bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the causal relationships between rheumatoid arthritis and oral phenotypes: a genetic correlation and Mendelian randomization study
Authors: Shen Jindan , Lou Yimei , Zhang Liping 
Published: May 2024

BackgroundRheumatoid arthritis (RA) frequently presents with oral manifestations, including gingival inflammation, loose teeth, and mouth ulcers; however, the causal connections between these conditions remain unclear. This study aims to explore the genetic correlations and causal relationships between RA and prevalent oral phenotypes.MethodsUsing summary data from genome-wide association studies of European populations, a cross-trait linkage disequilibrium score regression was conducted to estimate the genetic correlations between RA and six oral phenotypes. Subsequently, a two-sample Mendelian randomization (MR) approach was employed to assess the causal relationships, corroborated by various sensitivity analyses. Heterogeneity was addressed through the RadialMR method, while potential covariates were corrected using the multivariable MR approach.ResultsA significant negative genetic correlation was detected between RA and denture usage (rg = −0.192, p = 4.88 × 10−8). Meanwhile, a heterogenous causal relationship between RA and mouth ulcers was observed (OR = 1.027 [1.005–1.05], p = 0.016, Pheterogeneity = 4.69 × 10−8), which remained robust across sensitivity analyses. After excluding outlier variants, the results demonstrated robustly consistent (OR = 1.021 [1.008–1.035], p = 1.99 × 10−3, Pheterogeneity = 0.044). However, upon adjusting for covariates such as smoking, alcohol consumption, body mass index, and obesity, the significance diminished, revealing no evidence to support independent genetic associations.ConclusionGenetically predicted RA increases the risk of mouth ulcers, and a negative genetic correlation is identified between RA and denture use. The observed heterogeneity suggests that shared immunological mechanisms and environmental factors may play significant roles. These findings highlight the importance of targeted dental management strategies for RA patients. Further clinical guidelines are required to improve oral health among vulnerable RA patients.
Genetically predicted major depression causally increases the risk of temporomandibular joint disorders
Authors: Wu Shiqian , Chen Zhuo , Zhao Yawen , He Qiang , Yin Zhongxiu , Yao Hailiang , Liu Huili , Yan Lihui 
Published: May 2024

ObjectiveObservational studies have reported that mental disorders are comorbid with temporomandibular joint disorder (TMD). However, the causal relationship remains uncertain. To clarify the causal relationship between three common mental illnesses and TMD, we conduct this Mendelian Randomization (MR) study.MethodsThe large-scale genome-wide association studies data of major depression, bipolar disorder and schizophrenia were retrieved from the Psychiatric Genomics Consortium. The summary data of TMD was obtained from the Finn-Gen consortium, including 211,023 subjects of European descent (5,668 cases and 205,355 controls). The main approach utilized was inverse variance weighting (IVW) to evaluate the causal association between the three mental disorders and TMD. Five sensitivity analyses including MR-Egger, Maximum Likelihood, Weighted median, MR. RAPS and MR-PRESSO were used as supplements. We conducted heterogeneity tests and pleiotropic tests to ensure the robustness.ResultsAs shown by the IVW method, genetically determined major depression was associated with a 1.65-fold risk of TMD (95% CI = 1.10–2.47, p &lt; 0.05). The direction and effect size remained consistent with sensitivity analyses. The odds ratios (ORs) were 1.51 (95% CI = 0.24–9.41, p &gt; 0.05) for MR-Egger, 1.60 (95% CI = 0.98–2.61, p &gt; 0.05) for Weighted median, 1.68 (95% CI = 1.19–2.38, p &lt; 0.05) for Maximum likelihood, 1.56 (95% CI = 1.05–2.33, p &lt; 0.05) for MR. RAPS, and 1.65 (95% CI = 1.10–2.47, p &lt; 0.05) for MR-PRESSO, respectively. No pleiotropy was observed (both P for MR-Egger intercept and Global test &gt;0.05). In addition, the IVW method identified no significant correlation between bipolar disorder, schizophrenia and TMD.ConclusionGenetic evidence supports a causal relationship between major depression and TMD, instead of bipolar disorder and schizophrenia. These findings emphasize the importance of assessing a patient’s depressive status in clinical settings.
Association between protein intake, serum albumin and blood eosinophil in US asthmatic adults
Authors: Wen Jun , Xia Jing , He Qingliu , Giri Mohan , Guo Shuliang 
Published: May 2024

BackgroundPresently, numerous studies have indicated that protein consumption and levels of blood albumin serve as important biomarkers for a range of respiratory illnesses. However, there have been few investigations into the correlation between protein consumption, serum albumin, and asthma.MethodsOur analysis incorporated 2509 asthmatics from the 2011–2018 NHANES dataset. The investigation employed three linear regression models and XGBoost model to investigate the potential link between protein intake, serum albumin levels, and blood eosinophil counts (BEOC) in patients with asthma. The trend test, generalized additive model (GAM), and threshold effect model were utilized to validate this correlation. As well, we undertook stratified analyses to look at the correlation of serum albumin with BEOC among distinct populations.ResultsIn the univariable regression model, which did not account for any covariates, we observed a positive correlation between protein intake and BEOC. However, univariable and multivariable regression analyses all suggested a negative connection of serum albumin with BEOC in asthma populations. In Model C, which took into account all possible factors, BEOC dropped by 2.82 cells/uL for every unit increase in serum albumin (g/L). Additionally, the GAM and threshold effect model validated that serum albumin and BEOC showed an inverted U-shaped correlation.ConclusionOur investigation discovered there was no independent link between asthmatics’ protein intake and BEOC. However, we observed an inverted U-shaped relationship between serum albumin levels and BEOC, suggesting a possible relationship between the overall nutritional status of asthmatics and immune system changes. Our findings provide new directions for future research in the field of asthma management and therapy.
Sex-biased immunogenicity of a mucosal subunit vaccine against SARS-CoV-2 in mice
Authors: Li Jianping , Hsu Kevin S. , Howe Savannah E. , Hoang Tanya , Xia Zheng , Berzofsky Jay A. , Sui Yongjun 
Published: May 2024

IntroductionCurrent vaccines against COVID-19 administered via parenteral route have limited ability to induce mucosal immunity. There is a need for an effective mucosal vaccine to combat SARS-CoV-2 virus replication in the respiratory mucosa. Moreover, sex differences are known to affect systemic antibody responses against vaccines. However, their role in mucosal cellular responses against a vaccine remains unclear and is underappreciated.MethodsWe evaluated the mucosal immunogenicity of a booster vaccine regimen that is recombinant protein-based and administered intranasally in mice to explore sex differences in mucosal humoral and cellular responses.ResultsOur results showed that vaccinated mice elicited strong systemic antibody (Ab), nasal, and bronchiole alveolar lavage (BAL) IgA responses, and local T cell immune responses in the lung in a sex-biased manner irrespective of mouse genetic background. Monocytes, alveolar macrophages, and CD103+ resident dendritic cells (DCs) in the lungs are correlated with robust mucosal Ab and T cell responses induced by the mucosal vaccine.DiscussionOur findings provide novel insights into optimizing next-generation booster vaccines against SARS-CoV-2 by inducing spike-specific lung T cell responses, as well as optimizing mucosal immunity for other respiratory infections, and a rationale for considering sex differences in future vaccine research and vaccination practice.
Sex differences in immune protection in mice conferred by heterologous vaccines for pneumonic plague
Authors: Davies Michael L. , Biryukov Sergei S. , Rill Nathaniel O. , Klimko Christopher P. , Hunter Melissa , Dankmeyer Jennifer L. , Miller Jeremy A. , Shoe Jennifer L. , Mlynek Kevin D. , Talyansky Yuli , Toothman Ronald G. , Qiu Ju , Bozue Joel A. , Cote Christopher K. 
Published: May 2024

BackgroundYersinia pestis is the etiological agent of plague, which can manifest as bubonic, septicemic, and/or pneumonic disease. Plague is a severe and rapidly progressing illness that can only be successfully treated with antibiotics initiated early after infection. There are no FDA-approved vaccines for plague, and some vaccine candidates may be less effective against pneumonic plague than bubonic plague. Y. pestis is not known to impact males and females differently in mechanisms of pathogenesis or severity of infection. However, one previous study reported sex-biased vaccine effectiveness after intranasal Y. pestis challenge. As part of developing a safe and effective vaccine, it is essential that potential sex differences are characterized. MethodsIn this study we evaluated novel vaccines in male and female BALB/c mice using a heterologous prime-boost approach and monitored survival, bacterial load in organs, and immunological correlates. Our vaccine strategy consisted of two subcutaneous immunizations, followed by challenge with aerosolized virulent nonencapsulated Y. pestis. Mice were immunized with a combination of live Y. pestis pgm- pPst-Δcaf1, live Y. pestis pgm- pPst-Δcaf1/ΔyopD, or recombinant F1-V (rF1-V) combined with adjuvants. ResultsThe most effective vaccine regimen was initial priming with rF1-V, followed by boost with either of the live attenuated strains. However, this and other strategies were more protective in female mice. Males had higher bacterial burden and differing patterns of cytokine expression and serum antibody titers. Male mice did not demonstrate synergy between vaccination and antibiotic treatment as repeatedly observed in female mice.ConclusionsThis study provides new knowledge about heterologous vaccine strategies, sex differences in plague-vaccine efficacy, and the immunological factors that differ between male and female mice.
COVID-19 PBMCs are doubly harmful, through LDN-mediated lung epithelial damage and monocytic impaired responsiveness to live Pseudomonas aeruginosa exposure
Authors: Gaudin Clémence , Born-Bony Maëlys , Villeret Bérengère , Jaillet Madeleine , Faille Dorothée , Timsit Jean-François , Tran-Dinh Alexy , Montravers Philippe , Crestani Bruno , Garcia-Verdugo Ignacio , Sallenave Jean-Michel 
Published: May 2024

IntroductionAlthough many studies have underscored the importance of T cells, phenotypically and functionally, fewer have studied the functions of myeloid cells in COVID disease. In particular, the potential role of myeloid cells such as monocytes and low-density neutrophils (LDNs) in innate responses and particular in the defense against secondary bacterial infections has been much less documented.MethodsHere, we compared, in a longitudinal study, healthy subjects, idiopathic fibrosis patients, COVID patients who were either hospitalized/moderate (M-) or admitted to ICU (COV-ICU) and patients in ICU hospitalized for other reasons (non-COV-ICU).ResultsWe show that COVID patients have an increased proportion of low-density neutrophils (LDNs), which produce high levels of proteases (particularly, NE, MMP-8 and MMP-9) (unlike non-COV-ICU patients), which are partly responsible for causing type II alveolar cell damage in co-culture experiments. In addition, we showed that M- and ICU-COVID monocytes had reduced responsiveness towards further live Pseudomonas aeruginosa (PAO1 strain) infection, an important pathogen colonizing COVID patients in ICU, as assessed by an impaired secretion of myeloid cytokines (IL-1, TNF, IL-8,…). By contrast, lymphoid cytokines (in particular type 2/type 3) levels remained high, both basally and post PAO1 infection, as reflected by the unimpaired capacity of T cells to proliferate, when stimulated with anti-CD3/CD28 beads.DiscussionOverall, our results demonstrate that COVID circulatory T cells have a biased type 2/3 phenotype, unconducive to proper anti-viral responses and that myeloid cells have a dual deleterious phenotype, through their LDN-mediated damaging effect on alveolar cells and their impaired responsiveness (monocyte-mediated) towards bacterial pathogens such as P. aeruginosa.
Cynaroside ameliorates methotrexate-induced enteritis in rats through inhibiting NLRP3 inflammasome activation
Authors: Lang Wuying , Wen Xin , Zhang Shuangqi , Liang Xuhua , Chen Lin , Zhang Dezhu , Zhou Ruina , Ali Ihsan , Hu Xuansheng , Zhang Haihua , Cheng Min 
Published: May 2024

IntroductionCynaroside exhibits various biological properties, including anti-inflammatory, antiviral, antitumor, and cardioprotective effects. However, its involvement in methotrexate (MTX)-induced intestinal inflammation remains inadequately understood. Thus, we investigated the impact of cynaroside on MTX-induced intestinal inflammation and its potential mechanisms.MethodsTo assess the protective potential of cynaroside against intestinal inflammation, Sprague-Dawley rats were subjected to a regimen of 7 mg/kg MTX for 3 days, followed by treatment with cynaroside at varying doses (10, 20, or 40 mg/kg). Histopathological evaluations were conducted alongside measurements of inflammatory mediators to elucidate the involvement of the NLRP3 inflammasome in alleviating intestinal inflammation.ResultsAdministration of 7 mg/kg MTX resulted in decreased daily food intake, increased weight loss, and elevated disease activity index in rats. Conversely, treatment with cynaroside at 20 or 40 mg/kg ameliorated the reductions in body weight and daily food intake and suppressed the MTX-induced elevation in the disease activity index. Notably, cynaroside administration at 20 or 40 mg/kg attenuated inflammatory cell infiltration, augmented goblet cell numbers and lowered serum levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-18, as well as the CD68-positive cell rate in the intestines of MTX-induced rats. Furthermore, cynaroside downregulated the expression levels of NLRP3, cleaved caspase 1, and cleaved IL-1β in MTX-induced rats.DiscussionCollectively, our findings indicated that cymaroside alleviates intestinal inflammatory injury by inhibiting the activation of NLRP3 inflammasome in MTX-induced rats.
Are microplastics efficient remediation tools for removing the statin Lipitor? A laboratory experiment with meiobenthic nematodes
Authors: Aldraiwish Bayan M. , Alaqeel Maha M. , Al-Hoshani Nawal , Özdemir Sadin , Pacioglu Octavian , Necula Marian , Milea Eduard C. , Hedfi Amor , Rudayni Hassan A. , Boufahja Fehmi 
Published: May 2024

IntroductionThe current experiment investigated the multifaceted effects induced by microplastics and the statin Lipitor on marine benthic nematodes.MethodsThe nematodes were exposed to a single polystyrene and polyvinyl chlorides (both at 1 mg.kg-1 Dry Weight) and two Lipitor concentrations (0.1 and 1 mg.l-1), as well as to a mixture of both types of pollutants, for 30 days.ResultsThe results highlighted a significant decrease in the abundance, individual biomass, and diversity of nematodes directly with the addition of polyvinyl chlorides and/or Lipitor. These treatments induced a greater mortality rate among microvores and diatom feeders compared to other feeding types of nematodes.DiscussionThe nematofauna underwent a strong restructuring phase following exposure to microplastics and Lipitor when added alone, leading to the disappearance of sensitive species and their replacement by more tolerant taxa. The toxicity of Lipitor is attenuated by the physical bonding with polystyrene when added to a mixture and has no negative effect on marine nematode species.
Enhancing comfort of resident physicians treating adults with intellectual and developmental disabilities by facilitating meaningful interactions
Authors: Sanders Jessica Solomon , Williams Kathryn , Thompson Darcy , Shapiro Hannah F. 
Published: May 2024

BackgroundMany physicians feel uncomfortable caring for patients with intellectual and developmental disabilities (IDD). While some residency training programs include lecture content on IDD, few provide structured experiences with individuals with IDD. One strategy for improving comfort is “contact theory:” increasing interactions with “dissimilar” people can lead to decreased negative attitudes toward that population.ObjectiveEvaluate the impact of an interactive session on resident physicians’ comfort with adults with IDD.MethodsSmall groups of resident physicians and artists with IDD collaborated on art projects during the noon conference. A prospective pre-post-intervention survey, including the validated Interaction with Disabled Persons Scale (IDP), evaluated residents’ comfort with patients with IDD before and after the session.Results53 residents completed both pre- and post-conference surveys. Mean IDP scores decreased from 78.7 (10.9) to 75.8 (9.5; p &lt; 0.01), indicating decreasing discomfort. The mean level of comfort interacting with individuals with IDD increased from uncomfortable 3.6 (1.2), before the intervention, to comfortable 4.4 (1.2) after the intervention (p = &lt;0.01). The mean level of comfort treating individuals with IDD increased from uncomfortable 3.5 (1.1) to comfortable 4.1 (1.3) after the intervention (p &lt; 0.01).DiscussionProviding resident physicians with real-life connections with people with IDD was associated with increased comfort. If statistically significant improvements occurred after one session, future studies should evaluate if additional experiences with people with IDD could have more substantial, lasting impacts on future doctors’ comfort with and willingness to care for patients with IDD.
Genus_Ruminococcus and order_Burkholderiales affect osteoporosis by regulating the microbiota-gut-bone axis
Authors: Li Ning , Wang Haiyang , Pei Huan , Wu Yueying , Li Lei , Ren Yu , Wang Si , Ma Yuan , Luo Miao , Yuan Jiali , Li Lvyu , Qin Dongdong 
Published: May 2024

BackgroundThis study aimed to clarify the relationship between the gut microbiota and osteoporosis combining Mendelian randomization (MR) analysis with animal experiments.MethodsWe conducted an analysis on the relationship between differential bacteria and osteoporosis using open-access genome-wide association study (GWAS) data on gut microbe and osteoporosis obtained from public databases. The analysis was performed using two-sample MR analysis, and the causal relationship was examined through inverse variance weighting (IVW), MR Egger, weighted median, and weighted mode methods. Bilateral oophorectomy was employed to replicate the mouse osteoporosis model, which was assessed by micro computed tomography (CT), pathological tests, and bone transformation indexes. Additionally, 16S rDNA sequencing was conducted on fecal samples, while SIgA and indexes of IL-6, IL-1β, and TNF-α inflammatory factors were examined in colon samples. Through immunofluorescence and histopathology, expression levels of tight junction proteins, such as claudin-1, ZO-1, and occludin, were assessed, and conduct correlation analysis on differential bacteria and related environmental factors were performed.ResultsA positive correlation was observed between g_Ruminococcus1 and the risk of osteoporosis, while O_Burkholderiales showed a negative correlation with the risk of osteoporosis. Furthermore, there was no evidence of heterogeneity or pleiotropy. The successful replication of the mouse osteoporosis model was assessed, and it was found that the abundance of the O_Burkholderiales was significantly reduced, while the abundance of g_Ruminococcus was significantly increased in the ovariectomized (OVX)-mice. The intestinal SIgA level of OVX mice decreased, the expression level of inflammatory factors increased, barrier damage occurred, and the content of LPS in the colon and serum significantly increased. The abundance level of O_Burkholderiales is strongly positively correlated with bone formation factors, gut barrier indicators, bone density, bone volume fraction, and trabecular bone quantity, whereas it was strongly negatively correlated with bone resorption factors and intestinal inflammatory factors, The abundance level of g_Ruminococcus shows a strong negative correlation with bone formation factors, gut barrier indicators, and bone volume fraction, and a strong positive correlation with bone resorption factors and intestinal inflammatory factors.ConclusionO_Burkholderiales and g_Ruminococcus may regulate the development of osteoporosis through the microbiota-gut-bone axis.
Clarifying the association between Parkinson’s disease and vitiligo: a population-based large-scale study
Authors: Kridin Khalaf , Ofir Lior , Weinstein Orly , Badarny Samih 
Published: May 2024

ObjectiveOur knowledge about the association between vitiligo and Parkinson’s disease (PD) is sparse. We sought to investigate the bidirectional epidemiological association between vitiligo and PD.MethodsA population-based study was conducted using Clalit Health Services (CHS) database (2002–2019) using both a cohort study and a case–control study design. Adjusted hazard ratio (HR) and odds ratio (OR) were calculated by multivariate Cox and logistic regressions, respectively.ResultsOverall, 20,851 vitiligo patients and 102,475 controls were included. The incidence of new-onset PD was 2.9 (95% CI, 2.1–4.1) and 4.3 (95% CI, 3.8–4.9) cases per 10,000 person-years among patients with vitiligo and controls, respectively. Patients with vitiligo had a significantly decreased risk of developing new-onset PD [adjusted HR, 0.62; 95% confidence interval (CI), 0.43–0.89, p = 0.009]. On the other hand, the likelihood of having vitiligo after a preexisting diagnosis of PD was not statistically different (adjusted OR, 0.80; 95% CI, 0.61–1.06; p = 0.117). Relative to the remaining patients with vitiligo, those with vitiligo and comorbid PD experienced an elevated risk of all-cause mortality (adjusted HR, 2.63; 95% CI, 1.82–3.80; p &lt; 0.001) and higher prevalence of cardiometabolic comorbidities.ConclusionVitiligo is associated with a lower risk of developing PD. The presence of comorbid PD predisposes patients with vitiligo to elevated mortality and cardiometabolic outcomes.