Miracle-dz/UniFAR-FTUs huggingface dataset:
外泌体PD-L1在非小细胞肺癌免疫治疗的研究进展

肿瘤免疫疗法在当前癌症治疗领域中愈来愈受瞩目，相关研究也层出不穷。 对于非小细胞肺癌（non-small cell lung cancer, NSCLC）患者来说，近些年来，以程序性死亡受体1（programmed cell death 1, PD-1）/程序性死亡配体1（programmed cell death ligand 1, PD-L1）免疫抑制剂为代表的免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）已经成为治疗恶性肿瘤的一种最具前景的治疗方案。 免疫检查点阻断治疗包括抗细胞毒T淋巴细胞相关抗原4（cytotoxic T lymphocyte-associated antigen 4, CTLA-4）单抗、抗PD-1单抗和抗PD-L1单抗，其中最被人熟知的为PD-L1免疫疗法。 目前ICIs在临床治疗中取得了很不错的治疗效果，但有效率较低，因此我们希望获得更高的治疗有效率。 近几年外泌体PD-L1在NSCLC免疫治疗中发挥了重要作用。 本文就肿瘤外泌体PD-L1蛋白对肿瘤微环境的影响、预测免疫治疗效果以及作为NSCLC免疫治疗的新型治疗策略作一综述。
Serum Tau, NFL, GFAP and UHCL-1 are Associated with the Chronic Deterioration of Neurobehavioral Symptoms following Traumatic Brain Injury.

The purpose of this study was to examine the association of serum tau, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and ubiquitin carboxy-terminal hydrolase L1 (UCHL-1) concentrations evaluated within the first 12 months following a military-related TBI, with longitudinal changes in neurobehavioral functioning extending 2-or-more years post-injury. Participants were 84 United States service members and veterans (SMVs) prospectively enrolled in the Defense and Veterans Brain Injury Center/Traumatic Brain Injury Center 15-Year Longitudinal TBI Study, separated into three discreet groups: (a) uncomplicated mild TBI [MTBI; n=28], (b) complicated mild, moderate, severe, and penetrating TBI combined [STBI; n=29], and (c) non-injured controls [NIC, n=27]). Participants completed a battery of self-report neurobehavioral symptom measures (e.g., depression, PTSD, postconcussion, anxiety, somatic, cognitive, and neurological symptoms) within 12 months of injury (baseline), and then again at 2-or-more years-post-injury (follow-up). At baseline, participants also completed a blood draw to determine serum concentrations of tau, NFL, GFAP, and UCHL-1 using an ultra-sensitivity assay method. In the MTBI and STBI groups (using hierarchical regression analyses), [1] baseline tau concentrations predicted the deterioration of neurobehavioral symptoms from baseline to follow-up on measures of anxiety, PTSD, depression, postconcussion, somatic, and neurological symptoms (accounting for 10-28% of the variance); [2] NFL predicted the deterioration of depression, postconcussion, somatic, cognitive, and neurological symptoms (10-32% variance); [3] GFAP predicted the deterioration of postconcussion, PTSD, depression, anxiety, somatic, neurological, and cognitive symptoms (11-43% variance); and [4] UCHL-1 predicted the deterioration of anxiety, somatic, and neurological symptoms (10-16% variance). In the NIC group, no meaningful associations were found between baseline biomarker concentrations and the deterioration of neurobehavioral symptoms on the majority of measures. This study reports that elevated tau, NFL, GFAP, and UCHL-1 concentrations within the first 12 months of injury are associated with the deterioration of neurobehavioral symptoms that extends to the chronic phase of recovery following a TBI. These findings suggest that a blood-based panel including these biomarkers could be a useful prognostic tool to identifying those individuals at risk of poor future outcome following TBI.
Instability of localized buckling modes in a one-dimensional strut model

Stability of localized solutions arising in a fourth–order differential equation modelling struts is investigated. It was shown by Buffoni et al. in 1996 that the model exhibits many multimodal buckling states bifurcating from a primary buckling mode. In this article, using analytical and numerical techniques, the primary mode is shown to be unstable under dead loading for all axial loads, while it is likely to be stable under rigid loading for small axial loads. Furthermore, for general reversible or conservative systems, stability of the multimodal solutions is established assuming stability of the primary state. Since this hypothesis is not satisfied for the buckling mode arising in the strut model, any multimodal buckling state will be unstable under dead and rigid loading.
Nonlinear lattice waves in heterogeneous media

We discuss recent advances in the understanding of the dynamics of nonlinear lattice waves in heterogeneous media, which enforce complete wave localization in the linear wave equation limit, especially Anderson localization for random potentials, and Aubry–André localization for quasiperiodic potentials. Additional nonlinear terms in the wave equations can either preserve the phase-coherent localization of waves, or destroy it through nonintegrability and deterministic chaos. Spreading wave packets are observed to show universal features in their dynamics which are related to properties of nonlinear diffusion equations.
The Habitability of Proxima Centauri b I: Evolutionary Scenarios

We analyze the evolution of the potentially habitable planet Proxima Centauri b to identify environmental factors that affect its long-term habitability. We consider physical processes acting on size scales ranging from the galactic to the stellar system to the planet's core. We find that there is a significant probability that Proxima Centauri has had encounters with its companion stars, Alpha Centauri A and B, that are close enough to destabilize an extended planetary system. If the system has an additional planet, as suggested by the discovery data, then it may perturb planet b's eccentricity and inclination, possibly driving those parameters to non-zero values, even in the presence of strong tidal damping. We also model the internal evolution of the planet, evaluating the roles of different radiogenic abundances and tidal heating and find that magnetic field generation is likely for billions of years. We find that if planet b formed in situ, then it experienced 169 +/- 13 million years in a runaway greenhouse as the star contracted during its formation. This early phase could remove up to 5 times as much water as in the modern Earth's oceans, possibly producing a large abiotic oxygen atmosphere. On the other hand, if Proxima Centauri b formed with a substantial hydrogen atmosphere (0.01 - 1% of the planet's mass), then this envelope could have shielded the water long enough for it to be retained before being blown off itself. After modeling this wide range of processes we conclude that water retention during the host star's pre-main sequence phase is the biggest obstacle for Proxima b's habitability. These results are all obtained with a new software package called VPLANET.
Battery life of cardiac implantable electronic devices explanted in funeral homes: a potential resource for underserved nations

ABSTRACT Introduction Cardiac implantable electronic devices (CIEDs) could still have adequate battery life and functionality when they are explanted after the death of the carrier, supposing an important resource for low- and middle- income countries where patients cannot afford new devices. Objective The aim was to analyze the remaining battery life and reusability of CIEDs recovered from funeral homes. Method A descriptive study of postmortem explanted CIEDs was conducted. Devices were collected from three funeral homes in the Spanish region of the Basque Country (participation rate 33.3%). Devices with a remaining battery life of >75% or > 4 years, preserved external integrity and no evidence of malfunction were considered reusable. Results A total of 188 CIEDs were collected (175 pacemakers and 13 defibrillators). Of the total number of devices, 95 (50.5%) had enough battery to be interrogated. Among the interrogable devices, a total of 20 pacemakers (22.4%) had an estimated battery life of more than 4 years, as well as preserved integrity and no record of malfunction. Conclusions A non-negligible number of postmortem explanted devices had battery life, external integrity and functionality to be considered reusable. Postmortem CIED donation could provide treatment to patients unable to afford new devices.
Constrained Dynamic Mode Decomposition

Frequency-based decomposition of time series data is used in many visualization applications. Most of these decomposition methods (such as Fourier transform or singular spectrum analysis) only provide interaction via pre- and post-processing, but no means to influence the core algorithm. A method that also belongs to this class is Dynamic Mode Decomposition (DMD), a spectral decomposition method that extracts spatio-temporal patterns from data. In this paper, we incorporate frequency-based constraints into DMD for an adaptive decomposition that leads to user-controllable visualizations, allowing analysts to include their knowledge into the process. To accomplish this, we derive an equivalent reformulation of DMD that implicitly provides access to the eigenvalues (and therefore to the frequencies) identified by DMD. By utilizing a constrained minimization problem customized to DMD, we can guarantee the existence of desired frequencies by minimal changes to DMD. We complement this core approach by additional techniques for constrained DMD to facilitate explorative visualization and investigation of time series data. With several examples, we demonstrate the usefulness of constrained DMD and compare it to conventional frequency-based decomposition methods.
A Role for Uncertainty in the Neural Distinction Between Social and Nonsocial Thought

Neuroimaging research has identified a network of brain regions that is consistently more engaged when people think about the minds of other people than when they engage in nonsocial tasks. Activations in this “mentalizing network” are sometimes interpreted as evidence for the domain-specificity of cognitive processes supporting social thought. Here, we examine the alternative possibility that at least some activations in the mentalizing network may be explained by uncertainty. A reconsideration of findings from existing functional MRI studies in light of new data from independent raters suggests that (a) social tasks used in past studies have higher levels of uncertainty than their nonsocial comparison tasks and (b) activation in a key brain region associated with social cognition, the dorsomedial prefrontal cortex (DMPFC), may track with the degree of uncertainty surrounding both social and nonsocial inferences. These observations suggest that the preferential DMPFC response observed consistently in social scenarios may reflect the engagement of domain-general processes of uncertainty reduction, which points to avenues for future research into the core cognitive mechanisms supporting typical and atypical social thought.
DIFFICULTY IN THE FORMATION OF COUNTER-ORBITING HOT JUPITERS FROM NEAR-COPLANAR HIERARCHICAL TRIPLE SYSTEMS: A SUB-STELLAR PERTURBER

Among 100 transiting planets with a measured projected spin–orbit angle λ, several systems are suggested to be counter-orbiting. While these cases may be due to the projection effect, the mechanism that produces a counter-orbiting planet has not been established. A promising scenario for counter-orbiting planets is the extreme eccentricity evolution in near-coplanar hierarchical triple systems with eccentric inner and outer orbits. We examine this scenario in detail by performing a series of systematic numerical simulations, and consider the possibility of forming hot Jupiters (HJs), especially a counter-orbiting one under this mechanism with a distant sub-stellar perturber. We incorporate quadrupole and octupole secular gravitational interaction between the two orbits, and also short-range forces (correction for general relativity, star and inner planetary tide, and rotational distortion) simultaneously. We find that most systems are tidally disrupted and that a small fraction of the surviving planets turn out to be prograde. The formation of counter-orbiting HJs in this scenario is possible only in a very restricted parameter region, and thus is very unlikely in practice.
KRAS Mutation in Pediatric Intracranial Germ Cell Tumors

Background: Intracranial germ cell tumors (IGCTs) are rare, highly curable neoplasms. KRAS is a gene in the KIT/RAS signaling pathway, and KRAS mutations have been reported in patients diagnosed with IGCTs. Objectives: To describe the clinicopathologic and molecular features of KRAS mutation and the treatment outcome of children diagnosed with IGCTs. Methods: Patients diagnosed with IGCTs at the Department of Pediatrics, King Chulalongkorn Memorial Hospital from 2007 to 2016 were retrospectively reviewed. DNA was extracted from formalin-fixed, paraffin-embedded tissue and used for molecular study. Mutations in codons 12, 13, and 61 of the KRAS gene were detected using the cobas® KRAS mutation test and pyrosequencing. Results: Eighteen patients were diagnosed with IGCTs (11 males and 7 females): nine with germinomas and nine with non-germinomatous GCTs (NGGCTs). The age range of the patients was 5–14 years (median 10.5 years). Elevated markers were revealed in approximately 25% of the patients. Four patients (two with germinomas and two with NGGCTs) had leptomeningeal involvement. All patients underwent tumor biopsy and received neoadjuvant chemotherapy. Radiotherapy was administered in 16 patients, and craniospinal radiation was administered only in patients with leptomeningeal metastasis. With a median follow-up of 26 months, overall survival was 88.9% in the patients with germinomas and 37% in the patients with NGGCTs. Mutation of the KRAS gene was detected using pyrosequencing in one patient. The mutation located at codon 61, with frequency 38.3% units, nucleotide substitution CAA > CTA, and amino acid substitution, was Q61L. The patient carrying the mutant gene was diagnosed with germinoma with cerebrospinal fluid metastasis and eventually died from treatment-related toxicity. Conclusion: Our study revealed the treatment outcomes of IGCTs in Thai children. The metastatic germinoma patient with KRAS codon 61 mutation had a poor outcome, supporting that Q61L has a clinical correlation with IGCTs.
Pragmatic platform trials to improve the outcome of patients with acute kidney injury

Purpose of review There is an important need for improved diagnostic strategies and treatment among patients with acute kidney injury (AKI). Classical randomized clinical trials have generated relevant results in AKI but are associated with shortcomings, such as high costs and sometimes lack of generalizability. In this minireview, we discuss the value and limits of pragmatic trials and platform trials for AKI research. Recent findings The implementation of pragmatic and platform trials in critical care settings has generated relevant clinical evidence impacting clinical practice. Pragmatic and platform designs have recently been applied to patients at risk of AKI and represent a crucial opportunity to advance our understanding of optimized treatment and strategies in patients at risk of AKI or presenting with AKI. Trials embedded in electronic health records can facilitate patient enrollment and data collection. Platform trials have allowed for a more efficient study design. Although both pragmatic and platform trials have several advantages, they also come with the challenges and shortcomings discussed in this review. Summary Pragmatic and platform trials can provide clinical answers in ‘real-life’ settings, facilitate a significant sample size enrollment at a limited cost, and provide results that can have a faster implementation in clinical practice.
Fully Automated EUCAST Rapid Antimicrobial Susceptibility Testing (RAST) from Positive Blood Cultures: Diagnostic Accuracy and Implementation

The objective of this study was to evaluate the accuracy and robustness of a fully automated EUCAST RAST (rapid antimicrobial susceptibility test) directly from positive blood culture and to appreciate its implementation constraints. This study was conducted in two phases: (i) spiked blood culture bottles (BCs) using 779 non-duplicate clinical isolates and (ii) a prospective clinical trial including 534 positive BCs sequentially processed in routine at the Bacteriology Laboratory of Geneva University Hospitals. ABSTRACT The objective of this study was to evaluate the accuracy and robustness of a fully automated EUCAST RAST (rapid antimicrobial susceptibility test) directly from positive blood culture and to appreciate its implementation constraints. This study was conducted in two phases: (i) spiked blood culture bottles (BCs) using 779 non-duplicate clinical isolates and (ii) a prospective clinical trial including 534 positive BCs sequentially processed in routine at the Bacteriology Laboratory of Geneva University Hospitals. The RAST results were assessed against EUCAST standardized disk diffusion testing results. Our first finding was that the results of the spiked BCs precisely predicted the clinical trial results. The overall categorical agreements for all species analyzed were greater than 95% at the different time points. RAST for Pseudomonas aeruginosa, however, raised several challenges. The categorical agreement for imipenem was lower than 95% at 6 h and was not improved with longer incubation times. Additionally, piperacillin-tazobactam, ceftazidime, and cefepime cannot be released at 6 h due to suboptimal performances, but the categorical agreement substantially improved at 8 h. Our results establish that the performance of fully automated EUCAST RAST directly from positive blood culture bottles is consistently robust, even for the detection of extended-spectrum β-lactamase (ESBL), carbapenemase-producing bacteria, and methicillin-resistant Staphylococcus aureus (MRSA). The automation markedly enhanced the percentage of readable inhibition zones and reduced the percentage of isolates categorized in the area of technical uncertainty (ATU). In summary, a fully automated EUCAST RAST can substantially improve laboratory workflow by reducing hands-on time and removing the strong constraints linked to manual read-outs at precisely defined times.
Hospitalisations of patients with cancer in the last stage of life. Reason to improve advance care planning?

Abstract Objective The aim of this study is to examine why patients are hospitalised in the last stage of life. Methods Our study was conducted in a large Dutch teaching hospital. We conducted a retrospective chart review of patients aged ≥18 years who died of cancer either during hospitalisation or after discharge to receive terminal care outside the hospital. We collected data about the characteristics of these hospitalisations and indicators of advance care planning. Results Of the 264 deceased patients, 56% had died in the hospital and 44% after hospital discharge. Of all patients, 80% had been admitted to the hospital because of symptom distress. Dyspnoea (39%) and pain (33%) were the most common symptoms. Most patients underwent diagnostic procedures (laboratory tests [97%] and radiology tests [91%]) and received medical treatment (analgesics [71%] and antibiotics [55%]) during their hospitalisation. A ‘Do‐Not‐Resuscitate’ code had been recorded before admission in 42% of the patients and in an additional 52% during admission. Conclusion Our study shows that patients with cancer in the last stage of life were mainly admitted to the hospital because of symptom distress. Some hospitalisations and in‐hospitals deaths may be avoided by more timely recognition of patients' impending death and start of advance care planning.
The Anticancer Effects of Novel Imidazo[1,2-a]Pyridine Compounds against HCC1937 Breast Cancer Cells

Background: Anticancer drugs confront clinical obstacles such as drug resistance and adverse effects. Imidazo[1,2-a]pyridines (IPs) compounds have lately gained considerable interest as possible anticancer therapeutics due to their potent inhibitory function against cancers cells. This study was to determine the anticancer activities of three novel IPs (IP-5, IP-6, and IP-7) against the HCC1937 breast cancer cell line in vitro. Materials and Methods: The cytotoxic and anti-proliferative effects of IPs compounds in HCC1937 cells were determined by cell viability (MTT) assay, trypan blue assay, and clonogenic survival assay. Scratch motility assay was used to test the antimigration ability of the IPs. Western blot analysis was carried out to detect the level of apoptosis and cell cycle protein markers and to understand the mechanism of action of IPs compounds. Results: IP-5 and IP-6 have a strong cytotoxic impact against HCC1937 cells with IC50 values of 45µM and 47. 7µM respectively. IP-7 possesses less cytotoxic effect against HCC1937 cells with IC50 of 79. 6µM. Trypan blue assay showed that the three compounds induce significant cell death in the HCC1937 cells. Clonogenic and mammosphere assays demonstrated that IP-5 reduced the HCC1937 cells survival rate by more than 25.0% at 1000 cell concentrations. Western blotting analysis showed that IP-5 compound causes cell cycle arrest as noted by the increasing levels of p53 and p21 in treated cells. IP-5 induced an extrinsic apoptosis pathway as reveals from the increased activity of caspase 7, caspase 8, and the increasing level of PARP cleavage in treated cells. Also, IP-5 treated cells revealed segmented chromatin which is characteristic of apoptotic cells as shown by DAPI stain. Importantly, In comparison to control cells, IP-5-treated cells exhibited lower levels of pAKT. Conclusions: The novel three IPs compounds represent potential active anticancer compounds against HCC1937 breast cancer cells in vitro.
Male pelvic multi-organ segmentation using token-based transformer Vnet

Objective. This work aims to develop an automated segmentation method for the prostate and its surrounding organs-at-risk in pelvic computed tomography to facilitate prostate radiation treatment planning. Approach. In this work, we propose a novel deep learning algorithm combining a U-shaped convolutional neural network (CNN) and vision transformer (VIT) for multi-organ (i.e. bladder, prostate, rectum, left and right femoral heads) segmentation in male pelvic CT images. The U-shaped model consists of three components: a CNN-based encoder for local feature extraction, a token-based VIT for capturing global dependencies from the CNN features, and a CNN-based decoder for predicting the segmentation outcome from the VIT’s output. The novelty of our network is a token-based multi-head self-attention mechanism used in the transformer, which encourages long-range dependencies and forwards informative high-resolution feature maps from the encoder to the decoder. In addition, a knowledge distillation strategy is deployed to further enhance the learning capability of the proposed network. Main results. We evaluated the network using: (1) a dataset collected from 94 patients with prostate cancer; (2) and a public dataset CT-ORG. A quantitative evaluation of the proposed network’s performance was performed on each organ based on (1) volume similarity between the segmented contours and ground truth using Dice score, segmentation sensitivity, and precision, (2) surface similarity evaluated by Hausdorff distance (HD), mean surface distance (MSD) and residual mean square distance (RMS), (3) and percentage volume difference (PVD). The performance was then compared against other state-of-art methods. Average volume similarity measures obtained by the network overall organs were Dice score = 0.91, sensitivity = 0.90, precision = 0.92, average surface similarities were HD = 3.78 mm, MSD = 1.24 mm, RMS = 2.03 mm; average percentage volume difference was PVD = 9.9% on the first dataset. The network also obtained Dice score = 0.93, sensitivity = 0.93, precision = 0.93, average surface similarities were HD = 5.82 mm, MSD = 1.16 mm, RMS = 1.24 mm; average percentage volume difference was PVD = 6.6% on the CT-ORG dataset. Significance. In summary, we propose a token-based transformer network with knowledge distillation for multi-organ segmentation using CT images. This method provides accurate and reliable segmentation results for each organ using CT imaging, facilitating the prostate radiation clinical workflow.