bluuebunny/crossref_metadata_2025_split huggingface dataset:
CoreDetector: a flexible and efficient program for core-genome alignment of evolutionary diverse genomes
Authors: Fruzangohar Mario , Moolhuijzen Paula , Bakaj Nicolette , Taylor Julian 
Published: October 2023

Abstract

Motivation
Whole genome alignment of eukaryote species remains an important method for the determination of sequence and structural variations and can also be used to ascertain the representative non-redundant core-genome sequence of a population. Many whole genome alignment tools were first developed for the more mature analysis of prokaryote species with few current tools containing the functionality to process larger genomes of eukaryotes as well as genomes of more divergent species. In addition, the functionality of these tools becomes computationally prohibitive due to the significant compute resources needed to handle larger genomes.

Results
In this research, we present CoreDetector, an easy-to-use general-purpose program that can align the core-genome sequences for a range of genome sizes and divergence levels. To illustrate the flexibility of CoreDetector, we conducted alignments of a large set of closely related fungal pathogen and hexaploid wheat cultivar genomes as well as more divergent fly and rodent species genomes. In all cases, compared to existing multiple genome alignment tools, CoreDetector exhibited improved flexibility, efficiency, and competitive accuracy in tested cases.

Availability and implementation
CoreDetector was developed in the cross platform, and easily deployable, Java language. A packaged pipeline is readily executable in a bash terminal without any external need for Perl or Python environments. Installation, example data, and usage instructions for CoreDetector are freely available from https://github.com/mfruzan/CoreDetector.
LexicHash: sequence similarity estimation via lexicographic comparison of hashes
Authors: Greenberg Grant , Ravi Aditya Narayan , Shomorony Ilan 
Published: October 2023

Abstract

Motivation
Pairwise sequence alignment is a heavy computational burden, particularly in the context of third-generation sequencing technologies. This issue is commonly addressed by approximately estimating sequence similarities using a hash-based method such as MinHash. In MinHash, all k-mers in a read are hashed and the minimum hash value, the min-hash, is stored. Pairwise similarities can then be estimated by counting the number of min-hash matches between a pair of reads, across many distinct hash functions. The choice of the parameter k controls an important tradeoff in the task of identifying alignments: larger k-values give greater confidence in the identification of alignments (high precision) but can lead to many missing alignments (low recall), particularly in the presence of significant noise.

Results
In this work, we introduce LexicHash, a new similarity estimation method that is effectively independent of the choice of k and attains the high precision of large-k and the high sensitivity of small-k MinHash. LexicHash is a variant of MinHash with a carefully designed hash function. When estimating the similarity between two reads, instead of simply checking whether min-hashes match (as in standard MinHash), one checks how “lexicographically similar” the LexicHash min-hashes are. In our experiments on 40 PacBio datasets, the area under the precision–recall curves obtained by LexicHash had an average improvement of 20.9% over MinHash. Additionally, the LexicHash framework lends itself naturally to an efficient search of the largest alignments, yielding an O(n) time algorithm, and circumventing the seemingly fundamental O(n2) scaling associated with pairwise similarity search.

Availability and implementation
LexicHash is available on GitHub at https://github.com/gcgreenberg/LexicHash.
Assessing the Impact of the COVID-19 Pandemic on the Severity of Pediatric Inflammatory Bowel Disease Admissions and New Diagnoses
Authors: Waschmann Malika , Stuart Ariana , Trieschmann Kimberly , Lin Henry C , Hunter Anna K 
Published: October 2023

Abstract

Introduction
The COVID-19 pandemic has introduced new challenges to the diagnosis and management of pediatric inflammatory bowel disease (IBD). Many patients have had only limited access to their providers through telemedicine, and many chose to delay nonemergent treatment.

Methods
A retrospective chart review of patients with IBD seen by the Pediatric Gastroenterology Division at Doernbecher Children’s Hospital from January 2018 to August 2021 was conducted. The study cohort was divided into 2 groups: those presenting before the onset of the COVID-19 pandemic (January 1, 2018 to February 28, 2020) and those presenting during the pandemic (March 1, 2020 to August 1, 2021). Variables collected included: age, sex, race, ethnicity, IBD type, insurance type, location of residence. Primary outcome measures selected focused on disease severity, initial type of treatment, or surgical intervention offered. A subgroup analysis of the new diagnosis patients was performed. Data were analyzed using independent t-tests, chi-squared analysis, and Wilcoxon rank sum tests.

Results
Two hundred and eleven patients met inclusion criteria, 107 (72 new diagnoses, 35 admissions) within the pre-COVID epoch and 104 (67 new diagnoses, 37 admissions) within the during-COVID epoch. Patients in the during-COVID epoch had higher fecal calprotectin level and were more likely to be started on a biologic as initial treatment. Patients admitted during COVID for IBD flare were more likely to require surgical intervention. Subgroup analysis of newly diagnosed patients revealed higher incidence of comorbid depression and anxiety.

Conclusions
Our review identified increased disease severity in newly diagnosed pediatric patients with IBD as well as pediatric patients admitted for flare during COVID. Increases in anxiety and depression rates during COVID may have contributed to worsened disease severity.
A rare presentation of acute myocarditis as a manifestation of adult-onset Still’s disease: a case report
Authors: Dick Michael , Innes-Jones Kyra , Arri Satpal 
Published: October 2023

Abstract

Background
Adult-onset Still’s disease (AOSD) is a rare systemic autoinflammatory condition characterized by a classical triad of symptoms that include prolonged fever, polyarthritis, and a characteristic salmon-pink skin rash. It can affect a variety of organ systems resulting in many different clinical presentations and is usually a diagnosis of exclusion. Myocarditis complicated by cardiogenic shock is a rare and life-threatening manifestation of AOSD, typically affecting younger patients. There is a limited experience and evidence in how best to manage this challenging patient cohort.

Case summary
A previously fit and well 22-year-old male presented with fever, arthralgia, and general malaise. On clinical examination, he was pyrexial and hypotensive, requiring vasopressor support for presumed septic shock. Subsequent transthoracic echocardiography and cardiac MRI findings were in keeping with fulminant myocarditis. Further septic and auto-immune screens were negative although he responded well to high-dose intravenous corticosteroids. Attempts to wean immunosuppression were unsuccessful, and his ferritin was markedly elevated (20 233 μg/L). A diagnosis of AOSD was suspected after exclusion of other possible causes. The successful addition of tocilizumab (an interleukin-6 receptor antagonist) therapy allowed for gradual de-escalation of steroid therapy and disease remission, with on-going remission at 18 months on maintenance therapy.

Discussion
This case highlights the importance of considering AOSD as a rare cause for myocarditis, especially when fever is present, or disease is severe. Failure to improve with first-line therapy involving high-dose corticosteroids, or inability to wean that therapy, should prompt consideration for escalation of therapy, with tocilizumab seemingly an effective treatment option.
Right heart echocardiography findings in hypoxic pneumonia patients during the COVID-19 pandemic in a South African population
Authors: van Blydenstein S A , Omar S , Jacobson B , Menezes C N , Meel R 
Published: October 2023

Abstract

Aims
The right ventricle is affected by Coronavirus disease 19 (COVID-19) via multiple mechanisms, which can result in right ventricular dysfunction (RVD). This study aimed to provide an assessment of right heart function using conventional echocardiography and advanced strain imaging, in patients with hypoxic pneumonia during the COVID-19 pandemic.

Methods and results
This study was an observational, prospective, single-centre study, including adults with hypoxic pneumonia, in two groups: COVID-19 pneumonia; and non-COVID-19 pneumonia. Bedside echocardiography was performed according to a pre-specified protocol and all right heart measurements were done as per standard guidelines. Right ventricular free wall strain (RVFWS) was measured using Philips® QLAB 11.0 speckle tracking software. Descriptive and comparative statistics were used to analyse data. Spearman Rank Order Correlations were used to determine the correlation between right ventricular (RV) parameters and clinical parameters. Univariate and multivariate logistic regression analyses were performed to characterize the predictors of in-hospital mortality. We enrolled 48 patients with COVID-19 pneumonia and 24 with non-COVID-19 pneumonia. COVID-19 patients were significantly older with a higher frequency of hypertension and diabetes and a trend towards a lower severity of illness score. Mean RVFWS yielded the highest estimates for the prevalence of RVD (81%), with no difference between the two pneumonia groups. Median Tricuspid Annular Plane Systolic Excursion (TAPSE) and right ventricular systolic excursion velocity (RVS’) were not significantly different between COVID-19 (TAPSE 17.2 and RVS’ 12), and non-COVID-19 pneumonia (TAPSE 17.8 and RVS’ 12.1) with P values of 0.29 and 0.86, respectively. Non-COVID-19 pneumonia patients with moderate to severe hypoxaemia (PF &lt; 150) were at greater risk of an elevated RV Systolic Pressure &gt;30 mmHg respiratory rate = 3.25 (CI 1.35–7.82) on admission. Troponin levels discriminated between COVID-19 survivors (6 ng/L) and non-survivors (13 ng/L), P = 0.04. The mortality rate for COVID-19 was high (27%) compared to non-COVID-19 pneumonia (12%).

Conclusion
Patients with COVID-19 pneumonia had a similar admission prevalence of RVD when compared to patients with non-COVID-19 pneumonia. Despite preserved traditional parameters of RV systolic function, RVFWS was diminished in both groups, and we propose that RVFWS serves as an important marker of the subclinical disease of RV.
Non-invasive left ventricular pressure-volume loops from cardiovascular magnetic resonance imaging and brachial blood pressure: validation using pressure catheter measurements
Authors: Arvidsson Per M , Green Peregrine G , Watson William D , Shanmuganathan Mayooran , Heiberg Einar , De Maria Giovanni Luigi , Arheden Håkan , Herring Neil , Rider Oliver J 
Published: October 2023

Abstract

Aims
Left ventricular (LV) pressure-volume (PV) loops provide gold-standard physiological information but require invasive measurements of ventricular intracavity pressure, limiting clinical and research applications. A non-invasive method for the computation of PV loops from magnetic resonance imaging and brachial cuff blood pressure has recently been proposed. Here we evaluated the fidelity of the non-invasive PV algorithm against invasive LV pressures in humans.

Methods and results
Four heart failure patients with EF &lt; 35% and LV dyssynchrony underwent cardiovascular magnetic resonance (CMR) imaging and subsequent LV catheterization with sequential administration of two different intravenous metabolic substrate infusions (insulin/dextrose and lipid emulsion), producing eight datasets at different haemodynamic states. Pressure-volume loops were computed from CMR volumes combined with (i) a time-varying elastance function scaled to brachial blood pressure and temporally stretched to match volume data, or (ii) invasive pressures averaged from 19 to 30 sampled beats. Method comparison was conducted using linear regression and Bland-Altman analysis. Non-invasively derived PV loop parameters demonstrated high correlation and low bias when compared to invasive data for stroke work (R2 = 0.96, P &lt; 0.0001, bias 4.6%), potential energy (R2 = 0.83, P = 0.001, bias 1.5%), end-systolic pressure-volume relationship (R2 = 0.89, P = 0.0004, bias 5.8%), ventricular efficiency (R2 = 0.98, P &lt; 0.0001, bias 0.8%), arterial elastance (R2 = 0.88, P = 0.0006, bias −8.0%), mean external power (R2 = 0.92, P = 0.0002, bias 4.4%), and energy per ejected volume (R2 = 0.89, P = 0.0001, bias 3.7%). Variations in estimated end-diastolic pressure did not significantly affect results (P &gt; 0.05 for all). Intraobserver analysis after one year demonstrated 0.9–3.4% bias for LV volumetry and 0.2–5.4% for PV loop-derived parameters.

Conclusion
Pressure-volume loops can be precisely and accurately computed from CMR imaging and brachial cuff blood pressure in humans.
Clinical implementation of partial oral treatment in infective endocarditis: the Danish POETry study
Authors: Pries-Heje Mia Marie , Hjulmand Julie Glud , Lenz Ingrid Try , Hasselbalch Rasmus Bo , Povlsen Jonas Agerlund , Ihlemann Nikolaj , Køber Nana , Tofterup Marlene Lyngborg , Østergaard Lauge , Dalsgaard Morten , Faurholt-Jepsen Daniel , Wienberg Malene , Christiansen Ulrik , Bruun Niels Eske , Fosbøl Emil , Moser Claus , Iversen Kasper Karmark , Bundgaard Henning 
Published: October 2023

Abstract

Background and Aims
In the Partial Oral Treatment of Endocarditis (POET) trial, stabilized patients with left-sided infective endocarditis (IE) were randomized to oral step-down antibiotic therapy (PO) or conventional continued intravenous antibiotic treatment (IV), showing non-inferiority after 6 months. In this study, the first guideline-driven clinical implementation of the oral step-down POET regimen was examined.

Methods
Patients with IE, caused by Staphylococcus aureus, Enterococcus faecalis, Streptococcus spp. or coagulase-negative staphylococci diagnosed between May 2019 and December 2020 were possible candidates for initiation of oral step-down antibiotic therapy, at the discretion of the treating physician. The composite primary outcome in patients finalizing antibiotic treatment consisted of embolic events, unplanned cardiac surgery, relapse of bacteraemia and all-cause mortality within 6 months.

Results
A total of 562 patients [median age 74 years (IQR, interquartile range, 65–80), 70% males] with IE were possible candidates; PO was given to 240 (43%) patients and IV to 322 (57%) patients. More patients in the IV group had IE caused by S. aureus, or had an intra-cardiac abscess, or a pacemaker and more were surgically treated. The primary outcome occurred in 30 (13%) patients in the PO group and in 59 (18%) patients in the IV group (P = .051); in the PO group, 20 (8%) patients died vs. 46 (14%) patients in the IV group (P = .024). PO-treated patients had a shorter median length of stay [PO 24 days (IQR 17–36) vs. IV 43 days (IQR 32–51), P &lt; .001].

Conclusions
After clinical implementation of the POET regimen almost half of the possible candidates with IE received oral step-down antibiotic therapy. Patients in the IV group had more serious risk factors for negative outcomes. At 6-month follow-up, there was a numerically but not statistically significant difference towards a lower incidence of the primary outcome, a lower incidence of all-cause mortality and a reduced length of stay in the PO group. Due to the observational design of the study, the lower mortality may to some extent reflect selection bias and unmeasured confounding. Clinical implementation of PO regimens seemed feasible and safe.
Comparison of non-laser and laser transvenous lead extraction: a systematic review and meta-analysis
Authors: Akhtar Zaki , Kontogiannis Christos , Georgiopoulos Georgios , Starck Christoph T , Leung Lisa W M , Lee Sun Y , Lee Byron K , Seshasai Sreenivasa R K , Sohal Manav , Gallagher Mark M 
Published: October 2023

Abstract

Aims
Transvenous lead extraction (TLE) is performed using non-laser and laser techniques with overall high efficacy and safety. Variation in outcomes between the two approaches does exist with limited comparative evidence in the literature. We sought to compare non-laser and laser TLE in a meta-analysis.

Methods and results
We searched Medline, Embase, Scopus, ClinicalTrials.gov, and CENTRAL databases for TLE studies published between 1991 and 2021. From the included 68 studies, safety and efficacy data were carefully evaluated and extracted. Aggregated cases of outcomes were used to calculate odds ratio (OR), and pooled rates were synthesized from eligible studies to compare non-laser and laser techniques. Subgroup comparison of rotational tool and laser extraction was also performed. Non-laser in comparison with laser had lower procedural mortality (pooled rate 0% vs. 0.1%, P &lt; 0.01), major complications (pooled rate 0.7% vs. 1.7%, P &lt; 0.01), and superior vena cava (SVC) injury (pooled rate 0% vs. 0.5%, P &lt; 0.001), with higher complete success (pooled rate 96.5% vs. 93.8%, P &lt; 0.01). Non-laser comparatively to laser was more likely to achieve clinical [OR 2.16 (1.77–2.63), P &lt; 0.01] and complete [OR 1.87 (1.69–2.08), P &lt; 0.01] success, with a lower procedural mortality risk [OR 1.6 (1.02–2.5), P &lt; 0.05]. In the subgroup analysis, rotational tool compared with laser achieved greater complete success (pooled rate 97.4% vs. 95%, P &lt; 0.01) with lower SVC injury (pooled rate 0% vs. 0.7%, P &lt; 0.01).

Conclusion
Non-laser TLE is associated with a better safety and efficacy profile when compared with laser methods. There is a greater risk of SVC injury associated with laser sheath extraction.
Pseudomonas aeruginosa biofilm exopolysaccharides: assembly, function, and degradation
Authors: Gheorghita Andreea A , Wozniak Daniel J , Parsek Matthew R , Howell P Lynne 
Published: October 2023

Abstract
The biofilm matrix is a fortress; sheltering bacteria in a protective and nourishing barrier that allows for growth and adaptation to various surroundings. A variety of different components are found within the matrix including water, lipids, proteins, extracellular DNA, RNA, membrane vesicles, phages, and exopolysaccharides. As part of its biofilm matrix, Pseudomonas aeruginosa is genetically capable of producing three chemically distinct exopolysaccharides – alginate, Pel, and Psl – each of which has a distinct role in biofilm formation and immune evasion during infection. The polymers are produced by highly conserved mechanisms of secretion, involving many proteins that span both the inner and outer bacterial membranes. Experimentally determined structures, predictive modelling of proteins whose structures are yet to be solved, and structural homology comparisons give us insight into the molecular mechanisms of these secretion systems, from polymer synthesis to modification and export. Here, we review recent advances that enhance our understanding of P. aeruginosa multiprotein exopolysaccharide biosynthetic complexes, and how the glycoside hydrolases/lyases within these systems have been commandeered for antimicrobial applications.
“Terror Is a Better Word”: A Qualitative Analysis of Dementia-Related Anxiety
Authors: Maxfield Molly , Peckham Allie , James Dara L 
Published: October 2023

Abstract

Background and Objectives
Dementia-related anxiety (DRA) is the fear of a current or future diagnosis of Alzheimer’s disease or another type of dementia. Previous studies suggest diverse factors contribute to DRA, including emotional, social, and cognitive concerns. A mixed-methods investigation was designed to explore DRA’s underlying causes; we present a thematic analysis of these causes.

Research Design and Methods
A semistructured qualitative interview design was used to explore participant’s thoughts, feelings, and reactions about dementia. Fifty community-dwelling adults (aged 58–89, M = 70.80, SD = 6.02) without dementia diagnoses were interviewed, with a focus on why dementias are anxiety-provoking diagnoses. We engaged in a reflexive inductive thematic approach.

Results
We identified 7 themes positioned within previously established antecedents of DRA. Anticipated consequences were conveyed in statements identifying dementia as a feared diagnosis and its connection to how one would be treated if diagnosed. Low perceived control was associated with dementia’s anticipated effects including the ability of dementia to undermine core aspects of one’s personhood, limit independence, and increase reliance on others. Perceived risk was connected to past familial experiences with dementia and the implications of receiving different diagnoses with different trajectories and treatments.

Discussion and Implications
Findings offer insight into diverse factors contributing to DRA, which can be used to inform public health messaging and develop applicable and clinically relevant interventions to meet the needs of individuals experiencing DRA and their social support systems.
Computational prediction of human deep intronic variation
Authors: Barbosa Pedro , Savisaar Rosina , Carmo-Fonseca Maria , Fonseca Alcides 
Published: October 2023

Abstract

Background
The adoption of whole-genome sequencing in genetic screens has facilitated the detection of genetic variation in the intronic regions of genes, far from annotated splice sites. However, selecting an appropriate computational tool to discriminate functionally relevant genetic variants from those with no effect is challenging, particularly for deep intronic regions where independent benchmarks are scarce.

Results
In this study, we have provided an overview of the computational methods available and the extent to which they can be used to analyze deep intronic variation. We leveraged diverse datasets to extensively evaluate tool performance across different intronic regions, distinguishing between variants that are expected to disrupt splicing through different molecular mechanisms. Notably, we compared the performance of SpliceAI, a widely used sequence-based deep learning model, with that of more recent methods that extend its original implementation. We observed considerable differences in tool performance depending on the region considered, with variants generating cryptic splice sites being better predicted than those that potentially affect splicing regulatory elements. Finally, we devised a novel quantitative assessment of tool interpretability and found that tools providing mechanistic explanations of their predictions are often correct with respect to the ground - information, but the use of these tools results in decreased predictive power when compared to black box methods.

Conclusions
Our findings translate into practical recommendations for tool usage and provide a reference framework for applying prediction tools in deep intronic regions, enabling more informed decision-making by practitioners.
Urgent need for substance use disorder research among understudied populations: examining the Asian-American experience
Authors: Choi Sugy , Lim Sahnah , Kwon Simona C , Trinh-Shevrin Chau , Neighbors Charles J , Yi Stella S 
Published: October 2023

Abstract
Substance use disorder (SUD) among Asian Americans is understudied. Our review of National Institutes of Health–funded projects reveals a striking underrepresentation of research focused on SUD in this population, possibly perpetuated by the pervasive societal myth that Asian Americans are a healthy community. Moreover, the limited availability and disaggregation of data on SUD among Asian Americans further hinder our understanding of prevalence rates, treatment utilization, and associated disparities—thereby limiting opportunities for prevention and intervention. In light of these findings, our review serves as a crucial call to action, emphasizing the urgent need for increased research efforts and resources to address the significant gaps in knowledge and inform effective interventions for addressing SUD among Asian Americans.