Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Impact of Inhibitory G-Protein Signaling Pathways in Ventral Tegmental Area Dopamine Neurons on Behavioral Sensitivity to Cocaine and Morphine

Abstract Drugs of abuse engage overlapping but distinct molecular and cellular mechanisms to enhance dopamine (DA) signaling in the mesocorticolimbic circuitry. DA neurons of the ventral tegmental area (VTA) are key substrates of drugs of abuse and have been implicated in addiction-related behaviors. Enhanced VTA DA neurotransmission evoked by drugs of abuse can engage inhibitory G-protein-dependent feedback pathways, mediated by GABAB receptors (GABABRs) and D2 DA receptors (D2Rs). Chemogenetic inhibition of VTA DA neurons potently suppressed baseline motor activity, as well as the motor-stimulatory effect of cocaine and morphine, confirming the critical influence of VTA DA neurons and inhibitory G-protein signaling in these neurons on this addiction-related behavior. To resolve the relative influence of GABABR-dependent and D2R-dependent signaling pathways in VTA DA neurons on behavioral sensitivity to drugs of abuse, we developed a neuron-specific viral CRISPR/Cas9 approach to ablate D2R and GABABR in VTA DA neurons. Ablation of GABABR or D2R did not impact baseline physiological properties or excitability of VTA DA neurons, but it did preclude the direct somatodendritic inhibitory influence of GABABR or D2R activation. D2R ablation potentiated the motor-stimulatory effect of cocaine in male and female mice, whereas GABABR ablation selectively potentiated cocaine-induced activity in male subjects only. Neither D2R nor GABABR ablation impacted morphine-induced motor activity. Collectively, our data show that cocaine and morphine differ in the extent to which they engage inhibitory G-protein-dependent feedback pathways in VTA DA neurons and highlight key sex differences that may impact susceptibility to various facets of addiction.
Ibrutinib modulates Aβ/tau pathology, neuroinflammation, and cognitive function in mouse models of Alzheimer's disease

We previously demonstrated that ibrutinib modulates LPS‐induced neuroinflammation in vitro and in vivo, but its effects on the pathology of Alzheimer's disease (AD) and cognitive function have not been investigated. Here, we investigated the effects of ibrutinib in two mouse models of AD. In 5xFAD mice, ibrutinib injection significantly reduced Aβ plaque levels by promoting the non‐amyloidogenic pathway of APP cleavage, decreased Aβ‐induced neuroinflammatory responses, and significantly downregulated phosphorylation of tau by reducing levels of phosphorylated cyclin‐dependent kinase‐5 (p‐CDK5). Importantly, tau‐mediated neuroinflammation and tau phosphorylation were also alleviated by ibrutinib injection in PS19 mice. In 5xFAD mice, ibrutinib improved long‐term memory and dendritic spine number, whereas in PS19 mice, ibrutinib did not alter short‐ and long‐term memory but promoted dendritic spinogenesis. Interestingly, the induction of dendritic spinogenesis by ibrutinib was dependent on the phosphorylation of phosphoinositide 3‐kinase (PI3K). Overall, our results suggest that ibrutinib modulates AD‐associated pathology and cognitive function and may be a potential therapy for AD.
Development of a Heart Rate Variability Risk Score to Predict Organ Dysfunction and Death in Critically Ill Children

Supplemental Digital Content is available in the text. OBJECTIVES: Determine whether the Heart Rate Variability Dysfunction score, a novel age-normalized measure of autonomic nervous system dysregulation, is associated with the development of new or progressive multiple organ dysfunction syndrome or death in critically ill children. DESIGN, SETTING, AND PATIENTS: This was a retrospective, observational cohort study from 2012 to 2018. Patients admitted to the PICU with at least 12 hours of continuous heart rate data available from bedside monitors during the first 24 hours of admission were included in the analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Heart rate variability was measured using the integer heart rate variability, which is the sd of the heart rate sampled every 1 second over 5 consecutive minutes. The Heart Rate Variability Dysfunction score was derived from age-normalized values of integer heart rate variability and transformed, so that higher scores were indicative of lower integer heart rate variability and a proxy for worsening autonomic nervous system dysregulation. Heart Rate Variability Dysfunction score performance as a predictor of new or progressive multiple organ dysfunction syndrome and 28-day mortality were determined using the area under the receiver operating characteristic curve. Of the 7,223 patients who met inclusion criteria, 346 patients (4.8%) developed new or progressive multiple organ dysfunction syndrome, and 103 (1.4%) died by day 28. For every one-point increase in the median Heart Rate Variability Dysfunction score in the first 24 hours of admission, there was a 25% increase in the odds of new or progressive multiple organ dysfunction syndrome and a 51% increase in the odds of mortality. The median Heart Rate Variability Dysfunction score in the first 24 hours had an area under the receiver operating characteristic curve to discriminate new or progressive multiple organ dysfunction syndrome of 0.67 and to discriminate mortality of 0.80. These results were reproducible in a temporal validation cohort. CONCLUSIONS: The Heart Rate Variability Dysfunction score, an age-adjusted proxy for autonomic nervous system dysregulation derived from bedside monitor data is independently associated with new or progressive multiple organ dysfunction syndrome and mortality in PICU patients. The Heart Rate Variability Dysfunction score could potentially be used as a single continuous physiologic biomarker or as part of a multivariable prediction model to increase awareness of at-risk patients and augment clinical decision-making.
An updated review on exosomes: biosynthesis to clinical applications

Abstract Exosomes are membrane-based extracellular vesicles naturally released by the cells. Nano size range of exosomes and unique properties such as stability, biocompatibility and low immunogenicity are key parameters, which make them suitable as nanoparticulate drug delivery system and also considered as promising delivery carriers for future clinical use. This review outlines the composition, biogenesis, isolation and characterisation methods along with biological and clinical applications of exosomes. Further, the biopharmaceutical features of exosomes include loading method, modified exosomes and potential use of exosomes for different diseases are well explained with the current case studies. We well elaborate the future directions for clinical use of exosomes as drug delivery platforms.
Comparative anatomic and morphometric examination of the interosseous muscle, sesamoid ligaments and flexor tendons of the fetlock in South American camelids

This study presents a comparative morphological and morphometrical examination of the interosseous muscle (IOM), digital flexor tendons and associated structures of all four species of South American Camelids (SACs): Lama (Lama glama), alpaca (Vicugna pacos), guanaco (Lama guanicoe) and vicuna (Vicugna vicugna). Our findings show that the lamoid interosseous muscle and digital flexor tendons are very similar between species and differences, which have been reported previously, are possibly due to diverging examiner interpretation. Lumbricalis muscles were mostly found as single muscles in this study. The definition of the terminal and dorsal branches of the interosseous muscle is critically revised. The analysis of morphometric data indicates that the size of the individual has a substantial influence on the cross‐sectional area (CSA) of the examined structures. Metacarpal/metatarsal bone width is a main predictor of CSA, while the factor species only shows significance in specific sample points. For lama and alpaca, no differences in CSA in relation to species as factor were found. The IOM shows the largest CSAs of the three examined structures in all species, which implies an important load‐bearing function. Considerable individual variation remains unexplained by the mentioned factors. This lowers the prospect of CSA reaching diagnostic importance in SAC fetlock pathology.
Dynamics of T Lymphocyte between the Periphery and the Brain from the Acute to the Chronic Phase Following Ischemic Stroke in Mice

Stroke causes systemic immunosuppression. T lymphocytes are involved in infarct size in the early stages of stroke. However, the phenotypes of T lymphocytes and their functions in peripheral immune organs and the brain have not been well analyzed in the acute and chronic phases of stroke. Here, we investigated pathological phenotypic alterations in the systemic immune response, especially changes in T lymphocytes, from one day to six months after ischemic stroke in mice. Impairment in thymocyte numbers, development, proliferation, and apoptosis were observed for up to two weeks. The number of mature T cells in the spleen and blood decreased and showed reduced interferon-γ production. Increased numbers of CD4-CD8-CD3+ double-negative T cells were observed in the mouse brain during the early stages of stroke, whereas interleukin (IL)-10+Foxp3+ regulatory T lymphocytes increased from two weeks during the chronic phase. These phenotypes correlated with body weight and neurological severity scores. The recovery of T lymphocyte numbers and increases in IL-10+Foxp3+ regulatory T lymphocytes may be important for long-term neurological outcomes. Dynamic changes in T lymphocytes between the acute and chronic phases may play different roles in pathogenesis and recovery. This study provides fundamental information regarding the T lymphocyte alterations from the brain to the peripheral immune organs following stroke.
Sarcopenia is poor risk for unfavorable short- and long-term outcomes in stage I non-small cell lung cancer

Background Sarcopenia characterized by skeletal muscle loss may influence postoperative outcomes through physical decline and weakened immunity. We aimed to investigate clinical significance of sarcopenia in resected early-stage non-small cell lung cancer (NSCLC). Methods We retrospectively reviewed 315 consecutive patients with pathologic stage I NSCLC who had undergone lobectomy with systematic nodal dissection. Sarcopenia was defined as the lowest quartile of psoas muscle area on the 3rd vertebra on the high-resolution computed tomography (HRCT) image. Clinicopathological variables were used to investigate the correlation to postoperative complications as well as overall and recurrence-free survival. Results Upon multivariable analysis, male sex [odds ratio (OR) =5.780, 95% confidence interval (CI): 2.681–12.500, P<0.001], and sarcopenia (OR =21.00, 95% CI: 10.30–42.80, P<0.001) were independently associated with postoperative complications. The sarcopenia group showed significantly lower 5-over all survival (84.4% vs. 69.1%, P<0.001) and recurrence-free survival (77.2% vs. 62.0%, P<0.001) comparing with the non-sarcopenia group. In a multivariable analysis, sarcopenia was an independent prognostic factor [hazard ratio (HR) =1.978, 95% CI: 1.177–3.326, P=0.010] together with age ≥70 years (HR =1.956, 95% CI: 1.141–3.351, P=0.015) and non-adenocarcinoma histology (HR =1.958, 95% CI: 1.159–3.301, P=0.016). Conclusions This is the first study which demonstrates that preoperative sarcopenia is significantly associated with unfavorable postoperative complications as well as long-term survival in pathologic stage I NSCLC. This readily available factor on HRCT may provide valuable information to consider possible choice of surgical procedure and perioperative management.
The Effect of Vertebral Augmentation Procedure on Painful OVCFs: A Meta-Analysis of Randomized Controlled Trials

Study Design: Meta-analysis. Objective: To systematically compare the effectiveness and safety of vertebral augmentation procedure (VAP) with non-surgical management (NSM) for the treatment of osteoporotic vertebrate compression fractures (OVCFs). Methods: Systematic reviews and meta-analyses with the comparison between VAP and NSM were identified to extract randomized controlled trials from electronic database. Additionally, recently published RCTs were identified. Two researchers independently extracted the data. The primary outcome of this meta-analysis was pain relief evaluated by visual analogue scale (VAS). Results: Twenty RCTs involving 2566 patients with painful OVCFs were included. Significant differences were found between percutaneous vertebroplasty (PVP) and conservative treatment (CT) in VAS at each time point during follow-up period. The differences of VAS were not significant between PVP and sham procedure at most time points during follow-up period. In subgroup analysis based on fracture type and fracture location, significant differences of VAS were found between PVP and CT and were not found between PVP and sham procedure. In subgroup analysis of duration of back pain, significant differences were found between PVP and CT in VAS at 1 week, 3 month and 1 year. And the differences of VAS were not significant between PVP and CT at 1 month and 6 month. Conclusion: BKP is considered sufficient to achieve good clinical outcomes. PVP is associated with on beneficial effect on treatment of painful OVCFs compared with sham procedure. The indication and timing of VAP need further research. More independently high-quality RCTs with sufficiently large sample sizes reporting cost-effectiveness are needed.
Artificial intelligence in gastric cancer: a translational narrative review

Increasing clinical contributions and novel techniques have been made by artificial intelligence (AI) during the last decade. The role of AI is increasingly recognized in cancer research and clinical application. Cancers like gastric cancer, or stomach cancer, are ideal testing grounds to see if early undertakings of applying AI to medicine can yield valuable results. There are numerous concepts derived from AI, including machine learning (ML) and deep learning (DL). ML is defined as the ability to learn data features without being explicitly programmed. It arises at the intersection of data science and computer science and aims at the efficiency of computing algorithms. In cancer research, ML has been increasingly used in predictive prognostic models. DL is defined as a subset of ML targeting multilayer computation processes. DL is less dependent on the understanding of data features than ML. Therefore, the algorithms of DL are much more difficult to interpret than ML, even potentially impossible. This review discussed the role of AI in the diagnostic, therapeutic and prognostic advances of gastric cancer. Models like convolutional neural networks (CNNs) or artificial neural networks (ANNs) achieved significant praise in their application. There is much more to be fully covered across the clinical administration of gastric cancer. Despite growing efforts, adapting AI to improving diagnoses for gastric cancer is a worthwhile venture. The information yield can revolutionize how we approach gastric cancer problems. Though integration might be slow and labored, it can be given the ability to enhance diagnosing through visual modalities and augment treatment strategies. It can grow to become an invaluable tool for physicians. AI not only benefits diagnostic and therapeutic outcomes, but also reshapes perspectives over future medical trajectory.
Ocean warming and species range shifts affect rates of ecosystem functioning by altering consumer-resource interactions.

Recent warming trends have driven widespread changes in the performance and distribution of species in many regions, with consequent shifts in assemblage structure and ecosystem functioning. However, as responses to warming vary across species and regions, novel communities are emerging, particularly where warm-affinity range-expanding species have rapidly colonised communities still dominated by cold-affinity species. Such community reconfiguration may alter core ecosystem processes, such as productivity or nutrient cycling, yet it remains unclear whether novel communities function similarly to those they have replaced, and how continued warming will alter functioning in the near future. Using simplified kelp forest communities as a model system, we compared rates of respiration, consumption and secondary productivity between current cold-affinity and future warm-affinity kelp assemblages under both present-day temperatures and near future warming in a series of mesocosm experiments. Overall, respiration rates of gastropods and amphipods increased with warming but did not differ between cold and warm affinity kelp assemblages. Consumption rates of three consumers (urchin, gastropod and amphipod) differed between kelp assemblages but only amphipod consumption rates increased with warming. A diet derived from warm-affinity kelp assemblages led to a decrease in growth and biomass of urchins, whereas the response of other consumers was variable depending on temperature treatment. These results suggest that climate-driven changes in assemblage structure of primary producers will alter per capita rates of ecosystem functioning, and that specific responses may vary in complex and unpredictable ways, with some mediated by warming more than others. Understanding how differences in life history and functional traits of dominant species will affect ecological interactions and, in turn, important ecosystem processes is crucial to understanding the wider implications of climate-driven community reconfiguration.
On the Description of Symmetry of OD Structure (II) The Parameters

For the relative position of layers, the parameters are studied in detail. The number of independent parameters for an OD groupoid family may be determined by means of a table. Proposals are made for an extension of the symbols of some OD groupoid families, in order to give a full set of independent parameters. Rules for the linear dependence of parameters are examined. Die Parameter, die die Relativlage von Schichten beschreiben, werden genauer untersucht. Die Anzahl der unabhangigen Parameter fur eine OD-Gruppoid-Familie kann mit Hilfe einer Tabelle bestimmt werden. Zur Angabe eines vollstandigen Satzes unabhangiger Parameter ist bei einer Reihe von OD-Gruppoid-Familien eine Erweiterung der Symbole erforderlich. Es werden Regeln uber die lineare Abhangigkeit von Parametern angegeben.
The Co‐mutational Spectrum Determines the Therapeutic Response in Murine FGFR2 Fusion‐Driven Cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and a highly lethal malignancy. Chemotherapeutic options are limited, but a considerable subset of patients harbors genetic lesions for which targeted agents exist. Fibroblast growth factor receptor 2 (FGFR2) fusions belong to the most frequent and therapeutically relevant alterations in ICC, and the first FGFR inhibitor was recently approved for the treatment of patients with progressed, fusion‐positive ICC. Response rates of up to 35% indicate that FGFR‐targeted therapies are beneficial in many but not all patients. Thus far, no established biomarkers exist that predict resistance or response to FGFR‐targeted therapies in patients with ICC.
Event-Triggered Adaptive Neural Control for Fractional-Order Nonlinear Systems Based on Finite-Time Scheme

This article addresses the finite-time event-triggered adaptive neural control for fractional-order nonlinear systems. Based on the backstepping technique, a novel adaptive event-triggered control scheme is proposed, and finite-time stability criteria are introduced with the aim to ensure that the tracking error enters into a small region around the origin in finite time. Finally, the stability of the closed-loop system is ensured via a fractional Lyapunov function theory and two simulation examples were used to prove the validity of the designed control scheme.
The predictive value of urinary kidney injury molecular-1 for long-term graft function in kidney transplant patients: a prospective study

Background Monitoring allograft function during the early stages is crucial, and therefore requires biomarkers more sensitive than serum creatinine (Scr). Kidney injury molecular-1 (KIM-1) is a potent biomarker; however, disparities exist in the literature concerning its predictive value in allograft function. Therefore, this study aimed to evaluate its predictive value for the long-term prognosis of kidney transplantation patients. Methods A prospective study with a cohort comprising 160 patients scheduled for kidney transplantation was conducted to evaluate the predictive power of urinary KIM-1 (uKIM-1) and other renal ischemia-reperfusion biomarkers including urinary L-type fatty acid binding protein (uL-FABP), urinary N-acetyl-β-D glucosaminidase (uNAG), and urinary neutrophil gelatinase-related lipoprotein (uNGAL) for allograft prognosis. Results One hundred and forty kidney recipients who were admitted to our hospital between September 2014 and December 2017 with a median follow-up of 30.3 months were included. Thirty-seven recipients had functional delayed graft function (fDGF) in the first week post transplantation, and 42 recipients had progressed to allograft dysfunction [estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2] by the end of the study, while nine recipients deteriorated into allograft loss (defined by the initiation of dialysis). The levels of uKIM-1 in the fDGF group were higher than those in the immediate graft function (IGF) recipients (P<0.05) at 0 hour post transplantation [5.885 (4.420–7.913) vs. 4.605 (3.417–5.653) ng/mmol], and on the first day post transplantation [5.569 (4.181–6.722) vs. 4.002 (3.222–6.488) ng/mmol]. The levels of uL-FABP in the fDGF group were also higher than those in the IGF group at 0 hour post transplantation (89.818±39.332 vs. 69.187±37.926 µg/mmol) and on the third day post transplantation [77.835 (60.368–100.678) vs. 66.841 (28.815–89.783) µg/mmol]. Multivariate Cox regression analysis demonstrated that recipients with higher uKIM-1 levels on the first day post transplantation had a 23.5% increase in the risk of developing fDGF and a 27.3% increase in the risk of prolonged renal allograft dysfunction. Conclusions uKIM-1 on the first day post transplantation can predict short-term graft function and is a potent biomarker for the long-term prognosis of graft function.
Two-Stage Selective Ensemble of CNN via Deep Tree Training for Medical Image Classification

Medical image classification is an important task in computer-aided diagnosis systems. Its performance is critically determined by the descriptiveness and discriminative power of features extracted from images. With rapid development of deep learning, deep convolutional neural networks (CNNs) have been widely used to learn the optimal high-level features from the raw pixels of images for a given classification task. However, due to the limited amount of labeled medical images with certain quality distortions, such techniques crucially suffer from the training difficulties, including overfitting, local optimums, and vanishing gradients. To solve these problems, in this article, we propose a two-stage selective ensemble of CNN branches via a novel training strategy called deep tree training (DTT). In our approach, DTT is adopted to jointly train a series of networks constructed from the hidden layers of CNN in a hierarchical manner, leading to the advantage that vanishing gradients can be mitigated by supplementing gradients for hidden layers of CNN, and intrinsically obtain the base classifiers on the middle-level features with minimum computation burden for an ensemble solution. Moreover, the CNN branches as base learners are combined into the optimal classifier via the proposed two-stage selective ensemble approach based on both accuracy and diversity criteria. Extensive experiments on CIFAR-10 benchmark and two specific medical image datasets illustrate that our approach achieves better performance in terms of accuracy, sensitivity, specificity, and F1 score measurement.