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Care transitions among high-intensity units caring for patients with complex needs are a critical yet undeveloped area of patient safety research. In addition, effective communication and coordination across disciplines remain elusive. This study introduces and tests the Multi-Team Shared Expectations Tool (MT-SET), an exercise that aims to engage health care teams in eliciting needs and establishing agreed-upon expectations teams and individuals within a multi-team system have of one another. We piloted the exercise within hospital-based workflows for oncology inpatients and later adopted it to elicit data on mutual needs and expectations of teams across units involved in patient transitions in two patient safety projects. Our studies demonstrated that the exercise identified common cross-unit coordination problems of delays in care, unwanted variations in care, and lack of standardized communication among units. It also revealed mismatched prioritization of each of these problems between specific unit types. The participants reported that the MT-SET helped establish positive relationships for building better cross-unit and cross-disciplinary teamwork and coordination. There is a need for systematic approaches to understand and facilitate cross-unit communication and coordination in care delivery and transitions. Future studies should broaden the application of the exercise to additional types of multi-unit and multidisciplinary teams and observe intervention ideas generated from the exercise, as well as their implementation.

Joint diseases greatly impact the daily lives and occupational functioning of patients globally. However, conventional treatments for joint diseases have several limitations, such as unsatisfatory efficacy and side effects, necessitating the exploration of more efficacious therapeutic strategies. Mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have demonstrated high therapeutic efficacyin tissue repair and regeneration, with low immunogenicity and tumorigenicity. Recent studies have reported that EVs-based therapy has considerable therapeutic effects against joint diseases, including osteoarthritis, tendon and ligament injuries, femoral head osteonecrosis, and rheumatoid arthritis. Herein, we review the therapeutic potential of various types of MSC-EVs in the aforementioned joint diseases, summarise the mechanisms underlying specific biological effects of MSC-EVs, and discuss future prospects for basic research on MSC-EV-based therapeutic modalities and their clinical translation. In general, this review provides an in-depth understanding of the therapeutic effects of MSC-EVs in joint diseases, as well as the underlying mechanisms, which may be beneficial to the clinical translation of MSC-EV-based treatment.

Feature selection, an essential technique in data mining, is often confined to batch learning or online idealization of data scenarios despite its significance. Existing online feature selection methods have specific assumptions regarding the data stream, such as requiring a fixed feature space with an explicit pattern and complete labeling of samples. Unfortunately, data streams generated in many real scenarios commonly exhibit arbitrarily incomplete feature spaces and scarcity labels, making existing approaches unsuitable for real applications. To fill these gaps, this study proposes a new problem called Online Feature Selection with Varying Features Spaces (OFSVF). OFSVF has a three-fold main idea: 1) it leverages Gaussian Copula to model the incomplete feature correlation in a complete latent space, encoded by continuous variables, 2) it employs a novel tree-ensemble-based approach to select the most informative features on-the-fly, and 3) it develops the underlying geometric structure of instances to establish the relationship between unlabeled and labels. Experimental results are documented to demonstrate the feasibility and effectiveness of our proposed method.

Nd3+ ion-doped ZnO nanomaterial was prepared using chemical synthesis method and its fluorescence spectra have been investigated at room temperature. From SEM images of the synthesized ZnO: Nd3+ nanoparticles it is observed that an increase in concentration of Nd3+ ions leading to the decrease in the particle size. Nearly hexagonal shapes for the dark spots in the SAED images indicate that the ZnO nanoparticles are almost hexagonal. The oscillator strengths leading to 4f ↔ 4f transitions are characterized by different Judd-Ofelt intensity parameters Ωλ (λ = 2, 4 and 6). These Ωλ parameters along with the fluorescence data and various radiative properties viz., spontaneous emission probability (A), radiative life time (t), fluorescence branching ratio (b) and stimulated emission cross-section (sp) were evaluated and compared with the reported values. The values of these parameters indicate that the observed transitions 4F3/2 → 4I11/2, 4F3/2 → 4I13/2 and 4F3/2 → 4I15/2 can be considered to be good laser transitions in the near infrared region for different optoelectronic and spintronic uses.

Purpose: Radiotherapy (RT) is a commonly employed therapeutic strategy for the treatment of localized cancers, including prostate cancer (PCa). Despite significant advancements in radiotherapy technology over recent years, high recurrence and metastasis of PCa after RT remain critical challenges. Various mechanisms have been implicated in how cancer evades radiotherapy, and exosomes, a type of extracellular vesicles (EVs) has recently been identified as one of the contributing factors. This study aimed to investigate whether exosomes derived from irradiated PCa cells are involved in the cancer progression and to identify possible key factor in this process. Methods: Exosomes were isolated from irradiated or non-irradiated PCa cell lines (designated as Rad-Exo or Exo) and characterized by specific marker expression, morphology and size. PCa cells treated with Rad-Exo or Exo were analyzed for the effects of proliferation, specific gene expression, migration and cancer stem cell property. Differential protein expression in Rad-Exo and Exo were carried out by mass spectrometry. Results: Results showed that, compared to Exo, Rad-Exo treatment inhibited cell proliferation but significantly promoted migration and elevated the expression of genes related to epithelial to mesenchymal transition. Additionally, cells treated with Rad-Exo showed increased expression of genes related to cancer stem cells. Mass spectrometry identified POTEE as more abundant within Rad-Exo then in Exo, and its expression was confirmed to be elevated in PCa cells following irradiation. Furthermore, POTEE expression increased in cells after Rad-Exo treatment. Conclusion: This study suggests that exosomes derived from irradiated PCa cells may function as a driver of cancer progression, including recurrent or metastatic cancer. Also, exosomal POTEE may serve as a potential target for future therapeutic or diagnostic investigations in prostate cancer.

The comprehensive process of laser peening (LP) for forming and fatigue strengthening of 6005A-T6 integral stiffened structure (ISS) was investigated. The formation characteristics of ISS under the accumulation of multiple pulse lasers were emphasized. The stress distribution, microstructure response, and phase evolution of the LPed region and deformation region were analyzed. The fatigue crack propagation mode and the mechanism for extending fatigue life were revealed. The results demonstrate that a scanning method perpendicular to the target forming direction achieves better forming effects. For specimens scanned in unfold direction scanning, chord direction scanning, and unfold-chord directions, compressive stresses at the bottom of stiffeners are −87 MPa, −134 MPa, and −169 MPa, respectively. The overall bending elongation forming combined with local impact plastic deformation induced by LP refines surface grains, while slightly elongating those in the deformation region through compression. LP enhances the solid solubility of alloy elements, while residual compressive stress (RCS) does not significantly influence the dissolution of the second phase. The fatigue extension percentages for three specimens are 33.9%, 17.3%, and 43.5%, respectively. The increase in grain boundary density of refined grains impedes crack propagation, while RCS that brings materials on both sides of the crack tip closer together induces deviation from the original crack path. Under RCS, micropores and microcracks are closed to prevent further propagation. Fatigue striations propagate simultaneously parallel and perpendicular to the surface, and the multi-level dimple structure consisting of “large dimples containing small dimples” suppresses crack propagation.

The development of low-cost and efficient photocatalysts to achieve water splitting to hydrogen (H2) is highly desirable but remains challenging. Herein, we design and synthesize two porous polymers (Co–Salen–P and Fe–Salen–P) by covalent bonding of salen metal complexes and pyrene chromophores for photocatalytic H2evolution. The catalytic results demonstrate that the two polymers exhibit excellent catalytic performance for H2generation in the absence of additional noble-metal photosensitizers and cocatalysts. Particularly, the H2generation rate of Co–Salen–P reaches as high as 542.5 μmol g–1h–1, which is not only 6 times higher than that of Fe–Salen–P but also higher than a large amount of reported Pt-assisted photocatalytic systems. Systematic studies show that Co–Salen–P displays faster charge separation and transfer efficiencies, thereby accounting for the significantly improved photocatalytic activity. This study provides a facile and efficient way to fabricate high-performance photocatalysts for H2production.

Colorectal cancer (CRC) is notable for its high mortality and high metastatic characteristics. The shear force generated by bloodstream provides mechanical signals regulating multiple responses of cells, including metastatic cancer cells, dispersing in blood vessels. We, therefore, studied the effect of shear flow on circulating CRC cells in the present study. The CRC cell line SW620 was subjected to shear flow of 12.5 dynes/cm2for 1 and 2 h separately. Resulting elevated caspase‐9 and ‐3 indicated that shear flow initiated the apoptosis of SW620. Enlarged cell size associated with a higher level of cyclin D1 was coincident with the flow cytometric results indicating that the cell cycle was arrested at the G1phase. An elevated phosphor‐eNOSS1177increased the production of nitric oxide and led to reactive oxygen species‐mediated oxidative stress. Shear flow also regulated epithelial–mesenchymal transition (EMT) by increasing E‐cadherin and ZO‐1 while decreasing Snail and Twist1. The migration and invasion of sheared SW620 were also substantially decreased. Further investigations showed that mitochondrial membrane potential was significantly decreased, whereas mitochondrial mass and ATP production were not changed. In addition to the shear flow of 12.5 dynes/cm2, the expressions of EMT were compared at lower (6.25 dynes/cm2) and at higher (25 dynes/cm2) shear flow. The results showed that lower shear flow increased mesenchymal characteristics and higher shear flow increased epithelial characteristics. Shear flow reduces the malignancy of CRC in their metastatic dispersal that opens up new ways to improve cancer therapies by applying a mechanical shear flow device.

Laser powder bed fusion (LPBF) Al–Li alloy technology demonstrates adaptability to the development requirements of structural complexity and functional integration, making it a promising area of research in additive manufacturing for the aerospace, defense industry, and other fields. However, challenges such as microstructure anisotropy and metallurgical defects inevitably arise during the LPBF process of lightweight alloys, significantly impeding further enhancements in their formability properties. Some improvement measures offer a viable solution to enhance the microstructure, mitigate metallurgical defects, and optimize residual stress distribution in additive structures, thereby enabling high–performance Al–Li alloy production by LPBF. This paper first introduces the fundamental principle of LPBF and discusses the process of parameter optimization for LPBF Al–Li alloys. It then describes the typical microstructures and common metallurgical defects of LPBF Al–Li alloys, along with examining the evolution process of microstructures and formation mechanism of metallurgical defects. Specifically, it focuses on discussing the influence of Li element on solidification structure. On this basis, it presents the mechanical properties and anisotropy of mechanical properties for LPBF Al–Li alloys. Afterward, a comprehensive review is provided of the current research status regarding LPBF improvement measures, including powder alloying, heat treatment, and other technologies. Emphasis is placed on improvements in microstructure anisotropy and reductions in metallurgical defects through these improvement measures. Finally, this article summarizes the research progress made in LPBF Al–Li alloys and its improvement measures while also prospecting future research work.

Several studies have suggested a potential correlation between menopause and airflow limitation. However, the presence of protective factors in postmenopausal women remains uncertain. Therefore, our study seeks to examine potential protective factors associated with a reduced prevalence of airflow limitation among postmenopausal women.

The aim of this study was to assess the diagnostic yield and outcomes of intraoperative enteroscopy (IOE) in patients with overt small bowel bleeding in the era of balloon‐assisted enteroscopy and capsule endoscopy. We retrospectively reviewed the medical records of patients with small bowel bleeding who underwent IOE from January 2005 to April 2016 in a tertiary medical center. A total of 18 patients with overt small bowel bleeding who underwent a total 18 IOE procedures were included. The mean amount of blood transfusion was 35.7 units (SD, 21.4 units), and 11 patients had hypovolemic shock. The diagnostic yield of the IOE procedures was 94.4% (17/18). The most common pathologic diagnosis was ulcer. The rebleeding rate was 44.4% (8/18), and the overall survival rate was 61.1% (11/18). IOE remains a valuable tool for diagnosing overt small bowel bleeding. The usage of IOE might potentially be limited due to critical clinical conditions in the era of deep enteroscopy. A specific caution should be taken in performing IOE due to the high morbidity of the procedure.

This study explores the specific language learning strategies (LLS) employed by student-athletes in Higher Education institutions in Taiwan. Given these student-athletes’ challenges in balancing academic and athletic commitments, understanding their adoption of LLS provides valuable pedagogical insights. This quantitative research gathered 150 responses, considering variables such as academic year, gender, duration of English study, and athletic specialization. Our findings indicate a moderate overall LLS usage, with a pronounced preference for metacognitive strategies. Strategies such as watching English shows and actively engaging in conversations were particularly favored. Conversely, kinesthetic and mnemonic approaches were less popular, such as acting out words or using rhymes. Delving deeper into the data, there were limited gender-based differences in LLS adoption. However, athletic specialization significantly influenced LLS preferences. Especially, martial arts or combat sports athletes had the highest LLS mean scores across all categories. These results highlight the distinct LLS preferences among Taiwanese student-athletes and suggest potential pedagogical adaptations to enhance their language learning experiences.

IMPORTANCE: Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking. OBJECTIVE: To evaluate whether dual antiplatelet therapy is superior to single antiplatelet among patients with mild to moderate ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter, open-label, blinded end point, randomized clinical trial conducted at 66 hospitals in China from December 20, 2016, through August 9, 2022. The date of final follow-up was October 30, 2022. The analysis was reported on March 12, 2023. Of 3065 patients with ischemic stroke, 3000 patients with acute mild to moderate stroke within 48 hours of symptom onset were enrolled, after excluding 65 patients who did not meet eligibility criteria or had no randomization outcome. INTERVENTIONS: Within 48 hours after symptom onset, patients were randomly assigned to receive clopidogrel plus aspirin (n = 1541) or aspirin alone (n = 1459) in a 1:1 ratio. MAIN OUTCOMES AND MEASURES: The primary end point was early neurologic deterioration at 7 days, defined as an increase of 2 or more points in National Institutes of Health Stroke Scale (NIHSS) score, but not as a result of cerebral hemorrhage, compared with baseline. The superiority of clopidogrel plus aspirin to aspirin alone was assessed based on a modified intention-to-treat population, which included all randomized participants with at least 1 efficacy evaluation regardless of treatment allocation. Bleeding events were safety end points. RESULTS: Of the 3000 randomized patients, 1942 (64.6%) were men, the mean (SD) age was 65.9 (10.6) years, median (IQR) NIHSS score at admission was 5 (4-6), and 1830 (61.0%) had a stroke of undetermined cause. A total of 2915 patients were included in the modified intention-to-treat analysis. Early neurologic deterioration occurred in 72 of 1502 (4.8%) in the dual antiplatelet therapy group vs 95 of 1413 (6.7%) in the aspirin alone group (risk difference −1.9%; 95% CI, −3.6 to −0.2; P = .03). Similar bleeding events were found between 2 groups. CONCLUSIONS AND RELEVANCE: Among Chinese patients with acute mild to moderate ischemic stroke, clopidogrel plus aspirin was superior to aspirin alone with regard to reducing early neurologic deterioration at 7 days with similar safety profile. These findings indicate that dual antiplatelet therapy may be a superior choice to aspirin alone in treating patients with acute mild to moderate stroke. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02869009

Four ethanol fractionated crude extracts (EFCEs [A-D]) purified from the leaves of Cinnamomum macrostemonHayata were screened for antioxidative effects and mitochondrial function in HaCaT cells. The higher cell viability indicated that EFCE C was mildly toxic. Under the treatment of 50 ng/mL EFCE C, the hydrogen peroxide (H2O2)-induced cytosolic and mitochondrial reactive oxygen species levels were reduced as well as the H2O2-impaired cell viability, mitochondrial membrane potential (MMP), ATP production, and mitochondrial mass. The conversion of globular mitochondria to tubular mitochondria is coincident with EFCE C-restored mitochondrial function. The mitophagy activator rapamycin showed similar effects to EFCE C in recovering the H2O2-impaired cell viability, MMP, ATP production, mitochondrial mass, and also mitophagic proteins such as PINK1, Parkin, LC3 II, and biogenesis protein PGC-1α. We thereby propose the application of EFCE C in the prevention of oxidative stress in skin cells.Graphical AbstractThe ethanol fractionated crude extract C isolated from leaves of Cinnamomum macrostemonHayata showed regulatory effects on antioxidation and mitophagy in keratinocytes.

Healthy lifestyle might alleviate the socioeconomic inequities in health, but the extent of the joint and interactive effects of these two factors on dementia are unclear. This study aimed to detect the joint and interactive associations of socioeconomic status (SES) and lifestyle factors with incident dementia risk, and the underlying brain imaging alterations. Cox proportional hazards analysis was performed to test the joint and interactive associations. Partial correlation analysis was performed to reflect the brain imaging alterations. A total of 276,730 participants with a mean age of 55.9 (±8.0) years old from UK biobank were included. Over 8.5 (±2.6) years of follow-up, 3013 participants were diagnosed with dementia. Participants with high SES and most healthy lifestyle had a significantly lower risk of incident dementia (HR=0.19, 95% CI=0.14 to 0.26, P<2×10−16), Alzheimer’s disease (AD, HR=0.19, 95% CI=0.13 to 0.29, P=8.94×10−15), and vascular dementia (HR=0.24, 95% CI=0.12 to 0.48, P=7.57×10−05) compared with participants with low SES and an unhealthy lifestyle. Significant interactions were found between SES and lifestyle on dementia (P=0.002) and AD (P=0.001) risks; the association between lifestyle and dementia was stronger among those of high SES. The combination of high SES and healthy lifestyle was positively associated with higher volumes in brain regions vulnerable to dementia-related atrophy. These findings suggest that SES and lifestyle significantly interact and influence dementia with its related brain structure phenotypes.

IMPORTANCE: The incidence of brain metastasis is increasing in patients with metastatic breast cancer. Treatments to extend the control of brain metastasis are urgently required. OBJECTIVE: To investigate whether the addition of an induction treatment of bevacizumab, etoposide, and cisplatin (BEEP) improves brain-specific progression-free survival (PFS) after whole-brain radiotherapy (WBRT). DESIGN, SETTING, AND PARTICIPANTS: This open-label, randomized, multicenter clinical trial assessed patients with brain metastases from breast cancer (BMBC) in Taiwan from September 9, 2014, to December 24, 2018, with survival follow-up until December 31, 2021. Key inclusion criteria included metastatic brain tumors not suitable for focal treatment, WBRT naivety, age 20 to 75 years, and at least 1 measurable brain metastatic lesion. The primary end point was brain-specific PFS, with an expected hazard ratio of 0.60, a 2-sided α ≤ .20, and power of 0.8. INTERVENTIONS: Eligible patients were randomly assigned at a ratio of 2:1 to the experimental arm, which involved 3 cycles of BEEP followed by WBRT, or the control arm, which involved WBRT alone. MAIN OUTCOMES AND MEASURES: The primary end point was the determination of brain-specific PFS by local investigators according to the Response Evaluation Criteria in Solid Tumors, version 1.1, the initiation of other brain-directed treatment after WBRT, or death. Other key end points included brain-specific objective response rate after 8 weeks of BEEP treatment or WBRT and 8-month brain-specific PFS rate, PFS, and overall survival. RESULTS: A total of 118 patients with BMBC were randomized, with the intention-to-treat cohort comprising 112 patients. The median age was 56 years (range, 34-71 years), and 61 patients (54.5%) had ERBB2 (formerly HER2 or HER2/neu)-positive disease. The median (range) brain-specific PFS was 8.1 (0.3-29.5) vs 6.5 (0.9-25.5) months in the experimental and control arms, respectively (hazard ratio, 0.71; 95% CI, 0.44-1.13; P = .15; significant at predefined α ≤ .20). The brain-specific objective response rate at 2 months was not significantly different (BEEP treatment vs WBRT, 41.9% vs 52.6%), but the 8-month brain-specific PFS rate was significantly higher in the experimental group (48.7% vs 26.3%; P = .03). Adverse events were generally manageable with prophylactic granulocyte colony-stimulating factor treatment. CONCLUSIONS AND RELEVANCE: The findings show that induction BEEP before WBRT may improve the control of BMBC compared with using upfront WBRT, which could address an unmet need for an effective systemic treatment for intractable brain and extracranial metastases from metastatic breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02185352

One of the major challenges in preventing glaucoma progression is patient compliance with medication regimens. Since conventional ophthalmic dosage forms have numerous limitations, researchers have been intensively working on developing polymers-based delivery systems for glaucoma drugs. Specifically, research and development efforts have increased using polysaccharide polymers such as sodium alginate, cellulose, β-cyclodextrin, hyaluronic acid, chitosan, pectin, gellan gum, galactomannans for sustained release to the eye to overcome treatment challenges, showing promise in improving drug release and delivery, patient experience, and treatment compliance. In the recent past, multiple research groups have successfully designed sustained drug delivery systems, promoting the efficacy as well as the feasibility of glaucoma drugs with single/combinations of polysaccharides to eliminate the drawbacks associated with the glaucoma treatment. Naturally available polysaccharides, when used as drug vehicles can increase the retention time of eye drops on the ocular surface, leading to improved drug absorption and bioavailability. Additionally, some polysaccharides can form gels or matrices that can release drugs slowly over time, providing sustained drug delivery and reducing the need for frequent dosing. Thus, this review aims to provide an overview of the pre-clinical and clinical studies of polysaccharide polymers applied for glaucoma treatment along with their therapeutic outcomes.

The Extracorporeal Life Support Organization (ELSO) maintains the world’s largest extracorporeal membrane oxygenation (ECMO) registry by volume, center participation, and international scope. This 2022 ELSO Registry Report describes the program characteristics of ECMO centers, processes of ECMO care, and reported outcomes. Neonates (0–28 days), children (29 days–17 years), and adults (≥18 years) supported with ECMO from 2009 through 2022 and reported to the ELSO Registry were included. This report describes adjunctive therapies, support modes, treatments, complications, and survival outcomes. Data are presented descriptively as counts and percent or median and interquartile range (IQR) by year, group, or level. Missing values were excluded before calculating descriptive statistics. Complications are reported per 1,000 ECMO hours. From 2009 to 2022, 154,568 ECMO runs were entered into the ELSO Registry. Seven hundred and eighty centers submitted data during this time (557 in 2022). Since 2009, the median annual number of adult ECMO runs per center per year increased from 4 to 15, whereas for pediatric and neonatal runs, the rate decreased from 12 to 7. Over 50% of patients were transferred to the reporting ECMO center; 20% of these patients were transported with ECMO. The use of prone positioning before respiratory ECMO increased from 15% (2019) to 44% (2021) for adults during the coronavirus disease-2019 (COVID-19) pandemic. Survival to hospital discharge was greatest at 68.5% for neonatal respiratory support and lowest at 29.5% for ECPR delivered to adults. By 2022, the Registry had enrolled its 200,000th ECMO patient and 100,000th patient discharged alive. Since its inception, the ELSO Registry has helped centers measure and compare outcomes across its member centers and strategies of care. Continued growth and development of the Registry will aim to bolster its utility to patients and centers.

Different interfacial structures of diamond/Cu composites were synthesized by varying the boron (B) content. The microstructural, thermal, and mechanical properties of the composites were investigated. The results showed that diamond/Cu−B composites had a high thermal conductivity of 695 W/(m·K) and high bending strength of 535 MPa attributed to the formation of a micron-scale dentate B4C interface structure. The dentate B4C provided dual functions of metallurgical bonding and mechanical meshing for interface bonding. A semi-coherent interface was formed between the diamond and B4C, where the diamond(111) and B4C(104) planes were parallel. The micro/nano-scale dentate structure improved the phonon transmission efficiency and bonding strength at the interface.

Docetaxel‐based chemotherapy has generally been considered as one of the effective treatments for castration‐resistant prostate cancer (PCa). However, clinical treatment with docetaxel often encounters a number of undesirable effects, including drug resistance. Tubulin isoforms have been previously examined for their resistance to docetaxel in many cancers, but their real mechanisms remained unclear. In this study, a series of docetaxel‐resistant PC/DX cell sublines were established by chronically exposing PC3 to progressively increased concentrations of docetaxel. Western blotting results showed significantly higher expression of acetyl‐tubulin, α‐tubulin, β‐tubulin, γ‐tubulin, and βIII‐tubulin in PC/DX25 than in parental PC3 cells. PC/DX25 with greater resistance to docetaxel had higher levels of acetyl‐tubulin and mitotic centromere‐associated kinesin (MCAK) than PC3 cells. This study found that docetaxel induced the expression of acetyl‐tubulin and MCAK in PC3 cells at a dose‐ and time‐dependent manner. Both mRNA and protein levels of histone deacetylase 6 (HDAC6) were significantly decreased in PC/DX25 compared with PC3 cells. PC3 increased the resistance to docetaxel by HDAC6 knockdown and Tubastatin A (HDAC6 inhibitor). Conversely, PC/DX25 reversed the sensitivity to docetaxel by MCAK knockdown. Notably, flow cytometry analysis revealed that MCAK knockdown induced significantly sub G1 fraction in PC/DX cells. Overexpression of polo‐like kinase‐1 increased the cell survival rate and resistance to docetaxel in PC3 cells. Moreover, epidermal growth factor receptor (EGFR) activation induced the upregulation of acetyl‐tubulin in docetaxel‐resistant PCa cells. These findings demonstrated that the EGFR‐mediated upregulated expression of acetyl‐tubulin played an important role in docetaxel‐resistant PCa.

Objectives: The role of autoimmune diseases on the risk for acute epiglottitis remains uncertain. This study aimed to delineate the association between epiglottitis and autoimmune diseases using population database.Methods: A population-based retrospective study was conducted to analyze claims data from Taiwan National Health Insurance Research Database collected over January, 2000, to December, 2013.Results: In total, 2339 patients with epiglottitis were matched with 9356 controls without epiglottitis by sex, age, socioeconomic status, and urbanization level. The correlation between autoimmune diseases and epiglottitis was analyzed by multivariate logistic regression. Compared with controls, patients with epiglottitis were much more likely to have preexisting Sjögren syndrome (adjusted odds ratio [aOR]: 2.37; 95% CI: 1.14-4.91; P= .021). In addition, polyautoimmunity was associated with increased risk of epiglottitis (aOR: 2.08; 95% CI: 1.14-3.80; P= .018), particularly in those aged >50 years (aOR: 2.61; 95% CI: 1.21-5.66; P= .015).Conclusions: Among autoimmune diseases, we verify the association between epiglottitis and Sjögren syndrome in Taiwan. Furthermore, we present the novel discovery that patients with epiglottitis have an increased risk of polyautoimmunity, particularly those aged >50 years.

Olfactory dysfunction is increasingly recognized as an early indicator of Alzheimer’s disease (AD). Aberrations in GABAergic function and the excitatory/inhibitory (E/I) balance within the olfactory bulb (OB) have been implicated in olfactory impairment during the initial stages of AD. While the neuregulin 1 (NRG1)/ErbB4 signaling pathway is known to regulate GABAergic transmission in the brain and is associated with various neuropsychiatric disorders, its specific role in early AD-related olfactory impairment remains incompletely understood. This study demonstrated that olfactory dysfunction preceded cognitive decline in young adult APP/PS1 mice and was characterized by reduced levels of NRG1 and ErbB4 in the OB. Further investigation revealed that deletion of ErbB4 in parvalbumin interneurons reduced GABAergic transmission and increased hyperexcitability in mitral and tufted cells (M/Ts) in the OB, thereby accelerating olfactory dysfunction in young adult APP/PS1 mice. Additionally, ErbB4 deficiency was associated with increased accumulation of Aβ and BACE1-mediated cleavage of APP, along with enhanced CDK5 signaling in the OB. NRG1 infusion into the OB was found to enhance GABAergic transmission in M/Ts and alleviate olfactory dysfunction in young adult APP/PS1 mice. These findings underscore the critical role of NRG1/ErbB4 signaling in regulating GABAergic transmission and E/I balance within the OB, contributing to olfactory impairment in young adult APP/PS1 mice, and provide novel insights for early intervention strategies in AD.

Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 μM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg−1·d−1, i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis.

In this study, we investigated a novel approach to fabricate multifunctional ionic gel sensors by using deep eutectic solvents (DESs) as replacements for water. When two distinct DESs were combined, customizable mechanical and conductive properties were created, resulting in improved performance compared with traditional hydrogel-based strain sensors. DES ionic gels possess superior mechanical properties, transparency, biocompatibility, and antimicrobial properties, making them suitable for a wide range of applications such as flexible electronics, soft robotics, and healthcare. We conducted a comprehensive evaluation of the DES ionic gels, evaluating their performance under extreme temperature conditions (−70 to 80 °C), impressive optical transparency (94%), and biocompatibility. Furthermore, a series of tests were conducted to evaluate the antibacterial performance (Escherichia coli) of the DES ionic gels. Their wide strain (1–400%) and temperature (15–50 °C)-sensing ranges demonstrate the versatility and adaptability of DES ionic gels for diverse sensing requirements. The resulting DES ionic gels were successfully applied in human activity and vital sign monitoring, demonstrating their potential for biointegrated sensing devices and healthcare applications. This study offers valuable insights into the development and optimization of hydrogel sensors, particularly for applications that require environmental stability, biocompatibility, and antibacterial performance, thereby paving the way for future advancements in this field.

Several studies have reported an association between dipeptidyl peptidase 4 inhibitor (DPP4i), a commonly prescribed second‐line oral antihyperglycemic drug, and bullous pemphigoid (BP). However, the benefits of DPP4i withdrawal in patients with BP remain controversial. This study primarily aimed to evaluate the clinical severity of DPP4i‐associated BP by comparing it to those without Type 2 diabetes mellitus (DM). The secondary objective was to determine whether cessation of DPP4i is necessary for all patients with BP. This retrospective case–control study included 83 patients. The participants were divided into three groups according to their diabetic status and the status of discontinuance or continuance of DPP4i. The 12‐month follow‐up of the monthly dosage of systemic steroids per body weight (kg) and the percentage of systemic steroid off‐therapy in these participants were recorded since the diagnosis of BP. Compared to patients with BP without DM, the 1st, 3rd, and 12th systemic prednisolone doses were significantly lower in the DPP4i group (p= 0.01684, 0.02559, and 0.009336, respectively). The 12th systemic prednisolone dose was significantly lower in patients who discontinued DPP4i (p= 0.0338). Nevertheless, several spontaneous remissions with systemic steroid off‐therapy were also noted in the DPP4i‐continuance group within 12 months of follow‐up. This article supports the favorable impact of DPP4i withdrawal in patients with BP and shows that DPP4i may incite or aggravate BP, resulting in a milder disease course.

Owing to the limitation of a large genome size (~13 Gb), the genetic and gene mapping studies on faba bean (Vicia fabaL.) are lagging far behind those for other legumes. In this study, we selected three purified faba bean lines (Yundou 8137, H0003712, and H000572) as parents and constructed two F2populations. These two F2populations, namely 167 F2plants in Pop1 (Yundou 8137×H0003712) and 204 F2plants in Pop2 (H000572×Yundou 8137), were genotyped using a targeted next-generation sequencing (TNGS) genotyping platform, and two high-density single nucleotide polymorphisms (SNP) genetic linkage maps of faba bean were constructed. The map constructed from Pop1 contained 5 103 SNPs with a length of 1 333.31 cM and an average marker density of 0.26 cM. The map constructed from Pop2 contained 1 904 SNPs with a greater length of 1 610.61 cM. In these two F2populations, QTL mapping identified 98 QTLs for 14 agronomic traits related to the flowers, pods, plant types and grains. The two maps were then merged into an integrated genetic linkage map containing 6 895 SNPs, with a length of 3 324.48 cM. These results not only lay the foundation for fine mapping and map-based cloning of related genes, but can also accelerate the molecular marker-assisted breeding of faba bean.

Purpose: The purpose of this study is to address the lack of research on utilizing deep learning for the detection of peripheral artery disease (PAD) wounds. The main objective is to present a novel solution for automatic wound segmentation and detection using the Mask R-CNN framework. Methods: The study utilizes a dataset of 3329 clinical wound images, which includes wounds in patients with PAD as well as general trauma. The Mask R-CNN framework is implemented to detect and differentiate wounds. Results: The results of our approach are remarkable, achieving an Intersection over Union score of 0.69, recall of 0.72, precision of 0.77, F1 score of 0.75, and average precision of 0.71. These metrics demonstrate the accuracy and effectiveness of our proposed framework for wound segmentation and diagnosis. Conclusion: Our innovative approach utilizing the Mask R-CNN framework provides an accurate and efficient solution for the detection and classification of wounds, specifically in patients with PAD. The results highlight the practical applicability of our framework and its potential to improve the clinical healthcare of patients dealing with chronic wounds. This study represents a significant step forward in addressing the challenges of PAD and chronic wounds, opening up exciting possibilities for future research in this field.

Food allergies are becoming more prevalent globally. The purpose of this study was to investigate the epidemiology of food allergies in Taiwan.