bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aging and Hypercholesterolemia Differentially Affect the Unfolded Protein Response in the Vasculature of
ApoE
−/−
Mice
Authors: Zhou Yuxiang , Wan Xueping , Seidel Kerstin , Zhang Mo , Goodman Jena B. , Seta Francesca , Hamburg Naomi , Han Jingyan 
Published: September 2021

Background
Persistent activation of endoplasmic reticulum stress and the unfolded protein response (UPR) induces vascular cell apoptosis, contributing to atherogenesis. Aging and hypercholesterolemia are 2 independent proatherogenic factors. How they affect vascular UPR signaling remains unclear.

Methods and Results

Transcriptome analysis of aortic tissues from high fat diet–fed and aged
ApoE
−/−
mice revealed 50 overlapping genes enriched for endoplasmic reticulum stress‐ and UPR‐related pathways. Aortae from control, Western diet (WD)–fed, and aged
ApoE
−/−
mice were assayed for (1) 3 branches of UPR signaling (pancreatic ER eIF2‐alpha kinase /alpha subunit of the eukaryotic translation initiation factor 1/activating transcription factor 4, inositol‐requiring enzyme 1 alpha/XBP1s, activating transcription factor 6); (2) UPR‐mediated protective adaptation (upregulation of immunoglobulin heavy chain‐binding protein and protein disulfide isomerase); and (3) UPR‐mediated apoptosis (induction of C/EBP homologous transcription factor, p‐JNK, and cleaved caspase‐3). Aortic UPR signaling was differentially regulated in the aged and WD‐fed groups. Consumption of WD activated all 3 UPR branches; in the aged aorta, only the ATF6α arm was activated, but it was 10 times higher than that in the WD group. BiP and protein disulfide isomerase protein levels were significantly decreased only in the aged aorta despite a 5‐fold increase in their mRNA levels. Importantly, the aortae of aged mice exhibited a substantially enhanced proapoptotic UPR compared with that of WD‐fed mice. In lung tissues, UPR activation and the resultant adaptive/apoptotic responses were not significantly different between the 2 groups.

Conclusions
Using a mouse model of atherosclerosis, this study provides the first in vivo evidence that aging and an atherogenic diet activate differential aortic UPR pathways, leading to distinct vascular responses. Compared with dietary intervention, aging is associated with impaired endoplasmic reticulum protein folding and increased aortic apoptosis.
Long‐Term Mortality Associated With Use of Carvedilol Versus Metoprolol in Heart Failure Patients With and Without Type 2 Diabetes: A Danish Nationwide Cohort Study
Authors: Schwartz Brian , Pierce Colin , Madelaire Christian , Schou Morten , Kristensen Søren Lund , Gislason Gunnar H. , Køber Lars , Torp‐Pedersen Christian , Andersson Charlotte 
Published: September 2021

Background
Carvedilol may have favorable glycemic properties compared with metoprolol, but it is unknown if carvedilol has mortality benefit over metoprolol in patients with type 2 diabetes (T2D) and heart failure with reduced ejection fraction (HFrEF).

Methods and Results

Using Danish nationwide databases between 2010 and 2018, we followed patients with new‐onset HFrEF treated with either carvedilol or metoprolol for all‐cause mortality until the end of 2018. Follow‐up started 120 days after initial HFrEF diagnosis to allow initiation of guideline‐directed medical therapy. There were 39 260 patients on carvedilol or metoprolol at baseline (mean age 70.8 years, 35% women), of which 9355 (24%) had T2D. Carvedilol was used in 2989 (32%) patients with T2D and 10 411 (35%) of patients without T2D. Users of carvedilol had a lower prevalence of atrial fibrillation (20% versus 35%), but other characteristics appeared well‐balanced between the groups. Totally 11 306 (29%) were deceased by the end of follow‐up. We observed no mortality differences between carvedilol and metoprolol, multivariable‐adjusted hazard ratio (HR) 0.97 (0.90–1.05) in patients with T2D versus 1.00 (0.95–1.05) for those without T2D,
P
for difference =0.99. Rates of new‐onset T2D were lower in users of carvedilol versus metoprolol; age, sex, and calendar year adjusted HR 0.83 (0.75–0.91),
P
<0.0001.

Conclusions
In a contemporary clinical cohort of HFrEF patients with and without T2D, carvedilol was not associated with a reduction in long‐term mortality compared with metoprolol. However, carvedilol was associated with lowered risk of new‐onset T2D supporting the assertion that carvedilol has a more favorable metabolic profile than metoprolol.
Regeneration of vascular tissue through redifferentiation of interxylary phloem after complete girdling in Aquilaria sinensis
Authors: Luo Bei , Yoshinaga Arata , Awano Tatsuya , Takabe Keiji , Itoh Takao 
Published: September 2021

Abstract
We studied the time-course of stem response for six months following complete girdling in branches of Aquilaria sinensis to determine the potential role of interxylary phloem (IP) in this response. It was found that the vascular cambium, as well as its derivative secondary xylem and phloem, regenerated fully through redifferentiation of IP. We confirmed that vascular cambium regenerated within one month after girdling based on observation of new vessels, IP, and secondary phloem fibers. The time-course study showed that IPs made connections with each other, merged, and became larger through the proliferation of IPs parenchyma cells and the cleaving of secondary xylem in a narrow zone 400 to 1000 μm deep inside the girdled edge. This led to the formation of a complete circular sheath of vascular cambium, followed by the regeneration of vascular tissue. It is worth noting that the secondary xylem is regenerated always following the formation of a thick belt of wound xylem.
Impact of Wave–Vortical Interactions on Oceanic Submesoscale Lateral Dispersion
Authors: Hernández-Dueñas Gerardo , Lelong M.-Pascale , Smith Leslie M. 
Published: September 2021

AbstractSubmesoscale lateral transport of Lagrangian particles in pycnocline conditions is investigated by means of idealized numerical simulations with reduced-interaction models. Using a projection technique, the models are formulated in terms of wave-mode and vortical-mode nonlinear interactions, and they range in complexity from full Boussinesq to waves-only and vortical-modes-only (QG) models. We find that, on these scales, most of the dispersion is done by vortical motions, but waves cannot be discounted because they play an important, albeit indirect, role. In particular, we show that waves are instrumental in filling out the spectra of vortical-mode energy at smaller scales through nonresonant vortex–wave–wave triad interactions. We demonstrate that a richer spectrum of vortical modes in the presence of waves enhances the effective lateral diffusivity, relative to QG. Waves also transfer energy upscale to vertically sheared horizontal flows that are a key ingredient for internal-wave shear dispersion. In the waves-only model, the dispersion rate is an order of magnitude smaller and is attributed entirely to internal-wave shear dispersion.
Embodied meaning-making in the experiences and behaviours of persons with dementia
Authors: Isene Tor-Arne , Thygesen Hilde , Danbolt Lars J , Stifoss-Hanssen Hans 
Published: September 2021

Background The aim of the study was to explore and articulate how meaning-making appears and how meaningfulness is experienced in persons with severe dementia. Although there is little knowledge about meaning-making and experience of meaningfulness for this group, this article assumes that persons with dementia are as much in need of meaningfulness in life as any others, and hence, that they are involved in the process of meaning-making. Methods The study was conducted using a qualitative method with exploratory design. Ten patients with severe dementia at a specialized dementia ward at an old age psychiatric department in hospital were observed through participant observation performed over four months. The field-notes from the observation contained narratives carrying with them a dimension of meaning played out in an everyday setting and thus named Meaning-making dramas. The narratives were analyzed looking for expressions where experiences of meaning-making and meaningfulness could be identified. Results The narratives demonstrate that persons with severe dementia are involved in processes of meaning-making. The narratives include expressions of meaning-making, and of interactions that include apparent crises of meaning, but also transitions into what may be interpreted as meaningfulness based on experiences of significance, orientation and belonging. The role of the body and the senses has proved significant in these processes. The findings also suggest that experiences of meaning contribute to experience of personhood. Conclusions The relevance to clinical practice indicates that working from a person-centred approach in dementia care also includes paying attention to the dimension of meaning. This dimension is important both for the person living with dementia and for the people caring for them. Acknowledging meaning as a central human concern, it is crucial to seek understanding and knowledge about the significance of meaning in vulnerable groups such as persons with dementia.
Drivers of Organic Food Purchase Intention in a Developing Country: The Mediating Role of Trust
Authors: Ayyub Samia , Asif Muhammad , Nawaz Muhammad Asim 
Published: September 2021

The study’s objective is to explore the predictors of organic food purchase intention in a nascent organic market in one of the developing countries in South Asia. Further, the study also attempts to establish the mediating role of trust in organic food purchase intention. The quantitative data is collected from two cities of Pakistan through a structured questionnaire. A total of 325 responses are collected, out of which 312 responses are considered for further analysis. Structural equation modeling technique is used to test the hypothesis. “Personal attributes” is found to be a more significant predictor of organic food purchase intention than other attributes. Trust in organic food partially mediate personal attributes and product attributes with organic food purchase intention. The study contributes to understanding the primary attributes responsible for the purchase of organic food in a nascent organic market and establishes trust. This study also provides guidelines for the policymakers to shift their focus to organic farming, which will bring considerable benefits to health and the environment and a profitable business because consumer’s intentions coincide.
Synthesis and structure of calumetite-like SrCu4(OH)8Cl2⋅3.5H2O
Authors: Crichton Wilson A. , Müller Harald , Leoni Matteo 
Published: September 2021

AbstractThe synthesis and structure of the title compound, 1, is presented, refined using Rietveld against powder X-ray diffraction data. 1 crystallises dominantly in a pseudotetragonal C-centred orthorhombic lattice with dimensions a = 6.6791(6) Å, b = 15.5006(6) Å, c = 6.6811(6) Å and V = 691.70(10) Å3. The structural model proposed here refined by Rietveld is Sr0.928(8)Cu4(OH)8Cl2⋅3.60(21)H2O in space group Cmcm (63), with Z = 2. The chemistry and diffraction pattern of 1 are similar to that for the known Ca analogue, calumetite. The copper sites are arranged with square planar coordination at ¼ and ¾ height and are bonded to four (protonated) oxygens at an average of 1.966 Å (effective coordination of 3.82 Å). The more distant Cl sites (at Cu−Cl = 3.190(6) Å) complete the heavily Jahn–Teller distorted Cu[(OH)4,Cl2] polyhedra. The ½-occupied Sr sites are 8 coordinated to four protonated oxygens shared with the Cu-layer (at 2 × 2.438(8) Å, 2 × 2.566(15) Å) and by 4 bonds to the proposed water sites (Sr−Ow = 2.760(9) Å). The structure of 1 is predisposed towards defects, based on a notional tetragonal, P4/nmm, substructure with asub ≈ a1, csub = b½ dimensions. Average diffraction models have been further elaborated in order to resolve additional peaks (and peak-shapes) using DIFFaX+.
Association of allele-specific methylation of the ASNS gene with asparaginase sensitivity and prognosis in T-ALL
Authors: Akahane Koshi , Kimura Shunsuke , Miyake Kunio , Watanabe Atsushi , Kagami Keiko , Yoshimura Kentaro , Shinohara Tamao , Harama Daisuke , Kasai Shin , Goi Kumiko , Kawai Tomoko , Hata Kenichiro , Kiyokawa Nobutaka , Koh Katsuyoshi , Imamura Toshihiko , Horibe Keizo , Look A. Thomas , Minegishi Masayoshi , Sugita Kanji , Takita Junko , Inukai Takeshi 
Published: September 2021

Abstract
Asparaginase therapy is a key component of chemotherapy for patients with T-cell acute lymphoblastic leukemia (T-ALL). Asparaginase depletes serum asparagine by deamination into aspartic acid. Normal hematopoietic cells can survive due to asparagine synthetase (ASNS) activity, whereas leukemia cells are supposed to undergo apoptosis due to silencing of the ASNS gene. Because the ASNS gene has a typical CpG island in its promoter, its methylation status in T-ALL cells may be associated with asparaginase sensitivity. Thus, we investigated the significance of ASNS methylation status in asparaginase sensitivity of T-ALL cell lines and prognosis of childhood T-ALL. Sequencing of bisulfite polymerase chain reaction products using next-generation sequencing technology in 22 T-ALL cell lines revealed a stepwise allele-specific methylation of the ASNS gene, in association with an aberrant methylation of a 7q21 imprinted gene cluster. T-ALL cell lines with ASNS hypermethylation status showed significantly higher in vitro l-asparaginase sensitivity in association with insufficient asparaginase-induced upregulation of ASNS gene expression and lower basal ASNS protein expression. A comprehensive analysis of diagnostic samples from pediatric patients with T-ALL in Japanese cohorts (N = 77) revealed that methylation of the ASNS gene was associated with an aberrant methylation of the 7q21 imprinted gene cluster. In pediatric T-ALL patients in Japanese cohorts (n = 75), ASNS hypomethylation status was significantly associated with poor therapeutic outcome, and all cases with poor prognostic SPI1 fusion exclusively exhibited ASNS hypomethylation status. These observations show that ASNS hypomethylation status is associated with asparaginase resistance and is a poor prognostic biomarker in childhood T-ALL.
An IDO1-related immune gene signature predicts overall survival in acute myeloid leukemia
Authors: Ragaini Simone , Wagner Sarah , Marconi Giovanni , Parisi Sarah , Sartor Chiara , Nanni Jacopo , Cristiano Gianluca , Talami Annalisa , Olivi Matteo , Ocadlikova Darina , Ciciarello Marilena , Corradi Giulia , Ottaviani Emanuela , Papayannidis Cristina , Paolini Stefania , Vadakekolathu Jayakumar , Cavo Michele , Rutella Sergio , Curti Antonio 
Published: September 2021

Abstract
The contribution of the bone marrow (BM) immune microenvironment to acute myeloid leukemia (AML) development is well-known, but its prognostic significance is still elusive. Indoleamine 2,3-dioxygenase 1 (IDO1), which is negatively regulated by the BIN1 proto-oncogene, is an interferon-γ-inducible mediator of immune tolerance. With the aim to develop a prognostic IDO1-based immune gene signature, biological and clinical data of 982 patients with newly diagnosed, nonpromyelocytic AML were retrieved from public datasets and analyzed using established computational pipelines. Targeted transcriptomic profiles of 24 diagnostic BM samples were analyzed using the NanoString’s nCounter platform. BIN1 and IDO1 were inversely correlated and individually predicted overall survival. PLXNC1, a semaphorin receptor involved in inflammation and immune response, was the IDO1-interacting gene retaining the strongest prognostic value. The incorporation of PLXNC1 into the 2-gene IDO1-BIN1 score gave rise to a powerful immune gene signature predicting survival, especially in patients receiving chemotherapy. The top differentially expressed genes between IDO1lowand IDO-1high and between PLXNC1lowand PLXNC1high cases further improved the prognostic value of IDO1 providing a 7- and 10-gene immune signature, highly predictive of survival and correlating with AML mutational status at diagnosis. Taken together, our data indicate that IDO1 is pivotal for the construction of an immune gene signature predictive of survival in AML patients. Given the emerging role of immunotherapies for AML, our findings support the incorporation of immune biomarkers into current AML classification and prognostication algorithms.
Delayed headache after COVID-19 vaccination: a red flag for vaccine induced cerebral venous thrombosis
Authors: García-Azorín David , Do Thien Phu , Gantenbein Andreas R. , Hansen Jakob Møller , Souza Marcio Nattan P. , Obermann Mark , Pohl Heiko , Schankin Christoph J. , Schytz Henrik Winther , Sinclair Alexandra , Schoonman Guus G. , Kristoffersen Espen Saxhaug 
Published: September 2021

Abstract
Background
Headache is a frequent symptom following COVID-19 immunization with a typical onset within days post-vaccination. Cases of cerebral venous thrombosis (CVT) have been reported in adenovirus vector-based COVID-19 vaccine recipients.

Findings
We reviewed all vaccine related CVT published cases by April 30, 2021. We assessed demographic, clinical variables and the interval between the vaccination and onset of headache. We assessed whether the presence of headache was associated with higher probability of death or intracranial hemorrhage.
We identified 77 cases of CVT after COVID-19 vaccination. Patients’ age was below 60 years in 74/77 (95.8%) cases and 61/68 (89.7%) were women. Headache was described in 38/77 (49.4%) cases, and in 35/38 (92.1%) was associated with other symptoms. Multiple organ thrombosis was reported in 19/77 (24.7%) cases, intracranial hemorrhage in 33/77 (42.9%) cases and 19/77 (24.7%) patients died. The median time between vaccination and CVT-related headache onset was 8 (interquartile range 7.0–9.7) days. The presence of headache was associated with a higher odd of intracranial hemorrhage (OR 7.4; 95% CI: 2.7–20.8, p < 0.001), but not with death (OR: 0.51, 95% CI: 0.18–1.47, p = 0.213).

Conclusion
Delayed onset of headache following an adenovirus vector-based COVID-19 vaccine is associated with development of CVT. Patients with new-onset headache, 1 week after vaccination with an adenovirus vector-based vaccine, should receive a thorough clinical evaluation and CVT must be ruled out.
Analysis of multivariate longitudinal immuno-epidemiological data using a pairwise joint modelling approach
Authors: Lubyayi Lawrence , Mawa Patrice A. , Cose Stephen , Elliott Alison M. , Levin Jonathan , Webb Emily L. 
Published: September 2021

AbstractBackgroundImmuno-epidemiologists are often faced with multivariate outcomes, measured repeatedly over time. Such data are characterised by complex inter- and intra-outcome relationships which must be accounted for during analysis. Scientific questions of interest might include determining the effect of a treatment on the evolution of all outcomes together, or grouping outcomes that change in the same way. Modelling the different outcomes separately may not be appropriate because it ignores the underlying relationships between outcomes. In such situations, a joint modelling strategy is necessary. This paper describes a pairwise joint modelling approach and discusses its benefits over more simple statistical analysis approaches, with application to data from a study of the response to BCG vaccination in the first year of life, conducted in Entebbe, Uganda.MethodsThe study aimed to determine the effect of maternal latentMycobacterium tuberculosisinfection (LTBI) on infant immune response (TNF, IFN-γ, IL-13, IL-10, IL-5, IL-17A and IL-2 responses to PPD), following immunisation with BCG. A simple analysis ignoring the correlation structure of multivariate longitudinal data is first shown. Univariate linear mixed models are then used to describe longitudinal profiles of each outcome, and are then combined into a multivariate mixed model, specifying a joint distribution for the random effects to account for correlations between the multiple outcomes. A pairwise joint modelling approach, where all possible pairs of bivariate mixed models are fitted, is then used to obtain parameter estimates.ResultsUnivariate and pairwise longitudinal analysis approaches are consistent in finding that LTBI had no impact on the evolution of cytokine responses to PPD. Estimates from the pairwise joint modelling approach were more precise. Major advantages of the pairwise approach include the opportunity to test for the effect of LTBI on the joint evolution of all, or groups of, outcomes and the ability to estimate association structures of the outcomes.ConclusionsThe pairwise joint modelling approach reduces the complexity of analysis of high-dimensional multivariate repeated measures, allows for proper accounting for association structures and can improve our understanding and interpretation of longitudinal immuno-epidemiological data.
Risk factors for revascularization and in-stent restenosis in patients with triple-vessel disease after second-generation drug-eluting stent implantation: a retrospective analysis
Authors: Zeng MengYing , Yan XiaoWei , Wu Wei 
Published: September 2021

Abstract
Objectives
Coronary artery disease (CAD) is a common cardiac disease with high morbidity and mortality, and triple-vessel disease (TVD) is a severe type of CAD. This study investigated risk factors for revascularization and in-stent restenosis (ISR) in TVD patients who underwent second-generation drug-eluting stent implantation.

Methods
A retrospective clinical study was conducted, and 246 triple-vessel disease (TVD) patients with 373 vessels after second-generation drug-eluting stent (DES) implantation who received follow-up coronary angiography (CAG) were consequently enrolled. According to the follow-up angiography, patients were categorized into the revascularization group and nonrevascularization group as well as the in-stent restenosis (ISR) group and non-ISR group. Univariate and multivariate logistic regression analyses were used to identify risk factors for revascularization and ISR. Receiver operating characteristic (ROC) curve with area under the curve (AUC) analysis was performed to assess the predictive power of these risk factors.

Results
In the median follow-up period of 28.0 (14.0, 56.0) months, 142 TVD patients (57.7%) with 168 vessels underwent revascularization, and ISR occurred in 43 TVD patients (17.5%) with 47 vessels after second-generation DES implantation. Compared to the nonrevascularization group, the revascularization group presented with an increased rate of current smoking and higher levels of TC, LDL-C, HDL-C, non-HDL-c, ApoB, neutrophils, and Hs-CRP as well as a longer follow-up of months but with a lower level of HDL-C. In addition, patients in the ISR group had an older age, longer follow-up (months) and elevated rates of current smoking and stage 4–5 chronic kidney disease (CKD4-5). In multivariate analysis, current smoking and higher non-HDL-c were independent risk factors for revascularization. In addition, older age, current smoking and CKD4-5 were considered independent risk factors for ISR. Importantly, the receiver operating characteristic curve showed that non-HDL-C and age displayed predictive power for revascularization and ISR, respectively.

Conclusion
Current smoking is an independent risk factor for both revascularization and in-stent restenosis. Higher non-HDL-c is independently related to revascularization; moreover, increased age and CKD4-5 are potential risk factors for ISR in TVD patients after second-generation drug-eluting stent implantation.