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BackgroundHypertension is one of the leading risk factors for ischemic heart diseases, and high rates of hypertension prevalence have either remained the same or increased in developing countries in recent years. Unfortunately, about 20% to 50% of patients with chronic diseases have been nonadherent to their drug therapy. SMS text messaging and pharmacy student–led consultations have the potential to help patients manage their blood pressure (BP). ObjectiveThe aim of this study was to assess the effectiveness, feasibility, and acceptability of SMS text messaging and consultation to manage the BP of Chinese patients with hypertension. MethodsWe conducted a two-arm cluster randomized controlled trial among patients with hypertension in Xi’an City, Shaanxi Province, China, and recruited 384 patients from 8 community health care centers. Patients were randomized into an intervention group to receive SMS text messages and consultations or into a control group to receive usual care for 3 months. We sent SMS text messages at 3-day intervals and collected data at baseline (including demographics, clinical outcomes, medication complexity, side effects, patient behavior, knowledge about hypertension, BP, and medication adherence) and the 3-month follow-up (including BP, medication adherence, and knowledge about hypertension). ResultsWe assessed 445 patients with hypertension and excluded 61 patients who were not eligible or who had not filled out their questionnaires. The mean age of the patients was 68.5 (SD 7.9) years in the intervention group and 69.4 (SD 9.7) years in the control group, and the sample was primarily female (265/384, 69.0%). Patients in the intervention group showed significant improvements in systolic BP (SBP; mean 134.5 mm Hg, SD 15.5 mm Hg vs mean 140.7 mm Hg, SD 15.2 mm Hg; P=.001), medication adherence (mean 7.4, SD 1.2 vs mean 7.0, SD 1.3; P=.04), and knowledge about hypertension (mean 6.3, SD 0.9 vs mean 5.9, SD 1.2; P=.004) compared with those in the control group. In measures of diastolic BP (DBP), the two arms showed nonsignificant improvements (mean 78.2 mm Hg, SD 9.0 mm Hg vs mean 77.2 mm Hg, SD 10.3 mm Hg; P=.06). In total, 176 patients had controlled BP at the 3-month follow-up (98 patients in the intervention group vs 78 patients in the control group), but it was nonsignificant (P=.08). ConclusionsThe use of SMS text messaging and consultation to manage SBP and improve medication adherence is effective, feasible, and acceptable among Chinese patients with hypertension, although a significant difference was not observed with regard to DBP. It is important to maximize the potential of SMS text messaging and consultation by increasing the feasibility and acceptance of mobile interventions and conduct a cost-effectiveness analysis on this method. Trial RegistrationChinese Clinical Trial Registry ChiCTR1900026862; http://www.chictr.org.cn/showproj.aspx?proj=42717.

BackgroundIndividuals in stressful work environments often experience mental health issues, such as depression. Reducing depression rates is difficult because of persistently stressful work environments and inadequate time or resources to access traditional mental health care services. Mobile health (mHealth) interventions provide an opportunity to deliver real-time interventions in the real world. In addition, the delivery times of interventions can be based on real-time data collected with a mobile device. To date, data and analyses informing the timing of delivery of mHealth interventions are generally lacking. ObjectiveThis study aimed to investigate when to provide mHealth interventions to individuals in stressful work environments to improve their behavior and mental health. The mHealth interventions targeted 3 categories of behavior: mood, activity, and sleep. The interventions aimed to improve 3 different outcomes: weekly mood (assessed through a daily survey), weekly step count, and weekly sleep time. We explored when these interventions were most effective, based on previous mood, step, and sleep scores. MethodsWe conducted a 6-month micro-randomized trial on 1565 medical interns. Medical internship, during the first year of physician residency training, is highly stressful, resulting in depression rates several folds higher than those of the general population. Every week, interns were randomly assigned to receive push notifications related to a particular category (mood, activity, sleep, or no notifications). Every day, we collected interns’ daily mood valence, sleep, and step data. We assessed the causal effect moderation by the previous week’s mood, steps, and sleep. Specifically, we examined changes in the effect of notifications containing mood, activity, and sleep messages based on the previous week’s mood, step, and sleep scores. Moderation was assessed with a weighted and centered least-squares estimator. ResultsWe found that the previous week’s mood negatively moderated the effect of notifications on the current week’s mood with an estimated moderation of −0.052 (P=.001). That is, notifications had a better impact on mood when the studied interns had a low mood in the previous week. Similarly, we found that the previous week’s step count negatively moderated the effect of activity notifications on the current week’s step count, with an estimated moderation of −0.039 (P=.01) and that the previous week’s sleep negatively moderated the effect of sleep notifications on the current week’s sleep with an estimated moderation of −0.075 (P

Abstract Background It is challenging to correctly identify and diagnose breast nonmass lesions. This study aimed to explore the multimodal ultrasound features associated with malignant breast nonmass lesions (NMLs), and evaluate their combined diagnostic performance. Methods This retrospective analysis was conducted on 573 breast NMLs, including 309 were benign and 264 were malignant, their multimodal ultrasound features (B-mode, color Doppler and strain elastography) were assessed by two experienced radiologists. Univariate and multivariate logistic regression analysises were used to explore multimodal ultrasound features associated with malignancy, and a nomogram was developed. Diagnostic performance and clinical utility were evaluated and validated by the receiver operating characteristic (ROC) curve, calibration curve and decision curve in the training and validation cohorts. Results Multimodal ultrasound features including linear (odds ratio [OR] = 4.69) or segmental distribution (OR = 7.67), posterior shadowing (OR = 3.14), calcification (OR = 7.40), hypovascularity (OR = 0.38), elasticity scored 4 (OR = 7.00) and 5 (OR = 15.77) were independent factors associated with malignant breast NMLs. The nomogram based on these features exhibited diagnostic performance in the training and validation cohorts were comparable to that of experienced radiologists, with superior specificity (89.4%, 89.5% vs. 81.2%) and positive predictive value (PPV) (89.2%, 90.4% vs. 82.4%). The nomogram also demonstrated good calibration in both training and validation cohorts (all P > 0.05). Decision curve analysis indicated that interventions guided by the nomogram would be beneficial across a wide range of threshold probabilities (0.05-1 in the training cohort and 0.05–0.93 in the validation cohort). Conclusions The combined use of linear or segmental distribution, posterior shadowing, calcification, hypervascularity and high elasticity score, displayed as a nomogram, demonstrated satisfied diagnostic performance for malignant breast NMLs, which may contribute to the imaging interpretation and clinical management of tumors.

Developing adaptive skills poses a significant challenge for children with autism spectrum disorder (ASD). Personal hygiene, including hand-washing, was particularly important during the Covid-19 pandemic. Video self-modeling (VSM) is an effective strategy for teaching adaptive skills due to its inherent individualization nature. However, the production and implementation of VSM face certain barriers. To address this issue, the present study employed an innovative approach termed iVSM, which utilizes the head-swapping technique to generate self-modeling videos. To evaluate the efficacy of iVSM in teaching hand-washing skills, a single-subject multiple probe design was employed across three preschool children with ASD. The findings indicated that all participants successfully acquired the targeted skill, with two of them achieving mastery following a single intervention session. The implications of these findings underscore the potential of this novel approach to strike a balance between individualization and feasibility, thereby enhancing the broader implementation of VSM within the context of inclusive education. Furthermore, future studies can focus on the comparative research and explore more applications.

Abstract The prevalence of osteoporosis has drastically increased recently. It is not only the most frequent but is also a major global public health problem due to its high morbidity. There are many risk factors associated with osteoporosis were identified. However, most studies have used the traditional multiple linear regression (MLR) to explore their relationships. Recently, machine learning (Mach-L) has become a new modality for data analysis because it enables machine to learn from past data or experiences without being explicitly programmed and could capture nonlinear relationships better. These methods have the potential to outperform conventional MLR in disease prediction. In the present study, we enrolled a Chinese post-menopause cohort followed up for 4 years. The difference of T-score (δ-T score) was the dependent variable. Information such as demographic, biochemistry and life styles were the independent variables. Our goals were: (1) Compare the prediction accuracy between Mach-L and traditional MLR for δ-T score. (2) Rank the importance of risk factors (independent variables) for prediction of δ T-score. Totally, there were 1698 postmenopausal women were enrolled from MJ Health Database. Four different Mach-L methods namely, Random forest (RF), eXtreme Gradient Boosting (XGBoost), Naïve Bayes (NB), and stochastic gradient boosting (SGB), to construct predictive models for predicting δ-BMD after four years follow-up. The dataset was then randomly divided into an 80% training dataset for model building and a 20% testing dataset for model testing. A 10-fold cross-validation technique for hyperparameter tuning was used. The model with the lowest root mean square error for the validation dataset was viewed as the best model for each ML method. The averaged metrics of the RF, SGB, NB, and XGBoost models were used to compare the model performance of the benchmark MLR model that used the same training and testing dataset as the Mach-L methods. We defined that the priority demonstrated in each model ranked 1 as the most critical risk factor and 22 as the last selected risk factor. For Pearson correlation, age, education, BMI, HDL-C, and TSH were positively and plasma calcium level, and baseline T-score were negatively correlated with δ-T score. All four Mach-L methods yielded lower prediction errors than the MLR method and were all convincing Mach-L models. From our results, it could be noted that education level is the most important factor for δ-T Score, followed by DBP, smoking, SBP, UA, age, and LDL-C. All four Mach-L outperformed traditional MLR. By using Mach-L, the most important six risk factors were selected which are, from the most important to the least: DBP, SBP, UA, education level, TG and sleeping hour. δ T score was positively related to SBP, education level, UA and TG and negatively related to DBP and sleeping hour in postmenopausal Chinese women.

Abstract Background The reconstruction of complex wounds of the hand still has challenges in achieving aesthetic, functional and sensory recovery. We presented our experience of using the polyfoliate and chimeric radial collateral artery perforator flaps (RCAPF) to repair complex hand defects, aiming to explore the feasibility of special-form RCAPFs in hand coverage and enhance the comprehension of their respective indications. Methods From June 2014 to March 2021, 26 cases (19 males and 7 females, mean 44.4 years) underwent defect and sensation reconstruction of their hands with special-form RCAPFs, which manifested as multiple adjacent or irregular single wounds and composite tissue defects complicated with a degree of nerve injury. The clinical effects of the free RCAPFs were evaluated by integrating the postoperative and long-term follow-up outcomes of all cases. Results Altogether 8 polyfoliate flaps, 17 chimeric flaps and 1 polyfoliate-chimeric flap were harvested. Of them, 23 flaps survived uneventfully in one stage. Venous congestion occurred in 3 cases, two of which survived through vascular exploration and another one was finally repaired by the contralateral RCAPF. The follow-up results showed that the appearance of both the recipient and donor sites mostly recovered satisfactory. All the bone flaps properly healed. The BMRC sensory evaluation results of all skin flaps were S4 in 8 flaps, S3 in 18 flaps, and S2 in 9 flaps. Conclusions The free RCAPFs can be designed in various forms with a reliable blood supply, contributing to reconstructing simple and multiple wounds of the hand with or without bone defects and dead space.

Abstract T and B cell activation are equally important in triggering and orchestrating adaptive host responses to design multi-epitope African swine fever virus (ASFV) vaccines. However, few design methods have considered the trade-off between T and B cell immunogenicity when identifying promising ASFV epitopes. This work proposed a novel Pareto front-based ASFV screening method PFAS to identify promising epitopes for designing multi-epitope vaccines utilizing five ASFV Georgia 2007/1 sequences. To accurately predict T cell immunogenicity, four scoring methods were used to estimate the T cell activation in the four stages, including proteasomal cleavage probability, transporter associated with antigen processing transport efficiency, class I binding affinity of the major histocompatibility complex, and CD8 + cytotoxic T cell immunogenicity. PFAS ranked promising epitopes using a Pareto front method considering T and B cell immunogenicity. The coefficient of determination between the Pareto ranks of multi-epitope vaccines and survival days of swine vaccinations was R2 = 0.95. Consequently, PFAS scored complete epitope profiles and identified 72 promising top-ranked epitopes, including 46 CD2v epitopes, two p30 epitopes, 10 p72 epitopes, and 14 pp220 epitopes. PFAS is the first method of using the Pareto front approach to identify promising epitopes that considers the objectives of maximizing both T and B cell immunogenicity. The top-ranked promising epitopes can be cost-effectively validated in vitro. The Pareto front approach can be adaptively applied to various epitope predictors for bacterial, viral and cancer vaccine developments. The MATLAB code of the Pareto front method was available at https://github.com/NYCU-ICLAB/PFAS . Graphical Abstract

Abstract Background Severe heart failure (HF) has a higher mortality during vulnerable period while targeted predictive tools, especially based on drug exposures, to accurately assess its prognoses remain largely unexplored. Therefore, this study aimed to utilize drug information as the main predictor to develop and validate survival models for severe HF patients during this period. Methods We extracted severe HF patients from the MIMIC-IV database (as training and internal validation cohorts) as well as from the MIMIC-III database and local hospital (as external validation cohorts). Three algorithms, including Cox proportional hazards model (CoxPH), random survival forest (RSF), and deep learning survival prediction (DeepSurv), were applied to incorporate the parameters (partial hospitalization information and exposure durations of drugs) for constructing survival prediction models. The model performance was assessed mainly using area under the receiver operator characteristic curve (AUC), brier score (BS), and decision curve analysis (DCA). The model interpretability was determined by the permutation importance and Shapley additive explanations values. Results A total of 11,590 patients were included in this study. Among the 3 models, the CoxPH model ultimately included 10 variables, while RSF and DeepSurv models incorporated 24 variables, respectively. All of the 3 models achieved respectable performance metrics while the DeepSurv model exhibited the highest AUC values and relatively lower BS among these models. The DCA also verified that the DeepSurv model had the best clinical practicality. Conclusions The survival prediction tools established in this study can be applied to severe HF patients during vulnerable period by mainly inputting drug treatment duration, thus contributing to optimal clinical decisions prospectively.

AIM: To assess and compare the variations and agreements across different ocular biometric parameters using swept-source optical coherence tomography (SS-OCT) and Scheimpflug tomography in patients diagnosed with cataract. METHODS: This prospective case series was conducted at Tianjin Medical University Eye Hospital. In total, 212 eyes from 212 patients scheduled for phacoemulsification were included. Eyes were evaluated preoperatively using two SS-OCT devices (IOLMaster700 and CASIA2) and Scheimpflug tomography (Pentacam). Central corneal thickness (CCT), anterior chamber depth (ACD), aqueous depth (AQD), white-to-white distance (WTW), flat simulated keratometry (Kf), steep simulated keratometry (Ks), mean keratometry (Km), and total corneal keratometry (TKm) were measured. Intraclass correlation coefficient (ICC), 95% confidence intervals (CI) and limits of agreement (LoA) widths were conducted to assess differences and correlations between devices. RESULTS: All parameters, except for Ks, were significantly different. Pairwise comparison revealed no significant differences between keratometry obtained by IOLMaster 700 and Pentacam. LoA widths of all paired comparisons for Ks were >0.80 D. Except for WTW between IOLMaster 700 and CASIA2 and between CASIA2 and Pentacam, other Pearson's coefficients between devices showed a strong correlation (all r>0.95). The ICC of WTW (ICC=0.438, 95%CI 0.167-0.625) showed poor reliability. The reliability of CCT, ACD, and AQD was excellent (all ICC>0.95), whereas that of TKm was good (ICC=0.827, 95%CI 0.221-0.939). A significant linear correlation was also observed among devices. CONCLUSION: The ocular parameters derived from the use of IOLMaster700, CASIA2, and Pentacam exhibit significant discrepancies; as such, measurements from these devices should not be deemed as interchangeable.

Abstract Background Polydactyly is a prevalent congenital anomaly with an incidence of 2.14 per 1000 live births in China. GLI family zinc finger 3 (GLI3) is a classical causative gene of polydactyly, and serves as a pivotal transcription factor in the hedgehog signaling pathway, regulating the development of the anterior-posterior axis in limbs. Methods Three pedigrees of polydactyly patients were enrolled from Hunan Province, China. Pathogenic variants were identified by whole-exome sequencing (WES) and Sanger sequencing. Results Three variants in GLI3 were identified in three unrelated families, including a novel deletion variant (c.1372del, p.Thr458GlnfsTer44), a novel insertion-deletion (indel) variant (c.1967_1968delinsAA, p.Ser656Ter), and a nonsense variant (c.2374 C > T, p.Arg792Ter). These variants were present exclusively in patients but not in healthy individuals. Conclusions We identified three pathogenic GLI3 variants in polydactyly patients, broadening the genetic spectrum of GLI3 and contributing significantly to genetic counseling and diagnosis for polydactyly.

Abstract Background The emergence of Spodoptera frugiperda (fall armyworm; FAW) in the world has raised concerns regarding its impact on crop production, particularly on corn and sorghum. While chemical control and Bt crops have been effective in managing FAW damage, the development of pesticide-resistant and Bt-resistant strains necessitates alternative control methods. The push-pull farming system has gained attention, but direct utilization of African plant species in Taiwan faces challenges due to invasive potential and climatic disparities. Therefore, identifying and evaluating suitable local plant species, such as Napier grass (Pennisetum purpureum), Desmodium species, and signal grass (Brachiaria brizantha), is crucial for implementing effective FAW management strategies in Taiwan. Results In screening fifty Napier grass germplasms, all demonstrated an antibiotic effect, reducing leaf consumption compared to corn. Notably, thirty-five germplasms exhibited robust antibiotic traits, decreasing FAW consumption and increasing mortality rates. Three Napier grass germplasms also attracted more female moths for oviposition. Further evaluation of selected Napier grass germplasms and signal grass demonstrated efficacy in reducing FAW larval weight and survival duration. Additionally, Desmodium species, particularly D. uncinatum, showed promising toxicity against FAW larvae. Conclusion Our findings support the effectiveness of selected Napier grass germplasms and signal grass as pull plants, and highlight the potential of D. uncinatum as a push plant in FAW management strategies in Taiwan.

Abstract Previous studies have explored the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in reducing cardiovascular events in type 2 diabetes. Here we show that GLP-1 RAs are associated with lower risks of mortality, major cardiovascular events (MACEs), and major adverse kidney events (MAKEs) in type 2 diabetes patients with acute kidney disease (AKD). Utilizing global data from the TriNetX database (2002/09/01-2022/12/01) and propensity score matching, we compare 7511 GLP-1 RAs users to non-users among 165,860 AKD patients. The most common causes of AKI are sepsis (55.2%) and cardiorenal syndrome (34.2%). After a median follow-up of 2.3 years, GLP-1 RAs users exhibit reduced risks of mortality (adjusted hazard ratio [aHR]: 0.57), MACEs (aHR: 0.88), and MAKEs (aHR: 0.73). External validation in a multicenter dataset of 1245 type 2 diabetes patients with AKD supports the favorable outcomes. These results emphasize the potential of GLP-1 RAs in individualized treatment for this population.

Abstract Coronaviruses employ various strategies for survival, among which the activation of endogenous or exogenous apoptosis stands out, with viral proteins playing a pivotal role. Notably, highly pathogenic coronaviruses such as SARS-CoV-2, SARS-CoV, and MERS-CoV exhibit a greater array of non-structural proteins compared to low-pathogenic strains, facilitating their ability to induce apoptosis via multiple pathways. Moreover, these viral proteins are adept at dampening host immune responses, thereby bolstering viral replication and persistence. This review delves into the intricate interplay between highly pathogenic coronaviruses and apoptosis, systematically elucidating the molecular mechanisms underpinning apoptosis induction by viral proteins. Furthermore, it explores the potential therapeutic avenues stemming from apoptosis inhibition as antiviral agents and the utilization of apoptosis-inducing viral proteins as therapeutic modalities. These insights not only shed light on viral pathogenesis but also offer novel perspectives for cancer therapy.

Purpose – In 2022, the International Network for Quality Assurance (QA) Agencies in Higher Education (INQAAHE) published the new guidelines by adding three QA modules in response to the changing higher education landscape. The paper aims to investigate the transformative focus of quality assurance in higher education globally as well as Asian response to three new QA modules according to the INQAAHE ISGs. Design/methodology/approach – The research conducted a quantitative approach for data collection. An on-line survey was conducted to perceive QA practices, perceptions toward new emerging QA modules and challenges encountered. In total, there were 26 responses from 18 territories with 22 QA agencies. A total of 13 out of them have a national qualifications framework in place. Findings – Three are three major findings in the study. First, national policy and criteria and standards in distance education have been developed in the majority of Asian nations. Second, non-signatories of the Tokyo Convention had a higher proportion of having related policies, regulations and criteria in CBHE and distance education. Third, national policies and regulations; and lack of professional staff are two common challenges implementing QA in new types of providers. Originality/value – The findings are of value for policymakers, QA agencies and universities to advocate the new QA model as a systematic approach in response to changing higher education landscape in the post pandemic era.

Social value of green products have received considerable attention. Because few scholars have investigated the effects of prosocial norms on the formation of social value perceptions, this article explores whether prosocial descriptive and injunctive norms affect people’s perceived social value of green products, which affects their attitudes and purchase intentions toward green products. The research sample comprised consumers who possessed purchased green products previously 3 months, and 400 questionnaires were collected. The gathered data were assessed through structural equation modeling. The results state that consumer-perceived social value possesses a positive impact on attitude toward green products, which in turn positively influences repurchase intentions. Furthermore, both descriptive norms and injunctive norms positively impact consumer-perceived social value, whereas only descriptive norms positively have an effect on attitude toward green products. Depending on the aforementioned results, this research suggests that governments and green marketers adopt the social norms perspective to encourage consumers to continuously buy green products by generating consumer perceptions of social value and positive attitudes toward green products.

In this paper, we study the following Schrödinger–Hardy system \begin{equation*} \begin{cases} -\Delta_{\mathbb{G}}u-\mu\frac{\psi^2}{r(\xi)^2}u=F_u(\xi,u,v)\ &{\rm in}\ \Omega, \\ -\Delta_{\mathbb{G}}v-\nu\frac{\psi^2 }{r(\xi)^2}v=F_v(\xi,u,v)\ &{\rm in}\ \Omega, \\ u=v=0 \ \ & {\rm on}\ \partial\Omega, \end{cases} \end{equation*} where $\Omega $ is a smooth bounded domain on Carnot groups $\mathbb{G}$, whose homogeneous dimension is $Q\geq 3$, $\Delta_{\mathbb{G}}$ denotes the sub-Laplacian operator on $\mathbb{G}$, $\mu$ and $\nu$ are real parameters, $r(\xi)$ is the natural gauge associated with fundamental solution of $-\Delta_{\mathbb{G}}$ on $\mathbb{G}$, $\psi$ is the geometrical function defined as $\psi=|\nabla_{\mathbb{G}}r|$, and $\nabla_{\mathbb{G}}$ is the horizontal gradient associated with $\Delta_{\mathbb{G}}$. The difficulty is not only the nonlinearities $F_u$ and $F_v$ without Ambrosetti–Rabinowitz condition, but also the Hardy terms and the structure on Carnot groups. We obtain the existence of nonnegative solution for this system by mountain pass theorem in a new framework.

Abstract Pancreatic ductal adenocarcinoma (PDAC) poses challenges due to late-stage diagnosis and limited treatment response, often attributed to the hypoxic tumor microenvironment (TME). Sonoporation, combining ultrasound and microbubbles, holds promise for enhancing therapy. However, additional preclinical research utilizing commercially available ultrasound equipment for PDAC treatment while delving into the TME's intricacies is necessary. This study investigated the potential of using a clinically available ultrasound system and phase 2-proven microbubbles to relieve tumor hypoxia and enhance the efficacy of chemotherapy and immunotherapy in a murine PDAC model. This approach enables early PDAC detection and blood-flow-sensitive Power-Doppler sonoporation in combination with chemotherapy. It significantly extended treated mice's median survival compared to chemotherapy alone. Mechanistically, this combination therapy enhanced tumor perfusion and substantially reduced tumor hypoxia (77% and 67%, 1- and 3-days post-treatment). Additionally, cluster of differentiation 8 (CD8) T-cell infiltration increased four-fold afterward. The combined treatment demonstrated a strengthening of the anti-programmed death-ligand 1(αPDL1) therapy against PDAC. Our study illustrates the feasibility of using a clinically available ultrasound system with NH-002 microbubbles for early tumor detection, alleviating hypoxic TME, and improving chemotherapy and immunotherapy. It suggests the development of an adjuvant theragnostic protocol incorporating Power-Doppler sonoporation for pancreatic tumor treatment.

Abstract Background Few studies have compared the correlation between visceral fat area (VFA) and abdominal subcutaneous fat area (SFA) with arterial stiffness (AS) in patients with type 2 diabetes (T2D). In addition, there is currently controversy regarding the correlation between VFA and SFA with AS. We aimed to investigate the relationship between VFA and SFA with AS in patients with T2D. Methods In this cross-sectional study, 1475 Chinese T2D patients with an average age of 52.32 ± 10.96 years were included. VFA and SFA were determined by a dual bioelectrical impedance analyzer, and AS was determined by measurement of brachial-ankle pulse wave conduction velocity (baPWV). Atherosclerosis was deemed present in study participants with baPWV values higher than 75th percentile (1781 cm/s). Independent correlations of logVFA and logSFA with AS were assessed using multiple linear regression and multivariate logistic regression. Results The baPWV was linked with VFA, waist circumference, and women’s SFA in a general linear correlation study (P 0.05). Conclusions Compared with SFA, VFA had a stronger independent positive correlation with AS in Chinese T2D patients. Patients with T2D should pay more attention to monitoring VFA and lowering it to minimize cardiovascular events.

Ecosystems supply goods and services to humans and are the basis for sustainable development of human society. The study of the supply of ecosystem services and the demand and consumption of ecosystem services by human society, and the analysis of the supply and demand characteristics and flow relationships of ecosystem service flows are of great significance for the management of regional ecosystems and the development of ecological compensation. Taking the Yangtze River Economic Belt as an example, this paper calculates the supply and demand indices of ecosystem services in 2015 and 2020, and determines the ecosystem spatial flow paths and flow volumes from the ecosystem supply area to the demand area based on various methods and models such as the minimum cumulative resistance (MCR) model and distance decay model. The results indicate that 1). In 2015 and 2020, the supply and demand of ecosystem services in the Yangtze River Economic Zone show an increasing trend numerically, and there is spatial heterogeneity in the spatial distribution. In terms of ecosystem service supply per unit area, the midstream region is higher than the upstream and downstream regions. In terms of the demand for ecosystem services per unit area, the downstream is higher than the midstream and upstream. 2). From the supply-demand balance of ecosystem services in the Yangtze River Economic Zone, the midstream region is mainly the area of surplus supply of ecosystem services, and the downstream region is mainly the area of deficit supply. From 2015 to 2020, the number of areas with balanced supply and demand of ecosystem services in the Yangtze River Economic Belt decreases and the number of areas with unbalanced supply and demand increases, which is related to the changes in the level of economic development and land use patterns. 3). The flow of ecosystem services in the Yangtze River Economic Belt shows an increasing trend, from 726.59 billion yuan in 2015 to 1,450.54 billion yuan in 2020, with Jiangxi Province being the main ecosystem service supply area and Zhejiang Province being the main ecosystem service demand area in the Yangtze River Economic Belt.

Key Clinical Message We report a rare case of thyroid diffuse large B‐cell lymphoma with a BRAFV600E mutation, which mimics poorly differentiated thyroid cancer in fine needle aspiration cytology.

BackgroundWhile several studies have noted a higher SII correlates with multiple diseases, research on the association between SII and cataract remains limited. Our cross-sectional study seeks to examine the association between SII and cataract among outpatient US adults.MethodsThis compensatory cross-sectional study utilized NHANES data from 1999 to 2008 cycles, conducting sample-weighted multivariate logistic regression and stratified analysis of subgroups.ResultsAmong 11,205 adults included in this study (5,571 [46.2%] male; 5,634 [53.8%] female), 2,131 (15.2%) had cataract and 9,074 (84.8%) did not have cataract. A fully adjusted model showed that SII higher than 500 × 109/L was positively correlated with an increased risk of cataracts among women (OR, 1.27; 95% CI, 1.02–1.59) (p = 0.036). However, no difference was found in the men subgroup, and there was no significant interaction between SII and sex.ConclusionOur results indicated that a SII higher than 500 × 109/L was positively correlated with an increased risk of cataracts in women. This study is the first to specifically investigate the impact of a high SII on cataract risk in outpatient adults in the United States. By effectively addressing inflammation, it is possible to mitigate cataract progression and significantly enhance patient outcomes.

The trade-off and synergy relationship of ecosystem services is an important topic in the current assessment. The value of each service provided by the ecosystem is substantially affected by human activities, and conversely, its changes will also affect the relevant human decisions. Due to varying trade-offs among ecosystem services and synergies between them that can either increase or decrease, it is difficult to optimize multiple ecosystem services simultaneously, making it a huge challenge for ecosystem management. This study firstly develops a global Gross Ecosystem Product (GEP) accounting framework. It uses remote sensing data with a spatial resolution of 1 km to estimate the ecosystem services of forests, wetlands, grasslands, deserts, and farmlands in 179 major countries in 2018. The results show that the range of global GEP values is USD 112–197 trillion, with an average value of USD 155 trillion (the constant price), and the ratio of GEP to gross domestic product (GDP) is 1.85. The trade-offs and the synergies among different ecosystem services in each continent and income group have been further explored. We found a correspondence between the income levels and the synergy among ecosystem services within each nation. Among specific ecosystem services, there are strong synergies between oxygen release, climate regulation, and carbon sequestration services. A trade-off relationship has been observed between flood regulation and other services, such as water conservation and soil retention services in low-income countries. The results will help clarify the roles and the feedback mechanisms between different stakeholders and provide a scientific basis for optimizing ecosystem management and implementing ecological compensation schemes to enhance human well-being.

Objective To detect the pathological changes in obese mice liver and explore the effects of obesity on hepatic metabolism. Methods Obese mouse model was successfully constructed by consecutive 24 weeks of high fat diet (HFD), while control group was fed with a standard chow diet (CD). After 24 weeks, mice liver was dissected, and the pathological characteristics of liver were observed with hematoxylin-eosin (HE) staining and Sirius red staining. The metabolome of liver was detected by ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS) after extraction by 80% methanol. Principal component analysis (PCA), differential metabolite analysis and KEGG pathway enrichment analysis were performed to find the metabolic changes in the liver of obese mice. Results After 24 weeks of high fat diet, the body weight and liver weight of HFD group mice were much higher than that of CD group mice. Besides, HFD group mice liver showed severe steatosis and slight fibrosis. There were also significant differences in liver metabolites between HFD and CD groups, and the metabolic changes were mainly enriched in pathways of phenylalanine metabolism, citric acid cycle (TCA cycle), sphingolipid metabolism, arginine biosynthesis and primary bile acid biosynthesis. Conclusions The obese mouse model was successfully constructed, and the pathological characteristics of obese mice liver were elucidated. At the same time,the main metabolic pathway changes of obese mice liver were further revealed by metabonomics analysis.

Abstract Introduction Perioperative urinary tract infections (PUTIs) are common in the United States and are a significant contributor to high healthcare costs. There is a lack of large studies on the risk factors for PUTIs after total hysterectomy (TH). Methods We conducted a retrospective study using a national inpatient sample (NIS) of 445,380 patients from 2010 to 2019 to analyze the risk factors and annual incidence of PUTIs associated with TH perioperatively. Results PUTIs were found in 9087 patients overall, showing a 2.0% incidence. There were substantial differences in the incidence of PUTIs based on age group (P

Abstract Background Automated Breast Ultrasound (AB US) has shown good application value and prospects in breast disease screening and diagnosis. The aim of the study was to explore the ability of AB US to detect and diagnose mammographically Breast Imaging Reporting and Data System (BI-RADS) category 4 microcalcifications. Methods 575 pathologically confirmed mammographically BI-RADS category 4 microcalcifications from January 2017 to June 2021 were included. All patients also completed AB US examinations. Based on the final pathological results, analyzed and summarized the AB US image features, and compared the evaluation results with mammography, to explore the detection and diagnostic ability of AB US for these suspicious microcalcifications. Results 250 were finally confirmed as malignant and 325 were benign. Mammographic findings including microcalcifications morphology (61/80 with amorphous, coarse heterogeneous and fine pleomorphic, 13/14 with fine-linear or branching), calcification distribution (189/346 with grouped, 40/67 with linear and segmental), associated features (70/96 with asymmetric shadow), higher BI-RADS category with 4B (88/120) and 4 C (73/38) showed higher incidence in malignant lesions, and were the independent factors associated with malignant microcalcifications. 477 (477/575, 83.0%) microcalcifications were detected by AB US, including 223 malignant and 254 benign, with a significantly higher detection rate for malignant lesions (x 2 = 12.20, P

Abstract Background Hepatic encephalopathy (HE) is closely associated with inflammatory responses. However, as a crucial regulator of the immune and inflammatory responses, the role of leucine-rich repeat kinase 2 (LRRK2) in the pathogenesis of HE remains unraveled. Herein, we investigated this issue in thioacetamide (TAA)-induced HE following acute liver failure (ALF). Methods TAA-induced HE mouse models of LRRK2 wild type (WT), LRRK2 G2019S mutation (Lrrk2 G2019S) and LRRK2 knockout (Lrrk2 −/−) were established. A battery of neurobehavioral experiments was conducted. The biochemical indexes and pro-inflammatory cytokines were detected. The prefrontal cortex (PFC), striatum (STR), hippocampus (HIP), and liver were examined by pathology and electron microscopy. The changes of autophagy-lysosomal pathway and activity of critical Rab GTPases were analyzed. Results The Lrrk2 −/−-HE model reported a significantly lower survival rate than the other two models (24% vs. 48%, respectively, p

Abstract Introduction Graves’ ophthalmopathy (GO) is an autoimmune inflammatory disorder observed in a substantial proportion of patients with Graves’ disease (GD), with debilitating symptoms of disfiguring, periorbital pain, dry eyes, diplopia, and even visual disturbances. Previous studies involving Western populations have noted discrepancies in risk factors for GO. Therefore, this study aimed to determine the risk factors for GO development and the protective effect of statins in newly diagnosed patients with GD in Taiwan. Methods This retrospective case–control study was based on a tertiary center cohort involving patients with GD diagnosed between 2010 and 2019 at the National Taiwan University Hospital (n = 11,035). Patients who were diagnosed or treated elsewhere, had been followed up for less than 6 months or were with a diagnosis of orbital tumor were excluded. Overall, 3578 patients with GD met the inclusion criteria. Univariate and multivariate logistic regression analyses were used to ascertain the odds ratio (OR) of developing GO, with adjustment for sociodemographic factors, interventions for managing GD and thyroid hormone levels, to determine protective and risk factors for GO. Results In our multivariate model, the use of statins reduced the risk of GO development (OR 0.2; 95% confidence interval [CI] 0.08–0.50; p

Background/Aims: Early diagnosis of gastric cancer can improve the prognosis of patients, especially for those with early gastric cancer (EGC), but only 15% of patients, or less, are diagnosed with EGC and precancerous lesions. Magnifying endoscopy with narrow-band imaging (ME-NBI) can improve diagnostic accuracy. We assess the efficacy of ME-NBI in diagnosing ECG and precancerous lesions, especially some characteristics under NBI+ME. Materials and Methods: This was a retrospective analysis of 131 patients with EGC or gastric intraepithelial neoplasia (IN) who had undergone endoscopic submucosal dissection and were pathologically diagnosed with EGC or IN according to 2019 WHO criteria for gastrointestinal tract tumors. We studied the characteristics of lesions under ME-NBI ,compared the diagnostic efficacy of ME-NBI and white light endoscopy (WLI) plus biopsy, and investigated the effect of Helicobacter pylori infection on microvascular and microsurface pattern. Results: The diagnostic accuracy of ME-NBI for EGC, high-grade IN (HGIN), and low-grade IN (LGIN) was 76.06%, 77.96%, and 77.06%, respectively. The accuracy of WLI plus biopsy in diagnosing the above lesions was 69.7%, 57.5%, and 60.53%, respectively. The rate of gyrus-like tubular pattern was highest in LGIN (60.46%), whereas the highest rate of papillary pattern was 57.14% in HGIN and villous tubular pattern was 52% in EGC. Demarcation lines have better sensitivity for differentiating EGC from IN (92.06%). Conclusion: The ME-NBI has higher diagnostic accuracy for EGC than WLI plus biopsy. Demarcation lines and villous and papillary-like microsurface patterns are more specific as EGC and HGIN characteristics. The cerebral gyrus-like microsurface pattern is more specific for LGIN.

Background: The rating result reflects not only the performance of the candidate but some extent of the examiner’s preference. Examiner bias could be objective, which means it can’t be changed by the examiner like gender, age, race, educational level, or professional experience. No study about examiner bias was performed in the dental education realm, especially in the orthodontic field. Therefore, this study aimed to figure out possible influencing factors in examiners from examples of the Taiwan Board of Orthodontist examination. Methods: The examiner groups comprised 29 males and 21 females selected from the certificated Taiwan Board of Orthodontists. Every examiner would receive a series of lectures about rating standards before the exam. The score data were collected from 2009 to 2019. Results: As for the univariate regression model of the Taiwan Board of Orthodontist examination, the experienced examiner with a certification of more than 15 years tends to rate more leniently, but female examiners tend to rate harsher. The scores would increase with the examiner’s age in both the univariate regression model of self-prepared and assigned cases. Conclusion: As for the multivariate model of self-prepared exams, the elder and the examiner who work in private practice clinics tend to rate more leniently. As for the multivariate model of the assigned case exam, the score would be only affected by age. However, further studies are necessary to determine the direct relation among these factors.

Reprocessing of gastrointestinal (GI) endoscopes and accessories is an essential part of patient safety and quality control in GI endoscopy centers. However, current endoscopic reprocessing guidelines or procedures are not adequate to ensure patient-safe endoscopy. Approximately 5.4 % of the clinically used duodenoscopes remain contaminated with high-concern microorganisms. Thus, the Digestive Endoscopy Society of Taiwan (DEST) sets standards for the reprocessing of GI endoscopes and accessories in endoscopy centers. DEST organized a task force working group using the guideline-revision process. These guidelines contain principles and instructions of step-by-step for endoscope reprocessing. The updated guidelines were established after a thorough review of the existing global and local guidelines, systematic reviews, and health technology assessments of clinical effectiveness. This guideline aims to provide detailed recommendations for endoscope reprocessing to ensure adequate quality control in endoscopy centers.

Purpose:. According to the National Comprehensive Cancer Network guidelines, segmental ureterectomy (SU) of upper tract urothelial carcinoma (UTUC) is a considerable option for selected mid- and distal ureteral urothelial carcinoma (UC). As a UTUC endemic area, Taiwan lacks treatment outcome analysis of SU. Materials and methods:. This study retrospectively reviewed the treatment outcomes of SU for clinically localized UTUCs. Patients with biopsy or washing cytology-confirmed UTUCs who underwent open, laparoscopic, or robot-assisted management with curative intent were retrospectively reviewed for the eligibility of analysis. Cox regression was applied for univariable and multivariable analyses. Results:. A total of 161 patients who underwent SU were reviewed and analyzed. The median follow-up period was 44.5 (interquartile range, 21.6–84.9) months. After SU, 56/161 (34.8%) patients were free of UTUCs after the follow-up, 25/161 (15.5%) patients had local recurrence, and 35/161 (21.7%) had lymph node or distant metastasis. Surgical margin involvement was a risk factor associated with worse cancer-specific survival. Higher bladder recurrence and local recurrence rates were observed with concurrent bladder UC. Lymphovascular invasion and previous radical nephroureterectomy (RNU) for UC were related to higher local recurrence rates. Patients with pathological T3/T4 stage and end-stage renal disease tended to have higher metastasis rates. For the management of local recurrence, 19 patients received salvage RNU and 25 patients had adjuvant chemotherapy. However, 26/161 (16.1%) patients died of UTUCs and 2/161 (1.2%) patients died of surgery-related complications. Conclusion:. SU provides acceptable oncological outcomes if the surgeons select candidates carefully. SU is not recommended if the patient has T3 or higher stage or comorbidity of end-stage renal disease. Concurrent bladder UC is a risk factor for worse bladder recurrence-free survival and local recurrence-free survival. Lymphovascular invasion and previous RNU for UC were related to higher local recurrence rates. After SU, periodic follow-up is mandatory because the local recurrence rate is higher than radical surgery.

Abstract Acute gastric bleeding (AGB) is a common and potentially serious complication in patients with gastrointestinal disorders. Nursing interventions play a critical role in the management of acute gastric bleeding, but their impact on clinical outcomes is not well understood. The aim of this retrospective analysis was to evaluate the impact of nursing interventions on clinical outcomes in patients with acute gastric bleeding. A retrospective review of medical records was conducted for 220 patients with acute gastric bleeding who were admitted to the hospital between February 2022 and February 2023. Patients were divided into two groups based on whether or not they received nursing interventions during their hospital stay. Clinical outcomes, including length of hospital stay, blood transfusion requirements, and mortality rates, were compared between the two groups using descriptive statistics and logistic regression analysis. Of the 220 patients included in the study, 168 (76.4%) received nursing interventions during their hospital stay. Patients who received nursing interventions had a significantly shorter length of hospital stay (mean = 7.2 days, SD = 2.1) compared to those who did not receive nursing interventions (mean = 10.5 days, SD = 3.4, p

Although para-aminosalicylic acid (PAS) has been used to treat tuberculosis for decades, mechanisms of resistance to this drug in Mycobacterium tuberculosis (M. tuberculosis) clinical isolates have not been thoroughly investigated. Previously, we found that decreased methylenetetrahydrofolate reductase (MTHFR) activity of Rv2172c led to increased sensitivity to antifolates in M. tuberculosis. In this study, we collected the genome-sequencing data of 173 PAS-resistant and 803 PAS-sensitive clinical isolates and analyzed rv2172c mutations in those 976 isolates. The results showed that two mutations (T120P and M172V) on rv2172c could be identified in a certain proportion (6.36%) of PAS-resistant isolates. The results of AlphaFold2 prediction indicated that the T120P or M172V mutation might affect the enzymatic activity of Rv2172c by influencing nicotinamide adenine dinucleotide (NADH) binding, and this was verified by subsequent biochemical analysis, demonstrating the role of residues Thr120 and Met172 on NADH binding and enzymatic activity of Rv2172c. In addition, the effect of rv2172c T120P or M172V mutation on methionine production and PAS resistance was determined in M. tuberculosis. The results showed that both T120P and M172V mutations caused increased intracellular methionine concentrations and high level PAS resistance. In summary, we discovered new molecular markers and also a novel mechanism of PAS resistance in M. tuberculosis clinical isolates and broadened the understanding of the NADH-dependent MTHFR catalytic mechanism of Rv2172c in M. tuberculosis, which will facilitate the molecular diagnosis of PAS resistance and also the development of new drugs targeting Rv2172c.

Amidst the rapid advancement of Internet of Things (IoT) technology and the burgeoning field of Multimodal Learning Analytics (MMLA), this study employs spatial positioning technology as a case study to investigate the potential of multimodal data in assessing children's social development. This study combines the spatial positioning data of preschool children collected during free play sessions in natural educational settings and the spatial metrics constructed based on observational studies to establish and validate a sociometric status Decision Tree classification model. The findings suggest that the model can overall accurately identify children with three distinct sociometric statuses, albeit with some variability in efficacy across different sociometric groups and age groups. Notably, the model demonstrates a high hitting rate in identifying the potentially neglected children, providing valuable support for educators in understanding and fostering children's developmental needs. This study also highlights the advantages of emerging technology and multimodal data application in child development assessment.

Background: Emerging evidence has shown the potential involvement of phthalates (PAEs) exposure in the development of dementia with Lewy bodies (DLB). Metabolomics can reflect endogenous metabolites variation in the progress of disease after chemicals exposure. However, little is known about the association between PAEs, gut microbiota and metabolome in DLB. Objective: We aim to explore the intricate relationship among urinary PAEs metabolites (mPAEs), dysbiosis of gut bacteria, and metabolite profiles in DLB. Methods: A total of 43 DLB patients and 45 normal subjects were included in this study. Liquid chromatography was used to analyze the levels of mPAEs in the urine of the two populations. High-throughput sequencing and liquid chromatography-mass spectrometry were used to analyze gut microbiota and the profile of gut metabolome, respectively. The fecal microbiota transplantation (FMT) experiment was performed to verify the potential role of mPAEs on gut dysbiosis contribute to aggravating cognitive dysfunction in α-synuclein tg DLB/PD mice. Results: The DLB patients had higher DEHP metabolites (MEOHP, MEHHP and MEHP), MMP and MnBP, lower MBP and MBzP than the control group and different microbiota. A significantly higher abundance of Ruminococcus gnavus and lower Prevotella copri, Prevotella stercorea and Bifidobacterium were observed in DLB. Higher 3 DEHP metabolites, MMP, MnBP and lower MBP and MBzP were significantly negatively associated with Prevotella copri, Prevotella stercorea and Bifidobacterium. Additionally, using metabolomics, we found that altered bile acids, short-chain fatty acids and amino acids metabolism are linked to these mPAEs. We further found that FMT of fecal microbiota from highest DEHP metabolites donors significantly impaired cognitive function in the germ-free DLB/PD mice. Conclusion: Our study suggested that PAEs exposure may alter the microbiota-gut-brain axis and providing novel insights into the interactions among environmental perturbations and microbiome-host in pathogenesis of DLB.

Background: Outpatient parenteral antimicrobial therapy (OPAT) provides a safe and effective alternative to prolonged hospitalization for patients with infectious diseases requiring elongated antimicrobial therapy. One study found that 35.6% of OPAT episodes met the composite definition for treatment failure, with unplanned extension of OPAT as the most common reason for treatment failure. Our study sought to identify factors predicting higher likelihood of extension of OPAT due to slow clinical response to treatment and determine how therapy extension relates to complications. Method: This retrospective cohort study included all patients aged ≥18 years discharged on OPAT between April 2022 and October 2022. Demographic, treatment, outcome, and complications data were extracted through chart review. The primary outcome was the proportion and predictors of OPAT extension due to slow clinical response to treatment. The secondary outcomes were OPAT complication rate, 30-day ED visit and 30-day readmission rates related to OPAT complications. We used univariable and multivariable logistic regression models for the primary outcome of slow clinical response requiring OPAT extension. Variables with p < 0.1 in the univariable analyses were included in the multivariable model. Result: 231 patients received OPAT during the six-month study. Among them, 40 (17.3%) patients required an extension of therapy. In univariable analysis, patients who had slow clinical response requiring extension of OPAT were more likely to have intraabdominal infection (odds ratio [OR], 2.435; 95% confidence interval[CI], 1.053–5.628), receipt of metronidazole (OR, 3.729; 95% CI, 1.413–9.842), and were more likely to be followed up through office visit (OR, 5.033; 95%CI, 1.164–21.759) or combination of office visit and telemedicine (OR, 2.223; 95%CI 1.041–4.747). Other variable comparisons are detailed in Figure 1. In the multivariable regression analysis, the independent predictor associated with extended of OPAT was follow-up via office visit (adjusted OR, 4.630; 95% CI, 1.024-20.694). Rates of complications related to intravenous access and antibiotic were similar between patients with and without extension; 15% vs. 11% (p=0.430) and 7.5% vs. 7.3% (p=1.000), respectively. There were no significant differences in 30-day ED visits and readmission rates between the 2 groups: 7.5% vs. 5.8%(p=0.715) and 12.5% vs. 7.3% (p=0.338). Conclusion: Our study highlights patient’s office visit follow-up is associated with the OPAT extension due to slow clinical response. However, extended therapy did not result in a significant increase in complications or hospital readmissions. These findings suggest the importance of careful patient selection and monitoring for OPAT, potentially guiding more efficient and targeted healthcare practices.

Background: While Outpatient Parenteral Antibiotic Therapy (OPAT) offers patient convenience and reduced healthcare costs, its increasing utilization has brought various complications to light, including antibiotics-related and line-related OPAT complications. In a large prospective study, 18% of the patients experienced adverse drug events. Another study showed 8.45% of patients had vascular complications. Our study aims to identify clinical predictors associated with OPAT complications. Identifying predictors for suboptimal OPAT outcomes provides an opportunity to intervene, thereby minimizing the risk of OPAT-related complications. Method: We conducted a retrospective cohort study at Tufts Medical Center of all adult patients aged ≥18 years discharged on OPAT from April 2022 to October 2022. Demographic, treatment, outcome, and complications data were extracted through chart review. The primary outcome was the proportion and predictors of OPAT complications. The secondary outcomes were OPAT completion rate, 30-day ED visit, and 30-day readmission rates related to OPAT complications. We used univariable and multivariable analyses using logistic regression models for the predictors of OPAT complications. Variables with p5 (OR, 0.281, 95% CI 0.101–0.784), but they were more likely to have received two antibiotics (OR, 2.265; 95% CI 1.155-4.442). However, no significant independent predictor OPAT complications was identified in multivariable regression analysis (Figure 2). OPAT completion rates were lower in patients with complications (59.1% versus 75.4%). The 30-day ED visit and 30-day readmission rates were significantly higher in the complication group (31.8% vs. 0 and 34.1% vs. 2.1%, respectively). Conclusion: Our study highlights the significant difference in treatment completion rates and higher incidence of ED visits and readmissions rates among those with OPAT complications. Although specific independent predictor was not identified, the association with multiple antibiotic therapies and telemedicine follow-ups suggests areas for further investigation.

ABSTRACT HIV-1 replication is tightly regulated in host cells, and various restriction factors have important roles in inhibiting viral replication. SAMHD1, a well-known restriction factor, suppresses HIV-1 replication by hydrolyzing intracellular dNTPs, thereby limiting the synthesis of viral cDNA in quiescent cells. In this study, we revealed an additional and distinct mechanism of SAMHD1 inhibition during the postviral cDNA synthesis stage. Using immunoprecipitation and mass spectrometry analysis, we demonstrated the interaction between SAMHD1 and MX2/MxB, an interferon-induced antiviral factor that inhibits HIV-1 cDNA nuclear import. The disruption of endogenous MX2 expression significantly weakened the ability of SAMHD1 to inhibit HIV-1. The crucial region within SAMHD1 that binds to MX2 has been identified. Notably, we found that SAMHD1 can act as a sensor that recognizes and binds to the incoming HIV-1 core, subsequently delivering it to the molecular trap formed by MX2, thereby blocking the nuclear entry of the HIV-1 core structure. SAMHD1 mutants unable to recognize the HIV-1 core showed a substantial decrease in antiviral activity. Certain mutations in HIV-1 capsids confer resistance to MX2 inhibition while maintaining susceptibility to suppression by the SAMHD1-MX2 axis. Overall, our study identifies an intriguing antiviral pattern wherein two distinct restriction factors, SAMHD1 and MX2, collaborate to establish an alternative mechanism deviating from their actions. These findings provide valuable insight into the complex immune defense networks against exogenous viral infections and have implications for the development of targeted anti-HIV therapeutics.IMPORTANCEIn contrast to most restriction factors that directly bind to viral components to exert their antiviral effects, SAMHD1, the only known deoxynucleotide triphosphate (dNTP) hydrolase in eukaryotes, indirectly inhibits viral replication in quiescent cells by reducing the pool of dNTP substrates available for viral cDNA synthesis. Our study provides a novel perspective on the antiviral functions of SAMHD1. In addition to its role in dNTP hydrolysis, SAMHD1 cooperates with MX2 to inhibit HIV-1 nuclear import. In this process, SAMHD1 acts as a sensor for incoming HIV-1 cores, detecting and binding to them, before subsequently delivering the complex to the molecular trap formed by MX2, thereby immobilizing the virus. This study not only reveals a new antiviral pathway for SAMHD1 but also identifies a unique collaboration and interaction between two distinct restriction factors, establishing a novel line of defense against HIV-1 infection, which challenges the traditional view of restriction factors acting independently. Overall, our findings further indicate the intricate complexity of the host immune defense network and provide potential targets for promoting host antiviral immune defense.

Abstract Intratumor heterogeneity (ITH) of bladder cancer (BLCA) contributes to therapy resistance and immune evasion affecting clinical prognosis. The molecular and cellular mechanisms contributing to BLCA ITH generation remain elusive. It is found that a TM4SF1‐positive cancer subpopulation (TPCS) can generate ITH in BLCA, evidenced by integrative single cell atlas analysis. Extensive profiling of the epigenome and transcriptome of all stages of BLCA revealed their evolutionary trajectories. Distinct ancestor cells gave rise to low‐grade noninvasive and high‐grade invasive BLCA. Epigenome reprograming led to transcriptional heterogeneity in BLCA. During early oncogenesis, epithelial‐to‐mesenchymal transition generated TPCS. TPCS has stem‐cell‐like properties and exhibited transcriptional plasticity, priming the development of transcriptionally heterogeneous descendent cell lineages. Moreover, TPCS prevalence in tumor is associated with advanced stage cancer and poor prognosis. The results of this study suggested that bladder cancer interacts with its environment by acquiring a stem cell‐like epigenomic landscape, which might generate ITH without additional genetic diversification.

IntroductionPrevious studies highlight the negative impact of adverse socioeconomic conditions throughout life on motor skills and cognitive health. Factors such as cognitive activity, physical activity, lifestyle, and socioeconomic position significantly affect general health status and brain health. This pilot study investigates the relationships among the Area Deprivation Index (ADI)—a measure of neighborhood-level socioeconomic deprivation, brain structure (cortical volume and thickness), and cognitive status in adults in Arizona. Identifying measures sensitive to ADI could elucidate mechanisms driving cognitive decline.MethodsThe study included 22 adults(mean age = 56.2 ± 15.2) in Arizona, residing in the area for over 10 years(mean = 42.7 ± 15.8). We assessed specific cognitive domains using the NeuroTrax™ cognitive screening test, which evaluates memory, executive function, visual–spatial processing, attention, information processing speed, and motor function. We also measured cortical thickness and volume in 10 cortical regions using FreeSurfer 7.2. Linear regression tests were conducted to examine the relationships between ADI metrics, cognitive status, and brain health measures.ResultsResults indicated a significant inverse relationship between ADI metrics and memory scores, explaining 25% of the variance. Both national and state ADI metrics negatively correlated with motor skills and global cognition (r’s 0.40, p’s

IntroductionTo address issues related to shallow soil tillage, low soil nutrient content, and single tillage method in maize production in the Western Inner Mongolia Region, this study implemented various tillage and straw return techniques, including strip cultivation, subsoiling, deep tillage, no-tillage, straw incorporation with strip cultivation, straw incorporation with subsoiling, straw incorporation with deep tillage, and straw incorporation with no tillage, while using conventional shallow spinning by farmers as the control.MethodsWe employed Xianyu 696 (XY696) and Ximeng 6 (XM6) as experimental materials to assess maize 100-grains weight, grain filling rate parameters, and grain nutrient quality. This investigation aimed to elucidate how tillage and straw return influence the accumulation of grain material in different maize varieties.Results and discussionThe results indicated that proper implementation of tillage and straw return had a significant impact on the 100-grains weight of both varieties. In comparison to CK (farmer’s rotary rotation), the most notable rise in 100-grains weight was observed under the DPR treatment (straw incorporation with deep tillage), with a maximum increase of 4.84% for XY696 and 6.28% for XM6. The proper implementation of tillage and straw return in the field resulted in discernible differences in the stages of improving the grain filling rates of different maize varieties. Specifically, XY696 showed a predominant increase in the filling rate during the early stage (V1), while XM6 exhibited an increase in the filling rates during the middle and late stages (V2 and V3). In comparison to CK, V1 increased by 1.54% to 27.56% in XY696, and V2 and V3 increased by 0.41% to 10.42% in XM6 under various tillage and straw return practices. The proper implementation of tillage and straw return had a significant impact on the nutritional quality of the grains in each variety. In comparison to CK, the DPR treatment resulted in the most pronounced decrease in the soluble sugar content of grains by 25.43% and the greatest increase in the crude fat content of grains by 9.67%.ConclusionUltimately, the proper implementation of soil tillage and straw return facilitated an increase in grain crude fat content and significantly boosted grain weight by improving the grouting rate parameters at all stages for various maize varieties. Additionally, the utilization of DPR treatment proved to be more effective. Overall, DPR is the most promising strategy to improve maize yield and the nutritional quality of grain in the long term in the Western Inner Mongolia Region.

Objective To develop scores for predicting the need for artificial airway procedures for acute trauma patients in the emergency department (ED).Design Retrospective case–control.Setting A tertiary comprehensive hospital in China.Participants 8288 trauma patients admitted to the ED within 24 hours of injury and who were admitted from 1 August 2012 to 31 July 2020.Primary and secondary outcome measures The study outcome was the establishment of an artificial airway within 24 hours of admission to the ED. Based on the different feature compositions, two scores were developed in the development cohort by multivariable logistic regression. The predictive performance was assessed in the validation cohort.Results The O-SPACER (Oxygen saturation, Systolic blood pressure, Pulse rate, Age, Coma Scale, Eye response, Respiratory rate) score was developed based on the patient’s basic information with an area under the curve (AUC) of 0.85 (95% CI 0.80 to 0.89) in the validation group. Based on the basic information and trauma scores, the IO-SPACER (Injury Severity Score, Oxygen saturation, Systolic blood pressure, Pulse rate, Age, Coma Scale, Eye response, Respiratory rate) score was developed, with an AUC of 0.88 (95% CI 0.84 to 0.92). According to the O-SPACER and IO-SPACER scores, the patients were stratified into low, medium and high-risk groups. According to these two scores, the high-risk patients were associated with an increased demand for artificial airways, with an OR of 40.16–40.67 compared with the low-risk patients.Conclusions The O-SPACER score provides risk stratification for injured patients requiring urgent airway intervention in the ED and may be useful in guiding initial management. The IO-SPACER score may assist in further determining whether the patient needs planned intubation or tracheotomy early after trauma.

Objective: To examine the associations of cardiorespiratory fitness with executive function, episodic memory, and global cognition and sex differences in these associations in community-dwelling older adults with amnestic mild cognitive impairment. Design: A cross-sectional study using baseline data from the aerobic exercise and cognitive training (ACT) trial. Setting: The ACT trial conducted exercise testing in an exercise laboratory and data collections in a research facility. Participants: ACT trial participants were recruited through referrals, registries, exhibits, flyers, media, and advertisements and screened for eligibility. To be eligible for this study, ACT enrollees needed complete data on all study variables. Among 146 ACT enrollees, 142 met eligibility for this study (N=142). Interventions: None. Main Outcome Measures: Cardiorespiratory fitness was measured as peak oxygen consumption (Vo2peak) with a peak cycle-ergometer test, executive function with the EXAMINER, episodic memory with the Brief Visuospatial Memory Test-Revised, and global cognition with Montreal Cognitive Assessment. Results: The average age of the sample was 73.8±5.8 years with 16.9±2.9 years of education, with 87.3% White, 51.4% men, and 69.7% married. After controlling for covariates, Vo2peak was significantly related to executive function (b=.037, standard error [SE]=0.015, P=.0154, semipartial [sr] correlation coefficient=.239) and episodic memory (b=.590, SE=0.226, P=.0102, sr=.216), but not global cognition (b=.074, SE=0.055, P=.1837, sr=.125). For men, Vo2peak was significantly associated with executive function (b=.063, SE=0.024, P=.0099, r=.430) and episodic memory (b=1.088, SE=0.312, P=.0009, r=.382). Conclusions: Our findings show that Vo2peak was associated with executive function and episodic memory in the overall sample and in men. Future studies can examine the longitudinal relations between cardiorespiratory fitness and cognition.

Abstract Background Older adults with Mild Cognitive Impairment (MCI) are often subject to cognitive and gait deficits. Interactive Computerized Cognitive Training (ICCT) may improve cognitive function; however, the effect of such training on gait performance is limited. Transcranial Direct Current Stimulation (tDCS) improves cognition and gait performance. It remains unclear whether combining tDCS with ICCT produces an enhanced synergistic effect on cognition and complex gait performance relative to ICCT alone. This study aimed to compare the effects of tDCS combined with ICCT on cognition and gait performance in older adults with MCI. Method Twenty-one older adults with MCI were randomly assigned to groups receiving either anodal tDCS and ICCT ( tDCS + ICCT ) or sham tDCS and ICCT ( sham + ICCT ). Participants played Nintendo Switch cognitive games for 40 min per session, simultaneously receiving either anodal or sham tDCS over the left dorsolateral prefrontal cortex for the first 20 min. Cognitive and gait assessments were performed before and after 15 training sessions. Results The global cognition, executive function, and working-memory scores improved in both groups, but there were no significant interaction effects on cognitive outcomes. Additionally, the group × time interactions indicated that tDCS + ICCT significantly enhanced dual-task gait performance in terms of gait speed (p = 0.045), variability (p = 0.016), and dual-task cost (p = 0.039) compared to sham + ICCT. Conclusion The combined effect of tDCS and ICCT on cognition was not superior to that of ICCT alone; however, it had a significant impact on dual-task gait performance. Administering tDCS as an adjunct to ICCT may thus provide additional benefits for older adults with MCI. Trial registration This trial was registered at http://www.clinicaltrials.in.th/ (TCTR 20,220,328,009).

Abstract Background Follow-up visits for very preterm infants (VPI) after hospital discharge is crucial for their neurodevelopmental trajectories, but ensuring their attendance before 12 months corrected age (CA) remains a challenge. Current prediction models focus on future outcomes at discharge, but post-discharge data may enhance predictions of neurodevelopmental trajectories due to brain plasticity. Few studies in this field have utilized machine learning models to achieve this potential benefit with transparency, explainability, and transportability. Methods We developed four prediction models for cognitive or motor function at 24 months CA separately at each follow-up visits, two for the 6-month and two for the 12-month CA visits, using hospitalized and follow-up data of VPI from the Taiwan Premature Infant Follow-up Network from 2010 to 2017. Regression models were employed at 6 months CA, defined as a decline in The Bayley Scales of Infant Development 3rd edition (BSIDIII) composite score > 1 SD between 6- and 24-month CA. The delay models were developed at 12 months CA, defined as a BSIDIII composite score

Abstract Introduction The prevalence of type 2 diabetes (T2D) has increased dramatically in recent decades, and there are increasing indications that dementia is related to T2D. Previous attempts to analyze such relationships principally relied on traditional multiple linear regression (MLR). However, recently developed machine learning methods (Mach-L) outperform MLR in capturing non-linear relationships. The present study applied four different Mach-L methods to analyze the relationships between risk factors and cognitive function in older T2D patients, seeking to compare the accuracy between MLR and Mach-L in predicting cognitive function and to rank the importance of risks factors for impaired cognitive function in T2D. Methods We recruited older T2D between 60–95 years old without other major comorbidities. Demographic factors and biochemistry data were used as independent variables and cognitive function assessment (CFA) was conducted using the Montreal Cognitive Assessment as an independent variable. In addition to traditional MLR, we applied random forest (RF), stochastic gradient boosting (SGB), Naïve Byer’s classifier (NB) and eXtreme gradient boosting (XGBoost). Results Totally, the test cohort consisted of 197 T2D (98 men and 99 women). Results showed that all ML methods outperformed MLR, with symmetric mean absolute percentage errors for MLR, RF, SGB, NB and XGBoost respectively of 0.61, 0.599, 0.606, 0.599 and 0.2139. Education level, age, frailty score, fasting plasma glucose and body mass index were identified as key factors in descending order of importance. Conclusion In conclusion, our study demonstrated that RF, SGB, NB and XGBoost are more accurate than MLR for predicting CFA score, and identify education level, age, frailty score, fasting plasma glucose, body fat and body mass index as important risk factors in an older Chinese T2D cohort.

Abstract Background According to previous research, 2.8% of lesions clinically identified as endodontic pathosis were ultimately diagnosed as non-endodontic periapical lesions via histopathology, and 3.7% of these non-endodontic periapical lesions were malignant neoplasms. Rhabdomyosarcoma, a malignant tumor most commonly observed in children, is uncommon in the oral cavity. Case presentation This is a report of a rare case of embryonal rhabdomyosarcoma in a 41-year-old female, in which the lesion was in the maxillary gingiva. The biopsy reports confirmed the diagnosis of embryonal rhabdomyosarcoma. The wide excision of the tumor, free flap reconstruction, chemotherapy, and radiotherapy were performed. Clinical, radiological, and histopathological and management aspects of the neoplasm were also discussed. Conclusions This case report aimed to create awareness that rhabdomyosarcoma is one of the differential diagnoses of periapical lesions.

Abstract Background Application of the thoracodorsal artery perforator (TDAP) flap is known to be a popular and reliable method for extremity reconstruction. This manuscript presents our clinical outcomes in reconstructing soft tissue defects using simple and advanced TDAP flaps. Methods From 2013 to 2022, 53 patients with a mean age of 23 years (ranging from 2 to 72 years) underwent reconstructive surgery with different patterns of free TDAP flaps, including chimeric TDAP flaps, double skin paddle TDAP flaps, flow-through TDAP flaps, conjoined TDAP flaps, and microdissected debulking TDAP flaps. Results All TDAP flaps survived. The size of the TDAP skin paddle ranged between 5 × 3 and 25 × 10 cm2. Primary closure of the donor site was achieved in all patients in the simple application group, and one patient in the advanced application group underwent partial skin grafting. Partial flap loss occurred in one case in the simple TDAP flap group and four cases in the advanced application group. There was one case of flap bulkiness and two cases of scar hyperplasia in the simple TDAP flap group. The mean follow-up duration was 11 months (4–46 months). Conclusions The free TDAP flap, with five types of advanced applications, makes it versatile for reconstructing different kinds of soft tissue defects of the extremities that can be used to achieve individualized defect reconstruction, minimize donor site morbidities, and an aesthetic appearance.