bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-L1 regulates cell proliferation and apoptosis in acute myeloid leukemia by activating PI3K-AKT signaling pathway
Authors: Wang Fang , Yang Liqiong , Xiao Mintao , Zhang Zhuo , Shen Jing , Anuchapreeda Songyot , Tima Singkome , Chiampanichayakul Sawitree , Xiao Zhangang 
Published: July 2022

AbstractAs immune checkpoint inhibitors (ICIs) continue to advance, more evidence has emerged that anti-PD-1/PD-L1 immunotherapy is an effective treatment against cancers. Known as the programmed death ligand-1 (PD-L1), this co-inhibitory ligand contributes to T cell exhaustion by interacting with programmed death-1 (PD-1) receptor. However, cancer-intrinsic signaling pathways of the PD-L1 molecule are not well elucidated. Therefore, the present study aimed to evaluate the regulatory network of PD-L1 and lay the basis of successful use of anti-PD-L1 immunotherapy in acute myeloid leukemia (AML). Data for AML patients were extracted from TCGA and GTEx databases. The downstream signaling pathways of PD-L1 were identified via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The key PD-L1 related genes were selected by weighted gene co-expression network analysis (WGCNA), MCC algorithm and Molecular Complex Detection (MCODE). The CCK-8 assay was used to assess cell proliferation. Flow cytometry was used to determine cell apoptosis and cell cycle. Western blotting was used to identify the expression of the PI3K-AKT signaling pathway. PD-L1 was shown to be elevated in AML patients when compared with the control group, and high PD-L1 expression was associated with poor overall survival rate. The ECM-receptor interaction, as well as the PI3K-AKT signaling pathway, were important PD-L1 downstream pathways. All three analyses found eight genes (ITGA2B, ITGB3, COL6A5, COL6A6, PF4, NMU, AGTR1, F2RL3) to be significantly associated with PD-L1. Knockdown of PD-L1 inhibited AML cell proliferation, induced cell apoptosis and G2/M cell cycle arrest. Importantly, PD-L1 knockdown reduced the expression of PI3K and p-AKT, but PD-L1 overexpression increased their expression. The current study elucidates the main regulatory network and downstream targets of PD-L1 in AML, assisting in the understanding of the underlying mechanism of anti-PD-1/PD-L1 immunotherapy and paving the way for clinical application of ICIs in AML.
Gut microbiota composition in colorectal cancer patients is genetically regulated
Authors: Colombo Francesca , Illescas Oscar , Noci Sara , Minnai Francesca , Pintarelli Giulia , Pettinicchio Angela , Vannelli Alberto , Sorrentino Luca , Battaglia Luigi , Cosimelli Maurizio , Dragani Tommaso A. , Gariboldi Manuela 
Published: July 2022

AbstractThe risk of colorectal cancer (CRC) depends on environmental and genetic factors. Among environmental factors, an imbalance in the gut microbiota can increase CRC risk. Also, microbiota is influenced by host genetics. However, it is not known if germline variants influence CRC development by modulating microbiota composition. We investigated germline variants associated with the abundance of bacterial populations in the normal (non-involved) colorectal mucosa of 93 CRC patients and evaluated their possible role in disease. Using a multivariable linear regression, we assessed the association between germline variants identified by genome wide genotyping and bacteria abundances determined by 16S rRNA gene sequencing. We identified 37 germline variants associated with the abundance of the generaBacteroides, Ruminococcus, Akkermansia, FaecalibacteriumandGemmigerand with alpha diversity. These variants are correlated with the expression of 58 genes involved in inflammatory responses, cell adhesion, apoptosis and barrier integrity. Genes and bacteria appear to be involved in the same processes. In fact, expression of the pro-inflammatory genesGAL,GSDMDandLY6Hwas correlated with the abundance ofBacteroides, which has pro-inflammatory properties; abundance of the anti-inflammatory genusFaecalibacteriumcorrelated with expression of KAZN, with barrier-enhancing functions. Both the microbiota composition and local inflammation are regulated, at least partially, by the same germline variants. These variants may regulate the microenvironment in which bacteria grow and predispose to the development of cancer. Identification of these variants is the first step to identifying higher-risk individuals and proposing tailored preventive treatments that increase beneficial bacterial populations.
Microfluidic model for in vitro acute Toxoplasma gondii infection and transendothelial migration
Authors: Kim Hyunho , Hong Sung-Hee , Jeong Hyo Eun , Han Sewoon , Ahn Jinchul , Kim Jin-A. , Yang Ji-Hun , Oh Hyun Jeong , Chung Seok , Lee Sang-Eun 
Published: July 2022

AbstractThe protozoan parasiteToxoplasma gondii(T. gondii) causes one of the most common human zoonotic diseases and infects approximately one-third of the global population.T. gondiiinfects nearly every cell type and causes severe symptoms in susceptible populations. In previous laboratory animal studies,T. gondiimovement and transmission were not analyzed in real time. In a three-dimensional (3D) microfluidic assay, we successfully supported the complex lytic cycle ofT. gondiiin situ by generating a stable microvasculature. The physiology of theT. gondii-infected microvasculature was monitored in order to investigate the growth, paracellular and transcellular migration, and transmission ofT. gondii, as well as the efficacy ofT. gondiidrugs.
A unique peptide-based pharmacophore identifies an inhibitory compound against the A-subunit of Shiga toxin
Authors: Watanabe-Takahashi Miho , Senda Miki , Yoshino Ryunosuke , Hibino Masahiro , Hama Shinichiro , Terada Tohru , Shimizu Kentaro , Senda Toshiya , Nishikawa Kiyotaka 
Published: July 2022

AbstractShiga toxin (Stx), a major virulence factor of enterohemorrhagic Escherichia coli (EHEC), can cause fatal systemic complications. Recently, we identified a potent inhibitory peptide that binds to the catalytic A-subunit of Stx. Here, using biochemical structural analysis and X-ray crystallography, we determined a minimal essential peptide motif that occupies the catalytic cavity and is required for binding to the A-subunit of Stx2a, a highly virulent Stx subtype. Molecular dynamics simulations also identified the same motif and allowed determination of a unique pharmacophore for A-subunit binding. Notably, a series of synthetic peptides containing the motif efficiently inhibit Stx2a. In addition, pharmacophore screening and subsequent docking simulations ultimately identified nine Stx2a-interacting molecules out of a chemical compound database consisting of over 7,400,000 molecules. Critically, one of these molecules markedly inhibits Stx2a both in vitro and in vivo, clearly demonstrating the significance of the pharmacophore for identifying therapeutic agents against EHEC infection.
Early retinal functional alteration in relation to diabetes duration in patients with type 2 diabetes without diabetic retinopathy
Authors: Srinivasan Sangeetha , Sivaprasad Sobha , Rajalakshmi Ramachandran , Anjana Ranjit Mohan , Malik Rayaz A. , Kulothungan Vaitheeswaran , Natarajan Viswanathan , Raman Rajiv , Bhende Muna 
Published: July 2022

AbstractTo examine the retinal structure and function in relation to diabetes duration and glycemia in patients without diabetic retinopathy (DR). 85 adults with type 2 diabetes without DR or macular edema underwent dilated indirect ophthalmoscopy, optical coherence tomography (OCT), ultra-wide field fundus photography, multifocal electroretinography (mfERG) and HbA1C assessment. Patients were stratified as those with diabetes duration < 10 years and ≥ 10 years. Right eyes of all participants were analyzed. mfERG was analysed as ring 12, 34, 56. No significant differences were noted in OCT-derived retinal thickness measures between groups. mfERG P1 latencies were delayed, and amplitudes (nV/deg2) were reduced in all three rings in those with diabetes duration ≥ 10 years vs. < 10 years, with significant correlations to diabetes duration in all rings. Logistic regression showed that duration of diabetes ≥ 10 years was associated with greater age (odds ratio (OR) 1.081, 95% CI 1.022, 1.143) and lower P1 amplitudes in the middle ring (OR 0.924, 95% CI 0.854, 0.999). No significant correlations were observed between HbA1c and retinal measures. In the absence of DR, early retinal functional alterations are detectable on mfERG in patients with longer diabetes duration, but with no difference in OCT-derived retinal thickness.
A deep convolutional neural network for Kawasaki disease diagnosis
Authors: Xu Ellen , Nemati Shamim , Tremoulet Adriana H. 
Published: July 2022

AbstractKawasaki disease (KD), the most common cause of acquired heart disease in children, can be easily missed as it shares clinical findings with other pediatric illnesses, leading to risk of myocardial infarction or death. KD remains a clinical diagnosis for which there is no diagnostic test, yet there are classic findings on exam that can be captured in a photograph. This study aimed to develop a deep convolutional neural network, KD-CNN, to differentiate photographs of KD clinical signs from those of other pediatric illnesses. To create the dataset, we used an innovative combination of crowdsourcing images and downloading from public domains on the Internet. KD-CNN was then pretrained using transfer learning from VGG-16 and fine-tuned on the KD dataset, and methods to compensate for limited data were explored to improve model performance and generalizability. KD-CNN achieved a median AUC of 0.90 (IQR 0.10 from tenfold cross validation), with a sensitivity of 0.80 (IQR 0.18) and specificity of 0.85 (IQR 0.19) to distinguish between children with and without clinical manifestations of KD. KD-CNN is a novel application of CNN in medicine, with the potential to assist clinicians in differentiating KD from other pediatric illnesses and thus reduce KD morbidity and mortality.
Integrated electrocoagulation-flotation of microalgae to produce Mg-laden microalgal biochar for seeding struvite crystallization
Authors: Nageshwari Krishnamoorthy , Chang Scott X. , Balasubramanian Paramasivan 
Published: July 2022

AbstractDeveloping sustainable materials for recovering and recycling nutrients from wastewater is critically needed for nutrients such as phosphorus that have a diminishing supply. Struvite crystallization is emerging as a promising strategy for phosphorus recovery which can be enhanced with seeding through microalgal biochar. The main bottleneck of using microalgae is its high harvesting cost. In this study, an integrated electrocoagulation-flotation (ECF) process is used to recover and at the same time modify the algal surface with magnesium anode and inert carbon cathode. Harvesting efficiency of 98% was achieved with 40.78 mA cm−2, 0.5 cm inter-electrode distance and energy consumption of 4.03 kWh kg−1 in 15 min. The harvested microalgae were pyrolyzed to obtain a yield of 52.90% Mg-laden microalgal biochar. Simultaneously, surface impregnation of 28% magnesium was attained as confirmed by Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). Phosphorus recovery and struvite yield of 93.70% and 2.66 g L−1, respectively, were obtained from dosing 1.50 g L−1 Mg-laden microalgal biochar. Comparison of physicochemical characteristics of residual supernatant after microalgal harvesting and struvite recovery showed that the combined use of both the residuals can serve as a sustainable growth medium for microalgae. The overall operating cost of the integrated process was found to be 2.48 USD kg−1 with a total energy consumption of 10.76 kWh kg−1, which was found to be lower than conventional harvesting unit processes such as centrifugation and filtration. This novel approach can help attaining a circular bioeconomy by encompassing nutrient recovery and waste management in an integrated process.
Prognostic and therapeutic prediction by screening signature combinations from transcriptome–methylome interactions in oral squamous cell carcinoma
Authors: Shi Congyu , Liu Shan , Tian Xudong , Miao Cheng , Wang Renyi , Ma Xiangrui , Wang Xiaoyi , Cao Yubin 
Published: July 2022

AbstractDNA methylation pattern in oral squamous cell carcinoma (OSCC) remains poorly described. This study aimed to perform a genome-wide integrated analysis of the transcriptome and methylome and assess the efficacy of their prognostic signature model in patients with OSCC. We analyzed transcriptome and methylome data from 391 OSCC samples and 41 adjacent normal samples. A total of 8074 differentially expressed genes (DEGs) and 10,084 differentially expressed CpGs (DMCpGs) were identified. Then 241 DEGs with DMCpGs were identified. According to the prognostic analysis, the prognostic signature of methylation-related differentially expressed genes (mrDEGPS) was established. mrDEGPS consisted of seven prognostic methylation-related genes, including ESRRG, CCNA1, SLC20A1, COL6A6, FCGBP, CDKN2A, and ZNF43. mrDEGPS was a significant stratification factor of survival (P < 0.00001) irrespective of the clinical stage. The immune effector components, including B cells, CD4+ T cells, and CD8+ T cells, were decreased in the tumor environment of patients with high mrDEGPS. Immune checkpoint expressions, including CTLA-4, PD-1, LAG3, LGALS9, HAVCR2, and TIGHT, were comprehensively elevated (P < 0.001). The estimated half-maximal inhibitory concentration difference between low- and high-risk patients was inconsistent among chemotherapeutic drugs. In conclusion, the transcriptome–methylome interaction pattern in OSCC is complex. mrDEGPS can predict patient survival and responses to immunotherapy and chemotherapy and facilitate clinical decision-making in patients with OSCC.
Perceptual changes after learning of an arbitrary mapping between vision and hand movements
Authors: Kirsch Wladimir , Kunde Wilfried 
Published: July 2022

AbstractThe present study examined the perceptual consequences of learning arbitrary mappings between visual stimuli and hand movements. Participants moved a small cursor with their unseen hand twice to a large visual target object and then judged either the relative distance of the hand movements (Exp.1), or the relative number of dots that appeared in the two consecutive target objects (Exp.2) using a two-alternative forced choice method. During a learning phase, the numbers of dots that appeared in the target object were correlated with the hand movement distance. In Exp.1, we observed that after the participants were trained to expect many dots with larger hand movements, they judged movements made to targets with many dots as being longer than the same movements made to targets with few dots. In Exp.2, another group of participants who received the same training judged the same number of dots as smaller when larger rather than smaller hand movements were executed. When many dots were paired with smaller hand movements during the learning phase of both experiments, no significant changes in the perception of movements and of visual stimuli were observed. These results suggest that changes in the perception of body states and of external objects can arise when certain body characteristics co-occur with certain characteristics of the environment. They also indicate that the (dis)integration of multimodal perceptual signals depends not only on the physical or statistical relation between these signals, but on which signal is currently attended.
People with HIV have higher percentages of circulating CCR5+ CD8+ T cells and lower percentages of CCR5+ regulatory T cells
Authors: van Eekeren Louise E. , Matzaraki Vasiliki , Zhang Zhenhua , van de Wijer Lisa , Blaauw Marc J. T. , de Jonge Marien I. , Vandekerckhove Linos , Trypsteen Wim , Joosten Leo A. B. , Netea Mihai G. , de Mast Quirijn , Koenen Hans J. P. M. , Li Yang , van der Ven André J. A. M. 
Published: July 2022

AbstractCCR5 is the main HIV co-receptor. We aimed to (1) compare CCR5 expression on immune cells between people living with HIV (PLHIV) using combination antiretroviral therapy (cART) and HIV-uninfected controls, (2) relate CCR5 expression to viral reservoir size and (3) assess determinants of CCR5 expression. This cross-sectional study included 209 PLHIV and 323 controls. Percentages of CCR5+ cells (%) and CCR5 mean fluorescence intensity assessed by flow cytometry in monocytes and lymphocyte subsets were correlated to host factors, HIV-1 cell-associated (CA)-RNA and CA-DNA, plasma inflammation markers and metabolites. Metabolic pathways were identified. PLHIV displayed higher percentages of CCR5+ monocytes and several CD8+ T cell subsets, but lower percentages of CCR5+ naive CD4+ T cells and regulatory T cells (Tregs). HIV-1 CA-DNA and CA-RNA correlated positively with percentages of CCR5+ lymphocytes. Metabolome analysis revealed three pathways involved in energy metabolism associated with percentage of CCR5+ CD8+ T cells in PLHIV. Our results indicate that CCR5 is differently expressed on various circulating immune cells in PLHIV. Hence, cell-trafficking of CD8+ T cells and Tregs may be altered in PLHIV. Associations between energy pathways and percentage of CCR5+ CD8+ T cells in PLHIV suggest higher energy demand of these cells in PLHIV.
Short-term mercury exposure disrupts muscular and hepatic lipid metabolism in a migrant songbird
Authors: Seewagen Chad L. , Elowe Cory R. , Gerson Alexander R. , Groom Derrick J. E. , Ma Yanju , Yildirim Mustafa , Guglielmo Christopher G. 
Published: July 2022

AbstractMethylmercury (MeHg) is a global pollutant that can cause metabolic disruptions in animals and thereby potentially compromise the energetic capacity of birds for long-distance migration, but its effects on avian lipid metabolism pathways that support endurance flight and stopover refueling have never been studied. We tested the effects of short-term (14-d), environmentally relevant (0.5 ppm) dietary MeHg exposure on lipid metabolism markers in the pectoralis and livers of yellow-rumped warblers (Setophaga coronata) that were found in a previous study to have poorer flight endurance in a wind tunnel than untreated conspecifics. Compared to controls, MeHg-exposed birds displayed lower muscle aerobic and fatty acid oxidation capacity, but similar muscle glycolytic capacity, fatty acid transporter expression, and PPAR expression. Livers of exposed birds indicated elevated energy costs, lower fatty acid uptake capacity, and lower PPAR-γ expression. The lower muscle oxidative enzyme capacity of exposed birds likely contributed to their weaker endurance in the prior study, while the metabolic changes observed in the liver have potential to inhibit lipogenesis and stopover refueling. Our findings provide concerning evidence that fatty acid catabolism, synthesis, and storage pathways in birds can be dysregulated by only brief exposure to MeHg, with potentially significant consequences for migratory performance.
RETRACTED ARTICLE: Lateral palatal foramina do
not indicate baleen in fossil whales
Authors: Peredo Carlos Mauricio , Pyenson Nicholas D. , Uhen Mark D. 
Published: July 2022

Abstract
Today’s mysticetes filter-feed using baleen, a novel integumentary
structure with no apparent homolog in any living mammal. The origins of filter-feeding
and baleen can be informed by the fossil record, including rare instances of soft tissue
preservation of baleen and also by potential osteological correlates of baleen. Lateral
palatal foramina on the roof of the mouth have been proposed as potential osteological
correlates of baleen and their presence in some tooth-bearing stem mysticetes has led to
the hypothesis that these early mysticetes possessed both teeth and incipient baleen.
Here, we test this hypothesis by examining lateral palatal foramina in both
filter-feeding and non-filter-feeding cetaceans, including crown and stem odontocetes
and in stem cetaceans (or archaeocetes). We also confirm the presence of lateral palatal
foramina in 61 species of terrestrial artiodactyls. CT scanning demonstrates consistent
internal morphology across all observed taxa, suggesting that the lateral palatal
foramina observed in extant mysticetes are homologous to those of terrestrial
artiodactyls. The presence of lateral palatal foramina in terrestrial artiodactyls and
non-filter-feeding whales (odontocetes and archaeocetes) suggests that these structures
are not unique predictors for the presence of baleen in fossil whales; instead, these
structures are more probably associated with gingiva or other oral tissue.
Towards symbiotic approaches between universities, sustainable development, and cities
Authors: Leal Filho Walter , Caughman Liliana , Pimenta Dinis Maria Alzira , Frankenberger Fernanda , Azul Anabela Marisa , Salvia Amanda Lange 
Published: July 2022

AbstractUniversities are key actors and play a central role in the cities which host them, either as employers, consumers or simply as a magnet to young people and cultural activities. They can be also influencers and supporters of cities in the field of sustainable development. Through an exploratory method and aiming to explore the efforts deployed to foster closer links between universities, sustainable development, and cities and address a literature gap in this regard, this study considers the contribution of universities to sustainable development at the city level. Based on some of the ongoing initiatives worldwide and an international online survey documenting measures undertaken, this study translates the commitment to pursuing sustainable development within cities, with responses from a sample of 45 countries. This study lists some items which may help foster more symbiotic relations between cities and universities. The findings of this study may be used as baselines for strengthening the connections between universities and cities in addressing the sustainable development challenges, as demonstrated through the responses obtained. Accordingly, some suggested actions involving cooperation may include increased communication with city stakeholders and the undertaking of joint initiatives and projects, taking advantage of the ongoing sustainable development challenges worldwide.
Patterns of interest change in stack overflow
Authors: Fu Chenbo , Yue Xinchen , Shen Bin , Yu Shanqing , Min Yong 
Published: July 2022

AbstractStack Overflow is currently the largest programming related question and answer community, containing multiple programming areas. The change of user’s interest is the micro-representation of the intersection of macro-knowledge and has been widely studied in scientific fields, such as literature data sets. However, there is still very little research for the general public, such as the question and answer community. Therefore, we analyze the interest changes of 2,307,720 users in Stack Overflow in this work. Specifically, we classify the tag network in the community, vectorize the topic of questions to quantify the user’s interest change patterns. Results show that the change pattern of user interest has the characteristic of a power-law distribution, which is different from the exponential distribution of scientists’ interest change, but they are all affected by three features, heterogeneity, recency and proximity. Furthermore, the relationship between users’ reputations and interest changes is negatively correlated, suggesting the importance of concentration, i.e., those who focus on specific areas are more likely to gain a higher reputation. In general, our work is a supplement to the public interest changes in science, and it can also help community managers better design recommendation algorithms and promote the healthy development of communities.