bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome Regulation by Oncogenic ALK Pathway in Mammalian Cortical Development Revealed by Single-Cell RNA Sequencing
Authors: Mao Rui , Zhang Xiaoyun , Kong Youyong , Wu Shanshan , Huo Hai-qin , Kong Yue , Wang Zhen , Liu Yan , Jia Zhengping , Zhou Zikai 
Published: February 2021

Abstract
Precise regulation of embryonic neurodevelopment is crucial for proper structural organization and functioning of the adult brain. The key molecular machinery orchestrating this process remains unclear. Anaplastic lymphoma kinase (ALK) is an oncogenic receptor-type protein tyrosine kinase that is specifically and transiently expressed in developing nervous system. However, its role in the mammalian brain development is unknown. We found that transient embryonic ALK inactivation caused long-lasting abnormalities in the adult mouse brain, including impaired neuronal connectivity and cognition, along with delayed neuronal migration and decreased neuronal proliferation during neurodevelopment. scRNA-seq on human cerebral organoids revealed a delayed transition of cell-type composition. Molecular characterization identified a group of differentially expressed genes (DEGs) that were temporally regulated by ALK at distinct developmental stages. In addition to oncogenes, many DEGs found by scRNA-seq are associated with neurological or neuropsychiatric disorders. Our study demonstrates a pivotal role of oncogenic ALK pathway in neurodevelopment and characterized cell-type-specific transcriptome regulated by ALK for better understanding mammalian cortical development.
The vasculature: a therapeutic target in heart failure?
Authors: Luxán Guillermo , Dimmeler Stefanie 
Published: February 2021

AbstractIt is well established that the vasculature plays a crucial role in maintaining oxygen and nutrients supply to the heart. Increasing evidence further suggests that the microcirculation has additional roles in supporting a healthy microenvironment. Heart failure is well known to be associated with changes and functional impairment of the microvasculature. The specific ablation of protective signals in endothelial cells in experimental models is sufficient to induce heart failure. Therefore, restoring a healthy endothelium and microcirculation may be a valuable therapeutic strategy to treat heart failure. This review article will summarize the current understanding of the vascular contribution to heart failure with reduced or preserved ejection fraction. Novel therapeutic approaches including next generation pro-angiogenic therapies and non-coding RNA therapeutics, as well as the targeting of metabolites or metabolic signalling, vascular inflammation and senescence will be discussed.
Cardiac paraganglioma with sulfur subunit B gene mutation: a case report
Authors: Wu Chao , Yang Xu , Zhang Huimin , Song Yunhu 
Published: February 2021

Abstract

Background
Pheochromocytoma and paraganglioma is a rare disease with a prevalence of 0.2–0.6% in hypertensive patients from outpatient.

Case summary
A 21-year-old man complained of blood pressure elevation over one year and persistent hyperhidrosis near 5 years. In local hospital, a mass in the pericardial space with abundant blood flow was observed via echocardiography and confirmed under minimally invasive thoracotomy. With suspicion of malignant cardiac mass, the patient was recommended to transfer for further diagnosis and treatment. Combining evaluation for blood and urinary catecholamine levels, somatostatin receptor imaging, and iodine-131 metaiodobenzylguanidine scintigraphy, he was confirmed with the diagnosis of cardiac paraganglioma with blood supply from the right coronary artery identified via angiography. The cardiac tumour was then surgically resected and confirmed with a pathological diagnosis of paraganglioma. Subsequent genetic test suggested succinate dehydrogenase complex iron sulfur subunit B (SDHB) gene mutation. At 5-month follow-up, the patient was recovered with normal levels of blood catecholamines and catecholamine metabolites.

Discussion
Cardiac paraganglioma should be considered and evaluated in hypertensive patients with cardiac mass, even in non-typical population. Given a potential risk of developing malignancies, close follow-up is significant in patients with SDHB gene mutations.
Mid-term outcome of surgical treatment in patients with aorto-left ventricular tunnel
Authors: Liang Yu , Wang Jingjin , Li Dianyuan , Wan Linyuan , Gao Yiming , Liu Rui , Li Shoujun , Wang Hao , Pang Kunjing 
Published: February 2021

Abstract OBJECTIVESThe purpose of this study was to review the outcomes of surgical treatment in patients with aorto-left ventricular tunnel and to investigate what kind of patient cohort is more likely to have adverse events.METHODSTwenty-one patients with a median age of 6.58 [interquartile range (IQR) 4.17–24.50] years who received surgical treatment of aorto-left ventricular tunnel from March 2002 to December 2019 were reviewed. The median follow-up time was 64.50 (IQR 25.15–120.50) months. Clinical characteristics, surgical methods and follow-up outcomes were summarized in separate groups of patients with or without preoperative aortic valve (AoV) issues. Composite adverse events were defined as death or requirement of reoperation. Time-related analysis of freedom from death and requirement of reoperation was performed with the Kaplan–Meier method.RESULTSThe average tunnel size was 8.68 (standard deviation: 3.62) mm. The most common and the most important associated lesions were AoV lesions. Tunnels in 20 patients were closed with direct sutures or a patch. For 1 patient with an irreparable AoV, the tunnel was cut open simultaneously with aortic valve replacement and aortic root plasty. In the group of patients with preoperative AoV issues, 4 patients received aortic valve replacement with mechanical prosthetic valves and 6 patients received aortic valvuloplasty repair. The follow-up outcomes differed significantly between groups (the incidence of death was 15.38% and the incidence of requiring a reoperation was 46.15% in patients with preoperative AoV issues). In the group without preoperative AoV issues, there were no deaths and no reoperations (Fisher’s exact test; P = 0.018). The probability of freedom from death and of the requirement for reoperation between the 2 groups was not significantly different (log-rank, P = 0.09). Overall, the estimated probability of freedom from death and requirement of reoperation was 77.30% (standard error: 10.20%) [95% confidence interval (CI): 49.53–91.00] at 5 years, 67.64% (standard error: 12.70%) (95% CI: 36.71–85.84) at 10 years.CONCLUSIONSPatients with aorto-left ventricular tunnel with preoperative AoV issues are more prone to die or to require a reoperation. In contrast, patients without preoperative AoV issues can be free from death or reoperation for a longer period of time. Patients with preoperative AoV issues need much stricter postoperative long-term echocardiographic follow-up.
Transcriptome analysis ofCaenorhabditis eleganslacking heme peroxidase SKPO-1 reveals an altered response toEnterococcus faecalis
Authors: Liu Yi , Martinez-Martinez Daniel , Essmann Clara L , Cruz Melissa R , Cabreiro Filipe , Garsin Danielle A 
Published: February 2021

AbstractThe nematode Caenorhabditis elegans is commonly used as a model organism in studies of the host immune response. The worm encodes twelve peroxidase-cyclooxygenase superfamily members, making it an attractive model in which to study the functions of heme peroxidases. In previous work, loss of one of these peroxidases, SKPO-1 (ShkT-containing peroxidase), rendered C. elegans more sensitive to the human, Gram-positive pathogen Enterococcus faecalis. SKPO-1 was localized to the hypodermis of the animals where it also affected cuticle development as indicated by a morphological phenotype called “dumpy.” In this work, a better understanding of how loss of skpo-1 impacts both sensitivity to pathogen as well as cuticle development was sought by subjecting a deletion mutant of skpo-1 to transcriptome analysis using RNA sequencing following exposure to control (Escherichia coli) and pathogenic (E. faecalis) feeding conditions. Loss of skpo-1 caused a general upregulation of genes encoding collagens and other proteins related to cuticle development. On E. faecalis, these animals also failed to upregulate guanylyl cyclases that are often involved in environmental sensing. Hoechst straining revealed increased permeability of the cuticle and atomic force microscopy exposed the misalignment of the cuticular annuli and furrows. These findings provide a basis for better understanding of the morphological as well as the pathogen sensitivity phenotypes associated with loss of SKPO-1 function.
Convergence analysis of a numerical scheme for a tumour growth model
Authors: Droniou Jérôme , Nataraj Neela , Remesan Gopikrishnan C 
Published: February 2021

Abstract
A one–spatial dimensional tumour growth model Breward et al. ( 2001, 2002, 2003) that consists of three dependent variables of space and time is considered. These variables are volume fraction of tumour cells, velocity of tumour cells, and nutrient concentration. The model variables satisfy a coupled system of semilinear advection equation (hyperbolic), simplified linear Stokes equation (elliptic), and semilinear diffusion equation (parabolic) with appropriate conditions on the time–dependent boundary, which is governed by an ordinary differential equation. A reformulation of the model defined in a larger, fixed time–space domain is employed to overcome theoretical difficulties related to the time–dependent boundary. This reformulation reduces the complexity of the model by removing the need to explicitly track the time–dependent boundary. A numerical scheme that employs a finite volume method for the hyperbolic equation, a finite element method for the elliptic equation, and a backward Euler in time–mass lumped finite element in space method for the parabolic equation is developed. We establish the existence of a time interval $(0,T_{\ast })$ over which a convergent subsequence of the numerical approximations can be extracted using compactness techniques. The limit of any such convergent subsequence is proved to be a weak solution of the continuous model in an appropriate sense, which is called a threshold solution. Numerical tests and justifications that support the theoretical findings conclude the paper.
On Monge–Ampère Volumes of Direct Images
Authors: Finski Siarhei 
Published: February 2021

Abstract
This paper is devoted to the study of the asymptotics of Monge–Ampère volumes of direct images associated with high tensor powers of an ample line bundle. We study the leading term of this asymptotics and provide a classification of bundles saturating the topological bound of Demailly. In the special case of high symmetric powers of ample vector bundles, this provides a characterization of those admitting projectively flat Hermitian structures.
A platform for detecting cross-resistance in antibacterial drug discovery
Authors: Galarion Luiza H , Mohamad Merianne , Alzeyadi Zeyad , Randall Christopher P , O’Neill Alex J 
Published: February 2021

Abstract

Background
To address the growing antibiotic resistance problem, new antibacterial drugs must exert activity against pathogens resistant to agents already in use. With a view to providing a rapid means for deselecting antibacterial drug candidates that fail to meet this requirement, we report here the generation and application of a platform for detecting cross-resistance between established and novel antibacterial agents.

Methods
This first iteration of the cross-resistance platform (CRP) consists of 28 strains of defined resistance genotype, established in a uniform genetic background (the SH1000 strain of the clinically significant pathogen Staphylococcus aureus). Most CRP members were engineered through introduction of constitutively expressed resistance determinants on a low copy-number plasmid, with a smaller number selected as spontaneous resistant mutants.

Results
Members of the CRP collectively exhibit resistance to many of the major classes of antibacterial agent in use. We employed the CRP to test two antibiotics that have been proposed in the literature as potential drug candidates: γ-actinorhodin and batumin. No cross-resistance was detected for γ-actinorhodin, whilst a CRP member resistant to triclosan exhibited a 32-fold reduction in susceptibility to batumin. Thus, a resistance phenotype that already exists in clinical strains mediates profound resistance to batumin, implying that this compound is not a promising antibacterial drug candidate.

Conclusions
By detecting cross-resistance between established and novel antibacterial agents, the CRP offers the ability to deselect compounds whose activity is substantially impaired by existing resistance mechanisms. The CRP therefore represents a useful addition to the antibacterial drug discovery toolbox.
Assessing Risk of Breast Cancer: A Review of Risk Prediction Models
Authors: Kim Geunwon , Bahl Manisha 
Published: February 2021

Abstract
Accurate and individualized breast cancer risk assessment can be used to guide personalized screening and prevention recommendations. Existing risk prediction models use genetic and nongenetic risk factors to provide an estimate of a woman’s breast cancer risk and/or the likelihood that she has a BRCA1 or BRCA2 mutation. Each model is best suited for specific clinical scenarios and may have limited applicability in certain types of patients. For example, the Breast Cancer Risk Assessment Tool, which identifies women who would benefit from chemoprevention, is readily accessible and user-friendly but cannot be used in women under 35 years of age or those with prior breast cancer or lobular carcinoma in situ. Emerging research on deep learning-based artificial intelligence (AI) models suggests that mammographic images contain risk indicators that could be used to strengthen existing risk prediction models. This article reviews breast cancer risk factors, describes the appropriate use, strengths, and limitations of each risk prediction model, and discusses the emerging role of AI for risk assessment.
Detection ofRickettsia lusitaniaeAmongOrnithodoros sawaiiSoft Ticks Collected From Japanese Murrelet Seabird Nest Material From Gugul Island, Republic of Korea
Authors: Kim Heung-Chul , Jiang Ju , Hang Jun , Kim Su Yeon , Yun Seok-Min , Park Chang-uk , Kim Miran , Chong Sung-Tae , Farris Christina M , Richards Allen L , Klein Terry A 
Published: February 2021

AbstractIn a follow-up to the investigations of soft ticks identified from seabird nest soil and litter collected from coastal islands of the Republic of Korea (ROK), Ornithodoros sawaii and Ornithodoros capensis were assessed for the presence and identification of rickettsiae. Ticks collected from samples of 50–100 g of nest litter and soil from seabird nests were identified individually by morphological techniques, and species confirmed by sequencing of the mt-rrs gene. Subsequently, tick DNA preparations were screened for the presence of rickettsiae using a genus-specific nested PCR (nPCR) assay targeting the 17 kDa antigen gene. The amplicons from the 17 kDa assay and two additional nPCR assays targeting the gltA and ompB gene fragments were sequenced and used to identify the rickettsiae. A total of 134 soft ticks belonging to two species, O. sawaii Kitaoka & Suzuki 1973 (n = 125) and O. capensis Neumann 1901 (n = 9), were collected. Rickettsia lusitaniae DNA was detected and identified among O. sawaii ticks (n = 11, 8.8%) collected from nest litter and soil of the Japanese murrelet (Synthliboramphus wumizusume Temminck 1836) at Gugul Island along the western coastal area of the ROK. This study confirmed for the first time the presence of R. lusitaniae associated with O. sawaii collected from migratory seabird nests in the ROK.
A statistical measurement of the H i spin temperature in DLAs at cosmological distances
Authors: Allison James R 
Published: February 2021

ABSTRACT
Evolution of the cosmic star formation rate (SFR) and molecular gas mass density is expected to be matched by a similarly strong evolution of the fraction of atomic hydrogen (H i) in the cold neutral medium (CNM). We use results from a recent commissioning survey for intervening 21-cm absorbers with the Australian Square Kilometre Array Pathfinder (ASKAP) to construct a Bayesian statistical model of the NH i-weighted harmonic mean spin temperature (Ts) at redshifts between z = 0.37 and 1.0. We find that Ts ≤ 274 K with 95 per cent probability, suggesting that at these redshifts the typical H i gas in galaxies at equivalent DLA column densities may be colder than the Milky Way interstellar medium (Ts, MW ∼ 300 K). This result is consistent with an evolving CNM fraction that mirrors the molecular gas towards the SFR peak at z ∼ 2. We expect that future surveys for H i 21-cm absorption with the current SKA pathfinder telescopes will provide constraints on the CNM fraction that are an order of magnitude greater than presented here.
Compact groups from semi-analytical models of galaxy formation – II. Different assembly channels
Authors: Díaz-Giménez E , Zandivarez A , Mamon G A 
Published: February 2021

ABSTRACTWe study the formation of over 6000 compact groups (CGs) of galaxies identified in mock redshift-space galaxy catalogues built from semi-analytical models of galaxy formation (SAMs) run on the Millennium Simulations. We select CGs of four members in our mock SDSS galaxy catalogues and, for each CG, we trace back in time the real-space positions of the most massive progenitors of their four galaxies. By analysing the evolution of the distance of the galaxy members to the centre of mass of the group, we identify four channels of CG formation. The classification of these assembly channels is performed with an automatic recipe inferred from a preliminary visual inspection and based on the orbit of the galaxy with the fewest number of orbits. Most CGs show late assembly, with the last galaxy arriving on its first or second passage, while only 10–20 per cent form by the gradual contraction of their orbits by dynamical friction, and only a few per cent forming early with little subsequent contraction. However, a SAM from a higher resolution simulation leads to earlier assembly. Assembly histories of CGs also depend on cosmological parameters. At similar resolution, CGs assemble later in SAMs built on parent cosmological simulations of high density parameter. Several observed properties of mock CGs correlate with their assembly history: early-assembling CGs are smaller, with shorter crossing times, and greater magnitude gaps between their brightest two members, and their brightest galaxies have smaller spatial offsets and are more passive.
Parallel Genomic Changes Drive Repeated Evolution of Placentas in Live-Bearing Fish
Authors: van Kruistum Henri , Nijland Reindert , Reznick David N , Groenen Martien A M , Megens Hendrik-Jan , Pollux Bart J A 
Published: February 2021

Abstract
The evolutionary origin of complex organs challenges empirical study because most organs evolved hundreds of millions of years ago. The placenta of live-bearing fish in the family Poeciliidae represents a unique opportunity to study the evolutionary origin of complex organs, because in this family a placenta evolved at least nine times independently. It is currently unknown whether this repeated evolution is accompanied by similar, repeated, genomic changes in placental species. Here, we compare whole genomes of 26 poeciliid species representing six out of nine independent origins of placentation. Evolutionary rate analysis revealed that the evolution of the placenta coincides with convergent shifts in the evolutionary rate of 78 protein-coding genes, mainly observed in transporter- and vesicle-located genes. Furthermore, differences in sequence conservation showed that placental evolution coincided with similar changes in 76 noncoding regulatory elements, occurring primarily around genes that regulate development. The unexpected high occurrence of GATA simple repeats in the regulatory elements suggests an important function for GATA repeats in developmental gene regulation. The distinction in molecular evolution observed, with protein-coding parallel changes more often found in metabolic and structural pathways, compared with regulatory change more frequently found in developmental pathways, offers a compelling model for complex trait evolution in general: changing the regulation of otherwise highly conserved developmental genes may allow for the evolution of complex traits.
Single-molecule insight into stalled replication fork rescue inEscherichia coli
Authors: Bianco Piero R , Lu Yue 
Published: February 2021

AbstractDNA replication forks stall at least once per cell cycle in Escherichia coli. DNA replication must be restarted if the cell is to survive. Restart is a multi-step process requiring the sequential action of several proteins whose actions are dictated by the nature of the impediment to fork progression. When fork progress is impeded, the sequential actions of SSB, RecG and the RuvABC complex are required for rescue. In contrast, when a template discontinuity results in the forked DNA breaking apart, the actions of the RecBCD pathway enzymes are required to resurrect the fork so that replication can resume. In this review, we focus primarily on the significant insight gained from single-molecule studies of individual proteins, protein complexes, and also, partially reconstituted regression and RecBCD pathways. This insight is related to the bulk-phase biochemical data to provide a comprehensive review of each protein or protein complex as it relates to stalled DNA replication fork rescue.
Cardiovascular calcifications in kidney transplant recipients
Authors: Podestà Manuel Alfredo , Cucchiari David , Ciceri Paola , Messa Piergiorgio , Torregrosa José-Vicente , Cozzolino Mario 
Published: February 2021

Abstract
Vascular and valvular calcifications are highly prevalent in kidney transplant recipients (KTRs) and are associated with an increased risk of cardiovascular events, which represent the leading cause of long-term mortality in these patients. However, cardiovascular calcification has been traditionally considered as a condition mostly associated with advanced chronic kidney disease stages and dialysis, and comparatively fewer studies have assessed its impact after kidney transplantation. Despite partial or complete resolution of uraemia-associated metabolic derangements, KTRs are still exposed to several pro-calcifying stimuli that favour the progression of pre-existing vascular calcifications or their de novo development. Traditional risk factors, bone mineral disorders, inflammation, immunosuppressive drugs and deficiency of calcification inhibitors may all play a role, and strategies to correct or minimize their effects are urgently needed. The aim of this work is to provide an overview of established and putative mediators involved in the pathogenesis of cardiovascular calcification in kidney transplantation, and to describe the clinical and radiological features of these forms. We also discuss current evidence on preventive strategies to delay the progression of cardiovascular calcifications in KTRs, as well as novel therapeutic candidates to potentially prevent their long-term deleterious effects.