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Background: Overactivated microglia that cluster at neuritic plaques constantly release neurotoxins, which actively contribute to progressive neurodegeneration in Alzheimer's disease (AD). Therefore, attenuating microglial clustering can reduce focal neuroinflammation at neuritic plaques. Previously, we identified CCL5 and CCL2 as prominent chemokines that mediate the chemotaxis of microglia toward beta-amyloid (Abeta)aggregates. Although transforming growth factor-beta1 (TGF-beta1) has been shown to down-regulate the expression of chemokines in activated microglia, whether TGF-beta1 can reduce the chemotaxis of microglia toward neuritic plaques in AD remains unclear.Methods: In the present study, we investigated the effects of TGF-beta1 on Abeta-induced chemotactic migration of BV-2 microglia using time-lapse recording, transwell assay, real-time PCR, ELISA, and western blotting.Results: The cell tracing results suggest that the morphological characteristics and migratory patterns of BV-2 microglia resemble those of microglia in slice cultures. Using this model system, we discovered that TGF-beta1 reduces Abeta-induced BV-2 microglial clustering in a dose-dependent manner. Chemotactic migration of these microglial cells toward Abeta aggregates was significantly attenuated by TGF-beta1. However, these microglia remained actively moving without any reduction in migration speed. Pharmacological blockade of TGF-beta1 receptor I (ALK5) by SB431542 treatment reduced the inhibitory effects of TGF-beta1 on Abeta-induced BV-2 microglial clustering, while preventing TGF-beta1-mediated cellular events, including SMAD2 phosphorylation and CCL5 down-regulation.Conclusions: Our results suggest that TGF-beta1 reduces Abeta-induced microglial chemotaxis via the SMAD2 pathway. The down-regulation of CCL5 by TGF-beta1 at least partially contributes to the clustering of microglia at Abeta aggregates. The attenuating effects of SB431542 upon TGF-beta1-suppressed microglial clustering may be mediated by restoration of CCL5 to normal levels. TGF-beta1 may ameliorate microglia-mediated neuroinflammation in AD by preventing activated microglial clustering at neuritic plaques. [ABSTRACT FROM AUTHOR]

Patients with newly diagnosed hematological malignancies often present with a considerable cellular burden, leading to complications including hyperkalemia. However, pseudohyperkalemia, arising from in vitro cell lysis, can pose challenges in clinical practice. Although pseudohyperkalemia is frequently reported in adult hematological malignancies, its occurrence in pediatric patients is underreported, and its incidence in this demographic remains unclear. We retrospectively reviewed the medical records of pediatric patients who received a new diagnosis of hematological malignancies from 2011 to 2022 at Taichung Veterans General Hospital. Hyperkalemia was defined by a serum or plasma potassium level exceeding 5.5 mEq/L. Pseudohyperkalemia was defined by 1) a potassium decrease of over 1 mEq/L in within 4 h without intervention or 2) the absence of electrocardiography changes indicative of hyperkalemia. Cases with apparent red blood cell hemolysis were excluded. A total of 157 pediatric patients with a new diagnosis of hematological malignancies were included, 14 of whom exhibited hyperkalemia. Among these 14 cases, 7 cases (4.5%) were of pseudohyperkalemia. This rate increased to 21.2% in patients with initial hyperleukocytosis. Pseudohyperkalemia was associated with a higher initial white blood cell count and lower serum sodium level. All episodes of pseudohyperkalemia occurred in the pediatric emergency department, where samples were obtained as plasma, whereas all true hyperkalemia cases were observed in the ordinary ward or intensive care unit, where samples were obtained as serum. Timely recognition of pseudohyperkalemia is crucial to avoiding unnecessary potassium-lowering interventions in pediatric patients with newly diagnosed hematological malignancies.

Excessive or inappropriate fear responses can lead to anxiety-related disorders, such as post-traumatic stress disorder (PTSD). Studies have shown that microglial activation occurs after fear conditioning and that microglial inhibition impacts fear memory. However, the role of microglia in fear memory recall remains unclear. In this study, we investigated the activated profiles of microglia after the recall of remote-cued fear memory and the role of activated microglia in the extinction of remote-cued fear in adult male C57BL/6 mice. The results revealed that the expression of the microglia marker Iba1 increased in the medial prefrontal cortex (mPFC) at 10 min and 1 h following remote-cued fear recall, which was accompanied by amoeboid morphology. Inhibiting microglial activation through PLX3397 treatment before remote fear recall did not affect recall, reconsolidation, or regular extinction but facilitated recall-extinction and mitigated spontaneous recovery. Moreover, our results demonstrated reduced co-expression of Iba1 and postsynaptic density protein 95 (PSD95) in the mPFC, along with decreases in the p-PI3K/PI3K ratio, p-Akt/Akt ratio, and KLF4 expression after PLX3397 treatment. Our results suggest that microglial activation after remote fear recall impedes fear extinction through the pruning of synapses in the mPFC, accompanied by alterations in the expression of the PI3K/AKT/KLF4 pathway. This finding can help elucidate the mechanism involved in remote fear extinction, contributing to the theoretical foundation for the intervention and treatment of PTSD., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

According to the behavioral tagging theory, various stages of fear memory, such as contextual fear conditioning, memory retrieval, and fear extinction, can be facilitated by the exploration of a novel open field (OF). A critical time window of efficacy exists for this process. Novel exploration closely adjacent to weak learning may interfere with the setting of the learning tag, leading to a negative effect. In this mouse study, we consistently showed that exposure to a novel or familiar OF immediately prior to the retention test impaired the retrieval of long-term contextual fear memory. However, OF exposure had no effect on the retrieval of recent or remote cued fear memory or short-term contextual fear memory or the reconsolidation of contextual fear memory. In addition, OF exposure impaired spaced but not massed extinction of contextual fear memory. These results suggest that interfering stimulus may result in the transient forgetting of fear memory; however, temporary loss of fear may lead to retention failure of fear extinction. The results of this study are an important complement to the behavioral tagging theory and may provide new guidance for the treatment of post-traumatic stress disorder., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Research studies on gastric cancer have not investigated the combined impact of body composition, age, and tumor staging on gastric cancer prognosis. To address this gap, we used machine learning methods to develop reliable prediction models for gastric cancer., Methods: This study included 1,132 gastric cancer patients, with preoperative body composition and clinical parameters recorded, analyzed using Cox regression and machine learning models., Results: The multivariate analysis revealed that several factors were associated with recurrence-free survival (RFS) and overall survival (OS) in gastric cancer. These factors included age (≥65 years), tumor-node-metastasis (TNM) staging, low muscle attenuation (MA), low skeletal muscle index (SMI), and low visceral to subcutaneous adipose tissue area ratios (VSR). The decision tree analysis for RFS identified six subgroups, with the TNM staging I, II combined with high MA subgroup showing the most favorable prognosis and the TNM staging III combined with low MA subgroup exhibiting the poorest prognosis. For OS, the decision tree analysis identified seven subgroups, with the subgroup featuring high MA combined with TNM staging I, II showing the best prognosis and the subgroup with low MA, TNM staging II, III, low SMI, and age ≥65 years associated with the worst prognosis., Conclusion: Cox regression identified key factors associated with gastric cancer prognosis, and decision tree analysis determined prognoses across different risk factor subgroups. Our study highlights that the combined use of these methods can enhance intervention planning and clinical decision-making in gastric cancer., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Teacher-student relationships are beneficial for students and especially important in the middle school context. Suspensions are critical to reduce as it can be detrimental to the educational trajectory of students, particularly for marginalized students in underfunded schools. This study looked at the relations between teacher-student relationships and suspensions across the academic year in a sample of students (N = 541) and teachers (N = 51) in two urban school districts in the Midwest. A brief measure of teachers' perceptions of relationships with students completed in the fall of the academic year predicted the odds of receiving in-school suspension (ISS; odds ratio [OR] = 0.65) and out-of-school suspension (OSS; OR = 0.72) by the end of the school year. Student reports of the relationships were also associated with ISS (OR = 0.94), but not OSS. On average, teachers' report on the scale improved over the course of the school year (d = 0.11); however, student report of the relationships worsened (d = 0.30). The difference in the student report of the relationships from fall to spring was also associated with the odds of receiving ISS and OSS (ORs = 0.94). These findings suggest that student and teacher perceptions together are associated with harsh discipline practices that can negatively impact students' developmental trajectories. Relationships can change but direct action is necessary to develop, maintain, and repair relationships during the academic year., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Primary extragonadal choriocarcinoma (PEGCC) in male is rare. It is highly malignant, typically presents with distant metastasis at the time of diagnosis, and responds poorly to treatment. Because of its associated high levels of PD-L1, the PD-1/PD-L1 pathway is a likely therapeutic target. Herein, we report our experience of treating pediatric PEGCC in six boys at a tertiary hospital., Methods: We analyzed the data of six boys with pathologically confirmed PEGCC between 2009 and 2021. Their clinicodemographic and histopathological characteristics as well as treatments and clinical outcomes were retrieved from their medical charts., Results: The patients' median age was 15 (range: 12-17) years. The most common primary tumor site was the mediastinum (67%, 4/6), with one case each in the retroperitoneum (16.7%) and brain (16.7%). Except for the patient with brain PEGCC, all presented with metastasis at the time of diagnosis. The following metastatic sites were observed: the lungs (100%, 5/5), brain (3/5, 60%), liver (3/5, 60%), kidneys (2/5, 40%), and spleen (1/5, 20%). Most patients had dry cough, dyspnea, and hemoptysis at initial presentation, likely due to lung metastasis. Serum human chorionic gonadotropin (HCG) levels were highly elevated in all patients. All patients received platinum-based cytotoxic chemotherapy. The patient with brain choriocarcinoma underwent surgical tumor resection; all others underwent only surgical biopsy. Strong positive PD-L1 immunohistochemical staining was noted for two patients. One patient received the PD-L1 inhibitor pembrolizumab and achieved a good response. Our cohort's 1-year survival rate was 33.3%, with a median survival of 4.34 months. Serum HCG levels remained normal in the two survivors during follow-up visits., Conclusion: The poor response to current platinum-based chemotherapy remains a major challenge in the management of pediatric PEGCC. Adding pembrolizumab to a conventional chemotherapy regimen may improve the outcomes in boys with PEGCC., Competing Interests: Declaration of competing interest The authors have declared no conflicts of interest., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Cognitive behavioral therapy, rooted in exposure therapy, is currently the primary approach employed in the treatment of anxiety-related conditions, including post-traumatic stress disorder (PTSD). In laboratory settings, fear extinction in animals is a commonly employed technique to investigate exposure therapy; however, the precise mechanisms underlying fear extinction remain elusive. Casein kinase 2 (CK2), which regulates neuroplasticity via phosphorylation of its substrates, has a significant influence in various neurological disorders, such as Alzheimer's disease and Parkinson's disease, as well as in the process of learning and memory. In this study, we adopted a classical Pavlovian fear conditioning model to investigate the involvement of CK2 in remote fear memory extinction and its underlying mechanisms. The results indicated that the activity of CK2 in the medial prefrontal cortex (mPFC) of mice was significantly upregulated after extinction training of remote cued fear memory. Notably, administration of the CK2 inhibitor CX-4945 prior to extinction training facilitated the extinction of remote fear memory. In addition, CX-4945 significantly upregulated the expression of p-ERK1/2 and p-CREB in the mPFC. Our results suggest that CK2 negatively regulates remote fear memory extinction, at least in part, by inhibiting the ERK-CREB pathway. These findings contribute to our understanding of the underlying mechanisms of remote cued fear extinction, thereby offering a theoretical foundation and identifying potential targets for the intervention and treatment of PTSD., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study investigates the potential utility of IKZF1 deletion as an additional high-risk marker for paediatric acute lymphoblastic leukaemia (ALL). The prognostic impact of IKZF1 status, in conjunction with minimal/measurable residual disease (MRD), was evaluated within the MRD-guided TPOG-ALL-2013 protocol using 412 newly diagnosed B-ALL patients aged 1-18. IKZF1 status was determined using multiplex ligation-dependent probe amplification. IKZF1 deletions, when co-occurring with CDKN2A, CDKN2B, PAX5 or PAR1 region deletions in the absence of ERG deletions, were termed IKZF1 plus . Both IKZF1 deletion (14.6%) and IKZF1 plus (7.8%) independently predicted poorer outcomes in B-ALL. IKZF1 plus was observed in 4.1% of Philadelphia-negative ALL, with a significantly lower 5-year event-free survival (53.9%) compared to IKZF1 deletion alone (83.8%) and wild-type IKZF1 (91.3%) (p < 0.0001). Among patients with Day 15 MRD ≥0.01%, provisional high-risk patients with IKZF1 plus exhibited the worst outcomes in event-free survival (42.0%), relapse-free survival (48.0%) and overall survival (72.7%) compared to other groups (p < 0.0001). Integration of IKZF1 plus and positive Day 15 MRD identified a subgroup of Philadelphia-negative B-ALL with a 50% risk of relapse. This study highlights the importance of assessing IKZF1 plus alongside Day 15 MRD positivity to identify patients at increased risk of adverse outcomes, potentially minimizing overtreatment., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Smart city is an area where the Internet of things is used effectively with sensors. The data used by smart city can be collected through the cameras, sensors etc. Intelligent video surveillance (IVS) systems integrate multiple networked cameras for automatic surveillance purposes. Such systems can analyze and monitor video data and perform automatic functions required by users. This study performed main path analysis (MPA) to explore the development trends of IVS research. First, relevant articles were retrieved from the Web of Science database. Next, MPA was performed to analyze development trends in relevant research, and g-index and h-index values were analyzed to identify influential journals. Cluster analysis was then performed to group similar articles, and Wordle was used to display the key words of each group in word clouds. These key words served as the basis for naming their corresponding groups. Data mining and statistical analysis yielded six major IVS research topics, namely video cameras, background modeling, closed-circuit television, multiple cameras, person reidentification, and privacy, security, and protection. These topics can boost the future innovation and development of IVS technology and contribute to smart transportation, smart city, and other applications. According to the study results, predictions were made regarding developments in IVS research to provide recommendations for future research.

Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimer's disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature., Competing Interests: HH, HS, SH, GS, YT, MT, MI, MS, IH, KH, MH, AN, YM, SO, MM, AU, YK, AM, KN, SK, TS, TI, HN, YG, MR, TT, KY, NT, HK, JI, IN, TK, TT, MD, HN, KT, KS, KN, TT, HF, YS, KY, LR, NH, HM, TY, SW, TA, KT, TN, HK, FH, AH, HH, KT, TT, TK, TK, IG, GC, NA, HH, SK, TK, MH, YH, RM, KO, AH, LB, IY, YH, HK, YM, KI, HK, BK, HO, YY, AT, NK, SG, MI, MN, KM, EO, IO, TS, KY, HA, KT, KI, TS, AK, MF, NU, TK, TT, YY, MI, TH, KI, KN, SH, KE, KH, YT, SN, NS, TY, NU, TY, YK, RO, NS, KS, SH, KO, HM, TF, MT, HS, DS, YI, TI, YK, TY, KS, TM No competing interests declared, SY, NN Employee of Takeda Pharmaceutical Company, Ltd

Ampicillin (AMP) and cefazolin (CZO) are commonly used β-lactam antibiotics which are extensively globally produced. Additionally, AMP and CZO are known to have relatively high ecotoxicity. Notably, the mix of AMP and CZO creates a synergistic effect that is more harmful to the environment, and how exposure to AMP-CZO can induce synergism in algae remains virtually unknown. To yield comprehensive mechanistic insights into chemical toxicity, including dose-response relationships and variations in species sensitivity, the integration of multiple endpoints with de novo transcriptomics analyses were used in this study. We employed Selenastrum capricornutum to investigate its toxicological responses to AMP and CZO at various biological levels, with the aim of elucidating the underlying mechanisms. Our assessment of multiple endpoints revealed a significant growth inhibition in response to AMP at the relevant concentrations. This inhibition was associated with increased levels of reactive oxygen species (ROS) and perturbations in nitrogen metabolism, carbohydrate metabolism, and energy metabolism. Growth inhibition in the presence of CZO and the AMP-CZO combination was linked to reduced viability levels, elevated ROS production, decreased total soluble protein content, inhibited photosynthesis, and disruptions in the key signaling pathways related to starch and sucrose metabolism, ribosome function, amino acid biosynthesis, and the production of secondary metabolites. It was concluded from the physiological level that the synergistic effect of Chlorophyll a (Chla) and Superoxide dismutase (SOD) activity strengthened the growth inhibition of S. capricornutum in the AMP-CZO synergistic group. According to the results of transcriptomic analysis, the simultaneous down-regulation of LHCA4 , LHCA1 , LHCA5, and sodA destroyed the functions of the photosynthetic system and the antioxidant system, respectively. Such information is invaluable for environmental risk assessments. The results provided critical knowledge for a better understanding of the potential ecological impacts of these antibiotics on non-target organisms.

Among pediatric blood cancers, acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy. Within ALL, T-cell acute lymphoblastic leukemia (T-ALL) accounts for 10 to 15% of all pediatric cases, and ~25% of adult cases. For T-ALL, its recurrence and relapse after treatment remain problematic. Therefore, it is necessary to develop new therapies for T-ALL. Recent studies suggested regulating energy metabolism is a novel approach to inhibit tumor growth, likely a promising treatment. Transketolase (TKT) is an important enzyme for modulating glucose metabolize in the pentose phosphate pathway (PPP). In this study, we treated T-ALL cells with different doses of niclosamide and primary T-ALL PBMCs were analyzed by RNA sequencing. T-ALL cells treated with niclosamide were analyzed with the Western blotting and TKT activity assay. Metabolism of T-ALL cells was evaluated by ATP assay and seahorse analyses. Lastly, we used a T-ALL xenograft murine model to determine effects of TKT knockdown on T-ALL tumor growth. Tumor samples were analyzed by H&E and IHC stainings. We found that niclosamide reduced T-ALL cell viability, and reduced expressions of TKT, Transketolase-Like Protein 1/2 (TKTL1/2) and transaldolase. In addition, niclosamide inhibited TKT enzyme activity, aerobic metabolism and glycolysis, finally leading to lower production of ATP. TKT knockdown inhibited tumor growth of xenograft T-ALL mice. Findings showed that niclosamide inhibits T-ALL cell growth by inhibiting TKT and energy metabolism., Competing Interests: None., (AJCR Copyright © 2024.)

Background: Donor lymphocyte infusion (DLI) is effective for managing patients with hematologic malignancies after allogeneic hematopoietic stem cell transplant (HSCT). However, few studies have explored its optimal use in pediatric populations. Herein, we report our single-center experiences of DLI and factors for predicting its outcomes., Methods: This retrospective study included pediatric patients who had received DLI (between June 1998 and December 2022) after allogeneic HSCT. Data regarding patient characteristics, preemptive DLI disease status, and DLI characteristics were collected. The primary outcomes were overall survival (OS), event-free survival (EFS), and graft-vs-host-disease (GVHD) development., Results: The study cohort comprised 17 patients with acute leukemia, 3 with chronic leukemia, and 3 with lymphoma. Prophylactic, preemptive, and therapeutic DLI were used in seven, seven, and nine patients, respectively. Patients' median age and DLI dose were 9 years and 4.6 × 10 7 CD3 + cells/kg, respectively. The 5-year OS, EFS, and nonrelapse mortality were 43.5%, 38.3%, and 13.3%, respectively. Approximately 39% of the patients developed grade III or IV acute GVHD, whereas moderate/severe chronic GVHD (cGVHD) occurred in 30% of the evaluable patients. Patients' disease status before HSCT ( p = 0.009) and DLI ( p = 0.018) were the key factors influencing EFS. The implementation of a dose escalation schedule was associated with a marginal reduction in the risk of moderate/severe cGVHD ( p = 0.051). A DLI dose of ≥5 × 10 7 CD3 + cells/kg was significantly associated with a high moderate to severe cGVHD risk ( p = 0.002) and reduced OS ( p = 0.089)., Conclusion: Patients' disease status before HSCT and DLI may help predict EFS. The use of DLI as a prophylactic and preemptive modality leads to a favorable 5-year EFS. To safely deliver DLI in children, clinicians must maintain vigilant monitoring and prepare patients in advance when escalating the dose to ≥5 × 10 7 CD3 + cells/kg., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

The overuse of exclusionary discipline practices, such as out-of-school suspensions (OSS), has consistently been documented over several decades. The resulting racial discipline disparities and the negative outcomes related to OSS have led policy makers and educators to consider other approaches to school discipline. One such approach, which has gained increasing use in the USA, is restorative practices (RP). However, despite its popularity, the experimental evidence base of the effects of RP and suspensions is extremely limited. To add to this knowledge base, we present findings from a cluster randomized controlled trial with 18 K-12 schools in an urban district in the US Northeast with 5878 students. Multilevel regression results, after 1 year of the intervention, showed no differences in the likelihood of suspension between students in the intervention and control schools and that the effects of the intervention did not vary by race/ethnicity, gender, or student disability status. However, for students in the intervention group, we show reductions in the likelihood of receiving an OSS for students who had previously been suspended., (© 2023. Society for Prevention Research.)

It is acknowledged that azole fungicides may release into the environment and pose potential toxic risks. The combined toxicity interactions of azole fungicide mixtures, however, are still not fully understood. The combined toxicities and its toxic interactions of 225 binary mixtures and 126 multi-component mixtures on Chlorella pyrenoidosa were performed in this study. The results demonstrated that the negative logarithm 50% effect concentration (pEC 50 ) of 10 azole fungicides to Chlorella pyrenoidosa at 96 h ranged from 4.23 (triadimefon) to 7.22 (ketoconazole), while the pEC 50 values of the 351 mixtures ranged from 3.91 to 7.44. The high toxicities were found for the mixtures containing epoxiconazole. According to the results of the model deviation ratio (MDR) calculated from the concentration addition (MDR CA ), 243 out of 351 (69.23%) mixtures presented additive effect at the 10% effect, while the 23.08% and 7.69% of mixtures presented synergistic and antagonistic effects, respectively. At the 30% effect, 47.29%, 29.34%, and 23.36% of mixtures presented additive effects, synergism, and antagonism, respectively. At the 50% effect, 44.16%, 34.76%, and 21.08% of mixtures presented additive effects, synergism, and antagonism, respectively. Thus, the toxicity interactions at low concentration (10% effect) were dominated by additive effect (69.23%), whereas 55.84% of mixtures induced synergism and antagonism at high concentration (50% effect). Climbazole and imazalil were the most frequency of components presented in the additive mixtures. Epoxiconazole was the key component induced the synergistic effects, while clotrimazole was the key component in the antagonistic mixtures., (© 2023 Wiley Periodicals LLC.)

As a transcription factor in the RUNT domain core-binding factor family, RUNX1 is crucial in multiple stages of hematopoiesis, and its mutation can cause familial platelet disorder with a predisposition to acute myeloid leukemia. Previous work has established that RUNX1 is involved in the maturation of megakaryocytes (MKs) and the production of platelets. Recent studies have shown that there exists a subpopulation of hematopoietic stem cells (HSCs) with relatively high expression of von Willebrand factor and CD41 at the apex of the HSC hierarchy, termed MK-HSCs, which can give rise to MKs without going through the traditional differentiation trajectory from HSC via MPP (multipotent progenitors) and MEP (megakaryocyte-erythroid progenitor). Here, by using Runx1F/FMx1-Cre mouse model, we discovered that the MK-HSC to MK direct differentiation can occur within 1 cell division, and RUNX1 is an important regulator in the process. Runx1 knockout results in a drastic decrease in platelet counts and a severe defect in the differentiation from MK-HSCs to MKs. Single cell RNA sequencing (RNAseq) analysis shows that MK-HSCs have a distinct gene expression signature compared with non-MK-HSCs, and Runx1 deletion alters the platelet and MK-related gene expression in MK-HSCs. Furthermore, bulk RNAseq and Cut&Run analyses show that RUNX1 binds to multiple essential MK or platelet developmental genes, such as Spi1, Selp, and Itga2b and regulates their expressions in MK-HSCs. Thus, by modulating the expression of MK-related genes, RUNX1 governs the direct differentiation from MK-HSCs to MKs and platelets., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Homogeneity of variance (HOV) is a well-known but often untested assumption in the context of multilevel models (MLMs). However, depending on how large the violation is, how different group sizes are, and the variance pairing, standard errors can be over or underestimated even when using MLMs, resulting in questionable inferential tests. We evaluate several tests (e.g., the H statistic, Breusch Pagan, Levene's test) that can be used with MLMs to assess violations of HOV. Although the traditional robust standard errors used with MLMs require at least 50 clusters to be effective, we assess a robust standard error adjustment (i.e., the CR2 estimator) that can be used even with a few clusters. Findings are assessed using a Monte Carlo simulation and are further illustrated using an applied example. We show that explicitly modeling the heterogenous variance structures or using the CR2 estimator are both effective at ameliorating the issues associated with the fixed effects of the regression model related to violations of HOV resulting from between-group differences.

Binary outcomes are often encountered when analyzing cluster randomized trials (CRTs). A common approach to obtaining the average treatment effect of an intervention may involve using a logistic regression model. We outline some interpretive and statistical challenges associated with using logistic regression and discuss two alternative/supplementary approaches for analyzing clustered data with binary outcomes: the linear probability model (LPM) and the modified Poisson regression model. In our simulation and applied example, all models use a standard error adjustment that is effective even if a low number of clusters is present. Simulation results show that both the LPM and modified Poisson regression models can provide unbiased point estimates with acceptable coverage and type I error rates even with as little as 20 clusters., (© 2021. Society for Prevention Research.)

Background: This study analyzed data from two consecutive protocols for children newly diagnosed with acute lymphoblastic leukemia (ALL) to determine the clinical impact of minimal/measurable residual disease (MRD) and recently identified tumor genetic subtypes., Methods: Genetic subtypes were determined by sequential approaches including DNA indexing, reverse transcriptase-polymerase chain reaction, multiplex ligation-dependent probe amplification, and RNA-sequencing. MRD was assessed by flow cytometry. The Taiwan Pediatric Oncology Group TPOG-ALL-2013 study enrolled patients who received MRD-directed therapy., Results: The 5-year event-free survival (EFS) and overall survival rates in the 2013 cohort were 77.8% and 86.9% compared to those of the 2002 cohort, which were 62.4% and 76.5%. Among patients treated with MRD-guided therapy, those with ETV6-RUNX1 fusion and high hyperdiploidy had the highest 5-year EFS (91.4% and 89.6%, respectively). The addition of dasatinib improved outcomes in patients with BCR-ABL1 ALL. Recently identified subtypes like DUX4-rearranged, ZNF384-rearranged, MEF2D-rearranged, and PAX5alt subtypes were frequently positive for MRD after remission induction, and these patients consequently received intensified chemotherapy. Treatment intensification according to the MRD improved the outcomes of patients presenting DUX4 rearrangements. In high-risk or very-high-risk subtypes, the TPOG-ALL-2013 regimen did not confer significant improvements compared to TPOG-ALL-2002, and the outcomes of BCR-ABL1-like, MEF2D-rearranged, and KMT2A-rearranged ALL subtypes (in addition to those of T-cell ALL) were not sufficiently good. Novel agents or approaches are needed to improve the outcomes for these patients., Conclusions: The TPOG-ALL-2013 study yielded outcomes superior to those of patients treated in the preceding TPOG-ALL-2002 study. This study provides important data to inform the design of future clinical trials in Taiwan., Plain Language Summary: MRD-directed therapy improved the outcomes for pediatric ALL, especially standard-risk patients. Genomic analyses and MRD might be used together for risk-directed therapy of childhood ALL. Our work provides important data to inform the design of future clinical trials in Taiwan., (© 2022 American Cancer Society.)

Atrial fibrillation (AF) is closely related to abnormal cerebral blood flow. Inflammation and oxidative stress have always been important factors in the pathophysiology of AF. It remains unknown whether inflammation and oxidative stress are correlated to hippocampal perfusion in patients with AF.Sixty-three patients with AF with normal hippocampal blood perfusion (NHBP) were compared to 71 patients with AF with abnormal hippocampal blood perfusion (AHBP) using a case-control study design. The serum levels of inflammation and oxidative stress were measured. The hippocampal perfusion was detected. (1) The serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and oxidized low-density lipoprotein (ox-LDL) were statistically higher in the AHBP group than in the NHBP group. In the AHBP subgroup analysis, the serum levels of hs-CRP and IL-6 were statistically higher in patients with persistent AF than those with paroxysmal AF. (2) The relative cerebral blood volume (rCBV), mean transit time (MTT), and the time-to-peak (TTP) were statistically higher in the AHBP group than in the NHBP group. Moreover, cerebral blood flow (rCBF) was statistically lower in the AHBP group than in the NHBP group. (3) relative cerebral blood volume (rCBV), rCBF, MTT, and TTP were passively associated with serum hs-CRP and IL-6; rCBV, rCBF, and MTT were positively associated with ox-LDL. The serum levels of hs-CRP, IL-6, and ox-LDL were associated with AHBP in patients with AF after multivariate logistic regression analysis.Oxidative stress and inflammatory biomarkers were increased in patients with AF with AHBP, in which the serum levels of hs-CRP and IL-6 in the persistent AF group were statistically higher than those in the paroxysmal AF group. The serum levels of hs-CRP, IL-6, and ox-LDL were associated with AHBP in patients with AF.

Objective: Cervical fractures with ankylosing spondylitis (CAS) are a specific type of spinal fracture with poor stability, low healing rate, and high disability rate. Its treatment is mainly surgical, predominantly through the anterior approach, posterior approach, and the anterior-posterior approach. Although many clinical studies have been conducted on various surgical approaches, controversy still exists concerning the choice of these surgical approaches by surgeons. The authors present here a systematic evaluation and meta-analysis exploring the utility of the anterior-posterior approach versus the anterior approach and the posterior approach., Methods: After a comprehensive literature search of PubMed, Cochrane, Web of Science, and Embase databases, 12 clinical studies were included in the final qualitative analysis and 8 in the final quantitative analysis. Of these studies, 11 conducted a comparison between the anterior-posterior approach and the anterior approach and posterior approaches, while one examined only the anterior-posterior approach. Where appropriate, statistical advantage ratios and 95% confidence intervals were calculated., Results: The present meta-analysis of postoperative neurological improvement showed no statistical difference in the overall neurological improvement rate between the anterior-posterior approach and anterior approach (OR 1.70, 95% CI 0.61 to 4.75; p = 0.31). However, the mean change in postoperative neurological function was lower in patients who received the anterior approach than in those who received the anterior-posterior approach (MD 0.17, 95% CI -0.02 to 0.36; p = 0.08). There was an identical trend between the anterior-posterior approach and posterior approach, with no statistically significant difference in the overall rate of neurological improvement (OR 1.37, 95% CI 0.70 to 2.56; p = 0.38). Nevertheless, the mean change in neurological function was smaller in patients receiving the anterior-posterior approach compared with the posterior approach, but there was no statistically significant difference between the two (MD 0.17, 95% CI -0.02 to 0.36; p = 0.08)., Conclusions: The results of this review and meta-analysis suggest that the benefits of the anterior-posterior approach are different from those of the anterior and posterior approaches in the treatment of ankylosing spondylitis-related cervical fractures. In a word, there is no significant difference between the cervical surgical approach and the neurological functional improvement. Therefore, surgeons should pay more attention to the type of cervical fracture, the displacement degree of cervical fracture, the spinal cord injury, the balance of cervical spine and other aspects to comprehensively consider the selection of appropriate surgical methods., (© 2022. The Author(s).)

Background: Enhanced nonpharmaceutical interventions (NPIs) to prevent the Coronavirus Disease 2019 (COVID-19) have shown various levels of impact on common respiratory pathogens. We aimed to analyze the epidemiological changes seen in certain common respiratory viruses found in Taiwanese children (e.g., influenza virus, enterovirus, parainfluenza virus, adenovirus and respiratory syncytial virus (RSV)) after the implementation of public health measures, as well as interpret the possible meaning of these changes., Methods: This retrospective observational study examined the viral isolation from children younger than 18 years at a medical center in central Taiwan during the period January 2015-December 2020, a time frame of six years. Viral isolations prior to the COVID-19 pandemic (January 2015-December 2019), along with those during the post-COVID-19 period (January-December 2020) were analyzed and compared., Results: A total of 6899 throat swab samples were collected during the pre-pandemic period of 2015-2019, with 2681 of them having a positive result (38.86%). There were a total of 713 samples collected in 2020, with 142 of them showing positive results (19.92%). The overall positive rate of viral isolates significantly decreased in 2020 (p < 0.001). Declines in the isolation of the influenza virus, parainfluenza virus, adenovirus and enterovirus were observed. The RSV surprisingly became the leading isolate, with up to 47 (6.59%) instances in 2020, and showing an unusual peak in the winter of 2020. The rise began in September of 2020 and reached its plateau in November of that year., Conclusions: Most respiratory viruses decreased under NPIs regarding SARS-CoV-2. However, the RSV outbreak in the winter of 2020 had shown the limitation of current NPIs. Possible explanations have been discussed in details and public preventive measures should be reinforced for RSV, particularly amongst people having young children both at home and in care centers., Competing Interests: Declaration of competing interest The authors declare there are no conflicts of interest to disclose., (Copyright © 2021. Published by Elsevier B.V.)

Identification of specific leukemia subtypes is a key to successful risk-directed therapy in childhood acute lymphoblastic leukemia (ALL). Although RNA sequencing (RNA-seq) is the best approach to identify virtually all specific leukemia subtypes, the routine use of this method is too costly for patients in resource-limited countries. This study enrolled 295 patients with pediatric ALL from 2010 to 2020. Routine screening could identify major cytogenetic alterations in approximately 69% of B-cell ALL (B-ALL) cases by RT-PCR, DNA index, and multiplex ligation-dependent probe amplification. STIL-TAL1 was present in 33% of T-cell ALL (T-ALL) cases. The remaining samples were submitted for RNA-seq. More than 96% of B-ALL cases and 74% of T-ALL cases could be identified based on the current molecular classification using this sequential approach. Patients with Philadelphia chromosome-like ALL constituted only 2.4% of the entire cohort, a rate even lower than those with ZNF384-rearranged (4.8%), DUX4-rearranged (6%), and Philadelphia chromosome-positive (4.4%) ALL. Patients with ETV6-RUNX1, high hyperdiploidy, PAX5 alteration, and DUX4 rearrangement had favorable prognosis, whereas those with hypodiploid and KMT2A and MEF2D rearrangement ALL had unfavorable outcomes. With the use of multiplex ligation-dependent probe amplification, DNA index, and RT-PCR in B-ALL and RT-PCR in T-ALL followed by RNA-seq, childhood ALL can be better classified to improve clinical assessments., (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the effects of menopausal stage, age and other associated risk factors on symptoms of anxiety and depression among women in a community in Beijing. Methods: This study was a community-based prospective cohort. Participants who had transitioned through natural menopause, completed two or more depressive and anxiety symptoms evaluations, aged 35 to 64 years, and did not use hormone therapy were selected from the Peking Union Medical College Hospital aging longitudinal cohort of women in midlife to this analysis. The primary outcome variables were depressive and anxiety symptoms, assessed by hospital anxiety and depression scale (HADS). The generalized estimation equation was used in the statistical analysis. Results: Followed up from 2006 to 2014, 430 women and 2 533 HADS assessments were retained in the cohort. Depressive symptoms were more common than anxiety symptoms during all menopausal stages. The incidences of depressive and anxiety symptoms were 14.5% (19/191) and 3.1% (4/191) in the premenopausal -3 stage, respectively. The incidence increased in both menopausal transition and postmenopausal stage, with the highest incidence in the +1c stage [20.6% (155/751) and 8.8% (66/751), respectively]. However, these differences were not statistically significant (all P >0.05). Depressive symptoms were highest in the ≥60-<65 age group [20.8% (74/355)], and anxiety symptoms were highest in the ≥50-<55 age group [8.2% (62/754)]; but there were no statistical significances between different age groups and depressive and anxiety symptoms (all P >0.05). Multivariable analysis showed that high body mass index, low education status, and poor health status were independently associated with depressive symptoms (all P <0.05), and that poor health status, trouble falling asleep, and early awakening were independently associated with anxiety symptoms (all P <0.01). Conclusions: Depressive and anxiety symptoms are more common during menopausal transition and postmenopausal stage compared with reproductive stage. Depressive symptoms are more common than anxiety symptoms. To screen and assess depressive and anxiety symptoms in perimenopausal women is essential, especially for women with high risk factors.

In this paper, a polycrystalline diamond was synthesized by the direct detonation method using graphite as the carbon source. By comparing the numbers of the obtained diamond particles and the original graphite particles, it was found that when the graphite phase transformed into the polycrystalline diamond during the detonation process, a single graphite particle would form multiple diamond nuclei, and the nuclei would grow simultaneously to form polycrystals. Accordingly, a validation experiment was designed, which added different ratios of inert additives while keeping the ratio of graphite to hexogen (RDX) unchanged. It was found that increasing the ratio of inert additives within a certain range could increase the grain size of a polycrystalline diamond, which is consistent with the obtained polycrystalline mechanism.

Accounting for dependent observations in cluster-randomized trials (CRTs) using nested data is necessary in order to avoid misestimated standard errors resulting in questionable inferential statistics. Cluster-robust standard errors (CRSEs) are often used to address this issue. However, CRSEs are still well-known to underestimate standard errors for group-level variables when the number of clusters is low (e.g., < 50) and with CRTs, a small number of clusters, due to logistical or financial considerations, is the norm rather than the exception. Using a simulation with various conditions, we investigate the use of a small sample correction (i.e., CR2 estimator) proposed by Bell and McCaffrey (2002) together with empirically derived degrees of freedom estimates (dof BM ). Findings indicate that even with as few as 10 clusters, the CR2 estimator used with dof BM yields generally unbiased results with acceptable type I error and coverage rates. Results show that coverage and type I error rates can be largely influenced by the choice of dof, not just the standard error adjustments. An applied example is provided together with R syntax to conduct the analysis. To facilitate the use of different CRSEs, a free graphical, menu-driven SPSS add-on to compute the various cluster-robust variance estimates can be downloaded from https://github.com/flh3/CR2/tree/master/SPSS ., (© 2021. The Psychonomic Society, Inc.)

Tumor lysis syndrome (TLS) is a life-threatening condition that may occur in patients with lymphoma, leukemia, or cancers with high cellular burdens. Without appropriate treatment, electrolyte imbalances, namely hyperkalemia, hyperphosphatemia, and hypocalcemia, can be fatal in patients with TLS. In pseudohyperkalemia, concurrent hyperphosphatemia and hypocalcemia can render devising a treatment strategy challenging. We report an adolescent with T-lymphoblastic lymphoma who presented with pseudohyperkalemia but actual hyperphosphatemia and hypocalcemia, to highlight the importance of accurate clinical interpretations of laboratory data in patients with TLS., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

T‑cell acute lymphoblastic leukemia (T‑ALL) is a common pediatric malignancy, characterized by the abnormal presence of immature T‑cell progenitors. Conventional treatments for T‑ALL fail to prevent or cure the disease, with a high‑risk of recurrence after the first remission. Thus, medical options are in demand to develop novel therapies for patients suffering with T‑ALL. Niclosamide, a traditional oral anti‑helminthic drug, has been reported to be a potential anticancer agent that regulates intracellular signaling pathways. Few studies have yet investigated the effects of niclosamide on the development of T‑ALL. Here, the present study aimed to investigate the anti‑leukemia effects of niclosamide on T‑ALL. We first hypothesized that the suppressive effects of niclosamide on the tumor growth of T‑ALL are exerted by regulating autophagy and apoptosis. Following niclosamide treatment, T‑ALL cell viability was evaluated using MTT assay, and apoptosis with Annexin V/propidium iodide staining. In T‑ALL cells treated with niclosamide, changes in apoptosis‑ and autophagy‑related proteins were analyzed by western blotting. In addition, in an in vivo model, T‑ALL xenograft mice were used to study the anti‑leukemia effects of niclosamide. The results showed that niclosamide significantly reduced the viability of Jurkat and CCRF‑CEM T‑ALL cells in both a dose‑ and time‑dependent manner. Niclosamide significantly activated the early and late phases of apoptosis in Jurkat (at 2 µM) and CCRF‑CEM cells (at 1 µM). Furthermore, niclosamide upregulated protein expression of cleaved caspase‑3 and LC3B, while downregulated those of Bcl‑2 and p62, in a dose‑dependent manner in both Jurkat and CCRF‑CEM cells. The in vivo results showed that niclosamide treatment significantly suppressed tumor growth and the disease progression in T‑ALL xenograft mice by activating cleaved caspase‑3 and LC3B. We conclude that niclosamide plays an anti‑leukemia role, and that it represents a novel approach for the treatment of T‑ALL.

Background: The totally implanted vascular access device (TIVAD) is commonly used in patients with malignant tumors requiring chemotherapy or long-term intravenous infusion and those with difficulty placing peripheral venous catheters. It could also be used to draw blood in pediatric patients. Thus, how to maintain the patency and longevity of TIVAD is always emphasized., Methods: In this prospective study, TIVAD was randomly infused in patients under 18 years with three different concentrations of heparinized solutions: 10 mL with 100 U/mL heparin, 20 mL with 10 U/mL heparin, and 30 mL with 10 U/mL heparin., Results: A total of 81 patients (46 males and 35 females) were enrolled in this study from August 2, 2013 to February 1, 2017. The mean age of those who received TIVAD implantation was 7.2 ± 5.3 years, and the mean duration of using TIVAD was 1027.6 ± 369.1 days. Patients without catheter occlusion events experienced significantly shorter hospitalizations, fewer admissions, and fewer punctures than those with catheter occlusion events (p < 0.05). The administration and frequency of blood transfusions, history of bacteremia, and medication history did not increase the risk of catheter occlusion, but puncture frequency increased this risk. In patients with catheter occlusion events (38/81, 46.9%), catheter patency was restored after instillation of urokinase solution., Conclusion: In this study, the risk of TIVAD catheter occlusion was only related to puncture frequency regardless of the heparin flush composition or patient characteristics. A high puncture frequency of TIVAD during the 3.5-year study period significantly increased the risk of catheter occlusion. Besides, flushing and locking solutions for TIVAD using heparin at 10 U/mL was effective as using heparin at 100 U/mL regardless of the flushing volume of 10, 20, or 30 mL., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

The importance of math achievement in the early grades has been well documented. Two variables that have independently been found to be strong predictors of math achievement are student-teacher relationships (STR) and socioeconomic status (SES). The present study investigates the interaction between STR and SES on student math achievement using the Early Childhood Longitudinal Study, a nationally representative data set. The participants included approximately 8,380 first-grade students, 2,930 teachers, and 860 schools, representing a weighted sample of approximately 3.15 million students or 90% of the population. Multilevel modeling, controlling for student-, teacher-, and school-level factors, found that both STR and SES had a strong relationship with student math achievement. There was also a statistically significant moderation effect between close STR and SES on math achievement, suggesting that close STR are beneficial for all students, but are especially beneficial for students from low SES backgrounds. Further, educational implications for research, policy, and practice are provided. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The Coronavirus disease 2019 (COVID-19) pandemic created unprecedented challenges for the U.S. education system and for teachers. The present study examined correlates and predictors of teacher well-being in the immediate aftermath of school closures related to the pandemic. Data were collected as part of a larger group randomized trial. Six hundred and thirty-nine teachers completed surveys about their stress, coping, health, job satisfaction, and internalizing symptoms in Fall 2019, before the pandemic, and May 2020, during the pandemic. Teachers also provided ratings during COVID-19 of their teaching, student attendance and engagement, and concern about students and families. Teachers reported lower levels of work-related stress after the pandemic's onset compared to their prepandemic levels. Multilevel regression analyses revealed teacher confidence in their ability to manage student behaviors as a consistent and robust predictor of teacher well-being outcomes. Additionally, pre-COVID-19 school-level factors measured in Fall 2019, including collegial school leadership and fair and equitable school discipline structures, also predicted aspects of teacher well-being at the onset of COVID-19. Findings suggest the importance of teacher competence and perceived efficacy in managing student behavior and engaging them in learning to help them adapt to the stressors of a pandemic. Additionally, aspects of organizational health and climate may also help facilitate or hinder teacher adjustment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background: Gestational anemia is a serious public health problem that affects pregnant women worldwide. Pregnancy conditions and outcomes might be associated with the presence of gestational anemia. This study investigated the association of pregnancy characteristics with anemia, exploring the potential etiology of the disease., Aim: To assess the association of pregnancy parameters with gestational anemia., Methods: A nested case-control study was conducted based on the Chinese Pregnant Women Cohort Study-Peking Union Medical College Project (CPWCS-PUMC). A total of 3172 women were included. Patient characteristics and gestational anemia occurrence were extracted, and univariable and multivariable logistic regression models were used to analyze the association of pregnancy parameters with gestational anemia., Results: Among the 3172 women, 14.0% were anemic, 46.4% were 25-30 years of age, 21.9% resided in eastern, 15.7% in middle, 12.4% in western 18.0% in southern and 32.0% in northern regions of China. Most women (65.0%) had a normal prepregnancy body mass index. Multivariable analysis found that the occurrence of gestational anemia was lower in the middle and western regions than that in the eastern region [odds ratio (OR) = 0.406, 95% confidence interval (CI): 0.309-0.533, P < 0.001)], higher in the northern than in the southern region (OR = 7.169, 95%CI: 5.139-10.003, P < 0.001), lower in full-term than in premature births (OR = 0.491, 95%CI: 0.316-0.763, P = 0.002), and higher in cases with premature membrane rupture (OR=1.404, 95%CI: 1.051-1.876, P = 0.02)., Conclusion: Gestational anemia continues to be a health problem in China, and geographical factors may contribute to the situation. Premature birth and premature membrane rupture may be associated with gestational anemia. Therefore, we should vigorously promote local policy reformation to adapt to the demographic characteristics of at-risk pregnant women, which would potentially reduce the occurrence of gestational anemia., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Acute heart failure (AHF) is the major cause of death in children with severe enterovirus 71 (EV71) infection. This study aimed to report our clinical experience with EV71-related AHF, as well as to discuss its pathogenesis and relationship to Takotsubo syndrome (TTS). Methods: A total 27 children with EV71-related AHF between 1998 and 2018 were studied. The TTS diagnosis was based on the International Takotsubo Diagnostic Criteria. Results: Acute heart failure-related early death occurred in 10 (37%) of the patients. Sinus tachycardia, systemic hypertension, and pulmonary edema in 100, 85, and 81% of the patients, respectively, preceded AHF. Cardiac biomarkers were significantly increased in most patients. The main echocardiographic findings included transient and reversible left ventricular (LV) regional wall motion abnormality (RWMA) with apical ballooning. High concentrations of catecholamines either preceded or coexisted with AHF. Myocardial pathology revealed no evidence of myocarditis, which was consistent with catecholamine-induced cardiotoxic damage. Patients with EV71-related AHF who had received close monitoring of their cardiac function, along with early intervention involving extracorporeal life support (ECLS), had a higher survival rate (82 vs. 30%, p = 0.013) and better neurological outcomes (59 vs. 0%, p = 0.003). Conclusion: EV 71-related AHF was preceded by brain stem encephalitis-related hypercatecholaminemia, which resulted in a high mortality rate. Careful monitoring is merited so that any life-threatening cardiogenic shock may be appropriately treated. In view of the similarities in their clinical manifestations, natural course direction, pathological findings, and possible mechanisms, TTS and EV71-related AHF may represent the same syndrome. Therefore, we suggest that EV71-related AHF could constitute a direct causal link to catecholamine-induced secondary TTS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jan, Fu, Chi, Lee, Huang, Wang, Wei, Lin, Chen and Hwang.)

Background: The factors that predict the progression of Mycoplasma pneumoniae infection remain inconclusive. Therefore, we investigated macrolide resistance prevalence, M pneumoniae genotype, and clinical characteristics of childhood M pneumoniae respiratory tract infections in Taiwan., Methods: A total of 295 children hospitalized with respiratory tract infections with positive serological M pneumoniae immunoglobulin M test results were enrolled in this 3-year prospective study. Oropharyngeal swabs were obtained for M pneumoniae cultures and polymerase chain reaction tests. All M pneumoniae specimens were further characterized by P1 typing, multilocus variable-number tandem-repeat analysis (MLVA), and macrolide resistance genotyping. The clinical characteristics and blood cytokine profiles were analyzed accordingly., Results: Of 138 M pneumoniae specimens, type I P1 was the predominant (136 of 138, 98.6%). The MLVA type P (4-4-5-7-2) was the leading strain (42 of 138, 30.4%), followed by type J, U, A, and X. The overall macrolide-resistant rate was 38.4% (53 of 138); the resistance rate increased dramatically yearly: 10.6% in 2017, 47.5% in 2018, and 62.5% in 2019 ( P  < .001). All macrolide-resistant M pneumoniae (MRMP) harbored the A2063G mutation and were MLVA type 4-5-7-2 (49 of 53, 92.5%), especially type U and X. No significant differences in clinical symptoms, duration of hospital stay, and radiographic findings were identified among patients between MRMP and macrolide-sensitive M pneumoniae (MSMP) groups. Patients with MRMP infection had more febrile days before and during hospitalization and higher interleukin (IL)-13 and IL-33 levels than patients with MSMP infection ( P  < .05)., Conclusions: Macrolide-resistant M pneumoniae surged in Taiwan throughout the study period, but macrolide resistance was not a determinant factor of clinical severity., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective To explore the performance of mobile health platform for standardized management of pregnant women with gestational diabetes mellitus(GDM). Methods A randomized controlled trial was conducted,in which 295 women with GDM were randomized into two groups(traditional management group and mobile health management group)by a computer-generated sequence.The traditional management group accepted standardized GDM management,and the mobile health management group was supplemented by mobile health management based on the standardized management.The glycemic control rate and the incidences of low birth weight,macrosomia,preterm birth,premature rupture of membranes,postpartum hemorrhage after cesarean section,neonatal asphyxia,malformation,and admission to the neonatal intensive care unit were compared between the two groups. Results The glycemic control rate in mobile health management group was significantly higher than that in the traditional management group [(67.22±22.76)% vs. (60.69±21.28)%, P =0.004].The incidences of low birth weight,macrosomia,preterm birth,premature rupture of membranes,postpartum hemorrhage after cesarean section,neonatal asphyxia,malformation,and admission to the neonatal intensive care unit demonstrated no significant differences between groups(all P > 0.05). Conclusions Mobile health applied in standardized management is conducive to the glycemic control of GDM women,whereas it does not significantly improve the pregnancy outcomes.Due to the short time of intervention,the effects of mobile health on pregnancy outcomes need further study.

Objectives: Delay in diagnosis of tuberculosis (TB) is an important but under-appreciated problem. Our study aimed to analyse the patient pathway and possible risk factors of long diagnostic delay (LDD)., Methods: We enrolled 400 new bacteriologically diagnosed patients with pulmonary TB from 20 hospitals across China. LDD was defined as an interval between the initial care visit and the confirmation of diagnosis exceeding 14 days. Its potential risk factors were investigated by multivariate logistic regression and multilevel logistic regression. Hospitals in China were classified by increasing size, from level 0 to level 3. TB laboratory equipment in hospitals was also evaluated., Results: The median diagnostic delay was 20 days (IQR: 7-72 days), and 229 of 400 patients (57.3%, 95%CI 52.4-62.1) had LDD; 15% of participants were diagnosed at the initial care visit. Compared to level 0 facilities, choosing level 2 (OR 0.27, 95%CI 0.12-0.62, p 0.002) and level 3 facilities (OR 0.34, 95%CI 0.14-0.84, p 0.019) for the initial care visit was independently associated with shorter LDD. Equipping with smear, culture, and Xpert at initial care visit simultaneously also helped to avoid LDD (OR 0.28, 95%CI 0.09-0.82, p 0.020). The multilevel logistic regression yielded similar results. Availability of smear, culture, and Xpert was lower in level 0-1 facilities than in level 2-3 facilities (p < 0.001, respectively)., Conclusions: Most patients failed to be diagnosed at the initial care visit. Patients who went to low-level facilities initially had a higher risk of LDD. Improvement of TB laboratory equipment, especially at low-level facilities, is urgently needed., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)