bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the structural performance of T-section beams with construction defects utilizing numerical analysis
Authors: Al-Kader A. Al Sayed Abd , Al-jabali Hebah Mohammad , Fahmy Mohamed , Mohamed Ghada N. , Bayoumi El-Said Abd-Allah , Selouma Tarek Ibrahim 
Published: February 2024

This study investigates recent incidents of slabs collapse in reinforced concrete T-beam constructions attributed to deficiencies in design detailing and execution. It employs numerical analyses using the finite element method in ANSYS software to model T-section beams, with validation against experimental tests. Subsequently, a parametric study is conducted to explore the behavior of T-section beams under various design and construction variables, including the spacing of secondary reinforcements in the slab, the diameter of secondary main reinforcements, and slab thickness. The numerical analysis results are found to align well with experimental findings. The parametric study highlights that the eccentricity of reinforcing bars in the secondary direction of the slab is more detrimental than in the main direction. Furthermore, using 10 mm diameter reinforcement in the slab, either in the main or secondary direction, enhances the slab’s resistance to applied loads. Additionally, the study reveals that increasing the stiffness of the slab contributes to an improved resistance of the beam.
Commentary: trends in interests of new public health students concerning environmental health
Authors: Shendell Derek G. , Aggarwal Juhi 
Published: February 2024

IntroductionThis paper was based on data from the core course in environmental health (EH) for master’s in public health students at Rutgers School of Public Health (SPH), Rutgers Biomedical and Health Sciences at Rutgers, and The State University of New Jersey (NJ).MethodsThe multi-part poll or survey of students was in the first module (2 weeks) of the course’s eight module organization on Rutgers Canvas Learning Management System. We collected data every time the first author led this course section during the three academic semesters of each calendar year 2015-2023 (excluding winter 2022-summer 2023 due to grants buyout during COVID-19 pandemic).ResultsData suggested interesting trends and changes in geographic levels of interest over time for EH. When examining interests separately for urban EH and rural EH, the trend was toward approximately equal interests in local, county and state levels (lower than national level—U.S. or student’s home country/nation—but higher than global level). This is where many EH job opportunities are located. Overall, 95% of students reported they believed climate change is real, and 95% of students agreed (“yes”) human activities including combustion sources of pollution contribute to climate change. No one stated “no;” the rest were not sure at the time.DiscussionThese insights from new public health students across majors/concentrations in NJ could inform other accredited SPH across the U.S. and in other nations to help plan future versions of core courses in EH or SPH-wide integrated core courses in compliance with required competencies for accreditation.
Serum uric acid did not affect embryonic and pregnancy outcomes in women without PCOS during IVF procedures
Authors: Yan Niwei , Song Junli , Jie Huiying , Lee Pingyin , Liu Simin , Yuan Yuan 
Published: February 2024

ObjectivesSerum uric acid (UA) levels are associated with many systemic diseases. A previous study confirmed the association between high serum uric acid levels and poor prognosis of in vitro fertilization (IVF) treatment in polycystic ovary syndrome (PCOS) patients. This study aimed to explore the correlation between serum uric acid levels and reproductive outcomes in patients without PCOS.MethodsA retrospective study that included 1057 patients who underwent pre-implantation genetic testing for monogenic disorders (PGT-M) treatment from January 2013 to December 2020 was conducted. The study population was further divided into 3 groups according to serum UA levels: the ≤250 μmol/L group, the 251-360 μmol/L group, and the &gt;360 μmol/L group. The controlled ovarian hyperstimulation (COH) treatment outcomes, embryonic treatment outcomes and pregnancy outcomes of the first frozen embryo transfer (FET) cycle were compared among groups. Multivariable linear regression and binary regression were applied to detect the association between IVF outcomes and serum uric acid levels.ResultsThe number of retrieved oocytes, fertilization rate, viable embryo rate, blastocyst formation rate and euploid rate were not associated with serum uric acid levels. The mature oocyte rate was negatively correlated with serum uric acid levels. The pregnancy outcomes of the first FET cycle were also not associated with serum uric acid levels. After adjustment for BMI, the perinatal outcomes were not associated with serum uric acid levels.ConclusionIVF treatment outcomes were not associated with serum uric acid levels in patients without PCOS.
Characterizing hedgehog pathway features in senescence associated osteoarthritis through Integrative multi-omics and machine learning analysis
Authors: Wang Tao , Li Zhengrui , Zhao Shijian , Liu Ying , Guo Wenliang , Alarcòn Rodrìguez Raquel , Wu Yinteng , Wei Ruqiong 
Published: February 2024

Purpose: Osteoarthritis (OA) is a disease of senescence and inflammation. Hedgehog’s role in OA mechanisms is unclear. This study combines Bulk RNA-seq and scRNA-seq to identify Hedgehog-associated genes in OA, investigating their impact on the pathogenesis of OA.Materials and methods: Download and merge eight bulk-RNA seq datasets from GEO, also obtain a scRNA-seq dataset for validation and analysis. Analyze Hedgehog pathway activity in OA using bulk-RNA seq datasets. Use ten machine learning algorithms to identify important Hedgehog-associated genes, validate predictive models. Perform GSEA to investigate functional implications of identified Hedgehog-associated genes. Assess immune infiltration in OA using Cibersort and MCP-counter algorithms. Utilize ConsensusClusterPlus package to identify Hedgehog-related subgroups. Conduct WGCNA to identify key modules enriched based on Hedgehog-related subgroups. Characterization of genes by methylation and GWAS analysis. Evaluate Hedgehog pathway activity, expression of hub genes, pseudotime, and cell communication, in OA chondrocytes using scRNA-seq dataset. Validate Hedgehog-associated gene expression levels through Real-time PCR analysis.Results: The activity of the Hedgehog pathway is significantly enhanced in OA. Additionally, nine important Hedgehog-associated genes have been identified, and the predictive models built using these genes demonstrate strong predictive capabilities. GSEA analysis indicates a significant positive correlation between all seven important Hedgehog-associated genes and lysosomes. Consensus clustering reveals the presence of two hedgehog-related subgroups. In Cluster 1, Hedgehog pathway activity is significantly upregulated and associated with inflammatory pathways. WGCNA identifies that genes in the blue module are most significantly correlated with Cluster 1 and Cluster 2, as well as being involved in extracellular matrix and collagen-related pathways. Single-cell analysis confirms the significant upregulation of the Hedgehog pathway in OA, along with expression changes observed in 5 genes during putative temporal progression. Cell communication analysis suggests an association between low-scoring chondrocytes and macrophages.Conclusion: The Hedgehog pathway is significantly activated in OA and is associated with the extracellular matrix and collagen proteins. It plays a role in regulating immune cells and immune responses.
Immunological signatures unveiled by integrative systems vaccinology characterization of dengue vaccination trials and natural infection
Authors: Plaça Desirée Rodrigues , Fonseca Dennyson Leandro M. , Marques Alexandre H. C. , Zaki Pour Shahab , Usuda Júlia Nakanishi , Baiocchi Gabriela Crispim , Prado Caroline Aliane de Souza , Salgado Ranieri Coelho , Filgueiras Igor Salerno , Freire Paula Paccielli , Rocha Vanderson , Camara Niels Olsen Saraiva , Catar Rusan , Moll Guido , Jurisica Igor , Calich Vera Lúcia Garcia , Giil Lasse M. , Rivino Laura , Ochs Hans D. , Cabral-Miranda Gustavo , Schimke Lena F. , Cabral-Marques Otavio 
Published: February 2024

IntroductionDengue virus infection is a global health problem lacking specific therapy, requiring an improved understanding of DENV immunity and vaccine responses. Considering the recent emerging of new dengue vaccines, here we performed an integrative systems vaccinology characterization of molecular signatures triggered by the natural DENV infection (NDI) and attenuated dengue virus infection models (DVTs).Methods and resultsWe analyzed 955 samples of transcriptomic datasets of patients with NDI and attenuated dengue virus infection trials (DVT1, DVT2, and DVT3) using a systems vaccinology approach. Differential expression analysis identified 237 common differentially expressed genes (DEGs) between DVTs and NDI. Among them, 28 and 60 DEGs were up or downregulated by dengue vaccination during DVT2 and DVT3, respectively, with 20 DEGs intersecting across all three DVTs. Enriched biological processes of these genes included type I/II interferon signaling, cytokine regulation, apoptosis, and T-cell differentiation. Principal component analysis based on 20 common DEGs (overlapping between DVTs and our NDI validation dataset) distinguished dengue patients by disease severity, particularly in the late acute phase. Machine learning analysis ranked the ten most critical predictors of disease severity in NDI, crucial for the anti-viral immune response. ConclusionThis work provides insights into the NDI and vaccine-induced overlapping immune response and suggests molecular markers (e.g., IFIT5, ISG15, and HERC5) for anti-dengue-specific therapies and effective vaccination development.
Comparative analysis of human gut- and blood-derived mononuclear cells: contrasts in function and phenotype
Authors: Burke Schinkel Stephanie C. , Barros Priscila O. , Berthoud Tamara , Byrareddy Siddappa N. , McGuinty Michaeline , Cameron D. William , Angel Jonathan B. 
Published: February 2024

IntroductionAlterations in the gut immune system have been implicated in various diseases.The challenge of obtaining gut tissues from healthy individuals, commonly performed via surgical explants, has limited the number of studies describing the phenotype and function of gut-derived immune cells in health. MethodsHere, by means of recto-sigmoid colon biopsies obtained during routine care (colon cancer screening in healthy adults), the phenotype and function of immune cells present in the gut were described and compared to those found in blood.ResultsThe proportion of CD4+, CD8+, MAIT, γδ+ T, and NK cells phenotype, expression of integrins, and ability to produce cytokine in response to stimulation with PMA and ionomycin. T cells in the gut were found to predominantly have a memory phenotype as compared to T cells in blood where a naïve phenotype predominates. Recto-sigmoid mononuclear cells also had higher PD-1 and Ki67 expression. Furthermore, integrin expression and cytokine production varied by cell type and location in blood vs. gut.DiscussionThese findings demonstrate the differences in functionality of these cells when compared to their blood counterparts and validate previous studies on phenotype within gut-derived immune cells in humans (where cells have been obtained through surgical means). This study suggests that recto-sigmoid biopsies collected during colonoscopy can be a reliable yet more accessible sampling method for follow up of alterations of gut derived immune cells in clinical settings.
Oral administration of Manuka honey induces IFNγ-dependent resistance to tumor growth that correlates with beneficial modulation of gut microbiota composition
Authors: Masad Razan J. , Idriss Ienas , Mohamed Yassir A. , Al-Sbiei Ashraf , Bashir Ghada , Al-Marzooq Farah , Altahrawi Abeer , Fernandez-Cabezudo Maria J. , Al-Ramadi Basel K. 
Published: February 2024

BackgroundTo investigate the potential of Manuka honey (MH) as an immunomodulatory agent in colorectal cancer (CRC) and dissect the underlying molecular and cellular mechanisms.MethodsMH was administered orally over a 4 week-period. The effect of MH treatment on microbiota composition was studied using 16S rRNA sequencing of fecal pellets collected before and after treatment. Pretreated mice were implanted with CRC cells and followed for tumor growth. Tumors and lymphoid organs were analyzed by flow cytometry (FACS), immunohistochemistry and qRT-PCR. Efficacy of MH was also assessed in a therapeutic setting, with oral treatment initiated after tumor implantation. We utilized IFNγ-deficient mice to determine the importance of interferon signaling in MH-induced immunomodulation.ResultsPretreatment with MH enhanced anti-tumor responses leading to suppression of tumor growth. Evidence for enhanced tumor immunogenicity included upregulated MHC class-II on intratumoral macrophages, enhanced MHC class-I expression on tumor cells and increased infiltration of effector T cells into the tumor microenvironment. Importantly, oral MH was also effective in retarding tumor growth when given therapeutically. Transcriptomic analysis of tumor tissue highlighted changes in the expression of various chemokines and inflammatory cytokines that drive the observed changes in tumor immunogenicity. The immunomodulatory capacity of MH was abrogated in IFNγ-deficient mice. Finally, bacterial 16S rRNA sequencing demonstrated that oral MH treatment induced unique changes in gut microbiota that may well underlie the IFN-dependent enhancement in tumor immunogenicity.ConclusionOur findings highlight the immunostimulatory properties of MH and demonstrate its potential utilization in cancer prevention and treatment.
The significance of Hippo pathway protein expression in oral squamous cell carcinoma
Authors: Amano Yusuke , Matsubara Daisuke , Kihara Atsushi , Yoshimoto Taichiro , Fukushima Noriyoshi , Nishino Hiroshi , Mori Yoshiyuki , Niki Toshiro 
Published: February 2024

IntroductionThe Hippo pathway consists of mammalian sterile 20-like kinase 1/2 (MST1/2), large tumor suppressor 1/2 (LATS1/2), and yes-associated protein (YAP)1. Herein, we present the first report on the significance of major Hippo pathway protein expression in oral squamous cell carcinoma (OSCC).MethodsThe analyses included oral epithelial dysplasia (OED, n = 7), carcinoma in situ (CIS, n = 14), and oral squamous cell carcinoma (OSCC, n = 109).ResultsCytoplasmic expression of MST1, LATS1, and LATS2 was low in OED, CIS, and OSCC. The cytoplasmic expression of MST2 was high in OED (5/7 cases), CIS (9/14 cases), and poorly differentiated OSCC (8/8 cases) but was low/lost in a proportion of differentiated OSCC (60/101 cases). The expression of YAP1 was associated with differentiation; low YAP expression was significantly more frequent in well-differentiated OSCC (35/71 cases), compared to moderately and poorly differentiated OSCC (11/38 cases). An infiltrative invasion pattern was associated with a high expression of MST2 and high expression of YAP1. The high expression of YAP1 was associated with features of epithelial-to-mesenchymal transition (EMT), such as the loss of E-cadherin and high expression of vimentin, laminin 5, and Slug. High expression of protein arginine methyltransferase (PRMT) 1 or 5, which positively regulates YAP activity, was associated with the high expression of YAP1 (p &lt; 0.0001).ConclusionAmong the major Hippo pathway proteins, MST2 displayed a distinctive expression pattern in a significant proportion of differentiated OSCC, suggesting a possible differential role for MST2 depending on the course of OSCC progression. A high YAP1 expression may indicate aggressive OSCC with EMT via PRMTs at the invasive front.
Precision needle-punch tumor enrichment from paraffin blocks improves the detection of clinically actionable genomic alterations and biomarkers
Authors: Lin Douglas I. , Huang Richard S. P. , Ladas Ioannis , Keller Rachel B. , Patel Nimesh R. , Lakis Sotirios , Decker Brennan , Janovitz Tyler , Mata Douglas A. , Ross Jeffrey S. , Vergilio Jo-Anne , Elvin Julia A. , Herbst Roy S. , Mack Philip C. , Killian Jonathan K. 
Published: February 2024

BackgroundWhile many molecular assays can detect mutations at low tumor purity and variant allele frequencies, complex biomarkers such as tumor mutational burden (TMB), microsatellite instability (MSI), and genomic loss of heterozygosity (gLOH) require higher tumor purity for accurate measurement. Scalable, quality-controlled, tissue-conserving methods to increase tumor nuclei percentage (TN%) from tumor specimens are needed for complex biomarkers and hence necessary to maximize patient matching to approved therapies or clinical trial enrollment. We evaluated the clinical utility and performance of precision needle-punch enrichment (NPE) compared with traditional razor blade macroenrichment of tumor specimens on molecular testing success.MethodsPathologist-directed NPE was performed manually on formalin-fixed, paraffin embedded (FFPE) blocks. Quality control of target capture region and quantity of residual tumor in each tissue block was determined via a post-enrichment histologic slide recut. Resultant tumor purity and biomarker status were determined by the computational analysis pipeline component of the FDA-approved next-generation sequencing (NGS) assay, FoundationOne®CDx. Following NPE implementation for real-world clinical samples, assay performance and biomarker (MSI, TMB, gLOH) detection were analyzed.ResultsIn real-world clinical samples, enrichment rate via NPE was increased to ~50% over a 2.5-year period, exceeding the prior use of razor blade macro-enrichment (&lt;30% of cases) prior to NPE implementation due to proven efficacy in generating high quality molecular results from marginal samples and the ease of use for both pathologist and histotechnologists. NPE was associated with lower test failures, higher computational tumor purity, and higher rates of successful TMB, MSI and gLOH determination when stratified by pre-enriched (incipient) tumor nuclei percentage. In addition, challenging cases in which tumor content was initially insufficient for testing were salvaged for analysis of biomarker status, gene amplification/deletion, and confident mutant or wild-type gene status determination.ConclusionsPathologist-directed precision enrichment from tissue blocks (aka NPE) increases tumor purity, and consequently, yields a greater number of successful tests and complex biomarker determinations. Moreover, this process is rapid, safe, inexpensive, scalable, and conserves patient surgical pathology material. NPE may constitute best practice with respect to enriching tumor cells from low-purity specimens for biomarker detection in molecular laboratories.
Characteristics of bacterial communities in rhizosphere and bulk soil in Fe-deficient citrus growing in coastal saline-alkali land
Authors: Jiang Tianchi , Chen Jiuzhou , Huang Yu , Chang Xiaoyan , Wu Yuping , Liu Gaoping , Wang Runze , Xu Kuan , Lu Lingli , Lin Haizhong , Tian Shengke 
Published: February 2024

AimsCitruses often occur with imbalance in iron nutrition in coastal saline-alkali lands, which severely limits the yield and quality of the fruit. In the rhizosphere, the salt content plays a crucial role in reducing uptake of iron, as well as the activity and abundance of bacteria. However, few studies have explored how salt content affects the effectiveness of iron and the community structure of bacteria across different vertical spatial scales.MethodsWe investigated the citrus rhizosphere (0–30 cm) and bulk (0–60 cm) soil microenvironments of the coastal saline soil were analyzed using the 16S rRNA amplicon and inductively coupled plasma-optical emission spectroscopy.ResultsWe found that the nutrient-related elements in the rhizosphere and bulk soil decreased with increasing soil depth, while the salinity-related elements showed the opposite trend. The nutrient-related element content in the rhizosphere was higher than that in the bulk, whereas the salinity-alkaline-related element content was lower than that in the bulk. The structure and diversity of bacterial communities are affected by the rhizosphere and soil depth. In the bulk, there are enriched bacteria such as WB1-A12, Nitrospiraceae and Anaerolineae that are tolerant to salt-alkali stress. In the rhizosphere, bacteria that promote plant nutrient absorption and secretion of iron carriers, such as Pseudomonas, Streptomyces, and Duganella, are prominent.ConclusionsThe soil depth and rhizosphere affect soil nutrients and saline alkali-related factors. Changes in soil depth and rhizosphere determine the structure and diversity of bacterial communities. Rhizosphere enhances iron absorption promoting bacteria to alleviate iron deficiency stress in saline-alkali soils. Our results indicate that citrus roots maybe can resist the stress of iron deficiency in saline-alkali soils by enhancing iron absorption promoting bacteria.
Plant virus diversity in bee and pollen samples from apple (Malus domestica) and sweet cherry (Prunus avium) agroecosystems
Authors: Smadi Malek , Lee Eunseo , Phelan James , Wang Aiming , Bilodeau Guillaume J. , Pernal Stephen F. , Guarna M. Marta , Rott Mike , Griffiths Jonathan S. 
Published: February 2024

IntroductionHoney bee (Apis mellifera) pollination is widely used in tree fruit production systems to improve fruit set and yield. Many plant viruses can be associated with pollen or transmitted through pollination, and can be detected through bee pollination activities. Honey bees visit multiple plants and flowers in one foraging trip, essentially sampling small amounts of pollen from a wide area. Here we report metagenomics-based area-wide monitoring of plant viruses in cherry (Prunus avium) and apple (Malus domestica) orchards in Creston Valley, British Columbia, Canada, through bee-mediated pollen sampling.MethodsPlant viruses were identified in total RNA extracted from bee and pollen samples, and compared with profiles from double stranded RNA extracted from leaf and flower tissues. CVA, PDV, PNRSV, and PVF coat protein nucleotide sequences were aligned and compared for phylogenetic analysis.ResultsA wide array of plant viruses were identified in both systems, with cherry virus A (CVA), prune dwarf virus (PDV), prunus necrotic ringspot virus (PNRSV), and prunus virus F (PVF) most commonly detected. Citrus concave gum associated virus and apple stem grooving virus were only identified in samples collected during apple bloom, demonstrating changing viral profiles from the same site over time. Different profiles of viruses were identified in bee and pollen samples compared to leaf and flower samples reflective of pollen transmission affinity of individual viruses. Phylogenetic and pairwise analysis of the coat protein regions of the four most commonly detected viruses showed unique patterns of nucleotide sequence diversity, which could have implications in their evolution and management approaches. Coat protein sequences of CVA and PVF were broadly diverse with multiple distinct phylogroups identified, while PNRSV and PDV were more conserved.ConclusionThe pollen virome in fruit production systems is incredibly diverse, with CVA, PDV, PNRSV, and PVF widely prevalent in this region. Bee-mediated monitoring in agricultural systems is a powerful approach to study viral diversity and can be used to guide more targeted management approaches.