Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti-Nogo-A antibody promotes brain function recovery after cardiopulmonary resuscitation in rats by reducing apoptosis

Brain injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) is the main cause of neurological dysfunction and death in cardiac arrest. To assess the effect of Nogo-A antibody on brain function in rats following CPR and to explore the underlying mechanisms, CA/CPR (ventricular fibrillation) rats were divided into the CPR+Nogo-A, CPR+saline and sham groups. Hippocampal caspase-3 levels were detected by RT-PCR and immunoblotting. Next, Nogo-A, glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), cysteinyl aspartate specific proteinase-12 (casapse-12), Bcl-2 and Bax protein levels in the hippocampus were detected by immunoblotting. Coronal brain sections were analyzed by TUNEL assay to detect apoptosis at 72 h, while Nissl staining and electron microscopy were performed to detect Nissl bodies and microstructure at 24 h, respectively. Finally, rats were assessed for neurologic deficits at various times. Nissl staining revealed morphological improvement after Nogo-A antibody treatment. Sub-organelle structure was preserved as assessed by electron microscopy in model animals post-antibody treatment; neurological function was improved as well (P<0.05), while the apoptosis index was decreased (26.2±9.85 vs. 46.6±12.95%; P<0.05). Hippocampal caspase-3 mRNA and protein, Nogo-A protein levels were significantly decreased after antibody treatment (P<0.05). Hippocampal Nogo-A expression was positively correlated with caspase-3 (Pearson's correlation; r=0.790, P=0.000). Hippocampal GRP78 and Bcl-2 protein levels were higher after antibody treatment than these levels noted in the model animals (P<0.05), while CHOP, caspase-12 and Bax levels were reduced (P<0.05). Nogo-A antibody ameliorates neurological function after restoration of spontaneous circulation (ROSC), possibly by suppressing apoptosis induced by endoplasmic reticulum stress.
Formyl Peptide Receptor-1 Blockade Prevents Receptor Regulation by Mitochondrial Danger-Associated Molecular Patterns and Preserves Neutrophil Function After Trauma.

OBJECTIVES Trauma predisposes to systemic sterile inflammation (systemic inflammatory response syndrome) as well as infection, but the mechanisms linking injury to infection are poorly understood. Mitochondrial debris contains formyl peptides. These bind formyl peptide receptor-1, trafficking neutrophils to wounds, initiating systemic inflammatory response syndrome, and wound healing. Bacterial formyl peptides, however, also attract neutrophils via formyl peptide receptor-1. Thus, mitochondrial formyl peptides might suppress neutrophils antimicrobial function. Also, formyl peptide receptor-1 blockade used to mitigate systemic inflammatory response syndrome might predispose to sepsis. We examined how mitochondrial formyl peptides impact neutrophils functions contributing to antimicrobial responses and how formyl peptide receptor-1 antagonists affect those functions. DESIGN Prospective study of human and murine neutrophils and clinical cohort analysis. SETTING University research laboratory and level 1 trauma center. PATIENTS Trauma patients, volunteer controls. ANIMAL SUBJECTS C57Bl/6, formyl peptide receptor-1, and formyl peptide receptor-2 knockout mice. INTERVENTIONS Human and murine neutrophils functions were activated with autologous mitochondrial debris, mitochondrial formyl peptides, or bacterial formyl peptides followed by chemokines or leukotrienes. The experiments were repeated using formyl peptide receptor-1 antagonist cyclosporin H, "designer" human formyl peptide receptor-1 antagonists (POL7178 and POL7200), or anti-formyl peptide receptor-1 antibodies. Mouse injury/lung infection model was used to evaluate effect of formyl peptide receptor-1 inhibition. MEASUREMENTS AND MAIN RESULTS Human neutrophils cytosolic calcium, chemotaxis, reactive oxygen species production, and phagocytosis were studied before and after exposure to mitochondrial debris, mitochondrial formyl peptides, and bacterial formyl peptides. Mitochondrial formyl peptide and bacterial formyl peptides had similar effects on neutrophils. Responses to chemokines and leukotrienes were suppressed by prior exposure to formyl peptides. POL7200 and POL7178 were specific antagonists of human formyl peptide receptor-1 and more effective than cyclosporin H or anti-formyl peptide receptor-1 antibodies. Formyl peptides inhibited mouse neutrophils responses to chemokines only if formyl peptide receptor-1 was present. Formyl peptide receptor-1 blockade did not inhibit neutrophils bacterial phagocytosis or reactive oxygen species production. Cyclosporin H increased bacterial clearance in lungs after injury. CONCLUSIONS Formyl peptides both activate and desensitize neutrophils. Formyl peptide receptor-1 blockade prevents desensitization, potentially both diminishing systemic inflammatory response syndrome and protecting the host against secondary infection after tissue trauma or primary infection.
Problem drinking alters gray matter volume and food cue responses of the lateral orbitofrontal cortex

Alcohol misuse is associated with significant energy deficits. As feeding involves multiple sensory, cognitive, and affective processes, low food intake in problem drinkers likely reflects alterations in both regional and inter‐regional responses. To investigate the effects of problem drinking on feeding‐related neural activities and connectivities, we examined functional magnetic resonance imaging (fMRI) data in 82 drinkers who viewed palatable food and nonfood images in alternating blocks. Drinking severity was assessed with the Alcohol Use Disorders Identification Test (AUDIT). A whole‐brain multiple regression with AUDIT scores as the predictor showed a negative correlation between drinking severity and activation to food vs nonfood cues in the lateral orbitofrontal cortex (lOFC). AUDIT scores were also negatively correlated with the gray matter volume (GMV) of the lOFC and regions that responded preferentially to food stimuli, including the left middle frontal gyrus, bilateral middle insula, and occipital cortices. Connectivity strength between the lOFC and these regions was negatively modulated by drinking severity. In contrast, there was no relationship between AUDIT scores and lOFC connectivity with regions that did not show either selectivity to food images or GMV loss. A mediation analysis further suggested that alcohol misuse may have compromised lOFC's structural integrity, which in turn disrupted lOFC interactions with regions that support the processing of visual food cues. Overall, the findings provide evidence for the effects of problem drinking on the brain substrates of feeding, potentially shedding light on the neural mechanisms underlying energy deficits in at‐risk drinkers.
Histologic Evaluation of Nonvisual Afferent Sensory Upper Eyelid Proprioception

Purpose: Recent research has suggested a possible role for proprioception in ipsilateral frontalis activation in the setting of ptosis; however, there has not been any robust histologic or anatomic evidence to support this theory. To further elucidate proprioceptive structures in the eyelid, this investigation uses validated histologic techniques to explore the presence of proprioceptive structures or afferent neural networks in the Levator Palpebrae Superioris (LPS) and Müller muscle. Methods: Müller muscle and LPS samples were evaluated by a laboratory with extensive experience with the histology of extraocular muscle proprioception. Immunofluorescence and confocal laser scanning microscopy were used to analyze the tissue samples. Results: Thirty-four Müller muscle samples and 10 LPS samples were analyzed. Golgi tendon bodies and muscle spindles were not identified in the Müller muscle and LPS samples. This result is expected in the Müller muscle given that these structures are not typically present in smooth muscle, but noteworthy in the skeletal muscle of the LPS. Previously undescribed synaptophysin-positive free nerve terminals within the intermuscular connective tissue of the Müller muscle were identified. Conclusions: The nerve terminals identified are anatomically consistent with free nerve endings present in the extraocular muscles that have been implicated in proprioception. These findings advance our current knowledge of the ultrastructure of Müller muscle and the LPS and suggest a possible mechanism for proprioception in the upper eyelid that may have a role in ipsilateral brow elevation in the setting of ptosis. The authors describe proprioception in the upper eyelid: A histologic analysis.
Effect of Heterointerface on NO2 Sensing Properties of In-Situ Formed TiO2 QDs-Decorated NiO Nanosheets

In this work, TiO2 QDs-modified NiO nanosheets were employed to improve the room temperature NO2 sensing properties of NiO. The gas sensing studies showed that the response of nanocomposites with the optimal ratio to 60 ppm NO2 was nearly 10 times larger than that of bare NiO, exhibiting a potential application in gas sensing. Considering the commonly reported immature mechanism that the effective charge transfer between two phases contributes to an enhanced sensitivity, the QDs sensitization mechanism was further detailed by designing a series of contrast experiments. First, the important role of the QDs size effect was revealed by comparing the little enhanced sensitivity of TiO2 particle-modified NiO with the largely enhanced sensitivity of TiO2 QDs-NiO. Second, and more importantly, direct evidence of the heterointerface charge transfer efficiency was detailed by the extracted interface bond (Ti-O-Ni) using XPS peak fitting. This work can thus provide guidelines to design more QDs-modified nanocomposites with higher sensitivity for practical applications.
Multimodal pipe-climbing robot with origami clutches and soft modular legs

In nature, climbing trees and pipes of varying diameters or even navigating inside of hollow pipes and tree holes is easy for some climbing animals and insects. However, today’s pipe-climbing robots, which are important for automatically conducting periodic inspections and maintenance of pipelines to save time and keep humans away from hazardous environments, are designed mainly for a specific task, limiting their adaptability to different working scenarios and further implementation in real-life. In this paper, we propose a pipe-climbing robot with a soft linear actuator for bioinspired propulsion, two origami clutches to realize multi-degrees-of-freedom (DoF) motion and two pairs of soft modular legs for multimodal climbing. Design, modeling and experimental validation of the origami clutch are introduced in detail. Preliminary experimental results show that we can achieve a stroke of up to 289.6% and a maximum 45° bending angle on the soft linear actuator by regulating the air pressure inside the soft actuator and origami clutches. Additionally, by choosing the leg-type, three climbing modes, including out-pipe versatile mode, out-pipe high-force mode and in-pipe mode can be realized for particular working scenarios. A prototype climbing robot demonstrates that in out-pipe versatile mode, the robot can climb on the exterior of pipes made of various materials including PVC, rubber and metal with diameters ranging from 105 to 117 mm. In the out-pipe high-force mode, the climber can navigate along a specific pipe carrying maximum 675 g external load at the top or 200 g hanging from the bottom, as well as keeping functional without failure under static loads as high as 1968 g. In the in-pipe mode, the robot is able to travel inside pipes. This research might bridge the design gap between in-pipe and out-pipe climbing robots while offering an alternative option for soft robots to execute multi-DoF motion.
CT Prostate Segmentation Based on Synthetic MRI-aided Deep Attention Fully Convolution Network.

PURPOSE Accurate segmentation of the prostate on computed tomography (CT) for treatment planning is challenging due to CT's poor soft-tissue contrast. Magnetic resonance imaging (MRI) has been used to aid prostate delineation, but its final accuracy is limited by MRI-CT registration errors. We developed a deep attention-based segmentation strategy on CT-based synthetic MRI (sMRI) to deal with the CT prostate delineation challenge without MRI acquisition. METHODS AND MATERIALS We developed a prostate segmentation strategy which employs an sMRI-aided deep attention network to accurately segment the prostate on CT. Our method consists of three major steps. First, a cycle generative adversarial network was used to estimate an sMRI from CT images. Second, a deep attention fully convolution network was trained based on sMRI and the prostate contours deformed from MRIs. Attention models were introduced to pay more attention to prostate boundary. The prostate contour for a query patient was obtained by feeding the patient's CT images into the trained sMRI generation model and segmentation model. RESULTS The segmentation technique was validated with a clinical study of 49 patients by leave-one-out experiments and validated with an additional 50 patients by hold-out test. The Dice similarity coefficient, Hausdorff distance and mean surface distance indices between our segmented and deformed MRI-defined prostate manual contours were 0.92±0.09, 4.38±4.66 mm, and 0.62±0.89 mm, respectively, with leave-one-out experiments, and were 0.91±0.07, 4.57±3.03 mm, and 0.62±0.65 mm, respectively, with hold-out test. CONCLUSION We have proposed a novel CT-only prostate segmentation strategy using CT-based sMRI, and validated its accuracy against the prostate contours that were manually drawn on MRI images and deformed to CT images. This technique could provide accurate prostate volume for treatment planning without requiring MRI acquisition, greatly facilitating the routine clinical workflow.
Synthesis, Bioapplications, and Toxicity Evaluation of Chitosan-Based Nanoparticles

The development of advanced nanomaterials and technologies is essential in biomedical engineering to improve the quality of life. Chitosan-based nanomaterials are on the forefront and attract wide interest due to their versatile physicochemical characteristics such as biodegradability, biocompatibility, and non-toxicity, which play a promising role in biological applications. Chitosan and its derivatives are employed in several applications including pharmaceuticals and biomedical engineering. This article presents a comprehensive overview of recent advances in chitosan derivatives and nanoparticle synthesis, as well as emerging applications in medicine, tissue engineering, drug delivery, gene therapy, and cancer therapy. In addition to the applications, we critically review the main concerns and mitigation strategies related to chitosan bactericidal properties, toxicity/safety using tissue cultures and animal models, and also their potential environmental impact. At the end of this review, we also provide some of future directions and conclusions that are important for expanding the field of biomedical applications of the chitosan nanoparticles.
INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFR amplified glioblastoma

Abstract Background Depatuxizumab mafodotin (Depatux-M) is a tumor-specific antibody–drug conjugate consisting of an antibody (ABT-806) directed against activated epidermal growth factor receptor (EGFR) and the toxin monomethylauristatin-F. We investigated Depatux-M in combination with temozolomide or as a single agent in a randomized controlled phase II trial in recurrent EGFR amplified glioblastoma. Methods Eligible were patients with centrally confirmed EGFR amplified glioblastoma at first recurrence after chemo-irradiation with temozolomide. Patients were randomized to either Depatux-M 1.25 mg/kg every 2 weeks intravenously, or this treatment combined with temozolomide 150–200 mg/m2 day 1–5 every 4 weeks, or either lomustine or temozolomide. The primary endpoint of the study was overall survival. Results Two hundred sixty patients were randomized. In the primary efficacy analysis with 199 events (median follow-up 15.0 mo), the hazard ratio (HR) for the combination arm compared with the control arm was 0.71 (95% CI = 0.50, 1.02; P = 0.062). The efficacy of Depatux-M monotherapy was comparable to that of the control arm (HR = 1.04, 95% CI = 0.73, 1.48; P = 0.83). The most frequent toxicity in Depatux-M treated patients was a reversible corneal epitheliopathy, occurring as grades 3–4 adverse events in 25–30% of patients. In the long-term follow-up analysis with median follow-up of 28.7 months, the HR for the comparison of the combination arm versus the control arm was 0.66 (95% CI = 0.48, 0.93). Conclusion This trial suggests a possible role for the use of Depatux-M in combination with temozolomide in EGFR amplified recurrent glioblastoma, especially in patients relapsing well after the end of first-line adjuvant temozolomide treatment. (NCT02343406)
African Swine Fever Epidemiology and Control.

African swine fever is a devastating disease that can result in death in almost all infected pigs. The continuing spread of African swine fever from Africa to Europe and recently to the high-pig production countries of China and others in Southeast Asia threatens global pork production and food security. The African swine fever virus is an unusual complex DNA virus and is not related to other viruses. This has presented challenges for vaccine development, and currently none is available. The virus is extremely well adapted to replicate in its hosts in the sylvatic cycle in East and South Africa. Its spread to other regions, with different wildlife hosts, climatic conditions, and pig production systems, has revealed unexpected epidemiological scenarios and different challenges for control. Here we review the epidemiology of African swine fever in these different scenarios and methods used for control. We also discuss progress toward vaccine development and research priorities to better understand this complex disease and improve control. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 8 is February 15, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Single cell transcriptome atlas of the Drosophila larval brain

Cell diversity of the brain and how it is affected by starvation, remains largely unknown. Here, we introduce a single cell transcriptome atlas of the entire Drosophila first instar larval brain. We first assigned cell-type identity based on known marker genes, distinguishing five major groups: neural progenitors, differentiated neurons, glia, undifferentiated neurons and non-neural cells. All major classes were further subdivided into multiple subtypes, revealing biological features of various cell-types. We further assessed transcriptional changes in response to starvation at the single-cell level. While after starvation the composition of the brain remains unaffected, transcriptional profile of several cell clusters changed. Intriguingly, different cell-types show very distinct responses to starvation, suggesting the presence of cell-specific programs for nutrition availability. Establishing a single-cell transcriptome atlas of the larval brain provides a powerful tool to explore cell diversity and assess genetic profiles from developmental, functional and behavioral perspectives.
Prediction of crucial epigenetically-associated, differentially expressed genes by integrated bioinformatics analysis and the identification of S100A9 as a novel biomarker in psoriasis

Psoriasis is one of the most common immune-mediated inflammatory diseases of the skin. The identification of the pivotal molecular mechanisms responsible for the disease pathogenesis may lead to the development of novel therapeutic options. The present study aimed to identify pivotal differentially expressed genes (DEGs) and methylated DEGs in psoriasis. The raw data from gene microarrays were obtained from the Gene Expression Omnibus database. The data were processed using packages in Bioconductor. In total, 352 upregulated and 137 downregulated DEGs were identified. The upregulated DEGs were primarily enriched in the 'innate immune defense' response and the 'cell cycle'. The down-regulated DEGs were primarily enriched in 'cell adhesion' and 'tight junction pathways'. A total of 95 methylated DEGs were identified, which were significantly enriched in the 'interleukin (IL)-17 signaling pathway' and the 'response to interferon'. Based on a comprehensive evaluation of all algorithms in cytoHubba, the key epigenetic-associated hub genes (S100A9, SELL, FCGR3B, MMP9, S100A7, IL7R, IRF7, CCR7, IFI44, CXCL1 and LCN2) were screened out. In order to further validate these genes, the present study constructed a model of imiquimod (IMQ)-induced psoriasiform dermatitis using mice. The levels of these hub genes were increased in the IMQ group. The knockdown of methylation-regulating enzyme ten-eleven translocation (TET) 2 expression in mice attenuated the expression levels of S100A9, SELL, IL7R, MMP9, CXCL1 and LCN2. Furthermore, the hydroxymethylated level of S100A9 was highly expressed in the IMQ group and was significantly decreased by TET2 deficiency in mice. On the whole, using an integrative system bioinformatics approach, the present study identified a series of characteristic enrichment pathways and key genes that may serve as potential biomarkers in psoriasis.
A Perspective on the Development of TGF-β Inhibitors for Cancer Treatment

Transforming growth factor (TGF)-β is a secreted multifunctional cytokine that signals via plasma membrane TGF-β type I and type II receptors and intercellular SMAD transcriptional effectors. Aberrant inter- and intracellular TGF-β signaling can contribute to cancer progression. In normal cells and early stages of cancer, TGF-β can stimulate epithelial growth arrest and elicit a tumor suppressor function. However, in late stages of cancer, when the cytostatic effects of TGF-β in cancer cells are blocked, TGF-β signaling can act as tumor promoter by its ability to stimulate epithelial-to-mesenchymal transition of cancer cells, by stimulating angiogenesis, and by promoting evasion of immune responses. In this review, we will discuss the rationale and challenges of targeting TGF-β signaling in cancer and summarize the clinical status of TGF-β signaling inhibitors that interfere with TGF−β bioavailability, TGF-β/receptor interaction, or TGF-β receptor kinase function. Moreover, we will discuss targeting of TGF-β signaling modulators and downstream effectors as well as alternative approaches by using promising technologies that may lead to entirely new classes of drugs.