bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical characteristics and risk factors predictive of pulmonary embolism complicated in bronchiectasis patients: a retrospective study
Authors: Deng Tiantian , Xu Ke , Wu Beishou , Sheng Fei , Li Xu , Zhu Zhuxian , Zhang Ziqiang 
Published: June 2022

Abstract
Objective
Pulmonary embolism (PE) is a rare complication in bronchiectasis (BE) patients associated with a high rate of mortality and morbidity. However, data regarding bronchiectasis patients complicated with PE are limited. Early diagnosis of PE in bronchiectasis patients can improve the prognosis, this study aimed to investigate the clinical features and potential risk factors for early diagnosis of PE in bronchiectasis patients.

Methods
Data of Patients were collected from Tongji Hospital of Tongji University of China. Bronchiectasis patients complicated with pulmonary embolism were named as BE/PE group (n = 63), as well as contemporaneous aged- and sex-matched bronchiectasis patients without pulmonary embolism named as BE group (n = 189), at a ratio of 1:3(cases to controls). Clinical parameters and risk factors were analyzed.

Results
Univariate analysis shows that long-term bed rest, chronic lung disease, autoimmune disease, peripheral artery disease (PAD), tuberculosis history, dyspnea, blood homocysteine, CD4/CD8 ratio, or SIQIIITIII syndrome were closely correlated with the incidence of PE in the bronchiectasis patients (p < 0.05). Multivariate logistic regression analysis of significant variables showed that CD4/CD8 ratio (OR 1.409, 95% CI 1.045–1.901) and autoimmune disease (OR 0.264, 95% CI 0.133–0.524) are independent risk factors for BE/PE patients, compared with the BE patients. 53 out of 189 (28.0%) BE patients had hemoptysis, and 15 out of 63 (23.8%) BE/PE patients had hemoptysis (p > 0.05).

Conclusions
The coexistence of pulmonary embolism and bronchiectasis are rarely encountered and easily to be ignored. Early identification of the clinical characteristic and potential risk factors of pulmonary embolism in bronchiectasis patients may help optimize the treatment strategies.
Retention of bar clip attachment for mandibular implant overdenture
Authors: Nassar Hossam I. , Abdelaziz Medhat Sameh 
Published: June 2022

Abstract
Objectives
The aim of the present study was to evaluate the retention and loss of retention after fatigue testing at different time intervals between two types of bar clip materials (digitally designed PEEK bar clip and regular Nylon bar clip).

Materials and methods
An epoxy model was constructed for a completely edentulous mandible. Two implants were placed according to prosthetically driven implant placement by a computer-guided surgical stent. Bar clips were digitally designed, 3D printed, and pressed into Poly Ether Ether Ketone (PEEK). Pick up of PEEK and nylon clips was performed on the dentures fitting surface using self-cured acrylic resin. Each study group was subjected to an insertion and removal fatigue test simulating 3 years of patient usage. Retention values were recorded using the universal testing machine at initial retention and after 1, 2, and 3 years of simulated usage. For proper sample sizing, 24 models and dentures (12 for each group) were used. An independent sample t-test and repeated measures analysis of variance were used to compare the data.

Results
There were statistically significant differences in retention between the PEEK and nylon bar clips at the beginning of the experiment (p = 0.000*). But after 3 years of simulated use, there was no significant difference in retention between the test groups (p = 0.055, NS). After 3 years of simulated use, the retention of PEEK clips decreased by − 58.66% recording 17.37 ± 1.07 N, while the retention of nylon clip increased by + 2.99% recording 16.56 ± 0.88 N.

Conclusion
The digitally designed PEEK clip showed comparable retention results to the nylon clip after 3 years of simulated use.

Clinical relevance
Maintenance of bar attachment with PEEK clip offers a clinical solution after the wear of normal plastic clips, which is a cheap solution that is easily fabricated and picked up into the denture. Digital fabricated PEEK bar retentive inserts can be used in cases of bar attachment wear.
Nitrogen fixation by diverse diazotrophic communities can support population growth of arboreal ants
Authors: Nepel Maximilian , Pfeifer Josephine , Oberhauser Felix B. , Richter Andreas , Woebken Dagmar , Mayer Veronika E. 
Published: June 2022

Abstract
Background
Symbiotic ant-plant associations, in which ants live on plants, feed on plant-provided food, and protect host trees against threats, are ubiquitous across the tropics, with the Azteca-Cecropia associations being amongst the most widespread interactions in the Neotropics. Upon colonization of Cecropia’s hollow internodes, Azteca queens form small patches with plant parenchyma, which are then used as waste piles when the colony grows. Patches—found in many ant-plant mutualisms—are present throughout the colony life cycle and may supplement larval food. Despite their initial nitrogen (N)-poor substrate, patches in Cecropia accommodate fungi, nematodes, and bacteria. In this study, we investigated the atmospheric N2 fixation as an N source in patches of early and established ant colonies.

Results
Via 15N2 tracer assays, N2 fixation was frequently detected in all investigated patch types formed by three Azteca ant species. Quantified fixation rates were similar in early and established ant colonies and higher than in various tropical habitats. Based on amplicon sequencing, the identified microbial functional guild—the diazotrophs—harboring and transcribing the dinitrogenase reductase (nifH) gene was highly diverse and heterogeneous across Azteca colonies. The community composition differed between early and established ant colonies and partly between the ant species.

Conclusions
Our data show that N2 fixation can result in reasonable amounts of N in ant colonies, which might not only enable bacterial, fungal, and nematode growth in the patch ecosystems but according to our calculations can even support the growth of ant populations. The diverse and heterogeneous diazotrophic community implies a functional redundancy, which could provide the ant-plant-patch system with a higher resilience towards changing environmental conditions. Hence, we propose that N2 fixation represents a previously unknown potential to overcome N limitations in arboreal ant colonies.
Induction of high affinity monoclonal antibodies against SARS-CoV-2 variant infection using a DNA prime-protein boost strategy
Authors: Chiang Chen-Yi , Chen Mei-Yu , Hsu Chia-Wei , Liu Chia-Yeh , Tsai Yu-Wen , Liao Hung-Chun , Yan Jia-Ying , Chuang Zih-Shiuan , Wang Hsin-I. , Pan Chien-Hsiung , Yu Chia-Yi , Yu Guann-Yi , Liao Ching-Len , Liu Shih-Jen , Chen Hsin-Wei 
Published: June 2022

Abstract
Background
Calls for the coronavirus to be treated as an endemic illness, such as the flu, are increasing. After achieving high coverage of COVID-19 vaccination, therapeutic drugs have become important for future SARS-CoV-2 variant outbreaks. Although many monoclonal antibodies have been approved for emergency use as treatments for SARS-CoV-2 infection, some monoclonal antibodies are not authorized for variant treatment. Broad-spectrum monoclonal antibodies are unmet medical needs.

Methods
We used a DNA prime-protein boost approach to generate high-quality monoclonal antibodies. A standard ELISA was employed for the primary screen, and spike protein-human angiotensin-converting enzyme 2 blocking assays were used for the secondary screen. The top 5 blocking clones were selected for further characterization, including binding ability, neutralization potency, and epitope mapping. The therapeutic effects of the best monoclonal antibody against SARS-CoV-2 infection were evaluated in a hamster infection model.

Results
Several monoclonal antibodies were selected that neutralize different SARS-CoV-2 variants of concern (VOCs). These VOCs include Alpha, Beta, Gamma, Delta, Kappa and Lambda variants. The high neutralizing antibody titers against the Beta variant would be important to treat Beta-like variants. Among these monoclonal antibodies, mAb-S5 displays the best potency in terms of binding affinity and neutralizing capacity. Importantly, mAb-S5 protects animals from SARS-CoV-2 challenge, including the Wuhan strain, D614G, Alpha and Delta variants, although mAb-S5 exhibits decreased neutralization potency against the Delta variant. Furthermore, the identified neutralizing epitopes of monoclonal antibodies are all located in the receptor-binding domain (RBD) of the spike protein but in different regions.

Conclusions
Our approach generates high-potency monoclonal antibodies against a broad spectrum of VOCs. Multiple monoclonal antibody combinations may be the best strategy to treat future SARS-CoV-2 variant outbreaks.
Associations of the vasoactive peptides CT-proET-1 and MR-proADM with incident type 2 diabetes: results from the BiomarCaRE Consortium
Authors: Sujana Chaterina , Salomaa Veikko , Kee Frank , Seissler Jochen , Jousilahti Pekka , Neville Charlotte , Then Cornelia , Koenig Wolfgang , Kuulasmaa Kari , Reinikainen Jaakko , Blankenberg Stefan , Zeller Tanja , Herder Christian , Mansmann Ulrich , Peters Annette , Thorand Barbara ,   for the BiomarCaRE Consortium
Published: June 2022

Abstract
Background
Endothelin-1 (ET-1) and adrenomedullin (ADM) are commonly known as vasoactive peptides that regulate vascular homeostasis. Less recognised is the fact that both peptides could affect glucose metabolism. Here, we investigated whether ET-1 and ADM, measured as C-terminal-proET-1 (CT-proET-1) and mid-regional-proADM (MR-proADM), respectively, were associated with incident type 2 diabetes.

Methods
Based on the population-based Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium data, we performed a prospective cohort study to examine associations of CT-proET-1 and MR-proADM with incident type 2 diabetes in 12,006 participants. During a median follow-up time of 13.8 years, 862 participants developed type 2 diabetes. The associations were examined in Cox proportional hazard models. Additionally, we performed two-sample Mendelian randomisation analyses using published data.

Results
CT-proET-1 and MR-proADM were positively associated with incident type 2 diabetes. The multivariable hazard ratios (HRs) [95% confidence intervals (CI)] were 1.10 [1.03; 1.18], P = 0.008 per 1-SD increase of CT-proET-1 and 1.11 [1.02; 1.21], P = 0.016 per 1-SD increase of log MR-proADM, respectively. We observed a stronger association of MR-proADM with incident type 2 diabetes in obese than in non-obese individuals (P-interaction with BMI < 0.001). The HRs [95%CIs] were 1.19 [1.05; 1.34], P = 0.005 and 1.02 [0.90; 1.15], P = 0.741 in obese and non-obese individuals, respectively. Our Mendelian randomisation analyses yielded a significant association of CT-proET-1, but not of MR-proADM with type 2 diabetes risk.

Conclusions
Higher concentrations of CT-proET-1 and MR-proADM are associated with incident type 2 diabetes, but our Mendelian randomisation analysis suggests a probable causal link for CT-proET-1 only. The association of MR-proADM seems to be modified by body composition.
Elevated plasma triglyceride concentration and risk of adverse clinical outcomes in 1.5 million people: a CALIBER linked electronic health record study
Authors: Patel Riyaz S. , Pasea Laura , Soran Handrean , Downie Paul , Jones Richard , Hingorani Aroon D. , Neely Dermot , Denaxas Spiros , Hemingway Harry 
Published: June 2022

Abstract
Background
Assessing the spectrum of disease risk associated with hypertriglyceridemia is needed to inform potential benefits from emerging triglyceride lowering treatments. We sought to examine the associations between a full range of plasma triglyceride concentration with five clinical outcomes.

Methods
We used linked data from primary and secondary care for 15 M people, to explore the association between triglyceride concentration and risk of acute pancreatitis, chronic pancreatitis, new onset diabetes, myocardial infarction and all-cause mortality, over a median of 6–7 years follow up.

Results
Triglyceride concentration was available for 1,530,411 individuals (mean age 56·6 ± 15·6 years, 51·4% female), with a median of 1·3 mmol/L (IQR: 0.9.to 1.9). Severe hypertriglyceridemia, defined as > 10 mmol/L, was identified in 3289 (0·21%) individuals including 620 with > 20 mmol/L. In multivariable analyses, a triglyceride concentration > 20 mmol/L was associated with very high risk for acute pancreatitis (Hazard ratio (HR) 13·55 (95% CI 9·15–20·06)); chronic pancreatitis (HR 25·19 (14·91–42·55)); and high risk for diabetes (HR 5·28 (4·51–6·18)) and all-cause mortality (HR 3·62 (2·82–4·65)) when compared to the reference category of ≤ 1·7 mmol/L. An association with myocardial infarction, however, was only observed for more moderate hypertriglyceridaemia between 1.7 and 10 mmol/L. We found a risk interaction with age, with higher risks for all outcomes including mortality among those ≤ 40 years compared to > 40 years.

Conclusions
We highlight an exponential association between severe hypertriglyceridaemia and risk of incident acute and chronic pancreatitis, new diabetes, and mortality, especially at younger ages, but not for myocardial infarction for which only moderate hypertriglyceridemia conferred risk.
Atrioventricular coupling and left atrial abnormality in type 2 diabetes mellitus with functional mitral regurgitation patients verified by cardiac magnetic resonance imaging
Authors: Zhang Yi , Li Xue-Ming , Shen Meng-Ting , Huang Shan , Li Yuan , Yang Zhi-Gang 
Published: June 2022

Abstract
Background
Functional mitral regurgitation (FMR) in type 2 diabetes mellitus (T2DM) patients induced by left ventricular (LV) enlargement and mitral valve abnormality may aggravated the impairment in left atrial (LA) compliance. Thus, this study aimed to depict how FMR and LV dysfunction affect LA compliance in T2DM patients with FMR.

Materials and methods
A total of 148 patients with T2DM and 49 age- and sex-matched normal controls underwent cardiac magnetic resonance examination. LA longitudinal strain and LA and LV functional indices were compared among controls and different T2DM patients. The multivariate analysis was used to identify the independent indicators of LA longitudinal strain.

Results
T2DM Patients without FMR had a lower total LA empty fraction (LAEF) compared with the controls (all P < 0.05). T2DM patients with mild and moderate FMR showed increased LA volume (LAV) and LV volume while decreased LAEF, LA strain, and LV ejection fraction (P < 0.05). T2DM patients with severe FMR showed markedly increased LAV and LV volume while decreased LAEF, LA strain, and LVEF (P < 0.05). In T2DM patients with FMR, reservoir strain (εs) was independently correlated with LV end-diastolic volume (LVEDV) (β = − 0.334) and regurgitation degree (β = − 0.256). The passive strain (εe) was independently correlated with regurgitation degree (β = − 0.297), whereas the active strain (εa) was independently correlated with LVESV (β = − 0.352) and glycated haemoglobin (β = − 0.279).

Conclusion
FMR may aggravate LA and LV dysfunction in T2DM patients. Regurgitation degree was an independent determinant of the εs and the εe, LVEDV was an independent determinant of the εs, and LVESV was an independent determinant of the εa in T2DM patients with FMR.
Arterial stiffness in patients with type 1 diabetes and its comparison to cardiovascular risk evaluation tools
Authors: Helleputte Simon , Van Bortel Luc , Verbeke Francis , Op ‘t Roodt Jos , Calders Patrick , Lapauw Bruno , De Backer Tine 
Published: June 2022

AbstractBackgroundArterial stiffness is a potential biomarker for cardiovascular disease (CVD) risk in patients with type 1 diabetes (T1D). However, its relation with other CV risk evaluation tools in T1D has not been elucidated yet. This study aimed to evaluate arterial stiffness in T1D patients free from known CVD, and compare it to other CV risk evaluation tools used in T1D.MethodsCross-sectional study in adults with a T1D duration of at least 10 years and without established CVD. Patients were categorized in CVD risk groups based on2019 European Society of Cardiology (ESC) guidelines, and the STENO T1D risk engine was used to estimate 10-year risk for CV events. Arterial stiffness was evaluated with carotid-femoral pulse wave velocity (cf-PWV). Coronary artery calcium (CAC) score was assessed and carotid ultrasound was performed. Ambulatory 24-h blood pressure and central hemodynamic parameters were evaluated. Data on renal function and diabetic kidney disease was retrieved.Results54 patients (age: 46 ± 9.5 years; T1D duration: 27 ± 8.8 years) were included. One-fourth of patients showed prematurely increased aortic stiffness based on cf-PWV (24%). Cf-PWV was significantly associated with CAC score, carotid intima-media thickness, central hemodynamic parameters and diabetic kidney disease. Based on STENO, 20 patients (37%) were at low, 20 patients (37%) at moderate, and 14 patients (26%) at high 10-year risk for CV event. Cf-PWV was strongly associated with the STENO score (rs = + 0.81; R2 = 0.566, p < 0.001), increasing with each higher STENO group (p < 0.01). However, cf-PWV was not significantly different between the two CV risk groups (high versus very high) based on ESC criteria, and ESC criteria compared to STENO classified 10 patients more as having > 10% 10-year risk for CV events (n = 44/54; 81.5% versus n = 34/54; 63%).ConclusionsThis study demonstrated that a substantial proportion of long-standing T1D patients free from known CVD show premature arterial stiffening. Cf-PWV strongly associates with the STENO risk score for future CV events and with cardiovascular imaging and function outcomes, thereby illustrating the clinical importance of arterial stiffness. The data, however, also show considerable heterogeneity in CV risk and differences in risk categorisation between the STENO tool and ESC criteria.There is a need for refinement of CV risk classification in T1D, and future studies should investigate if evaluation of arterial stiffness should be implemented in T1D clinical practice and which patients benefit the most from its assessment.
CBX2 shapes chromatin accessibility promoting AML via p38 MAPK signaling pathway
Authors: Del Gaudio Nunzio , Di Costanzo Antonella , Liu Ning Qing , Conte Lidio , Dell’Aversana Carmela , Bove Guglielmo , Benedetti Rosaria , Montella Liliana , Ciardiello Fortunato , Carafa Vincenzo , Ambrosino Concetta , Tucci Valeria , Conte Mariarosaria , Martens Joost H. A. , Stunnenberg Hendrik G. , Nebbioso Angela , Altucci Lucia 
Published: June 2022

Abstract
Background
The dynamic epigenome and proteins specialized in the interpretation of epigenetic marks critically contribute to leukemic pathogenesis but also offer alternative therapeutic avenues. Targeting newly discovered chromatin readers involved in leukemogenesis may thus provide new anticancer strategies. Accumulating evidence suggests that the PRC1 complex member CBX2 is overexpressed in solid tumors and promotes cancer cell survival. However, its role in leukemia is still unclear.

Methods
We exploited reverse genetic approaches to investigate the role of CBX2 in human leukemic cell lines and ex vivo samples. We also analyzed phenotypic effects following CBX2 silencing using cellular and molecular assays and related functional mechanisms by ATAC-seq and RNA-seq. We then performed bioinformatic analysis of ChIP-seq data to explore the influence of histone modifications in CBX2-mediated open chromatin sites. Lastly, we used molecular assays to determine the contribution of CBX2-regulated pathways to leukemic phenotype.

Results
We found CBX2 overexpressed in leukemia both in vitro and ex vivo samples compared to CD34+ cells. Decreased CBX2 RNA levels prompted a robust reduction in cell proliferation and induction of apoptosis. Similarly, sensitivity to CBX2 silencing was observed in primary acute myeloid leukemia samples. CBX2 suppression increased genome-wide chromatin accessibility followed by alteration of leukemic cell transcriptional programs, resulting in enrichment of cell death pathways and downregulation of survival genes. Intriguingly, CBX2 silencing induced epigenetic reprogramming at p38 MAPK-associated regulatory sites with consequent deregulation of gene expression.

Conclusions
Our results identify CBX2 as a crucial player in leukemia progression and highlight a potential druggable CBX2-p38 MAPK network in AML.
Multiple roles for Bcl-3 in mammary gland branching, stromal collagen invasion, involution and tumor pathology
Authors: Carr David , Zein Aiman , Coulombe Josée , Jiang Tianqi , Cabrita Miguel A. , Ward Gwendoline , Daneshmand Manijeh , Sau Andrea , Pratt M. A. Christine 
Published: June 2022

Abstract
Background
The Bcl-3 protein is an atypical member of the inhibitor of -κB family that has dual roles as a transcriptional repressor and a coactivator for dimers of NF-κB p50 and p52. Bcl-3 is expressed in mammary adenocarcinomas and can promote tumorigenesis and survival signaling and has a key role in tumor metastasis. In this study, we have investigated the role of Bcl-3 in the normal mammary gland and impact on tumor pathology.

Methods
We utilized bcl-3−/− mice to study mammary gland structure in virgins and during gestation, lactation and early involution. Expression of involution-associated genes and proteins and putative Bcl-3 target genes was examined by qRT-PCR and immunoblot analysis. Cell autonomous branching morphogenesis and collagen I invasion properties of bcl-3−/− organoids were tested in 3D hydrogel cultures. The role of Bcl-3 in tumorigenesis and tumor pathology was also assessed using a stochastic carcinogen-induced mammary tumor model.

Results
Bcl-3−/− mammary glands demonstrated reduced branching complexity in virgin and pregnant mice. This defect was recapitulated in vitro where significant defects in bud formation were observed in bcl-3−/− mammary organoid cultures. Bcl-3−/− organoids showed a striking defect in protrusive collective fibrillary collagen I invasion associated with reduced expression of Fzd1 and Twist2. Virgin and pregnant bcl-3−/− glands showed increased apoptosis and rapid increases in lysosomal cell death and apoptosis after forced weaning compared to WT mice. Bcl-2 and Id3 are strongly induced in WT but not bcl-3−/− glands in early involution. Tumors in WT mice were predominately adenocarcinomas with NF-κB activation, while bcl-3−/− lesions were largely squamous lacking NF-κB and with low Bcl-2 expression.

Conclusions
Collectively, our results demonstrate that Bcl-3 has a key function in mammary gland branching morphogenesis, in part by regulation of genes involved in extracellular matrix invasion. Markedly reduced levels of pro-survival proteins expression in bcl-3 null compared to WT glands 24 h post-weaning indicate that Bcl-3 has a role in moderating the rate of early phase involution. Lastly, a reduced incidence of bcl-3−/− mammary adenocarcinomas versus squamous lesions indicates that Bcl-3 supports the progression of epithelial but not metaplastic cancers.