bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying characteristics of dermal fibroblasts in skin homeostasis and disease
Authors: Chen Fang-Zhou , Tan Poh-Ching , Yang Zihan , Li Qingfeng , Zhou Shuang-Bai 
Published: August 2023

Abstract
Heterogeneous dermal fibroblasts are the main components that constitute the dermis. Distinct fibroblast subgroups show specific characteristics and functional plasticity that determine dermal structure during skin development and wound healing. Although researchers have described the roles of fibroblast subsets, this is not completely understood. We review recent evidence supporting understanding about the heterogeneity of fibroblasts. We summarize the origins and the identified profiles of fibroblast subpopulations. The characteristics of fibroblast subpopulations in both healthy and diseased states are highlighted, and the potential of subpopulations to be involved in wound healing in different ways was discussed. Additionally, we review the plasticity of subpopulations and the underlying signalling mechanisms. This review may provide greater insights into potential novel therapeutic targets and tissue regeneration strategies for the future.
Increased thromboinflammatory load in hereditary angioedema
Authors: Gramstad Olav Rogde , Schjalm Camilla , Mollnes Tom Eirik , Nielsen Erik Waage 
Published: August 2023

Abstract
C1 inhibitor (C1Inh) is a serine protease inhibitor involved in the kallikrein-kinin system, the complement system, the coagulation system, and the fibrinolytic system. In addition to the plasma leakage observed in hereditary angioedema (HAE), C1Inh deficiency may also affect these systems, which are important for thrombosis and inflammation. The aim of this study was to investigate the thromboinflammatory load in C1Inh deficiency. We measured 27 cytokines including interleukins, chemokines, interferons, growth factors, and regulators using multiplex technology. Complement activation (C4d, C3bc, and sC5b-C9/TCC), haemostatic markers (β-thromboglobulin (β-TG), thrombin-antithrombin complexes (TAT), prothrombin fragment 1 + 2 (F1 + 2), active plasminogen activator inhibitor-1 (PAI-1), and the neutrophil activation marker myeloperoxidase (MPO) were measured by enzyme immunoassays. Plasma and serum samples were collected from 20 patients with HAE type 1 or 2 in clinical remission and compared with 20 healthy age- and sex-matched controls. Compared to healthy controls, HAE patients had significantly higher levels of tumour necrosis factor (TNF), interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-7, IL-9, IL-12, and IL-17A, chemokine ligand (CXCL) 8, chemokine ligand (CCL) 3, CCL4, IL-1 receptor antagonist (IL-1RA), granulocyte-macrophage colony-stimulating factor (GM-CSF), fibroblast growth factor (FGF) 2 and platelet-derived growth factor (PDGF)-BB. HAE patients also had higher levels of TAT and F1 + 2. Although granulocyte colony-stimulating factor (G-CSF), β-TG and PAI-1 were higher in HAE patients, the differences did not reach statistical significance after correction for multiple testing. In conclusion, C1Inh deficiency is associated with an increased baseline thromboinflammatory load. These findings may reflect that HAE patients are in a subclinical attack state outside of clinically apparent oedema attacks.
Epidemiology and predictors of hyponatremia in a contemporary cohort of patients with malignancy: a retrospective cohort study
Authors: Murashima Miho , Ambe Kaori , Aoki Yuka , Kasugai Takahisa , Tomonari Tatsuya , Ono Minamo , Mizuno Masashi , Tohkin Masahiro , Hamano Takayuki 
Published: August 2023

ABSTRACT

Background
Hyponatremia is associated with worse outcomes among patients with malignancy. However, contemporary cohort data on epidemiology and risk factors are lacking.

Methods
In this single-centre, retrospective cohort study, patients who received intravenous antineoplastic agents from 2018 to 2020 at Nagoya City University Hospital were enrolled. Associations of demographics, antineoplastic agents, types of malignancy and concomitant medications with hyponatremia, defined as serum sodium concentration ≤130 mmol/l, were analysed by mixed-effects logistic regression and the machine learning–based LightGBM model artificial intelligence technology.

Results
Among 2644 patients, 657 (24.8%) developed at least one episode of hyponatremia. Approximately 80% of hyponatremia was due to sodium wasting from the kidneys. Variables associated with hyponatremia both by mixed-effects logistic regression and the LightGBM model were older age, hypoalbuminemia and higher estimated glomerular filtration rate. Among antineoplastic agents, cisplatin {odds ratio [OR] 1.52 [95% confidence interval (CI) 1.18–1.96]}, pembrolizumab [OR 1.42 (95% CI 1.02–1.97)] and bortezomib [OR 3.04 (95% CI 1.96–4.71)] were associated with hyponatremia and these variables also had a positive impact on predicted hyponatremia in the LightGBM model.

Conclusions
Hyponatremia was common among patients with malignancy. In addition to older age and poor nutritional status, novel antineoplastic agents, including immune checkpoint inhibitors and bortezomib, should be recognized as risk factors for hyponatremia.
Improving mean-field network percolation models with neighbourhood information
Authors: Jones Chris , Wiesner Karoline 
Published: August 2023

Abstract
Mean field theory models of percolation on networks provide analytic estimates of network robustness under node or edge removal. We introduce a new mean field theory model based on generating functions that includes information about the tree-likeness of each node’s local neighbourhood. We show that our new model outperforms all other generating function models in prediction accuracy when testing their estimates on a wide range of real-world network data. We compare the new model’s performance against the recently introduced message-passing models and provide evidence that the standard version is also outperformed, while the ‘loopy’ version is only outperformed on a targeted attack strategy. As we show, however, the computational complexity of our model implementation is much lower than that of message-passing algorithms. We provide evidence that all discussed models are poor in predicting networks with highly modular structure with dispersed modules, which are also characterized by high mixing times, identifying this as a general limitation of percolation prediction models.
Hospital admissions in the last year of life of patients with heart failure
Authors: Abel Alexandra A I , Samuel Nathan A , Cuthbert Joseph J , Brown Oliver I , Pellicori Pierpaolo , Kazmi Syed , Cleland John G F , Johnson Miriam J , Clark Andrew L 
Published: August 2023

Abstract

Aim
To explore the frequency, causes, and pattern of hospitalisation for patients with chronic heart failure (HF) in the 12 months preceding death. We also investigated cause of death.

Methods
Patients referred to a secondary care HF clinic were routinely consented for follow-up between 2001 and 2020 and classified into three phenotypes: (i) HF with reduced ejection fraction (HFrEF), (ii) HF with preserved ejection fraction (HFpEF) with plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) 125–399 ng L−1, and (iii) HFpEF with NT-proBNP ≥400 ng L−1. Hospital admissions in the last year of life were classified as: HF, other cardiovascular (CV), or non-cardiovascular (non-CV). The cause of death was systematically adjudicated.

Results
A total of 4925 patients (38% women; median age at death 81 [75–87] years) had 9127 hospitalisations in the last year of life. The median number of hospitalisations was 2 (1–3) and total days spent in hospital was 12 (2–25). Out of the total, 83% of patients had ≥1 hospitalisation but only 20% had ≥1 HF hospitalisation; 24% had ≥1 CV hospitalisation; 70% had ≥1 non-CV hospitalisation. Heart failure hospitalisations were most common in patients with HFrEF, but in all groups, at least two thirds of admissions were for non-CV causes. There were 788 (16%) deaths due to progressive HF, of which 74% occurred in hospital.

Conclusion
For patients with chronic HF in the last year of life, most hospitalisations were for non-CV causes regardless of HF phenotype. Most patients had no HF hospitalisations in their last year of life. Most deaths were from causes other than progressive HF.
Relation between HLA and copy number variation of steroid 21-hydroxylase in a Swedish cohort of patients with autoimmune Addison's disease
Authors: Lundtoft Christian , Eriksson Daniel , Bianchi Matteo , Aranda-Guillén Maribel , Landegren Nils , Rantapää-Dahlqvist Solbritt , Söderkvist Peter , Meadows Jennifer R S ,   The DISSECT Consortium, Rönnblom Lars , Lindblad-Toh Kerstin , Wahren-Herlenius Marie , Nordmark Gunnel , Lundberg Ingrid E , Syvänen Ann-Christine , Sandling Johanna K , Kozyrev Sergey V , Eloranta Maija-Leena , Bianchi Matteo , Rantapää-Dahlqvist Solbritt , Meadows Jennifer R S , Nordin Jessika , Dahlqvist Johanna , Mathioudaki Argyri , Farias Fabiana H G , Tandre Karolina ,   The ImmunoArray Consortium, Lindblad-Toh Kerstin , Pielberg Gerli Rosengren , Lobell Anna , Karlsson Åsa , Murén Eva , Andersson Göran , Ahlgren Kerstin M , Rönnblom Lars , Landegren Nils , Kämpe Olle , Söderkvist Peter ,   The Swedish Addison Registry Study Group, Åkerman Anna-Karin , Hulting Anna-Lena , Lindberg Bengt , Lundberg Elena , Johannsson Gudmundur , Skov Jakob , Wahlberg Jeanette , Duchen Karel , Isaksson Magnus , Elfving Maria , Stenlid Maria Halldin , Landin-Olsson Mona , Nilsson Ola , Kämpe Olle , Ekwall Olov , Dahlqvist Per , Bergthorsdottir Ragnhildur , Nergårdh Ricard , Björnsdottir Sigridur , Bensing Sophie , Olsson Tommy , Bensing Sophie , Pielberg Gerli Rosengren , Lindblad-Toh Kerstin , Rönnblom Lars , Kämpe Olle 
Published: August 2023

Abstract

Objective
Autoantibodies against the adrenal enzyme 21-hydroxylase is a hallmark manifestation in autoimmune Addison's disease (AAD). Steroid 21-hydroxylase is encoded by CYP21A2, which is located in the human leucocyte antigen (HLA) region together with the highly similar pseudogene CYP21A1P. A high level of copy number variation is seen for the 2 genes, and therefore, we asked whether genetic variation of the CYP21 genes is associated with AAD.

Design
Case-control study on patients with AAD and healthy controls.

Methods
Using next-generation DNA sequencing, we estimated the copy number of CYP21A2 and CYP21A1P, together with HLA alleles, in 479 Swedish patients with AAD and autoantibodies against 21-hydroxylase and in 1393 healthy controls.

Results
With 95% of individuals carrying 2 functional 21-hydroxylase genes, no difference in CYP21A2 copy number was found when comparing patients and controls. In contrast, we discovered a lower copy number of the pseudogene CYP21A1P among AAD patients (P = 5 × 10−44), together with associations of additional nucleotide variants, in the CYP21 region. However, the strongest association was found for HLA-DQB1*02:01 (P = 9 × 10−63), which, in combination with the DRB1*04:04-DQB1*03:02 haplotype, imposed the greatest risk of AAD.

Conclusions
We identified strong associations between copy number variants in the CYP21 region and risk of AAD, although these associations most likely are due to linkage disequilibrium with disease-associated HLA class II alleles.
Arrhythmic mitral valve prolapse and mitral annular disjunction: pathophysiology, risk stratification, and management
Authors: Essayagh Benjamin , Sabbag Avi , El-Am Edward , Cavalcante João L , Michelena Hector I , Enriquez-Sarano Maurice 
Published: August 2023

Abstract
Mitral valve prolapse (MVP) is the most frequent valve condition but remains a conundrum in many aspects, particularly in regard to the existence and frequency of an arrhythmic form (AMVP) and its link to sudden cardiac death. Furthermore, the presence, frequency, and significance of the anatomic functional feature called mitral annular disjunction (MAD) have remained widely disputed. Recent case series and cohorts have shattered the concept that MVP is most generally benign and have emphasized the various phenotypes associated with clinically significant ventricular arrhythmias, including AMVP. The definition, evaluation, follow-up, and management of AMVP represent the focus of the present review, strengthened by recent coherent studies defining an arrhythmic MVP phenotypic that would affect a small subset of patients with MVP at concentrated high risk. The role of MAD in this context is of particular importance, and this review highlights the characteristics of AMVP phenotypes and MAD, their clinical, multimodality imaging, and rhythmic evaluation. These seminal facts lead to proposing a risk stratification clinical pathway with consideration of medical, rhythmologic, and surgical management and have been objects of recent expert consensus statements and of proposals for new research directions.
De novo genome assembly and comparative genomics for the colonial ascidian Botrylloides violaceus
Authors: Sumner Jack T , Andrasz Cassidy L , Johnson Christine A , Wax Sarah , Anderson Paul , Keeling Elena L , Davidson Jean M 
Published: August 2023

Abstract
Ascidians have the potential to reveal fundamental biological insights related to coloniality, regeneration, immune function, and the evolution of these traits. This study implements a hybrid assembly technique to produce a genome assembly and annotation for the botryllid ascidian, Botrylloides violaceus. A hybrid genome assembly was produced using Illumina, Inc. short and Oxford Nanopore Technologies long-read sequencing technologies. The resulting assembly is comprised of 831 contigs, has a total length of 121 Mbp, N50 of 1 Mbp, and a BUSCO score of 96.1%. Genome annotation identified 13 K protein-coding genes. Comparative genomic analysis with other tunicates reveals patterns of conservation and divergence within orthologous gene families even among closely related species. Characterization of the Wnt gene family, encoding signaling ligands involved in development and regeneration, reveals conserved patterns of subfamily presence and gene copy number among botryllids. This supports the use of genomic data from nonmodel organisms in the investigation of biological phenomena.
Counteracting Age-Related Netrin-1 Signaling Insufficiency Ameliorates Endothelial Cell Senescence and Angiogenesis Impairment
Authors: Yang Zhen , Li Han , Yan Dan , Luo Pengcheng , Guan Yuqi , Luo Mandi , Nie Hao , Huang Yi , Zhang Le , Ruan Lei , Yan Jinhua , Zhang Cuntai 
Published: August 2023

Abstract
Senescent cells that accumulate are regarded as promising therapeutic targets. However, senolytic therapy failed to achieve satisfactory results. We previously discovered that young human plasma improved vascular endothelial cell senescence, and UNC5B might be a novel intervention target. Netrin-1, as a natural ligand of UNC5B, plays roles in multiple age-related vascular disorders, but its involvement in aging is still unclear. Here, we observed a significant decrease in plasma Netrin-1 levels in old healthy subjects compared to the young. In vivo, adeno-associated-virus-mediated delivery of Netrin-1 into aged mice significantly improved functional recovery in a model of hindlimb ischemia, promoted angiogenesis in ischemic tissues, and activated the endothelial nitric oxide synthase. Furthermore, we revealed that low-dose Netrin-1 recombinant protein significantly reduced senescence-associated-β-galactosidase-positive cells, inhibited the P53 pathway, promoted cell migration, increased tubule formation, and elevated nitric oxide production in senescent endothelial cells. However, UNC5B inhibition blocked the pro-angiogenesis effect of low-dose Netrin-1 on senescent cells or aortic rings. In summary, this study depicts that modulating Netrin-1 signaling can result in improved vascular health and Netrin-1 may have therapeutic potential for age-related ischemic diseases.
An electrical resistivity image of the Hikurangi subduction margin
Authors: Heise Wiebke , Bertrand Edward A , Caldwell T Grant , Ogawa Yasuo , Bannister Stephen , Bennie Stewart L , Hart Rory , Palmer Neville , Tseng Kuo Hsuen , Fukai Masato , Ishikawa Masaki , Seki Kaori , Nishizawa Tatsuji , McGrath Jack 
Published: August 2023

SUMMARYAlong the Hikurangi subduction margin, on the east coast of New Zealand's North Island, the interplate coupling changes from locked in the south to weakly coupled in the north. New magnetotelluric (MT) data from 151 locations linking previous MT surveys into a single contiguous data set that encompasses the weakly coupled part of the margin are analysed. By inverting the combined data we have constructed a 3-D image of the electrical resistivity of the subduction interface shear zone along a 300-km-long segment of the margin. Our results show that the electrical resistivity of the subduction interface shear zone is heterogenous; the degree of heterogeneity decreasing from north to south. The resistivity heterogeneities correlate well with the distribution of near-plate interface seismicity, Vp/Vs values and the pattern of areal strain rate derived from GPS data. These correlations are consistent with variations in the fluid content of the subduction interface shear zone. In the northern part of this segment, conductive areas adjacent to the interface are interpreted to be fluid rich areas where seismicity is sparse, Vp/Vs ratios are high and the areal strain rate is extensional. In contrast, where the areal strain rate is compressional the plate interface is more resistive, and seismicity is more abundant consistent with greater interplate friction. In the south, the resistivity of the plate interface is more homogenous, and the overlying plate is more resistive at shallower levels than in the north. Our results support the hypothesis that the fluid and/or hydrated clay content of the subduction interface shear zone are an important control on interplate coupling.
Structure and dynamics of the Ecuador Fracture Zone, Panama Basin
Authors: Peirce C , Tedd J C , Hobbs R W 
Published: August 2023

SUMMARYIn this study, multiple geophysical data types are used to investigate the structure and dynamics of the Ecuador Fracture Zone—a complex multistranded strike-slip fault system located in the Panama Basin. Gravity modelling reveals a 25–30-km-wide region of ∼3-km-thick, low-density crust beneath this system and an anomalously low-density region in the uppermost mantle. Along both edges, the transition to the ‘normal’ structure and thickness oceanic crust formed at both the Ecuador and Costa Rica Rifts is abrupt. Within the Ecuador Fracture Zone itself, normal faults bound the median ridges. These faults traverse the entire thickness of accumulated sediment and offset the seabed, while sediment layer geometries document multiple phases of relative uplift, with the most recent phase still ongoing. Active extensional faulting, with an approximately spreading ridge-parallel strike, is also observed in 6–7 Ma Costa Rica Rift crust. The median ridges and the transverse ridge at the eastern edge of the Ecuador Fracture Zone also have contrasting crustal density structures. Both median ridges have a lower density crust than between the intervening valleys, while the transverse ridge crust has an equivalent thickness and density structure to that formed at the Costa Rica Rift. The active median valley basement-cutting normal faults allow seawater ingress and alternation of the crustal footwall, and also flow to mantle depth where, based on gravity modelling, 30–50 per cent serpentinization of mantle peridotite occurs. The resulting serpentinite-driven buoyancy acts as the primary control on the observed median ridge relative vertical tectonism. In contrast, the relative uplift of the transverse ridge results from lithospheric flexure in response to a change in spreading direction between the Ecuador and Costa Rica Rifts. Contrary to the widely accepted assumption that fracture zones are tectonically inactive systems, the Ecuador Fracture Zone provides evidence of extension, serpentinization due to ongoing hydrothermal circulation and relative uplift.
Staged surgically created type B aortic dissection model with endovascular reintervention for different morphological features
Authors: Guo Baolei , Akhtar Riaz , Liu Haofei , Yan Cheng , Guo Daqiao , Patterson Benjamin , Fu Weiguo 
Published: August 2023

Abstract

OBJECTIVES
Understanding morphology and how this relates to treatment strategy is critical for achieving remodelling in aortic dissection. A controllable and reproducible large animal model is required for investigating new therapeutic devices and interventions.

METHODS
Our experimental protocol involved the development of surgically created type B aortic dissection (TBAD) and endovascular reintervention-induced TBAD porcine models. The sample was randomly divided into 2 groups: 1 underwent a secondary tear creation (STC) procedure and the other underwent a false lumen extension (FLE) procedure. Anatomical features were observed at 1 and 3 months, and 2 animals in each group were euthanized at 3 months after the procedures. The aorta and main branches were harvested en bloc, cross-sectioned and prepared for histological examination.

RESULTS
All surgically created TBAD models were successfully generated, and no unintended complications occurred. The endovascular reintervention-induced TBAD model was successfully created in 11 of 12 animals, with 6 in the STC group and 5 in the FLE group. In the STC group, the intraoperative mean diameter of the new secondary tear was 7.23 mm, and a slight increase was observed at first 30 days (P = 0.0026). In the FLE group, the intraoperative new propagation length was (235.80 ± 84.94) mm. The FL propagation length at the 1-month follow-up was significantly longer than that measured intraoperatively (P = 0.0362). Histological evaluation demonstrated that the elastic fibres in the media layer of the aortic wall were disrupted and appeared to be significantly stretched on the adventitial side of the false lumen.

CONCLUSIONS
Our endovascular reintervention is a reliable, minimally invasive approach for producing specific TBAD models with different morphologies.
Quantitative PCR-Based Diagnosis and Follow-up of Chagas Disease Primary Infection After Solid Organ Transplant: A Multicentre Study
Authors: Barcan Laura A , Smud Astrid , Besuschio Susana A , Giorgio Patricia L , Temporiti Elena , Salgueira Claudia , Pinoni Maria V , Nagel Claudia , Schijman Alejandro G 
Published: August 2023

Abstract
Chagas disease in solid organ transplant recipients may present as a primary infection (PI). Early detection is crucial for timely treatment. This is the largest observational multicentre study evaluating qPCR for early diagnosis and treatment monitoring of PI in seronegative recipients of organs from seropositive donors. Of 34 patients admitted at 5 health centers, PI was detected by qPCR in 8 (23.5%) within a posttransplant period of 40 days (interquartile range [IQR], 31–50 days). No PI was detected by the Strout test or clinical symptoms/signs. All patients had favorable treatment outcome with negative qPCR 31 days (IQR, 18–35 days) after treatment, with no posttreatment relapse episodes.