bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heritable epigenetic variation facilitates long-term maintenance of epigenetic and genetic variation
Authors: Webster Amy K , Phillips Patrick C 
Published: December 2023

Abstract
How genetic and phenotypic variation are maintained has long been one of the fundamental questions in population and quantitative genetics. A variety of factors have been implicated to explain the maintenance of genetic variation in some contexts (e.g. balancing selection), but the potential role of epigenetic regulation to influence population dynamics has been understudied. It is well recognized that epigenetic regulation, including histone methylation, small RNA expression, and DNA methylation, helps to define differences between cell types and facilitate phenotypic plasticity. In recent years, empirical studies have shown the potential for epigenetic regulation to also be heritable for at least a few generations without selection, raising the possibility that differences in epigenetic regulation can act alongside genetic variation to shape evolutionary trajectories. Heritable differences in epigenetic regulation that arise spontaneously are termed “epimutations.” Epimutations differ from genetic mutations in 2 key ways—they occur at a higher rate and the loci at which they occur often revert back to their original state within a few generations. Here, we present an extension of the standard population genetic model with selection to incorporate epigenetic variation arising via epimutation. Our model assumes a diploid, sexually reproducing population with random mating. In addition to spontaneous genetic mutation, we included parameters for spontaneous epimutation and back-epimutation, allowing for 4 potential epialleles at a single locus (2 genetic alleles, each with 2 epigenetic states), each of which affect fitness. We then analyzed the conditions under which stable epialleles were maintained. Our results show that highly reversible epialleles can be maintained in long-term equilibrium under neutral conditions in a manner that depends on the epimutation and back-epimutation rates, which we term epimutation–back-epimutation equilibrium. On the other hand, epialleles that compensate for deleterious mutations cause deviations from the expectations of mutation–selection balance by a simple factor that depends on the epimutation and back-epimutation rates. We also numerically analyze several sets of fitness parameters for which large deviations from mutation–selection balance occur. Together, these results demonstrate that transient epigenetic regulation may be an important factor in the maintenance of both epigenetic and genetic variation in populations.
The chromosome-scale genome and the genetic resistance machinery against insect herbivores of the Mexican toloache,Datura stramonium
Authors: De-la-Cruz Ivan M , Oyama Ken , Núñez-Farfán Juan 
Published: December 2023

AbstractPlant resistance refers to the heritable ability of plants to reduce damage caused by natural enemies, such as herbivores and pathogens, either through constitutive or induced traits like chemical compounds or trichomes. However, the genetic architecture—the number and genome location of genes that affect plant defense and the magnitude of their effects—of plant resistance to arthropod herbivores in natural populations remains poorly understood. In this study, we aimed to unveil the genetic architecture of plant resistance to insect herbivores in the annual herb Datura stramonium (Solanaceae) through quantitative trait loci mapping. We achieved this by assembling the species’ genome and constructing a linkage map using an F2 progeny transplanted into natural habitats. Furthermore, we conducted differential gene expression analysis between undamaged and damaged plants caused by the primary folivore, Lema daturaphila larvae. Our genome assembly resulted in 6,109 scaffolds distributed across 12 haploid chromosomes. A single quantitative trait loci region on chromosome 3 was associated with plant resistance, spanning 0 to 5.17 cM. The explained variance by the quantitative trait loci was 8.44%. Our findings imply that the resistance mechanisms of D. stramonium are shaped by the complex interplay of multiple genes with minor effects. Protein–protein interaction networks involving genes within the quantitative trait loci region and overexpressed genes uncovered the key role of receptor-like cytoplasmic kinases in signaling and regulating tropane alkaloids and terpenoids, which serve as powerful chemical defenses against D. stramonium herbivores. The data generated in our study constitute important resources for delving into the evolution and ecology of secondary compounds mediating plant–insect interactions.
Scaling of earthquake waiting time distributions in northern Chile
Authors: Siegel Cristián E , Toledo Patricio A , Madariaga Raúl , Campos Jaime 
Published: December 2023

SUMMARY
In this study, we examine the scaling of earthquake waiting time distributions in Northern Chile. For this purpose, we analysed 7-yr high spatial resolution and low completeness magnitude IPOC seismic catalogue and 43-yr USGS catalogue. A unified earthquake moment–space–time scaling relation is empirically evaluated by calculating waiting times for different ranges of magnitude and epicentral area linear dimension and estimating the associated scaling coefficients, β analogue to b-value and γ, the correlation fractal dimension. We find a scaling function that can be characterized with three distinct regions, regions whose behaviour depends on whether seismicity is in the coastal area or at intermediate depth. Moreover, high resolution localizations from the IPOC catalogue allows us to further observe differences: the lower plane seismicity of the double seismic zone behaves just like that at intermediate depth, while the crustal upper plate and the upper plane from the double seismic zone seismicity behaves more like interface seismicity. Thus, the earthquake waiting time distribution primarily depends on whether seismicity is located in a crust-on-crust or in a crust–mantle system: having, respectively, high/low correlated behaviour in the short scale region, non-exponential/exponential decay in the transition middle region and, in all cases, long-term clustering with a slower than exponential decay in the long scale.
Partisanship supersedes race: effects of discussant race and partisanship on Whites’ willingness to engage in race-specific conversations
Authors: Appiah Osei , Eveland William P , Henry Christina M 
Published: December 2023

Abstract
White participants in the United States were asked to imagine having a hypothetical conversation about race-specific issues with either a White or Black discussant who was described as either a Republican or Democrat. Participants’ expectations of encountering negative outcomes during the conversation, and their intentions to avoid the conversation, were measured. The black sheep effect posits that harmful ingroup members are evaluated more negatively than comparable outgroup members because they threaten the ingroup’s social identity. Findings indicate discussants’ partisanship is more important than their race in guiding respondents’ expectations of and desire to engage in cross-group conversations. Whites expected more negative outcomes and intended to avoid conversations more when they imagined talking about race with White discussants from a different political party than they did Black discussants from a different party, Black discussants from the same party, or White discussants from the same party. Intergroup threat and social identity theories are discussed.
Factors associated with inappropriateness of antibiotic prescriptions for acutely ill children presenting to ambulatory care in high-income countries: a systematic review and meta-analysis
Authors: Dillen Hannelore , Wouters Jo , Snijders Daniëlle , Wynants Laure , Verbakel Jan Y 
Published: December 2023

Abstract

Background
Acutely ill children are at risk of unwarranted antibiotic prescribing. Data on the appropriateness of antibiotic prescriptions provide insights into potential tailored interventions to promote antibiotic stewardship.

Objectives
To examine factors associated with the inappropriateness of antibiotic prescriptions for acutely ill children presenting to ambulatory care in high-income countries.

Methods
On 8 September 2022, we systematically searched articles published since 2002 in MEDLINE, Embase, CENTRAL, Web of Science, and grey literature databases. We included studies with acutely ill children presenting to ambulatory care settings in high-income countries reporting on the appropriateness of antibiotic prescriptions. The quality of the studies was evaluated using the Appraisal tool for Cross-Sectional Studies and the Newcastle–Ottawa Scale. Pooled ORs were calculated using random-effects models. Meta-regression, sensitivity and subgroup analysis were also performed.

Results
We included 40 articles reporting on 30 different factors and their association with inappropriate antibiotic prescribing. ‘Appropriateness’ covered a wide range of definitions. The following factors were associated with increased inappropriate antibiotic prescribing: acute otitis media diagnosis [pooled OR (95% CI): 2.02 (0.54–7.48)], GP [pooled OR (95% CI) 1.38 (1.00–1.89)] and rural setting [pooled OR (95% CI) 1.47 (1.08–2.02)]. Older patient age and a respiratory tract infection diagnosis have a tendency to be positively associated with inappropriate antibiotic prescribing, but pooling of studies was not possible.

Conclusions
Prioritizing acute otitis media, GPs, rural areas, older children and respiratory tract infections within antimicrobial stewardship programmes plays a vital role in promoting responsible antibiotic prescribing. The implementation of a standardized definition of appropriateness is essential to evaluate such programmes.
7-Year (2015–21) longitudinal surveillance of lefamulin in vitro activity against bacterial pathogens collected worldwide from patients with respiratory tract infections including pneumonia and characterization of resistance mechanisms
Authors: Paukner Susanne , Mendes Rodrigo E , Arends S J Ryan , Gassner Gisela , Gelone Steven P , Sader Helio S 
Published: December 2023

Abstract

Objectives
Lefamulin (Xenleta™), a pleuromutilin antibiotic, was approved for the oral and IV treatment of community-acquired bacterial pneumonia (CABP) in adults in 2019/2020. This study evaluated the in vitro activity of lefamulin and comparators against 19 584 unique bacterial isolates collected from patients with community-acquired respiratory tract infections and hospitalized patients with pneumonia within the global SENTRY Antimicrobial Surveillance Program during 2015–21.

Methods
Isolates were susceptibility tested by the CLSI broth microdilution method, and resistance mechanisms were investigated in isolates with elevated lefamulin MICs.

Results
Lefamulin exhibited potent antibacterial activity against the most common and typical CABP pathogens tested, including Streptococcus pneumoniae [MIC50/90, 0.06/0.25 mg/L; 99.9% susceptible (S)], Staphylococcus aureus (MIC50/90, 0.06/0.12 mg/L; 99.6% S), Haemophilus influenzae (MIC50/90, 0.5/2 mg/L; 99.1% S) and Moraxella catarrhalis (MIC50/90, 0.06/0.12 mg/L; 100.0% S). Potent activity was also observed against the less common pneumonia pathogens: β-haemolytic (MIC50/90 of 0.03/0.06 mg/L) and viridans group Streptococcus spp. (MIC50/90 of 0.06/0.25 mg/L) and Haemophilus parainfluenzae (MIC50/90 of 1/4 mg/L). Lefamulin’s activity was not adversely affected by resistance to macrolides, penicillin, tetracyclines, fluoroquinolones and other resistance phenotypes. Non-susceptibility/resistance to lefamulin was rare and primarily determined by ribosomal protection through vga(A) variants in S. aureus, overexpression of AcrAB-TolC efflux pump in H. influenzae or modifications in L3, L4 and 23SrRNA in Streptococcus spp.

Conclusions
Based on the coverage of the most important CABP pathogens and lacking cross-resistance, lefamulin may represent a valuable empirical treatment option for ambulatory and hospitalized patients with CABP, particularly in settings with high prevalence of resistance.
Effect of (in)organic additives on microbially induced calcium carbonate precipitation
Authors: Haystead Jamie , Gilmour Katie , Sherry Angela , Dade-Robertson Martyn , Zhang Meng 
Published: December 2023

Abstract

Aim
This study aimed to understand the morphological effects of (in)organic additives on microbially induced calcium carbonate precipitation (MICP).

Methods and results
MICP was monitored in real time in the presence of (in)organic additives: bovine serum albumin (BSA), biofilm surface layer protein A (BslA), magnesium chloride (MgCl2), and poly-l-lysine. This monitoring was carried out using confocal microscopy to observe the formation of CaCO3 from the point of nucleation, in comparison to conditions without additives. Complementary methodologies, namely scanning electron microscopy, energy-dispersive X-ray spectroscopy and X-ray diffraction, were employed to assess the visual morphology, elemental composition, and crystalline structures of CaCO3, respectively, following the crystals’ formation. The results demonstrated that in the presence of additives, more CaCO3 crystals were produced at 100 min compared to the reaction without additives. The inclusion of BslA resulted in larger crystals than reactions containing other additives, including MgCl2. BSA induced a significant number of crystals from the early stages of the reaction (20 min) but did not have a substantial impact on crystal size compared to conditions without additives. All additives led to a higher content of calcite compared to vaterite after a 24-h reaction, with the exception of MgCl2, which produced a substantial quantity of magnesium calcite.

Conclusions
The work demonstrates the effect of several (in)organic additives on MICP and sets the stage for further research to understand additive effects on MICP to achieve controlled CaCO3 precipitation.
Data-driven automated classification algorithms for acute health conditions: applying PheNorm to COVID-19 disease
Authors: Smith Joshua C , Williamson Brian D , Cronkite David J , Park Daniel , Whitaker Jill M , McLemore Michael F , Osmanski Joshua T , Winter Robert , Ramaprasan Arvind , Kelley Ann , Shea Mary , Wittayanukorn Saranrat , Stojanovic Danijela , Zhao Yueqin , Toh Sengwee , Johnson Kevin B , Aronoff David M , Carrell David S 
Published: December 2023

Abstract

Objectives
Automated phenotyping algorithms can reduce development time and operator dependence compared to manually developed algorithms. One such approach, PheNorm, has performed well for identifying chronic health conditions, but its performance for acute conditions is largely unknown. Herein, we implement and evaluate PheNorm applied to symptomatic COVID-19 disease to investigate its potential feasibility for rapid phenotyping of acute health conditions.

Materials and methods
PheNorm is a general-purpose automated approach to creating computable phenotype algorithms based on natural language processing, machine learning, and (low cost) silver-standard training labels. We applied PheNorm to cohorts of potential COVID-19 patients from 2 institutions and used gold-standard manual chart review data to investigate the impact on performance of alternative feature engineering options and implementing externally trained models without local retraining.

Results
Models at each institution achieved AUC, sensitivity, and positive predictive value of 0.853, 0.879, 0.851 and 0.804, 0.976, and 0.885, respectively, at quantiles of model-predicted risk that maximize F1. We report performance metrics for all combinations of silver labels, feature engineering options, and models trained internally versus externally.

Discussion
Phenotyping algorithms developed using PheNorm performed well at both institutions. Performance varied with different silver-standard labels and feature engineering options. Models developed locally at one site also worked well when implemented externally at the other site.

Conclusion
PheNorm models successfully identified an acute health condition, symptomatic COVID-19. The simplicity of the PheNorm approach allows it to be applied at multiple study sites with substantially reduced overhead compared to traditional approaches.
Benchmarking the symptom-checking capabilities of ChatGPT for a broad range of diseases
Authors: Chen Anjun , Chen Drake O , Tian Lu 
Published: December 2023

Abstract

Objective
This study evaluates ChatGPT’s symptom-checking accuracy across a broad range of diseases using the Mayo Clinic Symptom Checker patient service as a benchmark.

Methods
We prompted ChatGPT with symptoms of 194 distinct diseases. By comparing its predictions with expectations, we calculated a relative comparative score (RCS) to gauge accuracy.

Results
ChatGPT’s GPT-4 model achieved an average RCS of 78.8%, outperforming the GPT-3.5-turbo by 10.5%. Some specialties scored above 90%.

Discussion
The test set, although extensive, was not exhaustive. Future studies should include a more comprehensive disease spectrum.

Conclusion
ChatGPT exhibits high accuracy in symptom checking for a broad range of diseases, showcasing its potential as a medical training tool in learning health systems to enhance care quality and address health disparities.
Low RNA disruption during neoadjuvant chemotherapy predicts pathologic complete response absence in patients with breast cancer
Authors: Cazzaniga Marina Elena , Ademuyiwa Foluso , Petit Thierry , Tio Joke , Generali Daniele , Ciruelos Eva M , Califaretti Nadia , Poirier Brigitte , Ardizzoia Antonio , Hoenig Arnd , Lex Benno , Mouret-Reynier Marie-Ange , Giesecke Dagmar , Isambert Nicolas , Masetti Ricardo , Pitre Lacey , Wrobel Denise , Augereau Paule , Milani Manuela , Rask Sara , Solbach Christine , Pritzker Laura , Noubir Sanaa , Parissenti Amadeo , Trudeau Maureen E 
Published: December 2023

Abstract
In previously reported retrospective studies, high tumor RNA disruption during neoadjuvant chemotherapy predicted for post-treatment pathologic complete response (pCR) and improved disease-free survival at definitive surgery for primary early breast cancer. The BREVITY (Breast Cancer Response Evaluation for Individualized Therapy) prospective clinical trial (NCT03524430) seeks to validate these prior findings. Here we report training set (Phase I) findings, including determination of RNA disruption index (RDI) cut points for outcome prediction in the subsequent validation set (Phase II; 454 patients). In 80 patients of the training set, maximum tumor RDI values for biopsies obtained during neoadjuvant chemotherapy were significantly higher in pCR responders than in patients without pCR post-treatment (P = .008). Moreover, maximum tumor RDI values ≤3.7 during treatment predicted for a lack of pCR at surgery (negative predictive value = 93.3%). These findings support the prospect that on-treatment tumor RNA disruption assessments may effectively predict post-surgery outcome, possibly permitting treatment optimization.
International travel increases risk of urinary tract infection caused by extended-spectrum beta-lactamase-producing Enterobacterales—three-arm case-control study
Authors: Patjas Anu , Martelius Antti , Ollgren Jukka , Kantele Anu 
Published: December 2023

Abstract

Background
Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) have worldwide become increasingly prevalent as pathogens causing urinary tract infections (UTIs), posing challenges in their treatment. Of particular concern are travellers to low- and middle-income countries (LMICs), a substantial proportion of whom become colonized by ESBL-PE, with UTIs as the most common clinical manifestation. Seeking tools for preventing ESBL-PE UTI, we explored factors associated with (i) any UTI (versus control), (ii) ESBL-PE UTI (versus control) and (iii) ESBL-PE versus non-ESBL-PE UTI.

Methods
During 2015–20, we recruited patients with recent ESBL-PE or non-ESBL-PE UTIs, and controls with no UTI to fill in questionnaires covering potential (ESBL-PE-)UTI risk factors.

Results
Of our 430 participants, 130 had ESBL-PE UTI and 187 non-ESBL-PE UTI; 113 were controls. Our three comparisons showed several risk factors as exemplified for any UTI versus controls by female sex, lower education, age, diabetes, antibiotic use, diarrhoea; for ESBL-PE UTI versus controls by travel to LMICs, antibiotic use, swimming; and ESBL-PE versus non-ESBL-PE UTI by male sex, higher education, LMIC travel (participant/household member), pets and antibiotic use. Weekly fish meals appeared protective against both UTI and ESBL-PE UTI.

Conclusions
Of the numerous factors predisposing to UTI and/or ESBL-PE UTI, our study highlights antibiotic use and LMIC travel. Household members’ LMIC travel appears to pose a risk of ESBL-PE UTI, pointing to household transmission of travel-acquired uropathogens. As predisposing factors to multidrug-resistant UTI, international travel and antibiotic use constitute practical targets for prevention efforts.
Simultaneous detection of mycotoxigenic Aspergillus species of sections Circumdati and Flavi using multiplex digital PCR
Authors: Palumbo Jeffrey D , Sarreal Siov Bouy L , Kim Jong H 
Published: December 2023

Abstract
Populations of ochratoxin-producing Aspergillus section Circumdati species and aflatoxin-producing Aspergillus section Flavi species frequently coexist in soil and are the main sources of mycotoxin contamination of tree nuts. Identification of mycotoxigenic Aspergillus species in these sections is difficult using traditional isolation and culture methods. We developed a multiplex digital PCR (dPCR) assay to detect and quantify Aspergillus ochraceus, Aspergillus westerdijkiae, and Aspergillus steynii (section Circumdati), as well as Aspergillus flavus and Aspergillus parasiticus (section Flavi), in environmental samples based on species-specific calmodulin gene sequences. Relative quantification of each species by dPCR of mixed-species templates correlated with corresponding DNA input ratios. Target species could be detected in soil inoculated with conidia from each species. Non-target species of sections Circumdati, Flavi, and Nigri were generally not detectable using this dPCR method. Detected non-target species (Aspergillus fresenii, Aspergillus melleus, Aspergillus sclerotiorum, and Aspergillus subramanianii) were discernible from A. ochraceus in dual-template dPCR reactions based on differential fluorescence intensity.