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Neonicotinoid insecticides (NEOs) have been extensively approved for application in agricultural production both in China and globally. Previous studies indicated that human exposure to NEOs would have adverse health effects. However, studies on occurrences of NEOs in kidney injury patients and their association with nephrotoxicity are limited. This study investigates the potential correlation between exposure to NEOs and kidney injury within a subset (n = 224) of the population residing in South China. Levels of 8 NEOs and 5 metabolites were quantified in blood samples obtained from both the 110 healthy and 114 kidney injury cohorts in South China. We found that target analytes were frequently detected in samples from the healthy and kidney injury cohorts (61%–100 %). Dinotefuran is the predominant NEO in the healthy (42.3 %) and kidney injury cohort (49.6 %). Significantly positive (p

We have previously shown that healthy subjects can transfer coordination skills to the unpracticed hand by performing a unimanual task with the other hand and visualizing a bimanual action using a game-like interactive system. However, whether this system could be used to transfer coordination skills to the paretic hand after stroke and its underlying neural mechanism remain unknown. Here, using a game-like interactive system for visualization during physical practice in an immersive virtual reality environment, we examined coordination skill improvement in the unpracticed/paretic hand after training in 10 healthy subjects and 13 chronic and sub-acute stroke patients. The bimanual movement task was defined as simultaneously drawing non-symmetric three-sided squares (e.g., U and C), while the training strategy was performing a unimanual task with the right/nonparetic hand and visualizing a bimanual action. We found large decreases in the intra-hand temporal and spatial measures for movement in the unpracticed/paretic hand after training. Furthermore, a substantial reduction in the inter-hand temporal and spatial interference was observed after training. Additionally, we examined the related cortical network evolution using EEG in both the healthy subjects and stroke patients. Our studies show that the cortical network became more efficient after training in the healthy subjects and stroke patients. These results demonstrate that our proposed method could contribute to the transference of coordination skill to the paretic/unpracticed hand by promoting the efficiency of cortical networks.

Summary: Background: Only a minority of melanoma patients experience durable responses to immunotherapies due to inter- and intra-tumoral heterogeneity in melanoma. As a result, there is a pressing need for suitable preclinical models to investigate resistance mechanisms and enhance treatment efficacy. Methods: Here, we report two different methods for generating melanoma patient-derived organoids (MPDOs), one is embedded in collagen gel, and the other is inlaid in Matrigel. MPDOs in Matrigel are used for assessing the therapeutic effects of anti-PD-1 antibodies (αPD-1), autochthonous tumor infiltrating lymphocytes (TILs), and small molecule compounds. MPDOs in collagen gel are used for evaluating the chemotaxis and migratory capacity of TILs. Finding: The MPDOs in collagen gel and Matrigel have similar morphology and immune cell composition to their parental melanoma tissues. MPDOs show inter- and intra-tumoral heterogeneity and contain diverse immune cells such as CD4+, CD8+ T, Treg, CD14+ monocytic, CD15+, and CD11b+ myeloid cells. The tumor microenvironment (TME) in MPDOs is highly immunosuppressive, and the lymphoid and myeloid lineages express similar levels of PD-1, PD-L1, and CTLA-4 as their parental melanoma tissues. Anti-PD-1 antibodies (αPD-1) reinvigorate CD8+ T cells and induce melanoma cell death in the MPDOs. TILs expanded by IL-2 and αPD-1 show significantly lower expression of TIM-3, better migratory capacity and infiltration of autochthonous MPDOs, and more effective killing of melanoma cells than TILs expanded by IL-2 alone or IL-2 with αCD3. A small molecule screen discovers that Navitoclax increases the cytotoxicity of TIL therapy. Interpretation: MPDOs may be used to test immune checkpoint inhibitors and cellular and targeted therapies. Funding: This work was supported by the NIH grants CA114046, CA261608, CA258113, and the Tara Miller Melanoma Foundation.

Abstract Background The brain area stimulated during repetitive transcranial magnetic stimulation (rTMS) treatment is important in altered states of consciousness. However, the functional contribution of the M1 region during the treatment of high‐frequency rTMS remains unclear. Objective The aim of this study was to examine the clinical [the Glasgow coma scale (GCS) and the coma recovery scale‐revised (CRS‐R)] and neurophysiological (EEG reactivity and SSEP) responses in vegetative state (VS) patients following traumatic brain injury (TBI) before and after a protocol of high‐frequency rTMS over the M1 region. Methods Ninety‐nine patients in a VS following TBI were recruited so that their clinical and neurophysiological responses could be evaluated in this study. These patients were randomly allocated into three experimental groups: rTMS over the M1 region (test group; n = 33), rTMS over the left dorsolateral prefrontal cortex (DLPFC) (control group; n = 33) and placebo rTMS over the M1 region (placebo group; n = 33). Each rTMS treatment lasted 20 min and was carried out once a day. The duration of this protocol was a month with 20 treatments (5 times per week) occurring with that time. Results We found that the clinical and neurophysiological responses improved after treatment in the test, control, and placebo groups; the improvement was highest in the test group compared to that in the control and placebo groups. Conclusions Our results demonstrate an effective method of high‐frequency rTMS over the M1 region for consciousness recovery after severe brain injury.

Abstract Purpose The detection of pleural effusion in chest radiography is crucial for doctors to make timely treatment decisions for patients with chronic obstructive pulmonary disease. We used the MIMIC-CXR database to develop a deep learning model to quantify pleural effusion severity in chest radiographs. Methods The Medical Information Mart for Intensive Care Chest X-ray (MIMIC-CXR) dataset was divided into patients ‘with’ or ‘without’ chronic obstructive pulmonary disease (COPD). The label of pleural effusion severity was obtained from the extracted COPD radiology reports and classified into four categories: no effusion, small effusion, moderate effusion, and large effusion. A total of 200 datasets were randomly sampled to manually check each item and determine whether the tags are correct. A professional doctor re-tagged these items as a verification cohort without knowing their previous tags. The learning models include eight common network structures including Resnet, DenseNet, and GoogleNET. Three data processing methods (no sampling, downsampling, and upsampling) and two loss algorithms (focal loss and cross-entropy loss) were used for unbalanced data. The Neural Network Intelligence tool was applied to train the model. Receiver operating characteristic curves, Area under the curve, and confusion matrix were employed to evaluate the model results. Grad-CAM was used for model interpretation. Results Among the 8533 patients, 15,620 chest X-rays with clearly marked pleural effusion severity were obtained (no effusion, 5685; small effusion, 4877; moderate effusion, 3657; and large effusion, 1401). The error rate of the manual check label was 6.5%, and the error rate of the doctor’s relabeling was 11.0%. The highest accuracy rate of the optimized model was 73.07. The micro-average AUCs of the testing and validation cohorts was 0.89 and 0.90, respectively, and their macro-average AUCs were 0.86 and 0.89, respectively. The AUC of the distinguishing results of each class and the other three classes were 0.95 and 0.94, 0.76 and 0.83, 0.85 and 0.83, and 0.87 and 0.93. Conclusion The deep transfer learning model can grade the severity of pleural effusion.

Abstract Background Falls are commonplace among elderly people. It is urgent to prevent falls. Previous studies have confirmed that there is a difference in plantar pressure between falls and non‐falls in elderly people, but the relationship between fall risk and foot pressure has not been studied. In this study, the differences in dynamic plantar pressure between elderly people with high and low fall risk were preliminarily discussed, and the characteristic parameters of plantar pressure were determined. Methods Twenty four high‐fall‐risk elderly individuals (HR) and 24 low‐fall‐risk elderly individuals (LR) were selected using the Berg Balance Scale 40 score. They wore wearable foot pressure devices to walk along a 20‐m‐long corridor. The peak pressure (PP), pressure time integral (PTI), pressure gradient (maximum pressure gradient (MaxPG), minimum pressure gradient (MinPG), full width at half maximum (FWHM)) and average pressure (AP) of their feet were measured for inter‐group and intra‐group analysis. Results The foot pressure difference comparing the high fall risk with low fall risk groups was manifested in PP and MaxPG, concentrated in the midfoot and heel (p

Abstract Background The transfer of the behaviors of a human’s upper limbs to an avatar is widely used in the field of virtual reality rehabilitation. To perform the transfer, movement tracking technology is required. Traditionally, wearable tracking devices are used for tracking; however, these devices are expensive and cumbersome. Recently, non-wearable upper-limb tracking solutions have been proposed, which are less expensive and more comfortable. However, most products cannot track the upper limbs, including the arms and all the fingers at the same time, which limits the limb parts for tracking in a virtual environment and may lead to a limited rehabilitation effect. Methods In this paper, a novel virtual reality rehabilitation system (VRRS) was developed for upper-limb rehabilitation. The VRRS could track the motion of both upper limbs, integrate fine finger motion and the range of motion of the entire arm and map the motion to an avatar. To test the performance of VRRS, two experiments were designed. In the first experiment, we investigated the effect of VRRS on virtual body ownership, agency and location of the body and usability in 8 healthy participants by comparing it with a partial upper-limb tracking method based on a Leap Motion controller (LP) in the same virtual environments. In the second experiment, we examined the feasibility of VRRS in upper-limb rehabilitation with 27 stroke patients. Results VRRS improved the users’ senses of body ownership, agency, and location of the body. The users preferred using the VRRS to using the LP. In addition, we found that although the upper limb motor function of patients from all groups was improved, the difference between the FM scores tested on the first day and the last day of the experimental group was more significant than that of the control groups. Conclusions A VRRS with motion tracking of the upper limbs and avatar control including the arms and all the fingers was developed. It resulted in an improved user experience of embodiment and effectively improved the effects of upper limb rehabilitation in stroke patients. Trial registration The study was registered at the First Affiliated Hospital of Jinan University Identifier: KY-2020–036; Date of registration: June 01, 2020.

Purpose: By analyzing the clinical characteristics, etiological characteristics and commonly used antibiotics of patients with ventilator-associated pneumonia (VAP) in intensive care units (ICUs) in the intensive care database. This study aims to provide guidance information for the clinical rational use of drugs for patients with VAP.Method: Patients with VAP information were collected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, including their sociodemographic characteristics, vital signs, laboratory measurements, complications, microbiology, and antibiotic use. After data processing, the characteristics of the medications used by patients with VAP in ICUs were described using statistical graphs and tables, and experiences were summarized and the reasons were analyzed.Results: This study included 2,068 patients with VAP. Forty-eight patient characteristics, including demographic indicators, vital signs, biochemical indicators, scores, and comorbidities, were compared between the survival and death groups of VAP patients. Cephalosporins and vancomycin were the most commonly used. Among them, fourth-generation cephalosporin (ForGC) combined with vancomycin was used the most, by 540 patients. First-generati49n cephalosporin (FirGC) combined with vancomycin was associated with the highest survival rate (86.7%). More than 55% of patients were infected with Gram-negative bacteria. However, patients with VAP had fewer resistant strains (

Abstract: This paper mainly focused on the surface-surface intersection problem in surface border modeling. This paper introduced the intersection testing algorithm to obtain the initial intersecting lines based on the Delaunay triangulation of two surfaces. After the detection of intersecting lines’ continuity, the “weighted surface border extension algorithm” was put forward to guarantee the continuity of intersecting lines. When the discrete data is deficiency, “weighted surface border extension algorithm” is applied to guarantee the existence of intersecting lines between the surfaces which have the tendency to intersect. This paper applied “weighted surface border extension algorithm” on the result of intersecting lines to guarantee that the endpoints of intersecting lines lie on the border of both surfaces, which can be convenient to the following Constrained Delaunay Triangulation and surface cutting steps. Simulation results showed the proposed algorithm was feasible. [Copyright &y& Elsevier]