bluuebunny/crossref_metadata_2025_split huggingface dataset:
DRP1 promotes lactate utilization in KRAS‐mutant non‐small‐cell lung cancer cells
Authors: Hu Mangze , Zhao Yu , Cao Yuejiao , Tang Qianru , Feng Ziqin , Ni Jun , Zhou Xiaorong 
Published: August 2020

AbstractMetabolic alterations are well documented in various cancers. Non‐small‐cell lung cancers (NSCLCs) preferentially use lactate as the primary carbon source, but the underlying mechanisms are not well understood. We developed a lactate‐dependent cell proliferation assay and found that dynamin‐related protein (DRP1), which is highly expressed in KRAS‐mutant NSCLC, is required for tumor cells to proliferate and uses lactate as fuel, demonstrating the critical role of DRP1 in the metabolic reprogramming of NSCLC. Metabolic and transcriptional profiling suggests that DRP1 orchestrates a supportive metabolic network to promote lactate utilization and redox homeostasis in lung cancer cells. DRP1 suppresses the production of reactive oxygen species (ROS) and protects cells against oxidative damage by enhancing lactate utilization. Moreover, targeting DRP1 not only reduces HSP90 expression but also enhances ROS‐induced HSP90 cleavage, thus inhibiting activation of mitogen activated protein kinase and PI3K pathways and leading to suppressed lactate utilization and increased ROS‐induced cell death. Taken together, these results suggest that DRP1 is a crucial regulator of lactate metabolism and redox homeostasis in KRAS‐mutant lung cancer, and that targeting lactate utilization by modulating DRP1 activity might be an effective treatment for lung cancer.
Efficacy of local therapy for oligoprogressive disease after programmed cell death 1 blockade in advanced non‐small cell lung cancer
Authors: Kagawa Yusuke , Furuta Hiromi , Uemura Takehiro , Watanabe Naohiro , Shimizu Junichi , Horio Yoshitsugu , Kuroda Hiroaki , Inaba Yoshitaka , Kodaira Takeshi , Masago Katsuhiro , Fujita Shiro , Niimi Akio , Hida Toyoaki 
Published: August 2020

AbstractImmune checkpoint inhibitors (ICIs) have dramatically changed the strategy used to treat patients with non‐small‐cell lung cancer (NSCLC); however, the vast majority of patients eventually develop progressive disease (PD) and acquire resistance to ICIs. Some patients experience oligoprogressive disease. Few retrospective studies have evaluated clinical efficacy in patients with oligometastatic progression who received local therapy after ICI treatment. We conducted a retrospective analysis of advanced NSCLC patients who received PD‐1 inhibitor monotherapy with nivolumab or pembrolizumab to evaluate the effects of ICIs on the patterns of progression and the efficacy of local therapy for oligoprogressive disease. Of the 307 patients treated with ICIs, 148 were evaluated in our study; 42 were treated with pembrolizumab, and 106 were treated with nivolumab. Thirty‐eight patients showed oligoprogression. Male sex, a lack of driver mutations, and smoking history were significantly correlated with the risk of oligoprogression. Primary lesions were most frequently detected at oligoprogression sites (15 patients), and 6 patients experienced abdominal lymph node (LN) oligoprogression. Four patients showed evidence of new abdominal LN oligometastases. There was no significant difference in overall survival (OS) between the local therapy group and the switch therapy group (reached vs. not reached, P = .456). We summarized clinical data on the response of oligoprogressive NSCLC to ICI therapy. The results may help to elucidate the causes of ICI resistance and indicate that the use of local therapy as the initial treatment in this setting is feasible treatment option.
Health promotion interventions to improve oral health of adolescents: A systematic review and meta‐analysis
Authors: Tsai Carrie , Raphael Sarah , Agnew Caitlin , McDonald Gordon , Irving Michelle 
Published: August 2020

AbstractObjectivesTo evaluate the effectiveness of health promotion interventions on oral health knowledge, behaviour and status of healthy adolescents.MethodsThis review included randomized controlled trials (RCTs) of oral health promotion interventions targeting adolescents. Primary clinical outcomes (gingival health, plaque scores, caries) and secondary proxy outcomes were evaluated. Meta‐analysis of primary outcomes was conducted where possible, with subgroup analysis based on intervention (comprehensive health promotion and education‐only).ResultsThirty‐seven eligible publications reporting on 28 unique RCTs of oral health promotion interventions were included. Quality appraisal of studies ranged from 48% to 96%. Interventions reported ranged from single‐session interventions to community‐wide programmes, including clinical preventive procedures and take‐home products. Half used a health behaviour change theory to inform their intervention. The meta‐analysis pooling of results favoured the intervention over control for all clinical outcomes, except DMFS in the education‐only subgroup. Stronger intervention effects were seen in the comprehensive intervention subgroup than the education‐only subgroup for DMFS (P = .02). This effect was slight, but not as clear in all other clinical categories. The majority of studies reported improvements in oral health knowledge, attitudes and behaviours. More positive outcomes were found with longer programmes, especially for dental caries outcomes.ConclusionsOral health promotion programmes targeting adolescents have the ability to improve clinical oral health outcomes in the short and long term. Programmes should use more behavioural theory‐based interactive and strategic methods, including self‐awareness and the use of the wider community and peers for oral health promotion activities over a longer intervention duration.
Food allergy promotes a Th2/Th17 response that drives house dust mite-induced allergic airway inflammation in humanized mice
Authors: Wang B , Hu J , Liu Y , Liu Q , Li D 
Published: August 2020

Summary
Food allergy is related to increasing risk of the development of allergic asthma, but the precise interplay between sensitization to different allergens in different compartments of the body is not fully understood. The aim of this study was to develop a novel humanized murine model of mixed food and respiratory allergy that recapitulates the human anaphylactic response and to more clearly understand the impact of food allergies on asthma. Immunodeficient mice transferred with peripheral blood mononuclear cells (PBMCs) from donors with peanut and house dust mite (HDM) allergy were exposed and challenged to peanut. Between peanut exposure and challenge, mice were intranasally treated to HDM. Allergic parameters were analyzed. Allergen-specific immunoglobulin (Ig)E in sera could only be measured in mice treated with peripheral blood mononuclear cells (PBMCs) plus allergen. A preceding peanut exposure increased IgE levels, histamine release, bronchial hyper-responsiveness and lung inflammation. Recruitment of inflammatory cells to the airways was aggravated associated with an enhanced T helper type 2 (Th2)/Th17 cytokine secretion when the two allergies were present. A preceding peanut exposure amplifies allergic asthma in this humanized model, which may contribute to the understanding of underlying immunological mechanism of polysensitization occurring in allergic individuals and evaluation of therapeutic interventions.
Mutation spectrum and polygenic score in German patients with familial hypercholesterolemia
Authors: Rieck Lorenz , Bardey Frieda , Grenkowitz Thomas , Bertram Lars , Helmuth Johannes , Mischung Claudia , Spranger Joachim , Steinhagen‐Thiessen Elisabeth , Bobbert Thomas , Kassner Ursula , Demuth Ilja 
Published: August 2020

AbstractAutosomal‐dominant familial hypercholesterolemia (FH) is characterized by increased plasma concentrations of low‐density lipoprotein cholesterol (LDL‐C) and a substantial risk to develop cardiovascular disease. Causative mutations in three major genes are known: the LDL receptor gene (LDLR), the apolipoprotein B gene (APOB) and the proprotein convertase subtilisin/kexin 9 gene (PCSK9). We clinically characterized 336 patients suspected to have FH and screened them for disease causing mutations in LDLR, APOB, and PCSK9. We genotyped six single nucleotide polymorphisms (SNPs) to calculate a polygenic risk score for the patients and 1985 controls. The 117 patients had a causative variant in one of the analyzed genes. Most variants were found in the LDLR gene (84.9%) with 11 novel mutations. The mean polygenic risk score was significantly higher in FH mutation negative subjects than in FH mutation positive patients (P < .05) and healthy controls (P < .001), whereas the score of the two latter groups did not differ significantly. However, the score explained only about 3% of the baseline LDL‐C variance. We verified the previously described clinical and genetic variability of FH for German hypercholesterolemic patients. Evaluation of a six‐SNP polygenic score recently proposed for clinical use suggests that it is not a reliable tool to classify hypercholesterolemic patients.
Data‐Driven Facial Simulation
Authors: Romeo M. , Schvartzman S. C. 
Published: August 2020

AbstractIn Visual Effects, the creation of realistic facial performances is still a challenge that the industry is trying to overcome. Blendshape deformation is used to reproduce the action of different groups of muscles, which produces realistic static results. However, this is not sufficient to generate believable and detailed facial performances of animated digital characters.To increase the realism of facial performances, it is possible to enhance standard facial rigs using physical simulation approaches. However, setting up a simulation rig and controlling material properties according to the performance is not an easy task and could take a lot of time and iterations to get it right.We present a workflow that allows us to generate an activation map for the fibres of a set of superficial patches we callpseudo‐muscles. The pseudo‐muscles are automatically identified using k‐means to cluster the data from the blendshape targets in the animation rig and compute the direction of their contraction (direction of the pseudo‐muscle fibres). We use an Extended Position–Based Dynamics solver to add physical simulation to the facial animation, controlling the behaviour of simulation through the activation map. We show the results achieved using the proposed solution on two digital humans and one fantastic cartoon character, demonstrating that the identified pseudo‐muscles approximate facial anatomy and the simulation properties are properly controlled, increasing the realism while preserving the work of animators.
Clinicopathological characteristics of lung cancer in patients with systemic sclerosis
Authors: Chen Minjiang , Liu Xiaoyan , Xu Yan , Zhou Qing , Shi Yuequan , Zhang Dongming , Liang Hongge , Zhao Jing , Zhong Wei , Wang Mengzhao 
Published: August 2020

AbstractBackground and objectivesSystemic sclerosis (SSc) is a connective tissue disorder (CTD) associated with an increased risk of malignancy including lung cancer (LC). Our objective was to provide a description of demographics and clinicopathological characteristics of LC patients with SSc.MethodsLung cancer patients with SSc admitted to Peking Union Medical College Hospital from January 2000 to August 2017 were reviewed. Demographic and clinicopathologic data were collected.ResultsOf the 12 cases included in our study, all were female. No patients had a history of smoking. The most common histological type was adenocarcinoma, followed by squamous cell carcinoma and small‐cell carcinoma. No driver mutation was identified in the five patients undergoing genetic testing. Eight patients had interstitial lung disease (ILD). Six were manifested as nonspecific interstitial pneumonia (NSIP) and two as usual interstitial pneumonia (UIP). Four (33.3%) patients underwent surgical resection. Among them, two had ILD with a normal preoperative pulmonary function tests (PFT). Eight (66.7%) patients received chemotherapy. Radiotherapy was administered in only one (8.3%) patient. No grade 3/4 adverse events were documented.ConclusionThe predominance of female patients in our study is different from that reported in general lung cancer patients. A high proportion of patients has SSc‐ILD, including NSIP and UIP. Surgery or radiotherapy could still be considered in carefully selected patients with ILD.
Fundamentals of Cancer Immunology and Their Application to Cancer Vaccines
Authors: Bullock Timothy N. J. 
Published: August 2020

The capacity of the immune system to influence tumor progression has been a long‐standing notion that first generated clinical traction over a 100 years ago when Dr. William Coley injected disaggregated bacterial components into sarcomas and noted that the ensuing inflammation commonly associated with tumor regression.1 Since then, our understanding of the individual components and the overall interaction of the immune system has expanded exponentially. This has led to the development of a robust understanding of how components of innate and adaptive immunity recognize and respond to tumors and leveraging this information for the development of tumor immunotherapies. However, clinical failures have also deepened our knowledge of how tumors might adapt/be selected to avoid or inhibit immune responses, which, in turn, has led to the further iteration of immunotherapies. In this tutorial, the established elements of tumor immunity are explained, and areas where our knowledge base is too thin is highlighted. The principles of tumor immunity that guide the development of cancer vaccines are further illustrated, and potential considerations of how to integrate cancer vaccines with conventional therapies and other immunotherapies are proposed.
Below the Belt? Territory and Development in China's International Rise
Authors: Mohan Giles 
Published: August 2020

ABSTRACTChina's internationalization has been heralded by some as a new era of South–South cooperation. Yet such framings of development are pitched at an abstract space of the ‘global South’ which conceals more than it reveals. With some theory moving towards ontologies of ‘global development’, we need to capture both the connectedness and the local specificity of increasingly diffuse processes. This article sets out a more fine‐grained understanding of how political territories and processes are imagined and produced by and through China's internationalization, focusing on infrastructure as a ‘technology’ of territorialization. Much of the focus on China's internationalization has been on state‐to‐state relations, but this obscures the ‘omni‐channel politics’ that China practises. Using a critical literature review and illustrative case study, this article develops the idea of omni‐channel politics to posit a view of ‘twisted’ territories in which political processes and development outcomes are more complex and contingent.
Predicting Daily Surgical Volumes Using Probabilistic Estimates of Providers’ Future Availability
Authors: Eun Joonyup , Tiwari Vikram , Sandberg Warren S. 
Published: August 2020

ABSTRACTProbability‐based models are developed using information from a variety of datasets to predict daily surgical volumes weeks in advance. The quest was motivated by the need to make real‐time adjustments to staff capacity and reallocation of the operating room block time based on predicted future demand. We test the notion that more data always leads to better predictions. Four probabilistic prediction models are presented, each parameterized based on real data and information from different sources. We hypothesize that the accuracy of the prediction improves by incorporating additional information. Models are tested for a surgical service at a large hospital using data of 20 months (January 19, 2015–August 31, 2016). We find that incorporating additional information may not improve prediction accuracy if that information is prone to data errors. However, deploying analytical data treatment to ameliorate these errors leads to better predictions. We also compare the predictive ability of the probability‐based models to neural network–based models and find that the neural network models do not outperform simpler models. Managers should critically review the accuracy of the data used in decision‐making. While a greater amount of inherently error‐free information is the best, analytics can enhance the utility of error‐prone data.
Cardiac involvement in a pediatric patient with COVID‐19: Looking beyond the nonspecific global cardiac injury
Authors: Bhansali Suneet , Minocha Prashant , Phoon Colin , Henry Gillian , Chakravarti Sujata , Ramirez Michelle , Bhatla Puneet 
Published: August 2020

AbstractWe report a case of a 17‐year‐old healthy male presenting with multisystem hyperinflammatory shock temporally associated with COVID‐19. Cardiac involvement was suspected based on evidence of significant cardiac injury (elevated cardiac biomarkers, electrocardiographic and echocardiographic abnormalities). Cardiac magnetic resonance imaging was performed demonstrating global biventricular systolic dysfunction, as well as a small area of T2 hyperintensity and mid‐wall late gadolinium enhancement. This case discusses the varied cardiac involvement in pediatric patients with COVID‐19 infection and highlights that cardiac injury is not just limited to hyperinflammatory syndrome related global dysfunction but a more focal myocarditis can also be seen.
Resting‐state functional magnetic resonance imaging with independent component analysis for presurgical seizure onset zone localization: A systematic review and meta‐analysis
Authors: Chakraborty Arpan R. , Almeida Nyle C. , Prather Kiana Y. , O’Neal Christen M. , Wells Allison A. , Chen Sixia , Conner Andrew K. 
Published: August 2020

AbstractObjectiveOne of the greatest challenges of achieving successful surgical outcomes in patients with epilepsy is the ability to properly localize the seizure onset zone (SOZ). Many techniques exist for localizing the SOZ, including intracranial electroencephalography, magnetoencephalography, and stereoelectroencephalography. Recently, resting‐state functional magnetic resonance imaging (rs‐fMRI) in conjunction with independent component analysis (ICA) has been utilized for presurgical planning of SOZ resection, with varying results. In this meta‐analysis, we analyze the current role of rs‐fMRI in identifying the SOZ for presurgical planning for patients with drug‐resistant epilepsy. Specifically, we seek to demonstrate its current effectiveness compared to other methods of SOZ localization.MethodsA literature review was conducted using the PubMed, MEDLINE, and Embase databases up to May of 2020. A total of 253 articles were screened, and seven studies were chosen for analysis. Each study was analyzed for SOZ localization by ground truth, SOZ localization by rs‐fMRI with ICA, principal component analysis, or intrinsic connectivity contrast, and outcomes of surgery. A meta‐analysis was performed to analyze how ground truth compares to rs‐fMRI in SOZ localization.ResultsThe odds ratio comparing ground truth to rs‐fMRI was 2.63 (95% confidence interval = 0.66‐10.56). Average concordance of rs‐fMRI SOZ localization compared with ground truth localization across studies was 71.3%.SignificanceIn the hunt for less invasive presurgical planning for epilepsy surgery, rs‐fMRI with ICA provides a promising avenue for future standard practice. Our preliminary results show no significant difference in surgical outcomes between traditional standards of SOZ localization and rs‐fMRI with ICA. We believe that rs‐fMRI could be a step forward in this search. Further investigation comparing rs‐fMRI to traditional methods of SOZ localization should be conducted, with the hope of moving toward relying solely on noninvasive screening methods.
Protective effect of fenofibrate against high‐fat–high‐fructose diet induced non‐obese NAFLD in rats
Authors: Abdelmoneim Doaa , El‐Adl Mohamed , El‐Sayed Gehad , El‐Sherbini El Said 
Published: August 2020

AbstractThe present study evaluated the protective effects of fenofibrate on liver function, oxidant–antioxidant balance, and insulin resistance (IR) in rats fed high‐fat–high‐fructose diet (HFFD). Twenty‐four male Sprague‐Dawley rats (110–130 gm) were allocated into four equal groups (n = 6). Rats in group I were fed a normal diet for 4 weeks. Rats in group II were fed a normal diet with fenofibrate at 50 mg/kg/day orally for four weeks. Rats in group III were fed a normal diet mixed with 25% palm oil and given 60% fructose solution orally for 4 weeks. Rats in group IV were fed a normal diet mixed with 25% palm oil, 60% oral fructose solution, and fenofibrate at 50 mg/kg/day orally for four weeks. After experimental induction, serum and liver tissue samples were collected to determine lipid profiles, glycemic status, antioxidant status, oxidative and stress markers, and histopathology of liver tissues. The results of the present study revealed that fenofibrate prevents the occurrence of fatty liver, enhancing glycemic status, decreasing oxidative stress, and improving antioxidant status. It can be concluded that fenofibrate has a lipotropic and antidiabetic role.
An alternative pentose phosphate pathway in human gut bacteria for the degradation of C5 sugars in dietary fibers
Authors: Garschagen Laura S. , Franke Thomas , Deppenmeier Uwe 
Published: August 2020

The microbial degradation of pentoses in the human gut is a crucial factor for the utilization of plant‐based dietary fibers. A vast majority of gut microbes are able to use these C5‐sugars as a carbon and energy source. However, the underlying metabolic pathways are not fully understood. Bioinformatic analysis showed that a large number of abundant gut bacteria lack genes encoding a transaldolase as a key enzyme of the pentose phosphate pathway. Among them was the important human gut microbe Prevotella copri, which was able to grow in minimal media containing xylose or hemicelluloses as the sole carbon source. Therefore, we looked for an alternative pathway for pentose conversion in P. copri using bioinformatics, enzyme activity assays, and the detection of intermediates of pentose metabolism. It became evident that the organism converted C5‐sugars via the sedoheptulose‐1,7‐bisphosphate pathway (SBPP) to connect pentose metabolism with glycolysis. To circumvent the transaldolase reaction, P. copri uses the combined catalysis of a pyrophosphate‐dependent phosphofructokinase and a fructose‐bisphosphate aldolase. Furthermore, we present strong evidence that the SBPP is widely distributed in important gut bacteria, including members of the phyla Bacteroides, Firmicutes, Proteobacteria, Verrucomicrobia, and Lentisphaerae.