bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic characterization and virulence gene profiling of Erysipelothrix rhusiopathiae isolated from widespread muskox mortalities in the Canadian Arctic Archipelago
Authors: Seru Lakshmi Vineesha , Forde Taya L. , Roberto-Charron Amélie , Mavrot Fabien , Niu Yan D. , Kutz Susan J. 
Published: July 2024

AbstractBackgroundMuskoxen are important ecosystem components and provide food, economic opportunities, and cultural well-being for Indigenous communities in the Canadian Arctic. Between 2010 and 2021,Erysipelothrix rhusiopathiaewas isolated from carcasses of muskoxen, caribou, a seal, and an Arctic fox during multiple large scale mortality events in the Canadian Arctic Archipelago. A single strain (‘Arctic clone’) ofE. rhusiopathiaewas associated with the mortalities on Banks, Victoria and Prince Patrick Islands, Northwest Territories and Nunavut, Canada (2010–2017). The objectives of this study were to (i) characterize the genomes ofE. rhusiopathiaeisolates obtained from more recent muskox mortalities in the Canadian Arctic in 2019 and 2021; (ii) identify and compare common virulence traits associated with the core genome and mobile genetic elements (i.e. pathogenicity islands and prophages) among Arctic clone versus otherE. rhusiopathiaegenomes; and iii) use pan-genome wide association studies (GWAS) to determine unique genetic contents of the Arctic clone that may encode virulence traits and that could be used for diagnostic purposes.ResultsPhylogenetic analyses revealed that the newly sequencedE. rhusiopathiaeisolates from Ellesmere Island, Nunavut (2021) also belong to the Arctic clone. Of 17 virulence genes analysed among 28 Arctic clone isolates, four genes – adhesin, rhusiopathiae surface protein-A (rspA), choline binding protein-B (cbpB) and CDP-glycerol glycerophosphotransferase (tagF) – had amino acid sequence variants unique to this clone when compared to 31 otherE. rhusiopathiaegenomes. These genes encode proteins that facilitateE. rhusiopathiaeto attach to the host endothelial cells and form biofilms. GWAS analyses using Scoary found several unique genes to be overrepresented in the Arctic clone.ConclusionsThe Arctic clone ofE. rhusiopathiaewas associated with multiple muskox mortalities spanning over a decade and multiple Arctic islands with distances over 1000 km, highlighting the extent of its spatiotemporal spread. This clone possesses unique gene content, as well as amino acid variants in multiple virulence genes that are distinct from the other closely relatedE. rhusiopathiaeisolates. This study establishes an essential foundation on which to investigate whether these differences are correlated with the apparent virulence of this specific clone through in vitro and in vivo studies.
Clinical characteristics and factors associated with survival rate of patients with non-muscle invasive bladder cancer attending at a Tertiary Hospital in Somalia
Authors: Mohamed Abdikarim Hussein , Mohamed Khaled Ali , Kayacan Ertan , Nur Yassin , Nur-amin Mohamed Abdikarim 
Published: July 2024

Abstract
Background
A few studies regarding the epidemiology and risk factors of Non-muscle Invasive Bladder Cancer (NMIBC) are reported from Sub-Saharan African countries (SSA), including Somalia, and the African literature is scant on the management of NMIBC. The present study aims to evaluate the clinical-histopathological characteristics and factors associated with the survival rate of patients with NMIBC.

Method
This six-year cohort study included 196 patients with NMIBC. It reviewed the clinical and histopathological characteristics and factors predicting cancer-specific survival for these patients.

Results
The mean patient age was 59.01 ± 11.50 years, with a male-to-female ratio of 2.8:1. Urothelial carcinoma (UC) constituted the most common pathological type, accounting for 90.8%; Ta LG and T1HG were the most common histopathological tumour stage and grade (n = 90, 45.9%, vs. n = 56, 28.6%), respectively. The mean tumour size was 4.72 ± 2.81 cm. The cancer-specific mortality(CSM) was 13.3%. Age [2.252(2.310–2.943], p < 0.001], Gender [1.031(0.981-1.1.242),p < 0.001], tumour stage and grade [4.902(3.607–5.614),p < 0.001], tumour location [1.135(0.806–1.172),p < 0.001], number [0.510(0.410–0.920),p = 0.03], tumour size [1.523(0.936–1.541),p < 0.001], use of intravesical chemotherapy or BCG [2.810(1.972–4.381),p < 0.001], preoperative hydronephrosis grade [1.517(1.172–2.154),p < 0.001], and follow-up compliance [3.376(2.633–5.018),p < 0.001] were all associated with CSM. The 5-year overall survival was 57.1%, and cardiovascular diseases were the leading cause of mortality (n = 34), followed by diabetes (n = 28).

Conclusion
Our study findings revealed that UC constituted the most common pathological subtype, though less than forty per cent of our patients receive intravesical adjuvant therapies, which are crucial to minimizing disease morbidity and mortality. Initiatives improving uro-oncological care, including subspecialty training in oncology and essential cancer therapies, better access to urology services, and cancer screening programs, are much needed for optimal management plans and care in the country.
Detection and disclosure of workplace mental health challenges: an exploratory study from India
Authors: Poddar Ankur , Chhajer Raina 
Published: July 2024

AbstractWorkplace mental health challenges have emerged as a significant concern post-pandemic. Despite this, the pervasive stigma surrounding mental illness leads to the concealment of symptoms and reluctance to seek professional help among employees. This study aims to explore the perception of different stakeholders towards the ‘Detection and disclosure’ of workplace mental health challenges in the Indian context. Fifteen semi-structured interviews were conducted with human resource professionals, counselors, and employees who had previously experienced mental health challenge(s). Thematic analysis was done to identify recurring themes and sub-themes. Three critical pathways were identified: minimizing the inhibitory factors, including lack of awareness, denial, low self-efficacy, stigma, and underestimating organizational capability; maximizing the encouraging factors, including psychological safety, perceived social support, and communicating success stories; and implementing supportive organizational practices, including generating awareness and literacy, build the organizational capability, strengthen the role of managers, leadership advocacy, policies, and processes. By fostering a culture of support and prioritizing employee well-being, organizations in India can create healthier and more resilient work environments, benefiting both individuals and the larger society.
Giant cell granuloma and neurofibroma in the mandible of a patient with neurofibromatosis type 1: a long-term follow-up case report with radiological and surgical aspects and a review of the literature
Authors: Barut Oya , Mukdad Marcel , Danielsson Karin , Legrell Per Erik , Sjöström Mats 
Published: July 2024

Abstract
Background
Magnetic resonance imaging (MRI) of the brain is frequently performed on patients with neurofibromatosis type 1 (NF1), to detect and follow-up intracranial findings. In addition, NF1-related pathologies can appear in the jaws. This case study investigates if it is advantageous to assess the depicted parts of the jaws in the imaging of NF1 patients with intracranial findings, thereby detecting jaw pathologies in their initial stages.

Case presentation
We report on the 3-year management with clinical and radiological follow-ups of a central giant cell granuloma and a neurofibroma in the mandible of a patient with NF1 who underwent examinations with brain MRIs. A review of the mandible in the patient’s MRIs disclosed lesions with clear differences in progression rates.

Conclusion
NF1-related jaw pathologies may be detected in the early stages if the depicted parts of the jaws are included in the assessment of the imaging of NF1 patients with intracranial findings. This could impact the treatment of eventual pathologies before lesion progression and further damage to the vicinity.
Impact of musculoskeletal disability limitations on the economic unmet dental needs in South Korea
Authors: Tak Na-Yeon , Ryu Jae-In 
Published: July 2024

Abstract
Background
Musculoskeletal disability (MSD) has been identified as having a negative impact on oral health. Patients with MSD have a greater burden of medical expenses and are expected to have an Economic unmet dental need (UDN). This study aimed to conduct a multifactorial analysis based on the Andersen model to determine the extent to which MSD contributes to inequitable dental care use.

Methods
This study used data from the Korea National Health and Nutrition Survey VIII. The study population was 17,903 adults aged 19 years and older. All data were analyzed using IBM SPSS Statistics for Windows version 26 and the level of statistical significance was set at 0.05.

Results
The people with MSD activity limitations were rare as only 3% in this study population. There were significant differences in sex and education as predisposing factors, income, and marital status as enabling factors, and current smoking, daily brushing, and MSD activity limitation as need factors for experiencing economic UDN. MSD activity limitation was associated with 1.5-fold increased odds of Economic UDN with a fully adjusted Anderson’s Behavior Model.

Conclusions
This finding suggests poorer access to dental care among adults with MSDs owing to financial difficulties. It is necessary to explore various ways to address oral health inequalities among adults with MSD activity limitations.
Reducing patients’ rate of frequent attendance through a training intervention for physicians
Authors: Ramos Alex , Pujol Ramon , Palma Carol 
Published: July 2024

Abstract
Background
Frequent attendance is a common issue for primary care health centres. The phenomenon affects the quality of care, increases doctors’ workloads and can lead to burnout.This study presents the results of an educational intervention for primary care physicians, aimed at helping them to decrease the prevalence rate of excessive attendance by patients at their centres.

Methods
A training programme was carried out for 11 primary care doctors in Barcelona who had patient lists totalling 20,064 patients. The goal of the training was to provide the participating physicians with techniques to curb frequent attendance. Additionally, the programme sought to offer them strategies to prevent professional burnout and tools to better organize their everyday medical practice. The study used a quasi-experimental design for an evaluation of an educational intervention, featuring a pre-test assessment (before the training programme) and a post-test assessment (after the training programme), as well as comparison with a control group that did not undergo the training. The study assessed the effects of the programme on the rates of frequent attendance of patients served by the participating physicians. These rates were compared with those registered by the patients seen by the control group physicians over the same period.

Results
Among the group of physicians who received the training, the mean prevalence of patients who qualified as frequent attenders decreased from 22% prior to the training programme to 8% after completion of the programme. In other words, 14% of patients (2,809) limited the frequency of their visits to primary care physicians after their physicians had completed the training programme. Meanwhile, the study recorded an average decrease of 3.1 visits per year by the patients of the physicians who had undergone the training. Statistically significant differences between this group and the control group were observed.

Conclusions
The educational intervention proved effective at helping primary care physicians to decrease their patients’ rates of frequent attendance. It also contributes to the impact research of continuing education on doctors and their patients. We need to increase primary care spending from the current 14% to the 25%, to address this problem, among others.
Exploring the role of CBLB in acute myocardial infarction: transcriptomic, microbiomic, and metabolomic analyses
Authors: You Hongjun , Chang Fengjun , Chen Haichao , Wang Yi , Han Wenqi 
Published: July 2024

Abstract
Background
Specific alterations in gut microbiota and metabolites have been linked to AMI, with CBLB potentially playing an essential role. However, the precise interactions remain understudied, creating a significant gap in our understanding. This study aims to address this by exploring these interactions in CBLB-intervened AMI mice using transcriptome sequencing, 16 S rDNA, and non-targeted metabolite analysis.

Methods
To probe the therapeutic potential and mechanistic underpinnings of CBLB overexpression in AMI, we utilized an integrative multi-omics strategy encompassing transcriptomics, metabolomics, and 16s rDNA sequencing. We selected these particular methods as they facilitate a holistic comprehension of the intricate interplay between the host and its microbiota, and the potential effects on the host’s metabolic and gene expression profiles. The uniqueness of our investigation stems from utilizing a multi-omics approach to illuminate the role of CBLB in AMI, an approach yet unreported to the best of our knowledge. Our experimental protocol encompassed transfection of CBLB lentivirus-packaged vectors into 293T cells, followed by subsequent intervention in AMI mice. Subsequently, we conducted pathological staining, fecal 16s rDNA sequencing, and serum non-targeted metabolome sequencing. We applied differential expression analysis to discern differentially expressed genes (DEGs), differential metabolites, and differential microbiota. We performed protein-protein interaction analysis to identify core genes, and conducted correlation studies to clarify the relationships amongst these core genes, paramount metabolites, and key microbiota.

Results
Following the intervention of CBLB in AMI, we observed a significant decrease in inflammatory cell infiltration and collagen fiber formation in the infarcted region of mice hearts. We identified key changes in microbiota, metabolites, and DEGs that were associated with this intervention. The findings revealed that CBLB has a significant correlation with DEGs, differential metabolites and microbiota, respectively. This suggests it could play a pivotal role in the regulation of AMI.

Conclusion
This study confirmed the potential of differentially expressed genes, metabolites, and microbiota in AMI regulation post-CBLB intervention. Our findings lay groundwork for future exploration of CBLB’s role in AMI, suggesting potential therapeutic applications and novel research directions in AMI treatment strategies.
The role of NAD-dependent deacetylase sirtuin-2 in liver metabolic stress through regulating pyruvate kinase M2 ubiquitination
Authors: Guo Jingru , Nie Junshu , Li Dongni , Zhang Huaixiu , Zhao Tianrui , Zhang Shoufeng , Ma Li , Lu Jingjing , Ji Hong , Li Shize , Tao Sha , Xu Bin 
Published: July 2024

AbstractNAD-dependent deacetylase Sirt2 is involved in mammalian metabolic activities, matching energy demand with energy production and expenditure, and is relevant to a variety of metabolic diseases. Here, we constructed Sirt2 knockout and adeno-associated virus overexpression mice and found that deletion of hepatic Sirt2 accelerated primary obesity and insulin resistance in mice with concomitant hepatic metabolic dysfunction. However, the key targets of Sirt2 are unknown. We identified the M2 isoform of pyruvate kinase (PKM2) as a key Sirt2 target involved in glycolysis in metabolic stress. Through yeast two-hybrid and mass spectrometry combined with multi-omics analysis, we identified candidate acetylation modification targets of Sirt2 on PKM2 lysine 135 (K135). The Sirt2-mediated deacetylation-ubiquitination switch of PKM2 regulated the development of glycolysis. Here, we found that Sirt2 deficiency led to impaired glucose tolerance and insulin resistance and induced primary obesity. Sirt2 severely disrupted liver function in mice under metabolic stress, exacerbated the metabolic burden on the liver, and affected glucose metabolism. Sirt2 underwent acetylation modification of lysine 135 of PKM2 through a histidine 187 enzyme active site-dependent effect and reduced ubiquitination of the K48 ubiquitin chain of PKM2. Our findings reveal that the hepatic glucose metabolism links nutrient state to whole-body energetics through the rhythmic regulation of Sirt2.
EGFR mutations induce the suppression of CD8+ T cell and anti-PD-1 resistance via ERK1/2-p90RSK-TGF-β axis in non-small cell lung cancer
Authors: Huang Huayan , Zhu Xiaokuan , Yu Yongfeng , Li Ziming , Yang Yi , Xia Liliang , Lu Shun 
Published: July 2024

Abstract
Background
Non-small cell lung cancer (NSCLC) patients with EGFR mutations exhibit an unfavorable response to immune checkpoint inhibitor (ICI) monotherapy, and their tumor microenvironment (TME) is usually immunosuppressed. TGF-β plays an important role in immunosuppression; however, the effects of TGF-β on the TME and the efficacy of anti-PD-1 immunotherapy against EGFR-mutated tumors remain unclear.

Methods
Corresponding in vitro studies used the TCGA database, clinical specimens, and self-constructed mouse cell lines with EGFR mutations. We utilized C57BL/6N and humanized M-NSG mouse models bearing EGFR-mutated NSCLC to investigate the effects of TGF-β on the TME and the combined efficacy of TGF-β blockade and anti-PD-1 therapy. The changes in immune cells were monitored by flow cytometry. The correlation between TGF-β and immunotherapy outcomes of EGFR-mutated NSCLC was verified by clinical samples.

Results
We identified that TGF-β was upregulated in EGFR-mutated NSCLC by EGFR activation and subsequent ERK1/2-p90RSK phosphorylation. TGF-β directly inhibited CD8+ T cell infiltration, proliferation, and cytotoxicity both in vitro and in vivo, but blocking TGF-β did not suppress the growth of EGFR-mutated tumors in vivo. Anti-TGF-β antibody combined with anti-PD-1 antibody significantly inhibited the proliferation of recombinant EGFR-mutated tumors in C57BL/6N mice, which was superior to their monotherapy. Mechanistically, the combination of anti-TGF-β and anti-PD-1 antibodies significantly increased the infiltration of CD8+ T cells and enhanced the anti-tumor function of CD8+ T cells. Moreover, we found that the expression of TGF-β1 in EGFR-TKI resistant cell lines was significantly higher than that in parental cell lines. The combination of anti-TGF-β and nivolumab significantly inhibited the proliferation of EGFR-TKI resistant tumors in humanized M-NSG mice and prolonged their survival.

Conclusions
Our results reveal that TGF-β expression is upregulated in NSCLC with EGFR mutations through the EGFR-ERK1/2-p90RSK signaling pathway. High TGF-β expression inhibits the infiltration and anti-tumor function of CD8+ T cells, contributing to the “cold” TME of EGFR-mutated tumors. Blocking TGF-β can reshape the TME and enhance the therapeutic efficacy of anti-PD-1 in EGFR-mutated tumors, which provides a potential combination immunotherapy strategy for advanced NSCLC patients with EGFR mutations.

Graphical Abstract
CD11b maintains West Nile virus replication through modulation of immune response in human neuroblastoma cells
Authors: Liu Yan-Gang , Peng Hao-Ran , Ren Rui-Wen , Zhao Ping , Zhao Lan-Juan 
Published: July 2024

Abstract
Background
West Nile virus (WNV) is a rapidly spreading mosquito-borne virus accounted for neuroinvasive diseases. An insight into WNV-host factors interaction is necessary for development of therapeutic approaches against WNV infection. CD11b has key biological functions and been identified as a therapeutic target for several human diseases. The purpose of this study was to determine whether CD11b was implicated in WNV infection.

Methods
SH-SY5Y cells with and without MEK1/2 inhibitor U0126 or AKT inhibitor MK-2206 treatment were infected with WNV. CD11b mRNA levels were assessed by real-time PCR. WNV replication and expression of stress (ATF6 and CHOP), pro-inflammatory (TNF-α), and antiviral (IFN-α, IFN-β, and IFN-γ) factors were evaluated in WNV-infected SH-SY5Y cells with CD11b siRNA transfection. Cell viability was determined by MTS assay.

Results
CD11b mRNA expression was remarkably up-regulated by WNV in a time-dependent manner. U0126 but not MK-2206 treatment reduced the CD11b induction by WNV. CD11b knockdown significantly decreased WNV replication and protected the infected cells. CD11b knockdown markedly increased TNF-α, IFN-α, IFN-β, and IFN-γ mRNA expression induced by WNV. ATF6 mRNA expression was reduced upon CD11b knockdown following WNV infection.

Conclusion
These results demonstrate that CD11b is involved in maintaining WNV replication and modulating inflammatory as well as antiviral immune response, highlighting the potential of CD11b as a target for therapeutics for WNV infection.
An ensemble deep learning models approach using image analysis for cotton crop classification in AI-enabled smart agriculture
Authors: Shahid Muhammad Farrukh , Khanzada Tariq J. S. , Aslam Muhammad Ahtisham , Hussain Shehroz , Baowidan Souad Ahmad , Ashari Rehab Bahaaddin 
Published: July 2024

Abstract
Background
Agriculture is one of the most crucial assets of any country, as it brings prosperity by alleviating poverty, food shortages, unemployment, and economic instability. The entire process of agriculture comprises many sectors, such as crop cultivation, water irrigation, the supply chain, and many more. During the cultivation process, the plant is exposed to many challenges, among which pesticide attacks and disease in the plant are the main threats. Diseases affect yield production, which affects the country’s economy. Over the past decade, there have been significant advancements in agriculture; nevertheless, a substantial portion of crop yields continues to be compromised by diseases and pests. Early detection and prevention are crucial for successful crop management.

Methods
To address this, we propose a framework that utilizes state-of-the-art computer vision (CV) and artificial intelligence (AI) techniques, specifically deep learning (DL), for detecting healthy and unhealthy cotton plants. Our approach combines DL with feature extraction methods such as continuous wavelet transform (CWT) and fast Fourier transform (FFT). The detection process involved employing pre-trained models such as AlexNet, GoogLeNet, InceptionV3, and VGG-19. Implemented models performance was analysed based on metrics such as accuracy, precision, recall, F1-Score, and Confusion matrices. Moreover, the proposed framework employed ensemble learning framework which uses averaging method to fuse the classification score of individual DL model, thereby improving the overall classification accuracy.

Results
During the training process, the framework achieved better performance when features extracted from CWT were used as inputs to the DL model compared to features extracted from FFT. Among the learning models, GoogleNet obtained a remarkable accuracy of 93.4% and a notable F1-score of 0.953 when trained on features extracted by CWT in comparison to FFT-extracted features. It was closely followed by AlexNet and InceptionV3 with an accuracy of 93.4% and 91.8% respectively. To further improve the classification accuracy, ensemble learning framework achieved 98.4% on the features extracted from CWT as compared to feature extracted from FFT.

Conclusion
The results show that the features extracted as scalograms more accurately detect each plant condition using DL models, facilitating the early detection of diseases in cotton plants. This early detection leads to better yield and profit which positively affects the economy.