bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRAF D594A mutation defines a unique biological and immuno-modulatory subgroup associated with functional CD8+ T cell infiltration in colorectal cancer
Authors: Li Wenjing , Zhao Chenyi , Li Wenhui , Gong Yang , Ma Kaili , Lu Yujie , Liu Xiaowei , Zhang Lianjun , Guo Feng 
Published: July 2023

Abstract
Background BRAF non-V600 mutation occupies a relatively small but critical subset in colorectal cancer (CRC). However, little is known about the biological functions and impacts of BRAF class III mutation in CRC. Here, we aim to explore how D594A mutation impacts on biological behaviors and immune related signatures in murine CRC cells.
Methods BRAF V600E (class I), G469V (class II) and D594A (class III) mutant cell lines were established based on MC38 cells. The biological behaviors of cells were evaluated in respect of cell growth, cell proliferation, cell apoptosis, cell migration and invasion by the methods of colony-forming assay, CCK-8 assay, Annexin V/PI staning and transwell assay. The concentration of soluble cytokines were detected by ELISA. The membrane expression of immuno-modulatory molecules and the pattern of tumor infiltrating lymphocyte were evaluated by flow cytometry. The molecular mechanism was explored by RNA sequencing. Immunohistochemistry (IHC) staining was used for the detection of CD8α in tumor tissues. qRT-PCR and western blot were performed to assess the mRNA and protein expression. Anti-PD-L1 treatment and cytokines neutralization experiments were conducted in in vivo models.
Results D594A mutant cells displayed lower grade malignancy characteristics than V600E (class I) and G469V (class II) mutant cells. Meanwhile, D594A mutation led to evident immuno-modulatory features including upregulation of MHC Class I and PD-L1. In vivo experiments displayed that the frequency of infiltrated CD8+ T cells was significantly high within D594A mutant tumors, which may provide potential response to anti-PD-L1 therapy. RNA sequencing analysis showed that D594A mutation led to enhanced expression of ATF3 and THBS1, which thus facilitated CXCL9 and CXCL10 production upon IFN-γ treatment. In addition, CXCL9 or CXCL10 neutralization reduced the infiltration of CD8+ T cells into THBS1-overexpressing tumors.
Conclusion D594A mutant CRC exhibited lower aggressiveness and immune-activated phenotype. ATF3-THBS1-CXCL9/CXCL10 axis mediated functional CD8+ T cells infiltration into the microenvironment of D594A mutant CRC. Our present study is helpful to define this mutation in CRC and provide important insights in designing effective immunotherapeutic strategies in clinic.
Accuracy of Pancreatic Stone Protein for diagnosis of sepsis in children admitted to pediatric intensive care or high-dependency care: a pilot study
Authors: Bottari Gabriella , Caruso Mariangela , Paionni Emanuel , De Luca Maia , Romani Lorenza , Pisani Mara , Grandin Annalisa , Gargiullo Livia , Zampini Giorgio , Gagliardi Chiara , Fegatelli Danilo Alunni , Vestri Annarita , Lancella Laura , Porzio Ottavia , Muda Andrea Onetti , Villani Alberto , Atti Marta Ciofi Degli , Raponi Massimiliano , Cecchetti Corrado 
Published: July 2023

Abstract

Background
Pancreatic Stone Protein (PSP) is one of the most promising diagnostic and prognostic marker. The aim of the study was to assess the accuracy of PSP, compared to C-Reactive Protein (CRP), and Procalcitonin (PCT) for diagnosis of sepsis in pediatric patients. Furthermore, we explored the correlation of PSP levels with sepsis severity and organ failure measured with PELOD-2 score.
Methods
40 pediatric patients were enrolled following admission to pediatric intensive care, high dependency care or pediatric ward. Blood levels of PSP were measured in Emergency Department (nanofluidic point-of-care immunoassay; abioSCOPE, Abionic SA, Switzerland) on day 1, 2, 3, 5 and 7 from the onset of the clinical signs and symptoms of sepsis or SIRS. Inclusion criteria were: 1) patient age (1 month to 18 years old), 2) signs and symptoms of SIRS, irrespective of association with organ dysfunction. Exclusion criteria were: 1) hemato-oncological diseases and/or immunodeficiencies, 2) pancreatic diseases.
Results
Septic patients showed higher PSP levels than patients with systemic inflammation of no infectious etiology. The optimal cut off in diagnosis of sepsis for PSP at day 1 was 167 ng/ml resulted in a sensitivity 59% (95% IC 36% − 79%) and a specificity 83% (95% IC 58%-96%) with an AUC of 0.636 for PSP in comparison AUC of 0.722 for PCT and 0.503 for C-RP. ROC analysis for outcome (survival versus no survival) has showed AUC 0.814 for PSP; AUC 0.814 for PCT; AUC of 0.657 for C-RP.
Conclusions
PSP could distinguish sepsis cases versus systemic inflammation of no infective etiology; however, our results need to be confirmed in larger pediatric population.
Synthesis of 6,6-Dimethyl-3-azabicyclo [3.1.0]hexane via Ru (II)-Catalyzed Intramolecular Cyclopropanation
Authors: Li Yu , Ma Yujie , Cheng Shihao , Dong Chenhu , Zhong Xueer , Xu Jun , Zhao Yu 
Published: July 2023

Abstract
6,6-Dimethyl-3-azabicyclo [3.1.0]hexane (6,6-DMABH) is a fundamental building block in numerous antiviral drugs, including boceprevir and pf-07321332. To enable more efficient synthesis of 6,6-DMABH, we developed an innovative approach that utilizes the intramolecular cyclopropanation of alpha-diazoacetates via Ru (II) catalysis and Gabriel synthesis. Our method enabled the synthesis of 6,6-DMABH from 3-methyl-2-butenol in seven distinct steps, yielding a total of 28%.
Scientificly Based Irrigation Procedure of Cotton and Winter Wheat in Different Soil and Hydrogeological Conditions of the Kashadarya Region of Uzbekistan
Authors: Khamidov Mukhammadkhon , Matyakubov Bakhtiyar Sh. , Gadaev Nodir N. , Isabaev Kasymbek , Juraev Umid A. 
Published: July 2023

Abstract
The purpose of this article is to analyze the monitoring data of irrigated land in the agrometeorological conditions of Kashkadarya region and CropWat 8.0. is to estimate and compare actual daily evapotranspiration (ETo) and seasonal irrigation rates of cotton and spring wheat using the model. These studies were conducted in experimental fields located in the main agricultural production zone of Kashkadarya. At the time of global climate change, and in order to prevent the decrease in the yield and quality of agricultural crops due to the lack of irrigation water compared to the crop demand, taking into account the water demand of cotton and winter wheat grown in Kashkadarya region, using the weather station data, the seasonal irrigation standard FAO methodology using the CropWat 8.0 program, the mechanical composition of the soil, the depth and mineralization of seepage water, and the values of the plant coefficient for the stages of cotton development were determined. In addition, scientifically based irrigation methods of water-saving irrigation technology of cotton and winter wheat were developed for the conditions of the Kashkadarya region according to the generally accepted hydromodule regions. Based on the developed software, the seasonal irrigation norms of cotton and winter wheat were 3500–6900 (cotton) and 2000–3400 (winter wheat) m3/ha in hydromodule regions. These values were compared with the results obtained from field experiments. The results of the study showed that the ETo values calculated by the method based on the CropWat model compared with the values obtained from field experiments, the difference was ± 8–10%.
Proof of concept for a biologic closure device in a rodent model with evaluation of the animals’ overall burden
Authors: Weidemann Friederike , Strauß Sarah , Schlottmann Frederik , Fedchenko Mykola , Reifenrath Janin , Dorothea Daentzer 
Published: July 2023

Abstract
Disk herniation is a common disease in the population. In case of relevant neurologic deficits and/or pain syndrome a surgical approach is necessary. Therefore, an incision has to be made in the outer ring of the disk to remove all parts of the prolapse. To date, a reliable closure device is missing and a recurrent herniation after a pain free interval is a postoperative problem well-known in spine surgeons. The current study works on proof of concept and is the first which discusses cocoon silk as a possible closure material in intervertebral disk defects in a rat model. In addition, the burden of each animal due to the surgical procedure has been evaluated by Von Frey-filament testing and stress evaluation. The rats represented no or only minor stress response. In the filament testing the animals showed low-grade reactions in general as well. In the histological examination, inflammatory tissue response was detected directly to the silk, predominantly associated with macrophage. In some areas, cell death was visible. These reactions might be associated with remaining particles of the egg, not the silk itself. Further investigations would be necessary to overcome this problem.
Identification and analysis of transcription factor encoding CBF1/ DREB1B gene in Viola tricolor L
Authors: nezami Elyas , deljou Ali 
Published: July 2023

Abstract
Transcription factors belonging to the CBF/ DREB1 (C-repeat binding factor/ Dehydration-Responsive Element Binding Protein B) gene family along with 3 other independent regulatory systems in plants (MYB, MYC and bZIP) play a significant role in activation of genes responding to environmental stresses including cold, heat, salinity and drought. In this study, in order to identify one of the genes of CBF family called CBF1 / DREB1B in the genome of Viola tricolor L., plants were subjected to temperature treatment at 4°C for 2 hours. Total RNA was extracted from viola leaves and used for cDNA synthesis. The presence of the gene in the V. tricolor genome was confirmed via PCR on cDNA, followed by sequencing of the resulting PCR fragments. The 573-nucleotide sequence identified, considering the significant conservation reported in the gene and protein sequence of the CBF gene family, as expected, revealed a high degree of sequence homology and conservation to the CBFs identified in taxonomically close and even far species with V. tricolor. The structure and phylogenetic status of the V. tricolor CBF1 was analyzed based on the identified region and the evolutionarily closest plant species were determined according to the nucleotide and protein sequence of this gene.
Leveraging Generative AI to Prioritize Drug Repurposing Candidates: Validating Identified Candidates for Alzheimer's Disease in Real-World Clinical Datasets
Authors: Wei Wei-Qi , Yan Chao , Grabowska Monika , Dickson Alyson , Li Bingshan , Wen Zhexing , Roden Dan , Stein C. , Embí Peter , Peterson Josh , Feng QiPing , Malin Bradley 
Published: July 2023

Abstract
Drug repurposing represents an attractive alternative to the costly and time-consuming process of new drug development, particularly for serious, widespread conditions with limited effective treatments, such as Alzheimer’s disease (AD). Emerging generative artificial intelligence (GAI) technologies like ChatGPT offer the promise of expediting the review and summary of scientific knowledge. To examine the feasibility of using GAI for identifying drug repurposing candidates, we iteratively tasked ChatGPT with proposing the twenty most promising drugs for repurposing in AD, and tested the top ten for risk of incident AD in exposed and unexposed individuals over age 65 in two large clinical datasets: 1) Vanderbilt University Medical Center and 2) the All of Us Research Program. Among the candidates suggested by ChatGPT, metformin, simvastatin, and losartan were associated with lower AD risk in meta-analysis. These findings suggest GAI technologies can assimilate scientific insights from an extensive Internet-based search space, helping to prioritize drug repurposing candidates and facilitate the treatment of diseases.
Exploring the Capture and Desorption of CO2 on Graphene Oxide Foams Supported by Computational Calculations
Authors: Hoyos B. E. Arango , Franco-Osorio H. , Gómez E. K. Valencia , Sánchez J. Guerrero , Palominos A. P. Del Canto , Benavides F. A. Larraín , Barragán J. J. Prías 
Published: July 2023

Abstract
In the last decade, the highest levels of greenhouse gases (GHG) in the atmosphere have been recorded, with carbon dioxide (CO2) being one of the GHGs that most concerns mankind due to the rate at which it is generated on the planet. Given its long time of permanence in the atmosphere (between 100 to 150 years); this has deployed research in the scientific field focused on the absorption and desorption of CO2 in the atmosphere. This work presents the study of CO2 adsorption employing materials based on graphene oxide (GO), such as GO foams with different oxidation percentages (3.00%, 5.25%, and 9.00%) in their structure, obtained via an environmentally friendly method. The characterization of CO2 adsorption was carried out in a closed system, within which were placed the GO foams and other CO2 adsorbent materials (zeolite and silica gel). Through a controlled chemical reaction, production of CO2 was conducted to obtain CO2 concentration curves inside the system and calculate from these the efficiency, yield, and effectiveness of CO2 adsorption of the materials under study. The results obtained suggest that GO foams are a promising material for carbon capture and the future development of a new clean technology, given their highest CO2 adsorption efficiency and yield.
The Median Isn’t the Message: Elucidating Soil Nutrient Hot Spots
Authors: Barnes Morgan , Johnson Dale W. , Hart Stephen C. 
Published: July 2023

Abstract
Soil nutrient distribution is heterogeneous in space and time, potentially altering nutrient acquisition by trees and microorganisms. Ecologists have distinguished “hot spots” (HSs) as areas with enhanced and sustained rates of nutrient fluxes relative to the surrounding soil matrix. We evaluated the spatial and temporal patterns in nutrient flux HSs in two mixed-conifer forest soils by repeatedly sampling the soil solution at the same spatial locations (horizontally and vertically) over multiple seasons and years using ion exchange resins incubated in situ. The climate of these forests is Mediterranean, with intense fall rains occurring following summers with little precipitation, and highly variable winter snowfall. Hot spots formed most often for NO3- and Na+. Although nutrient HSs often occurred in the same spatial location multiple times, HSs persisted more often for NO3-, NH4+, and PO43- and were more transient for Na+, Ca2+, and Mg2+. Sampling year (annual precipitation ranged from 701 to 1216 mm) impacted the occurrence of HSs for most nutrients, but season was only significant for PO43-, NH4+, NO3-, and Na+, with HSs forming more often after fall rains than spring snowmelt. The frequency of HSs significantly decreased with soil depth for all nutrients, forming most commonly immediately below the surficial organic horizon. Although HSs accounted for less than 17% of the sampling volume, they were responsible for 56-88% of PO43-, NH4+, and NO3- fluxes. Our results suggest that macronutrient HSs have a disproportional contribution to soil biogeochemical structure, with implications for vegetation nutrient acquisition strategies and biogeochemical models.
Examining Supporting and Constraining Factors of Physicians’ Acceptance of Telemedical Online Consultations: A Survey Study
Authors: Diel Sören , Doctor Eileen , Reith Riccardo , Buck Christoph , Eymann Torsten 
Published: July 2023

Abstract
As healthcare demands exceed outpatient physicians’ capacities, telemedicine holds far-reaching potential for both physicians and patients. It is crucial to holistically analyze physicians’ acceptance of telemedical applications, such as online consultation. This study seeks to identify supporting and constraining factors that influence outpatient physicians’ acceptance of telemedicine. We develop a model based on the unified theory of acceptance and use of technology (UTAUT). To empirically examine our research model, we conducted a survey among German physicians (n = 127) in 2018–2019. We used the partial least squares (PLS) modeling approach to test our model, including a mediation analysis. The results indicate that performance expectancy (β = .397, P < .001), effort expectancy (β = .134, P = .03), and social influence (β = .337, P < .001) strongly impact on the intention to conduct online consultations and explain 55% of its variance. Structural conditions regarding data security comprise a key antecedent, associating with performance expectancy (β = .193, P < .001) and effort expectancy (β = .295, P < .001). Regarding potential barriers to usage intentions, we find that IT anxiety predicts performance (β=–.342, P < .001) and effort expectancy (β=–.364, P < .001), while performance expectancy fully mediates (βdirect = .022, P = .71; βindirect=-.138, P < .001) the direct relationship between IT anxiety and the intention to use telemedical applications. This research provides explanations for physicians’ behavioral intention to use online consultation, underlining UTAUT’s applicability in healthcare contexts. Performance expectancy, effort expectancy, and social influence are the main drivers of the intention to use online consultations. Further, we identify IT anxiety and the importance of data security as significant antecedents that should be addressed by practitioners (e.g., in telemedical implementation projects) and by further research.
Multi-country collaborative citizen science projects to co-design cardiovascular disease prevention strategies and advocacy: findings from Ethiopia, Malawi, Rwanda, and South Africa
Authors: Okop Kufre J. , Lambert Estelle Victoria , Kedir Kiya , Getachew Hailemichael , Howe Rawleigh , Niyibizi Jean Berchmans , Bavuma Charlotte , Rulisa Stephen , Kasenda Stephen , Chipeta Effie , Bunn Christopher , Crampin Amelia C. , King Abby C. , Sell Kerstin , Puoane Thandi , Levitt Naomi S 
Published: July 2023

Abstract
Background
Cardiovascular diseases (CVD) are responsible for 17.9 million annual deaths globally, with a disproportionally high burden in sub-Saharan Africa (SSA). There is growing evidence of the use of citizen science and co-design approaches in developing interventions in different fields, but less so in the context of CVD prevention interventions in SSA. This paper reports on the outcomes of a multi-country collaborative project that employed a citizen science approach to explore, co-design, and implement CVD risk prevention and advocacy in SSA.
Methods
The study was implemented in rural and urban communities in Malawi, Ethiopia and Rwanda and urban South Africa, using citizen science and co-design approaches. Trained citizen scientists used a mobile app-based (EpiCollect) semi-structured survey questionnaire to collect data on CVD risk perceptions from participants purposively selected from two communities per country. Data collected per community included 100–150 photographs and 150–240 voice recordings on CVD risk perceptions, communication and health-seeking intentions. Thematic and comparative analysis were undertaken by citizen scientists and the results used to support citizen scientists-led advocacy workshops in each community.
Results
About 63% of 205 participants reported having a relative with CVD. The main perceived causes of CVD in all communities were substance use, food-related factors and litter, followed by physical inactivity, emotional factors, poverty, crime and violence. The perceived positive factors for cardiovascular health were nutrition, physical activity, green space, and clean/peaceful communities. Multi-level stakeholders (45–84 persons/country) including key decision-makers attended advocacy workshops, agreed on priority CVD prevention strategies, and supported successful implementation of CVD risk screening and referral to care interventions. The stakeholders in the health sector appreciated the citizen scientists’ work and indicated their support to utilise this approach in implementing national non-communicable disease prevention programmes. The citizen scientists were excited by the opportunity to lead research and advocacy. The collaborative engagement methods helped build capacity and relationships among citizen scientists, researchers, and stakeholders, leading to active and productive engagements that provided context-specific insights on CVD prevention.
Conclusion
Participatory citizen science can foster learning and co-designing of CVD risk prevention interventions and actionable advocacy strategies in different SSA settings.
Development of a highly efficient prime editor system in mice and rabbits
Authors: Qian Yuqiang , Wang Di , Niu Wenchao , Si Zheng , Wu Mao , Zhao Ding , Li Jinze , Gao Xun , Zhang Zhongtian , Lai Liangxue , li zhanjun 
Published: July 2023

Abstract
The recent prime editing (PE) technique is more precise and permits base-to-base conversion, replacement, and insertion and deletion in the genome. However, previous reports show that the efficiency of prime editing is insufficient for producing genome edited animals. In fact, prime-guide RNA (pegRNA) designs have been the drawback in achieving favorable editing efficiency. Here, we designed prime binding sites (PBS) with a melting temperature (Tm) of 42 ℃ leads to optimal performance in cells, and found the optimal Tm was affected by the culture temperature. In addition, the ePE3max system was developed by updating the PE architecture to PEmax and expressing engineered pegRNA (epegRNA) based on the original PE3 system. The updated ePE3max system can efficiently induce gene editing in mouse and rabbit embryos. Furthermore, we successfully generated Hoxd13 (c. 671 G > T) mutation in mice and Tyr (c. 572 del) mutation in rabbits by ePE3max. Collectively, the editing efficiency of modified ePE3max systems is superior to original PE3 system in producing genome editing animals, which can serve as an effective and versatile genome editing tool for precise genome modification in animal models.
A Metrics-Based Approach to Metadata Classification Applied in a Recommendation System
Authors: Santos Bruno Zolotareff dos , Vales Sandra Santos , Junior Jorge Rady Almeira 
Published: July 2023

Abstract
In this article we have presented a classification model for metadata extracted from tweets using collaborative filters, proposing a metadata recommendation system at the knowledge level. Due to the limited resources available for tagging in social media, the quality of metadata used for this practice often poses interpretation issues when selecting, resulting in a loss of engagement due to flaws in term formation or a lack of understanding of the shared metadata within the social network. In this study, we proposed a selection algorithm that filters and classifies metadata based on metrics that measure the collective intelligence aggregated in the metadata. We then index knowledge indexes that are readily identifiable visually. The proposed model involves two main steps for classifying and recommending metadata.