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To date, symptom documentation has mostly relied on clinical notes in electronic health records or patient-reported outcomes using disease-specific symptom inventories. To provide a common and precise language for symptom recording, assessment, and research, a comprehensive list of symptom codes is needed. The International Classification of Diseases, Ninth Revision or its clinical modification (International Classification of Diseases, Ninth Revision, Clinical Modification) has a range of codes designated for symptoms, but it does not contain codes for all possible symptoms, and not all codes in that range are symptom related. This study aimed to identify and categorize the first list of International Classification of Diseases, Ninth Revision, Clinical Modification symptom codes for a general population and demonstrate their use to characterize symptoms of patients with type 2 diabetes mellitus in the Cerner database. A list of potential symptom codes was automatically extracted from the Unified Medical Language System Metathesaurus. Two clinical experts in symptom science and diabetes manually reviewed this list to identify and categorize codes as symptoms. A total of 1888 International Classification of Diseases, Ninth Revision, Clinical Modification symptom codes were identified and categorized into 65 categories. The symptom characterization using the newly obtained symptom codes and categories was found to be more reasonable than that using the previous symptom codes and categories on the same Cerner diabetes cohort., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Interleukin-(IL) 22 production by intestinal group 3 innate lymphoid cells (ILC3) is critical to maintain gut homeostasis. However, IL-22 needs to be tightly controlled; reduced IL-22 expression is associated with intestinal epithelial barrier defect while its overexpression promotes tumor development. Here, using a single-cell ribonucleic acid sequencing approach, we identified a core set of genes associated with increased IL-22 production by ILC3. Among these genes, programmed cell death 1 (PD-1), extensively studied in the context of cancer and chronic infection, was constitutively expressed on a subset of ILC3. These cells, found in the crypt of the small intestine and colon, displayed superior capacity to produce IL-22. PD-1 expression on ILC3 was dependent on the microbiota and was induced during inflammation in response to IL-23 but, conversely, was reduced in the presence of Notch ligand. PD-1 + ILC3 exhibited distinct metabolic activity with increased glycolytic, lipid, and polyamine synthesis associated with augmented proliferation compared with their PD-1 - counterparts. Further, PD-1 + ILC3 showed increased expression of mitochondrial antioxidant proteins which enable the cells to maintain their levels of reactive oxygen species. Loss of PD-1 signaling in ILC3 led to reduced IL-22 production in a cell-intrinsic manner. During inflammation, PD-1 expression was increased on natural cytotoxicity receptor (NCR) - ILC3 while deficiency in PD-1 expression resulted in increased susceptibility to experimental colitis and failure to maintain gut barrier integrity. Collectively, our findings uncover a new function of the PD-1 and highlight the role of PD-1 signaling in the maintenance of gut homeostasis mediated by ILC3 in mice., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Tissue-resident innate lymphoid cells (ILCs) play a vital role in the frontline defense of various tissues, including the lung. The development of type 2 ILCs (ILC2s) depends on transcription factors such as GATA3, RORα, GFI1, and Bcl11b; however, the factors regulating lung-resident ILC2s remain unclear. Through fate mapping analysis of the paralog transcription factors GFI1 and GFI1B, we show that GFI1 is consistently expressed during the transition from progenitor to mature ILC2s. In contrast, GFI1B expression is limited to specific subsets of bone marrow progenitors and lung-resident ILC progenitors. We found that GFI1B + lung ILC progenitors represent a multi-lineage subset with tissue-resident characteristics and the potential to form lung-derived ILC subsets and liver-resident ILC1s. Loss of GFI1B in bone marrow progenitors led to the selective loss of lung-resident IL-18R + ILCs and mature ILC2, subsequently preventing the emergence of effector ILCs that could protect the lung against inflammatory or tumor challenge.

Fibroblastic reticular cells (FRCs) construct microanatomical niches that support lymph node (LN) homeostasis and coordination of immune responses. Transcription factors regulating the functionality of FRCs remain poorly understood. Here, we investigated the role of the transcription factor SpiB that is expressed in LN FRCs. Conditional ablation of SpiB in FRCs impaired the FRC network in the T-cell zone of LNs, leading to reduced numbers of FRCs and altered homeostatic functions including reduced CCL21 and interleukin-7 expression. The size and cellularity of LNs remained intact in the absence of SpiB but the space between the reticular network increased, indicating that although FRCs were reduced in number they stretched to maintain network integrity. Following virus infection, antiviral CD8 + T-cell responses were impaired, suggesting a role for SpiB expression in FRCs in orchestrating immune responses. Together, our findings reveal a new role for SpiB as an important regulator of FRC functions and immunity in LNs., (© 2024 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.)

Pyridine is a widely employed nitrogen-containing heterocyclic organic, and the discharge of pyridine wastewater poses substantial environmental challenges due to its recalcitrance and toxicity. Co-metabolic degradation emerged as a promising solution. In this study, readily degradable glucose and the structurally analogous phenol were used as co-metabolic substrates respectively, and the corresponding mechanisms were thoroughly explored. To treat 400 mg/L pyridine, all reactors achieved remarkably high removal efficiencies, surpassing 98.5%. And the co-metabolism reactors had much better pyridine-N removal performance. Batch experiments revealed that glucose supplementation bolstered nitrogen assimilation, thereby promoting the breakdown of pyridine, and resulting in the highest pyridine removal rate and pyridine-N removal efficiency. The high abundance of Saccharibacteria (15.54%) and the enrichment of GLU and glnA substantiated this finding. On the contrary, phenol delayed pyridine oxidation, potentially due to its higher affinity for phenol hydroxylase. Nevertheless, phenol proved valuable as a carbon source for denitrification, augmenting the elimination of pyridine-N. This was underscored by the abundant Thauera (30.77%) and Parcubacteria (7.21%) and the enriched denitrification enzymes (narH, narG, norB, norC, and nosZ, etc.). This study demonstrated that co-metabolic degradation can bolster the simultaneous conversion of pyridine and pyridine-N, and shed light on the underling mechanism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Antibody-secreting plasma cells (PCs) are generated in secondary lymphoid organs but are reported to reside in an emerging range of anatomical sites. Analysis of the transcriptome of different tissue-resident (Tr)PC populations revealed that they each have their own transcriptional signature indicative of functional adaptation to the host tissue environment. In contrast to expectation, all TrPCs were extremely long-lived, regardless of their organ of residence, with longevity influenced by intrinsic factors like the immunoglobulin isotype. Analysis at single-cell resolution revealed that the bone marrow is unique in housing a compendium of PCs generated all over the body that retain aspects of the transcriptional program indicative of their tissue of origin. This study reveals that extreme longevity is an intrinsic property of TrPCs whose transcriptome is imprinted by signals received both at the site of induction and within the tissue of residence., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: The study aims to compare the real-world effectiveness and economy of the budesonide/formoterol reliever and maintenance therapy (SMART) with fixed-dose inhaled corticosteroids (ICS)/long-acting b-agonist (LABA) or ICS alone plus as-needed, short-acting β2 agonists (SABA) in pediatric patients., Methods: The outpatient data warehouse of a hospital in China was used. A total of 103 patients under 18 years old in the SMART group and 63 patients in the control group were included from January 1, 2020 to December 31, 2021. The effectiveness was assessed using asthma attacks and lung function at baseline, 6 months and 12 months follow-up. Cost-effectiveness analysis was performed with a three-state Markov model from the healthcare system perspective. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to check the robustness of the results., Results: The SMART regimen was more effective than other strategies in reducing the risk of mild and severe attacks in the real-life management of childhood asthma. Patients in both groups showed significant improvement in lung function at 6 and 12 months in contrast to baseline. Compared with other strategies, the forced expiratory volume in 1 s (FEV 1 ) level in the SMART group was markedly improved at 6 months. The total cost of outpatient service using the SMART regimen was lower than that of other strategies, while the drug costs were similar in different groups. Incremental cost-effectiveness analysis results showed that using the SMART regimen reduced the total cost by approximately CNY 10,516.11 per year with a 0.12 quality-adjusted life year (QALYs) increase. Sensitive analyses supported that the SMART regimen was the dominant choice at the willingness-to-pay threshold of CNY 85,698, per capita GDP in China., Conclusions: Collectively, our findings indicate that the real-world effectiveness and economy of the SMART regimen are superior to the traditional strategies in pediatric asthma patients., (© 2023 Wiley Periodicals LLC.)

The safety retaining wall is a critical infrastructure in ensuring the safety of both rock removal vehicles and personnel. However, factors such as precipitation infiltration, tire impact from rock removal vehicles, and rolling rocks can cause local damage to the safety retaining wall of the dump, rendering it ineffective in preventing rock removal vehicles from rolling down and posing a huge safety hazard. To address these issues, this study proposed a safety retaining wall health assessment method based on modeling and analysis of UAV point-cloud data of the safety retaining wall of a dump, which enables hazard warning for the safety retaining wall. The point-cloud data used in this study were obtained from the Qidashan Iron Mine Dump in Anshan City, Liaoning Province, China. Firstly, the point-cloud data of the dump platform and slope were extracted separately using elevation gradient filtering. Then, the point-cloud data of the unloading rock boundary was obtained via the ordered crisscrossed scanning algorithm. Subsequently, the point-cloud data of the safety retaining wall were extracted using the range constraint algorithm, and surface reconstruction was conducted to construct the Mesh model. The safety retaining wall mesh model was isometrically profiled to extract cross-sectional feature information and to compare the standard parameters of the safety retaining wall. Finally, the health assessment of the safety retaining wall was carried out. This innovative method allows for unmanned and rapid inspection of all areas of the safety retaining wall, ensuring the safety of rock removal vehicles and personnel.

Due to the shrinking in size of nonvolatile memory devices, the two-dimensional ferroelectric van der Waals (vdW) heterostructures have received huge attention. However, it is still difficult to maintain the out-of-plane (OOP) ferroelectricity. In this work, we have theoretically investigated the relationship between the ferroelectricity and the strain of bulk and few-layer SnTe by first-principles calculations. The results indicate that the α -SnTe can exist stably within the strain between -6% and 6%, and the complete OOP polarization occurs within the strain between -4% and -2%. Unfortunately, the OOP polarization disappears while the bulk α -SnTe is thinned to a few layers. However, the complete OOP polarization recurs in monolayer SnTe/PbSe vdW heterostructures, which is due to the strong interface coupling. Our findings provide an effective way to enhance ferroelectric performance, which is beneficial for the design of ultra-thin ferroelectric devices., (© 2023 IOP Publishing Ltd.)

Studying the seed trait-stem trait-individual spatial pattern system is helpful for understanding the developmental direction of plant dynamics and populations under grazing disturbance as well as the antagonistic relationship between animals and plants, but few systematic analyses of this spatial pattern system have been carried out. Kobresia humilis is the dominant species in alpine grasslands. We studied K. humilis seed traits and their relationship with K. humilis reproductive individuals, the relationship between reproductive and vegetative stems, and the weights and spatial patterns of reproductive and nonreproductive individuals under four grazing treatments: no grazing (control), light grazing, moderate grazing and heavy grazing. We explored the relationship among seed size and seed number with reproductive stems and vegetative stems along the grazing gradient and assessed the spatial pattern changes between reproductive and nonreproductive individuals. The results showed the following: (1) Seed size increased with increasing grazing intensity, and the coefficient of variation for seed size and seed number in the heavy grazing treatment was greater than 0.6. (2) The structural equation model showed that grazing treatment had a positive effect on seed number, seed size and reproductive stem number and a negative effect on reproductive stem weight. (3) Grazing treatment did not affect the resource allocation to reproductive stems and vegetative stems per unit length of reproductive K. humilis individuals. (4) Compared with the number of reproductive individuals in the no grazing treatment, the number in the heavy grazing treatment decreased significantly, and the negative correlation between reproductive individuals and nonreproductive individuals changed from a full-scale negative correlation to a small-scale negative correlation and a large-scale positive correlation. Our study showed that grazing could activate and change the resource allocation pattern of dominant species in a grassland and have significant positive effects on reproductive stem number, reproductive stem weight, seed number and seed size. Along a grazing intensity gradient, with the increase in distance between reproductive and nonreproductive individuals, the transformation of intraspecific relationships from a negative correlation to a positive correlation is an ecological strategy conducive to population survival., 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 © 2023 Qin-Yuan, Quan-Min, Fang-Cao, Yu-Zhen, Bin, Xiao-Xia, Yang, Chun-Ping, Quan and Wen-ting.)

Background: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma with poor prognosis in children. The 5-year survival rate for early RMS has improved, whereas it remains unsatisfactory for advanced patients. Urine can rapidly reflect changes in the body and identify low-abundance proteins. Early screening of tumor markers through urine in RMS allows for earlier treatment, which is associated with better outcomes., Methods: RMS patients under 18 years old, including those newly diagnosed and after surgery, were enrolled. Urine samples were collected at the time points of admission and after four cycles of chemotherapy during follow-up. Then, a two-stage workflow was established. (1) In the discovery stage, differential proteins (DPs) were initially identified in 43 RMS patients and 12 healthy controls (HCs) using a data-independent acquisition method. (2) In the verification stage, DPs were further verified as biomarkers in 54 RMS patients and 25 HCs using parallel reaction monitoring analysis. Furthermore, a receiver operating characteristic (ROC) curve was used to construct the protein panels for the diagnosis of RMS. Gene Ontology (GO) and Ingenuity Pathway Analysis (IPA) software were used to perform bioinformatics analysis., Results: A total of 251 proteins were significantly altered in the discovery stage, most of which were enriched in the head, neck and urogenital tract, consistent with the most common sites of RMS. The most overrepresented biological processes from GO analysis included immunity, inflammation, tumor invasion and neuronal damage. Pathways engaging the identified proteins revealed 33 common pathways, including WNT/β-catenin signaling and PI3K/AKT signaling. Finally, 39 proteins were confirmed as urinary biomarkers for RMS, and a diagnostic panel composed of 5 candidate proteins (EPS8L2, SPARC, HLA-DRB1, ACAN, and CILP) was constructed for the early screening of RMS (AUC: 0.79, 95%CI = 0.66 ~ 0.92)., Conclusions: These findings provide novel biomarkers in urine that are easy to translate into clinical diagnosis of RMS and illustrate the value of global and targeted urine proteomics to identify and qualify candidate biomarkers for noninvasive molecular diagnosis., (© 2023. The Author(s).)

Pain is a hallmark symptom associated with intestinal inflammation. Two related articles published in Cell by Zhang et al. and by Yang et al. now report how sensory neurons in the gut, the most heavily innervated organ in the human body, flag bacterial pathogens to shape the composition of the gut microbiome and to trigger immunoregulatory mechanisms., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Dasatinib and imatinib are the recommended tyrosine kinase inhibitors (TKIs) for treating pediatric Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL), and the one which has been approved indication in China is imatinib. Recently, clinical demand for Ph + ALL treatment is becoming unmet gradually with the increasing resistance of imatinib. There are some studies reporting the better efficacy and comparative safety of dasatinib compared with imatinib, but no economic comparison has been published. This study aims to supplement economic evidence by comparing the cost-effectiveness between imatinib and dasatinib in treating pediatric patients with Ph+ ALL in China, and to help clinical rational drug use via multi-dimensional value assessment., Methods: A decision tree model combined with a 10-year Markov model were established based on the disease progression. The parameters were collected from published literatures and our hospital's electronic medical records. From the health system perspective, the incremental cost-effectiveness ratio (ICER) between the two treatment groups was calculated through cost-effectiveness analysis and then compared with the willingness-to-pay (WTP) threshold. The set WTP threshold in this study was 1 times per capita gross domestic product (GDP) of China, as recommended by the World Health Organization. Direct medical costs and quality-adjusted life years (QALYs) were calculated and discounted at 5%. The sensitivity analyses were conducted to assess the uncertainty and robustness of the results., Results: The total costs were CNY 1,020,995.35 and CNY 1,035,788.50 in imatinib group and dasatinib group during the 10-year simulation, and the total QALYs were 2.59 and 4.84. Compared with the imatinib treatment group, the ICER was around CNY 6,575.78/ QALY, which was less than the set threshold CNY 70,892/ QALY. The sensitive analyses indicated the robustness of the results., Conclusions: The cost-effectiveness analysis shows the potential cost-effective advantages of adding dasatinib comparing with adding imatinib for pediatric Ph + ALL patients in China under the set WTP threshold, which indicates that those patients could achieve more QALYs by paying acceptable fee., (© 2022. The Author(s).)

Background: Drug-induced kidney injury (DIKI) is one of the most common complications in clinical practice. Detection signals through post-marketing approaches are of great value in preventing DIKI in pediatric patients. This study aimed to propose a quantitative algorithm to detect DIKI signals in children using an electronic health record (EHR) database. Methods: In this study, 12 years of medical data collected from a constructed data warehouse were analyzed, which contained 575,965 records of inpatients from 1 January 2009 to 31 December 2020. Eligible participants included inpatients aged 28 days to 18 years old. A two-stage procedure was adopted to detect DIKI signals: 1) stage 1: the suspected drugs potentially associated with DIKI were screened by calculating the crude incidence of DIKI events; and 2) stage 2: the associations between suspected drugs and DIKI were identified in the propensity score-matched retrospective cohorts. Unconditional logistic regression was used to analyze the difference in the incidence of DIKI events and to estimate the odds ratio (OR) and 95% confidence interval (CI). Potentially new signals were distinguished from already known associations concerning DIKI by manually reviewing the published literature and drug instructions. Results: Nine suspected drugs were initially screened from a total of 652 drugs. Six drugs, including diazepam (OR = 1.61, 95%CI: 1.43-1.80), omeprazole (OR = 1.35, 95%CI: 1.17-1.54), ondansetron (OR = 1.49, 95%CI: 1.36-1.63), methotrexate (OR = 1.36, 95%CI: 1.25-1.47), creatine phosphate sodium (OR = 1.13, 95%CI: 1.05-1.22), and cytarabine (OR = 1.17, 95%CI: 1.06-1.28), were demonstrated to be associated with DIKI as positive signals. The remaining three drugs, including vitamin K1 (OR = 1.06, 95%CI: 0.89-1.27), cefamandole (OR = 1.07, 95%CI: 0.94-1.21), and ibuprofen (OR = 1.01, 95%CI: 0.94-1.09), were found not to be associated with DIKI. Of these, creatine phosphate sodium was considered to be a possible new DIKI signal as it had not been reported in both adults and children previously. Moreover, three other drugs, namely, diazepam, omeprazole, and ondansetron, were shown to be new potential signals in pediatrics. Conclusion: A two-step quantitative procedure to actively explore DIKI signals using real-world data (RWD) was developed. Our findings highlight the potential of EHRs to complement traditional spontaneous reporting systems (SRS) for drug safety signal detection in a pediatric setting., 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 © 2022 Yu, Nie, Zhao, Cao, Xie, Peng and Wang.)

Background: Severe drug hypersensitivity reactions (DHRs) refer to allergic reactions caused by drugs and usually present with severe skin rashes and internal damage as the main symptoms. Reporting of severe DHRs in hospitals now solely occurs through spontaneous reporting systems (SRSs), which clinicians in charge operate. An automatic identification system scrutinizes clinical notes and reports potential severe DHR cases., Objective: The goal of the research was to develop an automatic identification system for mining severe DHR cases and discover more DHR cases for further study. The proposed method was applied to 9 years of data in pediatrics electronic health records (EHRs) of Beijing Children's Hospital., Methods: The phenotyping task was approached as a document classification problem. A DHR dataset containing tagged documents for training was prepared. Each document contains all the clinical notes generated during 1 inpatient visit in this data set. Document-level tags correspond to DHR types and a negative category. Strategies were evaluated for long document classification on the openly available National NLP Clinical Challenges 2016 smoking task. Four strategies were evaluated in this work: document truncation, hierarchy representation, efficient self-attention, and key sentence selection. In-domain and open-domain pretrained embeddings were evaluated on the DHR dataset. An automatic grid search was performed to tune statistical classifiers for the best performance over the transformed data. Inference efficiency and memory requirements of the best performing models were analyzed. The most efficient model for mining DHR cases from millions of documents in the EHR system was run., Results: For long document classification, key sentence selection with guideline keywords achieved the best performance and was 9 times faster than hierarchy representation models for inference. The best model discovered 1155 DHR cases in Beijing Children's Hospital EHR system. After double-checking by clinician experts, 357 cases of severe DHRs were finally identified. For the smoking challenge, our model reached the record of state-of-the-art performance (94.1% vs 94.2%)., Conclusions: The proposed method discovered 357 positive DHR cases from a large archive of EHR records, about 90% of which were missed by SRSs. SRSs reported only 36 cases during the same period. The case analysis also found more suspected drugs associated with severe DHRs in pediatrics., (©Yuncui Yu, Qiuye Zhao, Wang Cao, Xiaochuan Wang, Yanming Li, Yuefeng Xie, Xiaoling Wang. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 13.09.2022.)

Step-feature lines are one of the important geometrical elements for drawing the status quo maps of open-pit mines, and the efficient and accurate automatic extraction and updating of step-feature lines is of great significance for open-pit-mine stripping planning and analysis. In this study, an automatic extraction method of step-feature lines in an open-pit mine based on unmanned-aerial-vehicle (UAV) point-cloud data is proposed. The method is mainly used to solve the key problems, such as low accuracy, local-feature-line loss, and the discontinuity of the step-feature-line extraction method. The method first performs the regular raster resampling of the open-pit-mine cloud based on the MLS algorithm, then extracts the step-feature point set by detecting the elevation-gradient change in the resampled point cloud, further traces the step-feature control nodes by the seed-growth tracking algorithm, and finally generates smooth step-feature lines by fitting the space curve to the step-feature control nodes. The results show that the method effectively improves the accuracy of step-feature-line extraction and solves the problems of local-feature-line loss and discontinuity.

Background: Drug-induced coagulopathy (DIC) is a severe adverse reaction and has become a significantly increased clinical problem in children. It is crucial to the detection of the DIC safety signal for drug post-marketing scientific supervision purposes. Therefore, this study aimed to detect potential signals for DIC in children using the routine electronic medical record (EMR) data. Methods: This study extracted EMR data from Beijing Children's Hospital between 2009 and 2020. A two-stage modeling method was developed to detect the signal of DIC. We calculated the crude incidence by mining cases of coagulopathy to select the potential suspected drugs; then, propensity score-matched retrospective cohorts of specific screened drugs from the first stage were constructed and estimated the odds ratio (OR) and 95% confidence interval (CI) using conditional logistic regression models. The current literature evidence was used to assess the novelty of the signal. Results: In the study, from a total of 340 drugs, 22 drugs were initially screened as potentially inducing coagulopathy. In total, we identified 19 positive DIC associations. Of these, potential DIC risk of omeprazole (OR: 2.23, 95% CI: 1.88-2.65), chlorpheniramine (OR:3.04, 95% CI:2.56-3.60), and salbutamol sulfate (OR:1.36, 95% CI:1.07-1.73) were three new DIC signals in both children and adults. Twelve associations between coagulopathy and drugs, meropenem (OR: 3.38, 95% CI: 2.72-4.20), cefoperazone sulbactam (OR: 2.80, 95% CI: 2.30-3.41), fluconazole (OR: 2.11, 95% CI: 1.71-2.59), voriconazole (OR: 2.82, 95% CI: 2.20-3.61), ambroxol hydrochloride (OR: 2.12, 95% CI: 1.74-2.58), furosemide (OR: 2.36, 95% CI: 2.08-2.67), iodixanol (OR: 2.21, 95% CI: 1.72-2.85), cefamandole (OR: 1.82, 95% CI: 1.56-2.13), ceftizoxime (OR: 1.95, 95% CI: 1.44-2.63), ceftriaxone (OR: 1.95, 95% CI: 1.44-2.63), latamoxef sodium (OR: 1.76, 95% CI: 1.49-2.07), and sulfamethoxazole (OR: 1.29, 95% CI: 1.01-1.64), were considered as new signals in children. Conclusion: The two-stage algorithm developed in our study to detect safety signals of DIC found nineteen signals of DIC, including twelve new signals in a pediatric population. However, these safety signals of DIC need to be confirmed by further studies based on population study and mechanism research., 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 © 2022 Nie, Yu, Jia, Zhao, Chen, Zhang, Cheng, Lyu, Cao, Wang and Peng.)

The new type of hollow mesoporous TiO 2 @BiOBr/Bi 4 O 5 Br 2 type-II/Z-scheme tandem heterojunction is synthesized using MIL-125(Ti) as the precursor based on the confinement effect caused by the outward shrinkage induced by the interface. Among them, the BiOBr shell is an indispensable component of forming a cavity during the pyrolysis of MIL-125(Ti). Not only that, BiOBr is partially converted into Bi-rich Bi 4 O 5 Br 2 at high temperature, and the remaining BiOBr acts as a bridge to connect TiO 2 and Bi 4 O 5 Br 2 to construct a type-II/Z-scheme tandem heterojunction. This new type of hollow mesoporous tandem heterojunction shows excellent degradation efficiency (95%) for 10 mg/L ciprofloxacin (CIP) within 40 min, with a rate constant (K) of 0.05930 min -1 . The Fukui index is used to determine the attack site of CIP, and the possible degradation pathway is proposed through LC-MS analysis. The results of the culture of Vibrio qinghaiensis-Q67 showed that ciprofloxacin and its intermediate products have biological toxicity, and the toxicity is reduced with the progress of photodegradation. This method of synthesizing novel hollow mesoporous TiO 2 @BiOBr/Bi 4 O 5 Br 2 type-II/Z-scheme tandem heterojunctions based on the confinement effect will provide a new idea for other use of MOF to synthesize hollow and high-efficiency heterojunctions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The spleen is a compartmentalized organ that serves as a blood filter and safeguard of systemic immune surveillance. Labyrinthine networks of fibroblastic stromal cells construct complex niches within the white pulp and red pulp that are important for tissue homeostasis and immune activation. However, the identity and roles of the global splenic fibroblastic stromal cells in homeostasis and immune responses are poorly defined. Here, we performed a cellular and molecular dissection of the splenic reticular stromal cell landscape. We found that white pulp fibroblastic reticular cells (FRCs) responded robustly during acute viral infection, but this program of gene regulation was suppressed during persistent viral infection. Single-cell transcriptomic analyses in mice revealed diverse fibroblast cell niches and unexpected heterogeneity among podoplanin-expressing cells that include glial, mesothelial, and adventitial cells in addition to FRCs. We found analogous fibroblastic stromal cell diversity in the human spleen. In addition, we identify the transcription factor SpiB as a critical regulator required to support white pulp FRC differentiation, homeostatic chemokine expression, and antiviral T cell responses. Together, our study provides a comprehensive map of fibroblastic stromal cell types in the spleen and defines roles for red and white pulp fibroblasts for splenic function and orchestration of immune responses.

Background: Drug-induced thrombocytopenia (DITP) is a severe adverse reaction and a significantly under-recognized clinical problem in children. However, for post-marketing pharmacovigilance purposes, detection of DITP signals is crucial. This study aimed to develop a signal detection model for DITP using the pediatric electronic medical records (EMR) data. Methods: This study used the electronic medical records collected at Beijing Children's Hospital between 2009 and 2020. A two-stage modeling method was developed to detect the signal of DITP. In the first stage, we calculated the crude incidence by mining cases of thrombocytopenia to select the potential suspected drugs. In the second stage, we constructed propensity score-matched retrospective cohorts of specific screened drugs from the first stage and estimated the odds ratio (OR) and 95% confidence interval (CI) using conditional logistic regression models. The novelty of the signal was assessed by current evidence. Results: In the study, from a total of 839 drugs, 21 drugs were initially screened as potentially inducing thrombocytopenia. In total, we identified 18 positive DITP associations. Of these, potential DITP risk of nystatin (OR: 1.75, 95% CI: 1.37-2.22) and latamoxef sodium (OR: 1.61, 95% CI: 1.38-1.88) were two new DITP signals in both children and adults. Six associations between thrombocytopenia and drugs including imipenem (OR: 1.69, 95% CI: 1.16-2.45), teicoplanin (OR: 4.75, 95% CI: 3.33-6.78), fusidic acid (OR: 2.81, 95% CI: 2.06-3.86), ceftizoxime sodium (OR: 1.83, 95% CI: 1.36-2.45), ceftazidime (OR: 2.16, 95% CI: 1.58-2.95), and cefepime (OR: 5.06, 95% CI: 3.77-6.78) were considered as new signals in children. Conclusion: This study developed a two-stage algorithm to detect safety signals of DITP and found eighteen positive signals of DITP, including six new signals in a pediatric population. This method is a promising tool for pharmacovigilance based on EMR data., 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 Nie, Jia, Peng, Zhao, Yu, Chen, Zhang, Cheng, Lyu, Cao, Wang, Ni and Zhan.)

Dendritic cells (DCs) and macrophages are at the forefront of immune responses, modifying their transcriptional programs in response to their tissue environment or immunological challenge. Posttranslational modifications of histones, such as histone H3 lysine-27 trimethylation (H3K27me3) by the Polycomb repressive complex 2 (PRC2), are tightly associated with epigenetic regulation of gene expression. To explore whether H3K27me3 is involved in either the establishment or function of the mononuclear phagocyte system, we selectively deleted core components of PRC2, either EZH2 or SUZ12, in CD11c-expressing myeloid cells. Unexpectedly, EZH2 deficiency neither prevented the deposition and maintenance of H3K27me3 in DCs nor hindered DC/macrophage homeostasis. In contrast, SUZ12 deficiency markedly impaired the capacity of DCs and macrophages to maintain H3K27me3. SUZ12 ablation induced a rapid loss of the alveolar macrophage and Langerhans cell networks under both steady state and inflammatory conditions because these cells could no longer proliferate to facilitate their self-renewal. Despite the reduced H3K27me3, DC development and function were unaffected by SUZ12 ablation, suggesting that PRC2-mediated gene repression was dispensable for DC homeostasis. Thus, the role of SUZ12 highlights the fundamentally different homeostatic mechanisms used by tissue-resident myeloid cells versus DCs.

The functional diversification of dendritic cells (DCs) is a key step in establishing protective immune responses. Despite the importance of DC lineage diversity, its genetic basis is not fully understood. The transcription factor DC-SCRIPT is expressed in conventional DCs (cDCs) and their committed bone marrow progenitors but not in plasmacytoid DCs (pDCs). We show that mice lacking DC-SCRIPT displayed substantially impaired development of IRF8 (interferon regulatory factor 8)-dependent cDC1, whereas cDC2 numbers increased marginally. The residual DC-SCRIPT-deficient cDC1s had impaired capacity to capture and present cell-associated antigens and to secrete IL-12p40, two functional hallmarks of this population. Genome-wide mapping of DC-SCRIPT binding and gene expression analyses revealed a key role for DC-SCRIPT in maintaining cDC1 identity via the direct regulation of cDC1 signature genes, including Irf8 Our study reveals DC-SCRIPT to be a critical component of the gene regulatory program shaping the functional attributes of cDC1s., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

In this study, a novel 3D flower-sphere BiOBr/Bi 4 O 5 Br 2 with proper-oxygen vacancies (OV) was successfully synthesized by using 3D BiOBr as a self-sacrificed template, NaOH as a structure-driving reagent and midwifery agent of OV. The synthesis mechanism was systematically studied. It revealed that Bi 4 O 5 Br 2 lamina generated via in-situ phase transfer tightly interspersed in the interior and surface of 3D BiOBr hierarchical structures; calcination temperature, stirring time and -OH concentration can optimize the composition and structure of materials. Also, the calcination conditions (temperatures and air or N 2 atmosphere) can regulate the OV's concentration. Ultimately, 3D hierarchical architectures, the optimal heterojunction composition and OV with proper concentrations three positive factors synergistically promoted the photoelectric activity of BiOBr/Bi 4 O 5 Br 2 -OV, making it exhibit ultrahigh photocatalytic activity for antibiotic photodegradation (tetracycline, TC; ciprofloxacin, CIP). We believe the synthesis methods and design idea mentioned in this paper have high instructive significance to prepare high-performance materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the outcome of toric intraocular lens (IOL) implantation in eyes with previous laser in situ keratomileusis/photorefractive keratectomy (LASIK/PRK)., Setting: Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA., Design: Retrospective case series., Methods: Consecutive cases that had previous myopic or hyperopic LASIK/PRK and had undergone cataract surgery with toric IOL implantation were retrospectively reviewed. Included were eyes that had (1) preoperative ocular biometry measurements with the Lenstar, (2) no intraoperative or postoperative complications, and (3) available postoperative manifest refraction at ≥3 weeks with corrected distance visual acuity of 20/30 or better. Vector analysis was used to assess the preoperative corneal and postoperative refractive astigmatism., Results: In 56 eyes with previous myopic LASIK/PRK and 19 eyes with previous hyperopic LASIK/PRK, respectively, the mean magnitudes of corneal astigmatism were 1.34 ± 0.62 diopters (D) and 1.66 ± 0.80 D, 5% and 0% of eyes had anterior corneal astigmatism ≤0.50 D, and the centroid values were 0.31 D at 19 degrees ± 1.45 D and 0.74 D at 92 degrees ± 1.72 D preoperatively. Postoperatively, the mean magnitudes of refractive astigmatism were 0.36 ± 0.31 D and 0.34 ± 0.34 D, 80% and 84% of eyes had refractive astigmatism of ≤0.50 D, and the centroid values were 0.12 D at 152 degrees ± 0.46 D and 0.05 D at 172 degrees ± 0.48 D (all P < .05)., Conclusions: Toric IOLs were effective to correct preexisting corneal astigmatism in eyes with previous excimer laser corneal refractive surgery.

The immune system plays a fundamental role at mucosal barriers in maintaining tissue homeostasis. This is particularly true for the gut where cells are flooded with microbial-derived signals and antigens, which constantly challenge the integrity of the intestinal barrier. Multiple immune cell populations equipped with both pro- and anti-inflammatory functions reside in the gut tissue and these cells tightly regulate intestinal health and functions. Dysregulation of this finely tuned system can progressively lead to autoimmune disease and inflammation-driven carcinogenesis. Over the last decade, the contribution of the adaptive immune system in controlling colorectal cancer has been studied in detail, but the role of the innate system, particularly innate lymphoid cells (ILCs), have been largely overlooked. By sensing their microenvironment, ILCs are essential in supporting gut epithelium repair and controling bacterial- and helminth-mediated intestinal infections, highlighting their important role in maintaining tissue integrity. Accumulating evidence also suggests that they may play an important role in carcinogenesis including intestinal cancers. In this review, we will explore the current knowledge about the pro- and anti-tumor functions of ILCs in colorectal cancer., (Copyright © 2020 Huang, Cao, Mielke, Seillet, Belz and Jacquelot.)

Proanthocyanidins have been shown to effectively protect ischemic neurons, but its mechanism remains poorly understood. Ginkgo proanthocyanidins (20, 40, 80 mg/kg) were intraperitoneally administered 1, 24, 48 and 72 hours before reperfusion. Results showed that ginkgo proanthocyanidins could effectively mitigate neurological disorders, shorten infarct volume, increase superoxide dismutase activity, and decrease malondialdehyde and nitric oxide contents. Simultaneously, the study on grape seed proanthocyanidins (40 mg/kg) confirmed that different sources of proanthocyanidins have a similar effect. The neurological outcomes of ginkgo proanthocyanidins were similar to that of nimodipine in the treatment of cerebral ischemia/reperfusion injury. Our results suggest that ginkgo proanthocyanidins can effectively lessen cerebral ischemia/reperfusion injury and protect ischemic brain tissue and these effects are associated with antioxidant properties., Competing Interests: Zhejiang Conba Pharmaceutical Co., Ltd. provided financial support.

Sperm protein 17 (Sp17) is selectively overexpressed in several human malignancies including ovarian carcinoma, but is absent or expressed at low levels in most normal tissues. Previous work from our group characterized an anti-Sp17 monoclonal antibody (clone 3C12) and showed that it specifically targeted tumor cells. In this report, we investigated whether a novel immunoconjugate containing 3C12 linked to the chemotherapeutic agent doxorubicin [(DOX) Adriamycin] had antitumor activity against ovarian cancer cell lines and tumor models. DOX was conjugated to 3C12 using a linker, and the specificity of 3C12-DOX was examined in Sp17-positive SKOV3 and Sp17-negative COC2 ovarian cancer cells using cell-based ELISA and internalization assays. The cytotoxicity of 3C12-DOX was assessed with the MTT assay, and its therapeutic effectiveness was evaluated in immunodeficient mice bearing SKOV3 cells. In vitro, the 3C12-DOX immunoconjugate specifically bound to and was internalized by Sp17-positive SKOV3 cells but did not bind to Sp17-negative cells. Treatment with 3C12-DOX (0.001 to 10 μg/mL) decreased the viability of SKOV3 cells in a Sp17-specific manner. In vivo, 3C12-DOX (3 mg/kg) induced the regression of established SKOV3 xenograft tumors in BALB/c mice compared with control treatment. The antitumor effects of 3C12-DOX were significantly associated with the induction of apoptosis in tumor cells. In addition, 3C12-DOX showed no observable adverse effects or toxicity when compared with DOX alone in mice bearing ovarian tumor xenografts. Our findings suggest that 3C12-DOX may be a potential antibody-drug conjugate for clinical development.

Background: Condylomata acuminata (genital warts) is the most common sexually transmitted disease, and imiquimod is the sole FDA-approved medication for combating this condition. Vitiligo associated with imiquimod treatment of condylomata acuminata is rare., Case Presentation: A 28-year-old male with condylomata acuminata of the penis presented to our clinic. After removing his condylomata acuminata, we advised him to use imiquimod 5% cream to prevent relapse. When he presented to our clinic again about 12 weeks later, he complained of vitiligo patches on his penis and scrotum. Physical examination showed vitiligo patches involving the glans penis, shaft of the penis, and scrotum, and remaining pigmented areas within the plaques of vitiligo.A skin biopsy of the dorsal surface of the penis showed a complete absence of melanocytes and melanin granules in the basal layer; the dermis was normal., Conclusion: This is the first report of a case of imiquimod-induced vitiligo diagnosed by histopathological examination. This adverse effect should be considered when dermatologists prescribe this medication.

We report a case of erythrodermic psoriasis with bullous pemphigoid (BP) in a 68-year-old male. The patient had a history of psoriasis for 35 years and tense, blisterlike lesions for 4 months. He presented with diffuse flushing, infiltrative swelling, and tense blisterlike lesions on his head, trunk, and limbs. This patient was successfully treated by a combination of methotrexate and compound glycyrrhizin. We also discuss the clinical manifestations, histopathological features, and differentiation of erythrodermic psoriasis with BP and present a review of the pertinent literature., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1853737109114076.

We report a case of recurrent cutaneous necrotizing eosinophilic vasculitis (RCNEV) in a 57-year-old male. The patient presented with papules and pruritus of the lower limbs of more than 1 month duration, and with angioedema and intensively pruritic, necrotizing lesions of the bilateral anterior tibias and feet for 2 weeks. Treatment with systemic corticosteroids was administered for 1 month, and resulted in a significant improvement. We also present a review of the pertinent literature and discuss the clinical features, histopathological features, and differentiation of RCNEV., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2065600765102207.

Sperm protein 17 (Sp17) is a cancer testis antigen that has been shown to be overexpressed in a variety of gynecologic malignancies, in particular ovarian cancer. Emerging evidences indicate that Sp17 is involved in tumorigenesis and in the migration of malignant cells. It has been proposed as a useful target for tumor-vaccine strategies and a novel marker to define tumor subsets and predict drug response. However, the antitumor activity of anti-Sp17 monoclonal antibody (anti-Sp17 mAb) has not been investigated. In this study, the in vitro cytotoxicity, antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activities of anti-Sp17 mAb were evaluated using Sp17-positive ovarian cancer cells as targets, Sp17-negative ovarian cancer cells as the control, and healthy human peripheral blood monocytes and healthy human serum as effectors. Our preliminary results indicate that the direct cytotoxicity of anti-Sp17 mAb against the investigated ovarian cancer cells was very weak. However, the cytotoxicity of anti-Sp17 mAb, mediated by peripheral blood mononuclear cells (PBMCs), as ADCC, or by human serum, as CDC, was relatively strong in the Sp17-positive ovarian cancer cells. This finding suggested that anti-Sp17 mAb could be a useful tool against ovarian cancer and may provide insight into the development of low side-effect targeting therapy for this malignant disease.

Objective: This study aims to survey respiratory infectious disease related health literacy (RIDHL) and health behavior (RIDHB) among residents in Fengtai district, Beijing, analyze impact factors of RIDHL , explore the association between RIDHL and RIDHB., Methods: Multistage sampling was employed and 1100 respondents were surveyed by self-designed questionnaires, which including social-demographic characteristics and evaluation of RIDHL and RIDHB. The survey results were described, the impact factors of RIDHL and the association between RIDHL and RIDHB were analyzed by analysis of variance or covariance., Results: A total of 998 qualified questionnaires were recollected with the effective rate of 90.7%. The respondents aged from 15 to 65, scored (71.3 +/- 19.0) points in RIDHL test. Of those respondents, 25.7% (256/998), 43.2% (432/998) and 31.1% (310/998) were evaluated as low( <60 points), medium (60 - 85 points), and high level ( > 85 points) of RIDHL, respectively. There were significant difference in RIDHL scores between registered and non-registered residents, who scored (74.1 +/- 18.9) and (68.4 +/- 18.8) points, respectively (P < 0.01). RIDHL sections were ranked as audiovisual (77.6%, 4647/5988), internet using (75.2%, 2251/2994), reading (74.6%, 3724/4990), map using (68.3%, 4090/5988) and quantitative (65.5%, 5230/7984) according to the accurate rates from high to low. Analysis of variance or covariance showed that RIDHL scores were significantly different among respondents with different ages, nationalities, educational levels, occupations, and incomes (P < 0.01), yet no significant differences among those with different genders and marital status (P > 0.05). Respondents scored (69.7 +/- 15.5) points in RIDHB test. The RIDHB scores ((64.5 +/- 15.0), (70.4 +/- 15.6), (72.5 +/- 14.9) points, respectively) increased among residents with low, medium and high level of RIDHL (P < 0.01)., Conclusion: Residents in Fengtai district, Beijing possessed medium level of RIDHL. The non-registered residents showed lower RIDHL than registered residents. Ages, nationalities, educational levels, occupations, and incomes were impact factors of RIDHL. People with higher level of RIDHL also showed a higher level of RIDHB.

ZnS:Cu, Al nanocrystals were synthesized by a hydrothermal method at 200 degrees C and their optical properties were studied. The analysis of XRD and TEM show that the spherical-like nanocrystals had a grain size of approximately 15 nm and were well dispersed, with a zinc blende structure. The energy dispersive X-ray spectroscopy (EDX) and atomic absorption spectrometry were applied to the analysis of S, Zn and Cu content in the sample. The results proved that a large number of zinc vacancies exist and Cu is incorporated into the sample lattice. The photoluminescence (PL) spectra were investigated. The PL mechanism is discussed. The excitation spectrum is broad. Under 337 nm excitation the sample emits bright green light. Under 370-410 nm excitation the sample emits white light. The broad emission spectra are almost coincident with any excitation wavelength of between 370 and 410 nm making them attractive as conversion phosphors for LED applications and full-color fluorescence display devices. The emitted white light under 375 nm excitation was found to be the result of blue, green, and orange emission bands. For Cu/Zn, Cu/Al and S/Zn molar ratios of 3 x 10(-4), 2 and 3, respectively, the near blue white light can be observed with the naked eye in daylight.

Highly luminescent ZnS : Au, Cu X-ray phosphor fine particles synthesized by hydrothermal method is reported for the first time and its photoluminescence (PL) and X-ray excited luminescence (XEL) properties were studied in detail. With direct hydrothermal treatment at 200 degrees C for 12 h, the average gain size of samples is about 15 nm; the synthesized sphere-like nanocrystals with well dispersity and narrow gain size distribution show cubic structure. After baking in argon at 1 000 degrees C for 1h the sample agglomerate size is about 1-2 microm and the roughly spherical fine particles show pure hexagonal structure. The PL and XEL spectra of all the samples show a broad emission band and an intense emission band in the range of 400-600 nm. The maximum XEL intensity of sample directly synthesized by hydrothermal treatment was observed when Cu/Zn and Cu/Al were 3 x 10(-5) and 2, respectively. In this condition, the strongest PL emission was observed for the direct synthesized sample being further baked in argon at 900 degrees C for 1 h and the PL peak was centered at about 529 nm. The strongest XEL emission was observed for the direct synthesized sample being further baked in argon at 1 000 degrees C for 1h and the XEL peak was centered at about 445 and 513 nm, respectively. In the meantime, the XEL intensity increased about ten times compared with that directly synthesized without baking. The difference between PL and XEL spectra is due to its different excitation mechanism. The luminescence mechanism and different excitation mechanism of PL and XEL were discussed. The red shift of XEL spectrum with directly synthesized sample was observed with increasing the Cu/Zn. The reason can also be explained by the luminescence mechanism and excitation mechanism of XEL.