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Abstract Background Evaluating outcome reliability is critical in real-world evidence studies. Overall survival is a common outcome in these studies; however, its capture in real-world data (RWD) sources is often incomplete and supplemented with linked mortality information from external sources. Conflicting recommendations exist for censoring overall survival in real-world evidence studies. This simulation study aimed to understand the impact of different censoring methods on estimating median survival and log hazard ratios when external mortality information is partially captured. Methods We used Monte Carlo simulation to emulate a non-randomized comparative effectiveness study of two treatments with RWD from electronic health records and linked external mortality data. We simulated the time to death, the time to last database activity, and the time to data cutoff. Death events after the last database activity were attributed to linked external mortality data and randomly set to missing to reflect the sensitivity of contemporary real-world data sources. Two censoring schemes were evaluated: (1) censoring at the last activity date and (2) censoring at the end of data availability (data cutoff) without an observed death. We assessed the performance of each method in estimating median survival and log hazard ratios using bias, coverage, variance, and rejection rate under varying amounts of incomplete mortality information and varying treatment effects, length of follow-up, and sample size. Results When mortality information was fully captured, median survival estimates were unbiased when censoring at data cutoff and underestimated when censoring at the last activity. When linked mortality information was missing, censoring at the last activity date underestimated the median survival, while censoring at the data cutoff overestimated it. As missing linked mortality information increased, bias decreased when censoring at the last activity date and increased when censoring at data cutoff. Conclusions Researchers should consider the completeness of linked external mortality information when choosing how to censor the analysis of overall survival using RWD. Substantial bias in median survival estimates can occur if an inappropriate censoring scheme is selected. We advocate for RWD providers to perform validation studies of their mortality data and publish their findings to inform methodological decisions better.

Abstract Background Previous studies have reported reduced acute exacerbation rates and improved symptom control in asthma patients treated using inhaled corticosteroids plus formoterol maintenance and reliever therapy (MART). Fluticasone furoate (FF) and vilanterol (VIL) also provide rapid bronchodilation and sustained anti-inflammatory effects, however no studies have investigated FF/VIL as MART for asthma control. Methods From October 1, 2021 to September 30, 2023, this retrospective study included asthma patients classified as step 3 or 4 according to the Global Initiative for Asthma guidelines, who were then divided into two groups. One group received BUD/FOR as MART, while the other received FF/VIL as MART. Pulmonary function tests, exacerbation rates, Asthma Control Test (ACT), fractional exhaled nitric oxide (FeNO) levels, and blood eosinophil counts were measured before and after 12 months of treatment. Results A total of 161 patients were included, of whom 36 received BUD/FOR twice daily as MART, and 125 received FF/VIL once daily as MART. After 12 months of treatment, the FF/VIL group showed a significant increase in ACT scores by 1.57 (p

In this study, polylactic acid (PLA) and thermoplastic polyurethane (TPU) were used to fabricate composite materials with different raster orientations by a 3D printing process. The idea of this study came from the fact that in nature, many plants have vertical or horizontal lines on their leaves or branches. The authors made use of the composite material of a material structure under a thermal effect to achieve the material concept. Finally, their characteristics were observed by applying a thermal effect, tensile tests (to evaluate toughness), and a dynamic mechanical analysis (tan [delta] to evaluate energy absorption). After a thermal effect (temperature) from a heat source was applied, it was found that the material exhibited negative Poisson's ratio (NPR) characteristic. A single material with two layers on 0[degrees] raster orientation of a material in this study had the maximum tan [delta] (energy absorption), an NPR, and toughness regardless of the kind of material. Among the composite materials, 0[degrees] raster orientation of them also had a larger NPR, and the absolute value of Poisson's ratio decreased as the temperature increased. Highlights * The innovative two-layer composite material fabricated by 3D printing. * The material characteristics with various raster orientations are discussed. * PLA0 has the largest tan [delta], toughness, and negative Poisson's ratio. KEYWORDS 3D printing, additive manufacturing, composite material, energy absorption, negative Poisson's ratio, raster orientation, thermal effect, 1 | INTRODUCTION Three-dimensional (3D) printing is a method of additive manufacturing (AM); it is also called rapid prototyping (RP) because it can quickly fabricate good finished products. The stereolithographic [...]

Background: The placement of immediate dental implants intrinsically displays crestal gaps, which may compromise implant osseointegration. Several grafting materials have been used to overcome this issue. Of the available materials, the use of bone cement is relatively new in oral implantology. This study aimed to examine the available literature on the utilization of bone cements in immediate placement of dental implants and assess its potential in oral implantology. Objectives: To synthesize evidence for appraising the impact of bone cements on implant stability and bone-to-implant contact (BIC) of dental implants placed immediately after extraction in humans and animals after 3 months of healing from tooth extraction. Methods: A systematic search was conducted in PubMed, Medline, and ScienceDirect for relevant studies published from inception to September 2021 using relevant search terms. Of the 1624 studies, 4 were selected for this systematic review. Results: Three of the four studies concluded that bone cements enhanced implant stability and/or BIC with better quality and/or quantity of bone surrounding the immediate dental implant. The conclusion drawn by one article remained indecisive. Meta-analysis could not be performed owing to the presence of substantial heterogeneity. Conclusion: Bone cement is a promising treatment alternative as it augments implant stability and/or BIC in immediate dental implants. Nonetheless, further prospective human clinical trials are required to establish its clinical effectiveness and arrive at a definitive conclusion to recommend its clinical use.

Abstract Background Cardiorespiratory fitness (CRF) could reduce the risk of metabolic syndrome (MetS) while the association between muscular endurance capacity (MEC) and incident MetS has rarely been investigated in young adults. Methods A total of 2890 military men and women, aged 18–39 years, free of baseline MetS in Taiwan, were followed for incident MetS from baseline (2014) until the end of 2020. All subjects received annual health examinations for assessment of MetS. Physical fitness was assessed by CRF (estimated maximal oxygen uptake, VO2 max [mL/kg/min], in a 3000‐m run) and MEC (numbers of 2‐min push‐ups). MetS was defined according to the International Diabetes Federation (IDF) criteria. Multiple Cox regression analysis was conducted with adjustments for baseline age, sex, substance use status and physical activity to determine the associations of CRF and MEC with incidences of new‐onset MetS and related features, for example, central obesity, hypertension, dyslipidaemia and prediabetes or diabetes. To examine the combined effects of CRF and MEC status on incidence of MetS, high and low levels of CRF and MEC were separately defined by over and under the sex‐specific median in each exercise test. Results During a median follow‐up of 5.8 years, there were 673 (23.3%) new‐onset MetS. Higher CRF was associated with a lower incidence of MetS (hazard ratio [HR] and 95% confidence interval: 0.905 [0.877–0.933]), and its components separately, except hypertension. No association was observed between MEC and incident MetS, and its components separately, except hypertension. When evaluating the combined effects of MEC and CRF status on the incidence of MetS, it was observed that compared with the low CRF/low MEC, the high CRF/high MEC (HR: 0.553 [0.439–0.697]) and the high CRF/low MEC (HR: 0.730 [0.580–0.918]) had a lower incidence of new‐onset MetS (P value for the intergroup difference = 0.04). There was no significant result for the low CRF/high MEC. Conclusions This study highlights that although the protective effects of MEC to reduce the incidence of MetS and most of its related features were mainly driven by CRF in young adults, there was an addictive effect of greater MEC on CRF to prevent the development of new‐onset MetS before midlife.

Abstract Background Epithelial cell adhesion molecule (EpCAM) has been widely studied as a tumor antigen due to its expression in varieties of solid tumors. Moreover, the glycoprotein contributes to critical cancer-associated cellular functionalities via its extracellular (EpEX) and intracellular (EpICD) domains. In colorectal cancer (CRC), EpCAM has been implicated in the Wnt signaling pathway, as EpICD and β-Catenin are coordinately translocated to the nucleus. Once in the nucleus, EpICD transcriptionally regulates EpCAM target genes that; however, remains unclear whether Wnt signaling is modulated by EpICD activity. Methods Patient-derived organoids (PDOs), patient-derived xenografts (PDXs), and various CRC cell lines were used to study the roles of EpCAM and EpICD in Wnt receptor expression. Fluorescence and confocal microscopy were used to analyze tumors isolated from PDX and other xenograft models as well as CRC cell lines. EpCAM signaling was intervened with our humanized form of EpCAM neutralizing antibody, hEpAb2-6. Wnt receptor promoters under luciferase reporters were constructed to examine the effects of EpICD. Luciferase reporter assays were performed to evaluate promoter, γ-secretase and Wnt activity. Functional assays including in vivo tumor formation, organoid formation, spheroid and colony formation experiments were performed to study Wnt related phenomena. The therapeutic potential of EpCAM suppression by hEpAb2-6 was evaluated in xenograft and orthotopic models of human CRC. Results EpICD interacted with the promoters of Wnt receptors (FZD6 and LRP5/6) thus upregulated their transcriptional activity inducing Wnt signaling. Furthermore, activation of Wnt-pathway-associated kinases in the β-Catenin destruction complex (GSK3β and CK1) induced γ-secretase activity to augment EpICD shedding, establishing a positive-feedback loop. Our hEpAb2-6 antibody blocked EpICD-mediated upregulation of Wnt receptor expressions and conferred therapeutic benefits in both PDX and orthotopic models of human CRC. Conclusions This study uncovers relevant functions of EpCAM where Wnt receptors are upregulated via the transcriptional co-factor activity of EpICD. The resultant enhancement of Wnt signaling induces γ-secretase activity further stimulating EpICD cleavage and its nuclear translocation. Our humanized anti-EpCAM antibody hEpAb2-6 blocks these mechanisms and may thereby provide therapeutic benefit in CRC.

The genus Lucasioides Kwon, 1993 (Isopoda: Oniscidea: Agnaridae) occurs in Asia, but confined only to China, Japan, Korea, and Russian Siberia. The ambiguously morphological differences among some members of the genus make a dilemma: the species recognition, whether morphologically similar or different, is uncertain. In this paper, we present first morphometric and molecular data for the genus from a broad sample. DNA sequences (mitochondrial COI, nuclear 18S rRNA, 28S rRNA, and NaK) were generated and integrated with morphological evidence to reveal the cryptic species and delimit the new species within the genus. Seven species are described as new to science: Lucasioides digitatus sp. nov., L. dissectus sp. nov., L. dianensis sp. nov., L. formosus sp. nov., L. gracilentus sp. nov., L. schmidti sp. nov. and L. subcurvatus sp. nov. To date, Lucasioides species from China are 44.4% as many as all the known congeners worldwide, showing the exceptional species diversity of Lucasioides species from China. The results demonstrate that the integrative taxonomy is especially important to reveal the cryptic species among the high morphological similarity of taxa, as well as providing an effective way for species identification to accelerate the exploration of woodlice biodiversity.

Background/purpose: Periodontitis is associated with various systemic diseases, potentially facilitated by the passage of Porphyromonas gingivalis outer membrane vesicles (Pg-OMVs). Several recent studies have suggested a connection between Pg-OMVs and neuroinflammation and neurodegeneration, but the precise causal relationship remains unclear. This study aimed to investigate the mechanisms underlying these associations using in vitro models. Materials and methods: Isolated Pg-OMVs were characterized by morphology, size, and gingipain activity. We exposed SH-SY5Y neuroblastoma cells and BV-2 microglial cells to various concentrations of Pg-OMVs. Cell morphology, a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, an enzyme-linked immunosorbent assay, and Western blot analysis were used to evaluate the cellular mechanism underlying Pg-OMV-induced neurotoxicity in neuronal cells and inflammatory responses in microglial cells. Results: Exposure to Pg-OMVs induced neurotoxicity in SH-SY5Y cells, as evidenced by cellular shrinkage, reduced viability, activation of apoptotic pathways, and diminished neuronal differentiation markers. Gingipain inhibition mitigated these effects, suggesting that gingipain mediates Pg-OMVs-induced neurotoxicity in SH-SY5Y cells. Our research on neuroinflammation suggests that upon endocytosis of Pg-OMVs by BV-2 cells, lipopolysaccharide (LPS) can modulate the production of inducible nitric oxide synthase and tumor necrosis factor-alpha by activating pathways that involve phosphorylated AKT and the phosphorylated JNK pathway. Conclusion: Our study demonstrated that following the endocytosis of Pg-OMVs, gingipain can induce neurotoxicity in SH-SY5Y cells. Furthermore, the Pg-OMVs-associated LPS can trigger neuroinflammation via AKT and JNK signaling pathways in BV-2 cells.

BackgroundGlobally, the increasing use of digital technologies such as mobile phones and the internet has allowed for the development of innovative mobile health interventions, particularly for reaching and engaging with youth. However, there is a risk that using such technologies may exclude those who lack access to them. ObjectiveIn this study, we investigated the sociodemographic factors associated with mobile phone ownership, internet use, and social media use among youth in Zimbabwe. MethodsA population-based prevalence survey was conducted in 24 urban and periurban communities across 3 provinces of Zimbabwe (Harare, Mashonaland East, and Bulawayo). Youths aged 18 to 24 years resident in randomly selected households in the study communities completed an interviewer-administered questionnaire. The primary outcomes were mobile phone ownership and current internet and social media use. A household wealth indicator was developed using principal components analysis, based on household asset ownership. Multivariable logistic regression was used to investigate the factors associated with each primary outcome. Age, sex, and province were considered a priori confounders. Household wealth, marital status, education level, employment status, time lived at current address, and HIV status were included in the final multivariable model if there was an age-, sex-, and province-adjusted association with a primary outcome on univariable analysis at a significance level of P

Drowning, as a leading cause of unintentional injury-related deaths worldwide, is a major public health concern. Swimming pool drowning is the main cause of most drowning incidents, and even with preventive measures such as surveillance cameras and lifeguards, tens of thousands of lives are lost to drowning every year. To address this issue, technology is being utilized to prevent drowning accidents and provide timely alerts for rescue. This paper explores the use of drowning prevention technology in embedded systems within enclosed environments, artificial intelligence (AI), and the Internet of Things (IoT) to decrease the likelihood of drowning incidents. Embedded systems play a critical role in such technology, enabling real-time monitoring, identification of dangerous situations, and prompt alerting. Due to their ease of installation and technical implementation, embedded devices are especially effective as drowning prevention devices. The image recognition capabilities of drowning prevention systems are enhanced through computer vision. Swimming pool drowning situations can be identified with the help of cameras and deep learning technologies, thereby increasing rescue efficiency. Finally, the IoT endows drowning prevention systems with comprehensive intelligence by connecting various devices and communication tools. Real-time alert transmission and analysis have become possible, enabling the early prediction of dangerous situations and the implementation of preventive measures, significantly reducing drowning incidents. In summary, the integration of these three types of drowning prevention technologies represents significant progress. The flexibility, accuracy, and intelligence of drowning prevention systems are enhanced through the incorporation of these technologies, providing robust support for safeguarding human lives and thus potentially saving tens of thousands of lives each year.

BackgroundThis study evaluates tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interferon-γ-induced protein-10 (IP-10) in pregnant women with COVID-19 and their newborns, exploring the effects of antiviral treatments and vaccine-induced neutralizing antibody (Nab) inhibition on these key viral infection biomarkers.MethodsWe studied 61 pregnant women with past COVID-19 and either three (n=56) or four (n=5) doses of vaccination, and 46 without COVID-19 but vaccinated. We analyzed them and their newborns’ blood for TRAIL, IP-10, and Nab levels using enzyme-linked immunosorbent assays (ELISA), correlating these with other clinical factors.ResultsOur study found lower TRAIL but higher IP-10 levels in maternal blood than neonatal cord blood, irrespective of past COVID-19 diagnosis. Cases diagnosed with COVID-19 < 4 weeks previously had higher maternal blood TRAIL levels (16.49 vs. 40.81 pg/mL, p=0.0064) and IP-10 (154.68 vs. 225.81 pg/mL, p=0.0170) than those never diagnosed. Antiviral medication lowered TRAIL and IP-10 in maternal blood without affecting Nab inhibition (TRAIL: 19.24 vs. 54.53 pg/mL, p=0.028; IP-10: 158.36 vs. 255.47 pg/mL, p=0.0089). TRAIL and IP-10 levels were similar with three or four vaccine doses, but four doses increased Nab inhibition (p=0.0363). Previously COVID-19 exposed pregnant women had higher Nab inhibition (p < 0.0001). No obvious correlation was found among TRAIL, IP-10, and Nab inhibition level.ConclusionsOur study suggests that lower maternal TRAIL and higher IP-10 levels compared to neonatal cord blood coupled with a rise in both markers following COVID-19 diagnosis that could be reduced by antivirals indicates a correlation to infection severity. Higher vaccine doses enhance Nab inhibition, irrespective of antiviral medication use and independent of TRAIL or IP-10 levels, highlighting the significance and safety of adequate vaccination and antiviral use post-diagnosis in pregnant women.

Prostate cancer rarely metastasizes to the stomach and kidneys. We report a 73-year-old male with such spread, highlighting significant clinical challenges. Initially diagnosed via biopsy and imaging, he received hormone therapy and cytoreductive radical prostatectomy. Despite initial management, the cancer progressed to metastatic castration-resistant prostate cancer, with gastric and renal metastases confirmed by imaging and biopsy. This case emphasizes the need for awareness of rare metastatic sites, comprehensive diagnostic evaluations, and further research into these atypical metastases to improve patient outcomes and develop better treatment strategies for managing advanced prostate cancer effectively.

The association between metal mixtures and kidney function has been reported. However, reports on the mechanism of metal toxicity were limited. Oxidative stress was reported as a possible cause. This study aimed to determine the association between of kidney function and metals, such as arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), lead (Pb), selenium (Se), and zinc (Zn), and to explore the possible mediating role of tumor necrosis factor alpha (TNF-α) between metal toxicity and kidney function. In this study, we recruited 421 adults from a health examination. The concentration of blood metals was analyzed using inductively coupled plasma mass spectrometry. We used linear regression models to assess the association between metals and TNF-α. Then, mediation analysis was applied to investigate the relationship between metal exposure, TNF-α, and kidney function. In univariate linear regression, blood As, Cd, Co, Cu, Pb, and Zn levels significantly increased TNF-α and decreased kidney function. Higher blood As and Pb levels significantly increased TNF-α in multivariable linear regressions after adjusting for covariates. We found that blood levels of As (coefficients = −0.021, p = 0.011), Pb (coefficients = −0.060, p < 0.001), and Zn (coefficients = −0.230, p < 0.001) showed a significant negative association with eGFR in the multiple-metal model. Furthermore, mediation analysis showed that TNF-α mediated 41.7 %, 38.8 %, and 20.8 % of blood Cd, As and Pb, respectively. Among the essential elements, TNF-α mediated 24.5 %, 21.5 % and 19.9 % in the effects of blood Co, Cu, and Zn on kidney function, respectively. TNF-α, acting as a mediator, accounted for 20.1 % of the contribution between the WQS score of metal mixtures and the eGFR (p

Abstract Rationale The prevalence, clinical characteristics, and outcomes of invasive pulmonary aspergillosis in patients with severe community-acquired pneumonia (CAP) in intensive care units remain underestimated because of the lack of a disease-recognition scheme and the inadequacy of diagnostic tests. Objectives To identify the prevalence, risk factors, and outcomes of severe CAP complicated with invasive pulmonary aspergillosis (IPA) in intensive care units (ICUs). Methods We conducted a retrospective cohort study including recruited 311 ICU-hospitalized patients with severe CAP without influenza or with influenza. Bronchoalveolar lavage fluid (BALF) samples were from all patients and subjected to mycological testing. Patients were categorized as having proven or probable Aspergillus infection using a modified form of the AspICU algorithm comprising clinical, radiological, and mycological criteria. Measurements and main results Of the 252 patients with severe CAP and 59 influenza patients evaluated, 24 met the diagnostic criteria for proven or probable Aspergillus infection in the CAP group and 9 patients in the influenza group, giving estimated prevalence values of 9.5% and 15.3%, respectively. COPD and the use of inhaled corticosteroids were independent risk factors for IPA. IPA in patients with severe CAP was significantly associated with the duration of mechanical support, the length of ICU stay, and the 28-day mortality. Conclusions An aggressive diagnostic approach for IPA patients with severe CAP and not only influenza or COVID-19 should be pursued. Further randomized controlled trials need to evaluate the timing, safety, and efficacy of antifungal therapy in reducing IPA incidence and improving clinical outcomes.

Abstract Background Non-insulin-based insulin resistance (NI-IR) indices have been reported to have an association with prevalent hypertension, however, no cohort studies to date have compared their prediction of hypertension among young adults. Methods A total of 2,448 military men and women, aged 18–39 years, without baseline hypertension in Taiwan were followed for incident hypertension events from 2014 until the end of 2020. All subjects underwent annual health examinations including measurements of blood pressure (BP) in mmHg. Systolic BP (SBP) 130–139/diastolic BP (DBP)

Background/purpose: It is unclear about whether the oral health has impact on physical performance. Therefore, this study aimed to examine the association between oral health and physical performance in 300 military adults in Taiwan. Materials and methods: Oral health was assessed by the presence of periodontitis and dental caries. The status of cardiorespiratory and muscular endurance capacity was respectively assessed by tertiles of time for a 3000-m run and 2-min push-up numbers. Multivariable logistic and linear regression analyses with adjustments for age, smoking, alcohol drinking, blood pressure, anthropometric variables, lipid profile, fasting glucose and physical activity were used to determine the association. Results: Participants with periodontitis were more likely to have worse 3000-m running performance classified in the lowest tertile [odds ratio (OR) and 95% confidence interval: 1.94 (1.03, 3.66)]. Participants with any dental caries were more likely to have worse push-ups performance classified in the lowest tertile [OR: 2.50 (1.27, 4.92)]. In linear regression analyses, dental caries numbers were inversely correlated with 2-min push-ups numbers [β = −1.04 (−2.07, −0.01)]. Conclusion: This study suggests that oral health is crucial to maintain physical fitness, and dental caries and periodontitis may affect differently on aerobic and muscular endurance capacities.