bluuebunny/crossref_metadata_2025_split huggingface dataset:
MD2 blockade prevents modified LDL-induced retinal injury in diabetes by suppressing NADPH oxidase-4 interaction with Toll-like receptor-4
Authors: Chen Huaicheng , Yan Tao , Song Zongming , Ying Shilong , Wu Beibei , Ju Xin , Yang Xi , Qu Jia , Wu Wencan , Zhang Zongduan , Wang Yi 
Published: April 2021

AbstractModified LDL-induced inflammation and oxidative stress are involved in the pathogenesis of diabetic retinopathy. Recent studies have also shown that modified LDL activates Toll-like receptor 4 (TLR4) to mediate retinal injury. However, the mechanism by which modified LDL activates TLR4 and the potential role of the TLR4 coreceptor myeloid differentiation protein 2 (MD2) are not known. In this study, we inhibited MD2 with the chalcone derivatives L2H17 and L6H21 and showed that MD2 blockade protected retinal Müller cells against highly oxidized glycated-LDL (HOG-LDL)-induced oxidative stress, inflammation, and apoptosis. MD2 inhibition reduced oxidative stress by suppressing NADPH oxidase-4 (NOX4). Importantly, HOG-LDL activated TLR4 and increased the interaction between NOX4 and TLR4. MD2 was required for the activation of these pathways, as inhibiting MD2 prevented the association of NOX4 with TLR4 and reduced NOX4-mediated reactive oxygen species production and TLR4-mediated inflammatory factor production. Furthermore, treatment of diabetic mice with L2H17 significantly reduced LDL extravasation in the retina and prevented retinal dysfunction and apoptosis by suppressing the TLR4/MD2 pathway. Our findings provide evidence that MD2 plays a critical role in mediating modified LDL-induced cell injury in the retina and suggest that targeting MD2 may be a potential therapeutic strategy.
Artificial Intelligence-based methods in head and neck cancer diagnosis: an overview
Authors: Mahmood Hanya , Shaban Muhammad , Rajpoot Nasir , Khurram Syed A. 
Published: April 2021

Abstract
Background
This paper reviews recent literature employing Artificial Intelligence/Machine Learning (AI/ML) methods for diagnostic evaluation of head and neck cancers (HNC) using automated image analysis.

Methods
Electronic database searches using MEDLINE via OVID, EMBASE and Google Scholar were conducted to retrieve articles using AI/ML for diagnostic evaluation of HNC (2009–2020). No restrictions were placed on the AI/ML method or imaging modality used.

Results
In total, 32 articles were identified. HNC sites included oral cavity (n = 16), nasopharynx (n = 3), oropharynx (n = 3), larynx (n = 2), salivary glands (n = 2), sinonasal (n = 1) and in five studies multiple sites were studied. Imaging modalities included histological (n = 9), radiological (n = 8), hyperspectral (n = 6), endoscopic/clinical (n = 5), infrared thermal (n = 1) and optical (n = 1). Clinicopathologic/genomic data were used in two studies. Traditional ML methods were employed in 22 studies (69%), deep learning (DL) in eight studies (25%) and a combination of these methods in two studies (6%).

Conclusions
There is an increasing volume of studies exploring the role of AI/ML to aid HNC detection using a range of imaging modalities. These methods can achieve high degrees of accuracy that can exceed the abilities of human judgement in making data predictions. Large-scale multi-centric prospective studies are required to aid deployment into clinical practice.
Body mass index and absolute lymphocyte count predict disease-free survival in Korean breast cancer patients
Authors: Ko Sung Min , Lee Janghee , Bae Soong June , Baik Su Jung , Ji Junghwan , Kim Dooreh , Ahn Sung Gwe , Jeong Joon 
Published: April 2021

Abstract
Background
Our study evaluated the association between body mass index (BMI) and absolute lymphocyte count (ALC) in breast cancer patients and healthy females. Additionally, we determined the prognostic value of these factors in breast cancer.

Methods
We retrospectively identified 1225 primary invasive breast cancer patients and 35,991 healthy females. Factors including BMI and complete blood count associated with disease-free survival (DFS) were assessed using a multi-variable Cox proportional hazard model.

Results
BMI and ALC were positively correlated in breast cancer patients and healthy females (both P < 0.001). In multi-variable analysis, overweight or obese participants had worse DFS (hazards ratio [HR], 1.98; 95% confidence interval [CI], 1.34–2.92; P = 0.001) than underweight or normal-weight individuals, but patients with high ALC had better DFS than those with low ALC (HR, 0.43; 95% CI, 0.29–0.65; P < 0.001). After risk stratification according to BMI/ALC, high-risk patients with high BMI/low ALC had worse DFS than others (HR, 2.48; 95% CI, 1.70–3.62; P < 0.001).

Conclusions
BMI and ALC were positive correlated, but their effect on breast cancer prognosis was opposite. Patients with high BMI/low ALC had worse DFS than others. Underlying mechanisms for effect of BMI/ALC on breast cancer prognosis should be studied in the future.
Automated production of CCR5-negative CD4+-T cells in a GMP-compatible, clinical scale for treatment of HIV-positive patients
Authors: Schwarze Lea Isabell , Sonntag Tanja , Wild Stefan , Schmitz Sabrina , Uhde Almut , Fehse Boris 
Published: April 2021

AbstractEx-vivo gene editing in T lymphocytes paves the way for novel concepts of immunotherapy. One of those strategies is directed at the protection of CD4+-T helper cells from HIV infection in HIV-positive individuals. To this end, we have developed and optimised a CCR5-targeting TALE nuclease, CCR5-Uco-hetTALEN, mediating high-efficiency knockout of C-C motif chemokine receptor 5 (CCR5), the HIV co-receptor essential during initial infection. Clinical translation of the knockout approach requires up-scaling of the manufacturing process to clinically relevant cell numbers in accordance with good manufacturing practice (GMP). Here we present a GMP-compatible mRNA electroporation protocol for the automated production of CCR5-edited CD4+-T cells in the closed CliniMACS Prodigy system. The automated process reliably produced high amounts of CCR5-edited CD4+-T cells (>1.5 × 109 cells with >60% CCR5 editing) within 12 days. Of note, about 40% of total large-scale produced cells showed a biallelic CCR5 editing, and between 25 and 42% of produced cells had a central memory T-cell phenotype. In conclusion, transfection of primary T cells with CCR5-Uco-hetTALEN mRNA is readily scalable for GMP-compatible production and hence suitable for application in HIV gene therapy.
Blood tryptase and thymic stromal lymphopoietin levels predict the risk of exacerbation in severe asthma
Authors: Ko Hsin-Kuo , Cheng Shih-Lung , Lin Ching-Hsiung , Lin Sheng-Hao , Hsiao Yi-Han , Su Kang-Cheng , Yu Chong-Jen , Wang Hao-Chien , Sheu Chau-Chyun , Chiu Kuo-Chin , Perng Diahn-Warng 
Published: April 2021

AbstractSome patients with severe asthma experience exacerbations despite receiving multiple therapy. The risk of exacerbation and heterogeneous response to treatment may be associated with specific inflammatory molecules that are responsive or resistant to corticosteroids. We aimed to identify the independent factors predictive for the future risk of exacerbation in patients with severe asthma. In this multi-center prospective observational study, 132 patients with severe asthma were enrolled and divided into exacerbation (n = 52) and non-exacerbation (n = 80) groups on the basis of exacerbation rate after a 1-year follow-up period. We found that previous history of severe-to-serious exacerbation, baseline blood eosinophil counts (≥ 291cells/μL), and serum tryptase (≤ 1448 pg/mL) and thrymic stromal lymphopoietin (TSLP) levels (≥ 25 pg/mL) independently predicted the future development of exacerbation with adjusted odds ratios (AOR) of 3.27, 6.04, 2.53 and 8.67, respectively. Notably, the patients with high blood eosinophil counts and low tryptase levels were likely to have more exacerbations than those with low blood eosinophil counts and high tryptase levels (AOR 16.9). TSLP potentially played the pathogenic role across different asthma phenotypes. TSLP and tryptase levels may be implicated in steroid resistance and responsiveness in the asthma inflammatory process. High blood eosinophil counts and low serum tryptase levels predict a high probability of future asthma exacerbation.
First approach to distinguish between cardiac and arteriosclerotic emboli of individual stroke patients applying the histological THROMBEX-classification rule
Authors: Roessler Florian C. , Kalms Nicolas , Jann Florian , Kemmling Andrè , Ribbat-Idel Julika , Stellmacher Florian , König Inke R. , Ohlrich Marcus , Royl Georg 
Published: April 2021

AbstractEndovascular treatment of strokes caused by large vessel occlusion enables the histopathological investigation of the retrieved embolus, possibly providing a novel opportunity to contribute to the diagnostic workup of etiology and to define secondary prevention measures in strokes with uncertain genesis. We aimed to develop a classification rule based on pathophysiological considerations and adjustment to reference thrombi for distinction between cardiac and arteriosclerotic emboli and to validate this classification rule on a patient cohort. From 125 patients with stroke due to large vessel occlusion and thrombectomy, 82 patients with known etiology (55 cardioembolic and 27 arterioembolic strokes) were included. The corresponding emboli were histologically evaluated by two raters blinded to the etiology of stroke by means of a novel classification rule. Presumed etiology and classification results were compared. Agreement concerning cardiac emboli was 72.2% (95% CI: 58.4–83.5) for rater I and 78.2% (95% CI: 65.0–88.2) for rater II. Agreement concerning arteriosclerotic emboli was 70.4% (95% CI: 49.8–86.3) for rater I and 74.1% (95% CI: 53.7–88.9) for rater II. Overall agreement reached 71.6% (95% CI: 60.5–81.1) for rater I and 76.8% (95% CI: 66.2–85.4) for rater II. Within the limits of generally restricted accuracy of histological evaluations, the classification rule differentiates between cardiac and arteriosclerotic emboli of acute ischemic stroke patients. Further improvement is needed to provide valuable complementary data for stroke etiology workup.
Controlling water-mediated interactions by designing self-assembled monolayer coatings
Authors: Chen Hsieh , Zhu S. Sherry 
Published: April 2021

AbstractEngineered nanoparticles have been broadly used in biological and geological systems. Hydrophilic molecules such as polyols have been used as coatings on nanoparticle surfaces due to their good biocompatibility and solubility in saline water. However, polyol coatings can cause huge retention of nanoparticles when encountering mineral surfaces. Here, molecular dynamics simulations enlightened that the strong adhesion of hydrophilic coatings to mineral surfaces stemming from the partitioning of the hydroxy groups on the hydrophilic molecules to the well-defined bound hydration layers on the mineral surfaces. To mitigate the nanoparticle adhesion, we investigated introducing small percentages of omniphobic fluoroalkanes to form a bicomponent system of hydrophilic and fluoroalkanes, which greatly perturbed the hydration layers on mineral surfaces and resulted in nonstick surface coatings. Our results provide important insight for the design of tunable “stickiness” nanoparticle coatings in different mineralogies, such as applications in subsurface environments or targeted delivery in mineralized tissues.
Endonuclease increases efficiency of osteoblast isolation from murine calvariae
Authors: Asano Yosuke , Matsumoto Yoshinori , La Rose Jose , He Fang , Katsuyama Takayuki , Ziyi Wang , Tsuji Shigetomo , Kamioka Hiroshi , Rottapel Robert , Wada Jun 
Published: April 2021

AbstractBone is a highly dynamic organ that undergoes remodeling equally regulated by osteoblast-mediated bone formation and osteoclast-mediated bone resorption. To clarify the regulation of osteoblastogenesis, primary murine osteoblasts are required for an in vitro study. Primary osteoblasts are isolated from neonatal calvariae through digestion with collagenase. However, the number of cells collected from one pup is not sufficient for further in vitro experiments, leading to an increase in the use of euthanized pups. We hypothesized that the viscosity of digested calvariae and digestion solution supplemented with collagenase results in cell clumping and reduction of isolated cells from bones. We simply added Benzonase, a genetically engineered endonuclease that shears all forms of DNAs/RNAs, in order to reduce nucleic acid-mediated viscosity. We found that addition of Benzonase increased the number of collected osteoblasts by three fold compared to that without Benzonase through reduction of viscosity. Additionally, Benzonase has no effect on cellular identity and function. The new osteoblast isolation protocol with Benzonase minimizes the number of neonatal pups required for an in vitro study and expands the concept that isolation of other populations of cells including osteocytes that are difficult to be purified could be modified by Benzonase.
Individual and collective foraging in autonomous search agents with human intervention
Authors: Schloesser Daniel S. , Hollenbeck Derek , Kello Christopher T. 
Published: April 2021

AbstractHumans and other complex organisms exhibit intelligent behaviors as individual agents and as groups of coordinated agents. They can switch between independent and collective modes of behavior, and flexible switching can be advantageous for adapting to ongoing changes in conditions. In the present study, we investigated the flexibility between independent and collective modes of behavior in a simulated social foraging task designed to benefit from both modes: distancing among ten foraging agents promoted faster detection of resources, whereas flocking promoted faster consumption. There was a tradeoff between faster detection versus faster consumption, but both factors contributed to foraging success. Results showed that group foraging performance among simulated agents was enhanced by loose coupling that balanced distancing and flocking among agents and enabled them to fluidly switch among a variety of groupings. We also examined the effects of more sophisticated cognitive capacities by studying how human players improve performance when they control one of the search agents. Results showed that human intervention further enhanced group performance with loosely coupled agents, and human foragers performed better when coordinating with loosely coupled agents. Humans players adapted their balance of independent versus collective search modes in response to the dynamics of simulated agents, thereby demonstrating the importance of adaptive flexibility in social foraging.
Urban agglomeration worsens spatial disparities in climate adaptation
Authors: Kim Seung Kyum , Bennett Mia M. , van Gevelt Terry , Joosse Paul 
Published: April 2021

AbstractMany countries promote urban agglomeration to enhance economic competitiveness, but the impacts of this strategy on local climate adaptation remain poorly understood. Here, we use variation in greenspaces to test the effectiveness of climate adaptation policy across climate impacts and vulnerability dimensions. Using satellite imagery and logistic regression, we analyze spatiotemporal correlation between greenspace and climate vulnerability in the Guangdong-Hong Kong-Macau Greater Bay Area, an area comprising ~ 70 million people and 11 cities, making it a useful natural experiment for our study. We find that while greenspace increases proportionally with climate exposure and sensitivity, many cities exhibit discrepancies between greenspace variation and climate vulnerability. Green adaptation funnels into wealthier, less vulnerable areas while bypassing more vulnerable ones, increasing their climate vulnerability and undermining the benefits of urban agglomeration. The results suggest that centrally-planned climate adaptation policy must accommodate local heterogeneity to improve urban sustainability. By neglecting local heterogeneity, urban agglomeration policy risks exacerbating spatial inequalities in climate adaptation.
Machine learning analysis to predict the need for ankle foot orthosis in patients with stroke
Authors: Choo Yoo Jin , Kim Jeoung Kun , Kim Jang Hwan , Chang Min Cheol , Park Donghwi 
Published: April 2021

AbstractWe investigated the potential of machine learning techniques, at an early stage after stroke, to predict the need for ankle–foot orthosis (AFO) in stroke patients. We retrospectively recruited 474 consecutive stroke patients. The need for AFO during ambulation (output variable) was classified according to the Medical Research Council (MRC) score for the ankle dorsiflexor of the affected limb. Patients with an MRC score of < 3 for the ankle dorsiflexor of the affected side were considered to require AFO, while those with scores ≥ 3 were considered not to require AFO. The following demographic and clinical data collected when patients were transferred to the rehabilitation unit (16.20 ± 6.02 days) and 6 months after stroke onset were used as input data: age, sex, type of stroke (ischemic/hemorrhagic), motor evoked potential data on the tibialis anterior muscle of the affected side, modified Brunnstrom classification, functional ambulation category, MRC score for muscle strength for shoulder abduction, elbow flexion, finger flexion, finger extension, hip flexion, knee extension, and ankle dorsiflexion of the affected side. For the deep neural network model, the area under the curve (AUC) was 0.887. For the random forest and logistic regression models, the AUC was 0.855 and 0.845, respectively. Our findings demonstrate that machine learning algorithms, particularly the deep neural network, are useful for predicting the need for AFO in stroke patients during the recovery phase.
Identification and functional analyses of host factors interacting with the 17-kDa protein of Barley yellow dwarf virus-GAV
Authors: Chen Siyu , Han Xiaoyu , Yang Lingling , Li Qinglun , Shi Yajuan , Li Honglian , Chen Linlin , Sun Bingjian , Shi Yan , Yang Xue 
Published: April 2021

AbstractBarley yellow dwarf viruses (BYDVs) cause significant economic losses on barley, wheat, and oats worldwide. 17-kDa protein (17K) of BYDVs plays a key role in viral infection in plants, whereas the underlying regulation mechanism of 17K in virus infection remains elusive. In this study, we determined that 17K of BYDV-GAV, the most common species found in China in recent years, was involved in viral pathogenicity. To identify the host factors interacting with 17K, the full length coding sequence of 17K was cloned into pGBKT7 to generate the bait plasmid pGBKT7-17K. 114 positive clones were identified as possible host factors to interact with 17K through screening a tobacco cDNA library. Gene ontology enrichment analysis showed that they were classified into 35 functional groups, involving three main categories including biological processes (BP), cellular components (CC), and molecular functions (MF). Kyoto Encyclopedia of Genes and Genome (KEGG) analysis indicated the acquired genes were assigned to 49 KEGG pathways. The majority of these genes were involved in glyoxylate and dicarboxylate metabolism, carbon fixation in photosynthetic organisms, and glycolysis/gluconeogenesis. The interactions between 17K and the 27 proteins with well-documented annotations were verified by conducting yeast two-hybrid assays and 12 of the 27 proteins were verified to interact with 17K. To explore the putative function of the 12 proteins in BYDV-GAV infection, the subcellular localization and expression alterations in the presence of BYDV-GAV were monitored. The results showed that, under the condition of BYDV-GAV infection, RuBisCo, POR, and PPD5 were significantly up-regulated, whereas AEP and CAT1 were significantly down-regulated. Our findings provide insights into the 17K-mediated BYDV-GAV infection process.
Revealing the spatial shifting pattern of COVID-19 pandemic in the United States
Authors: Zhu Di , Ye Xinyue , Manson Steven 
Published: April 2021

AbstractWe describe the use of network modeling to capture the shifting spatiotemporal nature of the COVID-19 pandemic. The most common approach to tracking COVID-19 cases over time and space is to examine a series of maps that provide snapshots of the pandemic. A series of snapshots can convey the spatial nature of cases but often rely on subjective interpretation to assess how the pandemic is shifting in severity through time and space. We present a novel application of network optimization to a standard series of snapshots to better reveal how the spatial centres of the pandemic shifted spatially over time in the mainland United States under a mix of interventions. We find a global spatial shifting pattern with stable pandemic centres and both local and long-range interactions. Metrics derived from the daily nature of spatial shifts are introduced to help evaluate the pandemic situation at regional scales. We also highlight the value of reviewing pandemics through local spatial shifts to uncover dynamic relationships among and within regions, such as spillover and concentration among states. This new way of examining the COVID-19 pandemic in terms of network-based spatial shifts offers new story lines in understanding how the pandemic spread in geography.
The effect of sirolimus on angiomyolipoma is determined by decrease of fat-poor compartments and includes striking reduction of vascular structures
Authors: Watanabe Elieser Hitoshi , Coelho Fernando Morbeck Almeida , Filho Hilton Leão , Balbo Bruno Eduardo Pedroso , Neves Precil Diego Miranda de Menezes , Franzin Fernanda Maria , Yamauchi Fernando Ide , Onuchic Luiz Fernando 
Published: April 2021

AbstractRenal angiomyolipomas hemorrhage is associated with their size and vascular constitution. The effects of sirolimus on different components of angiomyolipomas was analyzed in patients with tuberous sclerosis complex, sporadic lymphangioleiomyomatosis and multiple sporadic angiomyolipomas. Thirty angiomyolipomas from 14 patients treated with sirolimus were retrospectively evaluated. A Hounsfield-unit threshold was used to classify angiomyolipomas in fat-rich, fat-poor and intermediate-fat tumors, and to categorize tumor compartments in fat rich, fat poor, intermediate fat and highly vascularized. Diameter variations were measured to assess the effects on aneurysmatic/ectatic vascular formations. Volume reduction following treatment with sirolimus was higher in fat-poor than fat-rich angiomyolipomas. Tumor reduction was mainly determined by decrease of the fat-poor and highly-vascularized compartments while the volume of the fat-rich compartment increased. Broad liposubstitution was observed in some tumors. A median reduction of 100% (75 to 100) in the diameter of aneurysmatic/ectatic vascular structures was observed. Our study showed that sirolimus reduces the size of angiomyolipomas by decreasing primarily their highly-vascularized and fat-poor compartments. This effect is associated with a remarkable reduction of tumoral aneurysms/ectatic vessels, revealing the likely mechanism responsible for the risk-decreasing effect of mTOR inhibitors on angiomyolipoma bleeding. These findings support the role of mTOR in the development of angiomyolipoma blood vessels.