bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTLA-4 blockade boosts the expansion of tumor-reactive CD8+ tumor-infiltrating lymphocytes in ovarian cancer
Authors: Friese Christina , Harbst Katja , Borch Troels Holz , Westergaard Marie Christine Wulff , Pedersen Magnus , Kverneland Anders , Jönsson Göran , Donia Marco , Svane Inge Marie , Met Özcan 
Published: March 2020

AbstractAdoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TILs) can induce durable complete tumor regression in patients with advanced melanoma. Efforts are currently underway to expand this treatment modality to other cancer types. In the microenvironment of ovarian cancer, the engagement of co-inhibitory immune checkpoint molecules such as CTLA-4 can lead to the inactivation of TILs. Thus, approaches that directly manipulate co-inhibitory pathways within the tumor microenvironment might improve the expansion of tumor-reactive TILs. The initial expansion of TILs for ACT from tumor fragments provides a window of opportunity to manipulate an intact tumor microenvironment and improve CD8+ T-cell output and TIL tumor reactivity. To exploit this, we used a CTLA-4-blocking antibody, added during the initial TIL culture, and found that the blockade of CTLA-4 favored the propagation of CD8+ TILs from ovarian tumor fragments. Interestingly, adding the CTLA-4 blocking antibody in the initial phase of the TIL culture resulted in more potent anti-tumor TILs in comparison to standard TIL cultures. This phenotype was preserved during the rapid expansion phase. Thus, targeting CTLA-4 within the intact tumor microenvironment of tumor fragments enriches tumor-reactive TILs and may improve clinical outcome of TIL-based ACT in ovarian cancer.
Relationships between vocal pitch perception and production: a developmental perspective
Authors: Heller Murray Elizabeth S. , Stepp Cara E. 
Published: March 2020

AbstractThe purpose of this study was to examine the relationships between vocal pitch discrimination abilities and vocal responses to auditory pitch-shifts. Twenty children (6.6–11.7 years) and twenty adults (18–28 years) completed a listening task to determine auditory discrimination abilities to vocal fundamental frequency (fo) as well as two vocalization tasks in which their perceived fo was modulated in real-time. These pitch-shifts were either unexpected, providing information on auditory feedback control, or sustained, providing information on sensorimotor adaptation. Children were subdivided into two groups based on their auditory pitch discrimination abilities; children within two standard deviations of the adult group were classified as having adult-like discrimination abilities (N = 11), whereas children outside of this range were classified as having less sensitive discrimination abilities than adults (N = 9). Children with less sensitive auditory pitch discrimination abilities had significantly larger vocal response magnitudes to unexpected pitch-shifts and significantly smaller vocal response magnitudes to sustained pitch-shifts. Children with less sensitive auditory pitch discrimination abilities may rely more on auditory feedback and thus may be less adept at updating their stored motor programs.
Recombinant collagenase from Grimontia hollisae as a tissue dissociation enzyme for isolating primary cells
Authors: Tanaka Keisuke , Okitsu Teru , Teramura Naoko , Iijima Katsumasa , Hayashida Osamu , Teramae Hiroki , Hattori Shunji 
Published: March 2020

AbstractCollagenase products are crucial to isolate primary cells in basic research and clinical therapies, where their stability in collagenolytic activity is required. However, currently standard collagenase products fromClostridium histolyticumlack such stability. Previously, we produced a recombinant 74-kDa collagenase fromGrimontia hollisae, which spontaneously became truncated to~60 kDa and possessed no stability. In this study, to generateG. hollisaecollagenase useful as a collagenase product, we designed recombinant 62-kDa collagenase consisting only of the catalytic domain, which exhibits high production efficiency. We demonstrated that this recombinant collagenase is stable and active under physiological conditions. Moreover, it possesses higher specific activity against collagen and cleaves a wider variety of collagens than a standard collagenase product fromC. histolyticum. Furthermore, it dissociated murine pancreata by digesting the collagens within the pancreata in a dose-dependent manner, and this dissociation facilitated isolation of pancreatic islets with masses and numbers comparable to those isolated using the standard collagenase fromC. histolyticum. Implantation of these isolated islets into five diabetic mice led to normalisation of the blood glucose concentrations of all the recipients. These findings suggest that recombinant 62-kDa collagenase fromG. hollisaecan be used as a collagenase product to isolate primary cells.
Confirmation of the shell-boring oyster parasite Polydora websteri (Polychaeta: Spionidae) in Washington State, USA
Authors: Martinelli Julieta C. , Lopes Heather M. , Hauser Lorenz , Jimenez-Hidalgo Isadora , King Teri L. , Padilla-Gamiño Jacqueline L. , Rawson Paul , Spencer Laura H. , Williams Jason D. , Wood Chelsea L. 
Published: March 2020

AbstractInvasions by shell-boring polychaetes such as Polydora websteri Hartman have resulted in the collapse of oyster aquaculture industries in Australia, New Zealand, and Hawaii. These worms burrow into bivalve shells, creating unsightly mud blisters that are unappealing to consumers and, when nicked during shucking, release mud and detritus that can foul oyster meats. Recent findings of mud blisters on the shells of Pacific oysters (Crassostrea gigas Thunberg) in Washington State suggest a new spionid polychaete outbreak. To determine the identity of the polychaete causing these blisters, we obtained Pacific oysters from two locations in Puget Sound and examined them for blisters and burrows caused by polychaete worms. Specimens were also obtained from eastern oysters (Crassostrea virginica Gmelin) collected in New York for morphological and molecular comparison. We compared polychaete morphology to original descriptions, extracted DNA and sequenced mitochondrial (cytochrome c oxidase I [mtCOI]) and nuclear (small subunit 18S rRNA [18S rRNA]) genes to determine a species-level molecular identification for these worms. Our data show that Polydora websteri are present in the mud blisters from oysters grown in Puget Sound, constituting the first confirmed record of this species in Washington State. The presence of this notorious invader could threaten the sustainability of oyster aquaculture in Washington, which currently produces more farmed bivalves than any other US state.
Clinical and economic impact of methicillin-resistant Staphylococcus aureus: a multicentre study in China
Authors: Zhen Xuemei , Lundborg Cecilia Stålsby , Zhang Meiling , Sun Xueshan , Li Yuanyuan , Hu Xiaoqian , Gu Shuyan , Gu Yuxuan , Wei Jingming , Dong Hengjin 
Published: March 2020

AbstractMethicillin-resistant Staphylococcus aureus (MRSA) has become a serious threat to global health. In China, the proportion of S. aureus isolates that were MRSA was 44.6% in 2014. The clinical and economic impact of MRSA in China remains largely uninvestigated. This study aims to compare the differences in hospital costs, length of hospital stay, and hospital mortality rate between MRSA and methicillin-susceptible S. aureus (MSSA) colonization or infection and between MRSA cases and those without an S. aureus infection. A retrospective and multicentre study was conducted in four tertiary hospitals in China between 2013 and 2015. Inpatient characteristics and hospital costs were collected from electronic medical records. We conducted propensity score matching (PSM) to eliminate selection bias by balancing the potential confounding variables between the two groups. The main indicators included hospital costs, length of hospital stay, and hospital mortality rate. A total of 1,335 inpatients with MRSA, 1,397 with MSSA, and 33,606 without an S. aureus infection were included. PSM obtained 954 and 1,313 pairs between the MRSA and MSSA groups and between the MRSA and S. aureus-free groups, respectively. After PSM, MRSA colonization or infection is associated with an increased total hospital cost ranging from $3,220 to $9,606, an excess length of hospital stay of 6 days–14 days, and an attributable hospital mortality rate of 0–3.58%. Between the MRSA and MSSA groups, MRSA colonization or infection was significantly associated with a higher total hospital cost and longer length of hospital stay among survivors but not among non-survivors; however, there were no differences in the hospital mortality rate between these two groups. Between the MRSA and the S. aureus-free groups, MRSA colonization or infection was significantly associated with an increased total hospital cost, a prolonged length of hospital stay and a higher hospital mortality rate among both survivors and non-survivors. It is critical to quantify the clinical and economic impact of MRSA to justify resource allocation for the development of strategies to improve clinical outcomes and to reduce the economic burden.
Evaluating the holistic costs and benefits of corn production systems in Minnesota, US
Authors: Sandhu Harpinder , Scialabba Nadia El-Hage , Warner Chris , Behzadnejad Fatemeh , Keohane Kieran , Houston Richard , Fujiwara Daniel 
Published: March 2020

AbstractGlobal agriculture aims to minimize its impacts on environment and human health while maintaining its productivity. This requires a comprehensive understanding of its benefits and costs to ecosystems and society. Here, we apply a new evaluation framework developed by the Economics of Ecosystems and Biodiversity for Agriculture and Food (TEEBAgriFood) to assess key benefits and costs on the production side of genetically modified (GM) and organic corn systems in Minnesota, USA. The market value of GM corn is $4.5 billion, and only $31.8 million for organic corn using production data and market prices of 2017. GM corn generates revenue of $1488 per hectare (at $121 per MT), which is significantly lower than the organic corn at $2793 per hectare (at $294 per MT). Using a novel three-stage wellbeing valuation, analysis of the associations between corn production intensity and subjective measures of general health and wellbeing indicates that the total non-financial health cost associated with GM corn is $427.50 per hectare or $1.3 billion annually. We also find that the total annual environmental cost associated with GM corn production is $179 per hectare or $557.65 million within Minnesota. The use of the evaluation framework can help to improve decision making at farm and policy level to develop sustainable agriculture in order to minimize environmental and health related costs to society and economy.
Surface Enhanced Visible Absorption of Dye Molecules in the Near-Field of Gold Nanoparticles
Authors: Elhani S. , Ishitobi H. , Inouye Y. , Ono A. , Hayashi S. , Sekkat Z. 
Published: March 2020

AbstractSurface enhanced absorption is a plasmonic effect parenting to surface enhanced fluorescence and Raman scattering, and it was clearly reported to occur in the infrared region of the spectrum of light. In this paper, we unambiguously show that it also occurs in the visible region of the spectrum by using a dye; i.e. an azo-dye, which exhibits a good light absorption in that region, and gold nanoparticles, which act as plasmonic nanoantennas that capture and re-radiate light, when the azo-dyes and the nanoparticles are incorporated in the bulk of solid films of polymer. In such a configuration, it is possible to use a dye concentration much larger than that of the nanoparticles and absorption path lengths much larger than those of the molecularly thin layers used in surface enhanced effects studies. In addition, the dye undergoes shape and orientation change; i.e. isomerization and reorientation, upon polarized light absorption; and the observation of surface enhanced visible absorption is done by two separate experiments; i.e. UV-visible absorption spectroscopy and photo-induced birefringence, since the signals detected from both experiments are directly proportional to the extinction coefficient of the dye. Both the dye’s absorption and photoorientation are enhanced by the presence of the nanoparticles.
Reaction diffusion system prediction based on convolutional neural network
Authors: Li Angran , Chen Ruijia , Farimani Amir Barati , Zhang Yongjie Jessica 
Published: March 2020

AbstractThe reaction-diffusion system is naturally used in chemistry to represent substances reacting and diffusing over the spatial domain. Its solution illustrates the underlying process of a chemical reaction and displays diverse spatial patterns of the substances. Numerical methods like finite element method (FEM) are widely used to derive the approximate solution for the reaction-diffusion system. However, these methods require long computation time and huge computation resources when the system becomes complex. In this paper, we study the physics of a two-dimensional one-component reaction-diffusion system by using machine learning. An encoder-decoder based convolutional neural network (CNN) is designed and trained to directly predict the concentration distribution, bypassing the expensive FEM calculation process. Different simulation parameters, boundary conditions, geometry configurations and time are considered as the input features of the proposed learning model. In particular, the trained CNN model manages to learn the time-dependent behaviour of the reaction-diffusion system through the input time feature. Thus, the model is capable of providing concentration prediction at certain time directly with high test accuracy (mean relative error <3.04%) and 300 times faster than the traditional FEM. Our CNN-based learning model provides a rapid and accurate tool for predicting the concentration distribution of the reaction-diffusion system.
Functional Consequences of PDK4 Deficiency in Doberman Pinscher Fibroblasts
Authors: Bolfer Luiz , Estrada Amara H. , Larkin Chelsea , Conlon Thomas J. , Lourenco Francisco , Taggart Kathryn , Suzuki-Hatano Silveli , Pacak Christina A. 
Published: March 2020

AbstractA splice site mutation in the canine pyruvate dehydrogenase kinase 4 (PDK4) gene has been shown to be associated with the development of dilated cardiomyopathy (DCM) in Doberman Pinchers (DPs). Subsequent studies have successfully demonstrated the use of dermal fibroblasts isolated from DPs as models for PDK4 deficiency and have shown activation of the intrinsic (mitochondrial mediated) apoptosis pathway in these cells under starvation conditions. For this study, we sought to further explore the functional consequences of PDK4 deficiency in DP fibroblasts representing PDK4wt/wt, PDK4wt/del, and PDK4del/del genotypes. Our results show that starvation conditions cause increased perinuclear localization of mitochondria and decreased cell proliferation, altered expression levels of pyruvate dehydrogenase phosphatase (PDP) and pyruvate dehydrogenase (PDH), dramatically increased PDH activity, and an impaired response to mitochondrial stress in affected cells. In sum, these results show the broad impact of PDK4 deficiency and reveal mechanistic pathways used by these cells in an attempt to compensate for the condition. Our data help to elucidate the mechanisms at play in this extremely prevalent DP disorder and provide further support demonstrating the general importance of metabolic flexibility in cell health.
An atlas of evidence-based phenotypic associations across the mouse phenome
Authors: Tanaka Nobuhiko , Masuya Hiroshi 
Published: March 2020

AbstractTo date, reliable relationships between mammalian phenotypes, based on diagnostic test measurements, have not been reported on a large scale. The purpose of this study was to present a large mouse phenotype-phenotype relationships dataset as a reference resource, alongside detailed evaluation of the resource. We used bias-minimized comprehensive mouse phenotype data and applied association rule mining to a dataset consisting of only binary (normal and abnormal phenotypes) data to determine relationships among phenotypes. We present 3,686 evidence-based significant associations, comprising 345 phenotypes covering 60 biological systems (functions), and evaluate their characteristics in detail. To evaluate the relationships, we defined a set of phenotype-phenotype association pairs (PPAPs) as a module of phenotypic expression for each of the 345 phenotypes. By analyzing each PPAP, we identified phenotype sub-networks consisting of the largest numbers of phenotypes and distinct biological systems. Furthermore, using hierarchical clustering based on phenotype similarities among the 345 PPAPs, we identified seven community types within a putative phenome-wide association network. Moreover, to promote leverage of these data, we developed and published web-application tools. These mouse phenome-wide phenotype-phenotype association data reveal general principles of relationships among mammalian phenotypes and provide a reference resource for biomedical analyses.
Data-Driven Audiogram Classification for Mobile Audiometry
Authors: Charih François , Bromwich Matthew , Mark Amy E. , Lefrançois Renée , Green James R. 
Published: March 2020

AbstractRecent mobile and automated audiometry technologies have allowed for the democratization of hearing healthcare and enables non-experts to deliver hearing tests. The problem remains that a large number of such users are not trained to interpret audiograms. In this work, we outline the development of a data-driven audiogram classification system designed specifically for the purpose of concisely describing audiograms. More specifically, we present how a training dataset was assembled and the development of the classification system leveraging supervised learning techniques. We show that three practicing audiologists had high intra- and inter-rater agreement over audiogram classification tasks pertaining to audiogram configuration, symmetry and severity. The system proposed here achieves a performance comparable to the state of the art, but is significantly more flexible. Altogether, this work lays a solid foundation for future work aiming to apply machine learning techniques to audiology for audiogram interpretation.
Proteinuria is Associated with Urinary Loss of Cubilin and Vitamin D-Binding Protein in Patients with Preeclampsia
Authors: Albejante Maria Clara , Kunz Tânia Cristina Macedo , Ferreira Matheus Feliciano Costa , Júnior José Humberto Zago Ribeiro , de Almeida Robson José , Bacigalupo Lucas dos Santos , Matheus Luiz Henrique Gomes , Dalboni Maria Aparecida , Camacho Cleber Pinto , Dellê Humberto 
Published: March 2020

AbstractWomen with preeclampsia (PE) form a vulnerable group for vitamin D3 deficiency. Reabsorption of vitamin D3 occurs in the proximal tubule after being endocytosed in combination with DBP (vitamin D binding protein) by the megalin/cubilin receptor. Because proteinuria promotes tubule injury and dysfunction, we hypothesized that the proteinuria present in PE could promote the loss of these components into the urine. Twenty preeclamptic patients and ten normal pregnant women with a gestational age greater than 20 weeks composed three groups: NC, normotensive control pregnant patients; PE, non-proteinuric preeclamptic patients; and PPE, preeclamptic patients with proteinuria. When proteinuria was absent, preeclampsia was diagnosed accordingly to the American College of Obstetricians and Gynecologists’ (ACOG) guideline. The presence of 24-hour proteinuria equal to or greater than 300 mg was considered to form the PPE group. Urinary cubilin, megalin, and DBP were measured by ELISA and normalized by urinary creatinine. Regarding gestational age, there was no difference between the groups. NC group had arterial pressure within normal values, whereas PE and PPE groups had a significant increase (p < 0.01). As expected, PPE group presented elevated ACR (p < 0.05), accompanied by large amounts of cubilin and DBP in the urine (p < 0.05 vs. NC and PE). No difference was found in urinary megalin. PPE patients showed more chance of shedding cubilin into the urine compared to non-proteinuric patients (odds ratio 12.7 (1.2–136.3). In conclusion, this study further tightens the relationship between PE and vitamin D3deficiency, since proteinuria present in PE induces the loss of molecules responsible for renal tubular vitamin D3reabsorption for subsequent activation. Combined with other factors, the proteinuria may intensify vitamin D3deficiency in PE.
HIF1 driven transcriptional activity regulates steroidogenesis and proliferation of bovine granulosa cells
Authors: Baddela Vijay Simha , Sharma Arpna , Michaelis Marten , Vanselow Jens 
Published: March 2020

AbstractHypoxia-inducible factor 1 (HIF1) is a heterodimeric transcription factor, consisting of a constitutively expressed β-subunit (HIF1B) and a regulated α-subunit (HIF1A). In the present study, we analyzed the HIF1 driven transcriptional activity in bovine granulosa cells (GC). Treatment of GC with FSH (follicle stimulating hormone) and IGF1 (insulin-like growth factor 1) resulted in the upregulation of HIF1A mRNA expression under normoxia. Immunohistochemistry of bovine ovarian sections showed distinct staining of HIF1A in the GC layer of different staged ovarian follicles. Suppression of HIF1 using echinomycin and gene knockdown procedures revealed that HIF1 transcriptionally regulates the genes associated with steroidogenesis (STAR, HSD3B and CYP19A1) and proliferation (CCND2 and PCNA) of GC. Further, our data suggest that CYP19A1, the key gene of estradiol production, is one of the plausible downstream targets of HIF1 in bovine GC as shown by gene expression, radioimmunoassay, and chromatin precipitation analysis. Based on these results, we propose that HIF1 driven transcriptional activity plays a crucial role in GC functionality, especially steroidogenesis and proliferation in developing bovine ovarian follicles.
Decomposing Simon task BOLD activation using a drift-diffusion model framework
Authors: McIntosh James R. , Sajda Paul 
Published: March 2020

AbstractThe Simon effect is observed in spatial conflict tasks where the response time of subjects is increased if stimuli are presented in a lateralized manner so that they are incongruous with the response information that they represent symbolically. Previous studies have used fMRI to investigate this phenomenon, and while some have been driven by considerations of an underlying model, none have attempted to directly tie model and BOLD response together. It is likely that this is due to Simon models having been predominantly descriptive of the phenomenon rather than capturing the full spectrum of behavior at the level of individual subjects. Sequential sampling models (SSM) which capture full response distributions for correct and incorrect responses have recently been extended to capture conflict tasks. In this study we use our freely available framework for fitting and comparing non-standard SSMs to fit the Simon effect SSM (SE-SSM) to behavioral data. This model extension includes specific estimates of automatic response bias and a conflict counteraction parameter to individual subject behavioral data. We apply this approach in order to investigate whether our task specific model parameters have a correlate in BOLD response. Under the assumption that the SE-SSM reflects aspects of neural processing in this task, we go on to examine the BOLD correlates with the within trial expected decision-variable. We find that the SE-SSM captures the behavioral data and that our two conflict specific model parameters have clear across subject BOLD correlates, while other model parameters, as well as more standard behavioral measures do not. We also find that examining BOLD in terms of the expected decision-variable leads to a specific pattern of activation that would not be otherwise possible to extract.