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Background: Osteochondral autologous transplantation (OAT) has been widely used in the treatment of osteochondral lesion of the talus (OLT). Previous studies have reported successful outcomes following the use of osteochondral autogenous grafts from the intercondylar notch of the knee or a non-weight-bearing region of the femoral condyle. However, donor-site morbidity of the knee joint has been observed in several cases. This study aimed to investigate the outcomes and safety of OAT with autografts from the ipsilateral lateral talar articular facet as an alternative donor site for medial OLT. Methods: Among 40 patients who underwent OAT, 29 patients were excluded. Eleven patients who underwent OAT with an osteochondral graft harvested from the ipsilateral lateral talar articular facet from 2011 to 2022 were retrospectively analyzed. The size of OLT was measured on ankle magnetic resonance imaging, including coronal length, sagittal length, depth, and area. Clinical outcomes were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale and a visual analog scale (VAS). Weight-bearing ankle radiographs were obtained postoperatively and at 1 year after surgery. Results: The average follow-up time after surgery was 64.7 months (range, 14-137 months). The average diameter of lesions was 8.8 mm (range, 8-9.9 mm). The average size of lesions was 51.2 mm2 (range, 33.6-71.3 mm2) , and all lesions included subchondral cysts. The average depth of lesions was 7.3 mm (range, 6.2-9.1 mm). Graft sizes ranged from 8 to 10 mm in diameter (8 mm, n = 1; 10 mm, n = 10) All measured clinical outcomes improved postoperatively, including the AOFAS scores (preoperative, 55.4 ± 9.0; 1-year follow-up, 92.1 ± 7.6; p = 0.001) and VAS scores (preoperative, 5.5 ± 0.7; 1-year follow-up, 1.9 ± 0.8; p = 0.001). All weight-bearing ankle radiographs of the graft and donor sites did not reveal arthritic change in the ankle joint, lateral talar dome collapse, and graft-site delayed union or nonunion at 1 year after surgery. Conclusions: For a single medial OLT, harvesting autografts from the ipsilateral lateral talar articular facet without knee donor-site morbidities can be a good alternative in OAT for OLT.
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Transplante Ósseo , Tálus , Transplante Autólogo , Humanos , Tálus/cirurgia , Masculino , Feminino , Adulto , Estudos Retrospectivos , Transplante Ósseo/métodos , Pessoa de Meia-Idade , Cartilagem Articular/cirurgia , Adulto Jovem , Autoenxertos , Adolescente , Imageamento por Ressonância Magnética , Resultado do TratamentoRESUMO
Simultaneous monitoring of critical parameters (e.g., pressure, shear, and temperature) at bony prominences is essential for the prevention of pressure injuries in a systematic manner. However, the development of wireless sensor array for accurate mapping of risk factors has been limited due to the challenges in the convergence of wireless technologies and wearable sensor arrays with a thin and small form factor. Herein, a battery-free, wireless, miniaturized multi-modal sensor array is introduced for continuous mapping of pressure, shear, and temperature at skin interfaces. The sensor array includes an integrated pressure and shear sensor consisting of 3D strain gauges and micromachined components. The mechanically decoupled design of the integrated sensor enables reliable data acquisition of pressure and shear at skin interfaces without the need for additional data processing. The sensor platform enables the analysis of interplay among localized pressure, shear, and temperature in response to changes in the patient's movement, posture, and bed inclination. The validation trials using a novel combination of wireless sensor arrays and customized pneumatic actuator demonstrate the efficacy of the platform in continuous monitoring and efficient redistribution of pressure and shear without repositioning, thereby improving the patient's quality of life.
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For successful human-robot collaboration, it is crucial to establish and sustain quality interaction between humans and robots, making it essential to facilitate human-robot interaction (HRI) effectively. The evolution of robot intelligence now enables robots to take a proactive role in initiating and sustaining HRI, thereby allowing humans to concentrate more on their primary tasks. In this paper, we introduce a system known as the Robot-Facilitated Interaction System (RFIS), where mobile robots are employed to perform identification, tracking, re-identification, and gesture recognition in an integrated framework to ensure anytime readiness for HRI. We implemented the RFIS on an autonomous mobile robot used for transporting a patient, to demonstrate proactive, real-time, and user-friendly interaction with a caretaker involved in monitoring and nursing the patient. In the implementation, we focused on the efficient and robust integration of various interaction facilitation modules within a real-time HRI system that operates in an edge computing environment. Experimental results show that the RFIS, as a comprehensive system integrating caretaker recognition, tracking, re-identification, and gesture recognition, can provide an overall high quality of interaction in HRI facilitation with average accuracies exceeding 90% during real-time operations at 5 FPS.
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Gestos , Robótica , Robótica/métodos , Humanos , Reconhecimento Automatizado de Padrão/métodos , Algoritmos , Inteligência ArtificialRESUMO
In semiconductor fabrication (FAB), wafers are placed into carriers known as Front Opening Unified Pods (FOUPs), transported by the Overhead Hoist Transport (OHT). The OHT, a type of Automated Guided Vehicle (AGV), moves along a fixed railway network in the FAB. The routes of OHTs on the railway network are typically determined by a Single Source Shortest Path (SSSP) algorithm such as Dijkstra's. However, the presence of hundreds of operating OHTs often leads to path interruptions, causing congestion or deadlocks that ultimately diminish the overall productivity of the FAB. This research focused on identifying structurally vulnerable links within the OHT railway network in semiconductor FAB and developing a visualization system for enhanced on-site decision-making. We employed betweenness centrality as a quantitative index to evaluate the structural vulnerability of the OHT railway network. Also, to accommodate the unique hierarchical node-port structure of this network, we modified the traditional Brandes algorithm, a widely-used method for calculating betweenness centrality. Our modification of the Brandes algorithm integrated node-port characteristics without increasing computation time while incorporating parallelization to reduce computation time further and improve usability. Ultimately, we developed an end-to-end web-based visualization system that enables users to perform betweenness centrality calculations on specific OHT railway layouts using our algorithm and view the results through a web interface. We validated our approach by comparing our results with historically vulnerable links provided by Samsung Electronics. The study had two main outcomes: the development of a new betweenness centrality calculation algorithm considering the node-port structure and the creation of a visualization system. The study demonstrated that the node-port structure betweenness centrality effectively identified vulnerable links in the OHT railway network. Presenting these findings through a visualization system greatly enhanced their practical applicability and relevance.
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Algoritmos , Ferrovias , SemicondutoresRESUMO
Mosquitoes are the most notorious arthropod vectors of viral and parasitic diseases for which approximately half the world's population, ~4,000,000,000, is at risk. Integrated pest management programs (IPMPs) have achieved some success in mitigating the regional transmission and persistence of these diseases. However, as many vector-borne diseases remain pervasive, it is obvious that IPMP successes have not been absolute in eradicating the threat imposed by mosquitoes. Moreover, the expanding mosquito geographic ranges caused by factors related to climate change and globalization (travel, trade, and migration), and the evolution of resistance to synthetic pesticides, present ongoing challenges to reducing or eliminating the local and global burden of these diseases, especially in economically and medically disadvantaged societies. Abatement strategies include the control of vector populations with synthetic pesticides and eco-friendly technologies. These "green" technologies include SIT, IIT, RIDL, CRISPR/Cas9 gene drive, and biological control that specifically targets the aquatic larval stages of mosquitoes. Regarding the latter, the most effective continues to be the widespread use of Lysinibacillus sphaericus (Ls) and Bacillus thuringiensis subsp. israelensis (Bti). Here, we present a review of the health issues elicited by vector mosquitoes, control strategies, and lastly, focus on the biology of Ls and Bti, with an emphasis on the latter, to which no resistance has been observed in the field.
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Proprotein convertase subtilisin/kexin type-9 (PCSK9) binds to and degrades low-density lipoprotein (LDL) receptor, leading to increase of LDL cholesterol in blood. Its blockers have emerged as promising therapeutics for cardiovascular diseases. Here we show that PCSK9 itself directly induces inflammation and aggravates atherosclerosis independently of the LDL receptor. PCSK9 exacerbates atherosclerosis in LDL receptor knockout mice. Adenylyl cyclase-associated protein 1 (CAP1) is the main binding partner of PCSK9 and indispensable for the inflammatory action of PCSK9, including induction of cytokines, Toll like receptor 4, and scavenger receptors, enhancing the uptake of oxidized LDL. We find spleen tyrosine kinase (Syk) and protein kinase C delta (PKCδ) to be the key mediators of inflammation after PCSK9-CAP1 binding. In human peripheral blood mononuclear cells, serum PCSK9 levels are positively correlated with Syk, PKCδ, and p65 phosphorylation. The CAP1-fragment crystallizable region (CAP1-Fc) mitigates PCSK9-mediated inflammatory signal transduction more than the PCSK9 blocking antibody evolocumab does.
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Aterosclerose , Pró-Proteína Convertase 9 , Animais , Camundongos , Humanos , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo , NF-kappa B/metabolismo , Leucócitos Mononucleares/metabolismo , Aterosclerose/metabolismo , Receptores de LDL/metabolismo , Inflamação , LDL-Colesterol , Camundongos KnockoutRESUMO
BACKGROUND: Skin aging is characterized by wrinkles, rough skin texture, pigmentation, facial erythema, and telangiectasia through structural and functional changes in the epidermis and dermis. Recently, injectable poly(D, L-lactic acid), a biodegradable polymer, has been used widely for skin rejuvenation. AIMS: This study aims to assess the efficacy and safety of injectable dermal poly D, L-lactic acid) for skin rejuvenation. PATIENTS/METHODS: A total of 16 patients who desired skin rejuvenation were included. All participants received two or three procedure sessions with a 4 weeks interval between sessions. Clinical and three-dimensional images at baseline, before each procedural session, and follow-up visits were obtained. Therapeutic effects were assessed by evaluating signs of aging skin and overall improvement by dermatologists and patients. Histologic examinations with special stains were performed on the posterior auricular areas of consenting patients at baseline and follow-up visits after injecting poly D L-lactic acid into the postauricular area as in the face. RESULTS: Overall, statistically significant differences were observed in all signs of aging skin, such as fine wrinkles, skin texture, irregular pigmentation, telangiectasia, and facial erythema before and after treatments. Half (50%) of patients responded that there was more than 50% overall improvement. There were no severe adverse events. Histologic examination demonstrated increases in collagen and elastic fibers in the dermis. CONCLUSIONS: Results of this preliminary study suggest that injectable dermal poly D, L-lactic acid can significantly affect skin rejuvenation without causing any serious adverse events.
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Técnicas Cosméticas , Envelhecimento da Pele , Telangiectasia , Humanos , Ácido Hialurônico/efeitos adversos , Rejuvenescimento , Técnicas Cosméticas/efeitos adversos , Eritema/etiologia , Telangiectasia/tratamento farmacológico , Ácido Láctico/efeitos adversos , Resultado do Tratamento , Satisfação do PacienteRESUMO
BACKGROUND: Basal cell carcinoma (BCC) is the most common type of skin cancer. In patients with darker skin, most BCCs are pigmented. Studies suggest that increased pigmentation in BCC may be inversely associated with tumor aggressiveness. OBJECTIVE: This study analyzed the dermoscopic features and histopathologic patterns of BCCs to evaluate the correlation between BCC pigmentation and tumor aggressiveness. METHODS: A total of 76 BCC lesions were included in this retrospective study. The Mohs micrographic surgery (MMS) stage and tumor depth were measured as indices of tumor aggressiveness. The Fontana-Masson stain was performed for the identification of melanin, and immunohistochemical analysis was performed using Melan-A and HMB-45 to identify melanocytes. RESULTS: In MMS stage 1, the dermoscopic pigmentation value was 34.48%±14.22% (mean±standard deviation). In MMS stages 2 and 3, dermoscopic pigmentations were 13.72%±7.54% and 15.50%±17.52%, respectively. In the logistic regression model, higher dermoscopic pigmentation (95% confidence interval [CI], 0.68~0.99), melanin (95% CI, 0.63~0.89), and melanocyte-stained areas (95% CI, 0.70~0.92) were associated with a lower possibility of BCC tumor infiltration over the middle and lower layers. CONCLUSION: We found an inverse correlation between the pigmentation and aggressiveness of BCCs. Clinicians can predict the subclinical infiltration depth of BCC on the basis of the pigmentation observed on dermoscopy. Pigmentation can be considered a favorable prognostic factor for BCC.
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The Lysinibacillus sphaericus proteins Tpp49Aa1 and Cry48Aa1 can together act as a toxin toward the mosquito Culex quinquefasciatus and have potential use in biocontrol. Given that proteins with sequence homology to the individual proteins can have activity alone against other insect species, the structure of Tpp49Aa1 was solved in order to understand this protein more fully and inform the design of improved biopesticides. Tpp49Aa1 is naturally expressed as a crystalline inclusion within the host bacterium, and MHz serial femtosecond crystallography using the novel nanofocus option at an X-ray free electron laser allowed rapid and high-quality data collection to determine the structure of Tpp49Aa1 at 1.62 Å resolution. This revealed the packing of Tpp49Aa1 within these natural nanocrystals as a homodimer with a large intermolecular interface. Complementary experiments conducted at varied pH also enabled investigation of the early structural events leading up to the dissolution of natural Tpp49Aa1 crystals-a crucial step in its mechanism of action. To better understand the cooperation between the two proteins, assays were performed on a range of different mosquito cell lines using both individual proteins and mixtures of the two. Finally, bioassays demonstrated Tpp49Aa1/Cry48Aa1 susceptibility of Anopheles stephensi, Aedes albopictus, and Culex tarsalis larvae-substantially increasing the potential use of this binary toxin in mosquito control.
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Bacillaceae , Bacillus , Culex , Praguicidas , Animais , Bacillaceae/química , Bacillaceae/metabolismo , Controle de Mosquitos , Larva/metabolismoRESUMO
With an increasing demand for noninvasive skin rejuvenation techniques, several light-based devices have been introduced. Due to its ability to deliver thermal energy from the superficial to deeper levels of the dermis, a combined triple-wavelength laser (755 nm, 810 nm, and 1064 nm) can be used for skin rejuvenation. The objective of this study was to assess the effectiveness and safety of a combined triple-wavelength laser for skin rejuvenation. A total of 28 female patients seeking skin rejuvenation treatment were included. All patients underwent five consecutive treatment sessions at a two-week interval. Clinical improvement of aging-related cutaneous change was noted by the treating dermatologists and patients. Biopsies were performed on the faces of consenting patients before and two weeks after the final treatment. Significant clinical improvements were observed by both patients and evaluating dermatologists. Based on the patient satisfaction questionnaire, 78% of patients reported a self-assessed improvement of more than 25%. Additionally, 86% of patients showed an improvement of more than 25% on objective assessment by dermatologists. Histopathological findings revealed increased collagen and elastic bundles throughout the dermis. Except for transient pain during treatment, no serious adverse effects were reported. The findings of this study suggest that the combined triple-wavelength laser may be an effective and safe nonablative option for skin rejuvenation.
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Rejuvenescimento , Pele , Humanos , Feminino , Administração Cutânea , Biópsia , LasersRESUMO
BACKGROUND: Various operative methods for the treatment of Morton's neuroma have been discussed, and osteotomy of the metatarsal bone has been reported recently. However, there has been no report of pedobarographic changes after metatarsal osteotomy. Pedobarographic changes of other metatarsal area after the surgery may cause transfer metatarsalgia, and thorough analysis of the pedobarographic data should be performed peri-operatively. The purpose of this study is to investigate the post-operative pedobarographic changes of sliding osteotomy of the 3rd metatarsal bone for treating Morton's neuroma. METHODS: Forty patients (45 feet) who underwent metatarsal sliding osteotomy of the 3rd metatarsal bone for treating Morton's neuroma from November 2013 to December 2021 were retrospectively reviewed. Proximal sliding osteotomy was performed at the proximal 3rd metatarsal bone through dorsal approach. Clinical outcomes were evaluated with American Orthopaedic Foot and Ankle Society Lesser Metatarsophalangeal Interphalangeal Scale (AOFAS LMIS), Foot Function Index (FFI), and Visual Analogue Scale (VAS). Plain radiograph and pedobarogram were performed to evaluate the radiologic and pedobarographic outcomes. RESULTS: AOFAS score was improved from 52.8 ± 9.0 (18-62) to 88.8 ± 9.8 (78-100) and FFI was improved from 61.8 ± 4.9 (50-70) to 32.2 ± 5.1 (23-42) on average. The 3rd metatarsal bone was shortened by 3.1 ± 0.8 mm and dorsally shifted by 1.5 ± 0.4 mm after the surgery. Plantar intermetatarsal distances between 2nd and 3rd and 3rd and 4th metatarsal heads were significantly increased post-operatively. Average forefoot pressure and maximum pressure of the 2nd to 4th metatarsal head were not significantly changed between pre-operatively and post-operatively. CONCLUSION: Proximal metatarsal sliding osteotomy of the 3rd metatarsal bone shows a satisfactory result in both clinical and pedobarographical evaluations. It could be an effective treatment of permanent indirect decompression of Morton's neuroma with avoiding recurred neuroma, adhesion of tissue, paresthesia, and transfer metatarsalgia.
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The three most important commercial bacterial insecticides are all derived from subspecies of Bacillus thuringiensis (Bt). Specifically, Bt subsp. kurstaki (Btk) and Bt subsp. aizawai (Bta) are used to control larval lepidopteran pests. The third, Bt subsp. israelensis (Bti), is primarily used to control mosquito and blackfly larvae. All three subspecies produce a parasporal body (PB) during sporulation. The PB is composed of insecticidal proteins that damage the midgut epithelium, initiating a complex process that results in the death of the insect. Among these three subspecies of Bt, Bti is unique as it produces the most complex PB consisting of three compartments. Each compartment is bound by a multilaminar fibrous matrix (MFM). Two compartments contain one protein each, Cry11Aa1 and Cyt1Aa1, while the third contains two, Cry4Aa1/Cry4Ba1. Each compartment is packaged independently before coalescing into the mature spherical PB held together by additional layers of the MFM. This distinctive packaging process is unparalleled among known bacterial organelles, although the underlying molecular biology is yet to be determined. Here, we present structural and molecular evidence that the MFM has a hexagonal pattern to which Bti proteins Bt152 and Bt075 bind. Bt152 binds to a defined spot on the MFM during the development of each compartment, yet its function remains unknown. Bt075 appears to be derived from a bacteriophage major capsid protein (MCP), and though its sequence has markedly diverged, it shares striking 3-D structural similarity to the Escherichia coli phage HK97 Head 1 capsid protein. Both proteins are encoded on Bti's pBtoxis plasmid. Additionally, we have also identified a six-amino acid motif that appears to be part of a novel molecular process responsible for targeting the Cry and Cyt proteins to their cytoplasmic compartments. This paper describes several previously unknown features of the Bti organelle, representing a first step to understanding the biology of a unique process of sorting and packaging of proteins into PBs. The insights from this research suggest a potential for future applications in nanotechnology.
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This paper proposes a physics-informed neural network (PINN) for predicting the early-age time-dependent behaviors of prestressed concrete beams. The PINN utilizes deep neural networks to learn the time-dependent coupling among the effective prestress force and the several factors that affect the time-dependent behavior of the beam, such as concrete creep and shrinkage, tendon relaxation, and changes in concrete elastic modulus. Unlike traditional numerical algorithms such as the finite difference method, the PINN directly solves the integro-differential equation without the need for discretization, offering an efficient and accurate solution. Considering the trade-off between solution accuracy and the computing cost, optimal hyperparameter combinations are determined for the PINN. The proposed PINN is verified through the comparison to the numerical results from the finite difference method for two representative cross sections of PSC beams.
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This article presents a wireless and wearable body-pressure-monitoring system for the on-site, real-time prevention of pressure injuries for immobilized patients. For the prevention of pressure-induced skin injuries, a wearable pressure sensor system is designed to monitor the pressure at multiple sites on the skin and to alert the danger of prolonged application of pressure on the skin with a pressure-time integral (PTI) algorithm. The wearable sensor unit is developed using a pressure sensor based on a liquid metal microchannel and integrated with a flexible printed circuit board that includes a thermistor-type temperature sensor. The wearable sensor unit array is connected to the readout system board for the transmission of measured signals to a mobile device or PC via Bluetooth communication. We evaluate the pressure-sensing performances of the sensor unit and the feasibility of the wireless and wearable body-pressure-monitoring system through an indoor test and a preliminary clinical test at the hospital. It is shown that the presented pressure sensor has high-quality performance with excellent sensitivity to detect both high and low pressure. The proposed system measures the pressure at bony sites on the skin for about six hours continuously without any disconnection or failure, and the PTI-based alarming system operates successfully in the clinical setup. The system measures the pressure applied to the patient and provides meaningful information from the measured data for early diagnosis and prevention of bedsores to doctors, nurses, and healthcare workers.
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Pele , Dispositivos Eletrônicos Vestíveis , Humanos , Diagnóstico Precoce , Monitorização FisiológicaRESUMO
Peripheral nerve injuries cause various disabilities related to loss of motor and sensory functions. The treatment of these injuries typically requires surgical operations for improving functional recovery of the nerve. However, capabilities for continuous nerve monitoring remain a challenge. Herein, a battery-free, wireless, cuff-type, implantable, multimodal physical sensing platform for continuous in vivo monitoring of temperature and strain from the injured nerve is introduced. The thin, soft temperature, and strain sensors wrapped around the nerve exhibit good sensitivity, excellent stability, high linearity, and minimum hysteresis in relevant ranges. In particular, the strain sensor integrated with circuits for temperature compensation provides reliable, accurate strain monitoring with negligible temperature dependence. The system enables power harvesting and data communication to wireless, multiple implanted devices wrapped around the nerve. Experimental evaluations, verified by numerical simulations, with animal tests, demonstrate the feasibility and stability of the sensor system, which has great potential for continuous in vivo nerve monitoring from an early stage to complete regeneration.
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Fontes de Energia Elétrica , Próteses e Implantes , Animais , Temperatura , Tecnologia sem FioRESUMO
BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDA), with its highly metastatic propensity, is one of the most lethal subtypes of pancreatic cancer. Although recent large-scale transcriptomic studies have demonstrated that heterogeneous gene expressions play an essential role in determining molecular phenotypes of PDA, biological cues for and consequences of distinct transcriptional programs remain unclear. METHODS: We developed an experimental model that enforces the transition of PDA cells toward a basal-like subtype. We combined epigenome and transcriptome analyses with extensive in vitro and in vivo evaluations of tumorigenicity to demonstrate the validity of basal-like subtype differentiation in association with endothelial-like enhancer landscapes via TEA domain transcription factor 2 (TEAD2). Finally, we used loss-of-function experiments to investigate the importance of TEAD2 in regulating reprogrammed enhancer landscape and metastasis in basal-like PDA cells. RESULTS: Aggressive characteristics of the basal-like subtype are faithfully recapitulated in vitro and in vivo, demonstrating the physiological relevance of our model. Further, we showed that basal-like subtype PDA cells acquire a TEAD2-dependent proangiogenic enhancer landscape. Genetic and pharmacologic inhibitions of TEAD2 in basal-like subtype PDA cells impair their proangiogenic phenotypes in vitro and cancer progression in vivo. Last, we identify CD109 as a critical TEAD2 downstream mediator that maintains constitutively activated JAK-STAT signaling in basal-like PDA cells and tumors. CONCLUSIONS: Our findings implicate a TEAD2-CD109-JAK/STAT axis in the basal-like differentiated pancreatic cancer cells and as a potential therapeutic vulnerability.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Pâncreas/patologia , Diferenciação Celular , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição de Domínio TEA , Neoplasias PancreáticasRESUMO
The water solubility of molecules is one of the most important properties in various chemical and medical research fields. Recently, machine learning-based methods for predicting molecular properties, including water solubility, have been extensively studied due to the advantage of effectively reducing computational costs. Although machine learning-based methods have made significant advances in predictive performance, the existing methods were still lacking in interpreting the predicted results. Therefore, we propose a novel multi-order graph attention network (MoGAT) for water solubility prediction to improve the predictive performance and interpret the predicted results. We extracted graph embeddings in every node embedding layer to consider the information of diverse neighboring orders and merged them by attention mechanism to generate a final graph embedding. MoGAT can provide the atomic-specific importance scores of a molecule that indicate which atoms significantly influence the prediction so that it can interpret the predicted results chemically. It also improves prediction performance because the graph representations of all neighboring orders, which contain diverse range of information, are employed for the final prediction. Through extensive experiments, we demonstrated that MoGAT showed better performance than the state-of-the-art methods, and the predicted results were consistent with well-known chemical knowledge.
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Alzheimer's disease (AD) is a neurodegenerative disorder associated with cognitive decline. Despite worldwide efforts to find a cure, no proper treatment has been developed yet, and the only effective countermeasure is to prevent the disease progression by early diagnosis. The reason why new drug candidates fail to show therapeutic effects in clinical studies may be due to misunderstanding the cause of AD. Regarding the cause of AD, the most widely known is the amyloid cascade hypothesis, in which the deposition of amyloid beta and hyperphosphorylated tau is the cause. However, many new hypotheses were suggested. Among them, based on preclinical and clinical evidence supporting a connection between AD and diabetes, insulin resistance has been pointed out as an important factor in the development of AD. Therefore, by reviewing the pathophysiological background of brain metabolic insufficiency and insulin insufficiency leading to AD pathology, we will discuss how can insulin resistance cause AD.
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Doença de Alzheimer , Resistência à Insulina , Humanos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Resistência à Insulina/fisiologia , InsulinaRESUMO
BACKGROUND: Most extramedullary plasmacytomas (EMPs) aresolitary and located in the head and neck region. They may also occur in the visceral parts of the body. OBJECTIVES: Here, we report a case of oral EMP followed by neoplastic plasma cell metastasis to both kidneys in a neutered male Pomeranian. METHODS: Oral plasmacytoma recurred 11 months aftersurgical removal of an oral mass and partial maxillectomy was performed. Eighteen months after partial maxillectomy, neoplastic masses were detected in both kidneys on computed tomography. The dog died 12 months after detection of bilateral kidney neoplasms. The resected neoplastic masses were routinely processed for histopathological observation and immunohistochemistry against pan-cytokeratin, desmin, CD3, and MUM-1. RESULTS: The recurred mass mainly consisted of well-differentiated plasma cells and contained a small portion of aggressive cells with malignant features. Monoclonal gammopathy was not observed on serumelectrophoresis performed to exclude multiple myeloma. The mass was composed of plasma cells with high nuclear pleomorphism and abundant mitotic figures. The neoplasm stained positive for MUM-1 with a more aggressive morphology than in oral EMP. CONCLUSION: Based on serum biomarker and pathological observations, a diagnosis of recurrence and metastasis of oral-to-renal EMP was established. To the best of our knowledge, metastasis of oral EMP into the bilateral kidneys, as described in the current case, has not been previously reported in dogs.