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Abstract Background Some studies suggest that female patients have more concerns about receiving intimate care from male than female nurses. Thus, providing intimate care to female patients is a challenging experience for male nurses. The purpose of this study was to explore Chinese male nurses’ experiences and process of providing intimate clinical care to female patients. Methods A constructivist grounded theory approach was used to develop a theoretical understanding of male nurses’ experiences. This study included participants from 3 hospitals in different locations in China. Twenty-five male nurses were recruited using purposive and theoretical sampling. Semi-structured interviews were conducted. Data analysis was completed using initial coding, focused coding, theoretical coding and memo writing to produce core concepts and categories, and theory development. Results Chinese male nurses’ experiences of providing intimate care to female patients can be constructed as a three-stage process: (1) anticipation of the level of embarrassment, (2) deciding on the process: do it or not do it and (3) protecting both parties and dealing with embarrassment. Additionally, seven themes and associated categories were identified to represent the important factors in the process of male nurses providing intimate care to female patients in China. Conclusions Chinese traditional culture may affect the embarrassment in Chinese male nurses providing intimate care to female patients. The embarrassing situation can be divided into three different stages, and male nurses have different main concerns in each stage. Hospital nursing administrators should consider the experiences and needs of male nurses in providing intimate care and provide them with psychological support, education and training.

Background: Ambient particulate matter is classified as a human Class 1 carcinogen, and recent studies found a positive relationship between fine particulate matter (PM2.5) and liver cancer. Nevertheless, little is known about which specific metal constituent contributes to the development of liver cancer. Objective: To evaluate the association of long-term exposure to metal constituents in PM2.5 with the risk of liver cancer using a Taiwanese cohort study. Methods: A total of 13,511 Taiwanese participants were recruited from the REVEAL-HBV in 1991–1992. Participants’ long-term exposure to eight metal constituents (Ba, Cu, Mn, Sb, Zn, Pb, Ni, and Cd) in PM2.5 was based on ambient measurement in 2002–2006 followed by a land-use regression model for spatial interpolation. We ascertained newly developed liver cancer (ie, hepatocellular carcinoma [HCC]) through data linkage with the Taiwan Cancer Registry and national health death certification in 1991–2014. A Cox proportional hazards model was utilized to assess the association between exposure to PM2.5 metal component and HCC. Results: We identified 322 newly developed HCC with a median follow-up of 23.1 years. Long-term exposure to PM2.5 Cu was positively associated with a risk of liver cancer. The adjusted hazard ratio (HR) was 1.13 (95% confidence interval [CI], 1.02–1.25; P = 0.023) with one unit increment on Cu normalized by PM2.5 mass concentration in the logarithmic scale. The PM2.5 Cu-HCC association remained statistically significant with adjustment for co-exposures to other metal constituents in PM2.5. Conclusion: Our findings suggest PM2.5 containing Cu may attribute to the association of PM2.5 exposure with liver cancer.

Water-soluble lignin-carbohydrate complex (LCC) rich in polysaccharides exhibits benign in vitro antioxidant activities and distinguishes high biocompatibility from lignin-rich LCC and lignin. However, the antioxidant activity of water-soluble LCCs remains to be improved and its structure-antioxidant relationship is still uncertain. Herein, structurally diversified water-soluble LCCs were isolated under different ball-milling pretreatment durations (4, 6, 8 h), extraction pathways (homogeneous and heterogeneous), and isolation routines (water extracts and residues after water extraction). Their structures were characterized by wet chemistry, chromatography and spectroscopies. Antioxidant activities were evaluated by ferric reducing antioxidant power and 1,1-diphenyl-2-picrylhydrazyl radicals scavenging rate (RDPPH). Results show that altering ball-milling duration and isolation procedures cause varied structures and antioxidant activities of the water-soluble LCCs. Specifically, prolonging ball-milling duration to 8 hours and homogeneous extraction can enhance their antioxidant activity through releasing more phenolic structures and promoting the extraction of high-molecular-weight LCCs via reducing mass-transfer resistance, respectively. As a result, the RDPPH of water-soluble LCCs reaches up to 97.35%, which is associated with the arabinan content with statistical significance (P < 0.05). This study provides new insights into the structure-antioxidation relationship of herbaceous LCC as potential antioxidants.

Abstract Background A high percentage of cancer patients may experience emotional distress. Oncology nurses are expected to play an important role in recognizing emotional distress and planning and delivering care that meets the individual needs of each patient. However, few studies have focused on the experiences of clinical nurses in such cases. This study adopted a qualitative research method to gain an in-depth understanding of the experience of nursing staff in caring for cancer patients with emotional distress. Methods A qualitative descriptive design and semi-structured interviews were used in this study. Twenty-one oncology nurses were interviewed, and the qualitative content analysis suggested by Graneheim & Lundman (2004) was used to interpret the data. Results Six themes were identified, as follows: (1) dictating the abnormality of emotion, (2) soothing and comforting patients, (3) a lack of psychology knowledge and communication skills, (4) negative impacts of a lack of time, (5) managing emotional labor, and (6) reflecting on the experiences. Conclusion Hospital administrators should arrange pre-employment education and training as well as on-the-job education to help nurses in caring for cancer patients with emotional distress. They should also focus attention on the personal emotional states of nursing staff in a timely manner and provide psychological support and emotional counseling as necessary.

The ongoing COhort for Childhood Origin of Asthma and allergic diseases (COCOA) study is a prospective birth cohort investigating the origin and natural courses of childhood allergic diseases, including atopic dermatitis, food allergy, allergic rhinitis and asthma, with long-term prognosis. Initiated under the premise that allergic diseases result from a complex interplay of immune development alterations, environmental exposures, and host susceptibility, the COCOA study explores these dynamic interactions during prenatal and postnatal periods, framed within the hygiene and microbial hypotheses alongside the developmental origins of health and disease (DOHaD) hypothesis. The scope of the COCOA study extends to genetic predispositions, indoor and outdoor environmental variables affecting mothers and their offsprings such as outdoor and indoor air pollution, psychological factors, diets, and the microbiomes of skin, gut, and airway. We have embarked on in-depth investigations of diverse risk factors and the pathophysiological underpinnings of allergic diseases. By employing multi-omics approaches—proteomics, transcriptomics, and metabolomics—we gain deeper insights into the distinct pathophysiological processes across various endotypes of childhood allergic diseases, incorporating the exposome using extensive resources within the COCOA study. Integration with large-scale datasets, such as national health insurance records, enhances robustness and mitigates potential limitations inherent to birth cohort studies. As part of global networks focused on childhood allergic diseases, the COCOA study fosters collaborative research across multiple cohorts. The findings from the COCOA study are instrumental in informing precision medicine strategies for childhood allergic diseases, underpinning the establishment of disease trajectories.

Amyloid-beta peptide (Aβ) is a neurotoxic constituent of senile plaques in the brains of Alzheimer’s disease (AD) patients. The detailed mechanisms by which protein kinase C-delta (PKCδ) contributes to Aβ toxicity is not yet entirely understood. Using fully differentiated primary rat cortical neurons, we found that inhibition of Aβ25-35-induced PKCδ increased cell viability with restoration of neuronal morphology. Using cyclin D1, proliferating cell nuclear antigen (PCNA), and histone H3 phosphorylated at Ser-10 (p-Histone H3) as the respective markers for the G1-, S-, and G2/M-phases, PKCδ inhibition mitigated cell cycle reentry (CCR) and subsequent caspase-3 cleavage induced by both Aβ25-35 and Aβ1-42 in the post-mitotic cortical neurons. Upstream of PKCδ, signal transducers and activators of transcription (STAT)-3 mediated PKCδ induction, CCR, and caspase-3 cleavage upon Aβ exposure. Downstream of PKCδ, aberrant neuronal CCR was triggered by overactivating cyclin-dependent kinase-5 (CDK5) via calpain2-dependent p35 cleavage into p25. Finally, PKCδ and CDK5 also contributed to Aβ25-35 induction of p53-upregulated modulator of apoptosis (PUMA) in cortical neurons. Together, we demonstrated that, in the post-mitotic neurons exposed to Aβs, STAT3-dependent PKCδ expression triggers calpain2-mediated p35 cleavage into p25 to overactivate CDK5, thus leading to aberrant CCR, PUMA induction, caspase-3 cleavage, and ultimately apoptosis.

Objectives This study aimed to develop a predictive model using polygenic risk score (PRS) to forecast renal outcomes for adult systemic lupus erythematosus (SLE) in a Taiwanese population.Methods Patients with SLE (n=2782) and matched non-SLE controls (n=11 128) were genotyped using Genome-Wide TWB 2.0 single-nucleotide polymorphism (SNP) array. PRS models (C+T, LDpred2, Lassosum, PRSice-2, PRS-continuous shrinkage (CS)) were constructed for predicting SLE susceptibility. Logistic regression was assessed for C+T-based PRS association with renal involvement in patients with SLE.Results In the training set, C+T-based SLE-PRS, only incorporating 27 SNPs, outperformed other models with area under the curve (AUC) values of 0.629, surpassing Lassosum (AUC=0.621), PRSice-2 (AUC=0.615), LDpred2 (AUC=0.609) and PRS-CS (AUC=0.602). Additionally, C+T-based SLE-PRS demonstrated consistent predictive capacity in the testing set (AUC=0.620). Individuals in the highest quartile exhibited earlier SLE onset (39.06 vs 44.22 years, p150 mg/day (OR 2.07, 95% CI 1.49 to 2.89, p

Abstract. Objectives:. To compare mortality rates between patients treated surgically for periprosthetic fractures (PPF) after total hip arthroplasty (THA), total knee arthroplasty (TKA), peri-implant (PI), and interprosthetic (IP) fractures while identifying risk factors associated with mortality following PPF. Design:. Retrospective. Setting:. Single, Level II Trauma Center. Patients/Participants:. A retrospective review was conducted of 129 consecutive patients treated surgically for fractures around a pre-existing prosthesis or implant from 2013 to 2020. Patients were separated into 4 comparison groups: THA, TKA, PI, and IP fractures. Intervention:. Revision implant or arthroplasty, open reduction and internal fixation (ORIF), intramedullary nailing (IMN), percutaneous screws, or a combination of techniques. Main Outcome Measurements:. Primary outcome measures include mortality rates of different types of PPF, PI, and IP fractures at 1-month, 3-month, 6-month, 1-year, and 2-year postoperative. We analyzed risk factors associated with mortality aimed to determine whether treatment type affects mortality. Results:. One hundred twenty-nine patients were included for final analysis. Average follow-up was similar between all groups. The overall 1-year mortality rate was 1 month (5%), 3 months (12%), 6 months (13%), 1 year (15%), and 2 years (22%). There were no differences in mortality rates between each group at 30 days, 90 days, 6 months, 1 year, and 2 years (P-value = 0.86). A Kaplan–Meier survival curve demonstrated no difference in survivorship up to 2 years. Older than 65 years, history of hypothyroidism and dementia, and discharge to a skilled nursing facility (SNF) led to increased mortality. There was no survival benefit in treating patients with PPFs with either revision, ORIF, IMN, or a combination of techniques. Conclusion:. The overall mortality rates observed were 1 month (5%), 3 months (12%), 6 months (13%), 1 year (15%), and 2 years (22%), and no differences were found between each group at all follow-up time points. Patients aged 65 and older with a history of hypothyroidism and/or dementia discharged to an SNF are at increased risk for mortality. From a mortality perspective, surgeons should not hesitate to choose the surgical treatment they feel most comfortable performing. Level of Evidence:. Level III.

Abstract Background Hip fracture can lead to long-term loss of mobility and self-care ability in older adults. Despite initial decreases in functional performance after hip fracture surgery, patients tend to gradually recover. However, recovery can vary, with some regaining their abilities quickly while others becoming functionally dependent. In this study, we investigated whether the level of short-term postoperative decline in activity of daily living (ADL) performance and quality of life (QoL) can predict the 1-year outcomes for both following hip fracture surgery in older Taiwanese adults. Methods This prospective cohort study included 427 older adults (≥ 60 years) who underwent hip fracture surgery at a single tertiary medical center in Taiwan between November 2017 and March 2021. We collected pre-fracture data, including the patients’ demographics, Charlson comorbidity index (CCI) scores, and responses to a questionnaire (Short Portable Mental State Questionnaire [SPMSQ]) for dementia screening. Moreover, their scores on the EuroQol-5D questionnaire (for evaluating QoL) and the Barthel Index (for assessing ADL performance) were collected at pre-fracture status and at 3- and 12-months following surgery. Changes in ADL and QoL three months post-surgery compared to pre-fracture status were evaluated, and the associations of these parameters (and other potential factors) with 1-year outcomes for ADL and QoL were investigated. Results We analyzed the data of 318 patients with hip fracture and complete follow-up data regarding ADL performance and QoL at 3- and 12-months post-surgery. After adjusting for covariates, multivariate linear regression revealed that changes in ADL and QoL at 3 months post-surgery from pre-fracture status were positively and significantly associated with 1-year outcomes for both (p

The amyloid-beta peptide (Aβ) is the neurotoxic component in senile plaques of Alzheimer’s disease (AD) brains. Previously we have reported that Aβ toxicity is mediated by the induction of sonic hedgehog (SHH) to trigger cell cycle re-entry (CCR) and apoptosis in post-mitotic neurons. Basella alba is a vegetable whose polysaccharides carry immunomodulatory and anti-cancer actions, but their protective effects against neurodegeneration have never been reported. Herein, we tested whether polysaccharides derived from Basella alba (PPV-6) may inhibit Aβ toxicity and explored its underlying mechanisms. In differentiated rat cortical neurons, Aβ25-35 reduced cell viability, damaged neuronal structure, and compromised mitochondrial bioenergetic functions, all of which were recovered by PPV-6. Immunocytochemistry and western blotting revealed that Aβ25-35-mediated induction of cell cycle markers including cyclin D1, proliferating cell nuclear antigen (PCNA), and histone H3 phosphorylated at Ser-10 (p-Histone H3) in differentiated neurons was all suppressed by PPV-6, along with mitigation of caspase-3 cleavage. Further studies revealed that PPV-6 inhibited Aβ25-35 induction of SHH; indeed, PPV-6 was capable of suppressing neuronal CCR and apoptosis triggered by the exogenous N-terminal fragment of sonic hedgehog (SHH-N). Our findings demonstrated that, in the fully differentiated neurons, PPV-6 exerts protective actions against Aβ neurotoxicity via the downregulation of SHH to suppress neuronal CCR and apoptosis.

Introduction: Our previous nested-case-control study demonstrated elevated adiponectin increased liver cirrhosis and HCC risk in HBV carriers. We extended the analysis to the whole REVEAL-HBV cohort to prospectively evaluate whether adiponectin directly affected end-stage liver diseases, or through affecting HBV progression. Methods: Baseline plasma adiponectin was determined to investigate the association between adiponectin and subsequent HBeAg, HBsAg, and HBV DNA seroclearance, and the development of cirrhosis, HCC and liver-related death. Whether HBV characteristics modify the adiponectin-milestones associations was also examined. Results: Among 3,931 HBsAg(+)/anti-HCV(−) REVEAL-HBV participants, 3,684 had sufficient biosamples left for adiponectin assay. Elevated adiponectin was associated with a higher chance of HBeAg-seropositive, high HBV viral load (≥2 × 105 IU/mL) and high HBsAg titers (≥1,000 IU/mL) in a dose-response manner (OR = 2.25, 95% CI: 1.55–3.28; OR = 2.11, 95% CI: 1.47–3.04; and OR = 1.92, 95% CI: 1.47–2.52 for Q5 vs. Q1, respectively). Those with the highest quintile had a lower chance of achieving HBeAg (HR = 0.48, 95% CI: 0.27–0.85), HBsAg (HR = 0.69, 95% CI: 0.49–0.97), and HBV DNA seroclearance (HR = 0.63, 95% CI: 0.43–0.90) and a higher chance of developing liver cirrhosis (HR = 2.88, 95% CI: 1.98–4.20, HCC (HR = 2.38, 95% CI: 1.52–3.73), and died from liver-related causes (HR = 2.32, 95% CI: 1.51–3.54). HBV genotype significantly modified the adiponectin-HCC (Pinteraction = 0.005) and adiponectin-liver death associations (Pinteraction = 0.0157), with higher risk among genotype C. Conclusion: Elevated adiponectin is consistently associated with all important chronic HBV infection milestones toward progression to liver cancer. The exact mechanism of how adiponectin mediates HBV infection toward carcinogenesis remains unclear and warrants further investigation. Disentangling this may help us in finding new HBV treatment target, biomarker in HBV surveillance to identify high-risk patients, or even cancer prevention.

Background/Aims Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). Methods Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict three-year HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. Results The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. Conclusions The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.

Background/Aims Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients. Methods We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random-effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment. Results We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88–95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27–0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all P≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, P

Survival analysis is composed of a group of analytical approaches that can be used to predict the occurrence of harvest activities, which provides insightful information about the dynamics of natural resources utilization in a region. Recently, random survival forest (RSF) has been proposed in survival analysis to capture the complex relationships among variables. The main objective of this study was to employ the RSF algorithm to examine the temporal evolution of tree harvest, accounting for stand and environmental variables. Specifically, the predictability of the RSF model was compared with the Cox proportional hazard (Cox) model, a popular model in survival analysis. Important variables in explaining the variation of harvest time were identified. Data collected by the USDA Forest Service, Forest Inventory and Analysis (FIA) program from permanent plots in the southern Appalachian region were utilized in the analysis. Results showed that the RSF model consistently outperformed the Cox model based on prediction accuracy. Among 14 variables examined, ownership, forest type, elevation, state, and slope emerged as most important. Utilizing only these five variables in a reduced model produced satisfactory prediction accuracy compared to the full model (i.e., the models with all variables included). The findings of this work provide insights for forest managers and policy makers to utilize survival analysis methods in understanding harvest activities at the regional scale.

Abstract Background and aims Clinical comparisons of angiotensin receptor–neprilysin inhibitors (ARNI) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) treatment in patients with HFrEF and T2DM are limited. This study evaluated the clinical outcomes and treatment benefits of SGLT2i versus ARNI treatment in patients with HFrEF and T2DM in a large real-world data set. Methods We identified 1487 patients with HFrEF and T2DM who were undergoing ARNI or SGLT2i treatment for the first time (n = 647 and 840, respectively) between January 1, 2016, and December 31, 2021, and with clinical outcomes of CV death, hospitalization for heart failure (HHF), composite CV outcomes, or renal outcomes. Results The HHF risk reduction conferred by SGLT2i treatment was more significant than that conferred by ARNI treatment (37.7% vs. 30.4%; 95% confidence interval [CI] 1.06–1.41). SGLT2i use conferred significantly greater renal protection against the doubling of serum creatinine (13.1% vs. 9.3%; 95% CI 1.05–1.75), an estimated glomerular filtration rate decline of > 50% (24.9% vs. 20.0%; 95% CI 1.02–1.45), and progression to end-stage renal disease (3.1% vs. 1.5%; 95% CI 1.62–5.23). The improvements in echocardiographic parameters were comparable between the groups. Conclusions Compared with ARNI treatment, SGLT2i treatment was associated with a more significant HHF risk reduction and greater preservation of renal function in patients with HFrEF and T2DM. This study also supports the prioritization of SGLT2i use in these patients when patients' conditions or economic resources need to be considered.

Abstract Background To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) have cardiovascular and renal protective effects in patients with advanced diabetic kidney disease (DKD) with an estimated glomerular filtration rate (eGFR)

Fibroblast growth factor 21 (FGF21) plays a crucial role in metabolism and brain function. Glucosamine (GLN) has been recognized for its diverse beneficial effects. This study aimed to elucidate the modulation of FGF21 production by GLN and its impact on learning and memory functions. Using both in vivo and in vitro models, we investigated the effects of GLN on mice fed with a normal diet or high-fat diet and on mouse HT22 hippocampal cells, STHdhQ7/Q7 striatal cells, and rat primary cortical neurons challenged with GLN. Our results indicated that GLN promotes learning and memory functions in mice and upregulates FGF21 expression in the hippocampus, cortex, and striatum, as well as in HT22 cells, STHdhQ7/Q7 cells, and cortical neurons. In animals receiving GLN together with an FGF21 receptor FGFR1 inhibitor (PD173074), the GLN-enhanced learning and memory functions and induction of FGF21 production in the hippocampus were significantly attenuated. While exploring the underlying molecular mechanisms, the potential involvement of NF-κB, Akt, p38, JNK, PKA, and PPARα in HT22 and NF-κB, Akt, p38, and PPARα in STHdhQ7/Q7 were noted; GLN was able to mediate the activation of p65, Akt, p38, and CREB in HT22 and p65, Akt, and p38 in STHdhQ7/Q7 cells. Our accumulated findings suggest that GLN may increase learning and memory functions by inducing FGF21 production in the brain. This induction appears to be mediated, at least in part, through GLN’s activation of the NF-κB, Akt, p38, and PKA/CREB pathways.

Height-diameter relationship models, denoted as H-D models, have important applications in sustainable forest management which include studying the vertical structure of a forest stand, understanding the habitat heterogeneity for wildlife niches, analyzing the growth rate pattern for making decisions regarding silvicultural treatments. Compared to monocultures, characterizing allometric relationships for uneven-aged, mixed-species forests, especially tropical forests, is more challenging and has historically received less attention. Modeling how the competitive interactions between trees of varying sizes and multiple species affects these relationships adds a high degree of complexity. In this study, five regression methods and five distance-independent competition indices were evaluated for temperate and pantropical tree species in different physiographic regions. A total of 163,922 individual tree measurements from the US Department of Agriculture, Forest Inventory and Analysis (FIA) database were used in analyses, which cover Appalachian plateau (AP) and Ridge and Valley (VR) in the southeastern US, as well as Caribbean (CAR) and Pacific (PAC) islands. Results indicated that the generalized additive model (GAM) and the Pearl and Reed model provided more accurate predictions than other regression methods examined. Models with competition indices had a varying level of predictability, while diameter ratio, cumulative distribution function and partitioned stand density index (PSDI) were found to improve the prediction accuracy for AP, VR and CAR. The results of this work provide additional insights on modeling H-D relationships for a variety of species in temperate and pantropical forests.

Abstract Quantifying uncertainty in machine learning is important in new research areas with scarce high-quality data. In this work, we develop an explainable uncertainty quantification method for deep learning-based molecular property prediction. This method can capture aleatoric and epistemic uncertainties separately and attribute the uncertainties to atoms present in the molecule. The atom-based uncertainty method provides an extra layer of chemical insight to the estimated uncertainties, i.e., one can analyze individual atomic uncertainty values to diagnose the chemical component that introduces uncertainty to the prediction. Our experiments suggest that atomic uncertainty can detect unseen chemical structures and identify chemical species whose data are potentially associated with significant noise. Furthermore, we propose a post-hoc calibration method to refine the uncertainty quantified by ensemble models for better confidence interval estimates. This work improves uncertainty calibration and provides a framework for assessing whether and why a prediction should be considered unreliable. Graphical Abstract

Abstract Seroclearance of hepatitis B surface antigen (HBsAg) is regarded as the functional cure for chronic hepatitis B (CHB). The relationship between human leukocyte antigen (HLA) variants, hepatitis B virus genotype, and longitudinal HBsAg serodecline remains to be explored. A total of 1735 HBeAg-seronegative CHB patients with genotype B or C infection of the community-based REVEAL-HBV cohort were genotyped for rs1710 (HLA-G) and rs2770 (HLA-B) using TaqMan assay. Cox proportional hazard regression and generalized linear mixed models were used to analyze the association of HLA genetic variants with the rate of HBsAg seroclearance and longitudinal HBsAg serodecline. Rs1710 G allele was differentially associated with the HBsAg seroclearance in genotype B [aRR (95% CI) = 0.74 (0.56–0.98)] and genotype C [aRR (95%CI) = 1.43 (1.08–1.88)] infection. Rs2770 G allele was associated with HBsAg seroclearance only in genotype B infection [aRR (95% CI) = 0.69 (0.52–0.91)]. The alleles associated with HBsAg seroclearance were significant predictors for the serodecline of HBsAg levels in an HBV genotype-dependent manner (genotype B infection: rs1710, P = 0.013; rs2770, P = 0.0081; genotype C infection: rs1710, P = 0.0452). Our results suggest both spontaneous HBsAg seroclearance and serodecline are modified by the interaction between HLA variants and HBV genotype.

Objective: This article aims to provide the experiences of mindfulness treatments from the perspectives of patients with a history of substance abuse. Data source: Peer-reviewed articles on 5 databases, namely, PubMed, PsychINFO, Medline, CINAHL and the Cochrane Library, between the year of 2000 and 2023. Study Inclusion and Exclusion Criteria: Studies were included if they were published in the English language and reported on qualitative studies that directly engaged patients with experiences of substance abuse and mindfulness treatments. Data extraction: After our initial search, 5355 studies were reviewed by title and abstract, consequently, 10 studies were included. Data synthesis: Meta-ethnography were used in this study. Data were obtained from the quotations from participants and text under the heading “results” or “findings” from the included 10 studies. Results: Effective mindfulness-based interventions (MBI) influence recovery from substance abuse. Four themes were identified as factors influencing the MBI treatment effect. They were (1) engaging in mindfulness: entry and retention, (2) perceived benefits of MBIs, (3) implementation of treatment group and (4) maintenance of treatment effect. Conclusion: This article examines the scientific literature to date and presents the evidence on the factors that influentially impact the effect of MBIs in patients with substance abuse. The findings of this study should be helpful in guiding clinical practice, policy, and future research focused on the treatment effect of MBIs for person with substance use.

Forest variables measurement is indispensable to supervising the dynamic of forest carbon storage. As commonly quantified forest variables, canopy cover (CC), diameter at breast height (DBH), and tree height (TH) were the predicted objects in our study. Recently, remote sensing technology, with high efficiency and wide temporal and spatial coverage, has been extensively used in practice. However, integrating open access satellite resources Sentinel-1 (S1), Sentinel-2 (S2), and Landsat 8 (L8) to quantify forest CC, DBH, and TH has not been extensively examined in the literature. In this study, we explored the potential of individual satellite bands/indices and the integration of different sensors in predicting mean CC, mean DBH, and mean TH in the plots dominated by four tree species (total area 102,887.6 ha). We acquired the satellite patterns of S1, S2, and L8 covered our research plots in 2017, and extracted the mean pixel values of the spectral images for every plot we detected. Specifically, seven sets of features derived from the satellite images of S1, S2, and L8 were used to predict CC, DBH, and TH for the survey plots. The results mainly indicated that group S2 + L8 (RMSEr (the relative root mean square error) = 17.9%, 21.0%, 23.0%) or S2 + L8 + S1 (RMSEr = 17. 8%, 21.0%, 23.1%) achieved the best accuracy for CC, DBH, and TH of all plots. Additionally, group S2 + L8 outperformed the other groups within two sensors and was superior to the individual sensors. Adding S1 synthetic aperture radar (SAR, the sensor carried by S1) had no evident improvement or deviation for most models, nevertheless, numerous bands/indices of SAR occupied important positions in variable importance and were been selected by stepwise regression, which denoted that it is available and valuable for forest parameters of some dominant tree species. Moreover, shortwave infrared (SWIR) bands played a crucial role in the three forest parameters prediction during the rainy season. SWIR bands (RMSEr = 20.5%), NIR bands (RMSEr = 24.1%), and red-edge bands (RMSEr = 27.1%) exerted the most significant implication for predicting CC, DBH, and TH apiece as univariate models. Green bands and NIR also occupied more positions of higher variable importance in multivariate models for estimating DBH and TH, while SWIR took up more for CC in all dominant species. Furthermore, non-parametric models outperformed the parametric model on the whole. In the meanwhile, the best models also were influenced by the data analysis methods.In a nutshell, a combination of multiple satellite sensors was proposed for forest variable selection, especially different optical sensors. SAR data were also inspired to be pitched in related forest measurement work, but it requires some data processing before applying to the research in many cases.

Objective: Previous studies have shown that gabapentin or pregabalin use is associated with cognitive decline. Herein, we aimed to evaluate the association between gabapentin or pregabalin use and the risk of dementia.Methods: In this retrospective, population-based matched cohort study, all research data were collected from the 2005 Longitudinal Health Insurance Database, which contains data of 2 million people randomly selected from the National Health Insurance Research Database of Taiwan in 2005. The study extracted data from 1 January 2000, to 31 December 2017. Adult patients taking gabapentin or pregabalin were included in the exposure group, and patients not using gabapentin or pregabalin matched to exposure subjects in a 1:5 ratio by propensity scores composed of age, sex and index date were included in the non-exposure group.Results: A total of 206,802 patients were enrolled in the study. Of them, 34,467 gabapentin- or pregabalin-exposure and 172,335 non-exposure patients were used for analysis. The mean follow-up day (±standard deviation) after the index date was 1724.76 (±1282.32) and 1881.45 (±1303.69) in the exposure and non-exposure groups, respectively; the incidence rates of dementia were 980.60 and 605.48 per 100,000 person-years, respectively. The multivariate-adjusted hazard ratio of risk of dementia for gabapentin or pregabalin exposure versus the matched non-exposed group was 1.45 (95% confidence interval [CI], 1.36–1.55). The risk of dementia increased with higher cumulative defined daily doses during the follow-up period. Moreover, the stratification analysis revealed that the risk of dementia associated with gabapentin or pregabalin exposure was significant in all age subgroups; however, it was higher in younger patients (age

Abstract Background The obesity paradox, which suggests that high body weight is positively associated with survival in some diseases, has not been proven in patients with hip fracture. In this study, meta-analysis of previous studies on the impacts of body weight on postoperative mortality following hip fracture surgery in older adults was conducted. Methods PubMed, Embase, and Cochrane library were searched for studies investigating the correlation between mortality after hip fracture surgery and body weight. The search main items included: (“Body mass index” OR “BMI” or “body weight”) and (“hip fracture” or “hip fractures”). Studies contained data on short-term (≤ 30-day) and long-term (≥ 1 year) mortality after hip fracture and its association with distinct body weight or BMI groups were reported as full-text articles were included in this meta-analysis. Results Eleven separate studies were included. The definitions of underweight and obesity differed among the included studies, but the majority of the enrolled studies used the average body weight definition of a BMI of 18.5 to 24.9 kg/m2; underweight referred to a BMI of 30 kg/m2. Based on the generalized definitions of body-weight groups from the enrolled studies, the group with obesity had lower long-term (odds ratio [OR]: 0.63, 95% CI: 0.50–0.79, P

Abstract Background Soluble programmed death-1 (sPD-1) is a novel immune markers and possibly predictive of chronic hepatitis B (CHB) outcome. However, results were inconsistent by different ELISA kits. This study aims to compare the characteristics and correlations with other markers for sPD-1 measured by MyBioSource (MB) and R&D (RD) kits. Methods A total of 254 untreated CHB patients from three sites were assayed with sPD-1 by MB and RD kits at the same time. Spearman’s correlations between the kits, and those with viral markers and ALT levels were calculated. Multivariate linear regression analysis was applied for independent factors associated with the sPD-1 levels. Results There’s no correlation between sPD-1 level using MB and RD assays. sPD-1 by MB correlated profoundly with HBsAg (r = 0.8311, P

By employing semi-flexible multi-N donor auxiliary ligands, namely 1,4-bis(5-pyrimidyl)benzene (bpmb) in conjunction with azide, novel Co(II) 2D coordination polymers have been successfully synthesized and structurally characterized, along with magnetic analysis. The resulting compound, {Co(N3)(bpmb)(H2O)2·H2O}n (1), exhibits a unique 2D structure comprised of interconnected Co(II) chains bridged by single end-to-end (EE) azide moieties. These chains are further linked by twisted trans-μ2-N,N′-bpmb auxiliary ligands, forming a grid-like network. Additionally, the layers are held together in a 3D arrangement through hydrogen bonding interactions between the coordination water and the N atom of the bpmb ligands. Importantly, magnetic investigations reveal that compound 1 displays weak ferromagnetism attributed to spin canting, with a critical temperature (Tc) of 12 K.

Abstract Background Huntington’s disease (HD) is a neurodegenerative disorder caused by the expansion of the CAG repeat in the huntingtin (HTT) gene. When the number of CAG repeats exceeds 36, the translated expanded polyglutamine-containing HTT protein (mutant HTT [mHTT]) interferes with the normal functions of many cellular proteins and subsequently jeopardizes important cellular machineries in major types of brain cells, including neurons, astrocytes, and microglia. The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome, which comprises NLRP3, ASC, and caspase-1, is involved in the activation of IL-1β and IL-18 and has been implicated in various biological functions. Although the existence of the NLRP3 inflammasome in the brain has been documented, the roles of the NLRP3 inflammasome in HD remain largely uncharacterized. MCC950 is a highly selective and potent small-molecule inhibitor of NLRP3 that has been used for the treatment of several diseases such as Alzheimer’s disease. However, whether MCC950 is also beneficial in HD remains unknown. Therefore, we hypothesized that MCC950 exerts beneficial effects in a transgenic mouse model of HD. Methods To evaluate the effects of MCC950 in HD, we used the R6/2 (B6CBA-Tg[HDexon1]62Gpb/1J) transgenic mouse model of HD, which expresses exon 1 of the human HTT gene carrying 120 ± 5 CAG repeats. Male transgenic R6/2 mice were treated daily with MCC950 (10 mg/kg of body weight; oral administration) or water for 5 weeks from the age of 7 weeks. We examined neuronal density, neuroinflammation, and mHTT aggregation in the striatum of R6/2 mice vs. their wild-type littermates. We also evaluated the motor function, body weight, and lifespan of R6/2 mice. Results Systematic administration of MCC950 to R6/2 mice suppressed the NLRP3 inflammasome, decreased IL-1β and reactive oxygen species production, and reduced neuronal toxicity, as assessed based on increased neuronal density and upregulation of the NeuN and PSD-95 proteins. Most importantly, oral administration of MCC950 increased neuronal survival, reduced neuroinflammation, extended lifespan, and improved motor dysfunction in R6/2 mice. Conclusions Collectively, our findings indicate that MCC950 exerts beneficial effects in a transgenic mouse model of HD and has therapeutic potential for treatment of this devastating neurodegenerative disease.

Abstract Background Rheumatoid arthritis (RA) and systemic lupus erythematous (SLE) are autoimmune rheumatic diseases that share a complex genetic background and common clinical features. This study’s purpose was to construct machine learning (ML) models for the genomic prediction of RA and SLE. Methods A total of 2,094 patients with RA and 2,190 patients with SLE were enrolled from the Taichung Veterans General Hospital cohort of the Taiwan Precision Medicine Initiative. Genome-wide single nucleotide polymorphism (SNP) data were obtained using Taiwan Biobank version 2 array. The ML methods used were logistic regression (LR), random forest (RF), support vector machine (SVM), gradient tree boosting (GTB), and extreme gradient boosting (XGB). SHapley Additive exPlanation (SHAP) values were calculated to clarify the contribution of each SNPs. Human leukocyte antigen (HLA) imputation was performed using the HLA Genotype Imputation with Attribute Bagging package. Results Compared with LR (area under the curve [AUC] = 0.8247), the RF approach (AUC = 0.9844), SVM (AUC = 0.9828), GTB (AUC = 0.9932), and XGB (AUC = 0.9919) exhibited significantly better prediction performance. The top 20 genes by feature importance and SHAP values included HLA class II alleles. We found that imputed HLA-DQA1*05:01, DQB1*0201 and DRB1*0301 were associated with SLE; HLA-DQA1*03:03, DQB1*0401, DRB1*0405 were more frequently observed in patients with RA. Conclusions We established ML methods for genomic prediction of RA and SLE. Genetic variations at HLA-DQA1, HLA-DQB1, and HLA-DRB1 were crucial for differentiating RA from SLE. Future studies are required to verify our results and explore their mechanistic explanation.

Abstract Background and Aim Chronic hepatitis C virus (HCV) infection, long‐term alcohol use, cigarette smoking, and obesity are the major risk factors for hepatocellular carcinoma (HCC) in the United States, but the disease risk varies substantially among individuals with these factors, suggesting host susceptibility to and gene–environment interactions in HCC. To address genetic susceptibility to HCC, we conducted a genome‐wide association study (GWAS). Methods Two case‐control studies on HCC were conducted in the United States. DNA samples were genotyped using the Illumian microarray chip with over 710 000 single nucleotide polymorphisms (SNPs). We compared these SNPs between 705 HCC cases and 1455 population controls for their associations with HCC and verified our findings in additional studies. Results In this GWAS, we found that two SNPs were associated with HCC at P

Abstract Host immune response and chronic inflammation associated with chronic hepatitis B virus (HBV) infection play a key role in the pathogenesis of liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). We sampled 175 HCC, 117 cirrhotic and 165 non-cirrhotic controls from a prospective cohort study of chronically HBV-infected individuals. Multivariable polytomous logistic regression and canonical discriminant analysis (CDA) were used to compare baseline plasma levels for 102 markers in individuals who developed cirrhosis vs. controls and those who developed HCC vs. cirrhosis. Leave-one-out cross validation was used to generate receiver operating characteristic curves to compare the predictive ability of marker groups. After multivariable adjustment, HGF (Q4v1OR: 3.74; p-trend = 0.0001), SLAMF1 (Q4v1OR: 4.07; p-trend = 0.0001), CSF1 (Q4v1OR: 3.00; p-trend = 0.002), uPA (Q4v1OR: 3.36; p-trend = 0.002), IL-8 (Q4v1OR: 2.83; p-trend = 0.004), and OPG (Q4v1OR: 2.44; p-trend = 0.005) were all found to be associated with cirrhosis development compared to controls; these markers predicted cirrhosis with 69% accuracy. CDA analysis identified a nine marker model capable of predicting cirrhosis development with 79% accuracy. No markers were significantly different between HCC and cirrhotic participants. In this study, we assessed immunologic markers in relation to liver disease in chronically-HBV infected individuals. While validation in required, these findings highlight the importance of immunologic processes in HBV-related cirrhosis.

Abstract The quest for rejuvenation and prolonged lifespan through transfusion of young blood has been studied for decades with the hope of unlocking the mystery of the key substance(s) that exists in the circulating blood of juvenile organisms. However, a pivotal mediator has yet been identified. Here, atypical findings are presented that are observed in a knockin mouse model carrying a lysine to arginine substitution at residue 74 of Krüppel‐like factor 1 (KLF1/EKLF), the SUMOylation‐deficient Klf1K74R/K74R mouse, that displayed significant improvement in geriatric disorders and lifespan extension. Klf1K74R/K74R mice exhibit a marked delay in age‐related physical performance decline and disease progression as evidenced by physiological and pathological examinations. Furthermore, the KLF1(K74R) knockin affects a subset of lymphoid lineage cells; the abundance of tumor infiltrating effector CD8+ T cells and NKT cells is increased resulting in antitumor immune enhancement in response to tumor cell administration. Significantly, infusion of hematopoietic stem cells (HSCs) from Klf1K74R/K74R mice extends the lifespan of the wild‐type mice. The Klf1K74R/K74R mice appear to be an ideal animal model system for further understanding of the molecular/cellular basis of aging and development of new strategies for antiaging and prevention/treatment of age‐related diseases thus extending the healthspan as well as lifespan.

Heartwood, sapwood, and bark constitute the main components of the tree stem. The stem is the main component of the tree and plays an important role in supporting the tree and transporting nutrients and water. Therefore, quantifying the profiles of heartwood, sapwood, and bark is fundamental to understanding the different components of the tree stem. A seemingly unrelated mixed-effect model system was developed based on 179 destructively sampled trees for 31 permanent sample plots in Korean larch plantation in Northeast China. The heartwood radius and sapwood width were estimated and calibrated only by the observed bark thickness or by all response variables considering the correlations of submodel random effects. The results indicated that the model system achieved good fitting performance and prediction. In addition, after including one to ten bark thickness points and all response variables of sampling below the 2 m height of the tree, the estimated best linear predictor (EBLUP) for local calibration improved the prediction performance, indicating that the heartwood radius and sapwood width could be effectively calibrated by bark thickness while keeping intact the complete inner structure inside the stem. The results provided important information for forest managers and ecologists when selecting appropriate approaches for quantifying the profiles of heartwood, sapwood, and bark.

Abstract Breast cancer (BC) incidence is increasing around the globe, including in Taiwan, though the cause of the increasing incidence is less clear. We followed up 11,296 Taiwanese females who did not have BC at baseline, and ascertained new invasive BC (N = 351) through data linkage to the National Cancer Registry from 1991 to 2018 to examine whether reproductive, lifestyle and environmental risk factors including polycyclic aromatic hydrocarbons (PAH) were associated with BC risk. We conducted a nested case–control study using baseline blood available from a total of 305 women with BC and 598 women without BC matched on time in cohort. We examined the association of PAH-albumin adducts and BC risk using conditional logistic regression models. Age at menarche (HR 0.6 (95% CI 0.5–0.9) for ≥ 15 vs.

Summary: The removal of the N-terminal formyl group on nascent proteins by peptide deformylase (PDF) is the most prevalent protein modification in bacteria. PDF is a critical target of antibiotic development; however, its role in bacterial physiology remains a long-standing question. This work used the time-resolved analyses of the Escherichia coli translatome and proteome to investigate the consequences of PDF inhibition. Loss of PDF activity rapidly induces cellular stress responses, especially those associated with protein misfolding and membrane defects, followed by a global down-regulation of metabolic pathways. Rapid membrane hyperpolarization and impaired membrane integrity were observed shortly after PDF inhibition, suggesting that the plasma membrane disruption is the most immediate and primary consequence of formyl group retention on nascent proteins. This work resolves the physiological function of a ubiquitous protein modification and uncovers its crucial role in maintaining the structure and function of the bacterial membrane.

A cluster study to classify atopic dermatitis (AD) phenotypes into subgroups is required to better understand and manage the disease owing to the heterogeneity of its clinical features. This study aimed to identify the phenotypic subgroups of childhood AD according to allergic sensitization. In 258 children with AD, hierarchical cluster analysis based on specific immunoglobulin (Ig) E sensitization revealed four distinct clusters. Cluster A (n = 71) revealed no IgE sensitization, whereas cluster B (n = 28) showed sensitization to egg white only. Cluster B was highly associated with early-onset AD (12 months) and had more atopic comorbidities. In addition, cluster D showed the most severely impaired health-related quality of life and more frequent use of immunosuppressants. Therefore, childhood AD can be classified into 4 clusters based on the allergic sensitization status, and clinical phenotypes and treatment strategy may be different according to clusters.

IntroductionThe lateral habenula (LHb) is an epithalamic nucleus associated with negative valence and affective disorders. It receives input via the stria medullaris (SM) and sends output via the fasciculus retroflexus (FR). Here, we use tractography to reconstruct and characterize this pathway.MethodsMulti-shell human diffusion magnetic resonance imaging (dMRI) data was obtained from the human connectome project (HCP) (n = 20, 10 males) and from healthy controls (n = 10, 6 males) scanned at our institution. We generated LHb afferents and efferents using probabilistic tractography by selecting the pallidum as the seed region and the ventral tegmental area as the output target.ResultsWe were able to reconstruct the intended streamlines in all individuals from the HCP dataset and our dataset. Our technique also aided in identification of the LHb. In right-handed individuals, the streamlines were significantly more numerous in the left hemisphere (mean ratio 1.59 ± 0.09, p = 0.04). In left-handed individuals, there was no hemispheric asymmetry on average (mean ratio 1.00 ± 0.09, p = 1.0). Additionally, these streamlines were significantly more numerous in females than in males (619.9 ± 159.7 vs. 225.9 ± 66.03, p = 0.04).ConclusionWe developed a method to reconstruct the SM and FR without manual identification of the LHb. This technique enables targeting of these fiber tracts as well as the LHb. Furthermore, we have demonstrated that there are sex and hemispheric differences in streamline number. These findings may have therapeutic implications and warrant further investigation.

Background: Exposure to traffic-related pollution is positively associated with cardiovascular diseases (CVD), but little is known about how different sources of traffic pollution (eg, gasoline-powered cars, diesel-engine vehicles) contribute to CVD. Therefore, we evaluated the association between exposure to different types of engine exhaust and CVD mortality. Methods: We recruited 12,098 participants from REVEAL-HBV cohort in Taiwan. The CVD mortality in 2000–2014 was ascertained by the Taiwan Death Certificates. Traffic pollution sources (2005–2013) were based on information provided by the Directorate General of Highway in 2005. Exposure to PM2.5 was based on a land-use regression model. We applied Cox proportional hazard models to assess the association of traffic vehicle exposure and CVD mortality. A causal mediation analysis was applied to evaluate the mediation effect of PM2.5 on the relationship between traffic and CVD mortality. Results: A total of 382 CVD mortalities were identified from 2000 to 2014. We found participants exposed to higher volumes of small car and truck exhausts had an increased CVD mortality. The adjusted hazard ratio (HR) was 1.10 for small cars (95% confidence interval [CI], 0.94–1.27; P-value = 0.23) and 1.24 for truck (95% CI, 1.03–1.51; P-value = 0.03) per one unit increment of the logarithm scale. The findings were still robust with further adjustment for different types of vehicles. A causal mediation analysis revealed PM2.5 had an over 60% mediation effect on traffic-CVD association. Conclusions: Exposure to exhaust from trucks or gasoline-powered cars is positively associated with CVD mortality, and air pollution may play a role in this association.

Abstract Few studies have demonstrated an association of sarcopenia-associated body measurements with chronic diseases through a comprehensive methodology. This study aims to examine the relationship between sarcopenia-associated body measurements and chronic diseases. This is a cohort study. We recruited 316 community dwellers, including 76 patients with sarcopenia and 240 controls, and obtained their body measurements associated with sarcopenia. We collected three-dimensional anthropometric body-surface measurements from 11,158 participants during 2000–2008 and followed up this cohort for 15 years to examine the association of these measurements with the risk of chronic diseases such as hypertension, type 2 diabetes mellitus (T2DM), heart disease, and nephrotic syndrome. Univariate analysis, canonical correlation, and Cox regression analysis were performed to explore the associations. Decreased waist width, upper left arm circumference, and left thigh circumference were significantly associated with sarcopenia. The adverse body measure score (ABMS) was derived by combining significant measurements, namely left upper arm circumference, waist width, and left thigh circumference, and used to predict the risk of hypertension, T2DM, heart diseases, and nephrotic syndrome. A positive association was observed between the ABMS and chronic diseases. Considering the first quartile of the ABMS as a reference, we determined hazard ratios of 2.259, 2.495, 1.332, and 1.595 for hypertension, T2DM, heart disease, and nephrotic syndrome, respectively, in the fourth quartile. Chronic diseases were more strongly associated with the ABMS than with sarcopenia-related body measurements alone. A high ABMS, which includes higher upper arm circumference, higher waist width, and lower thigh circumference, can significantly predict chronic diseases.

Background and Objectives: The relationship between three-dimensional (3D) scanning-derived body surface measurements and biomarkers in patients with coronary artery disease (CAD) were assessed. Methods and Methods: The recruitment of 98 patients with CAD confirmed by cardiac catheterization and 98 non-CAD patients were performed between March 2016 and December 2017. A health questionnaire on basic information, life style variables, and past medical and family history was completed. 3D body surface measurements and biomarkers were obtained. Differences between the two groups were assessed and multivariable analysis performed. Results: It was found that chest width (odds ratio [OR] 0.761, 95% confidence interval [CI] = 0.586–0.987, p = 0.0399), right arm length (OR 0.743, 95% CI = 0.632–0.875, p = 0.0004), waist circumference (OR 1.119, 95% CI = 1.035–1.21, p = 0.0048), leptin (OR 1.443, 95% CI = 1.184–1.76, p = 0.0003), adiponectin (OR 0.978, 95% CI = 0.963–0.994, p = 0.006), and interleukin 6 (OR 1.181, 95% CI = 1.021–1.366, p = 0.0254) were significantly associated with CAD. The combination of biomarker scores and body measurement scores had the greatest area under the curve and best association with CAD (area under the curve of 0.8049 and 95% CI = 0.7440–0.8657). Conclusions: Our study suggests that 3D derived body surface measurements in combination with leptin, adiponectin, and interleukin 6 levels may direct us to those at risk of CAD, allowing a non-invasive approach to identifying high-risk patients.

Background/Purpose: The aim of this study was to evaluate the efficacy of antenatal corticosteroids for preventing very low birth weight (VLBW) infants with respiratory distress syndrome (RDS) from surfactant use at different gestational ages (GA). Methods: We retrospectively analyzed the VLBW preterm infants registered in the Premature Baby Foundation of Taiwan from 1997 through 2014. Infants at 20–37 weeks' gestation were included, and infants with lethal congenital anomaly, chromosomal anomaly, and congenital infection were excluded. Antenatal corticosteroid courses were classified into two groups (

Background: Clostridium difficile infection (CDI) is increasing in children. We aimed to compare the clinical characteristics between CDI and colonization and to identify the risk factors for severe diseases of CDI in children. Method: We retrospectively reviewed 124 children (1–18 years old) from 2011 to 2018. CDI was defined as diarrhea (≥3 loose stool in the past 24 h) with confirmed toxigenic strain. Colonization was defined as presence of C. difficile without clinical symptoms. Severe diseases included ileus, acute kidney injury, gastrointestinal bleeding or mortality. Patients younger than 1 year old and coinfections with other enteric pathogens were excluded. Results: Among 124 patients with C. difficile identified, 49 of them fulfilled CDI definition and 75 had C. difficile colonization. Children with CDI were more likely to present with watery (74% vs. 1%, p

Objectives The microRNAs (miRNAs) are known to be commonly expressed in papillary thyroid carcinoma. The BRAFV600E mutation is the most common genetic mutation in thyroid cancer. The main aim of this study was to determine the possible association between expression of the three miRNAs and that of BRAFV600E mutation and the clinicopathological features in papillary thyroid carcinoma. Methods This study was conducted on 51 paraffin-embedded tissues (42 thyroid cancer, 9 benign tumor) obtained from patients undergoing thyroidectomy at the Endocrine Center of OOO University Hospital. Results miRNAs expression was significantly high in patients with cervical lymph node metastasis and advanced TNM stage. In addition, miR-146b expression levels were significantly higher in papillary thyroid carcinoma patients with BRAFV600E mutation. The relative quantification (2-ΔΔCt) of miR-146b was also high among the miRNAs. Individually, the AUCs for miRNA-146b was 0.923 (cutoff value −1.97, sensitivity 88.9%, specificity 85.7%). Conclusions Especially, expression of miR-146b increased higher in PTC patients with BRAFV600E mutation. These findings showed a role of miR-146b as potential biomarkers in differentiating PTC from benign tumor and as a prognostic indicator of PTCs. Further investigation will need for the roles of miRNAs in the pathogenesis of papillary thyroid carcinomas.

Background & Aims: In addition to HBV/HCV causing hepatocellular carcinoma (HCC), other risk factors including obesity and alcohol drinking also increase risk. We describe the cumulative risk of HCC and mortality from liver-related disease by selected modifiable risk factors among a non-hepatitis virus-infected population. Methods: For a community-based cohort, residents aged 30–65 years living in 7 townships in Taiwan were recruited, and have been followed up since 1991. A total of 18,541 individuals were seronegative for markers of chronic infection of HBV/HCV and with no history of HCC at baseline. New non-HBV/HCV HCC cases and liver-related deaths were ascertained through data linkage to the National Cancer Registry and Death Certification System from 1 January 1991 through 31 December 2017. Results: There were 207 HCC cases and 215 liver-related deaths identified. The incidence rate of non-HBV/HCV HCC was 47.2 per 100,000 person-years. The mortality rate of liver-related death was 49.0 per 100,000 person-years. Baseline information on alcohol consumption, heart disease, diabetes, elevated aspartate aminotransferase, and alanine aminotransferase predicted higher risks of HCC, with hazard ratios (HRs) (95% CIs) of 1.7 (1.1–2.5), 2.2 (1.1–4.1), 1.9 (1.0–3.5), 1.7 (1.1–2.4), and 1.6 (1.0–2.4), respectively. The HRs (95% CIs) of liver-related death were 2.3 (1.6–3.2) for alcohol consumption, 1.4 (1.1–1.9) for BMI ≥25 kg/m2, 2.2 (1.4–3.3) for elevated aspartate aminotransferase, and 1.5 (1.0–2.4) for elevated alanine aminotransferase. The HR (95% CI) was 8.1 (3.6–18.5) for those with diabetes and elevated aspartate aminotransferase. Conclusions: Individuals with elevated liver enzymes are at high risk of liver disease. Prevention and treatment of diabetes and heart disease are critical for non-hepatitis B, non-hepatitis C (NonB/C)-HCC. Lay summary: We followed up individuals with no chronic HBV or HCV infection and described the risk of hepatocellular carcinoma (HCC, the most common form of primary liver cancer) and mortality from liver-related disease by modifiable risk factors. This study estimated the incidence rate of HCC by selected lifestyle risk factors and chronic diseases conditions. Alcohol consumption, heart disease, diabetes, and abnormal blood liver function tests showed a strong association with HCC risk and mortality.

Regression-based approaches are widely used in causal mediation analysis. The presence of multiple mediators, however, increases the complexity and difficulty of mediation analysis. In such cases, regression-based approaches cannot efficiently address estimation issues. Hence, a flexible approach to mediation analysis is needed. Therefore, we developed a method for using g-computation algorithm to conduct causal mediation analysis in the presence of multiple ordered mediators. Compared to regression-based approaches, the proposed simulation-based approach increases flexibility in the choice of models and increases the range of the outcome scale. The Taiwanese Cohort Study dataset was used to evaluate the efficacy of the proposed approach for investigating the mediating role of early and late HBV viral load in the effect of HCV infection on hepatocellular carcinoma (HCC) in HBV seropositive patients (n = 2,878; HCV carrier n = 123). Our results indicated that early HBV viral load had a negative mediating role in HCV-induced HCC. Additionally, early exposure to a low HBV viral load affected HCC through a lag effect on HCC incidence [OR = 0.873, 95% CI = (0.853, 0.893)], and the effect of early exposure to a low HBV viral load on HCC incidence was slightly larger than that of a persistently low viral load on HCC incidence [OR = 0.918, 95% CI = (0.896, 0.941)].

Abstract Background Use of humidifier disinfectants (HD) at home leads to chemical airborne exposure, causing HD associated lung injury (HDLI) with high mortality. However, the lung function in children diagnosed with HDLI is not well studied. We investigated the effect of HD exposure on lung function, prognosis, and exposure characteristics associated with the lung function phenotype in children. Methods Eighty-one children diagnosed with HDLI in a nationwide cohort were tested for spirometry and diffusing capacity of the lung for carbon monoxide (DLco) from July 2013 and followed up with at five time points over 2 years. The results were compared with 122 children without HD exposure as controls. Home investigation and questionnaire analysis were conducted to assess HD inhalation exposure. Results HDLI survivor’s mean percent of predicted forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and corrected DLco were significantly lower compared with the control group. On longitudinal assessment, FVC was within the normal range, but flattened, and spirometry showed a predominantly restrictive pattern. Corrected DLco did not normalize above 80% despite increasing age. The persistently low phenotype of lung function was associated with initial exposure age, especially less than 12 months of age. Higher density HD exposure during sleep and close distance between the bed and the humidifier were significantly associated with persistently low corrected DLco. Conclusions HD exposure affects prolonged decrement in lung function, especially DLco, particularly among children who are exposed within the first year of life. These results suggested that early-life HD exposure determines long-term prognosis of lung function in children.

Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is an ongoing pandemic. Detection and vaccination are essential for disease control, but they are distinct and complex operations that require significant improvements. Here, we developed an integrated detection and vaccination system to greatly simplify these efforts. We constructed recombinant baculoviruses to separately display the nucleocapsid (N) and spike (S) proteins of SARS-CoV-2. Insect cells infected by the recombinant baculoviruses were used to generate a cell-based system to accurately detect patient serum. Notably, although well-recognized by our newly developed detection system in which S-displaying insect cells acted as antigen, anti-S antibodies from many patients were barely detectable by Western blot, evidencing that COVID-19 patients primarily produce conformation-dependent anti-S antibodies. Furthermore, the same baculovirus constructs can display N (N-Bac) or S (S-Bac) on the baculovirus envelope and serve as vector vaccines. Animal experiments show that S-Bac or N-Bac immunization in mice elicited a strong and specific antibody response, and S-Bac in particular stimulated effective neutralizing antibodies without the need for adjuvant. Our integrated system maintains antigen conformation and membrane structure to facilitate serum detection and antibody stimulation. Thus, compared with currently available technologies, our system represents a simplified and efficient platform for better SARS-CoV-2 detection and vaccination.