Search

Entity resolution (ER) identifies data instances referring to the same real-world entity and has received enormous research attention. In this paper, we examine the task of ER from a broader perspective, with its input extended from textual records, which are conventionally studied in the literature, to other modalities such as check-in sequences, GPS trajectories and surveillance video frames to generate new applications. Our goal in this paper is to design an effective model to uniformly support all these ER applications with different input formats. Technically, we fully exploit the semantic contexts of embedding vectors for the pair of input instances. In particular, we propose an integrated multi-context attention framework that takes into account self-attention, pair-attention and global-attention from three types of context. The idea can be further extended to incorporate attribute attention in order to support structured datasets. We conduct extensive experiments on a diverse class of entity resolutions tasks, including tasks on unstructured, structured and dirty textual records, check-in sequences, GPS trajectories and surveillance video frames. The experimental results verified the effectiveness and generality of our model. When compared with strong baselines in these applications, our model can achieve superior or comparative performance.

Introduction Multivariate time series prediction of infectious diseases is significant to public health, and the deep learning method has attracted increasing attention in this research field. Material and methods An adaptively temporal graph convolution (ATGCN) model, which learns the contact patterns of multiple age groups in a graph-based approach, was proposed for COVID- 19 and influenza prediction. We compared ATGCN with autoregressive models, deep sequence learning models, and experience- based ATGCN models in short-term and long-term prediction tasks. Results Results showed that the ATGCN model performed better than the autoregressive models and the deep sequence learning models on two datasets in both short-term (12.5% and 10% improvements on RMSE) and long-term (12.4% and 5% improvements on RMSE) prediction tasks. And the RMSE of ATGCN predictions fluctuated least in different age groups of COVID- 19 (0.029 ± 0.003) and influenza (0.059±0.008). Compared with the Ones-ATGCN model or the Pre-ATGCN model, the ATGCN model was more robust in performance, with RMSE of 0.0293 and 0.06 on two datasets when horizon is one. Discussion Our research indicates a broad application prospect of deep learning in the field of infectious disease prediction. Transmission characteristics and domain knowledge of infectious diseases should be further applied to the design of deep learning models and feature selection. Conclusions The ATGCN model addressed the multivariate time series forecasting in a graph-based deep learning approach and achieved robust prediction on the confirmed cases of multiple age groups, indicating its great potentials for exploring the implicit interactions of multivariate variables.

A graphene/epoxy composite based broadband all-optical tunable fiber microcavity filter is presented. The graphene/epoxy composite based microcavity shows the excellent all-optical controlability. Since the light acts on the graphene/epoxy composite directly, the microcavity has stronger optical Kerr effect and photothermal effect induced by the optical pump. Experimental results show that its wavelength tuning range and tuning step reach 25.54 nm and 832 pm/mW, respectively. It is expected to be applied in the fields of tunable optical filters, optical communication, optical sensors, fiber lasers, and spectrum scanning.

Background: Sepsis is considered to be a systemic inflammatory response due to infection, resulting in organ dysfunction. Timely targeted interventions can reduce mortality and improve prognosis. Therefore, it is important to identify potential sepsis in time. Inflammation plays a crucial role in the process of sepsis. We combined inflammatory markers to develop and validate a nomogram model and a simple risk scoring model for predicting sepsis in critically ill patients. Furthermore, comparing the prediction performance of the two models.Methods: The medical records of adult patients admitted to our intensive care unit (ICU) from August 2017 to December 2020 were analyzed. The finally included patients were randomly divided into training cohort (70%) and validation cohort (30%). A nomogram model for sepsis was developed through multivariate logistic regression analysis in the training cohort. The continuous variables included in nomogram model were transformed into dichotomous variables. Then a multivariable logistic regression analysis was performed based on these dichotomous variables and the odds ratio (OR) for each variable was used to construct a simple risk scoring model for predicting sepsis. The receiver operating characteristic curves (ROC) were constructed and the area under the curve (AUC) was calculated to evaluate the discrimination performance of the two models. Results: According to our inclusion and exclusion criteria, 2074 patients were included in study. Finally, white blood cell (WBC), C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT) and neutrophil-to-lymphocyte ratio (NLR) were included in our models. The AUC of the nomogram model was 0.854 (95%CI: 0.835-0.872). The AUC of the simple risk scoring model was 0.842 (95%CI: 0.822-0.861). When the cut-off value was 7.5 points, the sensitivity was 77.03% and the specificity was 75.75%. The prediction performance of the two models on sepsis is comparable (p=0.1298) and better than that of Sequential Organ Failure Assessment (SOFA) scores (AUC=0.759).Conclusions: This study combining five commonly available inflammatory markers (WBC, CRP, IL-6, PCT and NLR) developed a nomogram model and a simple risk scoring model to predict sepsis in critically ill patients. Although the prediction performance of the two models is comparable, the simple risk scoring model may be simpler and more practical for clinicians to identify potential sepsis in critically ill patients at an early stage and make treatment strategies.

In order to realize high-sensitivity real-time monitoring of acid-base neutral solutions in the industrial field, it is very important to study how to improve the sensitivity of a pH sensor. Herein, the sensitivity of the pH sensor was improved by using both monolithic integrated planar multi-channel and photoconductive properties of gallium nitride (GaN) high electron-mobility transistors (HEMTs) as a core of the pH sensor. The sensitive area of aluminum gallium nitride/gallium nitride (Al $_{0.25}$ Ga $_{0.75}$ N/GaN) heterojunction HEMT channel surface was increased, and the channel effective resistance was reduced by planar multi-channels. And the photogenerated current was generated by 365-nm ultraviolet (UV) light based on the photoconductive effect. This investigation mainly shows as the sensitivity of the tri-channel was 37.04 μA/pH, which increased 30 times compared with that of the single-channel device under the dual action of planar multi-channel and 365-nm UV light coupling in potassium hydrogen phthalate, mixed phosphate, and borax pH correction buffer solutions. The concept of using the GaN HEMT-based pH sensor for direct quantification of pH values in waste water provides a simple and high-performance method for industrial applications.

Werner syndrome is a rare autosomal recessive premature progeroid syndrome caused by mutations in the WRN gene. It is characterized by early onset of age-related diseases, such as cataracts, atherosclerosis, diabetes mellitus, osteoporosis and malignancies, in which diabetes often onset in patients' 30-40s. Herein, we report a Chinese patient with Werner syndrome with uncommon early-onset diabetes at 18 years-of-age, who had low body mass index, insulin resistance, negative antibodies of diabetes and early onset of cataracts. Genome sequencing and reverse transcription polymerase chain reaction confirm the diagnosis. A novel heterozygous splice-site mutation in the WRN gene (c.1270-2A>T) was identified. The present case reminds clinicians that when young diabetes patients are encountered, if they are accompanied by premature aging, attention should be paid to identifying the possibility of Werner syndrome based on diagnostic criteria.

Purpose To evaluate the effects of the association between first trimester vitamin D (VitD) concentrations and increased prepregnancy body mass index (BMI) on early fetal growth restriction (FGR). Methods This retrospective cohort study included 15,651 women with singleton pregnancy who delivered at the International Peace Maternity and Child Health Hospital between January 2015 and November 2016. Women were classified in two groups based on their serum 25(OH)D vitamin levels status: VitD sufficient (SUFF) group and VitD insufficient or deficient (INSUFF/DEF). The cut-off point for VitD concentration was 50.00 nmol/L. Comparisons were made between women with normal prepregnancy body weight (BMI 18.5–23.9 kg/m2) and overweight and obese (OWO) women (BMI > 24.0 kg/m2). Early FGR was defined as first-trimester gestational age-adjusted crown-rump length (CRL) in the lowest 20th centile of the population. Multivariate logistic regression was used to evaluate the association between maternal serum 25(OH)D levels and prepregnancy BMI with first trimester CRL and early FGR. Results In VitD INSUFF/DEF group, the first trimester CRL was decreased (P = 0.005), and the risk of early FGR was increased by 13% (95% CI 1.04–1.24, P = 0.004) compared to the VitD SUFF group. In OWO group, the first trimester CRL was also significantly decreased (P P P for interaction = 0.02) and the risk of early FGR (P for interaction = 0.07). Conclusion Sufficient first trimester serum 25(OH)D concentration was a protective factor for early fetal growth, especially among OWO mothers. Chinese Clinical Trial Registry (Registration number: ChiCTR1900027447 with date of registration on November 13, 2019-retrospectively registered).

Radiation therapy (RT) modulates immune cells and cytokines, resulting in both clinically beneficial and detrimental effects. The changes in peripheral blood T lymphocyte subsets and cytokines during RT for pediatric brain tumors and the association of these changes with therapeutic outcomes have not been well described.The study population consisted of children (n = 83, aged 3~18) with primary brain tumors (medulloblastoma, glioma, germ cell tumors (GCT), and central nervous system embryonal tumor-not otherwise specified), with or without residual or disseminated (R/D) diseases who were starting standard postoperative focal or craniospinal irradiation (CSI). Peripheral blood T lymphocyte subsets collected before and 4 weeks after RT were enumerated by flow cytometry. Plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, interferon-γ, and IL-17A were measured by cytometric bead array.Patients with R/D lesions receiving CSI (n = 32) had a post-RT increase in the frequency of CD3+T and CD8+T cells, a decrease in CD4+T cells, and an increase in regulatory T cells (Tregs) and CD8+CD28- suppressor cells, which was more predominantly seen in these patients than in other groups. In the CSI group with such R/D lesions, consisting of patients with medulloblastoma and germ cell tumors, 19 experienced a complete response (CR) and 13 experienced a partial response (PR) on imaging at 4 weeks after RT. The post/pre-RT ratio of Tregs (P = .0493), IL-6 (P = .0111), and IL-10 (P = .0070) was lower in the CR group than in the PR group. Multivariate analysis revealed that the post/pre-RT ratios of Treg, IL-6, and IL-10 were independent predictors of CR (P.0001, P = .018, P.0001, respectively). The areas under the receiver operating curves and confidence intervals were 0.7652 (0.5831-0.8964), 0.7794 (0.5980-0.9067), and 0.7085 (0.5223-0.8552) for IL-6, IL-10, and Treg, respectively. The sensitivities of IL-6, IL-10, and Treg to predict radiotherapeutic responses were 100%, 92.3%, and 61.5%, and specificity was 52.6%, 57.9%, and 84.2%, respectively.CSI treatment to those with R/D lesions predominantly exerted an effect on antitumor immune response compared with both R/D lesion-free but exposed to focal or CSI RT and with R/D lesions and exposed to focal RT. Such CSI with R/D lesions group experiencing CR is more likely to have a decrease in immunoinhibitory molecules and cells than patients who only achieve PR. Measuring peripheral blood Treg, IL-6, and IL-10 levels could be valuable for predicting radiotherapeutic responses of pediatric brain tumors with R/D lesions to CSI for medulloblastoma and intracranial germ cell tumors.

The heliostat field of tower solar thermal power station accounts for 40%–50% of the total cost, and influences the concentrating efficiency. Accordingly, it is necessary to optimize the layout of the heliostat field. Based on the optical efficiency model, an improved Gray Wolf Optimization (GWO) algorithm is proposed to optimize the field parameters of the heliostats, improve the convergence factor and weight updating formula, and effectively avoid the local optimal problem. Then SolarPILOT software is used to simulate the heliostat field distribution. In order to reduce the shadow and shielding efficiency loss, improve the land utilization rate and atmospheric attenuation efficiency, the heliostat field is initialized by radial staggered arrangement, which is easy to be optimized. By using the optical efficiency model, the program of heliostat field optimization algorithm is developed, and a Delingha tower power station is used to verify the algorithm. After the improved GWO algorithm optimizing the heliostat field, the optical or concentrating efficiency of the heliostat field is increased by 8.2% compared with the GWO algorithm. The improved GWO algorithm reduces the heliostat number by 3.4% compared with the Gray Wolf algorithm, and that reducing the cost of the heliostat field.

Government subsidies have always been regarded as an essential policy tool to promote the development of new energy vehicle (NEV) industry. The NEV industry refers to the companies engaged in the production and application of NEVs, mainly including suppliers of raw materials, suppliers of core components, vehicle manufacturers and retailers. However, the effect of subsidies on NEV enterprises is controversial. In this regard, understanding the impact of subsidies on different firms operating at various levels across the NEV industrial chain is crucial to harness the benefits of subsidies effectively. Therefore, we use empirical data from China's 153 NEV listed firms between 2009 to 2018 operating at downstream, midstream, and upstream levels of the industrial chain to assess the impact of subsidies on firm financial performance. Our overall results indicate that subsidies have a significant negative effect on firms’ financial performance by employing the fixed-effect model. Moreover, we observe the heterogeneous impact of subsidies on companies’ financial performance when NEV enterprises are further divided into different groups based on their business characteristics, geographical location, and ownership structure. The findings suggest that the impact of subsidies on upstream firms’ financial performance is greater in comparison to the firms operating at midstream and downstream levels. Furthermore, the negative effect of subsidy on the firms located in the mid-western region and non-state-owned enterprises is stronger compared with the firms in the eastern region and state-owned enterprises. Our findings are robust with replacing the dependent variable, investigating the moderating of rent-seeking, and using the instrumental variable method.

Context Tangwang Mingmu granule (TWMM), a traditional Chinese medicine, has been widely used in the treatment of diabetic retinopathy (DR), the most common microvascular complication in diabetes mellitus. Objective To establish a method to select target compounds from herbs for a pharmacokinetic study using network pharmacology, which could be applied in clinical settings. Materials and methods First, UPLC/Q Exactive Q-Orbitrap and GCMS 2010 were used to determine the non-volatile and volatile ingredients of TWMM. Based on the identified compounds, network pharmacology was used to screen the key compounds and targets of TWMM in the treatment of DR. Based on the compound-target-pathway network and identification of components emigrant into blood, the potential compound markers in vivo were chosen. Then, Sprague-Dawley (SD) rats were administrated of TWMM at a 9.6 g/kg dose to investigating pharmacokinetic parameters using the UPLC-QQQ-MS. Results Ninety and forty-five compounds were identified by UPLC-MS and GC-MS, respectively. Based on the network pharmacology, nine compounds with a degree value above 15 were screened and implied that these compounds are the most active in DR treatment. Moreover, criteria of degree value greater than 7 were applied, and PTGS2, NOS2, AKT1, ESR1, TNF, and MAPK14 were inferred as the core targets in treating DR. After identification of components absorbed into blood, luteolin and formononetin were selected and used to investigate the pharmacokinetic parameters of TWMM after its oral administration. Conclusions The reported strategy provides a method that combines ingredient profiling, network pharmacology, and pharmacokinetics to determine luteolin and formononetin as the pharmacokinetic markers of TWMM. This strategy provides a clinically relevant methodology that allows for the screening of pharmacokinetic markers in Chinese medicines.

Introduction Guanidinoacetate methyltransferase (GAMT) deficiency is an inherited metabolic disorder that impairs the synthesis of creatine (CRE). Lack of CRE in the brain can cause intellectual disability, autistic-like behavior, seizures, and movement disorders. Identification at birth and immediate therapy can prevent intellectual disability and seizures. Here we report the first two cases of GAMT deficiency identified at birth by newborn screening (NBS) in Utah and New York. Methods NBS dried blood spots were analyzed by tandem mass spectrometry (MS/MS) using either derivatized or non-derivatized assays to detect guanidinoacetate (GUAC) and CRE. For any positive samples, a second-tier test using a more selective method, ultra-performance liquid chromatography (UPLC) combined with MS/MS, was performed to separate GUAC from potential isobaric interferences. Results NBS for GAMT deficiency began in Utah on June 1, 2015 using a derivatized method for the detection of GUAC and CRE. In May 2019, the laboratory and method transitioned to a non-derivatized method. GAMT screening was added to the New York State NBS panel on October 1, 2018 using a derivatized method. In New York, a total of 537,408 babies were screened, 23 infants were referred and one newborn was identified with GAMT deficiency. In Utah, a total of 273,902 infants were screened (195,425 with the derivatized method, 78,477 with the non-derivatized method), three infants referred and one was identified with GAMT deficiency. Mean levels of GUAC and CRE were similar between methods (Utah derivatized: GUAC = 1.20 ± 0.43 μmol/L, CRE = 238 ± 96 μmol/L; Utah non-derivatized: GUAC = 1.23 ± 0.61 μmol/L, CRE = 344 ± 150 μmol/L, New York derivatized: GUAC = 1.34 ± 0.57 μmol/L, CRE = 569 ± 155 μmol/L). With either Utah method, similar concentrations of GUAC are observed in first (collected around 1 day of age) and the second NBS specimens (routinely collected at 7–16 days of age), while CRE concentrations decreased in the second NBS specimens. Both infants identified with GAMT deficiency started therapy by 2 weeks of age and are growing and developing normally at 7 (Utah) and 4 (New York) months of age. Conclusions Newborn screening allows for the prospective identification of GAMT deficiency utilizing elevated GUAC concentration as a marker. First-tier screening may be incorporated into existing methods for amino acids and acylcarnitines without the need for new equipment or staff. Newborn screening performed by either derivatized or non-derivatized methods and coupled with second-tier testing, has a very low false positive rate and can prospectively identify affected children. SummaryCerebral creatine deficiency syndromes caused by defects in creatine synthesis can result in intellectual disability, and are preventable if therapy is initiated early in life. This manuscript reports the identification of two infants with GAMT deficiency (one of the cerebral creatine deficiency syndromes) by newborn screening and demonstrates NBS feasibility using a variety of methods.

Since the proposal of the Belt and Road initiative in March 2015, the Chinese government has continued to increase its investment in transportation infrastructure construction in West African count...

In order to avoid the bus voltage spikes caused by leakage inductance endangering the normal operation of the inverter, based on the improved Y-source inverter, the traditional clamping structure and voltage peak absorption circuit are introduced, and a high step-up and low-voltage stress improved Y-source inverter with the capability of absorbing bus voltage spike is proposed. This topology fully utilizes the structural characteristics of the improved Y-source inverter itself, and further increases the DC-side voltage gain on the basis of ensuring the busbar voltage peak absorption capacity, while reducing the capacitor voltage stress. This paper demonstrates the superiority of the proposed topology over improved Y-source inverter topology by analyzing its working principle and voltage gain, simulation and experiment platform are constructed to perform the circuit simulation and experiment, and the correctness of the theoretical analysis of the proposed inverter and the effectiveness of the busbar voltage peak absorption capacity are verified.

Meal ingestion elicits a variety of neuronal, physiological and hormonal responses that differ in healthy, obese or diabetic individuals. The mixed meal tolerance test (MMTT) is a well-established method to evaluate pancreatic β-cell reserve and glucose homeostasis in both preclinical and clinical research in response to calorically defined meal. Nonhuman primates (NHPs) are highly valuable for diabetic research as they can naturally develop type 2 diabetes mellitus (T2DM) in a way similar to the onset and progression of human T2DM. The purpose of this study was to investigate the reproducibility and effects of a MMTT containing acetaminophen on plasma glucose, insulin, C-peptide, incretin hormones, lipids, acetaminophen appearance (a surrogate marker for gastric emptying) in 16 conscious obese cynomolgus monkeys (Macaca fascicularis). Plasma insulin, C-peptide, TG, aGLP-1, tGIP, PYY and acetaminophen significantly increased after meal/acetaminophen administration. A subsequent study in 6 animals showed that the changes of plasma glucose, insulin, C-peptide, lipids and acetaminophen were reproducible. There were no significant differences in responses to the MMTT among the obese NHPs with (n = 11) or without (n = 5) hyperglycemia. Our results demonstrate that mixed meal administration induces significant secretion of several incretins which are critical for maintaining glucose homeostasis. In addition, the responses to the MMTTs are reproducible in NHPs, which is important when the MMTT is used for evaluating post-meal glucose homeostasis in research.

The occurrence of acute myocardial infarction (AMI) accompanied by ischemic cerebrovascular accidents has rarely been reported in previous articles. In this report, we present a 72-year-old female patient with massive cerebral infarction secondary to acute anterior and high lateral wall myocardial infarction, finally resulting in a deep coma. The patient ultimately failed to respond to aggressive resuscitation and succumbed to cardiogenic shock and fatal ventricular arrhythmias. We consider that the co-occurrence of these diseases is more than just a coincidence, and that there may be a connection between them. In this article, we performed an in-depth exploration and discussion of the explanation of this phenomenon. It is essential to recognize these situations in the early stages, which determines the follow-up treatment and prognosis. We suggest that decisions regarding patient management should be based on hemodynamic stability, close cardiac monitoring, and the site of cerebral infarction, and also emphasize that the evaluation of hemodynamic status in these patients is a prerequisite for deciding whether to treat the cerebral or coronary infarction first. The present report is written for the purpose of reminding readers of this rare and severe situation, and to emphasize the necessity for further research on how to deal with it best.

The aim of the study was to describe the electroclinical features of visual sensitivity in patients with familial cortical myoclonic tremor and epilepsy. We searched the EEG database using the terms "familial cortical myoclonic tremor and epilepsy" and "visual sensitivity" over a seven-year period from March 2013 to April 2020 in the Xijing hospital, Xi'an, China. The inclusion criteria were demonstrable electroclinical visual sensitivity in the form of eye-opening sensitivity, eye-closure sensitivity, eyes-closed sensitivity and photosensitivity. Clinical, EEG and imaging records of patients were screened, and subsequently, detailed analysis of their data was undertaken. We enrolled six patients with visual sensitivity, five of whom suffered with rare generalized tonic-clonic seizures. Neuroimaging was negative in all cases. All patients demonstrated photosensitivity; eye-opening sensitivity associated with cortical myoclonic in one patient, eyes-closed sensitivity associated with cortical myoclonic tremor status in three patients, and eye-closure sensitivity in two patients. At the last follow-up visit, cortical myoclonic tremor and epilepsy in all patients was well controlled with first-line treatment. Visual sensitivity is therefore likely to be an important reflex trait in some patients with familial cortical myoclonic tremor and epilepsy, and should be routinely evaluated in order to better define the electroclinical features in FCMTE syndrome. [Published with video sequences].

Persistent inflammation, immunosuppression and catabolism syndrome (PICS) in critically ill patients are associated with unreliable creatinine (Cr)-based estimated glomerular filtration rate (eGFR) and alteration in vancomycin clearance (CL) due to ongoing muscle wasting and renal dysfunction (RD). Currently, cystatin C (Cys) is of great interest for eGFR due to its muscle independence. Patients receiving intravenous vancomycin with trough concentration monitoring after intensive care unit stay ≥ 14 days were retrospectively enrolled. Those with C-reactive protein > 30.0 mg/L, lymphocytes count 10% were diagnosed with PICS. Impact of PICS on vancomycin trough achievement was analyzed. Plasma Cys and Cr levels with their eGFRs in RD were compared in patients with and without PICS. Furthermore, the performance of eGFRs in predicting vancomycin CL was quantificationally evaluated by population pharmacokinetics (PPK) analysis using the Phoenix NLME software. Of 69 enrolled patients, 32 (46.4%) were PICS. PICS was predictive of Cr-guided vancomycin supratherapeutic trough concentrations (OR = 5.26, P = 0.013). Significant elevation of Cys, not of Cr, was observed in patients with PICS suffering from RD (P = 0.022), causing substantial differences among eGFRs. Fifty-two and 17 patients were enrolled for the modeling group and validation group, respectively. A one-compartment PPK model with first-order elimination adequately described the data of 126 Ctrough. Prediction of vancomycin CL with Cys and Cr-based eGFR (CKD-EPIcys-cr) significantly reduced the interindividual variability of CL (from 75.6 to 28.5%). External validation with 34 Ctrough showed the robustness and accuracy of this model. This study showed the negative impact of PICS on Cr-guided vancomycin trough achievement. PPK model with CKD-EPIcys-cr can be used to optimize vancomycin dosage in patients with PICS.

A unique extra photoresponse of graphene field-effect transistor to the first laser pulse after a switch of back-gate voltage (VBG) is reported and explored here. It is referred as fresh-bias photoresponse (FBPR). FBPR suggests a unique prompt charge transfer process triggered by laser illumination with the help of the VBG and the transferred charge holds as far as the VBG holds unchanged. The responsible charge transfer process is proposed between ester oxygen and carbonyl carbon atoms in the ester side chains of poly(methyl methacrylate) (PMMA) molecule. The proposed mechanism explains perfectly all of the features of FBPR. The charge transfer process generates an inter-molecular dipole moment of PMMA. Such dipole moment generation is much fast than that introduced by a photo-triggered isomerization reaction of photochromic molecule, which have been used in graphene based photodetectors. This mechanism is further confirmed by the test result of a control device with mechanically exfoliated graphene channel and a control device fabricated on hexagonal boron nitride substrate. The mechanism behind FBPR may provide a new way of developing phototransistors, photodetectors or photoelectronic memory devices in the future.

Léri–Weill dyschondrosteosis (LWD) is usually caused by haploinsufficiency of the short stature homeobox‐containing gene (SHOX). The clinical manifestation of this disease is a classic triad, which are short stature, mesomelia and Madelung deformity. LWD also includes other features, such as high body mass index. Short stature and high body mass index are risk factors of type 2 diabetes mellitus and cardiovascular disease; however, LWD combined with type 2 diabetes mellitus or metabolic syndrome have not been described in the literature. In this article, we report a case of LWD caused by an M1T mutation of the start codon of the SHOX gene. The patient also had type 2 diabetes mellitus, hypertension and dyslipidemia. It is suggested that patients with LWD should be identified promptly, and the prevention and treatment of metabolic diseases and cardiovascular disease should be taken into consideration in patients with LWD., It is suggested that patients with Léri–Weill dyschondrosteosis should be identified promptly, and the prevention and treatment of metabolic diseases and cardiovascular disease should be taken into consideration in patients with Léri–Weill dyschondrosteosis.

To observe the effect of transient receptor potential ankyrin 1 (TRPA1) channel on the proliferation and inflammation of airway smooth muscle cells (SMC) in asthmatic rats, the rats were randomly allocated into three treatment groups: control, asthma, and Shenmai injection (SMI), with 15 rats in each group. Asthmatic rat models were induced by ovalbumin (OVA) inhalation. Rats in the control and asthma groups were intraperitoneally injected 2 mL NS daily, whereas rats in the SMI treatment group were intraperitoneally injected with 2 mL SMI daily. RT-qPCR and western blotting were used to test for TRPA1 and proliferating cell nuclear antigen (PCNA) mRNA and protein expression. ELISA was used to test the expression of interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13) in the serum. Compared with the control group, there were significantly higher levels of TRPA1 and PCNA mRNA and protein, as well as of IL-4, IL-5, and IL-13 in asthmatic rats (P< 0.05). After SMI treatment, there was significantly lower expression of TRPA1, PCNA, IL-4, IL-5, and IL-13 compared to the levels in asthmatic rats (P < 0.05). TRPA1, IL-4, IL-5, and IL-13 were highly expressed in the tracheal SMC of asthmatic rats. Inhibiting TRPA1, IL-4, IL-5, and IL-13 using SMI may be one of the mechanisms that can intervene chronic airway inflammation and asthma proliferation.

Concerns on nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) in the environment have mainly arisen from their mutagenic and carcinogenic effects. The objective of this study is to investigate whether nitro-PAH exposures are associated with biomarkers of cardiovascular pathophysiology. In a panel study design, urines and blood samples were collected up to four times with a 2-week interval from 89 healthy adults. We measured 1-naphthylamine, 2-naphthylamine, 9-aminophenanthrene, 2-aminofluorene, and 1-aminopyrene as biomarkers of nitro-PAH exposures. We measured three urinary metabolites of arachidonic acid (AA) including 20-hydroxyeicosatetraenoic acid (20-HETE) from the cytochrome P450 (CYP) pathway, 8-isoprostane from the nonenzymatic pathway, and 11-dehydro-thromboxane B2 (11-dhTXB2) from the cyclooxygenase (COX) pathway. Urinary malondialdehyde, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 6-sulfatoxymelatonin (aMT6s) were measured to reflect systemic oxidative stress. Plasma concentrations of the soluble P-selectin and von Willebrand factor (vWF) were measured as biomarkers of platelet activation and endothelial dysfunction. We found that increased urinary concentrations of amino-PAHs were significantly associated with increased 20-HETE, 11-dhTXB2, and 8-OHdG and with decreased 8-isoprostane and aMT6s. Increased amino-PAHs were positively associated with P-selectin and vWF, respectively. These results suggest that exposure to nitro-PAHs increases systemic oxidative stress and alters AA metabolism toward CYP and COX pathways, leading to an increased cardiovascular disease risk.

The Chinese government has established a three-tier maternal care system covering the entire country and providing integrated antenatal care (ANC) for pregnancies. This study aimed to analyze the direct and indirect effects of ANC services on early childhood development. A community-based cross-sectional survey was conducted for mothers' ANC visits and assessments of early childhood development in Shanxi and Guizhou provinces, China. A total of 1660 mother-child dyads were included in current analyses: 29.2% of mothers did not receive any ANC (ANC1), 23.3% of mothers received ANC three or fewer times (ANC2), and 47.5% of mothers received ANC four or more times (ANC3). Children whose mothers received ANC services had a significantly lower risk of overall developmental delay (OR = 0.60, 95% CI: 0.44-0.81 for ANC2; and OR = 0.44, 95% CI: 0.34-0.59 for ANC3) and social-emotional developmental delay (OR = 0.68, 95% CI: 0.49-0.94 for ANC3). Furthermore, a significant pathway relationship mediated by maternal depression and nurturing care was found between ANC and developmental delay. This study showed ANC services significantly reduced the risk of developmental delay in offspring. We also suggest that a nationwide ANC system can be a good delivery platform for scaled-up early childhood development interventions.

Purpose Eating epilepsy was previously known as a kind of focal reflex epilepsy. However, the development of eating-induced multiple generalized seizures and the associated EEG changes were rarely reported. Herein, we present a 13-year-old generalized epilepsy patient with eating-induced generalized seizures since the age of 5. Case presentation The 13-year-old male patient had suffered from late-onset eating-induced epileptic spasms during the meal since the age of 5. Meanwhile, he also experienced spontaneous epileptic spasms during the period of sleep. The seizure frequency and type gradually increased from 7 years of age. In addition to epileptic spasms, he started experiencing atypical absence with myoclonic jerks during the meal. Ictal EEG presented as the appearance of an irregular slow-wave mixed with generalized polyspike wave with the intake of food, and gradually evolved to bursts of generalized polyspike wave complexes. At the end of the meal, the EEG returned to normal. Nevertheless, at the age of 13, his seizure frequency increased and appeared new seizure type, and besides epileptic spasm and atypical absence, he began to experience myoclonic seizure during sleep and awaking-generalized tonic-clonic seizure in the morning. In this period he started taking valproic acid, topiramate and clonazepam, and his seizure frequency was reduced. Conclusion In conclusion, this case demonstrated the variability of eating induced multiple generalized seizure types, and eight years follow-up also indicates that generalized epilepsy progressed with age. The EEG and clinical changes of our patient contribute to a better understanding of the electro-clinical features of eating-induced multiple generalized seizures and the course of generalized epilepsy with such seizures.

Background Evidence concerning the long-term impact of Covid-19 in pregnancy on mother’s psychological disorder and infant’s developmental delay is unknown. Methods This study is a longitudinal single-arm cohort study conducted in China between May 1 and July 31, 2020. Seventy-two pregnant patients with Covid-19 participated in follow-up surveys until 3 months after giving birth (57 cases) or having abortion (15 cases). We collected data from medical records regarding Covid-19, delivery or abortion, testing results of maternal and neonatal specimens, and questionnaires of quarantine, mother–baby separation, feeding, and measuring of mothers’ mental disorders and infants’ neurobehavioral disorders. Results All cases infected in the first trimester and 1/3 of cases infected in the second trimester had an abortion to terminate the pregnancy. 22.2% of pregnant patients were suffering from post-traumatic stress disorder or depression at 3 months after delivery or induced abortion. Among 57 live births, only one neonate was positive of nucleic acid testing for throat swab, but negative in repeated tests subsequently. The median duration of mother–baby separation was 35 days (interquartile range 16 to 52 days). After the termination of maternal quarantine, 49.1% of mothers chose to prolong the mother–baby separation (median 8 days; IQR 5 to 23 days). The breastfeeding rate was 8.8% at 1 week after birth, 19.3% at the age of 1 month, and 36.8% at the age of 3 months, respectively. The proportion of “monitoring” and “risk” in the social–emotional developmental domain at the age of 3 months was 22.7% and 63.6%, respectively. After the adjustment of preterm, neonatal sex, admitted to NICU, and the mother’s Covid-19 condition, the negative associations were significantly identified (p Conclusions There is no definite evidence on vertical transmission of SARS-CoV-2. In addition to control infection risk, researchers and healthcare providers should pay more attention to maternal mental health and infant’s feeding, closeness with parents, and early development.

Blood stasis syndrome (BSS) is the pathological basis of many cardiovascular diseases. Ginger is often used as herbal medicine, condiment, and health food in China and Southeast Asia to improve some symptoms of cardiovascular disease, but its mechanism of efficacy and metabolic processes is not clear enough. In this study, a rat model of BSS was successfully established and treated with different doses of dried ginger extract. After the end of the administration period, the blood and urine of 5 groups of rats were collected for metabonomic analysis. Multivariate statistical analysis was used to explore metabolites and metabolic pathways, and the correlation between metabolites and pharmacodynamic indicators was further explored. The experimental results show that the pharmacodynamic indicators of dried ginger group (DG) extracts of different doses have different degrees of changes than model group (MG), and the high dose of dried ginger group (GJH) changes is the most significant (p, To study the effect of dried ginger on blood stasis syndrome from the perspective of metabolomics.Three metabolic pathways are the most critical ways for dry ginger to act on blood stasis syndrome.The correlation between biomarkers illustrates the dose effect.

Acute respiratory distress syndrome (ARDS) is common in intensive care units (ICUs), although it is associated with high mortality, no effective pharmacological treatments are currently available. Despite being poorly understood, the role of programmed cell death protein 1 (PD-1) and PD-ligand 1 (PD-L1) axis in ARDS may provide significant insights into the immunosuppressive mechanisms that occur after ARDS. In the present study, we observed that the level of soluble PD-L1 (sPD-L1), a potential activator of the PD-1 pathway, was upregulated in survivors of direct ARDS than in non-survivors. Administration of sPD-L1 in mice with direct ARDS relieved inflammatory lung injury and improved the survival rate, indicating the protective role of sPD-L1 in direct ARDS. Using high-throughput mass cytometry, we found a marked decrease in the number of lung monocyte-derived macrophages (MDMs) with proinflammatory markers, and the protective role of sPD-L1 diminished in ARDS mice with monocyte/macrophage depletion. Furthermore, PD-1 expression increased in the MDMs of patients and mice with direct ARDS. Finally, we showed that sPD-L1 induced MDM apoptosis in patients with direct ARDS. Taken together, our results demonstrated that the engagement of sPD-L1 on PD-1 expressing macrophages resulted in a decrease in pro-inflammatory macrophages and eventually improved direct ARDS. Our study identified a prognostic indicator for patients with direct ARDS and a potential target for therapeutic development in direct ARDS.

The introduction of graphene (Gr) with high thermal conductivity between GaAs and metal electrode can reduce the internal temperature rise and thermal stress accumulation of high-power chips, such as photoconductive switches, protect the contact electrode, and improve the device stability. Meanwhile, the introduction of graphene has the potential to decrease the interface contact resistance. It is valuable to study the effect of graphene on the contact characteristics of the metal–semiconductor interface. The metallic composite Ni/Ge/Au/Ni/Au was obtained by electron beam evaporation, and the graphene was grown by CVD. The current–voltage ( ${I}$ – ${V}$ ) characteristics of the devices over a high-temperature range 300 K–420 K were measured by a semiconductor parameter analyzer. The Schottky barrier properties of metal/semi-insulating GaAs (M/SI-GaAs) with and without graphene interlayer were analyzed by some analysis techniques, such as forward ${I}$ – ${V}$ and Norde’s methods. It was observed that the barrier heights (BHs) were inhomogeneous in the high-temperature range. The mean BHs were extracted by the experimental BH versus 1/T. We found that the homogeneous BH of M/Gr/SI-GaAs was lower that of M/SI-GaAs. It is helpful to improve the performance of semiconductor devices, as we realized the specific contact resistivity lower by two orders of magnitudes via graphene insertion.

Humidity sensors by exploiting transition metal dichalcogenides have attracted enormous attention in various applications. Here, we demonstrate a high-sensitivity fiber-optic humidity sensor based on microfibers overlaid with niobium disulfide (NbS2). Our experimental results show that this type of humidity sensor has high sensitivity, and good repeatability and reversibility. In the RH range of 72–97%, a sensitivity of up to 1.05 dB/RH% and an excellent linearity correlation of 99.5% were achieved. The transmission spectrum of the humidity sensor indicates that this sensor has a wide wavelength detection range from 1530 to 1565 nm. We applied the sensor to monitor human breath with a fast response. We anticipate that the humidity sensor will be useful for the environmental monitoring, food production, and semiconductor industries.

To reduce multiplication operations in convolution of convolutional neural networks (CNNs), there are three widely used convolutional acceleration algorithms, i.e., Winograd, FFT and FFA. However, current accelerators based on these convolutional acceleration algorithms have issues on flexibility and efficiency. Firstly, some accelerators utilized a combination of these acceleration algorithms and employed multiple types of computational units to achieve their respective advantages. As a result, some computational units are left unused when the best-performing unit is working, which causes much area inefficiency. Secondly, current accelerators tend to choose small parameters of these convolutional acceleration algorithms to avoid unacceptable precision loss, as a result, they are hardly to support large kernel sizes and lack of flexibility. Thirdly, these acceleration algorithms are typically presented for 1-stride convolutions, consequently, few implementation considers the acceleration of large-stride convolutions, which is a major restriction to hardware flexibility. This paper proposed a stride-based convolution decomposition method (SCDM) to reform different convolution shapes (i.e., kernel sizes & strides) to an identical pattern. With the aid of SCDM, a Winograd-stretched and hardware-efficient design (WHD) is presented to utilize one uniform computational unit for the acceleration of different convolution shapes, which combines complementary performance advantages on both Winograd F(4,3) and F(4,2) units. Compared to current FFT-based or FFA-based works, WHD can stretch the use range of Winograd and simplify implementation, thereby achieving hardware flexibility and efficiency. Evaluation results show that 34.08%~55.41% operation reduction were achieved on six CNN models, while incurring a slight hardware overhead.

Hand-foot-and-month disease (HFMD), especially the enterovirus A71 (EV-A71) subtype, is a major health problem in Beijing, China. Previous studies mainly used regressive models to forecast the prevalence of HFMD, ignoring its intrinsic age groups. This study aims to predict HFMD of EV-A71 subtype in three age groups (0–3, 3–6 and > 6 years old) from 2011 to 2018 using residual-convolutional-recurrent neural network (CNNRNN-Res), convolutional-recurrent neural network (CNNRNN) and recurrent neural network (RNN). They were compared with auto-regressio, global auto-regression and vector auto-regression on both short-term and long-term prediction. Results showed that CNNRNN-Res and RNN had higher accuracies on point forecast tasks, as well as robust performances in long-term prediction. Three deep learning models also had better skills in peak intensity forecast, and CNNRNN-Res achieved the best results in the peak month forecast. We also found that three age groups had consistent outbreak trends and similar patterns of prediction errors. These results highlight the superior performance of deep learning models in HFMD prediction and can assist the decision-makers to refine the HFMD control measures according to age groups.

BackgroundWith the spread of SARS-CoV-2 worldwide, understanding the basic epidemiological parameter values of COVID-19 from real-world data in mega-cities is essential for disease prevention and control.MethodsTo investigate the epidemiological parameters in SARS-CoV-2 infected cases in Beijing, we studied all confirmed cases and close contacts in Beijing from Jan 1st to Apr 3rd 2020. The epidemiological and virological characteristics of SARS-CoV-2 were analyzed.ResultsA total of 602 cases were positive for SARS-CoV-2, including 585 confirmed patients and 17 asymptomatic infections. The imported cases were mainly from Wuhan initially and then from abroad. Among 585 confirmed case-patients, the median age was 39 years old. The mean incubation period was 6.3 days. The secondary attack rate among households was higher than social contacts (15.6 vs 4.6%). The secondary attack rate of healthcare workers (HCWs) was higher than non-HCWs’ (7.3 vs 4.2%). The basic reproduction number was 2.0, and the average serial interval was 7.6 days. No significant genetic variant was identified.ConclusionsThe transmissibility of SARS-CoV-2 was relatively high, especially among households and from HCWs, which draws specific public health attention. So far, no evidence of widespread circulation of SARS-CoV-2 in communities in Beijing was found.

With the development of information and communication technologies, telemedicine has been widely used in different healthcare sectors. In this paper, we study a telemedicine service system consisti...

Face alignment and cross-modal face transfer are two important tasks for automatic face analysis in computer vision. Over the years, they have been extensively studied. Recently, deep neural networks have attracted much research attention for both face alignment and face transfer. With the prevalence of the consumer depth sensor, depth-based face alignment and cross-modal (image and depth) are increasingly important. Different from existing RGB- image based tasks, the main challenge of depth-based tasks is the lack of annotated data. To address the challenge, we observe that these two tasks are closely related and their learning processes may benefit each other. This paper develops a joint multi-task learning algorithm for both depth-based face alignment and face transfer using the deep convolutional neural network (CNN). The proposed approach allows the CNN model to simultaneously share visual knowledge and information between two tasks. We use a dataset of 10,000 face depth images for validation. Our experiments show that the proposed approach outperforms state-of-the-art algorithms. The results also show that learning these two related tasks simultaneously improves the performance of each individual task.

Understanding how plants use of various nitrogen (N) sources is important for improving plant N use efficiency in organic farming systems. This study investigated the effects of farming management ...

Background Several nervous and nerve-related biomarkers have been detected in colorectal cancer (CRC) and can contribute to the progression of CRC. However, the role of leucine-rich repeat neuronal 4 (LRRN4), a recently identified neurogenic marker, in CRC remains unclear. Methods We examined the expression and clinical outcomes of LRRN4 in CRC from TCGA-COREAD mRNA-sequencing datasets and immunohistochemistry in a Chinese cohort. Furthermore, colony formation, flow cytometry, wound healing assays and mouse xenograft models were used to investigate the biological significance of LRRN4 in CRC cell lines with LRRN4 knockdown or overexpression in vitro and in vivo. In addition, weighted coexpression network analysis, DAVID and western blot analysis were used to explore the potential molecular mechanism. Results We provide the first evidence that LRRN4 expression, at both the mRNA and protein levels, was remarkably high in CRC compared to controls and positively correlated with the clinical outcome of CRC patients. Specifically, LRRN4 was an independent prognostic factor for progression-free survival and overall survival in CRC patients. Further functional experiments showed that LRRN4 promoted cell proliferation, cell DNA synthesis and cell migration and inhibited apoptosis. Knockdown of LRRN4 can correspondingly decrease these effects in vitro and can significantly suppress the growth of xenografts. Several biological functions and signaling pathways were regulated by LRRN4, including proteoglycans in cancer, glutamatergic synapse, Ras, MAPK and PI3K. LRRN4 knockdown resulted in downregulation of Akt, p-Akt, ERK1/2 and p-ERK1/2, the downstream of the Ras/MAPK signaling pathway, overexpression of LRRN4 leaded to the upregulation of these proteins. Conclusions Our results suggest that LRRN4 could be a biological and molecular determinant to stratify CRC patients into distinct risk categories, and mechanistically, this is likely attributable to LRRN4 regulating several malignant phenotypes of neoplastic cells via RAS/MAPK signal pathways.

Perfect optical vortex beams (POV) have attracted considerable attention in many novel applications because they have the advantage of a radial profile that is independent of the topological charge (TC). Nowadays, there are few effective methods to measure both the integer and the fractional TCs of the POV. In this paper, we achieve the precise measurement of arbitrary TCs through the approach of dynamic angular double slits (ADS), which performs the transformation from the POV to the interference intensity patterns at the angular bisector direction of the ADS. The information of the TC can be obtained from the periodically changing interference pattern. The deviation is less than 2% by comparing the theoretical values with the fitting results, therefore the detection method is effective and reasonable.

Greenspace exposure is confirmed to reduce air pollution-related negative health impact. However, which type of greenspace exposure matters more on mitigating air pollution-related deaths and whether this effect is regionally different remain unclear. Here we show, greenspace usability exposure plays a more significant role in mitigating PM2.5-related premature deaths in 360 China cities generally speaking. By clustering 360 cities into urban-rural and Deprivation Index groups, we further find that greenspace availability and usability together work on respiratory health in rural regions, and greenspace availability matters more in very low deprived areas or urban and rural regions. Our results that increasing greenspace usability exposure is more helpful in reducing air pollution-related premature deaths may inform more effective and equitable greenspace planning policies in rapidly developing countries like China.

This paper investigates the seismic behavior of novel stone masonry joints using ductile engineered cementitious composite (ECC) as a substitute for ordinary mortar. Ten stone masonry joints with different types of mortar/ECC were tested under axial and cyclic loads. The filling materials of mortar joints tested included ordinary mortar, polymer mortar, ECC, and composite mortar with two combination proportions of ECC and ordinary mortar. The test results indicated that ECC specimens exhibited a more stable hysteretic response as well as an improvement in strength, deformation, energy dissipation, and strength degradation. The ECC mortar joints maintained integrity during the entire loading process due to the “self-confinement” effect of ECC. A partial substitution of mortar with ECC could provide effective reinforcement and confinement to prevent mortar failure and peeling, thereby allowing such specimens to approach the seismic performance of ECC specimens. Based on the trend of shear strength variations, a corresponding failure process is defined for ECC/mortar joints under cyclic and axial compressive loads, including four distinct stages: linear elastic, crack-developing stage, interface debonding, and friction sliding. New equations are proposed for predicting the shear strength and residual shear strength of the ECC/mortar joints on the basis of the test results, which are validated in the composite mortar specimens.

Atherosclerosis is a chronic inflammation of the arterial vessel wall driven by lipid metabolism disorders. Although helminthic infection and their derivatives have been identified to attenuate the chronic inflammatory diseases, the immunomodulatory effect of recombinant Schistosoma japonicum cystatin (rSj-Cys) on metabolic diseases and atherosclerosis has not been reported. In this study, we investigated the therapeutic efficacy of rSj-Cys on atherosclerotic renal damage and explored the related immunological mechanism. The results demonstrated that treatment with rSj-Cys significantly reduced body weight gain, hyperlipidemia, and atherosclerosis induced by the high-fat diet in apoE–/– mice. The treatment of rSj-Cys also significantly improved kidney functions through promoting macrophage polarization from M1 to M2, therefore inhibiting M1 macrophage–induced inflammation. The possible mechanism underlying the regulatory effect of rSj-Cys on reducing atherosclerosis and atherosclerotic renal damage is that rSj-Cys stimulates regulatory T cell and M2 macrophage polarization that produce regulatory cytokines, such as interleukin 10 and transforming growth factor β. The therapeutic effect of rSj-Cys on atherosclerotic renal damage is possibly through inhibiting the activation of TLR2/Myd88 signaling pathway. The results in this study provide evidence for the first time that Schistosoma-derived cystatin could be developed as a therapeutic agent to treat lipid metabolism disorder and atherosclerosis that threats million lives around the world.

BackgroundNKTR-255 is an investigational IL-15Rα-dependent, polymer-conjugated, recombinant human IL-15 agonist designed to provide sustained pharmacodynamic (PD) responses without the need for daily dosing. NKTR-255 engages all IL-15 receptor binding complexes to expand, proliferate and activate natural killer (NK) and CD8+ T-cells. This Phase 1b/2 trial (NCT04616196) evaluates NKTR-255+cetuximab in highly refractory patients with head-and-neck squamous cell carcinoma (HNSCC) or colorectal cancer (CRC).MethodsSuccessive cohorts received escalating doses of NKTR-255 (q3w) +cetuximab (250mg/m< sup >2 weekly), 1 week after a loading dose of cetuximab alone. Safety (CTCAEv5.0; MTD/recommended Phase 2 dose [RP2D]) and efficacy (RECISTv1.1) were measured. PK/PD analyses were conducted, including assessment by flow cytometry/plasma cytokine analysis. Fold-change was calculated as treatment over baseline for NKTR-255 (baseline=1).ResultsAs of August 15, 2021, 12 patients had received ≥1 dose of NKTR-255+cetuximab; (37–70 years; 92% male; HNSCC n=4, CRC n=8; NKTR-255 1.5µg/kg n=7, NKTR-255 3.0µg/kg n=5). Patients had received a median 3.5 lines of prior therapy for metastatic disease. 11 patients had no response to the most recent prior therapy. Of the 12 patients, seven remain on treatment, with five not yet reaching first scan. RP2D has not yet been reached; dose escalation is ongoing.10 patients experienced an AE; one G5 AE occurred (due to progression). Seven patients reported NKTR-255-related AEs (all G1-2, except one G3 [which resolved in 24 hours]). Any-cause AEs in ≥20% were acneiform dermatitis, fatigue, and infusion-related reaction.Treatment-induced transient changes in inflammatory cytokines, including IFNy, MCP-1 and IL-6, at 1.5µg/kg (n=3) peaked 4 hours post-infusion and resolved by 24-48 hours. Mean T1/2 of NKTR-255 (1.5µg/kg dose, first cycle) was 27.8 hours.Dose-dependent expansion of NK and CD8+ T-cells was observed in peripheral blood. For NK cells, mean peak fold-change was ~4-fold and ~6-fold, and for CD8+ T-cells was ~2-fold and ~3-fold (1.5µg/kg and 3µg/kg dose levels, respectively). NK and CD8+ T-cells demonstrated increased Ki67+ proliferative ability.As of August 15, four patients in the 1.5µg/kg NKTR-255 dose cohort were response-evaluable: one CRC patient (4 prior metastatic treatment lines) reported a confirmed PR (–52%) after 3 cycles; two HNSCC patients reported SD.ConclusionsNKTR-255 was biologically active and led to expansion and proliferation of NK and CD8+ T-cells. Early dose-escalation data suggest that NKTR-255+cetuximab is safe and tolerable with preliminary anti-tumor activity. Updated data will be presented. NKTR-255, alone and in combination with daratumumab and rituximab, is also being evaluated in liquid tumors.AcknowledgementsThe authors thank the patients and their families involved in the trial.Trial RegistrationNCT04616196Ethics ApprovalThe study was approved by site IRBs.ConsentN/A

In order to solve the problem of low accuracy, high cost, and difficult detection of traditional algorithms, a new algorithm based on ultrasound imaging is proposed in this paper. The algorithm is based on fuzzy clustering to diagnose the disease and effectively improve the accuracy of the algorithm. By testing the actual scene, it effectively proves the effectiveness and accuracy of the algorithm, which can find and treat diseases in time and can be widely used and popularized in clinical research in China.

This paper demonstrates an intelligent medical analysis system. We aim to address two main challenges: 1) medical data often contain heterogeneous information which are usually valuable but difficult to be modeled; 2) medical data are often lacking of large scale labeled data which usually require huge efforts to build. To resolve the first challenge, we propose a novel multi-modal heterogeneous graph model to represent the medical data. Based on this model, graph neural networks can be directly applied to effective medical case clustering. This helps to resolve the second challenge for label assignment in the same cluster. To further evaluate the practical use of the proposed model, the system also proposes an effective similar medical case retrieval framework based on a novel graph similarity learning model. We have implemented the system and the source codes are published at https://github.com/emmali808/ADDS. With our system, users can easily pinpoint valuable historical medical information they are interested in and obtain closely relevant medical cases for further diagnosis.

Background: The pathogenesis of T2DM is influenced by a combination of genetic and environmental factors, among which LncRNAs have a huge impact on diabetes.In this study, we investigated the diagnostic value of lncRNA GUSBP3 and lncRNA SAM4 for T2DM in Kazakhs in Xinjiang. Methods: In this study, differentially expressed lncRNAs and mRNAs were screened by microarray analysis microarray in a Kazakh population in Xinjiang, and the expression of two candidate lncRNAs (lnc-GUSBP-3 and lnc-SAM-4) was further validated by quantitative real-time polymerization chain reaction (qRT-PCR).Meanwhile, GO (Gene Ontology) enrichment analysis were used to reveal the biological functions of the two candidate lncRNAs. Spearman’s correlation analysis was used to elucidate the correlation between lnc-GUSBP-3 and lnc-SAM-4 expression and metabolic characteristics. We found that the expression of lnc-GUSBP-3 and lnc-SAM-4 was up-regulated in the T2DM group compared to healthy controls. Multivariate logistic regression analysis showed that DBP, FIns and lnc-GUSBP3 were associated with T2DM susceptibility.In addition, ROC curves were used to evaluate the diagnostic potential of lnc-GUSBP3 and lnc-SAM4. Results: We conducted a microarray analysis of PBMC collected from patients with T2DM and healthy controls, all of Kazakh origin. In the microanalysis, we identified 89 differentially expressed lncRNAs, and 147 differentially expressed mRNAs. real-time quantitative reverse transcription polymerase chain reaction analysis of peripheral blood mononuclear cell (PBMC) samples from T2DM patients and healthy controls from the Xinjiang Kazakh population revealed significantly increased levels of lncRNAs GUSBP3 and SAM4 in T2DM patients. Logistic regression analysis revealed that lncRNA GUSBP3 expression correlated negatively with FIns, but positively with creatinine and uric acid (UA). Furthermore, lncRNA SAM4 expression correlated negatively with low-density lipoprotein cholesterol levels, but positively with UA. The area under the receiver operating characteristic curve values for lnc-GUSBP3 and lnc-SAM4 were 0.789 (95% CI = 0.672–0.906) and 0.741 (95% CI = 0.616–0.866), respectively. Conclusion: There were significant changes in lncRNA and mRNA in Kazakh T2DM patients. LncRNA-GUSBP3 and lncRNA-SAM4 may serve as potential diagnostic biomarkers for T2DM in Kazakhs in Xinjiang.

In order to solve the problem of Fourier ptychographic microscopy imaging reconstruction, this paper proposes a new convolutional network feature fusion Fourier stacked microscopy reconstruction method to achieve image reconstruction from low resolution to high resolution. Use the open-source deep learning framework TensorFlow to build the network model and continuously adjust the hyperparameters of the network model. In order to train and test the network model, the FPM imaging model is used to construct a data set for network training and testing. At the same time, it is also tested on traditional methods and neural network-based reconstruction methods to evaluate network performance. The experimental results show that the model has better reconstruction effect and better robustness to noisy images.