bluuebunny/crossref_metadata_2025_split huggingface dataset:
NGF-releasing Prussian blue nanoparticles for nerve injury repair of lumbar disc herniation
Authors: Tang Xiaoxing , Sun Xin , Ji Yun , Huang Xuehua , Xiao Shilin , Zhou Yanjing , Ma Ke , Yuan Hongjie 
Published: December 2024

IntroductionCompression of the nerve root by a lumbar disc herniation can cause radiating pain in the lower limbs, and the nerve root decompression treatment may leave some patients with motor dysfunction and reduced sensory function. Studies have shown that nerve growth factor (NGF) can promote nerve growth and repair, but high doses, long duration, and immune response have become bottlenecks of its clinical application.MethodsTo overcome this obstacle, we developed Prussian blue (PBs) nanoparticles with the bio-delivery function and antioxidant effects of nanoenzymes. NGF was conjugated to the surface of PBs nanoparticles (PBs-NGF), which can be directly delivered to nerve cells.ResultsThe results showed that free PBs showed great advantages in scavenging oxygen free radicals and antioxidants, while PBs-NGF showed good biocompatibility. At the cellular level, cell proliferation assay and fluorescence microscopy analysis confirmed that PBs-NGF significantly promoted the proliferation, differentiation, and neurite outgrowth of neuron-like PC12 cells compared with free NGF. In a nerve root compression (NRC) rat model, behavioral observations (paw withdrawal threshold, PWT, and paw withdrawal latency, PWL) confirmed that PBs-NGF eased the pain caused by nerve root compression. H&amp;E staining showed that PBs-NGF could significantly reduce the inflammatory infiltration of nerve roots, and ELISA results showed that the concentrations of inflammatory markers (IL-6, IL-1β, and TNF-α) were also significantly reduced.ConclusionIn summary, the developed functional nanoplatform provides a basis for the clinical application of NGF in lumbar nerve root injury with disc herniation compression and a new treatment strategy for patients.
Gut microbiome and clinical and lifestyle host factors associated with recurrent positive RT-PCR for SARS-CoV-2
Authors: Jiménez-Arroyo Cristina , Molinero Natalia , Sabater Carlos , Margolles Abelardo , Terrón-Camero Laura Carmen , Andrés-León Eduardo , Ramos Manuel , del Val Margarita , Moreno-Arribas M. Victoria 
Published: December 2024

BackgroundSARS-CoV-2 and COVID-19 are still active in the population. Some patients remained PCR-positive for more than 4 weeks, called “persistently PCR-positive”. Recent evidence suggests a link between the gut microbiota and susceptibility to COVID-19, although no studies have explored persistent PCR conditions. We aimed to evaluate the relationship between persistent positive SARS-CoV-2 RT-PCR, the gut microbiome, and individual host determinants.MethodsA shotgun metagenomic analysis was conducted on fecal samples from 28 individuals affected by COVID-19. Patients were divided into two groups: those who had cleared the virus within 30 days (designated as the control group) (n = 15), and those who remained PCR-positive beyond 30 days (called the PCR+ group) (n = 13). We also investigated the correlation between prolonged viral clearance and several additional factors, including clinical parameters, immune responses, microbial metabolites, and dietary habits.ResultsThe composition and functionality of the microbiome varied based on the duration of positivity as determined by PCR. Compared to the control group, the persistent PCR+ group exhibited elevated pathogen levels and augmented diversity in functional gene families (p-value &lt; 0.05). A multi-omics analysis integrating metagenomics, metabolites, and metadata also revealed the specific contribution of certain blood markers in this group, including basophils, IgM, IgG (both general and specific for SARS-CoV-2), and markers of liver damage. Unhealthy diet was identified as a significant factor influencing the duration of PCR positivity.ConclusionsThese findings indicate that the gut microbiome may play a role in delayed viral clearance and persistent positive RT-PCR results. Our study also contributes to the understanding of the role of host factors as mediators linking the gut microbiota and disease outcomes. Further large-scale studies must confirm these data; however, they suggest the relevance of monitoring microbiome changes in the early post-viral years to control SARS-CoV-2 and providing individual healthcare support.
The association between the metabolic score for insulin resistance and mortality in patients with cardiovascular disease: a national cohort study
Authors: Su Xiaozhou , Rao Huiqing , Zhao Chunli , Zhang Xianwei , Li Donghua 
Published: December 2024

BackgroundThe metabolic score for insulin resistance (METS-IR) is a novel index for evaluating insulin resistance and identifying high-risk cardiovascular disease (CVD) patients. This study aims to assess the prognostic value of METS-IR in predicting mortality risk in CVD patients.MethodsWe analyzed data from 2,515 CVD patients in the National Health and Nutrition Examination Survey (NHANES). Associations between METS-IR and all-cause mortality and cardiovascular mortality were evaluated using multivariable Cox proportional hazards models and restricted cubic splines (RCS). Threshold effects and sensitivity analyses were conducted to ensure robustness.ResultsOver a median follow-up of 91.4 months, 1,090 patients died, including 447 from cardiovascular causes. A U-shaped relationship was identified between lnMETS-IR and all-cause and cardiovascular mortality, with thresholds at 3.70 and 3.67. Below thresholds, an increase of lnMETS-IR was associated with a 75% reduction in the risk of all-cause mortality (HR: 0.25, 95% CI: 0.14–0.46) and a 79% reduction in the risk of cardiovascular mortality (HR: 0.21, 95% CI: 0.07–0.56). While above thresholds, an increase of lnMETS-IR was associated with a 180% increase in the risk of all-cause mortality (HR: 2.80, 95% CI: 1.61–4.88) and a 233% increase in the risk of cardiovascular mortality (HR: 3.33, 95% CI: 1.43–7.75).ConclusionsThis study identified a U-shaped association between lnMETS-IR and mortality among CVD patients, underscoring the potential of METS-IR as a valuable prognostic marker for mortality risk in patients with CVD.
A systematic review of the association between insulin resistance surrogate indices and bone mineral density
Authors: Shirinezhad Amirhossein , Azarboo Alireza , Ghaseminejad-Raeini Amirhossein , Kanaani Nejad Fatemeh , Zareshahi Negar , Amiri Sheyda Mohtasham , Tahmasebi Yasamin , Hoveidaei Amir Human 
Published: December 2024

BackgroundThe relationship of insulin resistance with bone mineral density (BMD) remains unclear, offering an opportunity for novel indices to shed light on the matter. The aim of this review was to evaluate the association between surrogate indices of insulin resistance and BMD.MethodsA systematic review was conducted to evaluate observational studies that examined the relationship between insulin resistance surrogate indices and BMD in adults. Databases including PubMed, Web of Science, Scopus, and Embase were searched. Quality assessment was performed using Joanna Briggs Institute (JBI) critical appraisal tools.ResultsThis systematic review included 27 cohorts and cross-sectional studies with 71,525 participants to assess the potential link between insulin resistance surrogate indices like HOMA-IR, HOMA-β, TyG, TyG-BMI, TyG-WtHR, and TyG-WC, along with METS-IR, and VAI, and BMD at various sites. There seems to be no link between BMD and the HOMA index, despite being extensively studied in various studies (adjusted β ranging from -0.49 to 0.103). Most literature suggests that a higher TyG index is associated with decreased BMD levels (adjusted β ranging from -0.085 to 0.0124). Despite limited evidence, other insulin resistance indices such as VAI (adjusted β ranging from 0.007 to 0.016), TyG-BMI (adjusted β ranging from 0.002 to 0.415), METS-IR (adjusted β ranging from 0.005 to 0.060), TyG-WtHR (β = 0.012) and TyG-WC (β = 0.0001) have shown a positive association with BMD in a few studies.ConclusionThis systematic review emphasizes the intricate connection between insulin resistance and BMD. The lack of ability to perform a meta-analysis and the dependence on cross-sectional studies hinder the robustness of the findings, hence necessitating well-designed longitudinal studies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024512770.
SARS-CoV-2 strains and clinical profiles of COVID-19 patients in a Southern Brazil hospital
Authors: Fam Bibiana S. de Oliveira , Cadore Nathan Araujo , Sbruzzi Renan , Feira Marilea Furtado , Giudicelli Giovanna Câmara , de Almeida Luiz G. P. , Gerber Alexandra L. , Guimarães Ana Paula de C. , Vasconcelos Ana Tereza Ribeiro , Pereira Alexandre C. , Pereira Lygia V. , Hünemeier Tábita , Camey Suzi Alves , Vianna Fernanda S. Luiz 
Published: December 2024

IntroductionThe COVID-19 pandemic had a widespread global impact and presented numerous challenges. The emergence of SARS-CoV-2 variants has changed transmission rates and immune evasion, possibly impacting the severity. This study aims to investigate the impact of variants on clinical outcomes in southern Brazil.MethodsIn total, samples from 277 patients, hospitalized and non-hospitalized, were collected between March 2020 and March 2021, before the vaccine was made widely available to the general population in Brazil. Whole genome sequencing of SARS-CoV-2 was performed and bioinformatics and biostatistics analyses were implemented on molecular and clinical data, respectively.ResultsThe study identified significant demographic and clinical differences. The hospitalized group exhibited a higher proportion of males (51.9%) and an increased prevalence of comorbidities, including hypertension (66.0%), obesity (42.6%), and chronic kidney disease (23.6%). Patients were identified with twelve SARS-CoV-2 strains, predominantly B.1.1.28 and B.1.1.33 in the early 2020 first wave, and P.1 overlapping in the late 2020 and early 2021 second wave of COVID-19. Significant differences in hospitalization rates were found among patients infected with the different SARS-CoV-2 lineages: B.1.1.33 (46.0%), B.1.1.28 (65.9%), and P.1 (97.9%). Severity markers, such as pneumonia (62.5%, p=0.002), acute respiratory distress syndrome (ARDS, 72.9%, p&lt;0.001), and oxygen support &gt;6 L/min O2 (64.6%, p&lt;0.001), were more frequent in patients from the second wave. These findings highlight the impact of different variants on the clinical evolution and prognosis of COVID-19, especially when comparing the first and second waves of the pandemic.ConclusionsThe study underscores the association between SARS-CoV-2 strains and COVID-19 severity by integrating clinical and viral data for public health responses during different pandemic phases, highlighting the importance of adapting pandemic strategies as the pandemic evolves.
Serum fatty acid profiles in systemic lupus erythematosus and patient reported outcomes: The Michigan Lupus Epidemiology & Surveillance (MILES) Program
Authors: Gilley Kristen N. , Fenton Jenifer I. , Zick Suzanna M. , Li Kexin , Wang Lu , Marder Wendy , McCune W. Joseph , Jain Raghav , Herndon-Fenton Sidney , Hassett Afton L. , Barbour Kamil E. , Pestka James J. , Somers Emily C. 
Published: December 2024

IntroductionDespite progress in systemic lupus erythematosus (SLE) treatment, challenges persist in medication adherence due to side effects and costs. Precision nutrition, particularly adjusting fatty acid intake, offers a cost-effective strategy for enhancing SLE management. Prior research, including our own, indicates that increased consumption of omega-3 polyunsaturated fatty acids (PUFAs) correlates with improved outcomes in SLE patients. Here we build upon these findings by investigating associations between serum fatty acids—grouped as PUFAs, monounsaturated fatty acids (MUFAs), and saturated fatty acids (SFAs)—and lupus activity, pain, and sleep disturbance.MethodsUsing data from 418 participants with SLE in the Michigan Lupus Epidemiology and Surveillance (MILES) Cohort, we examined associations between serum levels of 25 fatty acids determined by GC-MS and patient-reported outcomes. Disease activity, pain, and sleep quality were assessed using standardized questionnaires. Generalized additive models and partial residual plots were utilized to examine the linearity of fatty acid effects. Variable selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO), followed by multiple linear regression adjusting for sociodemographic factors.ResultsFindings indicated favorable associations between ω-3 PUFAs—and, to a lesser extent, ω-6 PUFAs—and patient-reported outcomes, while MUFAs and SFAs showed unfavorable associations. Docosahexaenoic acid (DHA), an omega-3 PUFA, exhibited the most robust favorable associations across all outcomes. Additionally, the omega-3 α-linolenic acid (ALA) was linked to reduced pain, whereas eicosapentaenoic acid (EPA), another omega-3, was associated with worsened disease activity and pain. Among omega-6 PUFAs, dihomo-γ-linolenic acid (DGLA) was favorably associated with disease activity, while the omega-9 PUFA Mead acid was linked to increased pain.DiscussionThese findings underscore the prospect that increased tissue levels of long-chain omega-3 PUFAs, particularly DHA, are favorably associated with SLE outcomes. Although further research is needed to establish causal relationships, existing evidence supports the role of omega-3 PUFAs in managing cardiovascular and chronic kidney disease, common SLE comorbidities. Most study participants exhibited low omega-3 PUFA status, suggesting substantial potential for improvement through targeted dietary interventions and supplementation. This study supports a potential role for precision nutrition in comprehensive SLE management, considering the impact of PUFAs, SFAs and MUFAs.
Impact of COVID-19, lockdowns and vaccination on immune responses in a HIV cohort in the Netherlands
Authors: Otten Twan , Jiang Xun , Gupta Manoj Kumar , Vadaq Nadira , Cleophas-Jacobs Maartje , dos Santos Jéssica C. , Groenendijk Albert , Vos Wilhelm , van Eekeren Louise E. , Blaauw Marc J. T. , Meeder Elise M.G. , Richel Olivier , Matzaraki Vasiliki , van Lunzen Jan , Joosten Leo A. B. , Li Yang , Xu Cheng-Jian , van der Ven Andre , Netea Mihai G. 
Published: December 2024

IntroductionDuring the COVID-19 pandemic, major events with immune-modulating effects at population-level included COVID-19 infection, lockdowns, and mass vaccinations campaigns. As immune responses influence many immune-mediated diseases, population scale immunological changes may have broad consequences.MethodsWe investigated the impact of lockdowns, COVID-19 infection and vaccinations on immune responses in the 2000HIV study including 1895 asymptomatic virally-suppressed people living with HIV recruited between October 2019 and October 2021. Their inflammatory profile was assessed by targeted plasma proteomics, immune responsiveness by cytokine production capacity of circulating immune cells, and epigenetic profile by genome-wide DNA methylation of immune cells.ResultsPast mild COVID-19 infection had limited long-term immune effects. In contrast, COVID-19 vaccines and especially lockdowns significantly altered both the epigenetic profile in immune cells at DNA methylation level and immune responses. Lockdowns resulted in a strong overall exaggerated immune responsiveness, while COVID-19 vaccines moderately dampened immune responses. Lockdown-associated immune responsiveness alterations were confirmed in 30 healthy volunteers from the 200FG cohort that, like the 2000HIV study, is part of the Human Functional Genomics Project.DiscussionOur data suggest that lockdowns have unforeseen immunological effects. Furthermore, COVID-19 vaccines have immunological effects beyond anti-SARS-CoV-2 activity, and studies of their impact on non-COVID-19 immune-mediated pathology are warranted.
Revitalizing tetanus vaccine literacy post road accidents: a comprehensive examination of knowledge and awareness initiative among non-medical university students in Lahore, Pakistan
Authors: Ayub Fiza , Saleem Wahaj , Shahid Muhammad Awais , Hussain Khan Muhammad Afzal , Suleiman Amal K. , Akram Laiba , Sajid Sadaf , Bukhsh Allah , Baig Mirza Rafi , Khan Tahir Mehmood 
Published: December 2024

IntroductionTetanus, caused by Clostridium tetani, poses a life-threatening risk by affecting the nervous system and inducing muscle tightness. The objective of this study is to examine the knowledge, attitudes, and behaviors of non-medical university students regarding the tetanus vaccine in the context of post-road accidents.MethodsA descriptive cross-sectional study was conducted in 2023, involving 378 students from non-medical disciplines, primarily from information technology, business administration, and engineering faculties, with a mean age of 20.7 years. The sample size was calculated using the Raosoft sample calculator, and participants were selected via consecutive random sampling. Data was collected through a structured, self-administered questionnaire and analyzed using SPSS 22.0.ResultsGender distribution was 51.6% female and 48.4% male. Out of the 378 students, 53.4% (p=0.003) were unaware of tetanus contraction sources, 52.8% (p=0.004) lacked knowledge of its symptoms and 68.3% (p=0.004) were unfamiliar with the total number of doses. An appreciable 88.9% (p0.063) are willing to receive post-accident tetanus vaccination, reflecting positive attitudes and openness to preventive measures. Similarly, the p-values &gt;0.05 show no gender disparity in willingness to receive tetanus vaccination (p=0.063) and recommending vaccination to others after a road accident (p=0.879).ConclusionsNotwithstanding participants' positive attitudes, the results indicate poor knowledge of tetanus regarding its transmission, symptoms, and doses. Interventions should focus on refining practical aspects of education, including symptom recognition, vaccine efficacy, duration, and the importance of sustaining immunity.
High cumulative glucocorticoid dose is associated with increased levels of inflammation-related mediators in active rheumatoid arthritis
Authors: Petrackova Anna , Horak Pavel , Savara Jakub , Skacelova Martina , Kriegova Eva 
Published: December 2024

IntroductionGlucocorticoids (GCs) are widely used as a treatment for rheumatoid arthritis (RA), leading to high cumulative doses in long-term treated patients. The impact of a high cumulative GC dose on the systemic inflammatory response in RA remains poorly understood.MethodsWe investigated long-treated patients with RA (n = 72, median disease duration 14 years) through blood counts and the serum levels of 92 inflammation-related proteins, and disease activity was assessed using the Simple Disease Activity Index (SDAI). Patients were grouped based on the cumulative GC dose, with a cut-off value of 20 g (low/high, n = 49/23).Results and discussionPatients with a high cumulative GC dose within the active RA group had elevated serum levels in 23 inflammation-related proteins compared with patients with a low dose (cytokines/soluble receptors: CCL3, CCL20, CCL25, IL-8, CXCL9, IL-17A, IL-17C, IL-18, sIL-18R1, IL-10, sIL-10RB, OSM and sOPG; growth factors: sTGFα and sHGF; other inflammatory mediators: caspase 8, STAMBP, sCDCP1, sirtuin 2, 4E-BP1, sCD40, uPA and axin-1; pcorr &lt; 0.05). In non-active RA, the high and low GC groups did not differ in analysed serum protein levels. Moreover, patients with active RA with a high GC dose had an increased white blood cell count, increased neutrophil–lymphocyte and platelet–lymphocyte ratios and a decreased lymphocyte–monocyte ratio compared with the low dose group (p &lt; 0.05). This is the first study to report elevated serum levels in inflammation-related proteins and deregulated blood counts in patients with active RA with a high cumulative GC dose. The elevated systemic inflammation highlights the importance of improving care for patients receiving high cumulative GC doses.
Primary perianal alveolar rhabdomyosarcoma with uncommon metastatic sites: a case report and follow-up using 18F-FDG PET/CT
Authors: Yang Yihan , Chen Zhao , Qiu Yongkang , Cheng Jia , Na Ritai , Liu Min , Kang Lei 
Published: December 2024

BackgroundRhabdomyosarcoma (RMS), a rare pediatric soft tissue neoplasm, predominantly develops in late childhood and adolescence with no discernible gender bias. Alveolar rhabdomyosarcoma (ARMS) stems from mesenchymal cells and may develop most frequently in the trunk, extremities, and head/neck areas, while occurrences in the pelvic cavity are less frequent. The manifestation is typically characterized by a high rate of aggressive metastasis and a poor overall survival prognosis.Case reportWe present the case of an 11-year-old girl with ARMS initially presenting with a perianal mass. The diagnostic workup included MRI and PET/CT, which highlighted the tumor’s aggressive nature and metastatic potential. Subsequent metastases to the pleura, lymph nodes, and, less frequently, to the bone were detected using 2-deoxy-2-[fluorine-18]-fluoro-D-glucose positron emission tomography combined with computed tomography (18F-FDG PET/CT) imaging. The patient underwent a multi-regimen chemotherapy protocol but showed an incomplete response, indicating a poor prognosis.ConclusionThis report presents a rare case of ARMS primarily located in the perianal region with multiple metastases, including the uncommon occurrence of bone metastasis, which illustrates the challenges in diagnosing and treating ARMS, emphasizing the need for accurate and early diagnosis, advanced imaging for disease assessment, and more effective treatment strategies. 18F-FDG PET/CT imaging highlights its preeminence in detecting multiple rare metastatic lesions. However, the persistent disease activity despite treatment highlights the need for further research into the biology of ARMS and the development of novel therapeutics to improve patient outcomes.
Evaluation of post-COVID mortality risk in cases classified as severe acute respiratory syndrome in Brazil: a longitudinal study for medium and long term
Authors: Rodrigues Nádia Cristina Pinheiro , Andrade Mônica Kramer de Noronha 
Published: December 2024

BackgroundThere are few studies in the literature evaluating post-COVID mortality in Brazil, along medium and long term, especially in those who presented severe clinical disease.ObjectiveThis study aims to investigate the factors associated with post-COVID mortality of severe acute respiratory syndrome (SARS) cases from 2020 to 2023 in Brazil, along medium and long term.MethodsRetrospective cohort study using notification data of SARS classified as COVID-19 from the Brazilian National Information System, “Sistema de Vigilância Epidemiológica (SIVEP),” during the period 2020 to 2023. Data included demographics, comorbidities, vaccination status, number of COVID-19 vaccine doses, city of residence, and survival outcomes. Classic Cox, Cox mixed effects, and Cox fragility models were used to assess medium and long-term risks of dying post-COVID.ResultsIn the medium and long-term periods studied, 5,157 deaths were recorded out of 15,147 reported SARS/COVID-19 cases. Of these deaths, 91.5% (N = 4,720) occurred within the first year, while 8,5% (N = 437) after the first year. People without formal education, the older adult, had higher percentages of deaths in both periods. In the medium-term post-COVID period, the risk of death was reduced by 8% for those who had been vaccinated while in the long-term post-COVID period, the risk of death almost doubled for those who had been vaccinated. While in the medium term, there was a reduction in mortality risk for those who took two or three doses, in the long term the risk of death was greater for those who took one or two doses.ConclusionThe protective effect of COVID-19 immunization was observed up to one year after the first symptoms. After one year, the effect was reversed, showing an increased risk of death for those vaccinated. These results highlight the need for further research to elucidate the factors that contribute to these findings.