bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low incidence of malignancy in patients with suspected polymyalgia rheumatica or giant cell arteritis, examined with FDG-PET/CT
Authors: Gorlen Tanja Fromberg , Brittain Jane Maestri , Østergaard Mikkel , Fischer Barbara Malene , Døhn Uffe Møller , Terslev Lene 
Published: February 2024

IntroductionThe need to systematically examine patients suspected of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) for malignancy is controversial. The aim of this study was to assess the frequency of malignancy in patients with suspected PMR and/or GCA who have been referred to a 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography with computed tomography (FDG-PET/CT) as part of the diagnostic investigation.MethodThe records of all patients referred to FDG-PET/CT from Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup with the suspicion of PMR and/or GCA during a two-year period, were retrospectively reviewed. Data was analyzed with descriptive statistics, and a standard incidence ratio was calculated based on background cancer incidences extracted from the NORDCAN database.Results220 patients were included in the study. Findings suspicious of malignancy were found in 19 of the examinations, and in seven cases (3.2%), malignancy was confirmed. In three out of the seven cases the patients were diagnosed with PMR concomitantly with malignancy. The estimated standardized incidence ratio (SIR) for cancer compared to the background incidence of cancer in Denmark was 1.58 (95% CI 0.63–2.97), i.e., not statistically significant. There were no statistically significant differences in characteristics of the patients that were diagnosed with malignancy compared with those that were not.ConclusionThe frequency of malignancy in this cohort of patients with suspected PMR/GCA who underwent PET/CT was low. Our results, though based on a small cohort, do not suggest that all patients with suspected PMR/GCA should systematically be examined with FDG-PET/CT for excluding malignancy.
Risk and protective factors for Long COVID in Brazilian adults (CUME Study)
Authors: Eduvirgem Júlio , Bressan Josefina , Hermsdorff Helen Hermana Miranda , Montenegro Livia Cozer , Brandão Marlise Lima , Neves Alessandra Aparecida Tavares , da Silva Lucas Samuel Aristides , Gerake-Dias Thiago Alexandre , Pimenta Adriano Marçal 
Published: February 2024

BackgroundMost people recover from COVID-19, however, between 5 to 20% have experienced new, recurring, or continuous health problems four or more weeks after being infected, a phenomenon called Long COVID, and whose reasons for its manifestation are incipient. Our objective was to analyse the risk and protective factors for Long COVID in Brazilian adults participating in the CUME Study.MethodsThe CUME Study is a prospective cohort conducted with graduates from federal universities in the State of Minas Gerais, Brazil. In this study, 390 participants who answered the baseline questionnaire in 2016 and the third follow-up questionnaire in 2022 (which contained a block of questions about occurrence of COVID-19 and Long COVID) were included. The diagnosis of Long COVID was based on self-reporting of persistence of signs and symptoms of COVID-19 between 30 days and 6 months after remission of the disease. To estimate the risk and protective factors for Long COVID, a hierarchical multivariate statistical analysis was conducted using the Poisson regression technique.ResultsLong COVID was observed in 48.9% of the participants. The following characteristics were identified as risk factors for the outcome: female sex (RR = 1.56; 95% CI = 1.22–1.99); prior diagnosis of hypertension (RR = 1.46; 95% CI = 1.19–1.80); having contracted COVID-19 in the first (RR =1.38; 95% CI = 1.07–1.79) or in the second waves (RR = 1.33; 95% CI = 1.07–1.65) of the pandemic period; and having presented three or more signs and symptoms during the acute phase of COVID-19 (RR = 2.99; 95% CI = 1.08–8.24). On the other hand, having a doctoral/postdoctoral educational level (RR = 0.69; 95% CI = 0.50–0.94) was identified as a protective factor for the outcome.ConclusionHealth system managers and healthcare professionals should be aware of the socioeconomic profile and disease history of patients who have had COVID-19 because women, people with a prior diagnosis of hypertension, and those who manifested multiple signs and symptoms of COVID-19 during the acute phase of the disease were at greater risk of developing Long COVID.
Lactiplantibacillusplantarum APsulloc331261 (GTB1™) promotes butyrate production to suppress mucin hypersecretion in a murine allergic airway inflammation model
Authors: Kim Hye-Shin , Kim Bobae , Holzapfel Wilhelm H. , Kang Hyeji 
Published: February 2024

IntroductionAllergic airway diseases are one of the serious health problems in worldwide and allergic airway inflammation is a prerequisite led to the exacerbated situation such as mucus hypersecretion, epithelial barrier damage and microbiota dysbiosis. Because of side effects and low efficiencies of current therapeutics, the need for novel alternatives has been urged. Probiotics in which have diverse and beneficial modulatory effects have been applied to the airway inflammation model and the underlying mechanism needs to be investigated.MethodsWe aimed to evaluate whether our target strain, Lactiplantibacillus plantarum APsulloc331261 (GTB1TM) isolated from green tea, can ameliorate allergic airway inflammation in mice and to figure out the mechanism. We induced allergic airway inflammation to mice by ovalbumin (OVA) and administered GTB1 orally and the immune and epithelial barrier markers were assessed. The gut metabolite and microbiota were also analysed, and the in vitro cell-line experiment was introduced to confirm the hypothesis of the study.ResultsGTB1 ameliorated type 2 inflammation and suppressed mucin hypersecretion with the inhibition of MUC5AC in inflamed mice. Moreover, GTB1 increased the butyrate production and the relative abundance of butyrate producer, Clostridium cluster IV. We assumed that butyrate may have a potential role and investigated the effect of butyrate in mucin regulation via human airway epithelial cell line, A549. Butyrate significantly reduced the gene expression of MUC5AC in A549 cells suggesting its regulatory role in mucus production.ConclusionTherefore, our study demonstrates that the oral administration of GTB1 can ameliorate allergic airway inflammation and mucin hypersecretion by butyrate production.
Electroacupuncture at ST25 corrected gut microbial dysbiosis and SNpc lipid peroxidation in Parkinson’s disease rats
Authors: Hu Xuan-ming , Song Li-zhe-xiong , Zhang Zhi-zi , Ruan Xi , Li Hai-chang , Yu Zhi , Huang Lin 
Published: February 2024

IntroductionParkinson’s disease (PD) remains one kind of a complex, progressive neurodegenerative disease. Levodopa and dopamine agonists as widely utilized PD therapeutics have not shown significant positive long-term outcomes. Emerging evidences indicate that electroacupuncture (EA) have potential effects on the therapy of nervous system disorders, particularly PD, but its specific underlying mechanism(s) remains poorly understood, leading to the great challenge of clinical application and management. Previous study has shown that acupuncture ameliorates PD motor symptoms and dopaminergic neuron damage by modulating intestinal dysbiosis, but its intermediate pathway has not been sufficiently investigated.MethodsA rat model of PD was induced using rotenone. The therapeutic effect of EA on PD was assessed using the pole and rotarod tests and immunohistostaining for tyrosine hydroxylase (TH) in the substantia nigra (SN) of brain. The role of gut microbiota was explored using 16S rRNA gene sequencing and metabonomic analysis. PICRUSt2 analysis, lipidomic analysis, LPS and inflammatory factor assays were used for subsequent exploration and validation. Correlation analysis was used to identify the key bacteria that EA regulates lipid metabolism to improve PD.ResultsThe present study firstly reappeared the effects of EA on protecting motor function and dopaminergic neurons and modulation of gut microbial dysbiosis in rotenone-induced PD rat model. EA improved motor dysfunction (via the pole and rotarod tests) and protected TH+ neurons in PD rats. EA increased the abundance of beneficial bacteria such as Lactobacillus, Dubosiella and Bifidobacterium and decreased the abundance of Escherichia-Shigella and Morganella belonging to Pseudomonadota, suggesting that the modulation of gut microbiota by EA improving the symptoms of PD motility via alleviating LPS-induced inflammatory response and oxidative stress, which was also validated by various aspects such as microbial gene functional analysis, fecal metabolomics analysis, LPS and inflammatory factor assays and SNpc lipidomics analysis. Moreover, correlation analyses also verified strong correlations of Escherichia-Shigella and Morganella with motor symptoms and SNpc lipid peroxidation, explicating targets and intermediate pathways through which EA improve PD exercise symptom.ConclusionOur results indicate that the improvement of motor function in PD model by EA may be mediated in part by restoring the gut microbiota, which intermediate processes involve circulating endotoxins and inflammatory mediators, SNpc oxidative stress and lipid peroxidation. The gut-microbiome - brain axis may be a potential mechanism of EA treatment for the PD.
Iron-induced kidney cell damage: insights into molecular mechanisms and potential diagnostic significance of urinary FTL
Authors: Punchai Soraya , Chaiyagot Nachayada , Artkaew Nadthanicha , Jusakul Apinya , Cha’on Ubon , Thanan Raynoo , Vaeteewoottacharn Kulthida , Lert-Itthiporn Worachart 
Published: February 2024

Background: Iron overload can lead to organ and cell injuries. Although the mechanisms of iron-induced cell damage have been extensively studied using various cells, little is known about these processes in kidney cells.Methods: In this study, we first examined the correlation between serum iron levels and kidney function. Subsequently, we investigated the molecular impact of excess iron on kidney cell lines, HEK293T and HK-2. The presence of the upregulated protein was further validated in urine.Results: The results revealed that excess iron caused significant cell death accompanied by morphological changes. Transcriptomic analysis revealed an up-regulation of the ferroptosis pathway during iron treatment. This was confirmed by up-regulation of ferroptosis markers, ferritin light chain (FTL), and prostaglandin-endoperoxide synthase 2 (PTGS2), and down-regulation of acyl-CoA synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4) using real-time PCR and Western blotting. In addition, excess iron treatment enhanced protein and lipid oxidation. Supportively, an inverse correlation between urinary FTL protein level and kidney function was observed.Conclusion: These findings suggest that excess iron disrupts cellular homeostasis and affects key proteins involved in kidney cell death. Our study demonstrated that high iron levels caused kidney cell damage. Additionally, urinary FTL might be a useful biomarker to detect kidney damage caused by iron toxicity. Our study also provided insights into the molecular mechanisms of iron-induced kidney injury, discussing several potential targets for future interventions.
Meta-analysis of MMP-9 levels in the serum of patients with epilepsy
Authors: Wang Qin , Lin Zehua , Yao Chunyuan , Liu Jinwen , Chen Jiangwei , Diao Limei 
Published: February 2024

BackgroundEpilepsy’s pathogenesis and progression are significantly influenced by neuroinflammation, blood–brain barrier function, and synaptic remodeling function. Matrix metalloproteinase 9 (MMP-9), as a critical factor, may contribute to the development of epilepsy through one or more of the above-mentioned pathways. This study aims to evaluate and quantify the correlation between MMP-9 levels and epilepsy.MethodsWe conducted a comprehensive search of Embase, Web of Science, PubMed, Cochrane Library, WanFang DATA, VIP, and the CNKI to identify studies that investigate the potential association between MMP-9 and epilepsy. The data were independently extracted by two researchers and assessed for quality using the Cochrane Collaboration tool. The extracted data were analyzed using Stata 15 and Review Manager 5.4. The study protocol was registered prospectively at PROSPERO, ID: CRD42023468493.ResultsThirteen studies with a total of 756 patients and 611 matched controls met the inclusion criteria. Eight of these studies reported total serum MMP-9 levels, and the other five studies were used for a further subgroup analysis. The meta-analysis indicated that the serum MMP-9 level was higher in epilepsy patients (SMD = 4.18, 95% confidence interval = 2.18–6.17, p &lt; 0.00001) compared with that in the control group. Publication bias was not detected according to Begg’s test. The subgroup analysis of country indicated that the epilepsy patients in China, Poland, and Egypt had higher levels of serum MMP-9 than the control group, with the increase being more pronounced in Egypt. The subgroup analysis of the age category demonstrated that the serum MMP-9 levels of the adult patients with epilepsy were significantly higher than those of the matched controls. However, the serum MMP-9 levels did not significantly differ in children with epilepsy. The subgroup analysis of the seizure types demonstrated substantial difference in the MMP-9 levels between patients of seizure-free epilepsy (patients who have been seizure-free for at least 7 days) and the control group. Meanwhile, the serum MMP-9 level in patients with epileptic seizures was significantly higher than that in the control group. The subgroup analysis based on seizure duration in patients showed that the serum MMP-9 levels at 1–3, 24, and 72 h after seizure did not exhibit significant differences between female and male patients with epilepsy when compared with the control group. The serum MMP-9 levels at 1–3 and 24 h were significantly higher than those of the matched controls. Nevertheless, the serum MMP-9 level at 72 h was not significantly different from that in the control group.ConclusionThis meta-analysis presents the first comprehensive summary of the connection between serum MMP-9 level and epilepsy. The MMP-9 levels in epilepsy patients are elevated. Large-scale studies with a high level of evidence are necessary to determine the exact relationship between MMP-9 and epilepsy.
Clinical vitamin A deficiency among preschool aged children in southwest Ethiopia
Authors: Nuredin Abdilwahid , Melis Tamirat , Abdu Abdu Oumer 
Published: February 2024

BackgroundThe clinical manifestations of vitamin A deficiency (VAD) involve night blindness, bitot’s spots, corneal xerosis, and corneal scars. It is the most important cause of preventable childhood blindness among children and causes morbidity and mortality. Even though Ethiopia implemented high-potency vitamin A supplements, the occurrence of VAD remains significant. This study was to identify determinants of clinical VAD among preschool-aged children (PSC) in southwest Ethiopia.MethodA community-based survey was conducted among 411 randomly selected PSCs. A pretested and structured questionnaire coupled with clinical observation for signs of vitamin A deficiency by a trained ophthalmologist was used to collect the data. An anthropometric measurement of height was taken and analyzed using WHO Anthro to calculate Z-scores for each index. The public health significance of VAD was declared after comparison with international references. A bi-variable and multi-variable logistic analysis was done. We reported the adjusted odds ratio (AOR), 95% confidence interval, and p-value.ResultA total of 411 children were screened for clinical VAD, and the overall prevalence was 2.2% (95% CI: 1.5–2.5). Of which, night blindness affects 1.2%, bitot’s spots affects 0.7%, and corneal xerosis affects 0.2%, indicating a major public health problem compared to the international reference. The odds of clinical VAD were 81% lower among children who received vitamin A supplementation (VAS; AOR = 0.19, 95% CI: 0.04–0.92). On the other hand, PSC of mothers who had attended ANC visits were 89% less likely to develop clinical VAD (AOR = 0.11, 95% CI: 0.02–0.53). In addition, the study revealed that the odds of developing clinical VAD are 82% lower among PSC aged 36 to 47 months (AOR = 0.18; 95% CI: 0.03–0.97).ConclusionThe prevalence of clinical VAD among PSC is a public health problem and is associated with ANC visits, VAS status, and the age of the child, which could be used to target interventions to further reduce existing VAD. Further studies using reliable dietary intake and biomarker data could further depict the burden of subclinical VAD.
Tea intake and total body bone mineral density of all ages: a Mendelian randomization analysis
Authors: Xing Chen , Tan Yanrong , Ni Wentao 
Published: February 2024

BackgroundThere is increasing evidence indicating that tea intake affects bone mineral density levels; however, the causality between tea intake and bone mineral density is inconclusive. This study aimed to assess the causal relationship between tea intake and total body bone mineral density (TB-BMD) through two-sample Mendelian randomization (MR) analysis.MethodsWe conducted a two-sample MR approach to estimate the potential causal effects of tea intake on TB-BMD at all ages in a European population. The analyses were performed using summary statistics obtained for single-nucleotide polymorphisms (SNPs), identified from a genome-wide association meta-analysis of tea intake (N = up to 447,485 individuals) and from the GEnetic Factors for OSteoporosis (GEFOS) Consortium’s genome-wide association meta-analysis (N = up to 56,284 individuals), with baseline data collected in 2018 and populations derived from the European ancestry. The association between each SNP and TB-BMD was weighted by its association with tea intake, and estimates were combined mainly using an inverse-variance weighted meta-analysis. In addition, we explored the potential causal effects between green tea intake, herbal tea intake, and TB-BMD.ResultsThe MR analysis revealed that genetically determined tea intake exerts a causal impact on TB-BMD, with an odds ratio (OR) of 1.204 (95% CI: 1.062–1.366, p = 0.004), especially in the age group of 45–60 years (OR = 1.360, 95% CI: 1.088–1.700, p = 0.007). No horizontal pleiotropy and heterogeneity were observed. However, there was no causal effect of tea intake on TB-BMD in the age groups of 0–15, 15–30, 30–45, and over 60 years. In the subgroup analysis, when green tea intake was regarded as the exposure factor, no salient associations were found between green tea consumption and TB-BMD (IVW p = 0.368). Similarly, there was also no causal association between herbal tea intake and TB-BMD (IVW p = 0.264).ConclusionThe findings of this study support the evidence that tea consumption increases bone density and reduces the risk of osteoporosis in the age group of 45–60 years within the European population.
Associations of trajectories in body roundness index with incident cardiovascular disease: a prospective cohort study in rural China
Authors: Zhang Shiru , Han Su , Zheng Liqiang , Sun Yingxian , Sun Zhaoqing 
Published: February 2024

AimsThe body roundness index (BRI) has good predictive ability for both body fat and visceral adipose tissue. Longitudinal BRI trajectories can reveal the potential dynamic patterns of change over time. This prospective study assessed potential associations between BRI trajectories and incident cardiovascular disease (CVD) in rural regions of Northeast China.MethodsIn total, 13,209 participants (mean age: 49.0 ± 10.3 years, 6,856 [51.9%] male) were enrolled with three repeated times of BRI measurements at baseline (2004–2006), 2008, and 2010, and followed up until 2017 in this prospective study. Using latent mixture model, the BRI trajectories were determined based on the data from baseline, 2008 and 2010. Composite CVD events (myocardial infarction, stroke, and CVD death combined) was the primary endpoint. Cox proportional-hazards models were used to analyze the longitudinal associations between BRI trajectories and incident CVD.ResultsThree distinct BRI trajectories were identified: high-stable (n = 538), moderate-stable (n = 1,542), and low-stable (n = 11,129). In total, 1,382 CVD events were recorded during follow-up. After adjustment for confounders, the moderate-stable and high-stable BRI groups had a higher CVD risk than did the low-stable BRI group, and the HR (95%CI) were 1.346 (1.154, 1.571) and 1.751 (1.398, 2.194), respectively. Similar associations were observed between the trajectories of BRI and the risk of stroke and CVD death. The high-stable group was also significantly and independently associated with CVD, myocardial infarction, stroke, and CVD death in participants aged &lt;50 years.ConclusionBRI trajectory was positively associated with incident CVD, providing a novel possibility for the primary prevention of CVD in rural regions of China.
Study protocol for a zinc intervention in the elderly for prevention of pneumonia, a randomized, placebo-controlled, double-blind clinical pilot trial
Authors: Ortega Edwin F. , Wu Dayong , Guo Weimin , Meydani Simin Nikbin , Panda Alexander 
Published: February 2024

Pneumonia is a major public health problem for older adults, being one of the leading causes of hospitalization and death, particularly for elderly nursing home residents. We previously conducted a clinical trial in which we demonstrated that 29% of nursing home residents had low serum zinc levels coinciding with a two-fold increase in pneumonia incidence and duration in comparison to individuals with adequate serum zinc levels. However, causality could not be inferred and necessitates a double-blind clinical trial. To determine the appropriate supplementation dose for such a trial we are conducting a randomized, placebo-controlled, double-blind clinical pilot trial aimed at delineating the optimal dosage (30 and 60 mg/day elemental Zn) and establishing safety. The results from the pilot study will be leveraged to inform our larger randomized clinical trial designed to study the effect of zinc supplementation in nursing home elderly with low serum zinc levels on respiratory infections, antibiotic use, and duration of sick days with pneumonia. In tandem with dose optimization, we will evaluate the correlation between serum zinc and pan-T cell zinc levels, given that T cells and their zinc levels are important in the response and resolution of respiratory infections but whose correlation has only been extrapolated and not demonstrated. Herein we present the study rationale and protocol, as well as discuss specific challenges we encountered in securing a manufacturer for the study agents and when recruiting from nursing home populations during the COVID-19 pandemic. In light of these experiences, we provide recommendations for future clinical trials under circumstances where supply chains are disrupted, and recruitment pools are constrained or unavailable.Clinical trial registrationhttps://clinicaltrials.gov/, NCT05527899.