK‐NKCC1 pathway by regulating of Bcl‐2, IP3R and intracellular Ca2+. WNK4 expression levels are significantly higher in the WNK4‐overexpressed transfected A549 cells and significantly decrease after AEDS treatment. AEDS attenuates LPS‐induced inflammation by inhibiting the WNK4‐SPAK‐NKCC1 cascade. Therefore, AEDS is regarded as a potential therapeutic agent for ALI. [ABSTRACT FROM AUTHOR]

Background: Blood transfusion (BT) may be associated with an increased risk of thromboembolism. The associations between transfusion reactions (TRs) during BTs and potential risk factors for the development of thromboembolism in patients underwent blood transfusion have not been analyzed. Therefore, this study aimed to compare risk factors associated with the development of venous thromboembolism (VTE) or pulmonary embolism (PE) between patients underwent blood transfusion with and without TRs. Study Designs and Methods: The retrospective study was conducted between April 1, 2017, and March 31, 2020, at a medical center in Taiwan. Blood‐transfused patients were grouped into two cohorts as follows: those who experienced TRs and those who did not experience TRs. Both cohorts were subjected to follow‐up until March 31, 2021. The endpoints for both groups were the occurrence of VTE or PE or the date of March 31, 2021. To investigate between‐cohort risk differences, a Kaplan–Meier survival analysis and multiple Cox proportional hazard model was used. Results: A total of 10,759 patients underwent 59,385 transfusion procedures, with 703 patients in the TR group, and 10,056 patients in the non‐TR group. The risk of VTE or PE was twice as high in the TR group than in the non‐TR group (adjusted hazard ratio 2.53, 95% confidence interval 1.49–4.29, p =.001). Meanwhile, age, female sex, transfusion frequency increment, and being nondiabetic was associated with an increased risk of developing thromboembolism. Conclusion: TRs are associated with increased long‐term thromboembolism risk in patients underwent blood transfusion. It is imperative for clinicians to acknowledge this and maintain rigorous follow‐up. [ABSTRACT FROM AUTHOR]

In this study, three novel star‐shaped small molecules HYC‐oF, HYC‐mF, and HYC‐H are designed and synthesized and are applied in perovskite solar cells (PSCs) as efficient hole‐transporting materials (HTMs). Compared with non‐fluorinated HYC‐H, F‐substituted analogs HYC‐oF and HYC‐mF exhibited enhanced hole mobility, suitable energy level alignment, improved interfacial contact and hole extraction/transport capability, better passivation effect, as well as increased hydrophobicity. PSC fabrication by spin‐coating this series of HYC‐oF, HYC‐mF, and HYC‐H molecules on a bar‐coated perovskite layer yielded PCEs values of 19.64%, 18.38%, and 16.98%, respectively. In order to realize a fully scalable PSC preparation process, sequential coating of HYC‐oF layer on perovskite layer all by thermal‐assisted bar‐coating (TABC) method was carried out on 10 × 10 cm2 area. The TABC‐based HYC‐oF layer had a compact and uniform morphology with full surface coverage on the TABC‐based perovskite film. Under optimized condition, the PSCs fabricated from such film exhibited a PCE of 18.49% as compared with a lower power conversion efficiency (PCE) of 17.51% from the reference cell using TABC‐based spiro‐OMeTAD. This work demonstrates the potential of fluorinated star‐shaped cyclopenta[2,1‐b;3,4‐b′]dithiophene (CPDT)‐based molecule as HTM for achieving efficient PSC in both small and large scale. [ABSTRACT FROM AUTHOR]

The ability to deliver drugs with precise dosages at specific time points can significantly improve disease treatment while reducing side effects. Drug encapsulation for gradual delivery has opened the doors for a superior treatment regimen. To expand on this ability, programming bioelectronic devices to deliver small molecules enables ad‐hoc personalized therapeutic profiles that are more complex than gradual release. Here, a wearable bioelectronic device with an integrated electrophoretic ion pump that affords on‐demand drug delivery with precise dose control is introduced. Delivery of fluoxetine to wounds in mice result in a 27.2% decrease in the macrophage ratio (M1/M2) and a 39.9% increase in re‐epithelialization, indicating a shorter inflammatory phase and faster overall healing. Programmable drug delivery using wearable bioelectronics in wounds introduces a broadly applicable strategy for the long‐term delivery of a prescribed treatment regimen with minimal external intervention. [ABSTRACT FROM AUTHOR]

Carbonic anhydrase 8 (CA8) is a member of the α‐carbonic anhydrase family but does not catalyze the reversible hydration of carbon dioxide. In the present study, we examined the effects of CA8 on two human colon cancer cell lines, SW480 and SW620, by suppressing CA8 expression through shRNA knockdown. Our results showed that knockdown of CA8 decreased cell growth and cell mobility in SW620 cells, but not in SW480 cells. In addition, downregulated CA8 resulted in a significant decrease of glucose uptake in both SW480 and SW620 cells. Interestingly, stable downregulation of CA8 decreased phosphofructokinase‐1 expression but increased glucose transporter 3 (GLUT3) levels in SW620 cells. However, transient downregulation of CA8 fails to up‐regulate GLUT3 expression, indicating that the increased GLUT3 observed in SW620‐shCA8 cells is a compensatory effect. In addition, the interaction between CA8 and GLUT3 was evidenced by pull‐down and IP assays. On the other hand, we showed that metformin, a first‐line drug for type II diabetes patients, significantly inhibited cell migration of SW620 cells, depending on the expressions of CA8 and focal adhesion kinase. Taken together, our data demonstrate that when compared to primary colon cancer SW480 cells, metastatic colon cancer SW620 cells respond differently to downregulated CA8, indicating that CA8 in more aggressive cancer cells may play a more important role in controlling cell survival and metformin response. CA8 may affect glucose metabolism‐ and cell invasion‐related molecules in colon cancer, suggesting that CA8 may be a potential target in future cancer therapy. Significance statement: This study demonstrates that when compared to primary colon cancer SW480 cells, metastatic colon cancer SW620 cells respond differently to downregulated CA8, indicating that CA8 in more aggressive cancer cells may play a more important role in controlling cell survival and metformin response. [ABSTRACT FROM AUTHOR]

We aimed to investigate the association between air pollution and advanced fibrosis among patients with metabolic associated fatty liver disease (MAFLD) and chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. A total of 1376 participants who were seropositive for HBV surface antigen (HBsAg) or antibodies to HCV (anti‐HCV) or had abnormal liver function in a community screening program from 2019 to 2021 were enrolled for the assessment of liver fibrosis using transient elastography. Daily estimates of air pollutants (particulate matter ≤2.5 μm in diameter [PM2.5], nitrogen dioxide [NO2], ozone [O3] and benzene) were aggregated into mean estimates for the previous year based on the date of enrolment. Of the 1376 participants, 767 (52.8%) and 187 (13.6) had MAFLD and advanced fibrosis, respectively. A logistic regression analysis revealed that the factors associated with advanced liver fibrosis were HCV viremia (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.05–4.77; p < 0.001), smoking (OR, 1.79; 95% CI, 1.16–2.74; p = 0.01), age (OR, 1.04; 95% CI, 1.02–1.05; p < 0.001) and PM2.5 (OR, 1.10; 95% CI, 1.05–1.16; p < 0.001). Linear regression analysis revealed that LSM was independently correlated with PM2.5 (β: 0.134; 95% CI: 0.025, 0.243; p = 0.02). There was a dose‐dependent relationship between different fibrotic stages and the PM2.5 level (the PM2.5 level in patients with fibrotic stages 0, 1–2 and 3–4: 27.9, 28.4, and 29.3 μg/m3, respectively; trend p < 0.001). Exposure to PM2.5, as well as HBV and HCV infections, is associated with advanced liver fibrosis in patients with MAFLD. There was a dose‐dependent correlation between PM2.5 levels and the severity of hepatic fibrosis. [ABSTRACT FROM AUTHOR]

SUMMARY: Plants and bacteria have distinct pathways to synthesize the bioactive vitamin B1 thiamin diphosphate (TDP). In plants, thiamin monophosphate (TMP) synthesized in the TDP biosynthetic pathway is first converted to thiamin by a phosphatase, which is then pyrophosphorylated to TDP. In contrast, bacteria use a TMP kinase encoded by ThiL to phosphorylate TMP to TDP directly. The Arabidopsis THIAMIN REQUIRING2 (TH2)‐encoded phosphatase is involved in TDP biosynthesis. The chlorotic th2 mutants have high TMP and low thiamin and TDP. Ectopic expression of Escherichia coli ThiL and ThiL‐GFP rescued the th2‐3 mutant, suggesting that the bacterial TMP kinase could directly convert TMP into TDP in Arabidopsis. These results provide direct evidence that the chlorotic phenotype of th2‐3 is caused by TDP rather than thiamin deficiency. Transgenic Arabidopsis harboring engineered ThiL‐GFP targeting to the cytosol, chloroplast, mitochondrion, or nucleus accumulated higher TDP than the wild type (WT). Ectopic expression of E. coli ThiL driven by the UBIQUITIN (UBI) promoter or an endosperm‐specific GLUTELIN1 (GT1) promoter also enhanced TDP biosynthesis in rice. The pUBI:ThiL transgenic rice accumulated more TDP and total vitamin B1 in the leaves, and the pGT1:ThiL transgenic lines had higher TDP and total vitamin B1 in the seeds than the WT. Total vitamin B1 only increased by approximately 25–30% in the polished and unpolished seeds of the pGT1:ThiL transgenic rice compared to the WT. Nevertheless, these results suggest that genetic engineering of a bacterial vitamin B1 biosynthetic gene downstream of TMP can enhance vitamin B1 production in rice. Significance Statement: Introducing a bacterial gene encoding thiamin monophosphate kinase into Arabidopsis and rice creates an additional route for thiamin diphosphate biosynthesis and increases vitamin B1 contents. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is one of the leading causes of death worldwide and has a high prevalence. Insulin‐like growth factor‐II receptor α (IGF‐IIRα) acts as a stress‐inducible negative regulator. This study focused on the substantial impact of heightened expression of IGF‐IIRα in cardiac myoblasts and its association with the exacerbation of cardiac dysfunction. Using lipopolysaccharide (LPS)‐induced H9c2 cardiac myoblasts as a model for sepsis, we aimed to elucidate the molecular interactions between IGF‐IIRα and LPS in exacerbating cardiac injury. Our findings demonstrated a synergistic induction of cardiac inflammation and hypertrophy by LPS stimulation and IGF‐IIRα overexpression, leading to decreased cell survival. Excessive calcineurin activity, triggered by this combined condition, was identified as a key factor exacerbating the negative effects on cell survival. Cellular changes such as cell enlargement, disrupted actin filaments, and upregulation of hypertrophy‐related and inflammation‐related proteins contributed to the overall hypertrophic and inflammatory responses. Overexpression of IGF‐IIRα also exacerbated apoptosis induced by LPS in H9c2 cardiac myoblasts. Inhibiting calcineurin in LPS‐treated H9c2 cardiac myoblasts with IGF‐IIRα overexpression effectively reversed the detrimental effects, reducing cell damage and mitigating apoptosis‐related cardiac mechanisms. Our study suggests that under sepsis‐like conditions in the heart with IGF‐IIRα overexpression, hyperactivation of calcineurin worsens cardiac damage. Suppressing IGF‐IIRα and calcineurin expression could be a potential intervention to alleviate the impact of the illness and improve cardiac function. [ABSTRACT FROM AUTHOR]

Oxidative stress is a pivotal factor in the pathogenesis of various cardiovascular diseases. Rhodiola, a traditional Chinese medicine, is recognized for its potent antioxidant properties. Salidroside, a phenylpropanoid glycoside derived from Rhodiola rosea, has shown remarkable antioxidant capabilities. This study aimed to elucidate the potential protective mechanisms of Rhodiola and salidroside against H2O2‐induced cardiac apoptosis in H9c2 cardiomyoblast cells. H9c2 cells were exposed to H2O2 for 4 h, and subsequently treated with Rhodiola or salidroside for 24 h. Cell viability and apoptotic pathways were assessed. The involvement of insulin‐like growth factor 1 receptor (IGF1R) and the activation of extracellular regulated protein kinases 1/2 (ERK1/2) were investigated. H2O2 (100 μM) exposure significantly induced cardiac apoptosis in H9c2 cells. However, treatment with Rhodiola (12.5, 25, and 50 μg/mL) and salidroside (0.1, 1, and 10 nM) effectively attenuated H2O2‐induced cytotoxicity and apoptosis. This protective effect was associated with IGF1R‐activated phosphorylation of ERK1/2, leading to the inhibition of Fas‐dependent proteins, HIF‐1α, Bax, and Bak expression in H9c2 cells. The images from hematoxylin and eosin staining and immunofluorescence assays also revealed the protective effects of Rhodiola and salidroside in H9c2 cells against oxidative damage. Our findings suggest that Rhodiola and salidroside possess antioxidative properties that mitigate H2O2‐induced apoptosis in H9c2 cells. The protective mechanisms involve the activation of IGF1R and subsequent phosphorylation of ERK1/2. These results propose Rhodiola and salidroside as potential therapeutic agents for cardiomyocyte cytotoxicity and apoptosis induced by oxidative stress in heart diseases. Future studies may explore their clinical applications in cardiac health. [ABSTRACT FROM AUTHOR]