bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation analysis reveals local changes in resistant and susceptible soybean lines in response to Phytophthora sansomeana
Authors: DiBiase Charlotte N , Cheng Xi , Lee Gwonjin , Moore Richard C , McCoy Austin G , Chilvers Martin I , Sun Lianjun , Wang Dechun , Lin Feng , Zhao Meixia 
Published: August 2024

Abstract
Phytophthora sansomeana is an emerging oomycete pathogen causing root rot in many agricultural species including soybean. However, as of now, only one potential resistance gene has been identified in soybean, and our understanding of how genetic and epigenetic regulation in soybean contributes to responses against this pathogen remains largely unknown. In this study, we performed whole genome bisulfite sequencing (WGBS) on two soybean lines, Colfax (resistant) and Williams 82 (susceptible), in response to P. sansomeana at two time points: 4 and 16 hours post-inoculation to compare their methylation changes. Our findings revealed that there were no significant changes in genome-wide CG, CHG (H = A, T, or C), and CHH methylation. However, we observed local methylation changes, specially an increase in CHH methylation around genes and transposable elements (TEs) after inoculation, which occurred earlier in the susceptible line and later in the resistant line. After inoculation, we identified differentially methylated regions (DMRs) in both Colfax and Williams 82, with a predominant presence in TEs. Notably, our data also indicated that more TEs exhibited changes in their methylomes in the susceptible line compared to the resistant line. Furthermore, we discovered 837 DMRs within or flanking 772 differentially expressed genes (DEGs) in Colfax and 166 DMRs within or flanking 138 DEGs in Williams 82. These DEGs had diverse functions, with Colfax primarily showing involvement in metabolic process, defense response, plant and pathogen interaction, anion and nucleotide binding, and catalytic activity, while Williams 82 exhibited a significant association with photosynthesis. These findings suggest distinct molecular responses to P. sansomeana infection in the resistant and susceptible soybean lines.
A Dementia-Friendly Educational Program Using Virtual Reality for the General Public in Japan: A Randomized Controlled Trial for DRIVE
Authors: Suzuki Haruno , Igarashi Ayumi , Matsumoto Hiroshige , Kugai Haruna , Takaoka Manami , Sakka Mariko , Ito Kenichiro , Hagiwara Yasuhiro , Yamamoto-Mitani Noriko 
Published: August 2024

Abstract

Background and Objectives
Raising dementia awareness is essential for building a dementia-friendly community. However, existing studies have underexplored the effects of virtual reality (VR) dementia educational programs for the general public on enhancing positive attitude toward dementia. This study aimed to examine the effectiveness of a VR dementia-friendly educational program called the Drive for Dementia Readiness Inside Virtual Reality (DRIVE) program to improve attitude toward dementia of the general public.

Research Design and Methods
A two-arm randomized controlled trial was conducted. Eligibility criteria for participants included being 16 years and older in Japan and having no professional license in healthcare and social care. We randomized individuals to attend a multielement VR dementia-friendly educational program (intervention), including simulation, VR films, short films, lectures, and discussions or a lecture-based program (control). Data were collected 3 times, including at baseline, postintervention, and 3-month follow-up. The primary outcome was attitude toward dementia. The secondary outcomes were intention of helping behavior for people living with dementia and knowledge of dementia.

Results
We recruited 157 community residents, among whom 130 were included in the analysis. Although the mean changes in attitude score were not significantly different between the groups (Hedge’s g = 0.26), the intention of helping behavior score was significantly higher in the intervention group (g = 0.49).

Discussion and Implication
The DRIVE, a VR-based multielement dementia-friendly educational intervention, was shown as a promising tool for significantly affecting the intention of helping behavior for people living with dementia to establish dementia-friendly communities.

Clinical Trials Registration Number
UMIN000044901
Active and passive salt diapirs: a numerical study
Authors: Gou Yiren , Liu Mian 
Published: August 2024

SUMMARY
Salt diapirs dominate the structure in many sedimentary basins and control the preservation and migration of hydrocarbon. The formation of salt diapirs generally falls into two endmember models: active (up-building) and passive (down-building) diapirism. In the active model, salt diapirs rise from salt buoyancy to pierce through the sedimentary overburden, whereas in the passive model, salt diapirs result from differential loading of sediments during deposition. These endmember models are mostly conceptual or kinematic, the mechanics of active and passive diapirism and their relative roles and interactions in the formation of salt diapirs remain uncertain. Here, we use two-dimensional high-resolution numerical models to investigate the primary factors and critical conditions for active and passive diapirism. Our results indicate that it is improper to use driving mechanisms to classify salt diapirs, because the buoyancy-driven active salt diapirism involves differential loading, while the passive diapirism requires salt buoyancy. The rise of salt diapirs is more sensitive to the effective viscosity of the overburden than to the salt viscosity. Stiff overburdens could prevent the rise of salt diapirs, but they could be pierced by salt diapirs if plastic yield of the overburden is allowed. During deposition, the coupled salt-sediment deformation, driven by both salt buoyancy and differential loading of sediments, can lead to various diapiric salt structures and minibasins. Regional tectonic stress generally promotes salt diapirism by enhancing strain weakening of salts and overburdens. We suggest that the classification of active and passive salt diapirism is an oversimplification in most cases. We propose a general model of the formation of salt diapirs that usually begins with dome initiation driven by salt buoyancy, followed by syndepositional down-building controlled by sedimentation and differential loading and ends with canopy formation when sedimentation stops.
CsTs, a C-type lectin receptor-like kinase, regulates the development trichome development and cuticle metabolism in cucumber (Cucumis sativus)
Authors: Lv Duo , Wen HaiFan , Wang Gang , Liu Juan , Guo ChunLi , Sun Jingxian , Zhang Keyan , Li ChaoHan , You Jiaqi , Pan Ming , He Huanle , Cai Run , Pan Junsong 
Published: August 2024

Abstract
Cucumber (Cucumis sativus) fruit spines are a classic material for researching the development of multicellular trichomes. Some key genes that influence trichome development have been confirmed to be associated with cuticle biosynthesis and secondary metabolism. However, the biological mechanisms underlying trichome development, cuticle biosynthesis, and secondary metabolism in cucumber remain poorly understood. CsTs, a C-type lectin receptor-like kinase gene, reportedly causes a tender trichome phenotype in cucumber when it mutates. In this study, the role of CsTs in cucumber fruit spines morphogenesis was confirmed using gene editing technology. Sectioning and cell wall component detection were used to analyse the main reason of tender fruit spines in the ts mutant. Subsequently, transcriptome data and a series of molecular biology experiments were used to further investigate the relationship between CsTs and cytoskeletal homeostasis in cucumber. CsTs overexpression partially compensated for the abnormal trichome phenotype of an Arabidopsis homolog mutant. Genetic hybridization and metabolic analysis indicated that CsTs and CsMict can affect trichome development and cuticle biosynthesis in the same pathway. Our findings provide important background information for further researching on the molecular mechanism underlying cucumber trichome development and contribute to understanding the biological function of C-type lectin receptor-like kinases.
Evaluation of Medical Subject Headings assignment in simulated patient articles
Authors: Tonin Fernanda S , Negrão Luciana G , Meza Isabela P , Fernandez-Llimos Fernando 
Published: August 2024

Abstract

Objectives
To evaluate human-based Medical Subject Headings (MeSH) allocation in articles about ‘patient simulation’—a technique that mimics real-life patient scenarios with controlled patient responses.

Methods
A validation set of articles indexed before the Medical Text Indexer-Auto implementation (in 2019) was created with 150 combinations potentially referring to ‘patient simulation’. Articles were classified into four categories of simulation studies. Allocation of seven MeSH terms (Simulation Training, Patient Simulation, High Fidelity Simulation Training, Computer Simulation, Patient-Specific Modelling, Virtual Reality, and Virtual Reality Exposure Therapy) was investigated. Accuracy metrics (sensitivity, precision, or positive predictive value) were calculated for each category of studies.

Key findings
A set of 7213 articles was obtained from 53 different word combinations, with 2634 excluded as irrelevant. ‘Simulated patient’ and ‘standardized/standardized patient’ were the most used terms. The 4579 included articles, published in 1044 different journals, were classified into: ‘Machine/Automation’ (8.6%), ‘Education’ (75.9%) and ‘Practice audit’ (11.4%); 4.1% were ‘Unclear’. Articles were indexed with a median of 10 MeSH (IQR 8–13); however, 45.5% were not indexed with any of the seven MeSH terms. Patient Simulation was the most prevalent MeSH (24.0%). Automation articles were more associated with Computer Simulation MeSH (sensitivity = 54.5%; precision = 25.1%), while Education articles were associated with Patient Simulation MeSH (sensitivity = 40.2%; precision = 80.9%). Practice audit articles were also polarized to Patient Simulation MeSH (sensitivity = 34.6%; precision = 10.5%).

Conclusions
Inconsistent use of free-text words related to patient simulation was observed, as well as inaccuracies in human-based MeSH assignments. These limitations can compromise relevant literature retrieval to support evidence synthesis exercises.
Variants in the Late Cornified Envelope Gene Locus Are Associated With Elevated T-helper 17 Responses in Patients With Postinfectious Lyme Arthritis
Authors: Ehrbar Dylan , Arvikar Sheila L , Sulka Katherine B , Chiumento Geena , Nelson Nicole L J , Hernandez Sergio A , Williams Morgan A , Strle Franc , Steere Allen C , Strle Klemen 
Published: August 2024

AbstractBackgroundPostinfectious Lyme arthritis (LA) is associated with dysregulated immunity and autoreactive T- and B-cell responses in joints. Here we explored the role of host genetic variation in this outcome.MethodsThe frequency of 253 702 single-nucleotide polymorphisms (SNPs) was determined in 147 patients with LA (87 with postinfectious LA and 60 with antibiotic-responsive LA), and for comparison in 90 patients with erythema migrans or the general population (n = 2504). Functional outcome of candidate SNPs was assessed by evaluating their impact on clinical outcome and on immune responses in blood and synovial fluid in patients with LA.ResultsSix SNPs associated with late cornified envelope (LCE3) genes were present at greater frequency in patients with postinfectious LA compared to those with antibiotic-responsive LA (70% vs 30%; odds ratio, 2; P &lt; .01). These SNPs were associated with heightened levels of inflammatory Th17 cytokines in serum but lower levels of interleukin 27, a regulatory cytokine, implying that they may contribute to dysregulated Th17 immunity in blood. Moreover, in patients with postinfectious LA, the levels of these Th17 mediators correlated directly with autoantibody responses in synovial fluid, providing a possible link between LCE3 SNPs, maladaptive systemic Th17 immunity, and autoreactive responses in joints.ConclusionsVariation in the LCE3 locus, a known genetic risk factor in psoriasis and psoriatic arthritis, is associated with dysregulated systemic Th17 immunity and heightened autoantibody responses in joints. These findings underscore the importance of host genetic predisposition and systemic Th17 immunity in the pathogenesis of postinfectious (antibiotic-refractory) Lyme arthritis.
Laboratory Testing for Powassan Virus: Past, Present, and Future
Authors: Klontz Erik H , Chowdhury Navid , Branda John A 
Published: August 2024

Abstract
Powassan virus is a tick-borne flavivirus that can cause severe neuroinvasive disease, with areas of endemicity in the Northeast and Midwest United States, Canada, and Russia. Diagnosis is challenging and relies on a high index of suspicion and choosing the right test based on duration of infection and the patient's immune status. This review covers laboratory testing for Powassan virus, including historical considerations, modern options, and methods being developed in the research space.
Persistent Symptoms After Lyme Disease: Clinical Characteristics, Predictors, and Classification
Authors: Baarsma M E , Hovius Joppe W 
Published: August 2024

Abstract
Persistent symptoms after an infection have been described for a number of infectious diseases, including Lyme disease. Studies have confirmed a moderate but consistent increase in the prevalence of such symptoms after Lyme disease, though the risk increase varies dependent on study design and the definition of persistent symptoms. Various possible predictors have been proposed, including a dysregulation of the immune system, metabolic changes, increased sensitization to pain signals, cognitive-behavioral factors, or—controversially—the persistence of the causative Borrelia bacteria or remnants thereof. Research on the precise roles of any of these factors is still ongoing. The lack of biological underpinning also makes it difficult to assess with certainty which patients’ (generally nonspecific) persistent symptoms are etiologically related to the previous Lyme disease episode and which are not, particularly as these symptoms occur in the general population relatively frequently. The diagnostic criteria for posttreatment Lyme disease syndrome have shown their usefulness in both clinical and research settings but leave out a number of patients whose symptoms may fall just outside said criteria. Though the relationship between these symptoms and the previous Lyme disease episode may be very uncertain, we would argue that a uniform description and classification of these patients will aid in future research and patient management, regardless of the eventual underlying cause. Thus, we argue for an inclusive classification system for all persistent symptoms attributed to Lyme disease in order to promote validation of patient experiences and perspectives, while also maintaining scientific nuance regarding the very uncertain etiology of these patients’ symptoms.
Comparative Evaluation of Commercial Test Kits Cleared for Use in Modified Two-Tiered Testing Algorithms for Serodiagnosis of Lyme Disease
Authors: Lewandrowski Elizabeth L , Turbett Sarah E , Nigrovic Lise E , Klontz Erik H , Branda John A 
Published: August 2024

Abstract

Background
Modified 2-tiered testing (MTTT) for Lyme disease utilizes automatable, high throughput immunoassays (AHTIs) in both tiers without involving western immunoblots, offering performance and practical advantages over standard 2-tiered testing (STTT; first-tier AHTI followed by immunoglobulin M (IgM) and immunoglobulin G (IgG) western immunoblots). For MTTT, Centers for Disease Control and Prevention recommends using AHTI test kits that have been cleared by Food and Drug Administration (FDA) specifically for this intended use. We evaluated performance of FDA-cleared MTTT commercial test kits from 3 manufacturers by comparing with STTT results.

Methods
We performed MTTT (total antibody AHTI with reflex to separate IgM and IgG AHTIs) using test kits from Diasorin, Gold Standard Diagnostics (GSD), and Zeus Scientific on 382 excess serum samples submitted to the clinical laboratory for routine Lyme disease serologic testing in July 2018, measuring agreement between MTTT and STTT using the κ statistic.

Results
Overall agreement with STTT was 0.87 (95% confidence interval [CI], .77–.97) using Diasorin assays (almost perfect agreement), 0.80 (95% CI, .68–.93) using GSD assays (substantial agreement) and 0.79 (95% CI, .68–.90) using Zeus assays (substantial agreement). For detection of IgM reactivity, agreement between MTTT and STTT was 0.70 (.51–.90; substantial), 0.63 (95% CI, .44–.82; substantial) and 0.56 (95% CI, .38–.73; moderate), respectively. For detection of IgG reactivity, MTTT/STTT agreement was 0.73 (95% CI,.58–.88), 0.78 (95% CI, .62–.94), and 0.75 (95% CI, .60–.90), respectively (substantial agreement in all cases).

Conclusions
MTTT results obtained using commercial test kits from 3 different manufacturers had substantial to almost perfect agreement with STTT results overall and moderate to substantial agreement for IgM and IgG detection independently. Commercial MTTT tests can be used broadly for the diagnosis of Lyme disease.
Lyme Disease Surveillance and Epidemiology in the United States: A Historical Perspective
Authors: Mead Paul , Hinckley Alison , Kugeler Kiersten 
Published: August 2024

Abstract
In the 40 years since Steere and colleagues first described Lyme disease, the illness has increased in incidence and distribution to become the most common vector-borne disease in the United States. Public health officials have developed, implemented, and revised surveillance systems to describe and monitor the condition. Much has been learned about the epidemiology of the illness, despite practical and logistical constraints that have encumbered the collection and interpretation of surveillance data. Future development of automated data collection from electronic health records as a source of surveillance and clinical information will address practical challenges and help answer ongoing questions about complications and persistent symptoms. Robust surveillance will be essential to monitor the effectiveness and safety of future vaccines and other preventive measures.
Identification of Major Histocompatibility Complex Class II Epitopes From Lyme Autoantigen Apolipoprotein B-100 and Borrelia burgdorferi Mcp4 in Murine Lyme Arthritis
Authors: Danner Rebecca , Prochniak Lauren M , Pereckas Michaela , Rouse Joseph R , Wahhab Amanda , Hackner Lauren G , Lochhead Robert B 
Published: August 2024

Abstract

Background
During infection with the Lyme arthritis (LA) pathogen Borrelia burgdorferi, T-cell responses to both host and pathogen are dysregulated, resulting in chronic infection and frequent development of autoimmunity.

Methods
To assess CD4+ T-cell epitopes presented during development of LA, we used an unbiased, immunopeptidomics approach to characterize the major histocompatibility complex (MHC) class II immunopeptidome in B burgdorferi-infected C57BL/6 (B6) mice, which develop mild, self-limiting LA, and infected B6 Il10−/− mice, which develop severe, persistent LA at 0, 4, and 16 weeks postinfection (22–23 mice per group).

Results
Peptides derived from proteins involved in adaptive T- and B-cell responses and cholesterol metabolism, including human Lyme autoantigen apolipoprotein B-100 (apoB-100), were enriched in infected Il10−/− mice; whereas peptides derived from proteins involved in neutrophil extracellular net formation were enriched in infected B6 mice. Presentation of apoB-100 peptides showed evidence of epitope expansion during infection. Of several identified B burgdorferi peptides, only 1, a methyl-accepting chemotaxis protein peptide Mcp4442–462, was immunogenic.

Conclusions
ApoB-100, a human Lyme autoantigen, undergoes marked epitope expansion during LA development. The paucity of immunogenic B burgdorferi epitopes supports previous findings suggesting CD4+ T-cell responses are suppressed in murine LA.
Nitrite-oxidizing bacteria adapted to low-oxygen conditions dominate nitrite oxidation in marine oxygen minimum zones
Authors: Fortin Samantha G , Sun Xin , Jayakumar Amal , Ward Bess B 
Published: August 2024

Abstract
Nitrite is a central molecule in the nitrogen cycle because nitrite oxidation to nitrate (an aerobic process) retains fixed nitrogen in a system and its reduction to dinitrogen gas (anaerobic) reduces the fixed nitrogen inventory. Despite its acknowledged requirement for oxygen, nitrite oxidation is observed in oxygen-depleted layers of the ocean’s oxygen minimum zones (OMZs), challenging the current understanding of OMZ nitrogen cycling. Previous attempts to determine whether nitrite-oxidizing bacteria in the anoxic layer differ from known nitrite oxidizers in the open ocean were limited by cultivation difficulties and sequencing depth. Here, we construct 31 draft genomes of nitrite-oxidizing bacteria from global OMZs. The distribution of nitrite oxidation rates, abundance and expression of nitrite oxidoreductase genes, and relative abundance of nitrite-oxidizing bacterial draft genomes from the same samples all show peaks in the core of the oxygen-depleted zone (ODZ) and are all highly correlated in depth profiles within the major ocean oxygen minimum zones. The ODZ nitrite oxidizers are not found in the Tara Oceans global dataset (the most complete oxic ocean dataset), and the major nitrite oxidizers found in the oxygenated ocean do not occur in ODZ waters. A pangenomic analysis shows the ODZ nitrite oxidizers have distinct gene clusters compared to oxic nitrite oxidizers and are microaerophilic. These findings all indicate the existence of nitrite oxidizers whose niche is oxygen-deficient seawater. Thus, specialist nitrite-oxidizing bacteria are responsible for fixed nitrogen retention in marine oxygen minimum zones, with implications for control of the ocean’s fixed nitrogen inventory.
Navigating fluoroquinolone resistance in Gram-negative bacteria: a comprehensive evaluation
Authors: Kherroubi Linda , Bacon Joanna , Rahman Khondaker Miraz 
Published: August 2024

Abstract
Since the introduction of quinolone and fluoroquinolone antibiotics to treat bacterial infections in the 1960s, there has been a pronounced increase in the number of bacterial species that have developed resistance to fluoroquinolone treatment. In 2017, the World Health Organization established a priority list of the most critical Gram-negative resistant pathogens. These included Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli. In the last three decades, investigations into the mechanisms of fluoroquinolone resistance have revealed that mutations in the target enzymes of fluoroquinolones, DNA gyrase or topoisomerase IV, are the most prevalent mechanism conferring high levels of resistance. Alterations to porins and efflux pumps that facilitate fluoroquinolone permeation and extrusion across the bacterial cell membrane also contribute to the development of resistance. However, there is a growing observation of novel mutants with newer generations of fluoroquinolones, highlighting the need for novel treatments. Currently, steady progress has been made in the development of novel antimicrobial agents that target DNA gyrase or topoisomerase IV through different avenues than current fluoroquinolones to prevent target-mediated resistance. Therefore, an updated review of the current understanding of fluoroquinolone resistance within the literature is imperative to aid in future investigations.