bluuebunny/crossref_metadata_2025_split huggingface dataset:
How can artificial intelligence models assist PD-L1 expression scoring in breast cancer: results of multi-institutional ring studies
Authors: Wang Xinran , Wang Liang , Bu Hong , Zhang Ningning , Yue Meng , Jia Zhanli , Cai Lijing , He Jiankun , Wang Yanan , Xu Xin , Li Shengshui , Xiao Kaiwen , Yan Kezhou , Tian Kuan , Han Xiao , Huang Junzhou , Yao Jianhua , Liu Yueping 
Published: May 2021

AbstractProgrammed death ligand-1 (PD-L1) expression is a key biomarker to screen patients for PD-1/PD-L1-targeted immunotherapy. However, a subjective assessment guide on PD-L1 expression of tumor-infiltrating immune cells (IC) scoring is currently adopted in clinical practice with low concordance. Therefore, a repeatable and quantifiable PD-L1 IC scoring method of breast cancer is desirable. In this study, we propose a deep learning-based artificial intelligence-assisted (AI-assisted) model for PD-L1 IC scoring. Three rounds of ring studies (RSs) involving 31 pathologists from 10 hospitals were carried out, using the current guideline in the first two rounds (RS1, RS2) and our AI scoring model in the last round (RS3). A total of 109 PD-L1 (Ventana SP142) immunohistochemistry (IHC) stained images were assessed and the role of the AI-assisted model was evaluated. With the assistance of AI, the scoring concordance across pathologists was boosted to excellent in RS3 (0.950, 95% confidence interval (CI): 0.936–0.962) from moderate in RS1 (0.674, 95% CI: 0.614–0.735) and RS2 (0.736, 95% CI: 0.683–0.789). The 2- and 4-category scoring accuracy were improved by 4.2% (0.959, 95% CI: 0.953–0.964) and 13% (0.815, 95% CI: 0.803–0.827) (p < 0.001). The AI results were generally accepted by pathologists with 61% “fully accepted” and 91% “almost accepted”. The proposed AI-assisted method can help pathologists at all levels to improve the PD-L1 assay (SP-142) IC assessment in breast cancer in terms of both accuracy and concordance. The AI tool provides a scheme to standardize the PD-L1 IC scoring in clinical practice.
Treatment scheduling effects on the evolution of drug resistance in heterogeneous cancer cell populations
Authors: Patwardhan Gauri A. , Marczyk Michal , Wali Vikram B. , Stern David F. , Pusztai Lajos , Hatzis Christos 
Published: May 2021

AbstractThe effect of scheduling of targeted therapy combinations on drug resistance is underexplored in triple-negative breast cancer (TNBC). TNBC constitutes heterogeneous cancer cell populations the composition of which can change dynamically during treatment resulting in the selection of resistant clones with a fitness advantage. We evaluated crizotinib (ALK/MET inhibitor) and navitoclax (ABT-263; Bcl-2/Bcl-xL inhibitor) combinations in a large design consisting of 696 two-cycle sequential and concomitant treatment regimens with varying treatment dose, duration, and drug holiday length over a 26-day period in MDA-MB-231 TNBC cells and found that patterns of resistance depend on the schedule and sequence in which the drugs are given. Further, we tracked the clonal dynamics and mechanisms of resistance using DNA-integrated barcodes and single-cell RNA sequencing. Our study suggests that longer formats of treatment schedules in vitro screening assays are required to understand the effects of resistance and guide more realistically in vivo and clinical studies.
Radiation recall dermatitis following letrozole administration in patient with a remote history of radiation therapy
Authors: Sweren Evan , Aravind Pathik , Dembinski Robert , Klein Catherine , Habibi Mehran , Kerns Michelle L. 
Published: May 2021

AbstractWe report the case of letrozole-induced radiation recall dermatitis (RRD) in a patient with a remote history of radiation therapy. There is only one previously known case of RRD triggered by letrozole in a patient with a recent (<3 month) history of radiation. Previously, only four other cases of aromatase-inhibitor-induced RRD have been reported. This case is significant for cancer care teams considering personalized treatments. In addition, improved long-term outcomes in cancer patients may lead to increases in and underdiagnoses of RRD. Likewise, RRD is patient specific, exacerbating health concerns, and can be difficult to recognize without proper awareness, documentation, and classification of triggering drugs. The authors hope to address these issues in this report.
Corrosion performance and degradation mechanism of a bi-metallic aluminum structure processed by wire-arc additive manufacturing
Authors: Azar Amin S. , Lekatou Angeliki , Sunding Martin F. , Graff Joachim S. , Tzima Nicky , Diplas Spyros 
Published: May 2021

AbstractAn Al-5Mg alloy (AA5083) block, deposited over an AA6061 substrate by wire-arc additive manufacturing, was electrochemically tested along two different cross-sectional planes by cyclic polarization in 3.5 wt.% NaCl. The deposited layers and the interlayer boundaries showed similar polarization behavior regardless of the cross-sectional direction. The corrosion of both the substrate and the deposited layers was mainly attributed to the presence of relatively coarse intermetallic Al(Fe, Mn)Si particles. In the substrate, corrosion was governed by deep crevices along the interfaces of directionally aligned Al(Fe, Mn)Si particles with the Al matrix. The deposited layers and the interlayer boundaries showed pitting around numerous Al(Fe, Mn)Si particles and/or Al(Fe, Mn, Cr, Ti)Si at the interlayer boundaries, which were much finer compared to those of the substrate. The abundance of the fine precipitates and their intergranular location caused surface material removal, which was more extensive along the interlayer boundaries. The perpendicularz-yandz-xplanes of the deposited block did not show significant differences in anodic polarization behavior. Differences were more distinct in the case of cathodic polarization. Some anisotropy in polarization behavior was noted through the thickness of thez-yplane that complies with the obtained tensile behavior.
Inhibition of nuclear factor (erythroid-derived 2)-like 2 promotes hepatic progenitor cell activation and differentiation
Authors: Bellanti Francesco , di Bello Giorgia , Iannelli Giuseppina , Pannone Giuseppe , Pedicillo Maria Carmela , Boulter Luke , Lu Wei-Yu , Tamborra Rosanna , Villani Rosanna , Vendemiale Gianluigi , Forbes Stuart J. , Serviddio Gaetano 
Published: May 2021

AbstractThe stem cell ability to self-renew and lead regeneration relies on the balance of complex signals in their microenvironment. The identification of modulators of hepatic progenitor cell (HPC) activation is determinant for liver regeneration and may improve cell transplantation for end-stage liver disease. This investigation used different models to point out the Nuclear factor (erythroid-derived 2)-like 2 (NRF2) as a key regulator of the HPC fate. We initially proved that in vivo models of biliary epithelial cells (BECs)/HPC activation show hepatic oxidative stress, which activates primary BECs/HPCs in vitro. NRF2 downregulation and silencing were associated with morphological, phenotypic, and functional modifications distinctive of differentiated cells. Furthermore, NRF2 activation in the biliary tract repressed the ductular reaction in injured liver. To definitely assess the importance of NRF2 in HPC biology, we applied a xenograft model by inhibiting NRF2 in the human derived HepaRG cell line and transplanting into SCID/beige mice administered with anti-Fas antibody to induce hepatocellular apoptosis; this resulted in effective human hepatocyte repopulation with reduced liver injury. To conclude, NRF2 inhibition leads to the activation and differentiation of liver progenitors. This redox-dependent transcription factor represents a potential target to regulate the commitment of undifferentiated hepatic progenitors into specific lineages.
Aachen-Heerlen annotated steel microstructure dataset
Authors: Iren Deniz , Ackermann Marc , Gorfer Julian , Pujar Gaurav , Wesselmecking Sebastian , Krupp Ulrich , Bromuri Stefano 
Published: May 2021

AbstractStudying steel microstructures yields important insights regarding its mechanical characteristics. Within steel, microstructures transform based on a multitude of factors including chemical composition, transformation temperatures, and cooling rates. Martensite-austenite (MA) islands in bainitic steel appear as blocky structures with abstract shapes that are difficult to identify and differentiate from other types of microstructures. In this regard, material science may benefit from machine learning models that are able to automatically and accurately detect these structures. However, the training process of the state-of-the-art machine learning models requires a large amount of high-quality data. In this dataset, we provide 1.705 scanning electron microscopy images along with a set of 8.909 expert-annotated polygons to describe the geometry of the MA islands that appear on the images. We envision that this dataset will be useful for material scientists to explore the relationship between the morphology of bainitic steel and mechanical characteristics. Moreover, computer vision researchers and practitioners may use this data for training state-of-the-art object segmentation models for abstract geometries such as MA islands.
Computational design of single-stranded DNA hairpin aptamers immobilized on a biosensor substrate
Authors: Jeddi Iman , Saiz Leonor 
Published: May 2021

AbstractAptamer interactions with a surface of attachment are central to the design and performance of aptamer-based biosensors. We have developed a computational modeling approach to study different system designs—including different aptamer-attachment ends, aptamer surface densities, aptamer orientations, and solvent solutions—and applied it to an anti MUC1 aptamer tethered to a silica biosensor substrate. Amongst all the system designs explored, we found that attaching the anti MUC1 aptamer through the 5′ terminal end, in a high surface density configuration, and solvated in a 0.8 M NaCl solution provided the best exposure of the aptamer MUC1 binding regions and resulted in the least amount of aptamer backbone fluctuations. Many of the other designs led to non-functional systems, with the aptamer collapsing onto the surface. The computational approach we have developed and the resulting analysis techniques can be employed for the rational design of aptamer-based biosensors and provide a valuable tool for improving biosensor performance and repeatability.
Prenatal exposures to mixtures of endocrine disrupting chemicals and children’s weight trajectory up to age 5.5 in the SELMA study
Authors: Svensson Katherine , Tanner Eva , Gennings Chris , Lindh Christian , Kiviranta Hannu , Wikström Sverre , Bornehag Carl-Gustaf 
Published: May 2021

AbstractExposure to endocrine disrupting chemicals (EDCs) may impact early growth, although information is limited on exposure to combination of multiple EDCs. We aimed to evaluate the effect of prenatal exposure to EDC mixtures on birthweight z-scores and childhood weight trajectories. Twenty-six proven and suspected EDCs, were analyzed in prenatal urine and blood samples from 1118 mothers participating in the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) study. Two growth parameters were estimated from each child’s weight trajectory from birth to 5.5 years of age: infant growth spurt rate and age at infant peak growth velocity (PGV). Weighted quantile sum (WQS) regression was used to estimate the mixture effect and identify chemicals of concern. A one-unit increase in the EDC mixture WQS index, was associated with decreased birthweight z-scores of 0.11 (95% CI − 0.16, − 0.06), slower infant growth spurt rate of 0.01 (95% CI − 0.03, − 0.01, on the log10 scale), and delayed age at infant PGV of 0.15 months (95% CI 0.07, 0.24) after adjusting for potential confounders. Stratified analysis by sex, showed that delayed age at infant PGV was mostly observed in girls with 0.51 months (95% CI 0.26, 0.76). Identified chemicals of concern included perfluorinated alkyl substances (PFAS), Triclosan, phthalates, non-phthalate plasticizers, bisphenols, polycyclic aromatic hydrocarbons, pesticides and PCBs. Prenatal exposure to EDC mixtures was associated with lower birthweight and altered infant weight gain trajectories.
Live cell dynamics of the NF-Y transcription factor
Authors: Priest David G. , Bernardini Andrea , Lou Jieqiong , Mantovani Roberto , Hinde Elizabeth 
Published: May 2021

AbstractTranscription factors (TFs) are core players in the control of gene expression, evolutionarily selected to recognise a subset of specific DNA sequences and nucleate the recruitment of the transcriptional machinery. How TFs assemble and move in the nucleus to locate and bind their DNA targets and cause a transcriptional response, remains mostly unclear. NF-Y is a highly conserved, heterotrimeric TF with important roles in both housekeeping and lineage-specific gene expression, functioning as a promoter organiser. Despite a large number of biochemical, structural and genomic studies of NF-Y, there is a lack of experiments in single living cells; therefore, basic assumptions of NF-Y biology remain unproven in vivo. Here we employ a series of dynamic fluorescence microscopy methods (FLIM-FRET, NB, RICS and FRAP) to study NF-Y dynamics and complex formation in live cells. Specifically, we provide quantitative measurement of NF-Y subunit association and diffusion kinetics in the nucleus that collectively suggest NF-Y to move and bind chromatin as a trimeric complex in vivo.
Pulmonary effects of dexmedetomidine infusion in thoracic aortic surgery under hypothermic circulatory arrest: a randomized placebo-controlled trial
Authors: Kim Seongsu , Park Soo Jung , Nam Sang Beom , Song Suk-Won , Han Yeonseung , Ko Sangmin , Song Young 
Published: May 2021

AbstractDexmedetomidine has emerged as a promising organ protective agent. We performed prospective randomized placebo-controlled trial investigating effects of perioperative dexmedetomidine infusion on pulmonary function following thoracic aortic surgery with cardiopulmonary bypass and moderate hypothermic circulatory arrest. Fifty-two patients were randomized to two groups: the dexmedetomidine group received 1 µg/kg of dexmedetomidine over 20 min after induction of anesthesia, followed by 0.5 µg/kg/h infusion until 12 h after aortic cross clamp (ACC)-off, while the control group received the same volume of normal saline. The primary endpoints were oxygenation indices including arterial O2 partial pressure (PaO2) to alveolar O2 partial pressure ratio (a/A ratio), (A–a) O2 gradient, PaO2/FiO2 and lung mechanics including peak inspiratory and plateau pressures and compliances, which were assessed after anesthesia induction, 1 h, 6 h, 12 h, and 24 h after ACC-off. The secondary endpoints were serum biomarkers including interleukin-6, tumor necrosis factor-α, superoxide dismutase, and malondialdehyde (MDA). As a result, dexmedetomidine did not confer protective effects on the lungs, but inhibited elevation of serum MDA level, indicative of anti-oxidative stress property, and improved urine output and lower requirements of vasopressors.
Proteomic analysis-based discovery of a novel biomarker that differentiates intestinal Behçet’s disease from Crohn’s disease
Authors: Park Jihye , Jeong Daeun , Chung Youn Wook , Han Seunghan , Kim Da Hye , Yu Jongwook , Cheon Jae Hee , Ryu Ji-Hwan 
Published: May 2021

AbstractIntestinal Behçet’s disease (BD) and Crohn’s disease (CD) present similar manifestations, but there are no specific diagnostic tests to differentiate them. We used a proteomic approach to discover novel diagnostic biomarkers specific to intestinal BD. Colon mucosa tissue samples were obtained from patients with intestinal BD or CD using colonoscopy-guided biopsy of the affected bowel. Peptides from seven intestinal BD and seven CD patients were extracted and labeled using tandem mass tag (TMT) reagents. The labeled peptides were identified and quantified using liquid chromatography-tandem mass spectrometry (LC–MS/MS). The proteins were further validated using immunohistochemical (IHC) analysis with tissue samples and an ELISA test with serum samples from 20 intestinal BD and 20 CD patients. Using TMT/LC–MS/MS-based proteomic quantification, we identified 39 proteins differentially expressed between intestinal BD and CD. Beta-2 glycoprotein 1 (APOH) and maltase-glucoamylase (MGAM) showed higher intensity in the IHC staining of intestinal BD tissues than in CD tissues. The serum MGAM level was higher in intestinal BD patients. Proteomic analysis revealed that some proteins were differentially expressed in patients with intestinal BD compared with those with CD. Differential MGAM expression in intestinal BD suggests its role as a potential novel diagnostic biomarker.
A merged molecular representation learning for molecular properties prediction with a web-based service
Authors: Kim Hyunseob , Lee Jeongcheol , Ahn Sunil , Lee Jongsuk Ruth 
Published: May 2021

AbstractDeep learning has brought a dramatic development in molecular property prediction that is crucial in the field of drug discovery using various representations such as fingerprints, SMILES, and graphs. In particular, SMILES is used in various deep learning models via character-based approaches. However, SMILES has a limitation in that it is hard to reflect chemical properties. In this paper, we propose a new self-supervised method to learn SMILES and chemical contexts of molecules simultaneously in pre-training the Transformer. The key of our model is learning structures with adjacency matrix embedding and learning logics that can infer descriptors via Quantitative Estimation of Drug-likeness prediction in pre-training. As a result, our method improves the generalization of the data and achieves the best average performance by benchmarking downstream tasks. Moreover, we develop a web-based fine-tuning service to utilize our model on various tasks.
Abandonment and rapid infilling of a tide-dominated distributary channel at 0.7 ka in the Mekong River Delta
Authors: Gugliotta Marcello , Saito Yoshiki , Ta Thi Kim Oanh , Nguyen Van Lap , Tamura Toru , Wang Zhanghua , La Croix Andrew D. , Nakashima Rei 
Published: May 2021

AbstractThe Ba Lai distributary channel of the Mekong River Delta was abandoned and infilled with sediment during the Late Holocene, providing a unique opportunity to investigate the sediment fill, timing and mechanisms of channel abandonment in tide-dominated deltaic systems. Based on analysis and age dating of four sediment cores, we show that the channel was active since 2.6 ka and was abandoned at 0.7 ka as marked by the abrupt disappearance of the sand fraction and increase in organic matter and sediment accumulation rate. We estimate that the channel might have been filled in a time range of 45–263 years after detachment from the deltaic network, with sediment accumulation rates of centimetres to decimetres per year, rapidly storing approximately 600 Mt of organic-rich mud. We suggest that the channel was abandoned due to a sediment buildup favoured by an increase in regional sediment supply to the delta. This study highlights that mechanisms for abandonment and infilling of tide-dominated deltaic channels do not entirely fit widely used models developed for fluvial-dominated environments. Their abandonment might be driven by autogenic factors related to the river-tidal and deltaic dynamics and favoured by allogenic factors (e.g., human impact and/or climate change).
Infants exploit vowels to label objects and actions from continuous audiovisual stimuli
Authors: Jara Cristina , Moënne-Loccoz Cristóbal , Peña Marcela 
Published: May 2021

AbstractBefore the 6-months of age, infants succeed to learn words associated with objects and actions when the words are presented isolated or embedded in short utterances. It remains unclear whether such type of learning occurs from fluent audiovisual stimuli, although in natural environments the fluent audiovisual contexts are the default. In 4 experiments, we evaluated if 8-month-old infants could learn word-action and word-object associations from fluent audiovisual streams when the words conveyed either vowel or consonant harmony, two phonological cues that benefit word learning near 6 and 12 months of age, respectively. We found that infants learned both types of words, but only when the words contained vowel harmony. Because object- and action-words have been conceived as rudimentary representations of nouns and verbs, our results suggest that vowels contribute to shape the initial steps of the learning of lexical categories in preverbal infants.
ADAMTS12 acts as a tumor microenvironment related cancer promoter in gastric cancer
Authors: Hou Yangming , Xu Yingjuan , Wu Dequan 
Published: May 2021

AbstractThe infiltration degree of immune and stromal cells has been shown clinically significant in tumor microenvironment (TME). However, the utility of stromal and immune components in Gastric cancer (GC) has not been investigated in detail. In the present study, ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cell (TIC) in GC cohort, including 415 cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were screened by Cox proportional hazard regression analysis and protein–protein interaction (PPI) network construction. Then ADAMTS12 was regarded as one of the most predictive factors. Further analysis showed that ADAMTS12 expression was significantly higher in tumor samples and correlated with poor prognosis. Gene Set Enrichment Analysis (GSEA) indicated that in high ADAMTS12 expression group gene sets were mainly enriched in cancer and immune-related activities. In the low ADAMTS12 expression group, the genes were enriched in the oxidative phosphorylation pathway. CIBERSORT analysis for the proportion of TICs revealed that ADAMTS12 expression was positively correlated with Macrophages M0/M1/M2 and negatively correlated with T cells follicular helper. Therefore, ADAMTS12 might be a tumor promoter and responsible for TME status and tumor energy metabolic conversion.
Olfactory coding in the antennal lobe of the bumble bee Bombus terrestris
Authors: Mertes Marcel , Carcaud Julie , Sandoz Jean-Christophe 
Published: May 2021

AbstractSociality is classified as one of the major transitions in evolution, with the largest number of eusocial species found in the insect order Hymenoptera, including the Apini (honey bees) and the Bombini (bumble bees). Bumble bees and honey bees not only differ in their social organization and foraging strategies, but comparative analyses of their genomes demonstrated that bumble bees have a slightly less diverse family of olfactory receptors than honey bees, suggesting that their olfactory abilities have adapted to different social and/or ecological conditions. However, unfortunately, no precise comparison of olfactory coding has been performed so far between honey bees and bumble bees, and little is known about the rules underlying olfactory coding in the bumble bee brain. In this study, we used in vivo calcium imaging to study olfactory coding of a panel of floral odorants in the antennal lobe of the bumble bee Bombus terrestris. Our results show that odorants induce reproducible neuronal activity in the bumble bee antennal lobe. Each odorant evokes a different glomerular activity pattern revealing this molecule’s chemical structure, i.e. its carbon chain length and functional group. In addition, pairwise similarity among odor representations are conserved in bumble bees and honey bees. This study thus suggests that bumble bees, like honey bees, are equipped to respond to odorants according to their chemical features.