Miracle-dz/UniFAR-FTUs huggingface dataset:
Interleukin-6: A Masterplayer in the Cytokine Network

Interleukin-6 (IL-6) is a member of the pro-inflammatory cytokine family, induces the expression of a variety of proteins responsible for acute inflammation, and plays an important role in the proliferation and differentiation of cells in humans. IL-6 signaling is mediated by building a complex of IL-6, the transmembrane IL-6 receptor (mIL-6R) or with soluble forms of IL-6R (sIL-6R), and the signal-transducing subunit molecule gp130. Therefore, three modes for IL-6 signaling may occur in which IL-6 is binding to mIL-6R (classic), to sIL-6R (trans-signaling), or is joined through IL-6R to gp130 on nearby located cells (trans-presentation). These pathways, and the fact that gp130 is ubiquitously expressed, lead to the pleiotropic functions of IL-6. The control of IL-6 signaling is regulated through the induction of suppressor molecules after activation of the IL-6 pathways as well as through the presence of sIL-6R and gp130 forms in the blood. Vice versa, an overproduction of IL-6 and dysregulation of the IL-6 signaling pathways can result in inflammatory and autoimmune disorders as well as cancer development suggesting that IL-6 plays a significant role in the human cytokine network. Several therapeutic agents have been evaluated for inhibiting the cytokine itself, the signaling via the IL-6 receptor, or target kinases (e.g., JAK/STAT) associated with the signaling pathways. Amongst others, tocilizumab (anti-IL-6R humanized antibody) has been approved for the treatment of rheumatoid arthritis, cytokine release syndrome, and idiopathic multicentric Castleman’s disease (iMCD), whereas siltuximab (an IL-6 antagonist) received approval for iMCD only. Although not all IL-6-associated diseases respond to IL-6 blockade, a better understanding of the underlying mechanisms of the IL-6 pathways may, therefore, help to find the best treatment for IL-6-associated diseases in the near future.
Ursodeoxycholic acid attenuates the expression of proinflammatory cytokines in periodontal cells

Abstract Background Ursodeoxycholic acid (UDCA) is one of the first‐line therapeutic medications used in treatment of cholestatic liver disease. Considering that periodontitis is epidemiologically linked to liver diseases, the question arises weather UDCA holds anti‐inflammatory properties on periodontal health. Herein, we provide information that support anti‐inflammatory effects of UDCA on three different periodontium‐related cell types. Methods Gingival fibroblasts and the oral human squamous carcinoma cell line HSC‐2 were exposed to interleukin (IL)1β and tumor necrosis factor (TNF)α with and without UDCA. Murine RAW 264.7 macrophages were incubated with sterile‐filtered human saliva also in the presence of UDCA. The expression of inflammatory cytokines was measured by reverse transcription‐polymerase chain reaction. Immunoassay was applied to detect the production of IL6. Immunostaining was performed for the p65 subunit to further support the anti‐inflammatory role of UDCA. Results We report here that UDCA significantly reduced the IL1β and TNFα‐induced expression of IL1, IL6, and IL8 in gingival fibroblasts and the HSC‐2 cell line. In RAW 264.7 macrophages, UDCA attenuated the expression of IL1α, IL1β, and IL6 that was increased by saliva. Immunoassay confirmed the capacity of UDCA to reduce inflammation‐induced production of IL6 in gingival fibroblasts, HSC‐2 and RAW 264.7 cells. Immunostaining revealed the blocking of nuclear translocation of p65 in gingival fibroblasts. Conclusions Taken together, UDCA can attenuate the provoked expression of inflammatory cytokines in oral fibroblasts, oral human squamous carcinoma cells and macrophages in vitro. These data support the hypothesis that patients with cholestatic liver disease might benefit from UDCA with respect to periodontal health.
Exosomes from mesenchymal stem cells overexpressing MIF enhance myocardial repair

Accumulating evidence has shown that mesenchymal stem cell (MSC)‐derived exosomes (exo) mediate cardiac repair following myocardial infarction (MI). Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, plays a critical role in regulating cell homeostasis. This study aimed to investigate the cardioprotective effects of exo secreted from bone marrow‐MSCs (BM‐MSCs) overexpressing MIF in a rat model of MI. MIF plasmid was transducted in BM‐MSCs. Exo were isolated from the supernatants of BM‐MSCs and MIF‐BM‐MSCs, respectively. The morphology of mitochondria in neonatal mice cardiomyocytes (NRCMs) was determined by MitoTracker staining. The apoptosis of NRCMs was examined by deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling. BM‐MSC‐exo and MIF‐BM‐MSC‐exo were intramuscularly injected into the peri‐infarct region in a rat model of MI. The heart function of rats was assessed by echocardiography. The expression of MIF was greatly enhanced in MIF‐BM‐MSCs compared with BM‐MSCs. Both BM‐MSC‐exo and MIF‐BM‐MSC‐exo expressed CD63 and CD81. NRCMs treated with MIF‐BM‐MSC‐exo exhibited less mitochondrial fragmentation and cell apoptosis under hypoxia/serum deprivation (H/SD) challenge than those treated with BM‐MSC‐exo via activating adenosine 5′‐monophosphate‐activated protein kinase signaling. Moreover, these effects were partially abrogated by Compound C. Injection of BM‐MSC‐exo or MIF‐BM‐MSC‐exo greatly restored heart function in a rat model of MI. Compared with BM‐MSC‐exo, injection of MIF‐BM‐MSC‐exo was associated with enhanced heart function, reduced heart remodeling, less cardiomyocyte mitochondrial fragmentation, reactive oxygen species generation, and apoptosis. Our study reveals a new mechanism of MIF‐BM‐MSC‐exo‐based therapy for MI and provides a novel strategy for cardiovascular disease treatment.
Calcium‐sensing receptor regulates intestinal dipeptide absorption via Ca2+ signaling and IKCa activation

Although absorption of di‐ and tripeptides into intestinal epithelial cells occurs via the peptide transporter 1 (PEPT1, also called solute carrier family 15 member 1 (SLC15A1)), the detailed regulatory mechanisms are not fully understood. We examined: (a) whether dipeptide absorption in villous enterocytes is associated with a rise in cytosolic Ca2+ ([Ca2+]cyt), (b) whether the calcium sensing receptor (CaSR) is involved in dipeptide‐elicited [Ca2+]cyt signaling, and (c) what potential consequences of [Ca2+]cyt signaling may enhance enterocyte dipeptide absorption. Dipeptide Gly‐Sar and CaSR agonist spermine markedly raised [Ca2+]cyt in villous enterocytes, which was abolished by NPS‐2143, a selective CaSR antagonist and U73122, an phospholipase C (PLC) inhibitor. Apical application of Gly‐Sar induced a jejunal short‐circuit current (Isc), which was reduced by NPS‐2143. CaSR expression was identified in the lamina propria and on the basal enterocyte membrane of mouse jejunal mucosa in both WT and Slc15a1−/− animals, but Gly‐Sar‐induced [Ca2+]cyt signaling was significantly decreased in Slc15a1−/− villi. Clotrimazole and TRM‐34, two selective blockers of the intermediate conductance Ca2+‐activated K+ channel (IKCa), but not iberiotoxin, a selective blocker of the large‐conductance K+ channel (BKCa) and apamin, a selective blocker of the small‐conductance K+ channel (SKCa), significantly inhibited Gly‐Sar‐induced Isc in native tissues. We reveal a novel CaSR‐PLC‐Ca2+‐IKCa pathway in the regulation of small intestinal dipeptide absorption, which may be exploited as a target for future drug development in human nutritional disorders.
Dual antiplatelets in IV thrombolysis

Even after >20 years of experience, IV thrombolysis (IVT) for acute ischemic stroke apparently continues to elicit concern, largely due to fear of symptomatic intracerebral hemorrhage (sICH). While many of the major predisposing factors are well established,1 gray zones of uncertainty remain, including concurrent exposure to antiplatelet therapy. Although not a formal contraindication to thrombolysis per se, many perceive it as increasing the risk of sICH. Prior exposure to a single antiplatelet agent is common, due to either overlap of stroke with other vascular comorbid conditions with antiplatelet therapy indications or over-the-counter use for presumed primary prevention benefits, despite evidence to the contrary.2 The greater antiplatelet effects of dual antiplatelet therapy (DAPT) might make it even riskier. Despite higher rates of sICH with single antiplatelet exposure in the context of IVT,3–5 this does not translate into higher mortality or worse functional status. In fact, a large observational registry-based study in the United States showed more favorable functional outcomes in those pretreated with antiplatelets.3 The available and controversial data pertaining to prestroke DAPT exposure have not clarified the risks after IVT, with some studies showing elevated sICH risk while others not.6,7
Conservation of Angular Momentum in Direct Nonadiabatic Dynamics.

Direct nonadiabatic dynamics is used to study processes involving multiple electronic states from small molecules to materials. Compared with dynamics with fitted analytical potential energy surfaces, direct dynamics is more user-friendly in that it obtains all needed energies, gradients, and nonadiabatic couplings (NACs) by electronic structure calculations. The NAC that is usually used does not conserve angular momentum or the center of mass in widely used mixed quantum-classical nonadiabatic dynamics algorithms, in particular trajectory surface hopping, semiclassical Ehrenfest, and coherent switching with decay of mixing. We show that by using a projection operator to remove the translational and rotational components of the originally computed NAC, one can restore the conservation.
Linkages to HIV confirmatory testing and antiretroviral therapy after online, supervised, HIV self‐testing among Thai men who have sex with men and transgender women

Online, supervised, HIV self‐testing has potential to reach men who have sex with men (MSM) and transgender women (TGW) who never tested before and who had high HIV‐positive yield. We studied linkages to HIV confirmatory test and antiretroviral therapy (ART) initiation among Thai MSM and TGW who chose online and/or offline platforms for HIV testing and factors associated with unsuccessful linkages.
Identification of an immune-suppressed subtype of feline triple-negative basal-like invasive mammary carcinomas, spontaneous models of breast cancer

Feline invasive mammary carcinomas are characterized by their high clinical aggressiveness, rare expression of hormone receptors, and pathological resemblance to human breast cancer, especially triple-negative breast cancer (negative to estrogen receptor, progesterone receptor, and epidermal growth factor receptor type 2). Recent gene expression studies of triple-negative breast cancers have highlighted their heterogeneity and the importance of immune responses in their biology and prognostic assessment. Indeed, regulatory T cells may play a crucial role in producing an immune-suppressed microenvironment, notably in triple-negative breast cancers. Feline invasive mammary carcinomas arise spontaneously in immune-competent animals, in which we hypothesized that the immune tumor microenvironment also plays a role. The aims of this study were to determine the quantity and prognostic value of forkhead box protein P3-positive peritumoral and intratumoral regulatory T cells in feline invasive mammary carcinomas, and to identify an immune-suppressed subgroup of triple-negative basal-like feline invasive mammary carcinomas. One hundred and eighty female cats with feline invasive mammary carcinomas, treated by surgery only, with 2-year follow-up post-mastectomy, were included in this study. Forkhead box protein P3, estrogen receptor, progesterone receptor, Ki-67, epidermal growth factor receptor type 2, and cytokeratin 14 expression were assessed by automated immunohistochemistry. Peritumoral regulatory T cells were over 300 times more abundant than intratumoral regulatory T cells in feline invasive mammary carcinomas. Peritumoral and intratumoral regulatory T cells were associated with shorter disease-free interval and overall survival in both triple-negative (ER–, PR–, HER2–, N = 123 out of 180) and luminal (ER+ and/or PR+, N = 57) feline invasive mammary carcinomas. In feline triple-negative basal-like (CK14+) mammary carcinomas, a regulatory T-cell–enriched subgroup was associated with significantly poorer disease-free interval, overall survival, and cancer-specific survival than regulatory T-cell-poor triple-negative basal-like feline invasive mammary carcinomas. High regulatory T-cell numbers had strong and negative prognostic value in feline invasive mammary carcinomas, especially in the triple-negative basal-like subgroup, which might contain a “basal-like immune-suppressed” subtype, as described in triple-negative breast cancer. Cats with feline invasive mammary carcinomas may thus be interesting spontaneous animal models to investigate new strategies of cancer immunotherapy in an immune-suppressed tumor microenvironment.
Monitoring LAI, Chlorophylls, and Carotenoids Content of a Woodland Savanna Using Hyperspectral Imagery and 3D Radiative Transfer Modeling

Leaf pigment contents, such as chlorophylls a and b content (C a b ) or carotenoid content (Car), and the leaf area index (LAI) are recognized indicators of plants’ and forests’ health status that can be estimated through hyperspectral imagery. Their measurement on a seasonal and yearly basis is critical to monitor plant response and adaptation to stress, such as droughts. While extensively done over dense canopies, estimation of these variables over tree-grass ecosystems with very low overstory LAI (mean site LAI < 1 m 2 /m 2 ), such as woodland savannas, is lacking. We investigated the use of look-up table (LUT)-based inversion of a radiative transfer model to retrieve LAI and leaf C a b and Car from AVIRIS images at an 18 m spatial resolution at multiple dates over a broadleaved woodland savanna during the California drought. We compared the performances of different cost functions in the inversion step. We demonstrated the spatial consistency of our LAI, C a b , and Car estimations using validation data from low and high canopy cover parts of the site, and their temporal consistency by qualitatively confronting their variations over two years with those that would be expected. We concluded that LUT-based inversions of medium-resolution hyperspectral images, achieved with a simple geometric representation of the canopy within a 3D radiative transfer model (RTM), are a valid means of monitoring woodland savannas and more generally sparse forests, although for maximum applicability, the inversion cost functions should be selected using validation data from multiple dates. Validation revealed that for monitoring use: The normalized difference vegetation index (NDVI) outperformed other indices for LAI estimations (root mean square error (RMSE) = 0.22 m 2 /m 2 , R 2 = 0.81); the band ratio ρ 0.750 μ m ρ 0.550 μ m retrieved C a b more accurately than other chlorophylls indices (RMSE = 5.21 μ g/cm 2 , R 2 = 0.73); RMSE over the 0.5–0.55 μ m interval showed encouraging results for Car estimations.
Real-Time Detection of Ground Objects Based on Unmanned Aerial Vehicle Remote Sensing with Deep Learning: Application in Excavator Detection for Pipeline Safety

Unmanned aerial vehicle (UAV) remote sensing and deep learning provide a practical approach to object detection. However, most of the current approaches for processing UAV remote-sensing data cannot carry out object detection in real time for emergencies, such as firefighting. This study proposes a new approach for integrating UAV remote sensing and deep learning for the real-time detection of ground objects. Excavators, which usually threaten pipeline safety, are selected as the target object. A widely used deep-learning algorithm, namely You Only Look Once V3, is first used to train the excavator detection model on a workstation and then deployed on an embedded board that is carried by a UAV. The recall rate of the trained excavator detection model is 99.4%, demonstrating that the trained model has a very high accuracy. Then, the UAV for an excavator detection system (UAV-ED) is further constructed for operational application. UAV-ED is composed of a UAV Control Module, a UAV Module, and a Warning Module. A UAV experiment with different scenarios was conducted to evaluate the performance of the UAV-ED. The whole process from the UAV observation of an excavator to the Warning Module (350 km away from the testing area) receiving the detection results only lasted about 1.15 s. Thus, the UAV-ED system has good performance and would benefit the management of pipeline safety.
A Machine Learning-Based Classification System for Urban Built-Up Areas Using Multiple Classifiers and Data Sources

Information about urban built-up areas is important for urban planning and management. However, obtaining accurate information about urban built-up areas is a challenge. This study developed a general-purpose built-up area intelligent classification (BAIC) system that supports various types of data and classifiers. All of the steps in the BAIC were implemented using Python modules including Numpy, Pandas, matplotlib, and scikit-learn. We used the BAIC to conduct a classification experiment that involved seven types of input data; namely, Point of Interest (POI), Road Network (RN), nighttime light (NTL), a combination of POI and RN data (POI_RN), a combination of POI and NTL data (POI_NTL), a combination of RN and NTL data (RN_NTL), and a combination of POI, RN, and NTL data (POI_RN_NTL), and five classifiers, namely, Logistic Regression (LR), Decision Tree (DT), Random Forests (RF), Gradient Boosted Decision Trees (GBDT), and AdaBoost. The results show the following: (1) among the 35 combinations of the five classifiers and seven types of input data, the overall accuracy (OA) ranged from 76 to 89%, F1 values ranged from 0.73 to 0.86, and the area under the receiver operating characteristic (ROC) curve (AUC) ranged from 0.83 to 0.95. The largest F1 value and OA were obtained using the POI_RN_NTL data and AdaBoost, while the largest AUC was obtained using POI_RN_NTL and POI_NTL data against AdaBoost, LR, and RF; and (2) the advantages of the BAIC include its support for multi-source input data, its objective accuracy assessment, and its robust classifiers. The BAIC can quickly and efficiently realize the automatic classification of urban built-up areas at a reasonably low cost and can be readily applied to other urban areas in the world where any kind of POI, RN, or NTL data coverage is available. The results of this study are expected to provide timely and effective reference information for urban planning and urban management departments, and could also potentially be used to develop large-scale maps of urban built-up areas in the future.
A Method for Dehazing Images Obtained from Low Altitudes during High-Pressure Fronts

Unmanned aerial vehicles (UAVs) equipped with compact digital cameras and multi-spectral sensors are used in remote sensing applications and environmental studies. Recently, due to the reduction of costs of these types of system, the increase in their reliability, and the possibility of image acquisition with very high spatial resolution, low altitudes imaging is used in many qualitative and quantitative analyses in remote sensing. Also, there has been an enormous development in the processing of images obtained with UAV platforms. Until now, research on UAV imaging has focused mainly on aspects of geometric and partially radiometric correction. And consideration of the effects of low atmosphere and haze on images has so far been neglected due to the low operating altitudes of UAVs. However, it proved to be the case that the path of sunlight passing through various layers of the low atmosphere causes refraction and causes incorrect registration of reflection by the imaging sensor. Images obtained from low altitudes may be degraded due to the scattering process caused by fog and weather conditions. These negative atmospheric factors cause a reduction in contrast and colour reproduction in the image, thereby reducing its radiometric quality. This paper presents a method of dehazing images acquired with UAV platforms. As part of the research, a methodology for imagery acquisition from a low altitude was introduced, and methods of atmospheric calibration based on the atmosphere scattering model were presented. Moreover, a modified dehazing model using Wiener’s adaptive filter was presented. The accuracy assessment of the proposed dehazing method was made using qualitative indices such as structural similarity (SSIM), peak signal to noise ratio (PSNR), root mean square error (RMSE), Correlation Coefficient, Universal Image Quality Index (Q index) and Entropy. The experimental results showed that using the proposed dehazing method allowed the removal of the negative impact of haze and improved image quality, based on the PSNR index, even by an average of 34% compared to other similar methods. The obtained results show that our approach allows processing of the images to remove the negative impact of the low atmosphere. Thanks to this technique, it is possible to obtain a dehazing effect on images acquired at high humidity and radiation fog. The results from this study can provide better quality images for remote sensing analysis.
A Long-Term Passive Microwave Snowoff Record for the Alaska Region 1988-2016

Snowoff (SO) date—defined as the last day of observed seasonal snow cover—is an important governor of ecologic and hydrologic processes across Alaska and Arctic-Boreal landscapes; however, our understanding and capacity for the monitoring of spatial and temporal variability in the SO date is still lacking. In this study, we present a 6.25 km spatially gridded passive microwave (PMW) SO data record, complimenting current Alaskan SO records from Moderate Resolution Imaging Spectrometer (MODIS) and Landsat, but extending the SO record an additional 13 years. The PMW SO record was validated against in situ snow depth observations and showed favorable accuracy (0.66–0.92 mean correlations; 2–10 day mean absolute errors) for the major climate regions of Alaska. The PMW SO results were also within 10 days of finer spatial scale SO observational records, including Interactive Multisensor Snow and Ice Mapping System (IMS), MODIS, and Landsat, for a majority (75%) of Alaska. However, the PMW record showed a general SO delay at higher elevations and across the Alaska North Slope, and earlier SO in the Alaska interior and southwest regions relative to the other SO records. Overall, we assign an uncertainty +/−11 days to the PMW SO. The PMW SO record benefits from the near-daily temporal fidelity of underlying brightness temperature (Tb) observations and reveals a mean regional trend in earlier SO timing (−0.39 days yr−1), while significant (p < 0.1) SO trend areas encompassed 11% of the Alaska domain and ranged from −0.11 days yr−1 to −1.31 days yr−1 over the 29-year satellite record. The observed SO dates also showed anomalous early SO dates during markedly warm years. Our results clarify the pattern and rate of SO changes across Alaska, which are interactive with global warming and contributing to widespread permafrost degradation, changes in regional hydrology, ecosystems, and associated services. Our results also provide a robust means for SO monitoring from satellite PMW observations with similar precision as more traditional and finer scale observations.