bluuebunny/crossref_metadata_2025_split huggingface dataset:
ERAP1 is a critical regulator of inflammasome-mediated proinflammatory and ER stress responses
Authors: Blake Maja K. , O’Connell Patrick , Pepelyayeva Yuliya , Godbehere Sarah , Aldhamen Yasser A. , Amalfitano Andrea 
Published: March 2022

Abstract
Background
In addition to its role in antigen presentation, recent reports establish a new role for endoplasmic reticulum aminopeptidase 1 (ERAP1) in innate immunity; however, the mechanisms underlying these functions are not fully defined. We previously confirmed that loss of ERAP1 functions resulted in exaggerated innate immune responses in a murine in vivo model. Here, we investigated the role of ERAP1 in suppressing inflammasome pathways and their dependence on ER stress responses.

Results
Using bone marrow-derived macrophages (BMDMs), we found that loss of ERAP1 in macrophages resulted in exaggerated production of IL-1β and IL-18 and augmented caspase-1 activity, relative to wild type macrophages. Moreover, an in vivo colitis model utilizing dextran sodium sulfate (DSS) confirmed increased levels of proinflammatory cytokines and chemokines in the colon of DSS treated ERAP1−/− mice as compared to identically stimulated WT mice. Interestingly, stimulated ERAP1−/− BMDMs and CD4+ T cells simultaneously demonstrated exaggerated ER stress, assessed by increased expression of ER stress-associated genes, a state that could be reverted to WT levels with use of the ER stress inhibitor Tauroursodeoxycholic acid (TUDCA).

Conclusions
Together, these results not only suggest that ERAP1 is important for regulating inflammasome dependent innate immune response pathways in vivo, but also propose a mechanism that underlies these changes, that may be associated with increased ER stress due to lack of normal ERAP1 functions.
The influences of perfluoroalkyl substances on the rheumatoid arthritis clinic
Authors: Zhao Yun , Jin Hangbiao , Qu Jianli , Zhang Sunzhao , Hu Shilei , Xue Jing , Zhao Meirong 
Published: March 2022

Abstract
Background
The effect of environmental factors on genetically susceptible individuals is a basic link in the pathogenesis of rheumatoid arthritis. Perfluoroalkyl substances (PFASs) are a class of synthetic organic fluorine chemicals, which have been mass-produced and widely used in the past 60 years, and also have been shown to be one of the major pollutants affecting human health. The impact of fluoride on the development of Rheumatoid Arthritis (RA) is unclear. This study explored the relationship between common fluoride and clinical manifestations of rheumatoid arthritis.

Results
A cohort of 155 patients with RA and 145 health controls in Second Affiliated Hospital of Zhejiang University School of Medicine were investigated. Serum concentrations of all fluoride detected were higher in RA patients than in healthy controls. There were 43 male patients and 112 female patients in the RA cohort. Some of perfluoroalkyl substances (perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorotrdecanoate (PFTrA), perfluorooctanesulfonate (PFOS)) were correlated negatively with the Body Mass Index (BMI); some of them (PFOA, PFNA, PFTrA, PFOS, 8:2 Chlorinated polyfluorinated ether sulfonate (8:2Cl-PFESA)) were correlated positively with the Disease Activity Score 28 (DAS28); two (PFOA, PFOS) of them were correlated positively with the white blood cell count, and one (Perfluoroundecanoate (PFUnA)) of them was correlated negatively with the hemoglobin; two (Perfluorodecanoate (PFDA), PFUnA) of them were correlated negatively with the presence of interstitial lung disease.

Conclusion
These data suggest that exposure to perfluoroalkyl substances may promote the disease activity of rheumatoid arthritis and the visceral lesions.
Theranostic nanoplatforms of emodin-chitosan with blue laser light on enhancing the anti-biofilm activity of photodynamic therapy against Streptococcus mutans biofilms on the enamel surface
Authors: Pourhajibagher Maryam , Keshavarz Valian Nasrin , Bahador Abbas 
Published: March 2022

Abstract
Background
Combining photosensitizer and light irradiation, named antimicrobial photodynamic therapy (aPDT) is an adjuvant therapy for eliminating microbial biofilms. This ex vivo study evaluates the effect of anti-biofilm activity of aPDT based on emodin-chitosan nanoparticles (Emo-CS-NPs) plus blue laser light against Streptococcus mutans biofilm on the enamel surface.

Materials
After determination of the fractional inhibitory concentration index of Emo and CS by checkerboard array assay, Emo-CS-NPs were synthesized and characterized. Following treatment of pre-formed S. mutans biofilms on the enamel slabs, cellular uptake of Emo-CS-NPs and intracellular reactive oxygen species (ROS) production were determined. The anti-biofilm and anti-metabolic activities of aPDT were investigated. Eventually, lactic acid production capacity, concentrations of S. mutans extracellular DNA (eDNA) levels, and expression of the gene involved in the biofilm formation (gtfB) were evaluated.

Results
The maximum uptake of Emo-CS-NPs occurs in an incubation time of 5 min. When irradiated, Emo-CS-NPs were photoactivated, generating ROS, and led to a decrease in the cell viability and metabolic activity of S. mutans significantly (P < 0.05). S. mutans eDNA and lactic acid production outcomes indicated that Emo-CS-NPs-mediated aPDT led to a significant reduction of eDNA levels (48%) and lactic acid production (72.4%) compared to the control group (P < 0.05). In addition, gtfB mRNA expression in S. mutans was downregulated (7.8-fold) after aPDT in comparison with the control group (P < 0.05).

Conclusions
Our data support that, aPDT using Emo-CS-NPs revealed the highest cellular uptake and ROS generation. Emo-CS-NPs based aPDT could inhibit significantly biofilm formation and reduce effectively virulence potency of S. mutans; thus, it could be an adjuvant therapy against dental caries.
Calmodulin binding proteins and neuroinflammation in multiple neurodegenerative diseases
Authors: O’Day Danton H. , Huber Robert J. 
Published: March 2022

AbstractCalcium dysregulation (“Calcium Hypothesis”) is an early and critical event in Alzheimer’s and other neurodegenerative diseases. Calcium binds to and regulates the small regulatory protein calmodulin that in turn binds to and regulates several hundred calmodulin binding proteins. Initial and continued research has shown that many calmodulin binding proteins mediate multiple events during the onset and progression of Alzheimer’s disease, thus establishing the “Calmodulin Hypothesis”. To gain insight into the general applicability of this hypothesis, the involvement of calmodulin in neuroinflammation in Alzheimer’s, amyotrophic lateral sclerosis, Huntington’s disease, Parkinson’s disease, frontotemporal dementia, and other dementias was explored. After a literature search for calmodulin binding, 11 different neuroinflammatory proteins (TREM2, CD33, PILRA, CR1, MS4A, CLU, ABCA7, EPHA1, ABCA1, CH3L1/YKL-40 and NLRP3) were scanned for calmodulin binding domains using the Calmodulin Target Database. This analysis revealed the presence of at least one binding domain within which visual scanning demonstrated the presence of valid binding motifs. Coupled with previous research that identified 13 other neuroinflammation linked proteins (BACE1, BIN1, CaMKII, PP2B, PMCA, NOS, NMDAR, AchR, Ado A2AR, Aβ, APOE, SNCA, TMEM175), this work shows that at least 24 critical proteins involved in neuroinflammation are putative or proven calmodulin binding proteins. Many of these proteins are linked to multiple neurodegenerative diseases indicating that calmodulin binding proteins lie at the heart of neuroinflammatory events associated with multiple neurodegenerative diseases. Since many calmodulin-based pharmaceuticals have been successfully used to treat Huntington’s and other neurodegenerative diseases, these findings argue for their immediate therapeutic implementation.
Nitrate/ammonium-responsive microRNA-mRNA regulatory networks affect root system architecture in Populus × canescens
Authors: Zhou Jing , Wu Jiang-Ting 
Published: March 2022

Abstract
Background
Nitrate (NO3−) and ammonium (NH4+) are the primary forms of inorganic nitrogen (N) taken up by plant roots, and a lack of these N sources commonly limits plant growth. To better understand how NO3− and NH4+ differentially affect root system architecture, we analyzed the expression profiles of microRNAs and their targets in poplar roots treated with three forms of nitrogen S1 (NO3−), S2 (NH4NO3, normal), and S3 (NH4+) via RNA sequencing.

Results
The results revealed a total of 709 miRNAs. Among them, 57 significantly differentially expressed miRNAs and 28 differentially expressed miRNA-target pairs showed correlated expression profiles in S1 vs. S2. Thirty-six significantly differentially expressed miRNAs and 12 differentially expressed miRNA-target pairs showed correlated expression profiles in S3 vs. S2. In particular, NFYA3, a target of upregulated ptc-miR169i and ptc-miR169b, was downregulated in S1 vs. S2, while NFYA1, a target of upregulated ptc-miR169b, was downregulated in S3 vs. S2 and probably played an important role in the changes in root morphology observed when the poplar plants were treated with different N forms. Furthermore, the miRNA-target pairs ptc-miR169i/b-D6PKL2, ptc-miR393a-5p-AFB2, ptc-miR6445a-NAC14, ptc-miR172d-AP2, csi-miR396a-5p_R + 1_1ss21GA-EBP1, ath-miR396b-5p_R + 1-TPR4, and ptc-miR166a/b/c-ATHB-8 probably contributed to the changes in root morphology observed when poplar plants were treated with different N forms.

Conclusions
These results demonstrate that differentially expressed miRNAs and their targets play an important role in the regulation of the poplar root system architecture by different N forms.
Effectiveness of indapamide/amlodipine single-pill combination in patients with isolated systolic hypertension: post-hoc analysis of the ARBALET study
Authors: Kobalava Zh. D. , Kolesnik Eteri L. , Shavarova E. K. , Goreva L. A. , Karapetyan L. V. 
Published: March 2022

Abstract
Background
This study evaluated the effectiveness of treatment with an indapamide/amlodipine single-pill combination (SPC) in outpatients with uncontrolled isolated systolic hypertension (ISH) aged over 55 years in real-life clinical practice.

Methods
This was a post-hoc analysis of the subgroup of patients with ISH from ARBALET, a 3-month, multicenter, observational, open-label study conducted in Russia among patients with grade I or II hypertension who were either uncontrolled on previous antihypertensive treatment or treatment-naïve. The effectiveness of indapamide/amlodipine SPC was assessed by the change in office systolic blood pressure (SBP) and the rate of target SBP (< 140 mmHg) achievement at 2 weeks, 1 month and 3 months, in four age groups: 55–59 years, 60–69 years, 70–79 years, and 80 years or older.

Results
The ARBALET study recruited 2217 patients, of whom 626 had ISH and were included in this post-hoc analysis (mean age 66.1 ± 7.8 years; 165 men [26.4%] and 461 women [73.6%]). Target SBP < 140 mmHg was achieved in 43%, 75% and 93% of patients at 2 weeks, 1 and 3 months, respectively. SBP decreased from baseline by 18.8 ± 10.5 mmHg, 27.2 ± 10.6 mmHg and 31.8 ± 9.9 mmHg at 2 weeks, 1 month and 3 months, respectively. In the groups of patients aged 55–59, 60–69, 70–79, and ≥ 80 years, SBP reductions at 3 months compared with baseline were − 30.3 ± 9.4, − 32.4 ± 9.7, − 32.5 ± 10.7, and − 28.9 ± 9.6 mmHg, respectively.

Conclusion
This post-hoc analysis of the observational ARBALET study showed that indapamide/amlodipine SPC was associated with significant reductions in BP and high rates of target BP achievement in a broad age range of patients with ISH treated in routine clinical practice.

Study registration number
ISRCTN40812831.
Post myocardial infarction left ventricular intramural dissecting hematoma: a case report describing a very rare complication
Authors: Gurjar Hitesh , Saad Muhammad , Ali Nisha , Regmi Sudiksha , Upreti Prakash , Karna Sumit , Balaram Sandhya K. , Kamalakkannan Gayathri , Vittorio Timothy J. 
Published: March 2022

Abstract
Background
Dissecting intramural hematoma is a rare complication of acute myocardial infarction (AMI) and has been associated with increased mortality. There has been paucity of literature to establish protocols and guidelines for management in such cases.

Case presentation
We hereby report the case of a 45-year-old male patient with left ventricular intramural dissecting hematoma (LV-IDH) who presented with chest pain and breathlessness and diagnosed as non-ST-elevation myocardial infarction (NSTEMI). Transthoracic echocardiography (TTE) was performed showing LV-IDH, confirmed with cardiac magnetic resonant imaging (cMRI). Selective coronary arteriography (CAG) was performed showing significant obstructive coronary artery disease (CAD). Further management with conservative approach involved discussion with patient, cardiothoracic surgeon and cardiology team including heart failure specialist and interventional cardiology.

Conclusions
This case describes a rare complication of AMI and also focuses on utility of TTE and cMRI in the diagnosis of this rare complication. Both diagnosis and management are challenging and have to be individualized in similar cases. Multidisciplinary care coordination is important in management of patients with this diagnosis.
Relationship between epicardial fat volume on cardiac CT and atherosclerosis severity in three-vessel coronary artery disease: a single-center cross-sectional study
Authors: Sun Yu , Li Xiao-gang , Xu Kai , Hou Jie , You Hong-rui , Zhang Rong-rong , Qi Miao , Zhang Li-bo , Xu Li-sheng , Greenwald Stephen E. , Yang Ben-qiang 
Published: March 2022

AbstractBackgroundThe ideal treatment strategy for stable three-vessel coronary artery disease (CAD) patients are difficult to determine and for patients undergoing conservative treatment, imaging evidence of coronary atherosclerotic severity progression remains limited. Epicardial fat volume (EFV) on coronary CT angiography (CCTA) has been considered to be associated with coronary atherosclerosis. Therefore, this study aims to evaluate the relationship between EFV level and coronary atherosclerosis severity in three-vessel CAD.MethodsThis retrospective study enrolled 252 consecutive patients with three-vessel CAD and 252 normal control group participants who underwent CCTA between January 2018 and December 2019. A semi-automatic method was developed for EFV quantification on CCTA images, standardized by body surface area. Coronary atherosclerosis severity was evaluated and scored by the number of coronary arteries with ≥ 50% stenosis on coronary angiography. Patients were subdivided into groups on the basis of lesion severity: mild (score = 3 vessels, n = 85), moderate (3.5 vessels ≤ score < 4 vessels, n = 82), and severe (4 vessels ≤ score ≤ 7 vessels, n = 85). The independent samplet-test, analysis of variance, and logistic regression analysis were used to evaluate the associations between EFV level and severity of coronary atherosclerosis.ResultsCompared with normal controls, three-vessel CAD patients had significantly higher EFV level (65 ± 22 mL/m2vs. 48 ± 19 mL/m2;P < 0.001). In patients with three-vessel CAD, there was a progressive decline in EFV level as the score of coronary atherosclerosis severity increased, especially in those patients with a body mass index (BMI) ≥ 25 kg/m2(75 ± 21 mL/m2vs. 72 ± 22 mL/m2vs. 62 ± 17 mL/m2;P < 0.05). Multivariable regression analysis showed that both BMI (OR3.40, 95% CI 2.00–5.78,P < 0.001) and the score of coronary atherosclerosis severity (OR0.49, 95% CI 0.26–0.93,P < 0.05) were independently related to the change of EFV level.ConclusionThree-vessel CAD patients do have higher EFV level than the normal controls. While, there may be an inverse relationship between EFV level and the severity of coronary atherosclerosis in patients with three-vessel CAD.
Using HEART2 score to risk stratify chest pain patients in the Emergency Department: an observational study
Authors: Schrader Chet D. , Kumar Darren , Zhou Yuan , Meyering Stefan , Saltarelli Nicholas , Alanis Naomi , Iloma Chukwuagozie , Smiley Rebecca , Wang Hao 
Published: March 2022

Abstract
Background
A significant number of chest pain patients had previous cardiac imaging tests (CIT) performed before being presented to the Emergency Department (ED). The HEART (history, electrocardiogram, age, risk factors, and troponin) score has been used to risk-stratify chest pain patients in the ED, but not particularly for patients with CIT performed. We aim to modify the current HEART score with the addition of most recent CIT findings (referred to as HEART2 score), to predict a 30-day major adverse cardiac event (MACE) among ED chest pain patients, compare the performance accuracy of using HEART versus HEART2 score for 30-day MACE outcome predictions, and further determine the value of HEART2 in a subset group of ED chest pain patients (i.e., ones with previous CIT).

Methods
This is a single-center observational study. We included chest pain patients with HEART scores calculated during their index ED visits. A modified HEART2 score was developed with the addition of CIT findings as one of the HEART2 components. Patients were divided into three groups, including low (≤ 3), moderate (4–6), and high-risk HEART/HEART2 scores (≥ 7). MACE occurrence of a patient with different risks of HEART and HEART2 scores and overall performance accuracy of HEART versus HEART2 score predicting MACE outcomes were compared.

Results
We included a total of 9419 chest pain patients at ED, among which one out of five patients (1874/9419) had previous CIT performed. Fewer (38.2%) of such patients had low-risk HEART scores in comparison to 55.5% of low-risk HEART2 scores (p < 0.001). The MACE outcomes were similar in low-risk HEART patients compared with low-risk HEART2 patients (2.2% versus 3.1%, p = 0.3021). The overall performance accuracy of using the HEART2 score to stratify chest pain patients with previous CIT was better than using the HEART score’s (AUC 0.74 versus 0.71, p = 0.0082).

Conclusions
Using the HEART2 score might be suitable to stratify low-to-moderate risk chest pain patients at ED with a similar 30-days MACE occurrence compared to the HEART score. More importantly, with the use of similar low-risk criteria (HEART2 ≤ 3), over 45% more chest pain patients with previous CIT performed could be discharged directly from ED.
D-dimer as a predictor of cardiovascular outcomes in patients with diabetes mellitus
Authors: Cheng Lan , Fu Qianyu , Zhou Longhua , Fan Yuqin , Liu Fenfen , Fan Yuanyuan , Zhang Xin , Lin Weiqing , Wu Xiaohe 
Published: March 2022

Abstract
Objective
This study aimed to investigate the association between D-dimer and cardiovascular diseases outcomes in patients with type 2 diabetes.

Methods
This is a single-center retrospective cohort study which was performed in a population who had health examinations between 2010 and 2015 in Jiangxi Provincial People's Hospital. All adult patients who were diagnosed with type 2 diabetes were screened. The cardiovascular diseases events were defined as all-cause mortality, new cardiovascular diseases incidence (acute myocardial infarction, unstable angina, stroke), or cardiovascular mortality.

Results
The median age was 59.6 years; 50.1% of participants were women; D-dimer was significantly associated with endpoint events. After multivariable adjustment for form of treatments and traditional risk factors, the odds ratio was 3.62 (95% CI 2.07–6.03) for the highest quartile of D-dimer with the lowest quartile as reference. Meanwhile, higher D-dimer levels were associated with a significant and independent higher risk of cause-specific cardiovascular disease events.

Conclusion
High plasma concentrations of D-dimer were associated with increased risk of cardiovascular diseases events in patients with type 2 diabetes, even after adjusting for cardiovascular risk factors and form of treatments. Measurement of D-dimer may lead to a practical improvement in the current risk stratification criteria for patients with type 2 diabetes.
Impact of a personalised care plan for the elderly calling emergency medical services after a fall at home: The RISING-DOM multi-centre randomised controlled trial protocol
Authors: Bouzid Wafa , Tavassoli Neda , Berbon Caroline , Qassemi Soraya , Bounes Vincent , Azema Olivier , Shourick Jason , Nourhashémi Fati 
Published: March 2022

Abstract
Background
A growing number of emergency calls are made each year for elderly people who fall. Many of them are not taken to hospital or are rapidly discharged from the Emergency Department (ED). Evidence shows that, with no further support, this vulnerable population is particularly at risk of injuries, dependency and death. This study aims to determine the effectiveness of a comprehensive geriatric assessment and a tailored intervention in the elderly calling on an Emergency Medical Service (EMS) for a fall at home, but not conveyed to the ED or rapidly discharged from it (less than 24 h from hospitalisation), to the time to institutionalisation or death.

Methods
Rising-Dom is a two-arm randomised (ratio 1:1), interventional, multi-centre and open study. Community-dwelling elderly people (≥ 70 years) who call an EMS for a fall at home are recruited. The intervention group receives home visits by a nurse with a comprehensive fall risk assessment and a personalised intervention care plan with a planned follow-up (six nurse home visits and five nurse phone calls). Subjects enrolled in the usual care-control group continue to receive their routine care for the prevention or treatment of diseases. Primary (time to institutionalisation or death) and secondary (unscheduled hospitalisations, additional EMS calls relating to falls, functional decline and quality of life) outcome data will be collected for both groups through five phone calls made by Clinical Research Associates (CRA) blind to the participants’ group during the follow-up period (24-months). Twelve hospital centres in the South-West of France are participating in the study as study sites. The inclusion period started in October 2019 and will end in March 2022. By the end of this period, 1,190 subjects are expected to be enrolled.

Discussion
Studies on elderly home falls have rarely concerned people who were not taken to hospital. The Rising-Dom intervention scheme should enhance understanding of features related to this vulnerable population and investigate the impact of a nurse care at home on delaying death and institutionalisation.

Trial registration
Clinicaltrials.gov identifier: NCT04132544. Registration date: 18/10/2019. Sponsor: University Hospital, Toulouse. https://www.clinicaltrials.gov/ct2/show/NCT04132544?term=rising-dom&draw=2&rank=1