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Development of acquired resistance to lapatinib, a dual epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitor, severely limits the duration of clinical response in advanced HER2‐driven breast cancer patients. Although the compensatory activation of the PI3K/Akt survival signal has been proposed to cause acquired lapatinib resistance, comprehensive molecular mechanisms remain required to develop more efficient strategies to circumvent this therapeutic difficulty. In this study, we found that suppression of HER2 by lapatinib still led to Akt inactivation and elevation of FOX3a protein levels, but failed to induce the expression of their downstream pro‐apoptotic effector p27kip1, a cyclin‐dependent kinase inhibitor. Elevation of miR‐221 was found to contribute to the development of acquired lapatinib resistance by targeting p27kip1 expression. Furthermore, upregulation of miR‐221 was mediated by the lapatinib‐induced Src family tyrosine kinase and subsequent NF‐κB activation. The reversal of miR‐221 upregulation and p27kip1 downregulation by a Src inhibitor, dasatinib, can overcome lapatinib resistance. Our study not only identified miRNA‐221 as a pivotal factor conferring the acquired resistance of HER2‐positive breast cancer cells to lapatinib through negatively regulating p27kip1 expression, but also suggested Src inhibition as a potential strategy to overcome lapatinib resistance., The downregulation of p27kip1 by Src/NF‐κB axis‐induced miR‐221 expression as a novel mechanistic insight into lapatinib resistance. Targeting Src would be a promising strategy to overcome lapatinib resistance.

To observe the effects and safety of Tongyan Spray (通咽喷雾剂) on the range and time of hyoid motion in patients with ischemic post-stroke dysphagia. Seventy-two patients with ischemic post-stroke dysphagia were selected and randomly assigned to a treatment group (36 cases) and a control group (36 cases) by a random number table from January 2013 to October 2014. All patients swallowed 4 kinds of barium meals with different traits respectively, and each patient underwent video fluoroscopy (VF) examination twice. In the treatment group, Tongyan Spray was sprayed to the pharynx on both sides and the middle part once respectively. The spray was applied 30 min before the second examination. Purified water at room temperature was used as placebo in the control group. The changes in the range and time of hyoid motion in both groups were observed before and after treatment. Six patients dropped out in each group, and 60 patients completed the study and were included in the final analysis. Significant improvement was observed in the range of superior hyoid excursion distance and the time of hyoid motion in the treatment group compared with the control group (P

Using an all-fiber mode selective coupler (MSC) at the visible band, here we experimentally demonstrate a generating and wavelength multiplexing scheme for the cylindrical vector (CV) and vortex beams (VBs). The proposed MSCs act as efficient mode converters to produce spectrally insensitive high-order modes (HOMs) at the wavelength ranging from 450 to 980 nm, which have broad operation bandwidth (more than 7 nm), high mode conversion efficiency (94%), and purity (98%), and low insert loss (below 0.5 dB). By adjusting the polarization state and the phase shift of linear polarization (LP)11 mode respectively, the donut-shaped CVs and circular-polarization VBs are achieved. The focused intensity distribution of the donut beam on the cross- and axial-sections is monitored by using a confocal system. The all-fiber solution of producing and multiplexing HOMs opens a new route for stimulated emission depletion microscopy applications.

Effective warnings of potential collision risks are important countermeasures for drowsy and distracted driving. This study explores the possibility of using smart wearable devices to provide vibrotactile warnings. We assessed the effectiveness of a vibrating wearable device as a warning system. Participants performed a classic car-following task in a driving simulator under four conditions: no warning, warnings at the finger, wrist, temple area. When the lead vehicle braked intermittently, warnings would be delivered to the same vibrating device, which was placed at the finger, wrist, or temple area. Results showed that warnings at the finger and the wrist produced shorter brake response time than the no warning condition. Warnings at the temple area did not produce significant benefits in brake response time over the no warning condition. Participants preferred warnings at the finger and the wrist than the temple area. Quicker brake response time for warnings at the finger and wrist area may be explained by the relative sizes of cortex area in the brain which corresponds to the sensory organs, as visualized by the classic Penfield Homunculus. The current study of wearable tactile warnings can inform future designs of warning systems for drivers.

Background/Purpose: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been gradually introduced in the diagnosis of mediastinal tuberculous (TB) lymphadenitis. The purposes of this study were to evaluate the utility of polymerase chain reaction for Mycobacterium tuberculosis (TB-PCR) using EBUS-TBNA rinse fluid and to explore the factors that influence the accuracy of EBUS-TBNA. Methods: A retrospective study with prospective data collection was carried out with patients with unselected mediastinal lymphadenopathy who underwent EBUS-TBNA and a TB-PCR study from April 2010 to July 2017. Patients without TB were excluded. The diagnostic accuracy rate for each diagnostic modality (pathology, smear, culture, and TB-PCR) was calculated respectively. The characteristics of the lymph node (LN) and the pathologic findings were analyzed as possible impact factors. Results: 240 consecutive patients who received EBUS-TBNA were enrolled, and in the end, 21 patients with a diagnosis of TB lymphadenitis were included. When combined with histologic results and traditional microbiologic studies, the diagnostic accuracy of EBUS-TBNA was 57.1%. If TB-PCR was also utilized, the diagnostic accuracy would significantly increase to 71.4% (p

Advancements in the care of acutely ill patients has reduced intensive care unit (ICU) mortality but has also led to the emergence of a group of patients who have a prolonged dependency on life sup...

Background Allogenic hematopoietic stem cell transplantation may be the best currently available method to treat relapsed hemophagocytic lymphohistiocytosis (HLH) related to Epstein-Barr virus. The high rate of transplantation-related complications was initially the main obstacle preventing the wider adoption of this protocol; however, the previously more common complications, such as infection and graft failure, have fallen to very low levels with the development of new drugs and methods. Some other complications, such as veno-occlusive disease and transplantation associated thrombotic microangiopathy, are rare after allogenic hematopoietic stem cell transplantation, but the morbidity and mortality associated with them are very high. Case presentation A patient with relapsed HLH related to Epstein-Barr virus showed the sequential severe complications of veno-occlusive disease, transplantation-associated thrombotic microangiopathy, and acute graft-vs-host disease after haploidentical transplantation. This patient was successfully treated by stopping administration of calcineurin inhibitors and instead treating with defibrotide, rituximab, CD25 monoclonal antibody, atorvastatin calcium tablets, methylprednisolone, budesonide, continuous plasma exchange, and bedside ultrafiltration. At the last follow-up, the patient had been living disease free for 2 years without any other complications. Conclusion Epstein-Barr virus related-HLH patients have severe clinical features and currently poor prognosis. Allogenic hematopoietic stem cell transplantation may be the best way to treat this disease; however, the management of related complications is vital in the improvement of long-term survival.

Pegylated liposomal doxorubicin (Peg-Dox) treatment resulted in a good outcome for patients with lymphoma and multiple myeloma, with reduced cardiotoxicity and an improved pharmacokinetic profile when compared to those of conventional doxorubicin. However, the use of Peg-Dox in myeloid neoplasms remains poorly studied. In this study, we first tested the role of Peg-Dox in the killing of myeloid cell lines and of primary myeloid leukemia cells. Then, a Peg-Dox-based protocol was used to treat patients with myeloid neoplasms. The results showed that the Peg-Dox and Peg-Dox-based protocols had a similar killing ability in myeloid cell lines and in primary myeloid leukemia cells compared to that of conventional doxorubicin. The complete remission rate was 87.5% and 100% for patients with refractory/relapsed acute myeloid leukemia and myelodysplastic syndrome with excess blasts, respectively, after treatment with Peg-Dox. All patients developed grade 3 or 4 hematological toxicity and recovered approximately 2 weeks after completing chemotherapy. No deaths or other severe complications were reported. Our results showed that Peg-Dox can be used in the treatment of myeloid neoplasms with high rates of complete remission and with mild complications.

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of end-stage liver disease, leading to a rapidly growing global public health burden. The term “gut microbiome (GM)” refers to the approximately 100 trillion microbial cells that inhabit the host’s gastrointestinal tract. There is increasing evidence that GM is involved in the pathogenesis of NAFLD and may be a potential target for intervention. To explore GM-based strategies for precise diagnosis and treatment of NAFLD, great efforts have been made to develop a comprehensive and in-depth understanding of the host–microbe interaction. This review evaluates this interaction critically, mainly considering the intricate regulation of the metabolism, immunity, and inflammatory status during the evolution of the disease pathogenesis, revealing roles for the GM in NAFLD by examining advances in potential mechanisms, diagnostics, and modulation strategies.Synopsis: Considering the intricate metabolic and immune/inflammatory homeostasis regulation, we evaluate the latest understanding of the host–microbe interaction and reveal roles for the gastrointestinal microbiome in NAFLD. Strategies targeting the gastrointestinal microbiome for the diagnosis and treatment of NAFLD are proposed.

Accurate detection of objects in perception system is a basic task for autonomous vehicles to operate reliably. The current mainstream paradigms for perception and prediction are able to decompose into three sequential subtasks: detection, tracking and prediction. Much of the previous works focus on one of these subtasks and internal relationship between the various subtasks are therefore ignored. In this work we propose an end-to-end model that is able to jointly carry out 3D detection and motion prediction in the context of autonomous vehicles, which can benefit from joint optimization of two tasks. Considering computational consumption and memory cost, our approach utilizes 2D convolutions across space over a bird's eye view (BEV) representation of the 3D world, not 3D convolutions which require more inference time for a single point cloud. In this paper, the key model is the sequential multi-frame point clouds channels based on BEV, which can help perform object detection and learn temporal information at the same time. Experiments on nuScenes dataset show that the proposed network achieves state-of-the-art results, and the trade-off between accuracy and efficiency of two tasks are obtained. Additionally, we validate the effectiveness of our models through the ablation studies. Specifically, by sharing network, parameters and detection results we can perform two tasks within 32 FPS.

Exercise rhabdomyolysis is a potentially life-threatening medical condition if not adequately managed early. With the increase in the popularity of indoor cycling, known as Spinning®, over recent years, there has been an increased occurrence of spin-related rhabdomyolysis observed among previously fit adults after undertaking their first spin bike class session. They present with the triad of myalgia, muscle weakness, and dark tea-colored urine within a week of their first spin session. This case series highlights several admissions to the hospital with spin-related rhabdomyolysis and their clinical management.

Backgrounds:Reduced brain cortical activity over the frontotemporal regions measured by near infrared spectroscopy (NIRS) has been reported in patients with first-episode schizophrenia (FES). This study aimed to differentiate between patients with FES and healthy controls (HCs) on basis of the frontotemporal activity measured by NIRS with a support vector machine (SVM) and deep neural network (DNN) classifier. In addition, we compared the accuracy of performance of SVM and DNN.Methods:In total, 33 FES patients and 34 HCs were recruited. Their brain cortical activities were measured using NIRS while performing letter and category versions of verbal fluency tests (VFTs). The integral and centroid values of brain cortical activity in the bilateral frontotemporal regions during the VFTs were selected as features in SVM and DNN classifier.Results:Compared to HCs, FES patients displayed reduced brain cortical activity over the bilateral frontotemporal regions during both types of VFTs. Regarding the classifier performance, SVM reached an accuracy of 68.6%, sensitivity of 70.1%, and specificity of 64.6%, while DNN reached an accuracy of 79.7%, sensitivity of 88.8%, and specificity of 74.9% in the classification of FES patients and HCs.Conclusions:Compared to findings of previous structural neuroimaging studies, we found that using DNN to measure the NIRS signals during the VFTs to differentiate between FES patients and HCs could achieve a higher accuracy, indicating that NIRS can be used as a potential marker to classify FES patients from HCs. Future additional independent datasets are needed to confirm the validity of our model.

Background Reactivation of hepatitis B virus (HBV) is a documented risk during cytotoxic chemotherapy in patients with lung cancer. Cases of HBV reactivation in non–small-cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment have been reported; however, the incidence of HBV reactivation in patients treated with EGFR TKIs has not yet been reported. Materials and methods We enrolled 171 patients who were diagnosed as having NSCLC from 2011 through 2017 and who also had positive hepatitis B surface antigen (HBsAg). All patients had received EGFR TKIs as anticancer treatment for at least 2 weeks during their treatment course. Reactivation of HBV is defined as one of the following: an increase in HBV DNA by at least 10-fold compared to baseline or an absolute increase to >10ˆ5 IU/mL with abnormal liver function. Results The median duration of EGFR TKI treatment was 10.5 months (95% confidence interval: 8.2–12.8). Sixteen (9.36%) patients met the criteria of HBV reactivation during EGFR TKI treatment, with an annual incidence of 7.86%. HBV reactivation occurred during erlotinib treatment in 6 patients, followed by 5 patients with gefitinib treatments, 3 patients with osimertinib treatment and 2 with afatinib treatment. No independent risk factor for HBV reactivation was identified. Conclusion NSCLC patients receiving EGFR TKI treatment may have a clinically meaningful risk of HBV reactivation during the treatment period. Thus, monitoring liver function, HBV viral load and serology of HBV (i.e., HBeAg and anti-HBc) during EGFR TKI therapy is recommended for NSCLC patients with positive HBsAg.

Bioelectrical impedance analysis (BIA) is a technology that provides a rapid, non-invasive measurement of volume in body compartments and may aid the physician in the assessment of volume status. We sought to investigate the effect of BIA-measured volume status on duration of mechanical ventilation, 28-day mortality, and acute kidney injury requiring renal replacement therapy in a population of medical/surgical patients admitted to the intensive care unit (ICU). Prospective observational study of adult patients who required mechanical ventilation within 24 hr of admission to ICU. Bioelectrical impedance analysis measured extracellular water (ECW) and total body water (TBW) and these measurements were recorded on days 1, 3, 5, and 7. A total of 36 patients were enrolled. Mean (standard deviation) age was 61.8 (21.3) years and 31% of patients were female. The majority were admitted from the emergency department or operating room. The most common diagnosis was sepsis. At 28 days, eight patients (22%) had died. There was no association between ECW/TBW ratio at day 1 and 28-day mortality (odds ratio, 1.2; 95% confidence interval [CI], 0.6 to 2.3) after adjusting for age, sex, and Acute Physiology and Chronic Health Evaluation II score. The median [interquartile range] number of ventilator days was 5 [2.5–7.5]. On day 1, for each 1% increase in the ECW/TBW ratio, there was a 1.2-fold increase in ventilator days (95% CI, 1.003 to 1.4; P = 0.05). It is notable that 20% of eligible patients could not be enrolled because medical equipment interfered with correct electrode placement. Bioimpedance-measured ECW/TBW on day 1 of admission to the ICU is associated with time on the ventilator. While this technology may be a useful adjunct to the clinical assessment of volume status, there are technical barriers to its routine use in a general ICU population.

We demonstrate that the mode-locked all-fiber laser can simultaneously emit two-color broadband LP11 transverse mode in the near-infrared region by sharing a common mode-selective coupler (MSC). The MSC mode converter is designed to achieve simultaneous dual-channel mode conversion corresponding to the wavelength regions at 1.0 and $1.5~\mu \text{m}$ , in which each channel possesses broadband mode conversion from LP01 to LP11 mode with high mode purity. As a proof of concept, we implement an all-fiber ytterbium (Yb)- and erbium (Er)-doped fiber lasers with a mode-locked two-color LP11 modal output. The laser consists of two ring cavities combined with a common MSC mode converter. The generated LP11 modal pulses have a full width at half maximum of 11 and 8.1 nm for Yb- and Er-doped fiber laser, respectively. The presented fiber laser would represent a promising light source in the field of structured light and ultrafast optics.

The atomic magnetometer in the application of simultaneous multichannel biomagnetic field measurement has gained increasing attention in recent researches. In this paper, a novel asymmetrical heating method for improving the temperature spatial homogeneity of the vapor cell in atomic magnetometer based on the finite element method was investigated. The homogeneity of temperature spatial distribution and the consistency of output signal from multilocation in a large vapor cell were numerically analyzed considering multichannel magnetic field measurement. With this asymmetrical heating method, the multilocation measurement signal regularity in the large vapor cell has been improved and the minimum variation coefficient of nine sensing areas' measurement signals decrease over 70% compared with the common heating method with the same heating temperature for the quadrate cell. This method is of great interest for the applications in miniaturing magnetometers of multichannel biomagnetic field measurement.

With the development of deep learning technology, a large number of new technologies for video anomaly detection have emerged. This paper proposes a video anomaly detection algorithm based on the future frame prediction using Generative Adversarial Network (GAN) and attention mechanism. For the generation model, a U-Net model, is modified and added with an attention module. For the discrimination model, a Markov GAN discrimination model with self-attention mechanism is proposed, which can affect the generator and improve the generation quality of the future video frame. Experiments show that the new video anomaly detection algorithm improves the detection performance, and the attention module plays an important role in the overall detection performance. It is found that the more the attention modules are appliedthe deeper the application level is, the better the detection effect is, which also verifies the rationality of the model structure used in this project.

Collision warning system plays a key role in the prevention of driving distractions and drowsy driving. Previous studies have proven the advantages of tactile warnings in reducing driver’s brake response time. At the same time, tactile warnings have been proved effective in take-over request (TOR) for partially autonomous vehicles. How the performance of tactile warnings can be optimized is an ongoing hot research topic in this field. Thus, the presented low-cost driving simulation software and methods are introduced to attract more researchers to take part in the investigation. The presented protocol has been divided into five sections: 1) participants, 2) driving simulation software configuration, 3) driving simulator preparation, 4) vibrating toolkit configuration and preparation, and 5) conducting the experiment. In the exemplar study, participants wore the tactile vibrating toolkit and performed an established car-following task using the customized driving simulation software. The front vehicle braked intermittently, and vibrating warnings were delivered whenever the front vehicle was braking. Participants were instructed to respond as quickly as possible to the sudden brakes of the front vehicle. Driving dynamics, such as the brake response time and brake response rate, were recorded by the simulation software for data analysis. The presented protocol offers insight into the exploration of the effectiveness of tactile warnings on different body locations. In addition to the car-following task that is demonstrated in the exemplar experiment, this protocol also provides options to apply other paradigms to the driving simulation studies by making simple software configuration without any code development. However, it is important to note that due to its affordable price, the driving simulation software and hardware introduced here may not be able to fully compete with other high-fidelity commercial driving simulators. Nevertheless, this protocol can act as an affordable and user-friendly alternative to the general high-fidelity commercial driving simulators.

Reducing transmission delay and maximizing the network lifetime are important issues for wireless sensor networks (WSN). The existing approaches commonly let the nodes periodically sleep to minimize energy consumption, which adversely increases packet forwarding latency. In this study, a novel scheme is proposed, which effectively determines the duty cycle of the nodes and packet forwarding path according to the network condition by employing the event-based mechanism and reinforcement learning technique. This allows low-latency energy-efficient scheduling and reduces the transmission collision between the nodes on the path. The Monte Carlo evaluation method is also adopted to minimize the overhead of the computation of each node in making the decision. Computer simulation reveals that the proposed scheme significantly improves end-to-end latency, waiting time, packet delivery ratio, and energy efficiency compared to the existing schemes including S-MAC and event-driven adaptive duty cycling scheme.

In order to Study the Foundation Pit Surface Deformation Amount and its Three-Dimensional Visualization, The Surface Modeling Technique Based on the Grid-Type Discrete Point Cloud Data and Tin Data Model is proposed. Indoor Tests Show that the Minimum Value of the Maximum Residual Value of this Technology is 0.5612~0.9993, Which Meets the Requirements of the Software Spatial Coordinate Solution and Three-Dimensional Reconstruction. And Monitoring the Application Test, the Actual Value and Calculation Value Error is Less Than 1mm, Accuracy and Error Meet the Requirements of the Engineering Measurement Specifications. Finally, the Feasibility of the Technology is Verified by the Field Test.

The purpose of this research is to develop an active-control mechanism and its control law, to reduce the deformation of the relief bridge and weight of construction materials and improve the effective span of the bridge. The counter-force (control force) mechanism, provided by Neutral Equilibrium Mechanism, NEM, is applied to exert a counter-force at the selected position of the bridge and maintain the deflection at this selected position to be zero. This proposed NEM is used as a counter-force mechanism, which is an automatic control device consisting of a pair of pressed steel strands, rotary cantilever arm mechanisms, a displacement sensor and a controller to form as a virtual pier. In this study, these proposed counter-force mechanisms are installed at the positions of 1/3 and 2/3 span of the bridge: the effective span is only 1/3 of the original span, the maximum bending moment and maximum deflection is only 1/9 and 1/27 of the original bridge, respectively. The experimental results display that the ideal behavior of this NEM can be fully achieved in the dynamic moving load test. The deflection and the bending moment of the bridge at the position of installing these NEMs are near zero. The goals of reducing deformation and improving the carrying capacity of the bridge are realized.

Background Deep vein thrombosis (DVT) is associated with stroke. Here, we hypothesize that genes associated with DVT may also play roles in the development of stroke. Methods we firstly conducted large-scale literature based disease-gene relationship data analysis to explore the genes implicated with DVT and stroke. Further, a mega-analysis was conducted for each of these genes that were linked to DVT but not stroke, using 11 independent stroke RNA expression datasets (176 stroke cases and 102 healthy controls). Then, a multiple linear regression (MLR) model was employed to study possible influential factors on the gene expression levels in stroke. After that, a functional pathway analysis was performed to identify the potential biological linkage between stroke and the target genes suggested by mega-analysis. Results Over 81.10% genes implicated with DVT also suggested an association with stroke. Among the 24 DVT-specific genes, one DVT-inhibiting gene, SP1, presented significantly increased expression in stroke (LFC = 1.34, p-value = 0.0045). Pathway analysis showed that SP1 may play a therapeutic role in post-stroke patients by promoting multiple of stroke-inhibitors. Moreover, geographical region was indicated as an influential factor on the expression levels of SP1 in stroke samples (p-value = 0.037). Conclusion Our results suggested that DVT inhibitor SP1 could be a novel therapeutic target gene for post-stroke treatment. Further study of the potential relations between SP1 and stroke was guaranteed.

Wireless sensor network (WSN) is effective for monitoring the target environment, which consists of a large number of sensor nodes of limited energy. An efficient medium access control (MAC) protocol is thus imperative to maximize the energy efficiency and performance of WSN. The most existing MAC protocols are based on the scheduling of sleep and active period of the nodes, and do not consider the relationship between the load condition and performance. In this paper a novel scheme is proposed to properly determine the duty cycle of the WSN nodes according to the load, which employs the Q-learning technique and function approximation with linear regression. This allows low-latency energy-efficient scheduling for a wide range of traffic conditions, and effectively overcomes the limitation of Q-learning with the problem of continuous state-action space. NS3 simulation reveals that the proposed scheme significantly improves the throughput, latency, and energy efficiency compared to the existing fully active scheme and S-MAC.

This paper demonstrates a single-inductor dual-output (SIDO) buck converter, which is developed for implantable medical devices. The dual-mode operation, which combines pulse-skip modulation (PSM) and pulse-width modulation (PWM), is employed to regulate outputs under light load and heavy load conditions, respectively. The converter provides two output voltages: V OUT1 (2.5–3V) for charge pumps and V OUT2 (2V) for digital circuits. With the start-up circuits, the SIDO buck converter can act as self-start-up DC–DC buck converter. To avoid voltage stress issue under 3.2–4.2V battery operation in 180nm standard (CMOS) process, the stacked power stage is used. The proposed level shifter includes an additional level restorer to avoid a misjudgment issue during start-up period. The simulation results demonstrate that the converter achieves peak efficiency of 94.5% with PSM control, and it achieves peak efficiency of 89.1% with PWM control.

We introduce an efficient approach to generate vortex Bessel-like beams based on high-order fiber mode, which can produce radially polarized Bessel-Gauss beams. Anti -diffraction properties of the produced Bessel-like beams are investigated. © 2020 The Author(s)

While single-image object detectors can be naively applied to videos in a frame-by-frame fashion, the prediction is often temporally inconsistent. Moreover, the computation can be redundant since neighboring frames are inherently similar to each other. In this work we propose to improve video object detection via temporal aggregation. Specifically, a detection model is applied on sparse keyframes to handle new objects, occlusions, and rapid motions. We then use real-time trackers to exploit temporal cues and track the detected objects in the remaining frames, which enhances efficiency and temporal coherence. Object status at the bounding-box level is propagated across frames and updated by our aggregation modules. For keyframe scheduling, we propose adaptive policies using reinforcement learning and simple heuristics. The proposed framework achieves the state-of-the-art performance on the Imagenet VID 2015 dataset while running real-time on CPU. Extensive experiments are done to show the effectiveness of our training strategies and justify the model designs.

Introduction The aim of this study was to understand the knowledge and current situation of antibiotic use among primary doctors in Sichuan Province, 10 years after the new healthcare reform, to analyze the implementation and impact of the relevant policies of the new healthcare reform, to analyze the reasons for the irrational use of antibiotics, and to provide relevant suggestions for the rational use of antibiotics. Methods From August 2018 to March 2019, five counties (cities) were randomly selected according to the level of urban development and geographical distribution in Sichuan Province, China. Various primary medical institutions and private clinics were randomly selected at different levels. Questionnaires and on-site interviews were conducted to quantitatively analyze doctors’ knowledge of antibiotic use and current situation. Views on antibiotic use were analyzed qualitatively and from multiple perspectives. A total of 492 questionnaires were issued, 430 of which were valid, with an effective recovery rate of 87.4% Results Quantitative analysis showed that 92.1% of 430 doctors surveyed knew the rules and authority of antibiotic use; 83.5% participated in antibiotic knowledge training; 56.7% would abide by guidance on antibiotic use; 72.6% thought that their knowledge of antibiotics needed to be improved. The rank-sum test shows that the cognitive differences of doctors with or without relevant training experience are statistically significant (p=0.018), those with the relevant training were better than the untrained doctors; the cognitive differences of doctors with different working years were statistically significant (p=0.038), and the doctors working under 10 years were better than those with 10–20 years; There was no significant difference in the correct rate of antibiotic use among doctors with different academic qualifications (p=0.077). There was no significant difference in knowing the correct rate of antibiotic use among doctors of different genders (p=0.076). Conclusions Ten years after the introduction of the new healthcare reform policy, the improvement of antibiotic use is still far from the expected goal; the knowledge of antibiotic rational use of doctors in primary medical institutions needs to be strengthened, especially in village clinics and private clinics; joint efforts of doctors, patients and supervisors are needed to promote the rational use of antibiotics.

Programmed death-ligand 1 (PD-L1) expression in colorectal cancers (CRCs) was implicated in predicting anti-PD-1/PD-L1 therapy efficacy. However, therapeutic response has also been found in patients without PD-L1 expression in the primary tumor. Here we show that PD-L1 expression is significantly more prevalent in metastatic CRCs than in primary tumors, and the expression of PD-L1 in primary CRC may not represent the tumors that spread to distant organs. Positive expression of PD-L1 was found in 81.8% metastatic CRCs, being significantly more prevalent than in primary CRCs (40.9%; P = 0.012, Fisher's exact test). While comparing the primary and metastatic lesions of the same patients, we found that PD-L1 expression frequently increased during the metastatic process. However, PD-L1 expression is rarely decreased in metastatic lesion. Intratumoral heterogeneity expression of PD-L1 was found in both metastatic CRCs (28.6%) and primary CRCs (33.3%). In conclusion, PD-L1 is prevalently expressed in metastatic CRCs, and increased PD-L1 expression is frequently found in metastatic CRC as compared to primary tumor. These findings suggest that PD-L1 expression in metastatic CRC should be considered as an independent factor while evaluating the suitability of patients for immunotherapy.

We demonstrate electromagnetic induction imaging with an unshielded, portable radio-frequency atomic magnetometer scanning over the target object. This configuration satisfies standard requirements in typical applications, from security screening to medical imaging. The ability to scan the magnetometer over the object relies on the miniaturization of the sensor head and on the active compensation of the ambient magnetic field. Additionally, a procedure is implemented to extract high-quality images from the recorded spatial dependent magnetic resonance. The procedure is shown to be effective in suppressing the detrimental effects of the spatial variation of the magnetic environment., Letter

The association between central lymph node metastasis (LNM) and risk factors, including the presence of the BRAF mutation, BRAFV600E, in patients with papillary thyroid cancer (PTC) requires further investigation. A potent risk factor that can indicate LNM in different histological subtypes of PTC and in different preoperative central lymph node statuses also requires further research. A total of 287 patients with PTC who accepted thyroidectomy were included in the present study. Clinicopathological data of these patients were reviewed to examine the risk factors for central LNM through univariate and multivariate analyses. Overall, BRAFV600E in patients with cN0 (subclinical nodal disease) and cN1 (other than cN0) PTC was associated with central LNM. However, multivariate analyses demonstrated that BRAFV600E was not an independent risk factor in patients with cN1 or cN0 PTC. For patients with classical variant PTC (CVPTC), BRAFV600E was independently associated with central LNM. However, on further analysis, the association was only significant in patients with cN0 CVPTC. For patients with follicular variant PTC (FVPTC) or aggressive variant PTC (AVPTC), the BRAFV600E mutation rate was not significantly different between patients with and without central LNM. In conclusion, BRAFV600E was an independent risk factor for central LNM overall in patients with PTC and in patients with CVPTC, particularly in patients with cN0 CVPTC. However, BRAFV600E was not an independent risk factor for patients with FVPTC and AVPTC. Therefore, BRAFV600E provides varied clinical significance in different histological subtypes and preoperative central lymph node status.

BACKGROUND This study aimed to identify independent prognostic factors for overall survival (OS) of patients with advanced non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation and receiving gefitinib as first-line treatment in real-world practice. MATERIALS AND METHODS We enrolled 226 patients from June 2011 to May 2013. During this period, gefitinib was the only EGFR-tyrosine kinase inhibitor reimbursed by the Bureau of National Health Insurance of Taiwan. RESULTS The median progression-free survival and median OS were 11.9 months (95% confidence interval [CI]: 9.7-14.2) and 26.9 months (21.2-32.5), respectively. The Cox proportional hazards regression model revealed that postoperative recurrence, performance status (Eastern Cooperative Oncology Grade [ECOG] ≥2), smoking index (≥20 pack-years), liver metastasis at initial diagnosis, and chronic hepatitis C virus (HCV) infection were independent prognostic factors for OS (hazard ratio [95% CI] 0.3 [0.11-0.83], p = .02; 2.69 [1.60-4.51], p

Bundled payment programs for primary total joint arthroplasty (TJA) have identified reducing nonhome discharge as a major area of cost savings. Health care providers must therefore identify, risk stratify, and appropriately care for home-discharged TJA patients. This study aimed to analyze risk factors and timing of postdischarge complications among home-discharged primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients and risk stratify them to identify those who would benefit from higher level care.Patients discharged home after elective primary THA/TKA from 2011 to 2014 were identified in the National Surgical Quality Improvement Program database. Bivariate and multivariate analyses were performed using perioperative variables.A total of 50,376 and 71,293 home-discharged THA and TKA patients were included for analysis, of which, 1575 THA (3.1%) and 2490 TKA (3.5%) patients suffered postdischarge severe complications or unplanned readmissions. These patients were older, smokers, obese, and functionally dependent (P .001 for all). In multivariate analysis, severe adverse event predischarge, age, male gender, functional status, and 10 other variables were all associated with ≥1.22 odds of postdischarge severe adverse event or readmission (P.05). THA and TKA patients with 2, 3, or ≥4 risk factors had 1.43-5.06 times odds of complications within 14 days post discharge and 1.41-3.68 times odds of complications beyond 14 days compared to those with 0 risk factors (P.001 for all).Risk factors can be used to predict which home-discharged TJA patients are at greatest risk of postdischarge complications. Given that this is a growing population, we recommend the development of formal risk-stratification protocols for home-discharged TJA patients.

This study aimed at assessing short-term risk of serious cardiac events after elective total joint arthroplasty (TJA) as compared to a less-invasive procedure, knee arthroscopy (KA).Patients who underwent elective primary total hip arthroplasty (THA), total knee arthroplasty (TKA), or KA from 2011 to 2014 were identified in the American College of Surgeons National Surgical Quality Improvement Program database. A 1:1 propensity matching was used to generate 2 control cohorts of KA patients with similar characteristics. Bivariate and multivariate analyses were assessed using perioperative variables.A total of 24,203 THA, 21,740 TKA, and 45,943 KA patients were included. Bivariate analysis revealed significantly higher rates of serious 30-day cardiac events (myocardial infarction or cardiac arrest) among THA (0.15% vs 0.05%, P.001) and TKA patients (0.14% vs 0.05%, P.03) vs KA controls. In multivariate analysis controlling for patient characteristics and comorbidities, THA and TKA were associated with a 2.61 and 1.98 times odds of serious 30-day cardiac events as compared to controls (P ≤ .03 for both). Additional independent predictors of serious 30-day cardiac events included age, smoking, cardiac disease, and American Society of Anesthesiologists class 3/4. In the THA and TKA cohorts, serious cardiac events occurred within the first 3 days postoperation compared to 4 days in controls.After controlling for patient characteristics and comorbidities, TJA increased the short-term risk of serious cardiac event compared to a less-invasive procedure. This information better quantifies the risk differential for patients considering surgery as they engage in shared decision making with their providers. In addition, our data may have an impact on perioperative management of antithrombotic medications used in patients with cardiac disease. The median time in days to serious cardiac event was 2 in THA and 3 in TKA vs 4 in KA, which may have implications in postoperative monitoring of patients after surgery.

Extranodal NK/T-cell lymphoma, nasal type (ENTKL), is an aggressive hematological malignancy with poor prognosis, early detection of tumor at initial diagnosis or during routine surveillance is important for improving survival outcomes. Molecular profiling of circulating tumor DNA (ctDNA) is a promising non-invasive tool for monitoring disease status. Here, we assessed the gene mutation spectrum of plasma ctDNA in ENKTL by CAPP-Seq, we found that the mostly frequently mutated genes were MGA (33.3%), TP53 (30%), ASXL3 (28.3%), DDX3X (25%), BCORL1 (25%), TRAF3 (21.7%), NOTCH3 (21.7%), STAT5B (21.7%), EP300 (21.7%), APC (20%), ATM (18.3%), TNFRSF14 (16.7%), KMT2D (16.7%), EZH2 (16.7%) and SETD2 (16.7%), mutation frequency of MGA and TP53 were significantly higher in stage III-IV, and mutation of MGA, TP53, NOTCH3, et al were significantly correlated with metabolic tumor burden of the patients. Compared with tumor tissue DNA, ctDNA profiling showed well concordance. Serial ctDNA analysis showed that treatment with chemotherapy could decrease the number and mutation allele frequency of genes, compared with PET/CT, ctDNA has more advantage for track residual disease of the patients, in addition, we also found that patients with mutated MGA, TP53, SETD2, APC predicted poor prognosis. Collectively, our results provide evidence the proof of concept that ctDNA may serve as novel precision medicine biomarker in ENKTL. Trial Registration: ClinicalTrials identifier: ChiCTR1800014813. Funding Statement: This project was supported by grants from the National Natural Science Fund for Youth (No. 81600166), and the technique innovation and applied program of Chongqing (cstc2018jscx-msybX0052). Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: All participants provided informed written consent before undergoing any study-related procedures in accordance with the Declaration of Helsinki. This study was approved by China Ethics Committee of Registering Clinical Trials (ChiECRCT-20180005).

Recent deep learning methods for object detection rely on a large amount of bounding box annotations. Collecting these annotations is laborious and costly, yet supervised models do not generalize well when testing on images from a different distribution. Domain adaptation provides a solution by adapting existing labels to the target testing data. However, a large gap between domains could make adaptation a challenging task, which leads to unstable training processes and sub-optimal results. In this paper, we propose to bridge the domain gap with an intermediate domain and progressively solve easier adaptation subtasks. This intermediate domain is constructed by translating the source images to mimic the ones in the target domain. To tackle the domain-shift problem, we adopt adversarial learning to align distributions at the feature level. In addition, a weighted task loss is applied to deal with unbalanced image quality in the intermediate domain. Experimental results show that our method performs favorably against the state-of-the-art method in terms of the performance on the target domain., Comment: Accepted in WACV'20. Code and models will be available at https://github.com/kevinhkhsu/DA_detection

As a diagnosis of exclusion, Undifferentiated Pleomorphic Sarcoma (UPS) has unclear clinical characteristics. The objective of this retrospective cohort study is to investigate which clinical and prognostic factors of primary lower-extremity UPS will determine failure.We retrospectively reviewed 55 primary lower-extremity UPS cases treated at Stanford between 1998 and 2015. Overall Survival (OS) and Disease-Free Survival (DFS) curves were calculated. Univariate Fisher's Exact Tests were used to examine relationships between disease recurrence, treatment, patient factors, tumor characteristics, and surgical margins.5-year DFS and OS rates were 60% (95% CI, 45%-72%) and 68% (95% CI, 53%-79%), respectively. The 5-year DFS rate for patients with positive margins was 33.3% (95% CI, 5%-68%) compared with 63% (95% CI, 47%-76%) for patients with negative margins. (Log-rank, P=0.03). The OS rate for those with disease recurrence was 42% % (95% CI, 16%-67%) compared with 76% (95% CI, 59%-87%) for patients who did not have disease recurrence (log-rank, P=0.021). Local failure occurred more frequently with omission of radiation therapy (Fisher's exact test, P=0.009).Positive surgical margins are an important prognostic factor for predicting relapse in UPS. Relapse of any kind led to worse OS. Radiation therapy improved local control of disease but had no statistically significant effect on DFS, highlighting the need for improved diagnostics to identify those at highest risk for hematogenous metastasis and for selection of patients for adjuvant systemic treatment.

In the era of blossoming computer sciences and internet technology, people cannot abolish network in our lives. However, the large number of users, website services will make itself became the most favorite targets for hackers. Although these malicious behaviors can be detected by network intrusion detection system, it is difficult to generate accuracy result owing to the shortage of data. This paper proposed a solution using host intrusion detection system that focus on the host log detection of webserver. Besides using port monitoring to monitor network environment, this paper also collected signatures of web attack and malicious activities by using signature-based approach. Furthermore, this research will find out the source of the malicious files with file monitoring function, and take appropriate action to protect web services. By using the proposed mechanism of host-based intrusion detection methods, it can provide a high accuracy to bring safety for managers and users.

Ultrafast high-order mode (HOM) lasers are a relatively new class of ultrafast optics. They play a significant role in the fieldsof scientific research and industrial applications due to the high peak power and unique properties of spatial intensity and polarization distribution. Generation of ultrafast HOM beams in all-fiber systems has become an important research direction. In this paper, all-fiber mode conversion techniques, pulsed HOM laser strategies, and few-mode/multi-mode fiber (FMF/MMF) lasers are reviewed. The main motivation of this review is to highlight recent advances in the field of all-fiber ultrafast HOM lasers, for example, generating different HOM pulses based on fiber mode converters and mode-locking in the FMF/MMF lasers. These results suggest that mode selective coupler can be used as a broad bandwidth mode converter with fast response and HOM can be directly oscillated in the FMF/MMF laser cavity with high stability. In addition, spatiotemporal mode-locking in the FMF/MMF is also involved. It is believed that the development of all-fiber ultrafast HOM lasers will continue to deepen, thus laying a good foundation for future applications.

Summary Aim While bleeding is a well-known complication of warfarin use and is thought to be a contributory cause of treatment discontinuation, studies quantifying this association are limited. The objective of this study was to quantify the association between bleeding events and subsequent warfarin discontinuation in patients with nonvalvular atrial fibrillation (NVAF). Methods A nested case–control analysis was conducted within a cohort of patients with NVAF newly treated with warfarin. All patients who discontinued warfarin (at least 60 days from last day of warfarin supply) during follow-up were identified as cases and matched with up to 10 controls on age, sex, and duration of follow-up. The index date was defined as the date of warfarin treatment discontinuation of the cases. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of warfarin treatment discontinuation associated with a bleeding event in the 60 days before the index date. Results The cohort included 24,243 patients who initiated warfarin treatment, of whom 13,482 discontinued treatment during follow-up (cases). Bleeding was associated with an increased risk of warfarin treatment discontinuation (3.55% vs. 0.85%; OR, 4.31; 95% CI, 3.87–4.81). When including only bleeds as the first listed diagnosis, the unadjusted OR was 4.64 (95% CI, 4.10–5.26), and the adjusted OR was 4.65 (95% CI, 4.10–5.27). Conclusions Bleeding was significantly associated with warfarin discontinuation, and thus, the selection of an effective treatment regimen associated with a lower bleeding rate could be a desirable treatment approach.

We demonstrate visible-light all-fiber vortex lasers by incorporating the home-made mode selective couplers (MSCs). The MSC at green or red wavebands is fabricated by specially designing and fusing a single-mode fiber (SMF) and a few-mode fiber (FMF). The MSCs inserted into visible fiber cavities act as power splitters and mode converters from the LP01 to LP11 mode at green and red wavelengths, respectively. The red-light all-fiber vortex laser is formed by a 10-cm Pr3+/Yb3+:ZBLAN fiber, a fiber Bragg grating, a fiber end-facet mirror and the MSC at 635 nm, which generates vortex beams with OAM±1 at 634.4 nm and an output power of 13 mW. The green-light all-fiber vortex laser consists of a 12-cm Ho3+:ZBLAN fiber, two fiber pigtail mirrors, and the MSC at 550 nm, which generates vortex beams with OAM±1 at 548.9 nm and an output power of 3 mW.

We present two kinds of mode-selective-coupler-based ultrafast radially polarized lasers delivering switchable wavelengths and pulsewidths. One is a linear-cavity fiber laser mode locked in the 1.5 µm region, which produces not only wavelength-agile radially polarized pulses in the spatial domain, but also switchable femtosecond and picosecond pulses in the temporal domain. The other one is a nonlinear-polarization-rotation-technique-assisted passively mode-locked fiber ring laser in the 1.0 µm region, presenting an ideal broadband spectral switching with picosecond radially polarized pulses output. The presented fiber lasers offer a type of compact laser source, enabling a flexible option for radially polarized beams in spectral and temporal domains.

A previously healthy 22-year-old man presented to a community hospital with diarrhea, vomiting, and a fever of 40°C that had lasted for two days. He was admitted to the intensive care unit. Initially, the patient’s cardiopulmonary findings were normal. He had a soft but tender abdomen, and

Chronic neuropathic pain and depression are often comorbid. Ketamine has been used to treat refractory pain. There is emerging evidence for use in depression. We present a case of a pediatric patient who was successfully treated with subanesthetic intravenous ketamine infusion for chronic neuropathic pain and suicidality.

Objective The air medical transportation industry has seen a steady rise in the use of mechanical circulatory support devices (eg, intra-aortic balloon pumps, ventricular assist devices, and extracorporeal membrane oxygenation) during transport missions, either for definitive management or repatriation. As these complex devices become more common, the industry will have to adapt to support their use in their clientele. The goal of this narrative review was to assess our current experiences regarding mechanical circulatory support devices in air medical transportation and to identify important factors to ensure successful transport. Methods We conducted a systematic search on MEDLINE and Embase using the following search terms: aeromedical transportation, air transportation, intra-aortic balloon pump, ventricular assist device, and extracorporeal membrane oxygenation. Results were cross-referenced to identify articles addressing both air medical transport and mechanical circulatory support devices. Results After a systematic review of the available literature, 49 articles addressing mechanical support devices transported by rotary wing and fixed wing aircraft were reviewed. In summary, our review encompassed 811 total aerial transports (152 by balloon pumps, 12 by ventricular assist devices, and 647 by extracorporeal membrane oxygenation). We found air medical transportation with these devices carried out in the public, private, or military sectors, to be safe, with low rates of serious adverse events. Dedicated training sessions focused on device troubleshooting and problem-solving during transport, optimal medical crew composition, predeparture logistical preparations, and on-demand specialist consultation can improve mission success. Conclusion We report that air medical transportation of patients supported by mechanical circulatory support devices is safe. Complications can be mitigated by training and addressed either during the predeparture or in-transportation phase.

Vascular dementia (VaD) is one of the most common forms of dementia, and second only to Alzheimer's disease. The purpose of this study was to evaluate the potential diagnostic value of Framingham risk score (FRS) in VaD by investigating the relationship among cardiovascular risks, FRS, and VaD. Data were collected from patients (n = 130) at Tongji Hospital in Wuhan, China. They were divided into 2 groups, including the control group (n = 70) and the VaD group (n = 60). Statistical methods including t-test, logistic regression model, multiple linear regression model, and receiver-operating characteristic (ROC) curve were adopted for the assessment. A significant difference (all P