bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative Trait Locus Mapping for Fire Blight Resistance in an F2 Population of Malus fusca MAL0045 Uncovers Novel Resistance Loci
Authors: Emeriewen Ofere Francis , Richter Klaus , Flachowsky Henryk , Peil Andreas 
Published: October 2023

Several fire blight resistance loci in Malus genotypes map on different linkage groups (LGs) representing chromosomes of the domesticated apple. Prior genetics studies primarily focused on F1 populations. A strong resistance quantitative trait locus (QTL) explained up to 66% of phenotypic variance in an F1 progeny derived from crossing the highly resistant wild apple genotype Malus fusca MAL0045 and the highly susceptible apple cultivar ‘Idared’, which was previously mapped on LG10 ( Mfu10) of MAL0045. Strains of the causative bacterial pathogen Erwinia amylovora, notably those that show a single nucleotide polymorphism in the avrRpt2EA effector protein sequence at position 156 (e.g., Ea3049), are more virulent and overcome some known fire blight resistance donors and their QTLs. However, MAL0045 is resistant to Ea3049 and Mfu10 is not overcome, but most of the F1 progeny were highly susceptible to this strain. This phenomenon led to the assumption that other putative resistance factors not segregating in the F1 progeny might be present in the genome of MAL0045. Here, we crossed F1 progeny together to obtain 135 F2 individuals. Facilitated by genotyping-by-sequencing and phenotypic assessments, we identified and mapped two novel resistance QTLs in these F2 individuals on LGs 4 and 15, which were not identified in the F1. To our knowledge, these are the first resistance QTLs mapped in F2 progeny in Malus. In addition, we report that neither MAL0045 nor Mfu10 is broken down by a highly aggressive U.S. strain, LA635, after analyses in the original F1 individuals. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Multigenic Hairpin Transgenes in Tomato Confer Resistance to Multiple Orthotospoviruses Including Sw-5 Resistance-Breaking Tomato Spotted Wilt Virus
Authors: Oliver Jonathan E. , Rotenberg Dorith , Agosto-Shaw Karolyn , McInnes Holly A. , Lahre Kirsten A. , Mulot Michaël , Adkins Scott , Whitfield Anna E. 
Published: October 2023

Tomato spotted wilt virus (TSWV) and related thrips-borne orthotospoviruses are a threat to food and ornamental crops. Orthotospoviruses have the capacity for rapid genetic change by genome segment reassortment and mutation. Genetic resistance is one of the most effective strategies for managing orthotospoviruses, but there are multiple examples of resistance gene breakdown. Our goal was to develop effective multigenic, broad-spectrum resistance to TSWV and other orthotospoviruses. The most conserved sequences for each open reading frame (ORF) of the TSWV genome were identified, and comparison with other orthotospoviruses revealed sequence conservation within virus clades; some overlapped with domains with well-documented biological functions. We made six hairpin constructs, each of which incorporated sequences matching portions of all five ORFs. Tomato plants expressing the hairpin transgene were challenged with TSWV by thrips and leaf-rub inoculation, and four constructs provided strong protection against TSWV in foliage and fruit. To determine if the hairpin constructs provided protection against other emerging orthotospoviruses, we challenged the plants with tomato chlorotic spot virus and resistance-breaking TSWV and found that the same constructs also provided resistance to these related viruses. Antiviral hairpin constructs are an effective way to protect plants from multiple orthotospoviruses and are an important strategy in the fight against resistance-breaking TSWV and emerging viruses. Targeting of all five viral ORFs is expected to increase the durability of resistance, and combining them with other resistance genes could further extend the utility of this disease control strategy. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Complete Genome Sequence of Sclerotinia sclerotiorum (S1), One of the Pathogens Causing Sclerotinosis in Mulberry Fruit
Authors: Peng Fangfang , Li Xunlan , Wei Zhaoxin , Han Guohui 
Published: October 2023

Sclerotinia sclerotiorum is a fungal pathogen that infects an extremely wide range of hosts and can cause diseases in over 600 plant species. In this study, Sclerotinia sclerotiorum (strain S1), which causes sclerotinosis in mulberry fruits, was isolated from the mulberry orchard at the Chongqing Academy of Agricultural Sciences, China, and its complete genome was sequenced using PacBio Sequel II. The assembly consists of 24 contigs with an estimated genome size of 38.91 Mbp and is predicted to encode 9,920 protein-coding genes. This is the first genomic information for Sclerotinia sclerotiorum isolated from diseased mulberry fruit and represents a valuable resource for a comprehensive understanding of Sclerotinia spp. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Effect of Topical Antibiotic Powder Application in the Emergency Department on Deep Fracture Related Infection in Type III Open Lower Extremity Fractures
Authors: Taylor Shea , John Mitchell P , Grayson Whisper , Mir Hassan R. 
Published: October 2023

Abstract

Objective:
Despite advances in management, open fractures are at an elevated risk for deep fracture related infection (FRI). Time to systemic antibiotic (ABX) administration and intraoperative topical administration of ABX powder have been utilized to decrease FRI risk. The purpose of this study was to determine if topical application of antibiotic powder to type III open lower extremity fractures immediately upon presentation to the emergency department (ED) reduces the rate of FRI.

Methods:

Design:
Prospective cohort compared to retrospective historical control

Setting:
Level I trauma center

Intervention:
Application of 1g vancomycin and 1.2g tobramycin powder directly to open fracture wounds on presentation to the ED.

Patient Selection Criteria:
Patients with type III open lower extremity fractures treated from July 1, 2019 to September 17, 2022 who received topical ABX powder in the ED were compared to patients from a 4-year historical cohort from July 1, 2015 to June 30, 2019 who were treated without topical ABX powder.

Outcome Measures and Comparisons:
Development of a FRI within 6 months of follow up. Patient demographics, injury characteristics, and postoperative data were analyzed as risk factors for FRI.

Results:
Sixty-six patients received topical ABX powder in the ED and were compared to 129 patients who were treated without topical ABX powder.
The rate of FRI in the trial group was 6/66 (9.09%) versus 22/129 (17.05%) in the control cohort (p=.133). Multivariate analysis demonstrated higher BMI as a risk factor for development of FRI (p=0.036).

Conclusion:
No statistically significant difference in rates of FRI in open lower extremity fractures treated with immediate topical ABX administration in the ED versus standard of care treatment without topical ABX were found. These findings may have been limited by insufficient power. Further large-scale study is warranted to determine the significance of topical antibiotic powder application in the ED.

Level of Evidence:
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Successful Outcomes with Nonoperative Treatment and Immediate Weightbearing Despite Stress-Positive Radiographs in Isolated Distal Fibula (OTA/AO 44B) Fractures
Authors: Stockwell Erin , Thomas Phillip , Grossman Leonid , Lyden Elizabeth , Mormino Matthew , Siebler Justin , Putnam Sara 
Published: October 2023

Abstract
Objectives: To determine if a nonoperative management protocol results in equivalent outcomes in isolated OTA/AO 44B (Weber B) fractures without initial medial clear space (MCS) widening regardless of stress radiography findings
Design: Prospective cohort
Setting: Level 1 academic trauma center
Patients/Participants: Sixty-nine patients with isolated OTA/AO 44B fractures and MCS ≤ 4 mm on initial non-weightbearing injury radiographs over a 4-year period
Intervention: nonoperative management of isolated OTA/AO 44B fractures without initial MCS widening > 4 mm
Main Outcome Measurements: MCS measurements on weightbearing radiographs at first follow up, six weeks, 12 weeks, and six months post-injury; American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores
Results: None of the 38/69 (55%) patients with widening on gravity stress radiographs demonstrated persistent widening with weightbearing radiographs at any time point. Mean MCS measurement differences between the two cohorts were statistically significant for all time points (p=0.012), however with a model adjusted mean MCS value of 2.7 mm for the non-widening cohort and 2.9 mm for the widening cohort, these are not clinically significant. There was no statistically significant difference in overall final AOFAS scores between the two groups (p=0.451). Additionally, statistical equivalence using Schuirmann’s two one-sided tests was achieved between the two groups. Both cohorts had mean AOFAS scores representing excellent outcomes at final follow up.
Conclusions: Isolated OTA/AO 44B fractures without MCS widening on initial injury radiographs have equivalent outcomes regardless of gravity stress radiography findings when treated nonoperatively. Weightbearing radiographs at initial follow-up are a reliable assessment of ankle stability in these injuries and are an appropriate alternative to painful and time-consuming stress radiography.
Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Multistudy Research Operations in the ICU: An Interprofessional Pandemic-Informed Approach
Authors: Cook Deborah J. , Duan Erick H. , Clarke France J. , Matic Karlo , Culgin Sarah , Kelly Laurel , Nelson Katlynne S. , Wallace Christine V. , Soth Mark D. , Lewis Kimberley A. , Rudkowski Jill C. , Perri Dan , Ligori Tania L. , Jaeschke Roman Z. , Chagla Zain , Chaudhuri Dipayan , Wright Angela E. , Fu Zoe Y. , Reeve Brenda K. , Lee Hilary M. , Overington Jeffrey D. , Rozenberg Anna , Bloomfield Kimberly A. , Love Katryn , Gain Jennifer L. , Zytaruk Nicole L. , Cheung Jason H. , Thabane Lehana , Kho Michelle E. ,   for the Department of Critical Care Research Operations Committee
Published: October 2023

OBJECTIVES:
Proliferation of COVID-19 research underscored the need for improved awareness among investigators, research staff and bedside clinicians of the operational details of clinical studies. The objective was to describe the genesis, goals, participation, procedures, and outcomes of two research operations committees in an academic ICU during the COVID-19 pandemic.

DESIGN:
Two-phase, single-center multistudy cohort.

SETTING:
University-affiliated ICU in Hamilton, ON, Canada.

PATIENTS:
Adult patients in the ICU, medical stepdown unit, or COVID-19 ward.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
An interprofessional COVID Collaborative was convened at the pandemic onset within our department, to proactively coordinate studies, help navigate multiple authentic consent encounters by different research staff, and determine which studies would be suitable for coenrollment. From March 2020 to May 2021, five non-COVID trials continued, two were paused then restarted, and five were launched. Over 15 months, 161 patients were involved in 215 trial enrollments, 110 (51.1%) of which were into a COVID treatment trial. The overall informed consent rate (proportion agreed of those eligible and approached including a priori and deferred consent models) was 83% (215/259). The informed consent rate was lower for COVID-19 trials (110/142, 77.5%) than other trials (105/117, 89.7%; p = 0.01). Patients with COVID-19 were significantly more likely to be coenrolled in two or more studies (29/77, 37.7%) compared with other patients (13/84, 15.5%; p = 0.002). Review items for each new study were collated, refined, and evolved into a modifiable checklist template to set up each study for success. The COVID Collaborative expanded to a more formal Department of Critical Care Research Operations Committee in June 2021, supporting sustainable research operations during and beyond the pandemic.

CONCLUSIONS:
Structured coordination and increased communication about research operations among diverse research stakeholders cultivated a sense of shared purpose and enhanced the integrity of clinical research operations.
Elevated Driving Pressure and Elastance Does Not Increase In-Hospital Mortality Among Obese and Severely Obese Patients With Ventilator Dependent Respiratory Failure
Authors: Terry Charles , Brinton Daniel , Simpson Annie N. , Kirchoff Katie , Files D. Clark , Carter George , Ford Dee W. , Goodwin Andrew J. 
Published: October 2023

Importance:
Existing recommendations for mechanical ventilation are based on studies that under-sampled or excluded obese and severely obese individuals.

Objective:
To determine if driving pressure (DP) and total respiratory system elastance (Ers) differ among normal/overweight (body mass index [BMI] < 30 kg/m2), obese, and severely obese ventilator-dependent respiratory failure (VDRF) patients and if there any associations with clinical outcomes.

Design, Setting, and Participants:
Retrospective observational cohort study during 2016–2018 at two tertiary care academic medical centers using electronic health record data from the first 2 full days of mechanical ventilation. The cohort was stratified by BMI classes to measure median DP, time-weighted mean tidal volume, plateau pressure, and Ers for each BMI class.

Setting and Participants:
Mechanically ventilated patients in medical and surgical ICUs.

Main Outcomes and Measures:
Primary outcome and effect measures included relative risk of in-hospital mortality, ventilator-free days, ICU length of stay, and hospital length of stay with multivariable adjustment.

Results:
The cohort included 3,204 patients with 976 (30.4%) and 382 (11.9%) obese and severely obese patients, respectively. Severe obesity was associated with a DP greater than or equal to 15 cm H2O (relative risk [RR], 1.51 [95% CI, 1.26–1.82]) and Ers greater than or equal to 2 cm H2O/(mL/kg) (RR, 1.31 [95% CI, 1.14–1.49]). Despite elevated DP and Ers, there were no differences in in-hospital mortality, ventilator-free days, or ICU length of stay among all three groups.

Conclusions and Relevance:
Despite higher DP and ERS among obese and severely obese VDRF patients, there were no differences in in-hospital mortality or duration of mechanical ventilation, suggesting that DP has less prognostic value in obese and severely obese VDRF patients.
Indications of Effective Hyperbaric Oxygen Therapy Combined With Steroid Therapy for Sudden Hearing Loss
Authors: Ohira Shinya , Komori Manabu , Tsuna Yukari , Nakamura Mitsuto , Yamaguchi Yusei , Matsuura Kentaro , Osafune Hiroshi , Wada Kota 
Published: October 2023

Objective
This study evaluated the therapeutic effect of hyperbaric oxygen therapy (HBOT) combined with steroid therapy to treat sudden hearing loss and examined the index associated with excellent therapeutic effect.

Methods
We included 109 patients with sudden hearing loss. Patients were divided into the HBOT combination group (59 sides) treated with HBOT and steroid therapy and HBOT noncombination group (50 sides) involving steroid therapy only. The recovery rate of each group was compared according to the severity of hearing loss. Blood samples were evaluated and inflammatory markers, such as neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR), were calculated and compared by severity. We evaluated the usefulness of inflammatory markers for predicting recovery rate, and calculated cutoff values were also evaluated.

Results
The HBOT combination group exhibited a higher overall recovery rate than the HBOT noncombination group, particularly in severe cases. However, there was no significant difference in the severity of hearing loss based on various inflammatory markers. NLR and PLR are useful for predicting the effect in patients treated with concomitant HBOT. By setting 2.43 and 146.67 as cutoff values for NLR and PLR, respectively, we observed that lower values resulted in better recovery rates.

Conclusion
The use of HBOT is effective for severe cases and early blood flow disorders with low NLR and PLR and less inflammation. When determining treatment, not only should the severity of hearing loss be considered, but also the NLR and PLR should be evaluated and examined based on the cutoff values.
Predictive Factors for Subjective Vertigo Following Cochlear Implantation: A Regional Multicenter Cohort Study of 395 Patients
Authors: Ludbrook Isabella , Mair Manish , Phung Daniel , Corlette Toby , Huang Johnson , Kong (Worimi) Kelvin , Eisenberg Robert 
Published: October 2023

Introduction
Cochlear implantation (CI) is generally accepted as having a low rate of postoperative complications, but between 9.3% and 13% of cases experience vertigo postoperatively. This study aimed to examine patient, surgical, and device factors contributing toward the risk of postoperative vertigo.

Methodology
A retrospective review was conducted of adult patients who underwent cochlear implant in a regional area of New South Wales from 2007 to 2018. A total of 395 cochlear implant cases were included in the final study.

Results
The overall incidence of vertigo at 3 months of follow-up was 7.1% (n = 28/395). No difference was identified in this study between rates of postoperative vertigo between device factors, including implant make (Cochlear vs. Med-El), electrode shape (perimodiolar vs. straight), and electrode model. No significant difference was found also for surgical factors such as the number of electrode rings inserted, side of implantation, or surgical approach of tympanic ramp (round window insertion vs. cochleostomy).
A higher percentage of patients with preoperative vertigo experienced vertigo postoperatively (18.4%, n = 7/38), compared with the population without preoperative vertigo (6.0%, n = 21/352) (p = 0.005). Patients with previous mastoid surgery also reported a higher rate of postoperative vertigo (20%, n = 9/45) compared with those who had not had mastoid surgery (5.43%, n = 19/350) (p = 0.006). The mean age of patients experiencing postoperative vertigo was higher than the population without postoperative symptoms (67 vs. 63).

Conclusion
This study of a large multicenter population outlines that patient factors are more critical than surgical or device factors when considering risk factors for vertigo post-cochlear implant.
AF2BIND: Predicting ligand-binding sites using the pair representation of AlphaFold2
Authors: Gazizov Artem , Lian Anna , Goverde Casper , Ovchinnikov Sergey , Polizzi Nicholas F. 
Published: October 2023

AbstractPredicting ligand-binding sites, particularly in the absence of previously resolved homologous structures, presents a significant challenge in structural biology. Here, we leverage the internal pairwise representation of AlphaFold2 (AF2) to train a model, AF2BIND, to accurately predict small-molecule-binding residues given only a target protein. AF2BIND uses 20 “bait” amino acids to optimally extract the binding signal in the absence of a small-molecule ligand. We find that the AF2 pair representation outperforms other neural-network representations for binding-site prediction. Moreover, unique combinations of the 20 bait amino acids are correlated with chemical properties of the ligand.
Accurate identification of cancer cells in complex pre-clinical models using deep-learning: a transfection-free approach
Authors: Cortesi Marilisa , Liu Dongli , Powell Elyse , Barlow Ellen , Warton Kristina , Ford Caroline E. 
Published: October 2023

Abstract3D co-cultures are key tools forin vitrobiomedical research as they recapitulate more closely thein vivoenvironment, while allowing control of the density and type of cells included in the analysis, as well as the experimental conditions in which they are maintained. More widespread application of these models is hampered however by the limited technologies available for their analysis. The separation of the contribution of the different cell types, in particular, is a fundamental challenge.In this work, we present ORACLE, a deep neural network trained to distinguish between ovarian cancer and healthy cells based on the shape of their nucleus. The extensive validation that we have conducted includes multiple cell lines and patient derived cultures to characterise the effect of all the major potential confounding factors. High accuracy and reliability were maintained throughout the analysis demonstrating ORACLE effectiveness with this detection and classification task.ORACLE is freely available (https://github.com/MarilisaCortesi/ORACLE/tree/main) and can be used to recognise both ovarian cancer cell lines and primary patient-derived cells. This feature sets ORACLE apart from currently available analysis methods and opens the possibility of analysingin vitroco-cultures comprised solely of patient-derived cells.
ChEC-seq2: an improved Chromatin Endogenous Cleavage sequencing method and bioinformatic analysis pipeline for mappingin vivoprotein-DNA interactions
Authors: VanBelzen Jake , Duan Chengzhe , Brickner Donna Garvey , Brickner Jason H. 
Published: October 2023

AbstractDefining thein vivoDNA binding specificity of transcription factors (TFs) has relied nearly exclusively on chromatin immunoprecipitation (ChIP). While ChIP reveals TF binding patterns, its resolution is low. Higher resolution methods employing nucleases such as ChIP-exo, chromatin endogenous cleavage (ChEC-seq) and CUT&RUN resolve both TF occupancy and binding site protection. ChEC-seq, in which an endogenous TF is fused to micrococcal nuclease, requires neither fixation nor antibodies. However, the specificity of DNA cleavage during ChEC has been suggested to be lower than the specificity of the peaks identified by ChIP or ChIP-exo, perhaps reflecting non-specific binding of transcription factors to DNA. We have simplified the ChEC-seq protocol to minimize nuclease digestion while increasing the yield of cleaved DNA. ChEC-seq2 cleavage patterns were highly reproducible between replicates and with published ChEC-seq data. Combined with DoubleChEC, a new bioinformatic pipeline that removes non-specific cleavage sites, ChEC-seq2 identified high-confidence cleavage sites for three different yeast TFs that are strongly enriched for their known binding sites and adjacent to known target genes.