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Abstract Healthcare insurance fraud imposes a significant financial burden on healthcare systems worldwide, with annual losses reaching billions of dollars. This study aims to improve fraud detection accuracy using machine learning techniques. Our approach consists of three key stages: data preprocessing, model training and integration, and result analysis with feature interpretation. Initially, we examined the dataset’s characteristics and employed embedded and permutation methods to test the performance and runtime of single models under different feature sets, selecting the minimal number of features that could still achieve high performance. We then applied ensemble techniques, including Voting, Weighted, and Stacking methods, to combine different models and compare their performances. Feature interpretation was achieved through partial dependence plots (PDP), SHAP, and LIME, allowing us to understand each feature’s impact on the predictions. Finally, we benchmarked our approach against existing studies to evaluate its advantages and limitations. The findings demonstrate improved fraud detection accuracy and offer insights into the interpretability of machine learning models in this context.

An effective approach to deal with the structural failures of transmission towers in tornadic events is to develop good structural health monitoring (SHM) systems for them. However, the strategy for SHM of transmission towers against tornados should be different from the conventional atmospheric boundary layer (ABL) winds oriented ones, as the non-stationary nature of the tornados significantly differentiates them from the ABL winds. To satisfy the need of obtaining the highly time-varying whole-field stress on the structure in the course of the tornadic event for effective SHM, an innovative transient tornadic load distribution identification method is proposed for use, which is based on the field structural mode shape measurement and dynamic finite-element (FE) model updating. Via a numerical case study, it is noted that good effectiveness is achieved for the new load distribution identification method. Employing the Modal Assurance Criteria based FE model updating technique, the new method has the advantage of being easily embraced in practical SHM systems. It is found that when the transient tornadic velocity profile to be identified is noticeably different from the mode shape of the structure without undertaking external loads, the identified load pattern is very accurate for the new approach.

In this paper, AlGaN/GaN high electron mobility transistors (HEMTs) with different thicknesses of unintentional doping GaN (UID-GaN) channels were compared and discussed. In order to discuss the effect of different thicknesses of the UID-GaN layer on iron-doped tails, both AlGaN/GaN HEMTs share the same 200 nm GaN buffer layer with an Fe-doped concentration of 8 × 1017 cm−3. Due to the different thicknesses of the UID-GaN layer, the concentration of Fe trails reaching the two-dimensional electron gas (2DEG) varies. The breakdown voltage (Vbr) increases with the high concentration of Fe-doped in GaN buffer layer. However, the mobility of the low concentration of the Fe-doped tail is higher than that of the high concentration of the Fe-doped tail. Therefore, the effect of different thicknesses of UID-GaN on the DC and radio frequency (RF) performance of the device needs to be verified. It provides a reference to the epitaxial design for high-performance GaN HEMTs.

Intestinal obstruction, a rare manifestation of immunotherapy-related gastrointestinal adverse events, can be severe and even life-threatening with intestinal perforation. We present a 64-year-old man with HCC and currently under the therapy with Pembrolizumab, who was admitted in our hospital with abdominal distension. Radiologic findings were consistent with small bowel ileus. After conservative treatment, the patient underwent colonoscopy where no cause of ileus was discovered. The patient received high-dose prednisone due to the side effects of immune checkpoint inhibitor therapy. This resulted in a gradual improvement of symptoms.

Abstract Background Human milk fortifier (HMF) composition has been optimized recently. But clinical evidence of its safety and efficacy is limited in Chinese population. The aim of this study was to evaluate effects of a new HMF in growth, nutritional status, feeding intolerance, and major morbidities among very preterm (VPT) or very low birth weight (VLBW) infants in China. Methods VPT/VLBW infants admitted from March 2020 to April 2021 were prospectively included in the experimental (new HMF, nHMF) group, who received a new powdered HMF as a breast milk feeding supplement during hospitalization. Infants in the control group (cHMF) admitted from January 2018 to December 2019, were retrospective included, and matched with nHMF group infants for gestational age and birth weight. They received other kinds of commercially available HMFs. Weight gain velocity, concentrations of nutritional biomarkers, incidence of major morbidities, and measures of feeding intolerance were compared between the two groups. Results Demographic and clinical characteristics of infants in nHMF and cHMF groups were comparable. Weight gain velocity had no significant difference between the nHMF (14.0 ± 3.5 g/kg/d) and the cHMF group (14.2 ± 3.8 g/kg/d; P = 0.46). Incidence of morbidities, including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, culture-confirmed sepsis, and feeding intolerance during hospitalization between nHMF and cHMF, were similar (all P-values > 0.05). The time to achieve full enteral feeding [13.5 (10, 21) days] in the nHMF group was significantly shorter than that in the cHMF group [17 (12, 23) days, HR = 0.67, 95%CI: 0.49, 0.92; P = 0.01]. Compared with cHMF group, the decrease of blood urea nitrogen level over time in nHMF group was smaller (β = 0.6, 95%CI:0.1, 1.0; P = 0.01). Conclusions The new HMF can promote growth of preterm infants effectively without increasing the incidence of major morbidity and feeding intolerance. It can be used feasible in Chinese VPT/VLBW infants. Trial registration This study was registered on ClinicalTrials.gov (NCT04283799).

Abstract Ferromagnetism and superconductivity are two key ingredients for topological superconductors, which can serve as building blocks of fault-tolerant quantum computers. Adversely, ferromagnetism and superconductivity are typically also two hostile orderings competing to align spins in different configurations, and thus making the material design and experimental implementation extremely challenging. A single material platform with concurrent ferromagnetism and superconductivity is actively pursued. In this paper, we fabricate van der Waals Josephson junctions made with iron-based superconductor Fe(Te,Se), and report the global device-level transport signatures of interfacial ferromagnetism emerging with superconducting states for the first time. Magnetic hysteresis in the junction resistance is observed only below the superconducting critical temperature, suggesting an inherent correlation between ferromagnetic and superconducting order parameters. The 0-π phase mixing in the Fraunhofer patterns pinpoints the ferromagnetism on the junction interface. More importantly, a stochastic field-free superconducting diode effect was observed in Josephson junction devices, with a significant diode efficiency up to 10%, which unambiguously confirms the spontaneous time-reversal symmetry breaking. Our work demonstrates a new way to search for topological superconductivity in iron-based superconductors for future high Tc fault-tolerant qubit implementations from a device perspective.

Abstract Background Radiotherapy is one of the effective methods for treatment of breast cancer; however, controversies still exist with respect to radiotherapy for patients with TNBC. Here, we intend to explore the mechanism by which local radiotherapy promotes the recruitment of M-MDSCs in the lung and increases the risk of lung metastasis in TNBC tumor-bearing mice. Methods A single dose of 20 Gy X-ray was used to locally irradiate the primary tumor of 4T1 tumor-bearing mice. Tumor growth, the number of pulmonary metastatic nodules, and the frequency of MDSCs were monitored in the mice. Antibody microarray and ELISA methods were used to analyze the cytokines in exosomes released by irradiated (IR) or non-IR 4T1 cells. The effects of the exosomes on recruitment of MDSCs and colonization of 4T1 cells in the lung of normal BALB/c mice were observed with the methods of FCM and pathological section staining. T lymphocytes or 4T1 cells co-cultured with MDSCs were performed to demonstrate the inhibitory effect on T lymphocytes or accelerative migration effect on 4T1 cells. Finally, a series of in vitro experiments demonstrated how the exosomes promote the recruitment of M-MDSCs in lung of mice. Results Even though radiotherapy reduced the burden of primary tumors and larger lung metastatic nodules (≥ 0.4 mm2), the number of smaller metastases (

Structural analyses of transmission towers against tornados, which are of vital practical significance in design and maintenance of the structures in regions suffering from the convective weather, were rarely reported by the wind engineering community up to today. To balance the computing efficiency and the simulation accuracy, numerical calculations based on Wen’s tornadic velocity model are employed to analyze the tornado-induced structural responses of a 131-meter-high free-standing transmission tower in east China in this article. Results suggest that both the tornadic load and the structural response are noticeably greater in the lateral direction than in the longitudinal direction, and they are found to be highly nonstationary due to the traveling nature of the tornado. In addition, according to the present study, the transmission tower is not prone to the strength failure during the tornadic event and slight fatigue damages are accumulated on the tower body due to the tornadic action which can be timely warned using the structural health monitoring strategy based on field measurements of low-order structural natural frequencies. Besides the points mentioned above, the innovations of the present research additionally include the following: (1) tornado-induced structural responses and atmospheric boundary layer wind-induced structural behaviors have been compared to provide conclusions of theoretical significance; (2) a novel fatigue damage assessment method based on the high-circle fatigue damage accumulation theory has been applied to the analysis of tornado-induced structural damage; (3) the structural configuration of a key joint on a main chord has been optimized against the tornado based on the advanced response surface optimization method.

In quantum anomalous Hall (QAH) materials, the mesoscopic scattering length (L s) plays an instrumental role in determining transport properties. Here, the authors examine L s in three regimes (QAH, quantum critical, and insulating) with distinct transport behaviours, and find a universal L s across all regimes.

This study aimed to explore the phenotype and relationship of drug resistance genes in livestock and poultry farm wastewater and drinking water reservoirs to provide evidence for the transmission mechanisms of drug resistance genes, in order to reveal the spread of drug resistance genes in wastewater from intensive farms in Central China to urban reservoirs that serve as drinking water sources and provide preliminary data for the treatment of wastewater from animal farms to reduce the threat to human beings. DNA extraction and metagenomic sequencing were performed on eight groups of samples collected from four water reservoirs and four related wastewaters from animal farms in Central China. Metagenomic sequencing showed that the top 20 AROs with the highest abundance were vanT_gene, vanY_gene, adeF, qacG, Mtub_rpsL_STR, vanY_gene_, vanW_gene, Mtub_murA_FOF, vanY_gene, vanH_gene, FosG, rsmA, qacJ, RbpA, vanW_gene, aadA6, vanY_gene, sul4, sul1, and InuF. The resistance genes mentioned above belong to the following categories of drug resistance mechanisms: antibiotic target replacement, antibiotic target protection, antibiotic inactivation, and antibiotic efflux. The resistomes that match the top 20 genes are Streptococcus agalactiae and Streptococcus anginosus; Enterococcus faecalis; Enterococcus faecium; Actinomyces viscosus and Bacillus cereus. Enterococcus faecium; Clostridium tetani; Streptococcus agalactiae and Streptococcus anginosus; Streptococcus agalactiae and Streptococcus anginosus; Acinetobacter baumannii, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, Corynebacterium jeikeium, Corynebacterium urealyticum, Mycobacterium kansasii, Mycobacterium tuberculosis, Schaalia odontolytica, and Trueperella pyogenes; Mycobacterium avium and Mycobacterium tuberculosis; Aeromonas caviae, Enterobacter hormaechei, Vibrio cholerae, Vibrio metoecus, Vibrio parahaemolyticus, and Vibrio vulnificus; Pseudomonas aeruginosa and Pseudomonas fluorescens; Staphylococcus aureus and Staphylococcus equorum; M. avium, Achromobacter xylosoxidans, and Acinetobacter baumannii; Sphingobium yanoikuyae, Acinetobacter indicus, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, and Providencia stuartii. Unreported drug resistance genes and drug-resistant bacteria in Central China were identified in 2023. In the transmission path of drug resistance genes, the transmission path from aquaculture wastewater to human drinking water sources cannot be ignored. For the sake of human health and ecological balance, the treatment of aquaculture wastewater needs to be further strengthened, and the effective blocking of drug resistance gene transmission needs to be considered.

A quantum anomalous Hall (QAH) insulator breaks reciprocity by combining magnetic polarization and spin-orbit coupling to generate a unidirectional transmission of signals in the absence of an external magnetic field. Such behavior makes QAH materials a good platform for the innovation of circulator technologies. However, it remains elusive as to how the wavelength of the chiral edge plasmon relates to its frequency and how the plasmon wave packet is excited in the time domain in a QAH insulator. Here, we investigate the edge magnetoplasmon (EMP) resonances in Cr-(Bi,Sb)_{2}Te_{3} by frequency and time domain measurements. From disk shaped samples with various dimensions, we obtain the dispersion relation of EMPs and extract the drift velocity of the chiral edge state. From the time-resolved transport measurements, we identify the velocity of the plasmon wave packet and observe a transition from the edge to bulk transport at an elevated temperature. We show that the frequency and time domain measurements are well modeled by loss from the microwave induced dissipative channels in the bulk area. Our results demonstrate that the EMP decay rate can be significantly reduced by applying a low microwave power and fabricating devices of larger diameter ≥100µm. In a R=125µm sample, a nonreciprocity of 20 dB has been realized at 1.3 GHz, shining light on using QAH insulators to develop on-chip nonreciprocal devices.

Abstract The graphene boom has triggered a widespread search for novel elemental van der Waals materials thanks to their simplicity for theoretical modeling and easy access for material growth. Group VI element tellurium is an unintentionally p-type doped narrow bandgap semiconductor featuring a one-dimensional chiral atomic structure which holds great promise for next-generation electronic, optoelectronic, and piezoelectric applications. In this paper, we first review recent progress in synthesizing atomically thin Te two-dimensional (2D) films and one-dimensional (1D) nanowires. Its applications in field-effect transistors and potential for building ultra-scaled Complementary metal–oxide–semiconductor (CMOS) circuits are discussed. We will also overview the recent study on its quantum transport in the 2D limit and progress in exploring its topological features and chiral-related physics. We envision that the breakthrough in obtaining high-quality 2D Te films will inspire a revisit of the fundamental properties of this long-forgotten material in the near future.

Magnetic topological insulators (MTIs) are a group of materials that feature topological band structures with concurrent magnetism, which can offer new opportunities for technological advancements in various applications, such as spintronics and quantum computing. The combination of topology and magnetism introduces a rich spectrum of topological phases in MTIs, which can be controllably manipulated by tuning material parameters such as doping profiles, interfacial proximity effect, or external conditions such as pressure and electric field. In this paper, we first review the mainstream MTI material platforms where the quantum anomalous Hall effect can be achieved, along with other exotic topological phases in MTIs. We then focus on highlighting recent developments in modulating topological properties in MTI with finite-size limit, pressure, electric field, and magnetic proximity effect. The manipulation of topological phases in MTIs provides an exciting avenue for advancing both fundamental research and practical applications. As this field continues to develop, further investigations into the interplay between topology and magnetism in MTIs will undoubtedly pave the way for innovative breakthroughs in the fundamental understanding of topological physics as well as practical applications.

With the large-scale grid connection of wind and photovoltaic power, the contradiction between renewable energy and thermal power is becoming more and more serious. To solve this problem, this paper comprehensively considers the construction and operation costs of power plants, and constructs an optimal generation expansion planning model of a combined thermal–wind–photovoltaic​ power system with the objective of minimizing total cost. The planning is calculated under the boundary conditions of ensuring the safe operation of the power grid and taking into account the share requirement, utilization requirements and construction requirements for renewable energy. The model is applied to the self-use and supporting power plants in Xinjiang. The results show that the proposed generation expansion plan can realize the coordinated development of three types of power sources under multiple boundary conditions, which has good applicability.

ObjectThe current study was performed to construct a model with microRNA (miRNA/miR) expression profile and TNM staging system for prognosis predicting in patients with lung adenocarcinoma (LUAD). MethodsDifferentially expressed miRNAs were identified from miRNA data of LUAD in The Cancer Genome Atlas (TCGA) database. Potential prognostic miRNAs and TNM classification parameters, screened out by Cox proportional hazards regression analysis, were included in the prognostic model. The prognostic model was visualized with a nomogram, and tested by calculating the C-index and drawing the calibration curve in the training set and validating set, respectively. Finally, the prognostic miRNAs were analyzed with bioinformatics tools. ResultsA total of 194 differentially expressed miRNAs were identified between LUAD tissues and matched normal tissues, including 99 up-regulated and 95 down-regulated miRNAs. miRNA index (miR.index), constructed with nine miRNAs (hsa-let-7i, hsa-mir-1976, hsa-mir-199a-1, hsa-mir-31, hsa-mir-3940, hsa-mir-450a-2, hsa-mir-4677, hsa-mir-548v and hsa-mir-6803), was an independent prognostic indicator for the survival of patients with LUAD. Bioinformatics analysis suggests that the selected miRNAs are involved in the development and progress of LUAD. ConclusionThe prognostic model constructed with nine miRNA expression profile and TNM classification parameters can predict the survival in patients with LUAD, and the predictive power of the model are warranted for further validations.

The complex band structure and carrier decay response upon photoexcitation of the chiral semiconductor tellurium remain to be unveiled. Here, the authors report unusual dynamic band modifications in Te near band-edge structure due to photoinduced symmetry breaking and strong anisotropy in carrier decay dynamics.

Abstract Background Sepsis is the leading cause of acute kidney injury (AKI) in the neonatal intensive care unit (NICU). The aim of the study is to explore the efficacy and security of continuous renal replacement therapy (CRRT) in the treatment of neonatal sepsis-related AKI. Method Totally12 sepsis-related AKI neonates treated with CRRT were hospitalized in the NICU of Shanghai Children’s Hospital between November 2012 and November 2019, and the clinical data of these 12 cases were retrospectively analyzed. Renal function, acid-base balance, electrolytes, blood pressure and hemodynamics indexes were recorded before CRRT initiation, 12/24/48 h after CRRT initiation and at the end of CRRT respectively. The efficacy of CRRT was evaluated and the clinical outcome was observed in these 12 sepsis-related AKI neonates. Repeated measurement analysis of variance was used for statistical analysis of the data. Result (1) Continuous veno-venous hemodialysis filtration (CVVHDF) was used in 12 cases of sepsis-related AKI neonates. There were 6 cases with oliguria, 3 cases with fluid overload (FO), 3 cases with septic shock. The duration of CRRT was 49 ~ 110 h, average (76.2 ± 23.5) h. (2) The blood pressure (BP) of 12 sepsis -related AKI neonates could reach the normal level (40–60 mmHg) 12 h after CRRT initiation, and the normal BP level could be maintained during the CRRT treatment. After 12 h CRRT, the blood pH value increased to the normal range (7.35 ~ 7.45). After 12 h CRRT treatment, the oxygenation index of 12sepsis-related AKI neonates could reach 200 mmHg. After 24 h CRRT treatment, it could rise to more than 300 mmHg. Serum potassium, serum urea nitrogen and serum creatinine levels decreased significantly 12 h after CRRT initiation, and reached the normal range 24 h after CRRT initiation. The urine volume significantly increased 24 h after CRRT initiation. (3) Venous catheterization was performed successfully in all sepsis-related AKI neonates. We observed 2 cases of thrombocytopenia, 1 case of obstruction and 1 case of hypotension in the course of CRRT. There were no complications such as hypothermia, hemorrhage, thrombosis and infection.11 neonates were cured and discharged. One neonate was treated with CRRT and passed through the oliguria stage of AKI, but died after the parents gave up the treatment. Conclusions It is safe and effective to treat neonatal sepsis-related AKI with CRRT, which should be an effective measure for the treatment of sepsis-related AKI neonates.

Introduction The objective of the Chinese Neonatal Network (CHNN) is to provide a platform for collaborative research, outcomes evaluation and quality improvement for preterm infants with gestational age less than 32 weeks in China. The CHNN is the first national neonatal network and has the largest geographically representative cohort from neonatal intensive care units (NICUs) in China.Methods and analysis Individual-level data from participating NICUs will be collected using a unique database developed by the CHNN on an ongoing basis from January 2019. Data will be prospectively collected from all infants

Background: Basic data concerning the gut microbiota of the main animal husbandry breeds (pigs and chickens) are scarce in China. The dynamics of gut microbiota (pigs and chickens) in China and antibiotic resistance genes carried by microorganisms in the natural environment are unknown. Methods: Free range and factory-farmed Gushi chickens and Huainan pigs were divided into eight groups. Faecal samples were collected from each group, and the metagenomic sequencing method was used to detect each group of samples. Results: The resistance genes showed the following trend, from high to low relative abundance: tetW was the highest, followed by tetW/N/W, then lnuA; and others from high to low were mdtB, lnuC, ANT6-la, ErmB, mdtC, ErmQ, tetBP, vatE, evgS, acrB, cpxA, mefA, Escherichia coli-ampC, tetL, yojl, AcrF and mdtA. All groups administered enrofloxacin and oregano oil did not develop a drug-resistant phenotype during the 5-day treatment period, as grouped in this trial. In 2022, after Announcement No. 194 of the Ministry of Agriculture and Rural Affairs in China, the antimicrobial resistance (AMR) trend declined, but it did not fundamentally change, presumably due to the impact of environmental pollution caused by the long-term use of antimicrobials.

Background: The Chinese Neonatal Network (CHNN) is a nationwide neonatal network that aims to improve clinical neonatal care quality and short- and long-term health outcomes of infants. This study aims to assess the quality of the Chinese Neonatal Network database by conducting an internal audit of data extraction.Methods: A data audit was performed by independently replicating the data collection and entry process in all 58 tertiary neonatal intensive care units (NICU) participating in the CHNN. Eighty-eight data elements selected for re-abstraction were classified into three categories (critical, important, less important), and agreement rates for original and re-abstracted data were predefined. Three to five records were randomly selected at each site for re-abstraction, including one short- (0–7 days), two medium- (8–28 days), and two long-stay (more than 28 days) cases. Agreement rates for each data item were calculated for individual NICUs and across the network, respectively.Results: A total of 283 cases and 24,904 data fields were re-abstracted. The agreement rates for original and re-abstracted data elements were 96.1% overall, and 97.2, 94.3, and 96.6% for critical, important, and less important data elements, respectively. Individual site variation for discrepancies ranged between 0.0 and 18.4% for all collected data elements.Conclusion: The completeness, precision, and quality of data in the CHNN database are high, providing assurance for multipurpose use, including health service evaluation, quality improvement, clinical trials, and other research.

Abstract Objectives The present phenotype‐based disease classification causes ambiguity in diagnosing and determining timely, effective treatment options for primary immunodeficiency (PID). In this study, we aimed to examine the characteristics of early‐onset PID and proposed a JAK‐STATopathy subgroup based on their molecular defects. Methods We reviewed 72 patients (

To identify next-generation-sequencing (NGS) clinical usability and to propose a standard diagnostic routine for critically ill infants, aged less than 100 days and suspected of having a genetically heterogeneous condition, a retrospective study was conducted between January 2016 and December 2018 at neonatal intensive care units (NICUs) of three tertiary hospitals in Shanghai, China. Whole-exome sequencing (WES) or panel sequencing was performed on 307 patients. Trio-WES, trio-panel, proband-WES, and proband-panel diagnostic yields were 39.71% (83/209), 68.75% (22/32), 59.09% (26/44), and 33.33% (4/12), respectively. Definitive molecular diagnoses of 142 infants (46.25%) uncovered 99 disorders; 21 disorders displayed on 44.37% of the diagnosed patients. Genetic etiologies were identified for 61.73% (50/81) of the deceased infants. One in three (29.58%) diagnosed infants exhibited one of the following four clinical traits which had a higher odds of diagnostic rate: integument abnormality (adjusted odds ratio [aOR], 19.7; 95% confidence interval [CI], 2.5–156.3), complex immune-related phenotypes (aOR, 9.2; 95% CI, 1.4–83.5), mixed nervous system phenotypes and congenital anomalies (aOR, 5.0; 95% CI, 1.3–19.1), or mixed metabolism and nervous system phenotypes (aOR, 4.5; 95% CI, 1.0–21.5). Our results demonstrated that NGS was an effective diagnostic tool. Infants exhibiting integument, complex immune-related conditions, metabolism, and nervous signs have higher chances of carrying variants in known disease-causing genes. The number of specific phenotypes could be used as an independent predictor of a positive molecular diagnosis, rather than an isolated abnormality. We developed a molecular diagnostic procedure for the use of NGS for diagnosis in Chinese NICU population based on individual characteristics.

In wireless sensor network, the storage amount of information is high, and the transmission and scheduling of control information is reasonable. The node communication model, network structure model, and energy consumption model are constructed. On this basis, the high-density data in wireless sensor network are scheduled to optimize the time for nodes to perform tasks. The nodes in the network are fully scheduled to control the generation time of packets in the network and the generation time of packets in the network. Experimental results show that in different iterations, the proposed method has lower node delay and node energy consumption, with values less than 0.2 and 2, respectively, and the maximum data fusion quality can reach 98, with high fusion benefits, so as to improve the transmission and scheduling efficiency and quality of high-density data in wireless sensor network.

Abstract Tibial dyschondroplasia (TD) is the most-prevalent leg disorder in fast-growing chickens; it is intractable and characterized by abnormal endochondral bone formation of proximal tibial growth-plates (TGPs). Previous studies have shown that bone is a highly vascularized tissue dependent on the coordinated coupling between angiogenesis and osteogenesis, but the underlying mechanisms of bone formation and bone remodeling are poorly defined in TD chickens. Here, we observed that inhibition of vasculogenesis and angiogenesis remarkably impaired vascular invasion in the hypertrophic chondrocyte zone of the TGPs, resulting in the massive death of chondrocytes due to a shortage of blood vessels and nutrients. Moreover, the balance of the OPG (osteoprotegerin)/RANKL (receptor activator of nuclear factor-kB ligand) system is also severely disrupted during the osteogenesis process while coupling with angiogenesis, both of which eventually lead to abnormal endochondral bone formation in TD chickens. Thus, the process of vascular formation in endochondral bone appears to initiate the pathological changes in TD, and improvement of this process during coupling with osteogenesis may be a potential therapeutic approach to treat this intractable disease.

Abstract Background Bronchopulmonary dysplasia (BPD) is a neonatal chronic lung disease characterized by impaired pulmonary alveolar development in preterm infants. Until now, little is known about the molecular and cellular basis of BPD. There is increasing evidence that lncRNAs regulate cell proliferation and apoptosis during lung organogenesis. The potential role of lncRNAs in the pathogenesis of BPD is unclear. This study aims to clarify the role of MALAT1 during the process of BPD in preterm infants and illustrate the protective effect of MALAT1 involved in preterm infants. Methods We assessed the expression of MALAT1 in BPD mice lung tissues by reanalyzing dataset GSE25286 (Mouse GEO Genome 4302 Array) from gene expression database gene expression omnibus (GEO), and verified MALAT1 expression in BPD patients by realtime q-PCR. Then the role of MALAT1 in regulating cell biology was examined by profiling dataset GSE43830. The expression of CDC6, a known antiapoptopic gene was verified in BPD patients and the alveolar epithelial cell line A549 cells in which MALAT1 was knocked down. Cell apoptosis was determined by FACS using PI/Annexin-V staining. Results The expression of MALAT1 was significantly evaluated in lung tissues of BPD mice at day 14 and day 29 compared to WT (P

Abstract Tibial dyschondroplasia (TD) is an intractable poultry problem that is characterized by the appearance of non-vascularized and non-mineralized cartilage masses in tibial growth plates (TGPs). However, the role of angiogenesis inhibition in the occurrence of TD remains unknown. In this study, we found that, compared to low-altitude Arbor Acres chickens (AACs), high-altitude Tibetan chickens showed higher tibial vascular distributions that were accompanied by up-regulation of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor A (VEGFA) and VEGF receptors. These observations provide insights into hypoxia-induced angiogenesis, which may be related to the absence of TD in high-altitude native Tibetan chickens. Importantly, hypoxia experiments also showed that during hypoxia, tibial angiogenesis was enhanced, which was due to pro-angiogenic factor up-regulation (including VEGFA, VEGFR1, VEGFR2, and IL-8), in AACs. Moreover, we observed that thiram-induced TD could strongly inhibit tibial angiogenesis in the hypertrophic zone through coordinated down-regulation of HIF-1α and pro-angiogenic factors, leading to a disruption in the blood supply to the TGP. Taken together, these findings reveal that the occurrence of TD is highly associated with inhibition of tibial angiogenesis through down-regulated expression of HIF-1α, VEGFA and VEGF receptors, which results in suppression of TGP development.

The main goal of our study was to characterize the population pharmacokinetics of vancomycin in critically ill Chinese neonates to develop a pharmacokinetic model and investigate factors that have significant influences on the pharmacokinetics of vancomycin in this population. The study population consisted of 80 neonates in the neonatal intensive care unit (ICU) from which 165 trough and peak concentrations of vancomycin were obtained. Nonlinear mixed effect modeling was used to develop a population pharmacokinetic model for vancomycin. The stability and predictive ability of the final model were evaluated based on diagnostic plots, normalized prediction distribution errors and the bootstrap method. Serum creatinine (Scr) and body weight were significant covariates on the clearance of vancomycin. The average clearance was 0.309 L/h for a neonate with Scr of 23.3 μmol/L and body weight of 2.9 kg. No obvious ethnic differences in the clearance of vancomycin were found relative to the earlier studies of Caucasian neonates. Moreover, the established model indicated that in patients with a greater renal clearance status, especially Scr < 15 μmol/L, current guideline recommendations would likely not achieve therapeutic area under the concentration-time curve over 24 h/minimum inhibitory concentration (AUC24h/MIC) ≥ 400. The exceptions to this are British National Formulary (2016–2017), Blue Book (2016) and Neofax (2017). Recommended dose regimens for neonates with different Scr levels and postmenstrual ages were estimated based on Monte Carlo simulations and the established model. These findings will be valuable for developing individualized dosage regimens in the neonatal ICU setting.

In order to identify the abnormal road surface condition efficiently and at low cost, a road surface condition recognition method is proposed based on the vibration acceleration generated by a smartphone when the vehicle passes through the abnormal road surface. The improved Gaussian background model is used to extract the features of the abnormal pavement, and the k-nearest neighbor (kNN) algorithm is used to distinguish the abnormal pavement types, including pothole and bump. Comparing with the existing works, the influence of vehicles with different suspension characteristics on the detection threshold is studied in this paper, and an adaptive adjustment mechanism based on vehicle speed is proposed. After comparing the field investigation results with the algorithm recognition results, the accuracy of the proposed algorithm is rigorously evaluated. The test results show that the vehicle vibration acceleration contains the road surface condition information, which can be used to identify the abnormal road conditions. The test result shows that the accuracy of the recognition of the road surface pothole is 96.03%, and the accuracy of the road surface bump is 94.12%. The proposed road surface recognition method can be utilized to replace the special patrol vehicle for timely and low-cost road maintenance.

Objetivo: Explorar o efeito da eritromicina sobre lesões pulmonares induzidas por hiperóxia. Métodos: Uma prole de ratos Sprague-Dawley (SD) prematuros com um dia de vida foi dividida aleatoriamente em quatro grupos: grupo 1 ar + cloreto de sódio, grupo 2 ar + eritromicina, grupo 3 hiperóxia + cloreto de sódio e grupo 4 hiperóxia + eritromicina. Com um, sete e 14 dias de exposição, foram detectadas Glutationa (GSH) e Interleucina-1 beta (IL-1 beta) pelo ensaio imunossorvente ligado à enzima (ELISA), e o ácido bicinconinico (BCA) foi utilizado para detectar a proteína GSH. O mRNA da γ-glutamil-cisteina-sintetase (γ-GCS) foi detectado por reação em cadeia da polimerase via transcriptase reversa (RT-PCR). Resultados: Comparadas ao grupo 1, as expressões do mRNA da GSH e da γ-GCS no grupo 3 aumentaram significativamente com um e sete dias de exposição (p < 0,05), porém a expressão de mRNA da γ-GCS diminuiu significativamente aos 14 dias; a expressão de IL-1 beta no grupo 3 aumentou significativamente aos 7 dias de exposição (p < 0,05) e diminuiu significativamente aos 14 dias. Comparadas ao grupo 3, as expressões do mRNA da GSH e da γ-GCS no grupo 4 aumentaram significativamente com um, sete e 14 dias de exposição (p < 0,05), porém as expressões de GSH mostraram uma tendência de queda aos 14 dias; a expressão de IL-1 beta no grupo 4 foi reduzida significativamente com um e sete dias de exposição (p < 0,05). Conclusões: As variações de IL-1 beta e GSH mediadas por oxidantes estão envolvidas no desenvolvimento de lesão pulmonar induzida por hiperóxia. A eritromicina poderá regular positivamente a atividade da γ-GCS, aumentando a expressão de GSH, inibindo os níveis de interleucina-1beta mediada por oxidante e aliviando a lesão pulmonar induzida por hiperóxia por meio de um efeito antioxidante.

Tibial dyschondroplasia (TD) is one of the most common problems in the poultry industry and leads to lameness by affecting the proximal growth plate of the tibia. However, due to the unique environmental and geographical conditions of Tibet, no case of TD has been reported in Tibetan chickens (TBCs). The present study was designed to investigate the effect of high altitude hypoxia on blood parameters and tibial growth plate development in chickens using the complete blood count, morphology, and histological examination. The results of this study showed an undesirable impact on the overall performance, body weight, and mortality of Arbor Acres chickens (AACs) exposed to a high altitude hypoxic environment. However, AACs raised under hypoxic conditions showed an elevated number of red blood cells (RBCs) and an increase in hemoglobin and hematocrit values on day 14 compared to the hypobaric normoxia group. Notably, the morphology and histology analyses showed that the size of tibial growth plates in AACs was enlarged and that the blood vessel density was also higher after exposure to the hypoxic environment for 14 days, while no such change was observed in TBCs. Altogether, our results revealed that the hypoxic environment has a potentially new role in increasing the blood vessel density of proximal tibial growth plates to strengthen and enhance the size of the growth plates, which may provide new insights for the therapeutic manipulation of hypoxia in poultry TD.

Neonates are at high risk of meningitis and of resulting neurologic complications. Early recognition of neonates at risk of poor prognosis would be helpful in providing timely management. From January 2008 to June 2014, we enrolled 232 term neonates with bacterial meningitis admitted to 3 neonatology departments in Shanghai, China. The clinical status on the day of discharge from these hospitals or at a postnatal age of 2.5 to 3 months was evaluated using the Glasgow Outcome Scale (GOS). Patients were classified into two outcome groups: good (167 cases, 72.0%, GOS = 5) or poor (65 cases, 28.0%, GOS = 1-4). Neonates with good outcome had less frequent apnea, drowsiness, poor feeding, bulging fontanelle, irritability and more severe jaundice compared to neonates with poor outcome. The good outcome group also had less pneumonia than the poor outcome group. Besides, there were statistically significant differences in hemoglobin, mean platelet volume, platelet distribution width, C-reaction protein, procalcitonin, cerebrospinal fluid (CSF) glucose and CSF protein. Multivariate logistic regression analyses suggested that poor feeding, pneumonia and CSF protein were the predictors of poor outcome. CSF protein content was significantly higher in patients with poor outcome. The best cut-offs for predicting poor outcome were 1,880 mg/L in CSF protein concentration (sensitivity 70.8%, specificity 86.2%). After 2 weeks of treatment, CSF protein remained higher in the poor outcome group. High CSF protein concentration may prognosticate poor outcome in neonates with bacterial meningitis.

The diagnosis of neonatal invasive fungal disease (IFD) is difficult and often delayed. The platelet parameters and (1, 3)-β-D-Glucan (BG) may be useful for diagnosing IFD, but their diagnostic performance are not well characterized in neonates. We studied 63 preterm infants with IFD, 160 preterm infants without sepsis (preterm control), and 41 preterm infants with bacterial sepsis. Platelet parameters at the first day of onset of IFD and at the fourteenth day after antifungal treatment were evaluated. Serum BG was measured. Platelet count (PC), plateletcrit (PCT), and platelet distribution width (PDW) values were significantly lower, and mean platelet volume (MPV) values significantly higher in the IFD versus preterm control infants. PC and PCT values were much lower in infants with IFD versus bacterial sepsis, and there were significant differences in BG value between the two groups. After 14 days of antifungal treatment, significant elevations in PC, PCT, PDW and reductions in MPV levels in IFD group were observed. Receiver operating characteristic (ROC) curves showed that PC and PCT were strong predictors of IFD. The PC and PCT cut-offs for predicting IFD were 119.5 (sensitivity 78%, specificity 95%) and 0.21 (sensitivity 83%, specificity 85%), respectively. There were significant differences in PC and PCT levels between deceased and survived patients. The PC and PCT cut-offs for predicting deceased IFD were 39 (sensitivity 62%, specificity 86%) and 0.04 (sensitivity 50%, specificity 95%), respectively. The sensitivity in diagnosing IFD by a BG cutoff of ≥10 pg/ml was 68.3% and specificity was 75.6%. PC and PCT levels in the BG ≥400 pg/ml group were significantly lower compared to the BG

Although a variety of genetic strategies have been developed to inhibit HIV replication, few direct comparisons of the efficacy of these inhibitors have been carried out. Moreover, most studies have not examined whether genetic inhibitors are able to induce a survival advantage that results in an expansion of genetically-modified cells following HIV infection. We evaluated the efficacy of three leading genetic strategies to inhibit HIV replication: 1) an HIV-1 tat/rev-specific small hairpin (sh) RNA; 2) an RNA antisense gene specific for the HIV-1 envelope; and 3) a viral entry inhibitor, maC46. In stably transduced cell lines selected such that >95% of cells expressed the genetic inhibitor, the RNA antisense envelope and viral entry inhibitor maC46 provided the strongest inhibition of HIV-1 replication. However, when mixed populations of transduced and untransduced cells were challenged with HIV-1, the maC46 fusion inhibitor resulted in highly efficient positive selection of transduced cells, an effect that was evident even in mixed populations containing as few as 1% maC46-expressing cells. The selective advantage of the maC46 fusion inhibitor was also observed in HIV-1-infected cultures of primary T lymphocytes as well as in HIV-1-infected humanized mice. These results demonstrate robust inhibition of HIV replication with the fusion inhibitor maC46 and the antisense Env inhibitor, and importantly, a survival advantage of cells expressing the maC46 fusion inhibitor both in vitro and in vivo. Evaluation of the ability of genetic inhibitors of HIV-1 replication to confer a survival advantage on genetically-modified cells provides unique information not provided by standard techniques that may be important in the in vivo efficacy of these genes.

Background: Atherosclerosis (AS) is a chronic progressive inflammatory disease, and plaque stability plays a critical role in preventing acute events. Tanyu Tongzhi formula (TTF), a traditional Chinese medicine, has potential therapeutic effects on AS. Methods: We used an AS animal model to examine the effects of TTF on atherosclerotic plaque vulnerability and CD40+ monocyte differentiation. AS plaque area, collagen content, and lipid area were assessed using histological staining. AS plaque-related biomarkers (monocyte chemoattractant protein 1 (MCP-1), monocyte plus macrophage (MOMA-2), von Willebrand factor (vWF), CD31, and alpha-smooth muscle actin (a-SMA)) were detected using immunohistochemistry. Inflammatory cytokines were determined using enzyme-linked immunosorbent assay. CD40 mRNA expression was detected by real-time quantitative PCR. CD40+ monocyte differentiation was evaluated by flow cytometry analysis in ApoE-/- mice and peripheral blood mononuclear cells (PBMCs). AMPK/NF-κB signaling pathways-related protein expression was investigated through western blotting. Results: TTF treatment reduced AS plaque area, collagen content, and lipid area in AS model mice. Levels of MCP-1, MOMA-2, vWF, and CD31 were decreased, while a-SMA level was increased by TTF in model mice. TTF reduced inflammatory cytokines levels, including tumor necrosis factor receptor-a (TNF-a), high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6). TTF inhibited CD40+ monocyte differentiation and decreased the number of CD40+/CD40- and Ly6C+/Ly6C- cells and M1/M2 ratio in AS model mice and human PBMCs. Additionally, TTF modulated the AMPK/NF-κB signaling pathway in human PBMCs. Conclusion: TTF attenuates atherosclerotic plaque vulnerability by inhibiting CD40+ monocyte differentiation, possibly through the regulation of the AMPK/NF-κB signaling pathway. These findings suggest that TTF could be a potential therapeutic agent for preventing plaque rupture and subsequent cardiovascular events in patients with AS. [ABSTRACT FROM AUTHOR]