TextFormer: A Query-based End-to-End Text Spotter with Mixed Supervision

End-to-end text spotting is a vital computer vision task that aims to integrate scene text detection and recognition into a unified framework. Typical methods heavily rely on Region-of-Interest (RoI) operations to extract local features and complex post-processing steps to produce final predictions. To address these limitations, we propose TextFormer, a query-based end-to-end text spotter with Transformer architecture. Specifically, using query embedding per text instance, TextFormer builds upon an image encoder and a text decoder to learn a joint semantic understanding for multi-task modeling. It allows for mutual training and optimization of classification, segmentation, and recognition branches, resulting in deeper feature sharing without sacrificing flexibility or simplicity. Additionally, we design an Adaptive Global aGgregation (AGG) module to transfer global features into sequential features for reading arbitrarily-shaped texts, which overcomes the sub-optimization problem of RoI operations. Furthermore, potential corpus information is utilized from weak annotations to full labels through mixed supervision, further improving text detection and end-to-end text spotting results. Extensive experiments on various bilingual (i.e., English and Chinese) benchmarks demonstrate the superiority of our method. Especially on TDA-ReCTS dataset, TextFormer surpasses the state-of-the-art method in terms of 1-NED by 13.2%.Comment: MIR 2023, 15 page

OR-014 Chronic exercise potentiates anorectic effects of leptin in hypothalamic Pomc neurons

Objective Chronic imbalance of energy homeostasis leads to obesity and metabolic mellitus, which has developed as a major public health and economic burdens around the world. Disruption of “beige” fat mediated thermogenesis and hypothalamic neurons manipulated energy intake exaggerate this process. Multiple factors including hormonal regulation, fuel availability, and behavior contribute to energy utilization. The central nervous system (CNS) is critical for regulating energy balance and coordinating whole body metabolism. In the CNS, proopiomelanocortin (Pomc) neurons receive and integrate information about energy availability via responding to circulating hormones including insulin, leptin. Previous studies revealed that leptin receptors (LepRs) in arcuate Pomc neurons are required and sufficient for the proper regulation of energy balance and glucose homeostasis, including systemic insulin sensitivity and hepatic glucose production.  Exercise is an effective lifestyle intervention to combat obesity and metabolic diseases, which exerts many health benefits, including weight maintenance, appetite control, improved insulin sensitivity, improved mental health, and secondary prevention of chronic diseases such as obesity, type II diabetes mellitus, cancer, and hypertension. Moreover, the combined efficacy of exercise and dietary regimens on type two diabetes can surpass that of pharmacological interventions alone. Previous efforts aimed at identifying molecular mechanisms underlying the adaptive responses to exercise have mainly focused on the effects of exercise training in an organ or cell autonomous manner. However, the impact of exercise on performance, food intake after exercise, and more broadly, the healthy metabolic outcomes of exercise is not well-established. Despite the increased understanding of the importance of CNS underlying metabolic homeostasis, the specific neuronal groups and pathways that contribute to the metabolic responses during and following exercise remain largely unclear. In the current study, we aimed to investigate the role of exercise in mediating hypothalamic Pomc neuron activity, anorectic effects of leptin and glucose tolerance as well as insulin sensitivity.  Methods Animals All mice were housed under standard laboratory conditions (12 h on/off; lights on at 7:00 a.m.) and temperature-controlled environment with food and water available ad libitum. All experiments were performed in accordance with the guidelines established by the National Institute of Health Guide for the Care and Use of Laboratory Animals. Slice preparation and whole-cell recordings Male mice were deeply anesthetized with i.p. injection of 7% chloral hydrate and transcardially perfused with a modified ice-cold artificial CSF (ACSF) (described below). The mice were then decapitated, and the entire brain was removed and immediately submerged in ice-cold, carbogen-saturated (95% O2 and 5% CO2) ACSF (126 mM NaCl, 2.8 mM KCl, 1.2 mM MgCl2, 2.5 mM CaCl2, 1.25 mM NaH2PO4, 26 mM NaHCO3, and 5 mM glucose). Coronal sections (250 μm) were cut with a Leica VT1000S Vibratome and then incubated in oxygenated ACSF at room temperature for at least 1 h before recording. The slices were bathed in oxygenated ACSF (32 °C–34 °C) at a flow rate of ∼2 ml/min. All electrophysiology recordings were performed at room temperature. The pipette solution for whole-cell recording was modified to include an intracellular dye (Alexa Fluor350 hydrazide dye) for whole-cell recording: 120 mM K-gluconate, 10 mM KCl, 10 mM HEPES, 5 mM EGTA, 1 mM CaCl2, 1 mM MgCl2, and 2 mM MgATP, 0.03 mM Alexa Fluor 350 hydrazide dye (pH 7.3). Epifluorescence was briefly used to target fluorescent cells, at which time the light source was switched to infrared differential interference contrast imaging to obtain the whole-cell recording (Zeiss Axioskop FS2 Plus equipped with a fixed stage and a QuantEM:512SC electron-multiplying charge-coupled device camera). Electrophysiological signals were recorded using an Axopatch 700B amplifier (Molecular Devices), low-pass filtered at 2–5 kHz, and analyzed offline on a PC with pCLAMP programs (Molecular Devices). Membrane potential and firing rate were measured by whole-cell current clamp recordings from Pomc neurons in brain slices. Recording electrodes had resistances of 2.5–5 MΩ when filled with the K-gluconate internal solution. Input resistance was assessed by measuring voltage deflection at the end of the response to a hyperpolarizing rectangular current pulse steps (500 ms of −10 to −50 pA). Leptin (100 nM) was added to the ACSF for specific experiments. Solutions containing drug were typically perfused for 5 min. A drug effect was required to be associated temporally with peptide application, and the response had to be stable within a few minutes. A neuron was considered depolarized or hyperpolarized if a change in membrane potential was at least 2 mV in amplitude. Neurons were voltage-clamped at −75 mV (for excitatory postsynaptic currents) and −15 mV (for inhibitory postsynaptic currents). Frequency and peak amplitude were measured by using the Mini Analysis program (Synaptosoft, Inc.) Exercise protocols Motorized treadmills (Exer-6; Columbus Instruments, Columbus, OH) were used for exercise experiments. All mice were familiarized to the treadmills for 7 days prior to the exercise bout [Day 1: 5 min rest on the treadmill followed by running for 5 min at the speed of 8 m/min and then for 5 min at the speed of 10 m/min; Day 2-3: 5 min rest on the treadmill followed by running for 5 min at the speed of 10 m/min and then for 5 min at the speed of 12 m/min; Day 4-7: 5 min rest on the treadmill followed by running for 60 min at the speed of 12 m/min]. On Day 8, mice were subjected to a high intensity interval exercise (HIIE) bout to assess exercise-induced changes in plasma leptin, blood glucose, and food intake. Briefly, food was removed from all the mice at the start of the light cycle (7 AM) for a duration of 6 h, so as to eliminate any differences in food intake on the measured parameters. Mice were rested on the treadmill for 5 min prior to performing the 1 h of exercise consisting of 3 × 20 min intervals (5 min at the speed of 12 m/min, followed by 10 min at the speed of 17 m/min, and then 5 min at the speed of 22 m/min), without rest between intervals. Tolerance test and food intake For GTT, mice fasted for 16 h received an intraperitoneal injection of glucose (1 g/kg). For ITT, mice fasted for 6 h received an intraperitoneal injection of human insulin (0.75 IU/kg). Blood glucose concentrations were measured from tail blood at the indicated times using a One-Touch Ultra® glucometer (LifeScan Inc., Milpitas, CA). Food intake was measured hourly for 6 hours and then a single measurement at 24 hours. Results To assess the predominant role of exercise on the neuronal activation of hypothalamic Pomc neuron, electrophysiology studies was conducted on transgenic mice after treadmill habitation for 7 days. And we found that exercise significantly reduced food intake and enhanced glucose tolerance as well as insulin sensitivity. Notably, chronic exercise dramatically potentiates leptin-induced depolarization of Pomc neurons and exerts leptin induced anorectic effects in vivo and in vitro. Furthermore, gene assay demonstrated an upregulation of sirtin1 after exercise, suggest­­­­­ing a link between the exercise and key proteins involved in epigenetics, providing potential targets for the treatment of metabolic disease. Conclusions Our results demonstrated chronic exercise potentiates anorectic effects of leptin in hypothalamic Pomc neurons. Moreover, these data provide evidence for sirtin1 as a substrate of exercise to regulate food intake and glucose tolerance as well as leptin sensitivity via activating Pomc neurons

The pathophysiology of degenerative cervical myelopathy and the physiology of recovery following decompression

Background: Degenerative cervical myelopathy (DCM), also known as cervical spondylotic myelopathy is the leading cause of spinal cord compression in adults. The mainstay of treatment is surgical decompression, which leads to partial recovery of symptoms, however, long term prognosis of the condition remains poor. Despite advances in treatment methods, the underlying pathobiology is not well-known. A better understanding of the disease is therefore required for the development of treatments to improve outcomes following surgery. Objective: To systematically evaluate the pathophysiology of DCM and the mechanism underlying recovery following decompression. Methods: A total of 13,808 published articles were identified in our systematic search of electronic databases (PUBMED, WEB OF SCIENCE). A total of 51 studies investigating the secondary injury mechanisms of DCM or physiology of recovery in animal models of disease underwent comprehensive review. Results: Forty-seven studies addressed the pathophysiology of DCM. Majority of the studies demonstrated evidence of neuronal loss following spinal cord compression. A number of studies provided further details of structural changes in neurons such as myelin damage and axon degeneration. The mechanisms of injury to cells included direct apoptosis and increased inflammation. Only four papers investigated the pathobiological changes that occur in spinal cords following decompression. One study demonstrated evidence of axonal plasticity following decompressive surgery. Another study demonstrated ischaemic-reperfusion injury following decompression, however this phenomenon was worse when decompression was delayed. Conclusions: In preclinical studies, the pathophysiology of DCM has been poorly studied and a number of questions remain unanswered. The physiological changes seen in the decompressed spinal cord has not been widely investigated and it is paramount that researchers investigate the decompressed spinal cord further to enable the development of therapeutic tools, to enhance recovery following surgery

Corrigendum: The Pathophysiology of Degenerative Cervical Myelopathy and the Physiology of Recovery Following Decompression.

[This corrects the article DOI: 10.3389/fnins.2020.00138.]

Mechanism and Treatment Related to Oxidative Stress in Neonatal Hypoxic-Ischemic Encephalopathy

Hypoxic ischemic encephalopathy (HIE) is a type of neonatal brain injury, which occurs due to lack of supply and oxygen deprivation to the brain. It is associated with a high morbidity and mortality rate. There are several therapeutic strategies that can be used to improve outcomes in patients with HIE. These include cell therapies such as marrow mesenchymal stem cells (MSCs) and umbilical cord blood stem cells (UCBCs), which are being incorporated into the new protocols for the prevention of ischemic brain damage. The focus of this review is to discuss the mechanism of oxidative stress in HIE and summarize the current available treatments for HIE. We hope that a better understanding of the relationship between oxidative stress and HIE will provide new insights on the potential therapy of this devastating condition

Hydrodynamic Delivery of Chitosan-Folate-DNA Nanoparticles in Rats with Adjuvant-Induced Arthritis

50 kDa chitosan was conjugated with folate, a specific tissue-targeting ligand. Nanoparticles such as chitosan-DNA and folate-chitosan-DNA were prepared by coacervation process. The hydrodynamic intravenous injection of nanoparticles was performed in the right posterior paw in normal and arthritic rats. Our results demonstrated that the fluorescence intensity of DsRed detected was 5 to 12 times more in the right soleus muscle and in the right gastro muscle than other tissue sections. β-galactosidase gene expression with X-gal substrate and folate-chitosan-plasmid nanoparticles showed best coloration in the soleus muscle. Treated arthritic animals also showed a significant decrease in paw swelling and IL-1β and PGE2 concentration in serum compared to untreated rats. This study demonstrated that a nonviral gene therapeutic approach using hydrodynamic delivery could help transfect more efficiently folate-chitosan-DNA nanoparticles in vitro/in vivo and could decrease inflammation in arthritic rats

Efficient Nonviral Gene Therapy Using Folate-Targeted Chitosan-DNA Nanoparticles In Vitro

Nonviral cationic polymers like chitosan can be combined with DNA to protect it from degradation. The chitosan is a biocompatible, biodegradable, nontoxic, and cheap polycationic polymer with low immunogenicity. The objective of this study was to synthesize and then assess different chitosan-DNA nanoparticles and to select the best ones for selective in vitro transfection in human epidermoid carcinoma (KB) cell lines. It revealed that different combinations of molecular weight, the presence or absence of folic acid ligand, and different plasmid DNA sizes can lead to nanoparticles with various diameters and diverse transfection efficiencies. The intracellular trafficking, nuclear uptake, and localization are also studied by confocal microscopy, which confirmed that DNA was delivered to cell nuclei to be expressed

Dumbbell shaped craniorbital cavernous hemangioma.

BACKGROUND: Cavernous hemangioma of the orbit is a benign tumor mostly located behind the eye globe, but it rarely spread into the brain, which is called cerebral cavernous malformation as well, the lesion in the brain is irregular and enlarged blood. Here we report one particular case of craniorbital cavernous hemangioma. CASE PRESENTATION: A 53-year-old woman presented with exophthalmos of the right eye and reduced vision. Computerized tomographical (CT) scan showed osteolytic honeycomb radial changes of the outer plate of the skull. A magnetic resonance imaging (MRI) scan was performed to obtain further details. T1-weighted (T1W) imaging showed slightly low signal mixed with small patchy high signal. T2-weighted (T2W) imaging showed uneven high signal. There was obvious enhancement in the middle and no enhancement in the peripheral bars. A surgically manage was performed using a left frontotemporal approach, the tumor excised fully, and the histopathology results revealed a cavernous hemangioma. The patient recovered well in the follow-up. Post-operative CT scan identified the lesion was successfully resected, MRI scan also showed full resection and enhanced signal from the presence of fat. CONCLUSIONS: Craniorbital cavernous hemangioma is uncommon, however within the cranium, they can lead to numerous complications particularly if affecting the visual apparatus. it could be diagnosed by imaging, which CT scan shows osteolytic honeycomb radial changes of the outer plate of the skull, T1W imaging shows slightly low signal mixed with small patchy high signal, T2W imaging shows uneven high signal, it is obvious enhancement in the middle and no enhancement in the peripheral bars. The surgically manage is the ideally treatment when there are some symptoms

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery