bluuebunny/crossref_metadata_2025_split huggingface dataset:
3-Hydroxy coumarin demonstrates anti-biofilm and anti-hyphal efficacy against Candida albicans via inhibition of cell-adhesion, morphogenesis, and virulent genes regulation
Authors: Sushmitha T. J. , Rajeev Meora , Kathirkaman Vellaisamy , Shivam Singh , Rao Toleti Subba , Pandian Shunmugiah Karutha 
Published: July 2023

AbstractCandida albicans, a common fungus of human flora, can become an opportunistic pathogen and causes invasive candidiasis in immunocompromised individuals. Biofilm formation is the prime cause of antibiotic resistance during C. albicans infections and treating biofilm-forming cells is challenging due to their intractable and persistent nature. The study intends to explore the therapeutic potential of naturally produced compounds by competitive marine bacteria residing in marine biofilms against C. albicans biofilm. To this end, 3-hydroxy coumarin (3HC), a compound identified from the cell-free culture supernatant of the marine bacterium Brevundimonas abyssalis, was found to exhibit anti-biofilm and anti-hyphal activity against both reference and clinical isolates of C. albicans. The compound demonstrated significant inhibitory effects on biofilms and impaired the yeast-to-hyphal transition, wrinkle, and filament morphology at the minimal biofilm inhibitory concentration (MBIC) of 250 µg mL−1. Intriguingly, quantitative PCR analysis of 3HC-treated C. albicans biofilm revealed significant downregulation of virulence genes (hst7, ume6, efg1, cph1, ras1, als1) associated with adhesion and morphogenesis. Moreover, 3HC displayed non-fungicidal and non-toxic characteristics against human erythrocytes and buccal cells. In conclusion, this study showed that marine biofilms are a hidden source of diverse therapeutic drugs, and 3HC could be a potent drug to treat C. albicans infections.
SinusC-Net for automatic classification of surgical plans for maxillary sinus augmentation using a 3D distance-guided network
Authors: Hwang In-Kyung , Kang Se-Ryong , Yang Su , Kim Jun-Min , Kim Jo-Eun , Huh Kyung-Hoe , Lee Sam-Sun , Heo Min-Suk , Yi Won-Jin , Kim Tae-Il 
Published: July 2023

AbstractThe objective of this study was to automatically classify surgical plans for maxillary sinus floor augmentation in implant placement at the maxillary posterior edentulous region using a 3D distance-guided network on CBCT images. We applied a modified ABC classification method consisting of five surgical approaches for the deep learning model. The proposed deep learning model (SinusC-Net) consisted of two stages of detection and classification according to the modified classification method. In detection, five landmarks on CBCT images were automatically detected using a volumetric regression network; in classification, the CBCT images were automatically classified as to the five surgical approaches using a 3D distance-guided network. The mean MRE for landmark detection was 0.87 mm, and SDR for 2 mm or lower, 95.47%. The mean accuracy, sensitivity, specificity, and AUC for classification by the SinusC-Net were 0.97, 0.92, 0.98, and 0.95, respectively. The deep learning model using 3D distance-guidance demonstrated accurate detection of 3D anatomical landmarks, and automatic and accurate classification of surgical approaches for sinus floor augmentation in implant placement at the maxillary posterior edentulous region.
Effectiveness of deep learning classifiers in histopathological diagnosis of oral squamous cell carcinoma by pathologists
Authors: Sukegawa Shintaro , Ono Sawako , Tanaka Futa , Inoue Yuta , Hara Takeshi , Yoshii Kazumasa , Nakano Keisuke , Takabatake Kiyofumi , Kawai Hotaka , Katsumitsu Shimada , Nakai Fumi , Nakai Yasuhiro , Miyazaki Ryo , Murakami Satoshi , Nagatsuka Hitoshi , Miyake Minoru 
Published: July 2023

AbstractThe study aims to identify histological classifiers from histopathological images of oral squamous cell carcinoma using convolutional neural network (CNN) deep learning models and shows how the results can improve diagnosis. Histopathological samples of oral squamous cell carcinoma were prepared by oral pathologists. Images were divided into tiles on a virtual slide, and labels (squamous cell carcinoma, normal, and others) were applied. VGG16 and ResNet50 with the optimizers stochastic gradient descent with momentum and spectral angle mapper (SAM) were used, with and without a learning rate scheduler. The conditions for achieving good CNN performances were identified by examining performance metrics. We used ROCAUC to statistically evaluate diagnostic performance improvement of six oral pathologists using the results from the selected CNN model for assisted diagnosis. VGG16 with SAM showed the best performance, with accuracy = 0.8622 and AUC = 0.9602. The diagnostic performances of the oral pathologists statistically significantly improved when the diagnostic results of the deep learning model were used as supplementary diagnoses (p-value = 0.031). By considering the learning results of deep learning model classifiers, the diagnostic accuracy of pathologists can be improved. This study contributes to the application of highly reliable deep learning models for oral pathological diagnosis.
Circulating microRNAs in young individuals with long-duration type 1 diabetes in comparison with healthy controls
Authors: Swolin-Eide Diana , Forsander Gun , Pundziute Lyckå Auste , Novak Daniel , Grillari Johannes , Diendorfer Andreas B. , Hackl Matthias , Magnusson Per 
Published: July 2023

AbstractMicroRNAs (miRNAs) are short non-coding RNAs that are involved in post-transcriptional control of gene expression and might be used as biomarkers for diabetes-related complications. The aim of this case–control study was to explore potential differences in circulating miRNAs in young individuals with long-duration type 1 diabetes (T1D) compared to healthy controls, and how identified miRNAs are expressed across different tissues. Twelve adolescents, age 15.0–17.9 years, with T1D duration of more than 8 years (mean 11.1 years), were enrolled from the Swedish diabetes quality registry. An age-matched control group was recruited. Circulating miRNAs (n = 187) were analyzed by quantitative PCR. We observed that 27 miRNAs were upregulated and one was downregulated in T1D. Six of these miRNAs were tissue-enriched (blood cells, gastrointestinal, nerve, and thyroid tissues). Six miRNAs with the largest difference in plasma, five up-regulated (hsa-miR-101-3p, hsa-miR-135a-5p, hsa-miR-143-3p, hsa-miR-223-3p and hsa-miR-410-3p (novel for T1D)) and one down-regulated (hsa-miR-495-3p), with P-values below 0.01, were selected for further in-silico analyses. AKT1, VEGFA and IGF-1 were identified as common targets. In conclusion, 28 of the investigated miRNAs were differently regulated in long-duration T1D in comparison with controls. Several associations with cancer were found for the six miRNAs with the largest difference in plasma.
Activation of SARS-CoV-2 by trypsin-like proteases in the clinical specimens of patients with COVID-19
Authors: Yamazaki Emiko , Yazawa Shunsuke , Shimada Takahisa , Tamura Kosuke , Saga Yumiko , Itamochi Masae , Inasaki Noriko , Hasegawa Sumiyo , Morinaga Yoshitomo , Oishi Kazunori , Tani Hideki 
Published: July 2023

AbstractSARS-CoV-2 enters host cells through the angiotensin converting enzyme 2 (ACE2) receptor and/or transmembrane protease, serine 2 (TMPRSS2). In this study, we investigated whether proteases increased SARS-CoV-2 infectivity using pseudotyped viruses and clinical specimens from patients with COVID-19. First, we investigated how trypsin increased infectivity using the pseudotyped virus. Our findings revealed that trypsin increased infectivity after the virus was adsorbed on the cells, but no increase in infectivity was observed when the virus was treated with trypsin. We examined the effect of trypsin on SARS-CoV-2 infection in clinical specimens and found that the infectivity of the SARS-CoV-2 delta variant increased 36,000-fold after trypsin treatment. By contrast, the infectivity of SARS-CoV-2 omicron variant increased to less than 20-fold in the clinical specimens. Finally, using five clinical specimens containing delta variants, enhancement of viral infectivity was evaluated in the presence of the culture supernatant of several anaerobic bacteria. As a result, viral infectivities of all the clinical specimens containing culture supernatants ofFusobacterium necrophorumwere significantly increased from several- to tenfold. Because SARS-CoV-2 infectivity increases in the oral cavity, which may contain anaerobic bacteria, keeping the oral cavities clean may help prevent SARS-CoV-2 infection.
Updating the seismotectonic setting for the Gulf of Aqaba
Authors: Abdelazim Mona , ElGabry Mohamed N. , Gobashy Mohamed M. , Khalil Mohamed H. , Hussein Hesham M. 
Published: July 2023

AbstractThe Gulf of Aqaba is known for its high seismic activity in Egypt and the Middle East. An inversion technique was applied to 113 earthquakes of magnitude 2.5 to 7.2 to distinct subsets of data based on tectonic regionalization to define the stress regime in the Gulf of Aqaba involving the Eilat basin, Aragonese basin, and Dakar basin. The stress inversion revealed two active stress patterns; an active strike-slip in the Eilat basin and a dominant extensional regime in the Dakar basin, whereas both strike-slip and extensional regimes coexist in the Aragonese basin. The stress pattern in the Eilat basin is consistent with the movement along the Dead Sea Transform Fault. In contrast, the extensional regime in the Dakar basin aligns with the extensional stress field throughout the northern Red Sea. The coexistence of two dominant types of stress regimes in the Aragonese basin is likely a result of the superposition of the two main neighbouring stress regimes: the strike-slip regime along the Gulf of Aqaba Dead Sea Transform Fault and the extensional stress state across the northern Red Sea. The orientations of the minimum principal stress in the three basins are almost similar, indicating ENE trending, nearly horizontal extension.
An in-depth characterisation of European seabass intestinal segments for assessing the impact of an algae-based functional diet on intestinal health
Authors: Ferreira Mariana , Sousa Vera , Oliveira Beatriz , Canadas-Sousa Ana , Abreu H. , Dias J. , Kiron Viswanath , Valente Luisa M. P. 
Published: July 2023

AbstractSustainable farming of fish species depends on emerging new feed ingredients, which can alter the features of the digestive tract and influence animals’ overall health. Recent research has shown that functional feeds hold great potential for enhancing fish robustness by evoking appropriate responses at the intestine level. However, there is a lack of extensive and accurate descriptions of the morphology of the gastrointestinal tract of most farmed fish. We have characterised the intestine of European seabass thoroughly, by targeting four segments − anterior, mid, posterior and rectum. Results indicated that the anterior segment is mostly associated with absorption-related features; this segment has the largest absorptive area, the longest villi, and the highest number of neutral goblet cells (GC). The posterior segment and rectum have distinct histomorphometric features, but both seem to be important for immunity, displaying the highest count of acid GC and the highest expression of immune-related genes. The strongest proliferating cell nuclear antigen (PCNA) signal was observed in the anterior intestine and rectum, with PCNA+ cells appearing at the base of the villi and the corresponding villi branches. We have also evaluated the impact of a novel feed supplemented with a macro- and microalgae blend and found that there were no differences in terms of growth. However, the alterations observed in the mid intestine of fish fed the blend, such as thickening of the submucosa and lamina propria, an increased number of leucocytes, and higher expression of immune- and oxidative stress-related genes, suggest that algae may have an immunomodulatory effect. In the current article, we have described the morphology and expression patterns of the intestine segments of European seabass in detail and have presented a comprehensive report of the indices and methods used for the semi-quantitative and quantitative histomorphometric assessments, thereby providing useful information for future studies that aim to maintain intestinal health through dietary interventions.
Coral calcium carried hydrogen ameliorates the severity of non-alcoholic steatohepatitis induced by a choline deficient high carbohydrate fat-free diet in elderly rats
Authors: Ma Kuai , Hu Xin , Nambu Keiki , Ueda Daisuke , Ichimaru Naotsugu , Fujino Masayuki , Li Xiao-Kang 
Published: July 2023

AbstractHydrogen has been reported to act as an antioxidant, anti-apoptosis and anti-inflammatory agent. Coral calcium carried hydrogen (G2-SUISO) is a safer and more convenient form of hydrogen agent than others. The mechanism underlying the hepatoprotective effects of G2-SUISO using an elderly non-alcoholic steatohepatitis (NASH) rat model was investigated. Two days after fasting, six-month-old elderly male F344/NSlc rats were given a choline deficient high carbohydrate fat-free (CDHCFF) diet from day 0 to day 3 as CDHCFF control group, and then switched to a normal diet from days 4 to 7 with or without 300 mg/kg G2-SUISO. Rats in each group were finally being sacrificed on day 3 or day 7. In the CDHCFF diet group, G2-SUISO decreased the liver weight-to-body weight ratio, the serum AST, ALT, total cholesterol levels, inflammatory infiltration, pro-inflammatory cytokine expression and lipid droplets with inhibiting lipogenic pathways by reducing sterol regulatory element-binding protein-1c, acetyl-CoA carboxylase and fatty acid synthase gene expression compared with the CDHCFF diet alone. G2-SUISO had beneficial effects of anti-apoptosis as well the down-regulation of pro-apoptotic molecules including NF-κB, caspase-3, caspase-9 and Bax. These findings suggest that G2-SUISO treatment exerts a significant hepatoprotective effect against steatosis, inflammation and apoptosis in elderly NASH rats.
Photodynamic therapy changes tumour immunogenicity and promotes immune-checkpoint blockade response, particularly when combined with micromechanical priming
Authors: Lobo Catarina S. , Mendes Maria Inês P. , Pereira Diogo A. , Gomes-da-Silva Lígia C. , Arnaut Luis G. 
Published: July 2023

AbstractPhotodynamic therapy (PDT) with redaporfin stimulates colon carcinoma (CT26), breast (4T1) and melanoma (B16F10) cells to display high levels of CD80 molecules on their surfaces. CD80 overexpression amplifies immunogenicity because it increases same cell (cis) CD80:PD-L1 interactions, which (i) disrupt binding of T-cells PD-1 inhibitory receptors with their ligands (PD-L1) in tumour cells, and (ii) inhibit CTLA-4 inhibitory receptors binding to CD80 in tumour cells. In some cancer cells, redaporfin-PDT also increases CTLA-4 and PD-L1 expressions and virtuous combinations between PDT and immune-checkpoint blockers (ICB) depend on CD80/PD-L1 or CD80/CTLA-4 tumour overexpression ratios post-PDT. This was confirmed using anti-CTLA-4 + PDT combinations to increase survival of mice bearing CT26 tumours, and to regress lung metastases observed with bioluminescence in mice with orthotopic 4T1 tumours. However, the primary 4T1 responded poorly to treatments. Photoacoustic imaging revealed low infiltration of redaporfin in the tumour. Priming the primary tumour with high-intensity (~ 60 bar) photoacoustic waves generated with nanosecond-pulsed lasers and light-to-pressure transducers improved the response of 4T1 tumours to PDT. Penetration-resistant tumours require a combination of approaches to respond to treatments: tumour priming to facilitate drug infiltration, PDT for a strong local effect and a change in immunogenicity, and immunotherapy for a systemic effect.
Aesthetic Insight and Mental Agency
Authors: Prodoehl Christopher 
Published: July 2023

Abstract
Do artists have control over their ideas for new artworks? This is often treated as a question about spontaneity, or the experience of control: does the event of having an idea for a new artwork occur unexpectedly and without foresight? I suggest another way of interpreting the question—one that has mostly been neglected by philosophers, and that is not settled by claims about spontaneity. According to that interpretation, the question is about agency: are the events of having ideas for new artworks exercises of mental agency? I argue that the answer is no. I apply the results of this argument to questions about what is and is not intentional in the creative process. I conclude by examining another type of control artists might exercise over their creative mental events, which I call ‘facilitation’.
Spatial-MGCN: a novel multi-view graph convolutional network for identifying spatial domains with attention mechanism
Authors: Wang Bo , Luo Jiawei , Liu Ying , Shi Wanwan , Xiong Zehao , Shen Cong , Long Yahui 
Published: July 2023

Abstract

Motivation
Recent advances in spatial transcriptomics technologies have enabled gene expression profiles while preserving spatial context. Accurately identifying spatial domains is crucial for downstream analysis and it requires the effective integration of gene expression profiles and spatial information. While increasingly computational methods have been developed for spatial domain detection, most of them cannot adaptively learn the complex relationship between gene expression and spatial information, leading to sub-optimal performance.

Results
To overcome these challenges, we propose a novel deep learning method named Spatial-MGCN for identifying spatial domains, which is a Multi-view Graph Convolutional Network (GCN) with attention mechanism. We first construct two neighbor graphs using gene expression profiles and spatial information, respectively. Then, a multi-view GCN encoder is designed to extract unique embeddings from both the feature and spatial graphs, as well as their shared embeddings by combining both graphs. Finally, a zero-inflated negative binomial decoder is used to reconstruct the original expression matrix by capturing the global probability distribution of gene expression profiles. Moreover, Spatial-MGCN incorporates a spatial regularization constraint into the features learning to preserve spatial neighbor information in an end-to-end manner. The experimental results show that Spatial-MGCN outperforms state-of-the-art methods consistently in several tasks, including spatial clustering and trajectory inference.
Identifying the identifiers: How iNaturalist facilitates collaborative, research-relevant data generation and why it matters for biodiversity science
Authors: Campbell C J , Barve Vijay , Belitz Michael W , Doby Joshua R , White Elizabeth , Seltzer Carrie , Di Cecco Grace , Hurlbert Allen H , Guralnick Robert 
Published: July 2023

Abstract
The iNaturalist platform generates millions of research-grade biodiversity records via a system in which users collectively reach consensus on taxonomic identification. In the present article, we examine how identifiers and their efforts, an understudied component of the platform, support data generation. Identification is keeping pace with rapid growth of observations, assisted by a small subset of highly active users who tend to be taxonomically specialized. Identifier experience is the primary determinant of whether records reach research grade, and the time it takes to do so. Time to reach research grade has fallen rapidly with growing identification effort and use of computer vision, and research-grade identifications are generally stable. Most observations are vetted by experienced identifiers, although identifications are not free of biases. We close by providing suggestions for enhanced identification quality and continuing steps to enhance equitable credit and trust across the ecosystem of observers, identifiers, and data users.
Evolution under a model of functionally buffered deleterious mutations can lead to positive selection in protein-coding genes
Authors: Shen Runxi , Wenzel Miwa , Messer Philipp W , Aquadro Charles F 
Published: July 2023

Abstract
Selective pressures on DNA sequences often result in departures from neutral evolution that can be captured by the McDonald–Kreitman (MK) test. However, the nature of such selective forces often remains unknown to experimentalists. Amino acid fixations driven by natural selection in protein-coding genes are commonly associated with a genetic arms race or changing biological purposes, leading to proteins with new functionality. Here, we evaluate the expectations of population genetic patterns under a buffering mechanism driving selective amino acids to fixation, which is motivated by an observed phenotypic rescue of otherwise deleterious nonsynonymous substitutions at bag of marbles (bam) and Sex lethal (Sxl) in Drosophila melanogaster. These two genes were shown to experience strong episodic bursts of natural selection potentially due to infections of the endosymbiotic bacteria Wolbachia observed among multiple Drosophila species. Using simulations to implement and evaluate the evolutionary dynamics of a Wolbachia buffering model, we demonstrate that selectively fixed amino acid replacements will occur, but that the proportion of adaptive amino acid fixations and the statistical power of the MK test to detect the departure from an equilibrium neutral model are both significantly lower than seen for an arms race/change-in-function model that favors proteins with diversified amino acids. We find that the observed selection pattern at bam in a natural population of D. melanogaster is more consistent with an arms race model than with the buffering model.
Safety and Immunogenicity of a Delayed Heterologous Avian Influenza A(H7N9) Vaccine Boost Following Different Priming Regimens: A Randomized Clinical Trial
Authors: El Sahly Hana M , Yildirim Inci , Frey Sharon E , Winokur Patricia , Jackson Lisa A , Bernstein David I , Creech C Buddy , Chen Wilbur H , Rupp Richard E , Whitaker Jennifer A , Phadke Varun , Hoft Daniel F , Ince Dilek , Brady Rebecca C , Edwards Kathryn M , Ortiz Justin R , Berman Megan A , Weiss Julia , Wegel Ashley ,   DMID 17-0090 Study Group, Keitel Wendy A , Atmar Robert L , Rostad Christina A , Rouphael Nadine , Anderson Evan J , Frenck Robert W , Dickey Michelle , Kotloff Karen , Neuzil Kathleen , Graham Irene , Abate Getahun 
Published: July 2023

Abstract

Background
Influenza A (H7N9) has caused multiple disease waves with evidence of strain diversification. Optimal influenza A (H7N9) prime-boost vaccine strategies are unknown.

Methods
We recruited participants who had received monovalent inactivated A/Shanghai/2/2013 (H7N9) vaccine (MIV) approximately 5 years earlier, as follows: MIV with MF59 (MF59 × 2 group), MIV with AS03 (AS03 × 2 group), unadjuvanted MIV (No Adj group), MIV with MF59 or AS03 followed by unadjuvanted MIV (Adjx1 group), and A/H7-naive (unprimed group). Participants were randomized to receive 1 dose of AS03-adjuvanted or unadjuvanted A/Hong Kong/125/2017 (H7N9) MIV and were followed for safety and immunogenicity using hemagglutination inhibition (HAI) and neutralizing antibody assays.

Results
We enrolled 304 participants: 153 received the adjuvanted boost and 151 received the unadjuvanted boost. At 21 days postvaccination, the proportion of participants with HAI antibody titers against the boosting vaccine strain of ≥40 in the adjuvanted and unadjuvanted arms, respectively, were 88% and 49% in MF59 × 2 group, 89% and 75% in AS03 × 2 group, 59% and 20% in No Adj group, 94% and 55% in Adjx1group, and 9% and 11% in unprimed group.

Conclusions
Serologic responses to a heterologous A(H7N9) MIV boost were highest in participants primed and boosted with adjuvant-containing regimens.

Clinical Trials Registration
NCT03738241.