bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetically engineered eucalyptus expressing pesticidal proteins from Bacillus thuringiensis for insect resistance: a risk assessment evaluation perspective
Authors: Avisar Dror , Manoeli Alexandre , dos Santos Anselmo Azevedo , Porto Antonio Carlos Da Mota , Rocha Carolina Da Silva , Zauza Edival , Gonzalez Esteban R. , Soliman Everton , Gonsalves José Mateus Wisniewski , Bombonato Lorena , Galan Maria P. , Domingues Maurício M. , Candelaria Murici Carlos , Mafia Reginaldo , Graça Rodrigo Neves , Azulay Shelly , Livne Sivan , Dias Tatiane Buono , Drezza Thaís Regina , Silva William Jose , Pinheiro Ana Cristina 
Published: March 2024

Eucalyptus covers approximately 7.5 million hectares in Brazil and serves as the primary woody species cultivated for commercial purposes. However, native insects and invasive pests pose a significant threat to eucalyptus trees, resulting in substantial economic losses and reduced forest productivity. One of the primary lepidopteran pests affecting eucalyptus is Thyrinteina arnobia (Stoll, 1782) (Lepidoptera: Geometridae), commonly referred to as the brown looper caterpillar. To address this issue, FuturaGene, the biotech division of Suzano S.A., has developed an insect-resistant (IR) eucalyptus variety, which expresses Cry pesticidal proteins (Cry1Ab, Cry1Bb, and Cry2Aa), derived from Bacillus thuringiensis (Bt). Following extensive safety assessments, including field trials across various biomes in Brazil, the Brazilian National Technical Commission of Biosafety (CTNBio) recently approved the commercialization of IR eucalyptus. The biosafety assessments involved the analysis of molecular genomics, digestibility, thermostability, non-target organism exposure, degradability in the field, and effects on soil microbial communities and arthropod communities. In addition, in silico studies were conducted to evaluate allergenicity and toxicity. Results from both laboratory and field studies indicated that Bt eucalyptus is as safe as the conventional eucalyptus clone for humans, animals, and the environment, ensuring the secure use of this insect-resistant trait in wood production.
MicroRNA-155 mediates multiple gene regulations pertinent to the role of human adipose-derived mesenchymal stem cells in skin regeneration
Authors: Shahin Hady , Belcastro Luigi , Das Jyotirmoy , Perdiki Grigoriadi Marina , Saager Rolf B. , Steinvall Ingrid , Sjöberg Folke , Olofsson Pia , Elmasry Moustafa , El-Serafi Ahmed T. 
Published: March 2024

Introduction: The role of Adipose-derived mesenchymal stem cells (AD-MSCs) in skin wound healing remains to be fully characterized. This study aims to evaluate the regenerative potential of autologous AD-MSCs in a non-healing porcine wound model, in addition to elucidate key miRNA-mediated epigenetic regulations that underlie the regenerative potential of AD-MSCs in wounds.Methods: The regenerative potential of autologous AD-MSCs was evaluated in porcine model using histopathology and spatial frequency domain imaging. Then, the correlations between miRNAs and proteins of AD-MSCs were evaluated using an integration analysis in primary human AD-MSCs in comparison to primary human keratinocytes. Transfection study of AD-MSCs was conducted to validate the bioinformatics data.Results: Autologous porcine AD-MSCs improved wound epithelialization and skin properties in comparison to control wounds. We identified 26 proteins upregulated in human AD-MSCs, including growth and angiogenic factors, chemokines and inflammatory cytokines. Pathway enrichment analysis highlighted cell signalling-associated pathways and immunomodulatory pathways. miRNA-target modelling revealed regulations related to genes encoding for 16 upregulated proteins. miR-155-5p was predicted to regulate Fibroblast growth factor 2 and 7, C-C motif chemokine ligand 2 and Vascular cell adhesion molecule 1. Transfecting human AD-MSCs cell line with anti-miR-155 showed transient gene silencing of the four proteins at 24 h post-transfection.Discussion: This study proposes a positive miR-155-mediated gene regulation of key factors involved in wound healing. The study represents a promising approach for miRNA-based and cell-free regenerative treatment for difficult-to-heal wounds. The therapeutic potential of miR-155 and its identified targets should be further explored in-vivo.
A budget impact model and a cost–utility analysis of reducer device (Neovasc) in patients with refractory angina
Authors: Fortunato Agostino , Valentini Ilaria , Rumi Filippo , Antonini Debora , Siviero Ludovica , Di Brino Eugenio , Basile Michele , Cicchetti Americo 
Published: March 2024

BackgroundRefractory angina (RA) is a chronic condition characterized by the presence of debilitating angina symptoms due to established reversible ischemia in the presence of obstructive coronary artery disease (CAD). Treatments for this condition have undergone major developments in recent decades; however, the treatment for RA remains a challenge for medicine. In this sense, the Coronary Sinus Reducer System (CSRS) stands as the last line of therapy for ineligible patients for revascularization with reversible ischemia. The purpose of this report is to evaluate the potential burden on the National Health Service (NHS) and measure the health effects in terms of both quantity (life years) and quality-of-life aspects related to the reducer.MethodsTwo different economic evaluation models were developed as part of the analysis. The budget impact was developed to estimate the potential burden on the NHS from incremental uptake of the use of the reducer in the target population. The utility cost analysis compares and evaluates the quality of life and health resource use and costs between the two alternatives, based on the research of Gallone et al. A deterministic and probabilistic sensitivity analysis was carried out to characterize the uncertainty around the parameters of the model.ResultsIn the budget impact analysis (BIA), the reducer is shown to be more expensive in the first 2 years of the model, due to the gradual uptake in the market and the cost of the device. Starting from the third year, assuming maintenance of effectiveness, there are savings in terms of resource absorption in direct healthcare costs arising from hospitalizations, emergency department accesses, coronarography, and visits avoided.ConclusionThe BIA and cost-effectiveness model show that the reducer device, despite an increase in resources absorbed in the first years of implementation and use, has the potential to result in increased quality of life in patients with RA. These costs are largely offset in the short term by the improved clinical outcomes achievable leading to savings from the third year onward in the BIA and a dominance ratio in the cost–utility analysis.
Variability of salivary analytes under daily conditions and their implications for periodontitis biomarkers
Authors: Rocha Amanda Carolina Souza Delfino , Orlandini Renata Klemp , Motta Ana Carolina Fragoso , Pinheiro Juliana Barchelli , Silva Gilberto André e , Oliveira Viviane de Cássia , Lourenço Alan Grupioni 
Published: March 2024

IntroductionRecent studies have identified inflammatory mediators as potential biomarkers for monitoring or diagnosing periodontitis. However, the brief half-life of these mediators, coupled with their variability among different individuals and across different stages of periodontal disease, may limit their reliability as biomarkers.MethodsIn this study, we assessed the concentration profile of salivary biomarkers (IL-6, IL-8, and total protein) through repeated measurements within the same day and across different days in 79 patients exhibiting various states of periodontal health: intact periodontium, stable periodontitis, and active periodontitis. Additionally, we explored how daily variations, such as the interval between toothbrushing and eating, impact the levels of these salivary biomarkers and their diagnostic efficacy for periodontitis activity.ResultsOur results showed high salivary levels of IL-6 and total proteins in periodontitis patients (p &lt; 0.001), with detection ability reflected by an Area Under the Receiver Operating Characteristic Curve (AUC-ROC) ranging between 0.709 and 0.852. Conversely, IL-8 levels were higher in patients with intact periodontium (p &lt; 0.001), with an AUC-ROC for periodontitis detection between 0.671 and 0.815. Daily activities such as toothbrushing and eating influenced the levels of specific analytes, particularly total proteins (p &lt; 0.001), but this did not affect their ability to detect periodontal disease activity. The highest measurement agreement, assessed by Intraclass Correlation Coefficients (ICC), was found for IL-6, with no significant differences in agreement between same-day and different-day measurements.ConclusionsOur study demonstrated consistency in the repeated measurements of salivary analytes, both within the same day and across different days, except for salivary total protein levels. These analytes exhibited variability within a range that did not undermine their effectiveness as biomarkers for periodontal disease.
Identifying diagnostic indicators for type 2 diabetes mellitus from physical examination using interpretable machine learning approach
Authors: Lv Xiang , Luo Jiesi , Huang Wei , Guo Hui , Bai Xue , Yan Pijun , Jiang Zongzhe , Zhang Yonglin , Jing Runyu , Chen Qi , Li Menglong 
Published: March 2024

BackgroundIdentification of patients at risk for type 2 diabetes mellitus (T2DM) can not only prevent complications and reduce suffering but also ease the health care burden. While routine physical examination can provide useful information for diagnosis, manual exploration of routine physical examination records is not feasible due to the high prevalence of T2DM.ObjectivesWe aim to build interpretable machine learning models for T2DM diagnosis and uncover important diagnostic indicators from physical examination, including age- and sex-related indicators.MethodsIn this study, we present three weighted diversity density (WDD)-based algorithms for T2DM screening that use physical examination indicators, the algorithms are highly transparent and interpretable, two of which are missing value tolerant algorithms.PatientsRegarding the dataset, we collected 43 physical examination indicator data from 11,071 cases of T2DM patients and 126,622 healthy controls at the Affiliated Hospital of Southwest Medical University. After data processing, we used a data matrix containing 16004 EHRs and 43 clinical indicators for modelling.ResultsThe indicators were ranked according to their model weights, and the top 25% of indicators were found to be directly or indirectly related to T2DM. We further investigated the clinical characteristics of different age and sex groups, and found that the algorithms can detect relevant indicators specific to these groups. The algorithms performed well in T2DM screening, with the highest area under the receiver operating characteristic curve (AUC) reaching 0.9185.ConclusionThis work utilized the interpretable WDD-based algorithms to construct T2DM diagnostic models based on physical examination indicators. By modeling data grouped by age and sex, we identified several predictive markers related to age and sex, uncovering characteristic differences among various groups of T2DM patients.
Spring-mediated distraction enterogenesis may alter the course of adaptation in porcine short bowel syndrome
Authors: Bautista Geoanna M. , Dubrovsky Genia , Sweeney Nicolle K. , Solórzano-Vargas R.S. , Tancredi Daniel J. , Lewis Michael , Stelzner Mattias , Martín Martín G. , Dunn James C.Y. 
Published: March 2024

IntroductionSevere forms of short bowel syndrome (SBS) resulting in chronic intestinal failure (IF) have limited therapeutic options, all of which are associated with significant morbidities. Spring-mediated distraction enterogenesis (SMDE) uses an intraluminal self-expanding spring to generate mechanical force to induce intestinal stretching and sustained axial growth, providing a promising novel approach for patients with SBS. Previous studies have established this method to be safe and effective in small and large animal models. However, SMDE has previously not been implemented in a large, clinically relevant animal model.MethodsJuvenile mini-Yucatan pigs with 75% of their small intestine resected had intraluminal springs placed after an initial adaptive period. Morphological and histological assessments were performed on SMDE segments compared to the control region of the intestine undergoing normal adaptive responses to resection.ResultsWhile the initial histologic adaptive response observed following resection was attenuated after a month, the SMDE segments instead augmented these adaptive changes. Specifically, intestinal length increased 2-fold in SMDE segments, and the widths of the epithelial, muscularis, and serosal layers were enhanced in SMDE compared with control segments of the same animal. This data suggests that morphologic intestinal adaptation may be enhanced with SMDE in the setting of SBS.DiscussionHere we demonstrate the successful and reproducible implementation of SMDE in a large animal model in the setting of prior intestinal resection, making SMDE a viable and novel approach for SBS to be explored further.
The monocyte-derived cytokine response in whole blood from preterm newborns against sepsis-related bacteria is similar to term newborns and adults
Authors: Jans Jop , van Dun Sven C. J. , Gorissen Renske , Pieterman Roel F. A. , Voskamp Tess S. , Schoenmakers Sam , Taal Hendrik Robert , Unger Wendy W. J. 
Published: March 2024

IntroductionSepsis is characterized by a dysregulated innate immune response. It is a leading cause of morbidity and mortality in newborns, in particular for newborns that are born premature. Although previous literature indicate that the pro-inflammatory response may be impaired in preterm newborns, serum levels of monocyte-derived cytokines, such as TNF-α and IL-6, vary highly between newborns and can reach adult-like concentrations during sepsis. These contradictory observations and the severe consequences of neonatal sepsis in preterm newborns highlight the need for a better understanding of the pro-inflammatory cytokine response of preterm newborns to improve sepsis-related outcomes.Methods and resultsUsing an in vitro model with multiple read outs at the transcriptional and protein level, we consistently showed that the monocyte-derived cytokine response induced by sepsis-related bacteria is comparable between preterm newborns, term newborns and adults. We substantiated these findings by employing recombinant Toll-like receptor (TLR) ligands and showed that the activation of specific immune pathways, including the expression of TLRs, is also similar between preterm newborns, term newborns and adults. Importantly, we showed that at birth the production of TNF-α and IL-6 is highly variable between individuals and independent of gestational age.DiscussionThese findings indicate that preterm newborns are equally capable of mounting a pro-inflammatory response against a broad range of bacterial pathogens that is comparable to term newborns and adults. Our results provide a better understanding of the pro-inflammatory response by preterm newborns and could guide the development of interventions that specifically modulate the pro-inflammatory response during sepsis in preterm newborns.
JNK signaling mediates acute rejection via activating autophagy of CD8+ T cells after liver transplantation in rats
Authors: Wang Xiaowen , Zhu Wenfeng , Chen Haoqi , Li Xuejiao , Zheng Wenjie , Zhang Yuan , Fan Ning , Chen Xiaolong , Wang Genshu 
Published: March 2024

BackgroundAcute rejection (AR) after liver transplantation (LT) remains an important factor affecting the prognosis of patients. CD8+ T cells are considered to be important regulatory T lymphocytes involved in AR after LT. Our previous study confirmed that autophagy mediated AR by promoting activation and proliferation of CD8+ T cells. However, the underlying mechanisms regulating autophagy in CD8+ T cells during AR remain unclear.MethodsHuman liver biopsy specimens of AR after orthotopic LT were collected to assess the relationship between JNK and CD8+ T cells autophagy. The effect of JNK inhibition on CD8+ T cells autophagy and its role in AR were further examined in rats. Besides, the underlying mechanisms how JNK regulated the autophagy of CD8+ T cells were further explored.ResultsThe expression of JNK is positive correlated with the autophagy level of CD8+ T cells in AR patients. And similar findings were obtained in rats after LT. Further, JNK inhibitor remarkably inhibited the autophagy of CD8+ T cells in rat LT recipients. In addition, administration of JNK inhibitor significantly attenuated AR injury by promoting the apoptosis and downregulating the function of CD8+ T cells. Mechanistically, JNK may activate the autophagy of CD8+ T cells through upregulating BECN1 by inhibiting the formation of Bcl-2/BECN1 complex.ConclusionJNK signaling promoted CD8+ T cells autophagy to mediate AR after LT, providing a theoretical basis for finding new drug targets for the prevention and treatment of AR after LT.
Comparison of time to negative conversion of SARS-CoV-2 between young and elderly among asymptomatic and mild COVID-19 patients: a cohort study from a national containment center
Authors: Zemni Imen , Bennasrallah Cyrine , Charrada Ines , Dhouib Wafa , Maatouk Amani , Hassine Donia Ben , Klii Rim , Kacem Meriem , Fredj Manel Ben , Abroug Hela , Mhalla Salma , Mastouri Maha , Loussaief Chawki , Jlassi Ines , Bouanène Ines , Belguith Asma Sriha 
Published: March 2024

ObjectiveWe aimed to study the relationship between age and time to negative conversion of SARS-CoV-2 in patients with asymptomatic and mild forms of COVID-19.MethodsWe conducted a cohort study including all patients diagnosed with COVID-19 from the national COVID-19 containment center of Tunisia. Patients were subdivided into two cohorts: (under 60 years) and (over 60 years) and were followed up until PCR negativization. Log rank test and Cox regression were applied to compare time to negative conversion between the old group and the young group.ResultsThe study included 289 patients with non-severe forms of COVID-19. Age over 60 was significantly associated with delayed negative conversion in male sex (Hazard ratio (HR): 1.9; 95% CI: 1.2–3.07) and among patients with morbid conditions (HR:1.68; 95% CI: 1.02–2.75) especially diabetics (HR: 2.06; 95% CI: 1.01–4.21). This association increased to (HR:2.3; 95% CI: 1.13–4.66) when male sex and comorbidities were concomitantly present and rose to (HR: 2.63; 95% CI: 1.02–6.80) for men with diabetes. Cox regression analysis revealed a significantly delayed negative conversion in symptomatic patients. Significant interaction was observed between gender and age and between age and chronic conditions.ConclusionAge is associated with delayed negative conversion of viral RNA in certain subgroups. Identifying these subgroups is crucial to know how prioritize preventive strategies in elderly.
Association between the gut microbiota, inflammatory factors, and colorectal cancer: evidence from Mendelian randomization analysis
Authors: Ma Mingwei , Zheng Zicheng , Li Jie , He Yixuan , Kang Weiming , Ye Xin 
Published: March 2024

BackgroundColorectal cancer (CRC) is one of the most common malignant tumors primarily affecting individuals over the age of 50 years. Recent studies have suggested that the dysbiosis of the gut microbiota, a community of microorganisms in the human gut, is closely associated with the occurrence and development of CRC. Additionally, inflammatory factors (IFs) have also been reported to play a significant role in the development of CRC. However, the causal relationships between the gut microbiota, IFs, and CRC remain unclear.MethodsIn this study, we performed Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) data to explore the causal relationship between the gut microbiota, IFs, and CRC. The gut microbiota GWAS data were obtained from the MiBioGen study, while the IFs GWAS data were derived from the comprehensive analysis of three independent cohorts. Causal relationship analysis was conducted using appropriate instrumental variables (IVs) and statistical models.ResultsMR analysis of the gut microbiota and CRC revealed a negative correlation between the Lachnospiraceae species in the gut and CRC risk, while a positive correlation was observed between Porphyromonadaceae species, Lachnospiraceae UCG010 genus, Lachnospira genus, and Sellimonas genus in the gut, and CRC risk. Additionally, we observed a causal relationship between IL-10 and CRC risk. These findings suggest that the dysbiosis of the gut microbiota might be associated with an increased risk of CRC and that specific bacterial groups may play a crucial role in the occurrence and development of CRC.ConclusionUsing MR analysis, this study revealed the causal relationships between the gut microbiota, IFs, and CRC. The negative correlation between the Lachnospiraceae species in the gut and CRC risk, as well as the causal relationship between IL-10 and CRC, provide important clues for the potential roles of gut microbiota regulation and inflammatory factor control in the prevention and treatment of CRC.
Bacillus sp. alone or combined with salicylic acid inhibited Trichoderma spp. infection on harvested white Hypsizygus marmoreus
Authors: Yang Xiuqing , Li Tianhao , Liu Yu , Gu Yuyi , Li Jing , Wang Chaoping , Zhao Longgang , Wang Xiaofeng , Li Wenxiang , Sun Yanan , Cheng Fansheng , Zhu Dan 
Published: March 2024

IntroductionWhite Hypsizygus marmoreus is a popular edible mushroom. It is rich in nutrition and flavor but vulnerable to fungal disease, resulting in nutrient loss and aging.MethodsIn this study, the pathogenic fungus Trichoderma spp. BBP-6 and its antagonist Bacillus sp. 1–23 were isolated and identified. The negative effects caused by this pathogen were judged by detecting a series of changes in the infected white H. marmoreus. The effects of Bacillus sp. 1–23 on Trichoderma spp. BBP-6 and the infected white H. marmoreus were detected. The effect of Bacillus sp. 1–23 treatment combined with salicylic acid (SA) was also considered.ResultsThe results showed that Trichoderma spp. BBP-6 could affect the activities of antioxidant enzymes PAL, POD, CAT, SOD, GR, PPO, and APX to interfere with the stability of the white H. marmoreus antioxidant enzyme system and cause the mushroom severe browning and nutrition loss, as well as general quality deterioration. Bacillus sp. 1–23 could produce chitinase and chitosanase enzymes to inhibit Trichoderma spp. BBP-6 directly. SA reinforced this inhibitory. Bacillus sp. 1–23 alone or combined with SA could help white H. marmoreus from the Trichoderma spp. BBP-6 infection to effectively maintain nutrients, restore and stabilize the antioxidant system, and reduce the production of malondialdehyde, superoxide anion and hydrogen peroxide.DiscussionThus, such treatments could be considered potential methods to alleviate damage from disease and extend the shelf life of white H. marmoreus.