bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitro-fatty acids decrease type I interferons and monocyte chemoattractant protein 1 in ex vivo models of inflammatory arthritis
Authors: Hansen A. L. , Rahbek L. S. J. , Sørensen A. S. , Hundahl M. P. , Lomholt S. , Holm C. K. , Kragstrup Tue W. 
Published: December 2021

Abstract
Background
Inflammatory arthritis including rheumatoid arthritis (RA) and spondyloarthritis (SpA) is characterized by inflammation and destruction of the joints. Approximately one third of patients do not respond to first-line treatments. Nitro-fatty acids are bioactive lipids with anti-inflammatory properties and tissue-protective functions. The nitro-fatty acid 10-NO2-oleic acid (10-NO2-OA) is being tested in clinical trials for patients with fibrotic and inflammatory conditions. Here, we tested whether 10-NO2-OA could inhibit immune reactions involved in the inflammatory and joint destructive processes in inflammatory arthritis.

Methods
Synovial fluid and blood samples were obtained from 14 patients with active RA or SpA. The in vitro models consisted of synovial fluid mononuclear cells (SFMCs) cultured for 48 h, SFMCs cultured for 21 days, and fibroblast-like synovial cells (FLSs) co-cultured with peripheral blood mononuclear cells (PBMCs) for 48 h. Cells were treated with or without 10-NO2-OA or the tumor necrosis factor alpha (TNFα) inhibitor etanercept. Supernatants were analyzed for type I interferon, monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase 3 (MMP3) and tartrate resistant acid phosphatase (TRAP).

Results
In SFMCs cultured for 48 h, 10-NO2-OA dose-dependently decreased the secretion of bioactive type I interferons and MCP-1 but not MMP3 (P = 0.032, P = 0.0001, and P = 0.58, respectively). Both MCP-1 and MMP3 were decreased by etanercept (P = 0.0031 and P = 0.026, respectively). In SFMCs cultured for 21 days, 10-NO2-OA significantly decreased the production of MCP-1 but not TRAP (P = 0.027 and P = 0.1523, respectively). Etanercept decreased the production of TRAP but not MCP-1 (P < 0.001 and P = 0.84, respectively). In co-cultures of FLSs and PBMCs, 10-NO2-OA decreased the production of MCP-1 (P < 0.0001). This decrease in MCP-1 production was not seen with etanercept treatment (P = 0.47).

Conclusion
10-NO2-OA decreased the release of MCP-1 in three models of inflammatory arthritis. Of particular interest, 10-NO2-OA inhibited type I interferon, and 10-NO2-OA was more effective in reducing MCP-1 production in cultures dominated by FLSs compared with etanercept. Our results encourage clinical investigations of 10-NO2-OA in patients with inflammatory arthritis.
Relationship between internet research data of oral neoplasms and public health programs in the European Union
Authors: Lan Romain , Campana Fabrice , Tardivo Delphine , Catherine Jean-Hugues , Vergnes Jean-Noel , Hadj-Saïd Mehdi 
Published: December 2021

Abstract
Background
Tobacco and alcohol are the main risk factors for oral squamous cell carcinoma, the low survival rate of which is a public health problem. European-wide health policies (a prevention campaign, tobacco packaging) have been put in place to inform the population of the risks associated with consumption. Due to the increase in smoking among women, the incidence of this disease remains high. The identification of internet research data on the population could help to measure the impact of and better position these preventive measures. The objective was to analyze a potential temporal association between public health programs and interest in oral cancers on the internet in the European Union (EU).

Methods
A search of data from Google ©, Wikipedia © and Twitter © users in 28 European countries relating to oral cancer between 2004 and 2019 was completed. Bibliometric analysis of press and scientific articles over the same period was also performed. The association between these data and the introduction of public health programs in Europe was studied.

Results
There was a temporal association between changes in tobacco packaging and a significant increase in internet searches for oral cancer in seven countries. Unlike national policies and ad campaigns, the European awareness program Make Sense has had no influence on internet research. There was an asymmetric correlation in internet searches between publications on oral cancer from scientific articles or "traditional" media (weak association) and those from internet media such as Twitter © or Wikipedia © (strong association).

Conclusion
Our work highlights seven areas around which oral cancer awareness in Europe could be refocused, such as a change in the communication of health warnings on cigarette packs, the establishment of a more explicit campaign name regarding oral cancer, the involvement of public figures and associations in initiatives to be organized at the local level and the strengthening of awareness of the dangers of tobacco in the development of oral cancer.
Dopaminergic stimulation leads B-cell infiltration into the central nervous system upon autoimmunity
Authors: Prado Carolina , Osorio-Barrios Francisco , Falcón Paulina , Espinoza Alexandra , Saez Juan José , Yuseff María Isabel , Pacheco Rodrigo 
Published: December 2021

AbstractBackgroundRecent evidence has shown dopamine as a major regulator of inflammation. Accordingly, dopaminergic regulation of immune cells plays an important role in the physiopathology of inflammatory disorders. Multiple sclerosis (MS) is an inflammatory disease involving a CD4+T-cell-driven autoimmune response to central nervous system (CNS) derived antigens. Evidence from animal models has suggested that B cells play a fundamental role as antigen-presenting cells (APC) re-stimulating CD4+T cells in the CNS as well as regulating T-cell response by mean of inflammatory or anti-inflammatory cytokines. Here, we addressed the role of the dopamine receptor D3 (DRD3), which displays the highest affinity for dopamine, in B cells in animal models of MS.MethodsMice harbouringDrd3-deficient orDrd3-sufficient B cells were generated by bone marrow transplantation into recipient mice devoid of B cells. In these mice, we compared the development of experimental autoimmune encephalomyelitis (EAE) induced by immunization with a myelin oligodendrocyte glycoprotein (MOG)-derived peptide (pMOG), a model that leads to CNS-autoimmunity irrespective of the APC-function of B cells, or by immunization with full-length human MOG protein (huMOG), a model in which antigen-specific activated B cells display a fundamental APC-function in the CNS. APC-function was assessed in vitro by pulsing B cells with huMOG-coated beads and then co-culturing with MOG-specific T cells.ResultsOur data show that the selectiveDrd3deficiency in B cells abolishes the disease development in the huMOG-induced EAE model. Mechanistic analysis indicates that although DRD3-signalling did not affect the APC-function of B cells, DRD3 favours the CNS-tropism in a subset of pro-inflammatory B cells in the huMOG-induced EAE model, an effect that was associated with higher CXCR3 expression. Conversely, the results show that the selectiveDrd3 deficiencyin B cells exacerbates the disease severity in the pMOG-induced EAE model. Further analysis shows that DRD3-stimulation increased the expression of the CNS-homing molecule CD49d in a B-cell subset with anti-inflammatory features, thus attenuating EAE manifestation in the pMOG-induced EAE model.ConclusionsOur findings demonstrate that DRD3 in B cells exerts a dual role in CNS-autoimmunity, favouring CNS-tropism of pro-inflammatory B cells with APC-function and promoting CNS-homing of B cells with anti-inflammatory features. Thus, these results show DRD3-signalling in B cells as a critical regulator of CNS-autoimmunity.
Mechanisms underlying antidepressant effect of transcutaneous auricular vagus nerve stimulation on CUMS model rats based on hippocampal α7nAchR/NF-κB signal pathway
Authors: Wang Jun-ying , Zhang Yue , Chen Yu , Wang Yu , Li Shao-yuan , Wang Yi-fei , Zhang Zi-xuan , Zhang Jinling , Rong Peijing 
Published: December 2021

Abstract
Background
Stress-induced neuroinflammation was considered to play a critical role in the pathogenesis of depression. Transcutaneous auricular vagus nerve stimulation (taVNS) is a relatively non-invasive alternative treatment for patients suffering from major depressive disorder. The anti-inflammatory signal of vagus nerve is mediated by α7 nicotinic acetylcholine receptor (α7nAchR), and the hippocampus, the region with the most distribution of α7nAchR, regulates emotions. Here, we investigated the role of α7nAchR mediating hippocampal neuroinflammation in taVNS antidepressant effect though homozygous α7nAChR (−/−) gene knockout and α7nAchR antagonist (methyllycaconitine, MLA).

Methods
There were control, model, taVNS, α7nAChR(−/−) + taVNS, hippocampus (Hi) MLA + taVNS and Hi saline + taVNS groups. We used the chronic unpredicted mild stress (CUMS) method to establish depressive model rats for 42 days, excepting control group. After the successful modeling, except the control and model, the rats in the other groups were given taVNS, which was applied through an electroacupuncture apparatus at the auricular concha (2/15 Hz, 2 mA, 30 min/days) for 21 days. Behavioral tests were conducted at baseline, after modeling and after taVNS intervention, including sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST). These tests are widely used to evaluate depression-like behavior in rats. The samples were taken after experiment, the expressions of α7nAchR, NF-κB p65, IL-1β and the morphology of microglia were detected.

Results
Depression-like behavior and hippocampal neuroinflammation in CUMS model rats were manifested by down-regulated expression of α7nAchR, up-regulated expression of NF-κB p65 and IL-1β, and the morphology of microglia was in amoebic-like activated state. TaVNS could significantly reverse the above-mentioned phenomena, but had rare improvement effect for α7nAChR(−/−) rats and Hi MLA rats.

Conclusion
The antidepressant effect of taVNS is related to hippocampal α7nAchR/NF-κB signal pathway.
NLRP1 inflammasome involves in learning and memory impairments and neuronal damages during aging process in mice
Authors: Sun Dan , Gao Guofang , Zhong Bihua , Zhang Han , Ding Shixin , Sun Zhenghao , Zhang Yaodong , Li Weizu 
Published: December 2021

Abstract
Background
Brain aging is an important risk factor in many human diseases, such as Alzheimer’s disease (AD). The production of excess reactive oxygen species (ROS) mediated by nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and the maturation of inflammatory cytokines caused by activation of the NOD-like receptor protein 1 (NLRP1) inflammasome play central roles in promoting brain aging. However, it is still unclear when and how the neuroinflammation appears in the brain during aging process.

Methods
In this study, we observed the alterations of learning and memory impairments, neuronal damage, NLRP1 inflammasome activation, ROS production and NOX2 expression in the young 6-month-old (6 M) mice, presenile 16 M mice, and older 20 M and 24 M mice.

Results
The results indicated that, compared to 6 M mice, the locomotor activity, learning and memory abilities were slightly decreased in 16 M mice, and were significantly decreased in 20 M and 24 M mice, especially in the 24 M mice. The pathological results also showed that there were no significant neuronal damages in 6 M and 16 M mice, while there were obvious neuronal damages in 20 M and 24 M mice, especially in the 24 M group. Consistent with the behavioral and histological changes in the older mice, the activity of β-galactosidase (β-gal), the levels of ROS and IL-1β, and the expressions of NLRP1, ASC, caspase-1, NOX2, p47phox and p22phox were significantly increased in the cortex and hippocampus in the older 20 M and 24 M mice.

Conclusion
Our study suggested that NLRP1 inflammasome activation may be closely involved in aging-related neuronal damage and may be an important target for preventing brain aging.
Polytraumatization in young male refugees from the Middle East and its association with internalizing and externalizing symptoms
Authors: EL-Awad Usama , Reinelt Tilman , Braig Johanna , Nilles Hannah , Kerkhoff Denise , Schmees Pia , Rueth Jana-Elisa , Fathi Atefeh , Vasileva Mira , Petermann Franz , Eschenbeck Heike , Lohaus Arnold 
Published: December 2021

Abstract
Background
Young Middle Eastern male refugees are currently among the most vulnerable groups in Europe. Most of them have experienced potentially traumatic events (PTEs) such as rape, torture, or violent assaults. Compared to their peers, young refugees suffer more from internalizing and externalizing symptoms, especially when unaccompanied. Little is known about the cumulative impact of experiencing different types of PTEs on mental health outcomes (polytraumatization) of young male refugees from the Middle East. We investigated (1) whether there is a dose–response relationship between multiple PTE types experienced and mental health outcomes, (2) whether individual types of PTEs are particularly important, and (3) to what extent these are differentially associated with mental health outcomes among unaccompanied or accompanied peers.

Methods
In total, 151 young Middle Eastern male refugees in Germany (Mage = 16.81 years, SDage = 2.01) answered questionnaires on PTEs, mental health, and post-migration stress.

Results
Hierarchical regression analyses revealed, while controlling for age, duration of stay, unaccompanied status, and post-migration stress, (1) a dose–effect between PTE types on both internalizing and externalizing symptoms. Moreover, (2) regarding internalizing symptoms, violent family separation and experiencing life-threatening medical problems were particularly crucial. The latter was driven by unaccompanied refugees, who also reported higher levels of substance use.

Conclusions
The results extend findings from the literature and suggest that not only may greater polytraumatization be related to greater depression among refugees, but also to a range of other mental health outcomes from the internalizing and externalizing symptom domains. Furthermore, the results highlight the mental health risks that unaccompanied and accompanied refugee adolescents face after exposure to PTEs, and provide information for practitioners as well as researchers about event types that may be particularly relevant.
An epigenetic aging analysis of randomized metformin and weight loss interventions in overweight postmenopausal breast cancer survivors
Authors: Nwanaji-Enwerem Jamaji C. , Chung Felicia Fei-Lei , Van der Laan Lars , Novoloaca Alexei , Cuenin Cyrille , Johansson Harriet , Bonanni Bernardo , Hubbard Alan E. , Smith Martyn T. , Hartman Sheri J. , Cardenas Andres , Sears Dorothy D. , Herceg Zdenko 
Published: December 2021

AbstractMetformin and weight loss relationships with epigenetic age measures—biological aging biomarkers—remain understudied. We performed a post-hoc analysis of a randomized controlled trial among overweight/obese breast cancer survivors (N = 192) assigned to metformin, placebo, weight loss with metformin, or weight loss with placebo interventions for 6 months. Epigenetic age was correlated with chronological age (r = 0.20–0.86; P < 0.005). However, no significant epigenetic aging associations were observed by intervention arms. Consistent with published reports in non-cancer patients, 6 months of metformin therapy may be inadequate to observe expected epigenetic age deceleration. Longer duration studies are needed to better characterize these relationships.Trial Registration: Registry Name: ClincialTrials.Gov.Registration Number: NCT01302379.Date of Registration: February 2011.URL:https://clinicaltrials.gov/ct2/show/NCT01302379
Subcapsular hepatic hematoma as a complication of severe preeclampsia: a case report
Authors: Luhning Kiel , MacCormick Hilary , Macaulay Bruce , Saunders Marianna , Craig Catherine 
Published: December 2021

AbstractBackgroundSubcapsular hepatic hematoma is a rare and life-threatening complication of pregnancy. It is most commonly associated with severe preeclampsia and hemolytic anemia, elevated liver enzymes, and low platelets syndrome. Patients with subcapsular hepatic hematoma typically present with epigastric, right upper quadrant or shoulder pain, nausea and vomiting, and/or shortness of breath. Here we describe a patient with a classic pain presentation, a large unruptured hematoma, and an unusual postpartum course.CaseA 40-year-old gravida 1 para 0 Caucasian woman presented at 39 + 6 weeks gestational age with a 3-day history of new onset pain in an otherwise uncomplicated pregnancy. She described the pain along her right torso as severe, shooting, and sharp, but at times pleuritic in nature. She was found to have new onset preeclampsia and hemolytic anemia, elevated liver enzymes, and low platelets syndrome. Induction of labor was initiated and eventually she delivered by cesarean section. Her pain persisted in the postpartum period and abdominal computed tomography scan revealed a 16 cm subcapsular hepatic hematoma. Despite the hematoma being thin walled, conservative management was recommended by the general surgeon. She then re-presented on postpartum day 15 with tachypnea, dyspnea, and pleuritic chest pain. Secondary to the subcapsular hepatic hematoma, she then developed an infected and loculated, large pleural effusion. This required video-assisted thoracoscopic surgery before her eventual discharge home on postpartum day 21.ConclusionsThere should be high clinical suspicion of subcapsular hepatic hematoma in patients with persistent pain in the right upper quadrant of the abdomen. Urgent imaging to investigate for subcapsular hepatic hematoma is then indicated. Cesarean delivery without labor and treatment for severe preeclampsia should be undertaken if subcapsular hepatic hematoma is found. Conservative management and serial imaging are reasonable for the follow-up of a large, unruptured hematoma. Hepatic artery embolization should also be considered. Subcapsular hepatic hematoma may be complicated by infected pleural effusions and require video-assisted thoracoscopic surgery.
Response of soil biological properties and bacterial diversity to different levels of nitrogen application in sugarcane fields
Authors: Yang Shangdong , Xiao Jian , Liang Tian , He Weizhong , Tan Hongwei 
Published: December 2021

AbstractTo select an eco-friendly nitrogen (N) application level for sugarcane production, soil fertility and soil bacterial diversity under different nitrogen application levels were analyzed. Four levels of urea applications were high Nitrogen (H, 964 kg ha−1), medium Nitrogen (M, 482 kg ha−1), low Nitrogen (L, 96 kg ha−1) and no Nitrogen (CK, 0 kg ha−1) treatments, respectively. The results showed that the soil microbial biomass carbon and phosphorus were altered significantly by CK and L treatments. Moreover, the indexes of soil bacterial richness and diversity in the sugarcane field could be significantly improved by L. At the genus level, SC-I-84, Mycobacterium, Micropepsaceae, Saccharimonadales, Subgroup_2 and Acetobacteraceae were the unique dominant bacteria in the soil with the H treatment. JG30-KF-CM45 and Jatrophihabitans were the unique dominant genera in the M treatment. Subgroup_6, HSB_OF53-F07, Streptomyces, 67–14, SBR1031 and KD4-96 were the unique dominant genera in the L treatment. In contrast, FCPS473, Actinospica, 1921–2, Sinomonas, and Ktedonobacteraceae were the unique dominant genera in the CK treatment. The findings suggest that soil fertility all could be changed by different N application levels, but the most increasing integral effect only could be found in L. Moreover, even though soil bacterial richness could be significantly promoted by the M and H treatments, but soil bacterial diversity could not be significantly improved. On the contrary, soil bacterial diversity and richness all could be improved by L treatment. In addition, higher abundance of unique soil dominant bacteria could be only found in L treatment which compared to the CK, M and H treatments. These findings suggest that the rate of 96 kg ha−1 N application is ecofriendly for sugarcane production in Guangxi.
Small molecule targeting amyloid fibrils inhibits Streptococcus mutans biofilm formation
Authors: Chen Yuanyuan , Cui Guxin , Cui Yuqi , Chen Dongru , Lin Huancai 
Published: December 2021

AbstractAmyloid fibrils are important scaffold in bacterial biofilms. Streptococcus mutans is an established cariogenic bacteria dwelling within biofilms, and C123 segment of P1 protein is known to form amyloid fibrils in S. mutans biofilms, among which C3 segment could serve as a promising anti-amyloid target due to its critical role in C123-P1 interactions. Recently, small molecules have been found to successfully inhibit biofilms by targeting amyloid fibrils. Thus, our study aimed to screen small molecules targeting C3 segment with the capacity to influence amyloid fibrils and S. mutans biofilms. In silico screening was utilized to discover promising small molecules, which were evaluated for their effects on bacterial cells and amyloid fibrils. We selected 99 small molecules and enrolled 55 small molecules named D1–D55 for crystal violet staining. Notably, D25 selectively inhibit S. mutans biofilms but had no significant influence on biofilms formed by Streptococcus gordonii and Streptococcus sanguinis, and D25 showed no bactericidal effects and low cytotoxicity. In addition, amyloid fibrils in free-floating bacteria, biofilms and purified C123 were quantified with ThT assays, and the differences were not statistically significant in the presence or absence of D25. Morphological changes of amyloid fibrils were visualized with TEM images, where amorphous aggregates were obvious coupled with long and atypical amyloid fibrils. Moreover, amyloid-related genes were upregulated in response to D25. In conclusion, D25 is a promising antimicrobial agent with the capacity to influence amyloid fibrils and inhibit S. mutans biofilms.
Proportional assist ventilation relieves clinically significant dyspnea in critically ill ventilated patients
Authors: Bureau Côme , Decavèle Maxens , Campion Sébastien , Nierat Marie-Cécile , Mayaux Julien , Morawiec Elise , Raux Mathieu , Similowski Thomas , Demoule Alexandre 
Published: December 2021

Abstract
Introduction
Dyspnea is common and often severe symptom in mechanically ventilated patients. Proportional assist ventilation (PAV) is an assist ventilatory mode that adjusts the level of assistance to the activity of respiratory muscles. We hypothesized that PAV reduce dyspnea compared to pressure support ventilation (PSV).

Patients and methods
Mechanically ventilated patients with clinically significant dyspnea were included. Dyspnea intensity was assessed by the Dyspnea—Visual Analog Scale (D-VAS) and the Intensive Care-Respiratory Distress Observation Scale (IC-RDOS) at inclusion (PSV-Baseline), after personalization of ventilator settings in order to minimize dyspnea (PSV-Personalization), and after switch to PAV. Respiratory drive was assessed by record of electromyographic activity of inspiratory muscles, the proportion of asynchrony was analyzed.

Results
Thirty-four patients were included (73% males, median age of 66 [57–77] years). The D-VAS score was lower with PSV-Personalization (37 mm [20‒55]) and PAV (31 mm [14‒45]) than with PSV-Baseline (62 mm [28‒76]) (p < 0.05). The IC-RDOS score was lower with PAV (4.2 [2.4‒4.7]) and PSV-Personalization (4.4 [2.4‒4.9]) than with PSV-Baseline (4.8 [4.1‒6.5]) (p < 0.05). The electromyographic activity of parasternal intercostal muscles was lower with PAV and PSV-Personalization than with PSV-Baseline. The asynchrony index was lower with PAV (0% [0‒0.55]) than with PSV-Baseline and PSV-Personalization (0.68% [0‒2.28] and 0.60% [0.31‒1.41], respectively) (p < 0.05).

Conclusion
In mechanically ventilated patients exhibiting clinically significant dyspnea with PSV, personalization of PSV settings and PAV results in not different decreased dyspnea and activity of muscles to a similar degree, even though PAV was able to reduce asynchrony more effectively.