bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug cytotoxicity screening using human intestinal organoids propagated with extensive cost-reduction strategies
Authors: Takahashi Yu , Inoue Yu , Sato Shintaro , Okabe Takayoshi , Kojima Hirotatsu , Kiyono Hiroshi , Shimizu Makoto , Yamauchi Yoshio , Sato Ryuichiro 
Published: January 2023

Abstract
Background:Physiologically relevant cell models, including organoids, are considered to be reliable tools for recapitulating human biology. Although organoids are useful for cell-based compound screening, which may facilitate drug development, their applications are limited. Intestinal organoids are composed of multiple types of intestinal epithelial cells found in vivoand replicate organ structures and complexities. A major limitation of using organoids in screening studies is the high cost of their culture when commercially available recombinant proteins are used.
Methods: We previously succeeded in reducing the cost of human intestinal organoid culture by using the conditioned medium (CM) of L cells that stably co-express Wnt3a, R-spondin1, and Noggin via lentiviral infection. Based on this, we worked on further cost reduction by replacing expensive materials with cheaper ones and expanded the organoids in a more cost-effective way for a large-scale assay.
Results: We replaced recombinant hepatocyte growth factor protein with CM for human intestinal organoid culture.Moreover, collagen gel was used instead of Matrigel for organoid culture, and organoid proliferation rate, as well as marker gene expression, was largely unchanged. The combination of these replacements significantly contributed to cost reduction for culturing organoids and organoid-oriented monolayer cells. Furthermore, compound screening of thousands of known bioactive substances was performed using human intestinal organoids cultured with the refined cost-reduction strategies, and several compounds with more selective cytotoxicity against organoid-derived cells than Caco-2 cells were identified. The mechanism of action of one of these compounds, YC-1, was further elucidated. We showed that YC-1 induces apoptosis through the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway.
Conclusions:These results indicate that our methodologies for cost reduction enable large-scale organoid culture and subsequent compound screening, which may further expand the application of intestinal organoids and organoids in general in various research fields, including both theoretical and applied science.
Exploring potential causal genes for mouth ulcers: A Mendelian randomization and transcriptome- wide association analysis
Authors: Shi Mengru , Wang Tianqi , Xie Qi , Meng Xiaofei , Shi Jiamin , Zhu Yining , Zhang Xinchun , Xia Juan , Xie Weili , Chen Xiaobing 
Published: January 2023

Abstract
In this study, we explored genes that were pleiotropically associated with mouth ulcers. We adopted the summary data-based Mendelian randomization (SMR) method which estimated the pleiotropic effect of gene expression on mouth ulcers. We performed separate SMR analysis using GTEx and CAGE eQTL data. We also conducted transcriptome-wide association study (TWAS) to explore genes whose cis-regulated expression levels were associated mouth ulcers. Using GTEx eQTL data, the SMR identified 70 probes, with CCR1 (ENSG00000163823.3, PSMR=9.20×10–17), PPP5C (ENSG00000011485.10, PSMR=6.86×10–16) and HLA-DRB5 (ENSG00000198502.5, PSMR=1.54×10–15) being the top three genes. Using the CAGE eQTL data, our SMR analysis identified 137 probes tagging 111 unique genes with CCR3 (ILMN_1763322, PSMR=7.76×10–41), CCR1 (ILMN_1678833, PSMR=3.89×10–38) and CA425595 (ILMN_1725170, PSMR=4.15×10–19) being the top three genes. TWAS analysis identified 181 significant genes whose expression was associated with mouth ulcers, 58 of which were also identified by SMR analysis using GTEx eQTL data and 39 by the SMR analysis using CAGE eQTL data. Our findings highlight the important roles of genes in the CCR family and the HLA complex in the pathogenesis of mouth ulcers. More studies are needed to explore the underlying mechanisms in the etiology of mouth ulcers.
Combined application of zinc oxide and iron nanoparticles enhanced Red Sails Lettuce growth and antioxidants enzymes activities while reducing the chromium uptake by plants grown in a Cr-contaminated soil
Authors: Sameer Alisha , Rabia Sara , Khan Aamir Amanat Ali , Hussain Afzal , Ali Basharat , Zaheer Muhammad Saqlain , Ali Habib , Sheteiwy Mohamed S. , Ali Shafaqat 
Published: January 2023

Abstract
Soils contaminated with chromium (Cr) have become a major ecological concern. Chromium poses serious health issues when become the part of our food chain. So, the key objective of the present experiment was to evaluate the impact of foliar applied zinc oxide nanoparticles (ZnO NPs) as varying levels (0, 25, 50, 100 mg L-1) as well as iron nanoparticles (Fe NPs) as varying levels (0, 5, 10, 20 mg L-1) on lettuce growth, biomass, photosynthetic process as well as essential nutrients and Cr uptake by lettuce plants under Cr stress. Foliar spray of ZnO and Fe NPs was applied as foliar spray and plants harvesting was done at maturity. Our results depicted that foliar application of ZnO NPs and Fe NPs improved the growth, photosynthesis, antioxidants enzymes activities and reduced the oxidative damage in lettuce plants by stimulating the antioxidative defense machinery. Additionally, application of ZnO and Fe NPs resulted in enhancement of Zn and Fe fortification in Red Sails Lettuce, respectively. Moreover, Zn and Fe NPs enhanced the uptake of the essential nutrients while limiting the Cr uptake by lettuce plants and Cr concentration in lettuce leaves was under the threshold limit for Cr.
Ultra-low Ag Loadings for CO2 Reduction via Tailored Molecular Electrocatalysts
Authors: Apfel Ulf-Peter , Pellumbi Kevinjeorjios , Krisch Dominik , Sun He , Sanden Sebastian , Hoof Lucas , Puring Kai junge , Siegmund Daniel , Schöfberger Wolfgang , Messing Leonard 
Published: January 2023

Abstract
Decreasing the catalytic loading and complexity of electrocatalysts for the reduction of CO2 is a critical necessity towards globally generating carbon-negative synthons. This effort therefore calls for the development of not only more active catalysts per employed g but also for more financially sound ones. Notably, molecular electrocatalysts allow for tuning the electronic and geometric environment around single-atom catalytic centers. Nevertheless, synthetic complexity, cost and electrochemical instability still hamper their large-scale implementation. With industrial application in mind, we herein present a holistic design approach starting from different Ag(I) N,N´-bis(arylimino)acenaphtene complexes to sophisticated architectures of electrolyzer components. Performed in industrially applicable cells at 60°C, this approach allows us to reach catalytic activity for CO formation close to 1 A cm-2, while achieving the highest mass activity reported for CO at 100.000 A gAg-1, accompanied by cost decreases up to a factor of 80 against the current heterogeneous standards. This study thus represents an unprecedented example to show the applicability of homogenous catalysts under industrially relevant conditions.
Usefulness of Non-invasive Assessment of Liver Fibrosis on Serum and Transient Elastography Markers in Pediatric Autoimmune Hepatitis
Authors: ALVARENGA Lucas Rocha , HESSEL Gabriel , PEREIRA Tiago Sevá , BELLOMO-BRANDÃO Maria Ângela 
Published: January 2023

Abstract
BACKGROUND
Liver biopsy is an invasive method to assess liver fibrosis in chronic liver diseases and, therefore, non-invasive methods are becoming common in daily practice. There is a lack of pediatric clinical trials using non-invasive markers. The aim of the study is to evaluate the correlation of non-invasive markers of liver fibrosis in pediatric Autoimmune Hepatitis (AIH) with Transient Liver Elastography (TLE).
METHODS
A cross-sectional study was done in a cohort of AIH pediatric patients at a tertiary care center between May 2016 and February 2020. Twenty-eight patients (between 3 and 20 years of age) with AIH were enrolled, all of them on immunosuppressive treatment and biochemical remission. They had undergone TLE (FibroScan®) and biochemical tests. Patients were divided into 2 groups: (1) ≥ F2 (TLE ≥ 6.45 kPa) and (2) < F2 (TLE < 6.45 kPa). The comparison between groups 1 and 2 was performed using Mann-Whitney test for quantitative variables and Fisher's exact test for categorical variables. The correlation between TE, APRI, FIB-4 and Platelet Count was assessed using Spearman coefficient (Rs) and the level of significance adopted for the study was 5%.
RESULTS
Twenty-eight pediatric patients with AIH were enrolled, 21 female and 22 AIH-1; 20 patients in group 1 and 8 in group 2. A statistically significant difference was found between the two groups on APRI and FIB-4 results (p = 0.0306 and p = 0.0055, respectively). When TLE (in kPa values) was compared with the other markers, there was a significant correlation with APRI and FIB-4 (Rs = 0.67 and 0.78, respectively; p <0.01) as well as with Platelet Count (Rs = - 0.68; p <0.01).
CONCLUSIONS
APRI, FIB-4 and Platelet Count showed positive correlation with TLE to predict liver fibrosis in pediatric AIH.
Effects of Ascophyllum Nodosum and Soil Amendments on the Development of Maize Seedlings Cultivated Under Acid Oxisol
Authors: Trindade Polyanna Ribeiro , Mooney Sacha J , Rodrigues Carlos Ribeiro , Castoldi Gustavo , Veneziano Vitor Martins , Atkinson Brian , Sturrock Craig J , Chagas Marcos Gustavo Kemmerich , Alves Guyanlukia Brito , Rodrigues Arthur Almeira , Filho Sebastião Carvalho Vasconcelos 
Published: January 2023

Abstract
Introduction
Maize (Zea mays L.) plays a fundamental role in Brazilian agriculture, and it is mostly cultivated in Brazilian Savannah areas, under high Al content and acidic pH.
Aims
The aim of this work was to evaluate the effects of soil amendments and A. nodosum extract on the initial development of the root system and nitrogen use efficiency of maize under aluminum toxicity.
Methods
The effects of lime and gypsum in combination with seed treatment + foliar application of Ascophyllum nodosum on shoot and root growth, plant nutrition and photosynthesis of 14-day-old maize seedlings were tested in two experiments. The experimental design was randomized 4x2 factorial, with the following treatments: lime (L), gypsum (G), lime + gypsum (LG) and control (C), cultivated with and without seed treatment and foliar application of the Ascophyllum nodosum.
Results
The treatments with A. nodosum extract led to an increase in the root area in the treatments with lime, and to a smaller transport of aluminum to the shoot of the plants. The lime and gypsum treatments were efficient in minimizing the deleterious effects of aluminum toxicity, even with their short-term application in sandy clay loam medium textured soil, providing better photochemical activity, better use efficiency of nutrients, better rooting and, consequently, higher dry weight of shoot and root.
Conclusions
The results show that the use of A. nodosum and soil amendments in acidic soils lead to promising physiological and morphological improvement, and by consequence, may influence in crop production.
Classifying knowledge on climate change induced landslides in retrospect and prospect: A state-of-the-art review
Authors: Sharma Aastha , Sajjad Haroon , . Roshani , Rahaman Md Hibjur 
Published: January 2023

Abstract
The frequency and intensity of landslides have increased due to variability in precipitation and temperature across the globe. Assessment of landslide risk is essential for devising effective mitigation and making societies resilient. Through an in-depth literature review from 1996 to 2021, this study carried out descriptive, thematic, and mechanism analyses of the current literature to identify the gaps in the literature and suggest a way forward. Findings revealed a steady increase in the publication of landslide studies over the years. Most of the studies were conducted on a regional scale. Modeling, landslides, climate change, multi-hazards, and vulnerability figured as the prominent keywords in the reviewed articles. Slope, precipitation, land use/land cover, proximity to coastal areas, risk, and adaptation strategies were found as the dominant thematic variables. A large number of reviewed articles utilized statistical models. Uncertainty in landslide-climate modeling, lack of advanced and interactive models for predicting landslide susceptibility; and less attention to environmental and economic vulnerability were identified as the major research gaps. Effective early warning systems, timely forecasting for landslides and effective risk assessment are also scant in the existing literature. The current study proposed a comprehensive future framework for landslide risk assessment and implies timely and appropriate landslide mitigation based on climate scenario data, deterministic models, and policy beliefs. Strengthening preventive actions, preparedness as an early warning system, immediate response mechanism, landslide adaptation behavior, socio-economic vulnerability, and decision support systems are suggested for future research.
Depletion of TAFIB Gene Inhibits Ribosome Biosynthesis and Proliferation of Gastric Tumor through Enhancing c-MYC mRNA Degradation
Authors: chen hangfei , Zhang Feng 
Published: January 2023

Abstract
With population growth and aging, the number of new cases about Stomach adenocarcinoma (STAD) is expected to continue to increase in the future. Increased ribosome biosynthesis (RiBi), a hallmark of many cancers for over 100 years, as a result of an emerging target for cancer therapy. The first key step of RiBi, the transcription of RNA polymerase I (Pol I) into the precursor ribosomal RNA (pre-rRNA), needs a Pol I specific Pre-initiation Complex (PIC) for accurate recruitment. Mammalian PIC of Pol I includes selectivity factor 1 (SL1), RRN3 and upstream binding factor (UBF), of which SL1 is essential and can stabilize the PIC structure. TAF1B, TBP-associated factor 1B, is one of the component subunits of SL1. TAF1B is required for Pre-initiation Complex of RNA polymerase I, but its function in cancers is not fully understood. In this study, when we knocked down TAF1B gene in STAD ,we found that the transcription and content of c-MYC decreased, which was associated with RPL 5, RPL 11 and RISC.
Artificial neural network prediction and comparative evaluation of pharmaceutical important flavones and antioxidant compositions in Teucrium polium callus culture elicited with methyl jasmonate and TiO2 nanoparticles
Authors: Tabarifard Mahshid , Cheniany Monireh , Khalilian-movahhed Mohammad 
Published: January 2023

Abstract
The present research study evaluated the effects of four concentrations of Benzylaminopurine (BAP) in combination with three concentrations of Naphthalene acetic acid (NAA), as well as methyl jasmonate and nano-sized TiO2 elicitors on callus induction, pharmaceutical important flavones and antioxidant compositions in leaf-derived calli of Teucrium polium. The feed-forward Artificial Neural Network (ANN) model, as well, was applied to predict the effects of hormones and elicitors on phenolic compounds production. The best callus induction was obtained with basal media fortified with 1.5 mg L− 1 BAP plus 0.5 mg L− 1 NAA, followed by 1.5 mg L− 1 BAP. Based on biochemical features (the total content of phenols, Ortho-diphenols, flavonoid, flavone, and rosmarinic acid), the extraction has substantially by elicitation raised in comparison to control, with the maximum ones in calli elicited with methyl jasmonate (50 µM). The exception was phenolic acids possessed much greater content in 10 mg L− 1 nano TiO2-treated calli. The high antioxidant activities (IC50 2.066 ± 0.24 µg mL− 1 and 383.79 ± 33.60 mg Fe+ 2 100 g− 1 DW) with approximate 2- and 1.5-fold increases compared to control, was observed in hydromethanolic extracts of calli elicited by 50 µM methyl jasmonate on an MS medium containing 1.5 mg L− 1 BAP plus 0.5 mg L− 1 NAA. Likewise, the highest contents of anti-genotoxic flavones apigenin and luteolin were measured at pretreatment of callus with 50 µM methyl jasmonate on the media supplemented with 1 mg L− 1 BAP (180.67 ± 2.52 and 201.11 ± 3.63 µg 100 g− 1 extract, respectively) and 1.5 mg L− 1 BAP plus 0.5 mg L− 1 NAA (206.01 ± 7 and 256.22 ± 2.1 µg 100 g− 1 extract, respectively). ANN with hyperbolic-tangent (10-1-3) activation function, R2 0.99, SSE 0.01, and RE 0.001 showed a strong correlation between ANN model outputs and the experimental amounts of polyphenols, Ortho-diphenols, and phenolic acids. The results support that methyl jasmonate elicitation could more trigger and increase the pharmaceutical phenolic compositions in T. polium callus cultures as compared with nano-sized TiO2 treatment. Meanwhile, the ANN model could successfully interconnect the output parameters (phenolic metabolites) to input variables (hormone and elicitor).
Profiling of circulating serum exosomal microRNAs in elderly patients with infectious stress hyperglycaemia
Authors: Zeng Kejing , He haozhe , Lv zhenjing , Lei Ming , wu weikun , sun hao , Wong Gordon , Kwok YatSze , Tian Junzhang , xu gugen 
Published: January 2023

Abstract
Early diagnosis of hospitalized elderly patients with infectious stress hyperglycaemia (ISH) is clinically important, as without timely prevention and effective treatment, it is likely to deteriorate into septic shock, which significantly worsen patients’ survival rate. Systematic screening of specific biomarkers of serum small extracellular vesicles (sEVs) from ISH patient has not yet been reported. In this study, serum sEVs were derived from 10 elderly patients with ISH and 5 control patients with disease-match without hyperlycemia (non-ISH). RNA sequencing identified a total number of 49 sEVs enriched fraction derived miRNAs with differential expression between ISH and control group. Of which, top 22 miRNAs ranked by sensitivity × specificity were chosen for further research. Moreover,7 out of 22 miRNAs that related to glucose metabolism or immune disorder, were picked up for further validation in an independent cohort consisting of 52 participants (31 ISH and 21 non-ISH). A validation analysis revealed that 3 miRNAs (hsa-miR-21-5p，hsa-miR-335-5p，hsa-miR-28-3p) were statistically up-regulated in exosomes from ISH patients. In the validation cohort and discovery cohort, the AUC of 3 individual miRNAs ranged from 0.73 to 0.88. A logistic model combining three miRNAs achieved an AUC of 0.96. Besides,sEV‐miRNA‐based signatures effectively characterized patients’ poor clinical outcome. Survival curve analysis showed that miR-335-5p, miR-28-3p but not miR-21-5p, were significantly closely related to mortality, and the combination of the three could also predict patients outcome.(P<0.05).This study depicted the circulating exosomal miRNAs change in ISH patient and which could be used as a promising biomarker to detect ISH at an early stage, and predict patients clinical outcome.
Short-range DNA translocation initiates long-range 1-dimensional DNA diffusion by the Type III restriction enzyme EcoP15I
Authors: Goese Martin , Magill Emma , Diffin Fiona , Rawson Tara , Nagy Zsofia , Seidel Ralf , Szczelkun Mark 
Published: January 2023

Abstract
Cleavage of bacteriophage DNA by the Type III Restriction-Modification enzymes requires long-range interaction between DNA sites. This is facilitated by 1-dimensional diffusion (“DNA sliding”) initiated by ATP hydrolysis catalysed by a superfamily 2 helicase-like ATPase. Here we combined ultrafast twist measurements based on plasmonic DNA origami nano-rotors with stopped-flow fluorescence and gel-based assays to examine the role(s) for ATP hydrolysis. Our data shows that the helicase-like domain plays multiple roles. Firstly, stabilising initial DNA-interactions alongside the methyltransferase subunits. Secondly, causing environmental changes in the flipped adenine base following hydrolysis of the first ATP. And thirdly, remodelling nucleoprotein interactions via constrained translocation of a ~5-20 bp dsDNA loop. Initiation of DNA sliding requires 10-15 bp DNA downstream of the motor, corresponding to the site of nuclease domain binding. Our data unifies previous contradictory communication models for Type III enzymes.
Analyzing the Environment of International Health Regulations Capacities in Lebanon: Protracted Crises, Economic Meltdown and Refugee Waves
Authors: Hassan Maya , Jamal Diana , El-Jardali Fadi 
Published: January 2023

Abstract
Background: Lebanon ratified the International Health Regulations IHR (2005) in 2007, and since then, it has been facing complex political deadlocks, financial deterioration, and infectious disease emergencies. Little is known about implementing IHR (2005) capacities in the Lebanese context. We aimed to understand the milestones of IHR capacities implementation, and the challenges of maintaining these capacities and explore the barriers refugees impose on the development of Lebanon's capacities.
Methods: We used a mixed-method design. The study combined the use of secondary data analysis of the 2020 SPAR submissions and qualitative design using semi-structured interviews with key informants. Semi-structured interviews were conducted with nine key informants. The analysis of the data generated was based on thematic analysis.
Results: In 2020, Lebanon had levels of 4 (≤ 80%) in the prevention, detection, response, enabling functions, and operational readiness capacities. The country scored more than its neighboring countries, Syria, and Jordan, which have similar contexts of economic crises, emergencies, and refugee waves. Despite this high level of commitment to meeting IHR (2005) capacities, the qualitative findings demonstrated several gaps in IHR (2005) implementation as resources shortage, governance, and political and economic challenges. The study also showed contradictory results regarding the impact of refugees on IHR (2005) capacities implementation. Some key informants agreed that the Syrian crisis had a positive impact, while others suggested the opposite. Whether refugees interfere with IHR development is still an area that needs further investigation.
Conclusion: The study shows that urgent interventions are needed to strengthen the implementation of the IHR capacities in Lebanon and crisis-stuck countries. The study recommends 1) reconsidering the weight given to IHR (2005) capacities; 2) promoting governance to strengthen IHR compliance; 3) integrating refugees and displaced persons in IHR (2005) framework and its assessment tools; 4) strengthening the multisectoral coordination mechanisms; 5) mobilizing and advancing the capacities of human resources at the central and sub-national levels; 6) ensuring sustainable financing; 7) acknowledging risk mapping as a pre-requisite to a successful response; 8) strengthening research on IHR (2005) implementation in Lebanon, and; 9) reinforcing risk communication strategies constantly.