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Mycoplasma pneumoniae is a major cause of respiratory tract infections, particularly in children and young adults. M. pneumoniae accounts for 10%-30%) of community-acquired pneumonia (1). Macrolides are the primary treatment, [...]

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

Effective professional development is critical for improving implementation of evidence-based practices (EBPs) in special education. The present systematic review sought to gather evidence exploring the effects and key components of in-service special education teacher training in EBPs. This review identifies six essential components of training programs, including didactic presentation, live modeling, video modeling, practical exercise, performance feedback, and on-site coaching. Our findings suggest that training programs containing all or some of these components demonstrated 90% of effectiveness on teachers' outcomes. Specifically, practical exercises and performance feedback are key components to improve the rate of implementing EBPs with sufficient fidelity and on-site coaching is critical for sustaining the outcomes. Recommendations for effective professional development for special education teachers are discussed.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

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.

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.

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