bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrophage ALDH2 (Aldehyde Dehydrogenase 2) Stabilizing Rac2 Is Required for Efferocytosis Internalization and Reduction of Atherosclerosis Development
Authors: Zhang Jian , Zhao Xiangkai , Guo Yunyun , Liu Zhiping , Wei Shujian , Yuan Qiuhuan , Shang Haixia , Sang Wentao , Cui Sumei , Xu Tonghui , Yang Kehui , Guo Jialin , Pan Chang , Wang Jiali , Pang Jiaojiao , Han Tianrui , Chen Yuguo , Xu Feng 
Published: March 2022

Background:
Clinical studies show that the most common single-point mutation in humans, ALDH2 (aldehyde dehydrogenase 2) rs671 mutation, is a risk factor for the development and poor prognosis of atherosclerotic cardiovascular diseases, but the underlying mechanism remains unclear. Apoptotic cells are phagocytosed and eliminated by macrophage efferocytosis during atherosclerosis, and enhancement of arterial macrophage efferocytosis reduces atherosclerosis development.

Methods:

Plaque areas, necrotic core size, apoptosis, and efferocytosis in aortic lesions were investigated in APOE
−/−
mice with bone marrow transplanted from APOE
−
/−
ALDH2
−
/−
and APOE
−
/−
mice. RNA-seq, proteomics, and immunoprecipitation experiments were used to screen and validate signaling pathways affected by ALDH2. Efferocytosis and protein levels were verified in human macrophages from wild-type and rs671 mutation populations.

Results:

We found that transplanting bone marrow from APOE
−
/−
ALDH2
−
/−
to APOE
−
/−
mice significantly increased atherosclerosis plaques compared with transplanting bone marrow from APOE
−
/−
to APOE
−
/−
mice. In addition to defective efferocytosis in plaques of APOE
−
/−
mice bone marrow transplanted from APOE
−
/−
ALDH2
−
/−
mice in vivo, macrophages from ALDH2
−
/−
mice also showed significantly impaired efferocytotic activity in vitro. Subsequent RNA-seq, proteomics, and immunoprecipitation experiments showed that wild-type ALDH2 directly interacted with Rac2 and attenuated its degradation due to decreasing the K48-linked polyubiquitination of lysine 123 in Rac2, whereas the rs671 mutant markedly destabilized Rac2. Furthermore, Rac2 played a more crucial role than other Rho GTPases in the internalization process in which Rac2 was up-regulated, activated, and clustered into dots. Overexpression of wild-type ALDH2 in ALDH2
−
/−
macrophages, rather than the rs671 mutant, rescued Rac2 degradation and defective efferocytosis. More importantly, ALDH2 rs671 in human macrophages dampened the apoptotic cells induced upregulation of Rac2 and subsequent efferocytosis.

Conclusions:
Our study has uncovered a pivotal role of the ALDH2-Rac2 axis in mediating efferocytosis during atherosclerosis, highlighting a potential therapeutic strategy in cardiovascular diseases, especially for ALDH2 rs671 mutation carriers.
Impact of Age on Systemic Inflammatory Profile of Patients With ST-Segment–Elevation Myocardial Infarction and Acute Ischemic Stroke
Authors: Bochaton Thomas , Leboube Simon , Paccalet Alexandre , Crola Da Silva Claire , Buisson Marielle , Mewton Nathan , Amaz Camille , Varillon Yvonne , Bonnefoy-Cudraz Eric , Rioufol Gilles , Cho Tae-Hee , Ovize Michel , Bidaux Gabriel , Nighoghossian Norbert , Mechtouff Laura 
Published: March 2022

Background:
Aging is associated with a chronic low-grade inflammatory state. This condition may affect the acute inflammatory response involved in ST-segment–elevation myocardial infarction (STEMI) or acute ischemic stroke (AIS). We sought to compare the profile of a set of circulating inflammatory markers between young and older patients admitted for STEMI or AIS.

Methods:
HIBISCUS-STEMI (Cohort of Patients to Identify Biological and Imaging Markers of Cardiovascular Outcomes in ST Elevation Myocardial Infarction) and HIBISCUS-STROKE (Cohort of Patients to Identify Biological and Imaging Markers of Cardiovascular Outcomes in Stroke) are 2 cohort studies that enrolled patients with STEMI treated with primary percutaneous coronary intervention in the cardiac intensive care unit of Lyon and patients with AIS treated with mechanical thrombectomy in the Lyon Stroke Center, respectively from 2016 to 2019. Patients were classified as older if they were ≥65 years and as young if they were <65 years. In both cohorts, CRP (C-reactive protein), IL (interleukin)-6, IL-8, IL-10, MCP (monocyte chemoattractant protein), sTNF-RI (soluble tumor necrosis factor receptor I), sST2 (soluble form suppression of tumorigenicity 2), and VCAM-1 (vascular cellular adhesion molecule-1) were measured on serum collected at 5 time points using enzyme-linked immunosorbent assay. A multiple logistic regression model was performed to detect an association between area under the curve of circulating inflammatory markers within the first 48 hours and older age.

Results:
A total of 260 patients with STEMI and 164 patients with AIS were included. Of them, there were 76 (29%) and 105 (64%) older patients with STEMI and AIS, respectively. Following multivariable analysis, a high area under the curve of IL-6 and sTNF-RI, a low lymphocyte count, and a high neutrophil-lymphocyte ratio at 24 hours were associated with older age in patients with STEMI and AIS.

Conclusions:
Older patients had higher IL-6 and sTFN-RI levels within the first 48 hours associated with a lower lymphocyte count and a higher neutrophil-lymphocyte ratio at 24 hours in both cohorts.
Age Alters Prevalence of Left Atrial Enlargement and Nonstenotic Carotid Plaque in Embolic Stroke of Undetermined Source
Authors: Oak Solomon , Cucchiara Brett L. , Thau Lauren , Nguyen Thanh N. , Sathya Anvitha , Reyes-Esteves Sahily , Vigilante Nicholas , Kamen Scott , Hall Jillian , Patel Parth , Garg Rahul , Abdalkader Mohamad , Thon Jesse M. , Siegler James E. 
Published: March 2022

Background:
Nonstenotic carotid plaque and undetected atrial fibrillation are potential mechanisms of embolic stroke of undetermined source (ESUS), but it is unclear which is more likely to be the contributing stroke mechanism. We explored the relationship between left atrial enlargement (LAE) and nonstenotic carotid plaque across age ranges in an ESUS population.

Methods:
A retrospective multicenter cohort of consecutive patients with unilateral, anterior circulation ESUS was queried (2015 to 2021). LAE and plaque thickness were determined by transthoracic echocardiography and computed tomography angiography, respectively. Descriptive statistics were used to compare plaque features in relation to age and left atrial dimensions.

Results:

Among the 4155 patients screened, 273 (7%) met the inclusion criteria. The median age was 65 years (interquartile range [IQR] 54–74), 133 (48.7%) were female, and the median left atrial diameter was 3.5 cm (IQR 3.1–4.1). Patients with any LAE more frequently had hypertension (85.9% versus 67.2%,
P
<0.01), diabetes (41.0% versus 25.6%,
P
=0.01), dyslipidemia (56.4% versus 40.0%,
P
=0.01), and coronary artery disease (22.8% versus 11.3%,
P
=0.02). Carotid plaque thickness was greater ipsilateral versus contralateral to the stroke hemisphere in the overall cohort (median 1.9 mm [IQR 0–3] versus 1.5 mm [IQR 0–2.6],
P
<0.01); however, this was largely driven by the subgroup of patients without any LAE (median 1.8 mm [IQR 0–2.9] versus 1.5 mm [IQR 0–2.5],
P
<0.01). Compared with patients ≥70 years, younger patients had more carotid plaque ipsilateral versus contralateral (mean difference 0.42 mm±1.24 versus 0.08 mm±1.54,
P
=0.047) and less moderate-to-severe LAE (6.3% versus 15.3%,
P
=0.02).

Conclusions:
Younger patients with ESUS had greater prevalence of ipsilateral nonstenotic plaque, while the elderly had more LAE. The differential effect of age on the probability of specific mechanisms underlying ESUS should be considered in future studies.
Drag Coefficient and Its Sea State Dependence under Tropical Cyclones
Authors: Zhou Xiaohui , Hara Tetsu , Ginis Isaac , D’Asaro Eric , Hsu Je-Yuan , Reichl Brandon G. 
Published: March 2022

Abstract
The drag coefficient under tropical cyclones and its dependence on sea states are investigated by combining upper-ocean current observations [using electromagnetic autonomous profiling explorer (EM-APEX) floats deployed under five tropical cyclones] and a coupled ocean–wave (Modular Ocean Model 6–WAVEWATCH III) model. The estimated drag coefficient averaged over all storms is around 2–3 × 10−3 for wind speeds of 25–55 m s−1. While the drag coefficient weakly depends on wind speed in this wind speed range, it shows stronger dependence on sea states. In particular, it is significantly reduced when the misalignment angle between the dominant wave direction and the wind direction exceeds about 45°, a feature that is underestimated by current models of sea state–dependent drag coefficient. Since the misaligned swell is more common in the far front and in the left-front quadrant of the storm (in the Northern Hemisphere), the drag coefficient also tends to be lower in these areas and shows a distinct spatial distribution. Our results therefore support ongoing efforts to develop and implement sea state–dependent parameterizations of the drag coefficient in tropical cyclone conditions.
Measuring Displacement Errors with Complex Wavelets
Authors: Buschow Sebastian 
Published: March 2022

Abstract
When highly resolved precipitation forecasts are verified against observations, displacement errors tend to overshadow all other aspects of forecast quality. The appropriate treatment and explicit measurement of such errors remains a challenging task. This study explores a new verification technique that uses the phase of complex wavelet coefficients to quantify spatially varying displacements. Idealized and realistic test cases from the MesoVICT project demonstrate that our approach yields helpful results in a variety of situations where popular alternatives may struggle. Potential benefits of very high spatial resolutions can be identified even when the observational dataset is coarsely resolved itself. The new score can furthermore be applied not only to precipitation but also variables such as wind speed and potential temperature, thereby overcoming a limitation of many established location scores.

Significance Statement
One important requirement for a useful weather forecast is its ability to predict the placement of weather events such as cold fronts, low pressure systems, or groups of thunderstorms. Errors in the predicted location are not easy to quantify: some established quality measures combine location and other error sources in one score, others are only applicable if the data contain well-defined and easily identifiable objects. Here we introduce an alternative location score that avoids such assumptions and is thus widely applicable. As an additional benefit, we can separate displacement errors into different spatial scales and localize them on a weather map.
Drug-eluting balloon (DEB) versus plain old balloon angioplasty (POBA) in the treatment of failing dialysis access: A prospective randomized trial
Authors: Fransson Torbjörn , Gottsäter Anders , Abdulrasak Mohammad , Malina Martin , Resch Timothy 
Published: March 2022

Objective To compare the efficacy of angioplasty using drug-eluting balloons (DEB) compared with plain old balloon angioplasty (POBA) to reduce the rate of restenosis. Methods This prospective, single-centre, single-blinded, 1:1 randomized, clinical trial enrolled patients that had primary or restenotic lesions in native upper extremity arteriovenous (AV) fistulas or at the graft-venous anastomosis. Patients were randomized to angioplasty with a POBA or a DEB. The primary effectiveness endpoints were freedom from target lesion revascularization (TLR) and functional status of access circuit at 12 months. Results A total of 42 (28 male, 14 female; age range, 42–83 years) patients were enrolled. Patients were followed for 12 months. No significant differences were detected between the POBA and DEB groups regarding total number of TLR procedures (31 versus 36, respectively), freedom from TLR (3 versus 4, respectively) and functional status of the access circuit at 12 months (14 of 20 patients [70%] versus 17 of 22 patients [77%], respectively). Conclusion This clinical trial did not demonstrate any significant differences between DEB angioplasty and standard balloon angioplasty when treating dysfunctional haemodialysis access.
Invisible children: The out-of-home care and education of babies and toddlers
Authors: Jackson Sonia , Figueira-Bates Cora , Hollingworth Katie 
Published: March 2022

Many thousands of very young children pass through the UK care system every year. Understandably, social workers are reluctant to separate children from their parents, and legal protections designed to prevent the separation from becoming permanent lead to constant delay in making longer-term plans. The aim is that the children should either be returned to their birth families or placed for adoption, but this is not achieved in up to 50% of cases. Consequently, many infants and toddlers remain in foster care, intended to be temporary, for long periods. Yet we know little about their lives in care or who looks after them. Research on foster care and on early childhood education and care (ECEC) has developed on separate and unrelated lines, resulting in an extreme shortage of empirical evidence about the care and education of fostered children under school age. Lack of attention to this critical period of life fails to take account of advances in research both on early brain development and on the lasting effects of adverse childhood experiences. Meanwhile, young children continue to be moved between short-term foster placements for administrative reasons, ignoring the undisputed importance of stable early attachments. The potential of foster care as a learning and therapeutic resource in the early years has also been largely overlooked. Better mental health and educational attainment for children in out-of-home care require a much stronger policy focus on their earliest experiences and developmental progress. This article argues that there is an urgent need for research-based information to guide policy and practice.
Incident cases of vision impairment and blindness among adult foreign-born and Swedish-born individuals: A national Swedish study
Authors: Wändell Per , Li Xinjun , Carlsson Axel C , Sundquist Jan , Sundquist Kristina 
Published: March 2022

Purpose To analyse risk of vision impairment (VI) and blindness in adult foreign-born individuals and Swedish-born individuals. Methods A nationwide study of individuals 18 years of age and older (N = 6,042,891; 2,902,918 men and 3,139,973 women) in Sweden. VI (in general) and blindness was defined as at least one registered diagnosis in the National Patient Register between January 1, 1998 and December 31, 2015. Cox regression analysis was used to estimate the relative risk (hazard ratios (HR) with 95% confidence intervals (CI)) of incident VI in foreign-born compared to Swedish-born individuals. The Cox regression models were stratified by sex and adjusted for age, co-morbidities, and for sociodemographic status. Results A total of 14,597 cases (6433 men and 8164 women) of VI were registered, with an age-standardized incidence per 100,000 person-years of 10.37 in men and 11.03 in women. VI (in general) was more common in immigrants, fully adjusted HRs (95% CI) were for immigrant men 1.38 (95% CI, 1.29–1.48) and women 1.24 (95% CI, 1.16–1.32), with significantly higher HRs among men and women from Eastern Europe, Africa, Latin America and Asia. Higher risks of blindness were also seen for immigrant men, HR 1.75 (95% CI 1.36–2.25), as well as for the other degrees of VI among immigrant men, HR 1.36 (95% CI 1.26–1.47), and immigrant women, HR 1.26 (95% CI 1.18–1.35). Conclusions We observed a generally higher risk of VI among foreign-born men and women, especially from some regions.
Metagenomics of infective canaliculitis: The Lacriome paper 3
Authors: Ali Mohammad Javed 
Published: March 2022

Purpose To study the metagenomics of the microbes isolated from the canaliculus of patients with infective canaliculitis. Methods A prospective study was performed on five consecutive canalicular samples obtained for the metagenomic analysis from the patients with infective canaliculitis who underwent non-incisional canalicular curettage at a tertiary care Dacryology service. The canalicular concretions were collected intraoperatively soon after a canalicular curettage and immediately transported on ice to the laboratory. Following DNA extraction and library preparation, a whole shotgun metagenome sequencing was performed on the Illumina™ platform. The downstream processing and bioinformatics of the samples were performed using multiple software packaged in SqueezeMeta™ pipeline or MG-RAST™ pipeline. Results The taxonomic hit distribution across the samples showed that bacteria were the most common isolates (mean—80.5%), followed by viruses (mean—0.74%), and archaea (0.01%). The five major phyla identified across the samples of infective canaliculitis were, Fusobacteria, Bacteroidetes, Proteobacteria, Actinobacteria, and Firmicutes. The prevalent organisms include Fusobacterium nucelatum, Fusobacterium periodonticum, Parvimonas micra, Prevotella oris, Selonomonas noxia, Pseudopropionobacterium propoinicum, Campylobacter showae, and Streptococcus anginosus, amongst few others. Actinomycetes israelii was noted in all the samples, though it was not the most abundant. The microbial gene mapping and protein prediction demonstrated proteins with known functions to range from 69.91% to 87.09% across the samples. The functional subsystem profiling demonstrated genes associated with carbohydrate, amino acid, and co-enzyme transport and metabolism, cell wall or cell membrane biogenesis, energy production and conversion, transcription, translation, and cellular communications. Conclusion This is the first whole metagenome sequencing of infective canaliculitis. Infected canaliculi harbor diverse microbial communities, including bacteria, viruses, and archaea. Functional analysis has provided newer insights into the ecosystem dynamics and strategies of microbial communities.
Rapid Improvement in Skin Pain Severity and Its Impact on Quality of Life in Adult Patients With Moderate-to-Severe Atopic Dermatitis From a Double-Blind, Placebo-Controlled Baricitinib Phase 3 Study
Authors: Rosmarin David , Fretzin Scott , Strowd Lindsay , Casillas Marta , DeLozier Amy M. , Dawson Zach , Chen Sherry , Lu Na , Thyssen Jacob P. 
Published: March 2022

Background Skin pain (discomfort/soreness) is a common symptom associated with atopic dermatitis (AD). Objective To evaluate rapid changes in skin pain severity with baricitinib, and its impact on patient quality of life (QoL) in adults with moderate-to-severe AD who were inadequate responders to topical therapy. Methods Adult patients with moderate-to-severe AD who were inadequate responders to topical therapies ( N = 440, BREEZE-AD5 [NCT03435081]) were randomized to once-daily placebo, baricitinib 1 mg, or baricitinib 2 mg for 16 weeks. Change in Skin Pain Numeric Rating Scale (NRS) scores were assessed for the randomized population. Skin Pain NRS and Dermatology Life Quality Index (DLQI) scores were assessed for Skin Pain Response groups and patients with Body Surface Area (BSA) 10% to 50%. Results Skin Pain NRS improvement was significant versus placebo by day 1 baricitinib 2 mg (least squares mean [LSM] difference −4.4%, P = .048) and by day 2 for baricitinib 1 mg (−6.7%, P = .011). As measured weekly, improvement was significant starting at Week 1 and remained significant through Week 16 for both doses. At Week 16, 70.9% of Skin Pain NRS responders vs 10.4% of nonresponders had a clinically meaningful improvement in DLQI ( P < .0001). At week 16, LSM DLQI change from baseline was −11.1 for all Skin Pain NRS responders versus −3.5 for nonresponders ( P < .0001). Patients with BSA 10% to 50% showed similar trends. Conclusions Patients with moderate-to-severe AD, treated with baricitinib, reported rapid improvements in skin pain severity by day 1 for baricitinib 2 mg and day 2 for baricitinib 1 mg and remained effective through 16 weeks of treatment, which positively impacted patient QoL.
High Prevalence of Pain Sensitization in Knee Osteoarthritis: A Meta-Analysis with Meta-Regression
Authors: Previtali Davide , Capone Gianluigi , Marchettini Paolo , Candrian Christian , Zaffagnini Stefano , Filardo Giuseppe 
Published: March 2022

Objective The aim of this meta-analysis was to study the evidence on pain sensitization in knee osteoarthritis (OA), providing a quantitative synthesis of its prevalence and impact. Factors associated with pain sensitization were also investigated. Methods Meta-analysis; PubMed (MEDLINE), Cochrane Central Register (CENTRAL), and Web of Science were searched on February 2021. Level I to level IV studies evaluating the presence of pain sensitization in patients with symptomatic knee OA, documented through a validated method (questionnaires or quantitative sensory testing), were included. The primary outcome was the prevalence of pain sensitization. Factors influencing the prevalence were also evaluated, as well as differences in terms of pain thresholds between knee OA patients and healthy controls. Results Fifty-three articles including 7,117 patients were included. The meta-analysis of proportion documented a prevalence of pain sensitization of 20% (95% confidence interval [CI] = 16%-26%) with a significant heterogeneity of results ( I2 = 89%, P < 0.001). The diagnostic tool used was the main factor influencing the documented prevalence of pain sensitization ( P = 0.01). Knee OA patients presented higher pain sensitivity compared with healthy controls, both in terms of local pressure pain threshold (standardized mean difference [SMD] = −1.00, 95% CI = −1.67 to −0.32, P = 0.007) and distant pressure pain threshold (SMD = −0.54, 95% CI = −0.76 to −0.31, P < 0.001). Conclusions Knee OA pain presents features that are consistent with a significant degree of pain sensitization. There is a high heterogeneity in the reported results, mainly based on the diagnostic tool used. The identification of the best methods to detect pain sensitization is warranted to correctly evaluate and manage symptoms of patients affected by knee OA. Registration: PROSPERO CRD42019123347.