bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do genomic passports leave us more vulnerable or less vulnerable? Perspectives from an online citizen engagement
Authors: Mayeur Chloé , Mertes Heidi , Van Hoof Wannes 
Published: March 2023

AbstractSince genomics is becoming commonplace in healthcare for the diagnosis, treatment, and prevention, the prospect of generating a genomic passport for all citizens is gaining traction. While this would have many advantages, it raises ethical issues requiring societal debate alongside academic reflection. Hence, Sciensano—the Belgian scientific Institute of Public Health—organised an online citizen engagement on genomic information usage, including a question on a genomic passport for all. The inductive thematic analysis of participants’ contributions highlighted vulnerability as a fundamental concern, while this has not received sufficient attention so far in genomics. Participants expressed their vulnerability in two ways. First, the genomic passport would inform them about their ontological vulnerability. By revealing their constitutional weaknesses (predisposition to diseases), it reminds them that everyone is unavoidably and perennially at risk of being harmed. Second, the misuse of the genomic passport can add situational vulnerabilities (e.g., discrimination causing psychological and economic harm). Moreover, the fundamental uncertainty in genomics—how will such sensitive information be used, and how will the science evolve?—exacerbates these vulnerabilities. This article ends with recommendations to alleviate these vulnerabilities in genomics now and in the future in which the genomic passport may become a reality.
Implementation of an HIV RNA Qualitative PCR Assay in an HIV Diagnostic Algorithm: A Single-Institution Experience
Authors: Medeiros Isabela , Vadlamudi Charitha , Doonan Katie , Nielsen Marisa C , Miller Nancy S 
Published: March 2023

Abstract

Objectives
Boston Medical Center (BMC) is a private, not-for-profit 514-bed academic medical center and legacy safety net hospital serving a diverse global patient population. BMC recently implemented a new HIV-1/HIV-2 Qualitative RNA PCR (HIV RNA QUAL) cleared by the US Food and Drug Administration to (1) replace antibody discrimination follow-up testing after a reactive fourth-generation (4G) serology screen and (2) use as a stand-alone diagnostic for suspected seronegative acute HIV infection.

Methods
This report summarizes the results of a production monitor for the first 3 months postimplementation.

Results
The monitor characterized test utilization, diagnostic turnaround time, impact on send-out testing, results reflexed to HIV RNA discrimination follow-up, and discrepancies between screening and HIV RNA results that necessitated additional investigation. Another element was the novelty of using HIV RNA QUAL while awaiting the existing Centers for Disease Control and Prevention HIV testing algorithm update. The 4G screening components and the HIV RNA QUAL were also used to create an algorithm specific to and compliant with current guidelines for screening patients on HIV preexposure prophylaxis.

Conclusions
Based on our findings, this new test algorithm may be reproducible and instructive at other institutions.
Chemical and genetic carotenoid deficiency delays growth in dark-grownEuglena gracilis
Authors: Tamaki Shun , Koshitsuka Yuki , Miyamoto Koji , Ishikawa Takahiro , Shinomura Tomoko 
Published: March 2023

ABSTRACTLight-independent functions of carotenoids in photosynthetic organisms are poorly understood. Here, we investigated the growth properties of microalga, Euglena gracilis, under altered light and temperature using norflurazon-treated carotenoid-deficient cells and genetically modified strains, including nonphotosynthetic SM-ZK and colorless cl4. Norflurazon treatment decreased carotenoid and chlorophyll contents, causing cell bleaching. SM-ZK strain had lower carotenoid content than wild-type (WT) strain, and it was below the detectable level in the cl4 strain. Norflurazon treatment decreased phytoene synthase EgCrtB levels, although EgcrtB was transcriptionally induced. Carotenoid deficiency in norflurazon-treated cells and the cl4 strain caused similar extents of delayed growth under light and dark conditions at 25 °C, indicating that carotenoids promote growth in darkness. Both WT and SM-ZK strains exhibited similar growth rates. Dark conditions at 20 °C enhanced the growth delay of norflurazon-treated cells and the cl4 strain. These results indicate that carotenoids impart environmental stress tolerance to E. gracilis in light-dependent and light-independent manners.
scGAD: a new task and end-to-end framework for generalized cell type annotation and discovery
Authors: Zhai Yuyao , Chen Liang , Deng Minghua 
Published: March 2023

AbstractThe rapid development of single-cell RNA sequencing (scRNA-seq) technology allows us to study gene expression heterogeneity at the cellular level. Cell annotation is the basis for subsequent downstream analysis in single-cell data mining. As more and more well-annotated scRNA-seq reference data become available, many automatic annotation methods have sprung up in order to simplify the cell annotation process on unlabeled target data. However, existing methods rarely explore the fine-grained semantic knowledge of novel cell types absent from the reference data, and they are usually susceptible to batch effects on the classification of seen cell types. Taking into consideration the limitations above, this paper proposes a new and practical task called generalized cell type annotation and discovery for scRNA-seq data whereby target cells are labeled with either seen cell types or cluster labels, instead of a unified ‘unassigned’ label. To accomplish this, we carefully design a comprehensive evaluation benchmark and propose a novel end-to-end algorithmic framework called scGAD. Specifically, scGAD first builds the intrinsic correspondences on seen and novel cell types by retrieving geometrically and semantically mutual nearest neighbors as anchor pairs. Together with the similarity affinity score, a soft anchor-based self-supervised learning module is then designed to transfer the known label information from reference data to target data and aggregate the new semantic knowledge within target data in the prediction space. To enhance the inter-type separation and intra-type compactness, we further propose a confidential prototype self-supervised learning paradigm to implicitly capture the global topological structure of cells in the embedding space. Such a bidirectional dual alignment mechanism between embedding space and prediction space can better handle batch effect and cell type shift. Extensive results on massive simulation datasets and real datasets demonstrate the superiority of scGAD over various state-of-the-art clustering and annotation methods. We also implement marker gene identification to validate the effectiveness of scGAD in clustering novel cell types and their biological significance. To the best of our knowledge, we are the first to introduce this new and practical task and propose an end-to-end algorithmic framework to solve it. Our method scGAD is implemented in Python using the Pytorch machine-learning library, and it is freely available at https://github.com/aimeeyaoyao/scGAD.
DRdriver: identifying drug resistance driver genes using individual-specific gene regulatory network
Authors: Huang Yu-e , Zhou Shunheng , Liu Haizhou , Zhou Xu , Yuan Mengqin , Hou Fei , Chen Sina , Chen Jiahao , Wang Lihong , Jiang Wei 
Published: March 2023

AbstractDrug resistance is one of principal limiting factors for cancer treatment. Several mechanisms, especially mutation, have been validated to implicate in drug resistance. In addition, drug resistance is heterogeneous, which makes an urgent need to explore the personalized driver genes of drug resistance. Here, we proposed an approach DRdriver to identify drug resistance driver genes in individual-specific network of resistant patients. First, we identified the differential mutations for each resistant patient. Next, the individual-specific network, which included the genes with differential mutations and their targets, was constructed. Then, the genetic algorithm was utilized to identify the drug resistance driver genes, which regulated the most differentially expressed genes and the least non-differentially expressed genes. In total, we identified 1202 drug resistance driver genes for 8 cancer types and 10 drugs. We also demonstrated that the identified driver genes were mutated more frequently than other genes and tended to be associated with the development of cancer and drug resistance. Based on the mutational signatures of all driver genes and enriched pathways of driver genes in brain lower grade glioma treated by temozolomide, the drug resistance subtypes were identified. Additionally, the subtypes showed great diversity in epithelial–mesenchyme transition, DNA damage repair and tumor mutation burden. In summary, this study developed a method DRdriver for identifying personalized drug resistance driver genes, which provides a framework for unlocking the molecular mechanism and heterogeneity of drug resistance.
Linear: a framework to enable existing software to resolve structural variants in long reads with flexible and efficient alignment-free statistical models
Authors: Pan Chenxu , Rahn René , Heller David , Reinert Knut 
Published: March 2023

AbstractAlignment is the cornerstone of many long-read pipelines and plays an essential role in resolving structural variants (SVs). However, forced alignments of SVs embedded in long reads, inflexibility of integrating novel SVs models and computational inefficiency remain problems. Here, we investigate the feasibility of resolving long-read SVs with alignment-free algorithms. We ask: (1) Is it possible to resolve long-read SVs with alignment-free approaches? and (2) Does it provide an advantage over existing approaches? To this end, we implemented the framework named Linear, which can flexibly integrate alignment-free algorithms such as the generative model for long-read SV detection. Furthermore, Linear addresses the problem of compatibility of alignment-free approaches with existing software. It takes as input long reads and outputs standardized results existing software can directly process. We conducted large-scale assessments in this work and the results show that the sensitivity, and flexibility of Linear outperform alignment-based pipelines. Moreover, the computational efficiency is orders of magnitude faster.
GPTree Cluster: phylogenetic tree cluster generator in the context of supertree inference
Authors: Koshkarov Aleksandr , Tahiri Nadia 
Published: March 2023

AbstractSummaryFor many years, evolutionary and molecular biologists have been working with phylogenetic supertrees, which are oriented acyclic graph structures. In the standard approaches, supertrees are obtained by concatenating a set of phylogenetic trees defined on different but overlapping sets of taxa (i.e. species). More recent approaches propose alternative solutions for supertree inference. The testing of new metrics for comparing supertrees and adapting clustering algorithms to overlapping phylogenetic trees with different numbers of leaves requires large amounts of data. In this context, designing a new approach and developing a computer program to generate phylogenetic tree clusters with different numbers of overlapping leaves are key elements to advance research on phylogenetic supertrees and evolution. The main objective of the project is to propose a new approach to simulate clusters of phylogenetic trees defined on different, but mutually overlapping, sets of taxa, with biological events. The proposed generator can be used to generate a certain number of clusters of phylogenetic trees in Newick format with a variable number of leaves and with a defined level of overlap between trees in clusters.Availability and implementationA Python script version 3.7, called GPTree Cluster, which implements the discussed approach, is freely available at: https://github.com/tahiri-lab/GPTree/tree/GPTreeCluster
Semiparametric counterfactual density estimation
Authors: Kennedy E H , Balakrishnan S , Wasserman L A 
Published: March 2023

AbstractCausal effects are often characterized with averages, which can give an incomplete picture of the underlying counterfactual distributions. Here we consider estimating the entire counterfactual density and generic functionals thereof. We focus on two kinds of target parameters: density approximations and the distance between counterfactual densities. We study nonparametric efficiency bounds, giving results for smooth but otherwise generic models and distances. Importantly, we show how these bounds connect to means of particular nontrivial functions of counterfactuals, linking the problems of density and mean estimation. We propose doubly robust-style estimators, and study their rates of convergence, showing that they can be optimally efficient in large nonparametric models. We also give analogous methods for model selection and aggregation, when many models may be available and of interest. Our results all hold for generic models and distances, but we highlight results for L2 projections on linear models and Kullbach–Leibler projections on exponential families. Finally, we illustrate our method by estimating the density of the CD4 count among patients with HIV, had all been treated with combination therapy versus zidovudine alone, as well as a density effect. Our methods are implemented in the R package npcausal on GitHub.
Morphological factors associated with progression of subaneurysmal aortas
Authors: Thorbjørnsen Knut , Svensjö Sverker , Mani Kevin , Wanhainen Anders 
Published: March 2023

Abstract

Background
The aim of this population-based cohort study was to assess the association between aortic morphological baseline factors in 65-year-old men with subaneurysmal aortic diameter (25–29 mm) and risk of later progression to abdominal aortic aneurysm (AAA) generally considered to be at a diameter for repair (at least 55 mm).

Methods
Men with a screening-detected subaneurysmal aorta between 2006 and 2015 in mid-Sweden were re-examined using ultrasonography after 5 and 10 years. Cut-off values for baseline subaneurysmal aortic diameter, aortic size index, aortic height index, and relative aortic diameter (with respect to proximal aorta) were analysed using receiver operating characteristic (ROC) curves, and their associations with progression to AAA diameter at least 55 mm evaluated by means of Kaplan–Meier curves and a multivariable Cox proportional hazard analysis adjusted for traditional risk factors.

Results
Some 941 men with a subaneurysmal aorta and median follow-up of 6.6 years were identified. The cumulative incidence of AAA diameter at least 55 mm at 10.5 years was 28.5 per cent for an aortic size index of 13.0 mm/m2 or more (representing 45.2 per cent of the population) versus 1.1 per cent for an aortic size index of less than 13.0 mm/m2 (HR 9.1, 95 per cent c.i. 3.62 to 22.85); 25.8 per cent for an aortic height index of at least 14.6 mm/m (58.0 per cent of the population) versus 2.0 per cent for an aortic height index of less than 14.6 mm/m (HR 5.2, 2.23 to 12.12); and 20.7 per cent for subaneurysmal aortic diameter 26 mm or greater (73.6 per cent of the population) versus 1.0 per cent for a diameter of less than 26 mm (HR 5.9, 1.84 to 18.95). Relative aortic diameter quotient (HR 1.2, 0.54 to 2.63) and difference (HR 1.3, 0.57 to 3.12) showed no association with development of AAA of 55 mm or greater.

Conclusion
Baseline subaneurysmal aortic diameter, aortic size index, and aortic height index were all independently associated with progression to AAA at least 55 mm, with aortic size index as the strongest predictor, whereas relative aortic diameter was not. These morphological factors may be considered for stratification of follow-up at initial screening.
Genetic variables, population features and reproductive success ofGymnocalycium monvillei(Cactaceae) along an altitudinal gradient
Authors: Bauk Karen , Gurvich Diego E , Liber Zlatko , Šatović Zlatko , Las Peñas M Laura 
Published: March 2023

AbstractAltitudinal gradients in mountain environments impose selection pressures that could result in marked heterogeneity in genetic characteristics, population features and reproductive success. Most Cactaceae occur in arid and semi-arid areas of the American continent, from sea level to 4500 m a.s.l., and some species have wide altitudinal ranges. The aim of this work was to analyse how cytogenetic features (mitotic chromosomes analysed using molecular cytogenetic techniques, DNA content estimated by flow cytometry), amplified fragment length polymorphism genetic diversity, population features (population density and individual size) and reproductive success (seeds per plant and fruit production) are related to an altitudinal gradient in five sites of Gymnocalycium monvillei located between 878 and 2230 m a.s.l. Our results showed that the sites at three intermediate altitude have optimal conditions as greatest genetic diversity, highest population density and highest seed production, whereas extreme sites are characterized by greatest reproductive isolation and highest DNA content and seed mass. The results indicate that the species has various mechanisms to survive along altitudinal gradients.
Single-cell transcriptome analysis reveals endometrial immune microenvironment in minimal/mild endometriosis
Authors: Huang Xin , Wu Lukanxuan , Pei Tianjiao , Liu Dong , Liu Chang , Luo Bin , Xiao Li , Li Yujing , Wang Ruiying , Ouyang Yunwei , Zhu Huili , Huang Wei 
Published: March 2023

AbstractEndometriosis is a common inflammatory disorder in women of reproductive age due to an abnormal endometrial immune environment and is associated with infertility. This study aimed to systematically understand the endometrial leukocyte types, inflammatory environment, and impaired receptivity at single-cell resolution. We profiled single-cell RNA transcriptomes of 138 057 endometrial cells from endometriosis patients (n = 6) and control (n = 7), respectively, using 10x Genomics platform. We found that one cluster of epithelial cells that expressed PAEP and CXCL14 was mostly from the control during the window of implantation (WOI). This epithelial cell type is absent in the eutopic endometrium during the secretory phase. The proportion of endometrial immune cells decreased in the secretory phase in the control group, whereas the cycle variation of total immune cells, NK cells, and T cells was absent in endometriosis. Endometrial immune cells secreted more IL-10 in the secretory phase than in the proliferative phase in the control group; the opposite trend was observed in endometriosis. Proinflammatory cytokines levels in the endometrial immune cells were higher in endometriosis than in the control group. Trajectory analysis revealed that the secretory phase epithelial cells decreased in endometriosis. Ligand–receptor analysis revealed that 11 ligand–receptor pairs were upregulated between endometrial immune and epithelial cells during WOI. These results provide new insights into the endometrial immune microenvironment and impaired endometrial receptivity in infertile women with minimal/mild endometriosis.
Left ventricular pseudoaneurysm in Lemierre’s syndrome: a case report
Authors: Gall Alexander , Sandhu Manraj Singh , Ahmed Eltayeb Mohamed , McAloon Christopher James 
Published: March 2023

AbstractBackgroundLemierre’s syndrome is an infectious phenomenon characterized by oropharyngeal infection with bacteraemia, thrombophlebitis, and distant septic emboli. Septic emboli are a recognized cause of a Type 2 myocardial infarction, with a left ventricular pseudoaneurysm being a rare but important complication of this.Case summaryA 19-year-old male presented with acute confusion, fevers, and a cough. Blood cultures were positive for Fusobacterium necrophorum and initial imaging showed a cavitating pneumonia. Further evaluation revealed septic emboli in the distal digits and brain. The patient initially responded to antibiotic therapy but developed chest pain with increased troponin levels. An electrocardiogram showed inferolateral ST elevation. A transthoracic echocardiogram (TTE) showed hypokinaesia of the mid to apical lateral wall, and a computed tomography (CT) scan showed a pericardial effusion with a possible purulent effusion or abscess. The patient underwent surgical drainage of a sterile effusion. A post-operative TTE and CT demonstrated a left ventricular pseudoaneurysm that was surgically repaired. The venous thrombus was encountered intra-operatively confirming a diagnosis of Lemierre’s syndrome. The patient completed the regimen of antibiotics and showed a good post-operative recovery.DiscussionThis is the first case described of left ventricular pseudoaneurysm as a complication of Lemierre’s syndrome. It highlights not only the importance of serial, multimodality imaging in both diagnostic workup and identification of complications, but also the importance of a multidisciplinary team in the management of patients with complex and rare presentations.
Modern tools in cardiac imaging to assess myocardial inflammation and infection
Authors: Hutt Erika , Kaur Simrat , Jaber Wael A 
Published: March 2023

Abstract
Myocardial forms of infection and inflammation are highly heterogeneous in clinical course and presentation but associated with diagnostic and treatment uncertainty, high morbidity, mortality, and financial burden. Historically, these pathologies were diagnosed invasively with biopsy, surgical pathology, or explanted hearts. However, in the current era, the diagnosis has been aided by a variety of non-invasive imaging tools in the appropriate clinical presentation. This review provides a comprehensive understanding of the available imaging modalities for guiding the diagnosis, treatment, and prognosis of cardiac infection and inflammation.
Malocclusions, pathologic tooth migration, and the need for orthodontic treatment in subjects with stage III–IV periodontitis. A cross-sectional study
Authors: Zasčiurinskienė Eglė , Rastokaitė Liveta , Lindsten Rune , Basevičienė Nomeda , Šidlauskas Antanas 
Published: March 2023

SummaryBackgroundLiterature is scarce on malocclusion prevalence and orthodontic treatment need (OTN) in subjects with stage III–IV periodontitis. Study aims were to assess prevalence of primary and secondary malocclusions in subjects with stage III–IV periodontitis and OTN based on pathologic tooth migration (PTM) and occlusal trauma of anterior teeth (AT).Subjects and methodsOne hundred and twenty-one subjects with stage III–IV periodontitis were examined. A comprehensive periodontal–orthodontic examination was performed. Exclusion criteria: age &lt;30 years, removable prosthetics, uncontrolled diabetes, pregnancy/lactation, and oncologic disease.ResultsClass II malocclusion was found in 49.6% (Class II div 1—20.7%, Class II div 2—9.9%, subdivision Class II—19.0%), Class I—31.4%, Class III—10.7%, no malocclusion—8.3% of subjects. PTM was observed in 74.4% of maxillary and 60.3% of mandibular AT. Spacing and extrusion were the main types of PTM of AT. Odds ratio for PTM of maxillary AT was 9.3 in cases with &gt;30% of sites with clinical attachment loss ≥5 mm (P = 0.001). Spacing of maxillary AT was influenced by periodontitis, Class III malocclusion, and lost teeth. Tongue habit had impact on spacing of mandibular AT. Dental Health Component of Index of Orthodontic Treatment Need yielded that OTN was found in &gt;50% and OTN due PTM, occlusal trauma and impaired function in 66.1% of subjects.ConclusionsThe most prevalent malocclusion was Class II. Spacing and extrusion were prevalent types of PTM of AT. OTN was found in more than half of the subjects. The study highlights the need for preventive measures for PTM in subjects with stage III–IV periodontitis.