Body composition has emerged as a prognostic factor in cancer patients. We investigated whether sarcopenia at diagnosis and loss of skeletal muscle during palliative chemotherapy were associated with ...survival in patients with pancreatic cancer.
We retrospectively reviewed the clinical outcomes of pancreatic cancer patients receiving palliative chemotherapy between 2003 and 2010. The cross-sectional area of skeletal muscle at L3 by computed tomography was analyzed with Rapidia 3D software. We defined sarcopenia as a skeletal muscle index (SMI)< 42.2 cm2/m2 (male) and < 33.9 cm2/m2 (female) using ROC curve.
Among 484 patients, 103 (21.3%) patients were sarcopenic at diagnosis. Decrease in SMI during chemotherapy was observed in 156 (60.9%) male and 65 (40.6%) female patients. Decrease in body mass index (BMI) was observed in 149 patients (37.3%), with no gender difference. By multivariate analysis, sarcopenia (P< 0.001), decreasedBMI and SMI during chemotherapy (P = 0.002, P = 0.004, respectively) were poor prognostic factors for overall survival (OS). While the OS of male patients was affected with sarcopenia (P< 0.001) and decreased SMI (P = 0.001), the OS of female patients was influenced with overweight at diagnosis (P = 0.006), decreased BMI (P = 0.032) and decreased SMI (P = 0.014). Particularly, while the change of BMI during chemotherapy did not have impact on OS within the patients with maintained SMI (P = 0.750), decrease in SMI was associated with poor OS within the patients with maintained BMI (HR 1.502; P = 0.002).
Sarcopenia at diagnosis and depletion of skeletal muscle, independent of BMI change, during chemotherapy were poor prognostic factors in advanced pancreatic cancer.
Sequence alterations in microsatellites and an elevated mutational burden are observed in 20% of gastric cancers and associated with clinical response to anti-PD-1 antibodies. However, 50% of ...microsatellite instability-high (MSI-H) cancers are intrinsically resistant to PD-1 therapies. We conducted a phase II trial of pembrolizumab in patients with advanced MSI-H gastric cancer and included serial and multi-region tissue samples in addition to serial peripheral blood analyses. The number of whole-exome sequencing (WES)-derived nonsynonymous mutations correlated with antitumor activity and prolonged progression-free survival (PFS). Coupling WES to single-cell RNA sequencing, we identified dynamic tumor evolution with greater on-treatment collapse of mutational architecture in responders. Diverse T-cell receptor repertoire was associated with longer PFS to pembrolizumab. In addition, an increase in PD-1
CD8
T cells correlated with durable clinical benefit. Our findings highlight the genomic, immunologic, and clinical outcome heterogeneity within MSI-H gastric cancer and may inform development of strategies to enhance responsiveness. SIGNIFICANCE: This study highlights response heterogeneity within MSI-H gastric cancer treated with pembrolizumab monotherapy and underscores the potential for extended baseline and early on-treatment biomarker analyses to identify responders. The observed markers of intrinsic resistance have implications for patient stratification to inform novel combinations among patients with intrinsically resistant features.
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Humans have a myriad of sensory receptors in different sense organs that form the five traditionally recognized senses of sight, hearing, smell, taste, and touch. These receptors detect diverse ...stimuli originating from the world and turn them into brain‐interpretable electrical impulses for sensory cognitive processing, enabling us to communicate and socialize. Developments in biologically inspired electronics have led to the demonstration of a wide range of electronic sensors in all five traditional categories, with the potential to impact a broad spectrum of applications. Here, recent advances in bioinspired electronics that can function as potential artificial sensory systems, including prosthesis and humanoid robots are reviewed. The mechanisms and demonstrations in mimicking biological sensory systems are individually discussed and the remaining future challenges that must be solved for their versatile use are analyzed. Recent progress in bioinspired electronic sensors shows that the five traditional senses are successfully mimicked using novel electronic components and the performance regarding sensitivity, selectivity, and accuracy have improved to levels that outperform human sensory organs. Finally, neural interfacing techniques for connecting artificial sensors to the brain are discussed.
Unconventional electronics and sensors inspired by biological sensory systems have proved impeccable sensing performance and accuracy for diverse external stimuli. From systems inspired by human receptors to those inspired by nontraditional receptors, recent advances in bioinspired electronics for artificial sensory systems are reviewed. Together, these progressive efforts provide practical approaches for creating artificial organs, such as prosthesis and humanoid robots.
Bright organic/inorganic hybrid perovskite light‐emitting diodes (PrLEDs) are realized by using CH3NH3PbBr3 as an emitting layer and self‐organized buffer hole‐injection layer (Buf‐HIL). The PrLEDs ...show high luminance, current efficiency, and EQE of 417 cd m−2, 0.577 cd A−1, and 0.125%, respectively. Buf‐HIL can facilitate hole injection into CH3NH3PbBr3 as well as block exciton quenching.
Recently, piezoelectricity has been observed in 2D atomically thin materials, such as hexagonal‐boron nitride, graphene, and transition metal dichalcogenides (TMDs). Specifically, exfoliated ...monolayer MoS2 exhibits a high piezoelectricity that is comparable to that of traditional piezoelectric materials. However, monolayer TMD materials are not regarded as suitable for actual piezoelectric devices due to their insufficient mechanical durability for sustained operation while Bernal‐stacked bilayer TMD materials lose noncentrosymmetry and consequently piezoelectricity. Here, it is shown that WSe2 bilayers fabricated via turbostratic stacking have reliable piezoelectric properties that cannot be obtained from a mechanically exfoliated WSe2 bilayer with Bernal stacking. Turbostratic stacking refers to the transfer of each chemical vapor deposition (CVD)‐grown WSe2 monolayer to allow for an increase in degrees of freedom in the bilayer symmetry, leading to noncentrosymmetry in the bilayers. In contrast, CVD‐grown WSe2 bilayers exhibit very weak piezoelectricity because of the energetics and crystallographic orientation. The flexible piezoelectric WSe2 bilayers exhibit a prominent mechanical durability of up to 0.95% of strain as well as reliable energy harvesting performance, which is adequate to drive a small liquid crystal display without external energy sources, in contrast to monolayer WSe2 for which the device performance becomes degraded above a strain of 0.63%.
WSe2 bilayers with turbostratic stacking have reliable piezoelectric properties that cannot be obtained from a WSe2 monolayer. The flexible piezoelectric WSe2 bilayers exhibit a prominent mechanical durability of up to 0.95% of strain as well as reliable energy harvesting performance, which is adequate to drive a small liquid crystal display without external energy sources.
Objective
There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to ...verify the reliability and validity of the developed scale.
Methods
The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38).
Results
A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient ICC = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p < 0.001), and had acceptable internal consistency (Cronbach α = 0.88). Additionally, in the validation cohort, the scale showed high interobserver reliability (ICC = 0.99) and internal consistency (Cronbach α = 0.92).
Interpretation
CASE is a novel clinical scale for AE with a high level of clinimetric properties. It would be suitable for application in clinical practice and might help overcome the limitations of current outcome scales for AE. ANN NEUROL 2019;85:352–358.
Objective
To demonstrate the immune landscape of blood and synovial cells in the setting of ankylosing spondylitis (AS) through the analysis of both single‐cell transcriptome and surface protein ...expression, and to unveil the molecular characteristics of pathogenic Th17 cells.
Methods
This study included 40 individuals with active AS, 20 individuals with stable AS, 40 patients with active rheumatoid arthritis, and 20 healthy controls. Surface phenotype and intracellular staining were assessed using flow cytometry after peripheral blood mononuclear cells and synovial fluid mononuclear cells were stimulated with T cell receptor. Single‐cell transcriptomes of 6 patients with active AS were studied along with cellular indexing of transcriptomes and epitopes by sequencing. We also assessed the outcome of targeting OX40 and glucocorticoid‐induced tumor necrosis factor receptor (GITR) on the surface of Th17 cells in a mouse model of curdlan‐injected SKG mice in which anti‐GITR ligand and/or anti‐OX40 ligand were used.
Results
We identified pathogenic Th17 cells as polyfunctional interleukin‐17A (IL‐17A)– and interferon‐γ (IFNγ)–producing memory CD4+ T cells, with clinically supportive evidence for their pathogenic roles at sites of inflammation in AS. Transcriptome and flow cytometric analyses revealed that the coexpression of TNFRSF4 (OX40) and TNFRSF18 (GITR) is increased in pathogenic Th17 cells. Suppression of ligand receptor interactions in vivo through OX40 and GITR effectively suppressed clinical arthritis and decreased pathogenic Th17 cells in the curdlan‐injected SKG mouse model.
Conclusion
Our results have implications for the understanding of pathogenic Th17 cells in AS patients and suggest potential therapeutic targets.
•A novel computer-aided diagnosis system based on deep learning techniques is proposed.•The proposed YOLO-based CAD system simultaneously handles both detection and classification of breast cancer ...masses.•YOLO-based CAD has a capability to handle most challenging cases of breast abnormalities.
Automatic detection and classification of the masses in mammograms are still a big challenge and play a crucial role to assist radiologists for accurate diagnosis. In this paper, we propose a novel Computer-Aided Diagnosis (CAD) system based on one of the regional deep learning techniques, a ROI-based Convolutional Neural Network (CNN) which is called You Only Look Once (YOLO). Although most previous studies only deal with classification of masses, our proposed YOLO-based CAD system can handle detection and classification simultaneously in one framework.
The proposed CAD system contains four main stages: preprocessing of mammograms, feature extraction utilizing deep convolutional networks, mass detection with confidence, and finally mass classification using Fully Connected Neural Networks (FC-NNs). In this study, we utilized original 600 mammograms from Digital Database for Screening Mammography (DDSM) and their augmented mammograms of 2,400 with the information of the masses and their types in training and testing our CAD. The trained YOLO-based CAD system detects the masses and then classifies their types into benign or malignant.
Our results with five-fold cross validation tests show that the proposed CAD system detects the mass location with an overall accuracy of 99.7%. The system also distinguishes between benign and malignant lesions with an overall accuracy of 97%.
Our proposed system even works on some challenging breast cancer cases where the masses exist over the pectoral muscles or dense regions.
Recent technological advances in nanomaterials have driven the development of high‐performance light‐emitting devices with flexible and stretchable form factors. Deformability in such devices is ...mainly achieved by replacing the rigid materials in the device components with flexible nanomaterials and their assemblies (e.g., carbon nanotubes, silver nanowires, graphene, and quantum dots) or with intrinsically soft materials and their composites (e.g., polymers and elastomers). Downscaling the dimensions of the functional materials to the nanometer range dramatically decreases their flexural rigidity, and production of polymer/elastomer composites with functional nanomaterials provides light‐emitting devices with flexibility and stretchability. Furthermore, monolithic integration of these light‐emitting devices with deformable sensors furnishes the resulting display with various smart functions such as force/capacitive touch‐based data input, personalized health monitoring, and interactive human–machine interfacing. These ultrathin, lightweight, and deformable smart optoelectronic devices have attracted widespread interest from materials scientists and device engineers. Here, a comprehensive review of recent progress concerning these flexible and stretchable smart displays is presented with a focus on materials development, fabrication techniques, and device designs. Brief overviews of an integrated system of advanced smart displays and cutting‐edge wearable sensors are also presented, and, to conclude, a discussion of the future research outlook is given.
The recent research developments and progress regarding flexible and stretchable smart displays are reviewed comprehensively. Important advancements concerning materials development, fabrication techniques, and device designs are summarized, compared, and discussed, with a detailed description of smart display applications. In addition, the outlook for future research in this field is discussed.
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