bluuebunny/crossref_metadata_2025 huggingface dataset:
Excess demand amid quality misperceptions: the case for low-cost seed quality signalling strategies
Authors: Maredia Mywish K , Bartle Brian
Published: September 2022

Planting quality seed is essential for increasing crop productivity. We study the potato seed market in Kenya and estimate farmers’ willingness to pay for certified, clean and ware potato seeds that use reputation and certification strategies at varying costs to provide quality signal. We find that farmers are prone to quality misperceptions and adjust their bids for high (low) quality seed upward (downward) in response to positive (negative) quality signals. Effective demand for quality seeds exceeds supply 286 per cent after correcting quality misperceptions. We make a strong case for the need of low-cost alternatives to meet this excess demand for quality seeds.
Self-reported health and adverse outcomes among women living with symptoms of angina or unspecific chest pain but no diagnosis of obstructive coronary artery disease—findings from the DenHeart study
Authors: Dalsgaard Jane Lange , Hansen Michael Skov , Thrysoee Lars , Ekholm Ola , Thorup Charlotte Brun , Mols Rikke Elmose , Rasmussen Trine Bernholdt , Christensen Anne Vinggaard , Berg Selina Kikkenborg , Pedersen Andreas Kristian , Jensen Lisette Okkels , Mogensen Christian Backer , Borregaard Britt
Published: September 2022

Aims

The objectives were to describe differences in self-reported health at discharge between women diagnosed with angina or unspecific chest pain and investigate the association between self-reported health and adverse outcomes within 3 years.

Methods and results

Data from a national cohort study were used, including data from the DenHeart survey combined with 3 years of register-based follow-up. The population included two groups of women with symptoms of angina but no diagnosis of obstructive coronary artery disease at discharge (women with angina and women with unspecific chest pain). Self-reported health measured with validated instruments was combined with register-based follow-up on adverse outcomes (a composite of unplanned cardiac readmissions, revascularization, or all-cause mortality). Associations between self-reported health and time to first adverse outcomes were investigated with Cox proportional hazard models, reported as hazards ratios with 95% confidence intervals. In total, 1770 women completed the questionnaire (49%). Women with angina (n = 931) reported significantly worse self-reported health on several outcomes compared to women with unspecific chest pain (n = 839). Within the 3 years follow-up, women with angina were more often readmitted (29 vs. 23%, P = 0.011) and more underwent revascularization (10 vs. 1%, P < 0.001), whereas mortality rates were similar (4 vs. 4%, P = 0.750). Self-reported health (physical and mental) was associated with adverse outcomes between both groups (on most instruments).

Conclusion

Women with angina reported significantly worse self-reported health on most instruments compared to women with unspecific chest pain. Adverse outcomes varied between groups, with women diagnosed with angina experiencing more events.

Registration

ClinicalTrials.gov (NCT01926145).
Transvenous phrenic nerve stimulation to treat central sleep apnoea in patients with heart failure may improve sleep, quality of life, and symptoms
Authors: Hill Loreena , Meyer Timothy , McKane Scott , Lainscak Mitja , Ahmed Qanta A
Published: September 2022

Aims

Sleep disorder breathing is an important non-cardiovascular comorbidity in patients with heart failure (HF). However, central sleep apnoea (CSA) remains poorly diagnosed and treated. This post hoc analysis examined symptoms and quality of life in patients with CSA and HF following 12 months of transvenous phrenic nerve stimulation (TPNS) therapy.

Methods and results

Patients enrolled in the remedē System Pivotal trial were invited to complete self-reported questionnaires. Symptoms and responses to three validated questionnaires were examined. Percentage of patients noting an impairment was calculated at baseline. At 12 months, % of patients experiencing improvement, no change, or worsening was calculated. Shifts from symptom presence at baseline to absence at 12 months were assessed for those symptoms experienced by ≥50% of patients at baseline. Seventy-five patients were included. Most frequently reported symptoms were fatigue and daytime sleepiness. Following 12 months of TPNS, a variety of subjective improvements were observed; 45% of patients indicating cessation of daytime sleepiness, 44% cessation of fatigue/weakness, and 52% no longer having difficulty falling/staying asleep. Specific questions related to tiredness/fatigue, motivation, and chance of dozing provided an insight into potential areas of improvement. Furthermore, at least 60% of patients reported resolution of insomnia/fragmented sleep and snoring on therapy.

Conclusion

Adult patients with CSA and HF experience distressing symptoms and limitations. Transvenous phrenic nerve stimulation was found to improve many of these. Awareness of key symptoms or limitations patients experience can be used to inform the development of a CSA-specific patient questionnaire to identify CSA sooner and aid treatment decisions.
Risk of ionizing radiation in pregnancy: just a myth or a real concern?
Authors: Saada Majdi , Sanchez-Jimenez Erick , Roguin Ariel
Published: September 2022

There are natural concerns regarding the risks posed to the foetus by ionizing radiation exposure during pregnancy. Therefore, many female physicians select to avoid working in an environment associated with ionizing radiation exposure like the catheterization laboratory and even exclude training as electrophysiology, interventional cardiologists, or radiologists. For those already working in this field, pregnancy involves usually a 1-year interruption (pregnancy and maternity leave) to their careers, leading at times to delays in the decision to become pregnant. This review describes the low added risk of malformation/cancer in the offspring, highlight gaps in our understanding, discuss several common wrong beliefs, and recommend how to further decrease radiation dose, especially during pregnancy.
Non-invasive assessment of pulmonary vein isolation durability using late gadolinium enhancement magnetic resonance imaging
Authors: Padilla-Cueto David , Ferro Elisenda , Garre Paz , Prat Susanna , Guichard Jean-Baptiste , Perea Rosario J , Tolosana Jose Maria , Guasch Eduard , Arbelo Elena , Porta-Sanchéz Andreu , Roca-Luque Ivo , Sitges Marta , Brugada Josep , Mont Lluís , Althoff Till F
Published: September 2022

Aims

Electrical reconnection of pulmonary veins (PVs) is considered an important determinant of recurrent atrial fibrillation (AF) after pulmonary vein isolation (PVI). To date, AF recurrences almost automatically trigger invasive repeat procedures, required to assess PVI durability. With recent technical advances, it is becoming increasingly common to find all PVs isolated in those repeat procedures. Thus, as ablation of extra-PV targets has failed to show benefit in randomized trials, more and more often these highly invasive procedures are performed only to rule out PV reconnection. Here we aim to define the ability of late gadolinium enhancement (LGE)-magnetic resonance imaging (MRI) to rule out PV reconnection non-invasively.

Methods and results

This study is based on a prospective registry in which all patients receive an LGE-MRI after AF ablation. Included were all patients that—after an initial PVI and post-ablation LGE-MRI—underwent an invasive repeat procedure, which served as a reference to determine the predictive value of non-invasive lesion assessment by LGE-MRI.: 152 patients and 304 PV pairs were analysed. LGE-MRI predicted electrical PV reconnection with high sensitivity (98.9%) but rather low specificity (55.6%). Of note, LGE lesions without discontinuation ruled out reconnection of the respective PV pair with a negative predictive value of 96.9%, and patients with complete LGE lesion sets encircling all PVs were highly unlikely to show any PV reconnection (negative predictive value: 94.4%).

Conclusion

LGE-MRI has the potential to guide selection of appropriate candidates and planning of the ablation strategy for repeat procedures and may help to identify patients that will not benefit from a redo-procedure if no ablation of extra-PV targets is intended.
d-StructMAn: Containerized structural annotation on the scale from genetic variants to whole proteomes
Authors: Gress Alexander , Srikakulam Sanjay K , Keller Sebastian , Ramensky Vasily , Kalinina Olga V
Published: September 2022

Background

Structural annotation of genetic variants in the context of intermolecular interactions and protein stability can shed light onto mechanisms of disease-related phenotypes. Three-dimensional structures of related proteins in complexes with other proteins, nucleic acids, or ligands enrich such functional interpretation, since intermolecular interactions are well conserved in evolution.

Results

We present d-StructMAn, a novel computational method that enables structural annotation of local genetic variants, such as single-nucleotide variants and in-frame indels, and implements it in a highly efficient and user-friendly tool provided as a Docker container. Using d-StructMAn, we annotated several very large sets of human genetic variants, including all variants from ClinVar and all amino acid positions in the human proteome. We were able to provide annotation for more than 46% of positions in the human proteome representing over 60% proteins.

Conclusions

d-StructMAn is the first of its kind and a highly efficient tool for structural annotation of protein-coding genetic variation in the context of observed and potential intermolecular interactions. d-StructMAn is readily applicable to proteome-scale datasets and can be an instrumental building machine-learning tool for predicting genotype-to-phenotype relationships.
A consistent multiparameter Bayesian full waveform inversion scheme for imaging heterogeneous isotropic elastic media
Authors: Kan Li-Yu , Chevrot Sébastien , Monteiller Vadim
Published: September 2022

The inversion of complete seismic waveforms offers new perspectives to better constrain the elastic properties of Earth’s interior. However, models of density and seismic velocities obtained from full waveform inversions are generally characterized by very different and uneven spatial resolutions. Because the 3-D structure of the Earth represents small deviations from average reference Earth models, the absolute values of density, VP and VS in the Earth are strongly correlated. Here, we exploit this strong correlation between model parameters as a priori information introduced into a new full waveform inversion algorithm, by considering a non-diagonal 3-D model covariance matrix in which the spatial correlations of elastic properties are described with an exponential covariance function. The inverse of such a model covariance matrix is easy to compute, and we thus have all the ingredients to construct a consistent Bayesian full waveform inversion scheme. We show that taking into account the correlations between density and seismic velocities can lead to dramatic improvements on the reconstructed models of density, seismic velocities and VP/VS ratio. This new imaging approach opens new perspectives for refining tomographic images of density and seismic velocities in the lithosphere and upper mantle on a regional scale by full waveform inversion of teleseismic body waves.
Can GPS and GRACE data be used to separate past and present-day surface loading in a data-driven approach?
Authors: Ziegler Yann , Vishwakarma Bramha Dutt , Brady Aoibheann , Chuter Stephen , Royston Sam , Westaway Richard M , Bamber Jonathan L
Published: September 2022

Glacial isostatic adjustment (GIA) and the hydrological cycle are both associated with mass changes and vertical land motion (VLM), which are observed by GRACE and GPS, respectively. Hydrology-related VLM results from the instantaneous response of the elastic solid Earth to surface loading by freshwater, whereas GIA-related VLM reveals the long-term response of the viscoelastic Earth mantle to past ice loading history. Thus, observations of mass changes and VLM are interrelated, making GIA and hydrology difficult to quantify and study independently. In this work, we investigate the feasibility of separating these processes based on GRACE and GPS observations, in a fully data-driven and physically consistent approach. We take advantage of the differences in the spatio-temporal characteristics of the GIA and hydrology fields to estimate the respective contributions of each component using a Bayesian hierarchical modelling framework. A closed-loop synthetic test confirms that our method successfully solves this source separation problem. However, there are significant challenges when applying the same approach with actual observations and the answer to the main question of this study is more nuanced. In particular, in regions where GPS station coverage is sparse, the lack of informative data becomes a limiting factor.
Atmospheric model inversion using infrasound signals from the North Korean underground nuclear explosion and the subsequent collapse event in 2017
Authors: Park Junghyun , Assink Jelle , Stump Brian , Hayward Chris , Arrowsmith Stephen , Che Il-Young
Published: September 2022

This study focuses on the infrasound signals from the September 2017 North Korean underground nuclear explosion (UNE17) and subsequent collapse event (SCE17) that occurred close to the autumnal equinox when the atmospheric temperature structure undergoes rapid change. Multiple arrivals, including contributions from local, diffracted and epicentral infrasound, generated by UNE17, were observed at eight infrasound arrays in the Korean Peninsula and one IMS infrasound station (IS45) in Russia while at the closest five arrays for SCE17 only epicentral infrasound was observed. The UNE17 signals provide the opportunity to explore the utility of each distinct arrival in constraining atmospheric conditions during the change associated with the equinox. The observed characteristics of the multiple epicentral infrasonic phases (celerity, backazimuth, phase velocity and spectra) suggest propagation paths through the tropospheric, stratospheric and thermospheric waveguides, although geometric ray paths based on a global atmospheric model at the time of the explosion predict only thermospheric returns. The absence of predicted stratospheric returns may reflect errors in the atmospheric models due to the lack of predicted stratospheric winds which are weak and changing close to the autumnal equinox or the limited resolution of the fine-scale structure not captured by current atmospheric models. The differences between the model predictions and the observations suggest that the numerical weather forecast models need to be modified to fully explain the observations. In order to explore the model space that can explain the UNE17 data set, an inversion scheme is applied to atmospheric wind model parameters constrained by the multi-array observations. Zonal and meridional wind profiles are parametrized using empirical orthogonal functions (EOFs) estimated from 1-yr of Ground-to-Space atmospheric specifications. A best-fitting atmospheric model is estimated using a Bayesian approach that assesses the uncertainty in the inverse solution using a joint likelihood function combining components of azimuth deviation, traveltime and phase velocity. The updated atmospheric models from six different EOFs inversions have up to 20 m s–1 stronger zonal and meridional wind speeds in the stratosphere compared to the original model, and explain the stratospheric observations in the data set. This investigation illustrates that modest changes to atmospheric wind models at the time of autumnal equinox can improve the prediction of stratospheric returns.
High-quality chromosome-scale genomes facilitate effective identification of large structural variations in hot and sweet peppers
Authors: Lee Joung-Ho , Venkatesh Jelli , Jo Jinkwan , Jang Siyoung , Kim Geon Woo , Kim Jung-Min , Han Koeun , Ro Nayoung , Lee Hea-Young , Kwon Jin-Kyung , Kim Yong-Min , Lee Tae-Ho , Choi Doil , Van Deynze Allen , Hill Theresa , Kfir Nir , Freiman Aviad , Davila Olivas Nelson H , Elkind Yonatan , Paran Ilan , Kang Byoung-Cheorl
Published: September 2022

Pepper (Capsicum annuum) is an important vegetable crop that has been subjected to intensive breeding, resulting in limited genetic diversity, especially for sweet peppers. Previous studies have reported pepper draft genome assemblies using short read sequencing, but their capture of the extent of large structural variants (SVs), such as presence–absence variants (PAVs), inversions, and copy-number variants (CNVs) in the complex pepper genome falls short. In this study, we sequenced the genomes of representative sweet and hot pepper accessions by long-read and/or linked-read methods and advanced scaffolding technologies. First, we developed a high-quality reference genome for the sweet pepper cultivar ‘Dempsey’ and then used the reference genome to identify SVs in 11 other pepper accessions and constructed a graph-based pan-genome for pepper. We annotated an average of 42 972 gene families in each pepper accession, defining a set of 19 662 core and 23 115 non-core gene families. The new pepper pan-genome includes informative variants, 222 159 PAVs, 12 322 CNVs, and 16 032 inversions. Pan-genome analysis revealed PAVs associated with important agricultural traits, including potyvirus resistance, fruit color, pungency, and pepper fruit orientation. Comparatively, a large number of genes are affected by PAVs, which is positively correlated with the high frequency of transposable elements (TEs), indicating TEs play a key role in shaping the genomic landscape of peppers. The datasets presented herein provide a powerful new genomic resource for genetic analysis and genome-assisted breeding for pepper improvement.
Recoloring tomato fruit by CRISPR/Cas9-mediated multiplex gene editing
Authors: Yang Tianxia , Ali Muhammad , Lin Lihao , Li Ping , He Hongju , Zhu Qiang , Sun Chuanlong , Wu Ning , Zhang Xiaofei , Huang Tingting , Li Chang-Bao , Li Chuanyou , Deng Lei
Published: September 2022

Fruit color is an important horticultural trait, which greatly affects consumer preferences. In tomato, fruit color is determined by the accumulation of different pigments, such as carotenoids in the pericarp and flavonoids in the peel, along with the degradation of chlorophyll during fruit ripening. Since fruit color is a multigenic trait, it takes years to introgress all color-related genes in a single genetic background via traditional crossbreeding, and the avoidance of linkage drag during this process is difficult. Here, we proposed a rapid breeding strategy to generate tomato lines with different colored fruits from red-fruited materials by CRISPR/Cas9-mediated multiplex gene editing of three fruit color-related genes (PSY1, MYB12, and SGR1). Using this strategy, the red-fruited cultivar ‘Ailsa Craig’ has been engineered to a series of tomato genotypes with different fruit colors, including yellow, brown, pink, light-yellow, pink-brown, yellow-green, and light green. Compared with traditional crossbreeding, this strategy requires less time and can obtain transgene-free plants with different colored fruits in less than 1 year. Most importantly, it does not alter other important agronomic traits, like yield and fruit quality. Our strategy has great practical potential for tomato breeding and serves as a reference for improving multigene-controlled traits of horticultural crops.
Acute Kidney Injury after High-Flow Regional Cerebral Perfusion in Neonatal and Infant Aortic Arch Repair
Authors: Shikata Fumiaki , Miyaji Kagami , Kohira Satoshi , Goto Hiroshi , Shinzo Torii , Kitamura Tadashi , Mishima Toshiaki , Fukuzumi Masaomi , Fujioka Shunichiro , Sasahara Akihiro , Araki Haruna
Published: September 2022

OBJECTIVES

We applied high-flow regional cerebral perfusion (HFRCP) for aortic arch reconstruction in neonates and infants by monitoring regional oxygen saturation of the thigh (rSO2T) using near-infrared spectroscopy to maintain peripheral perfusion. This study was designed to investigate the optimal perfusion flow of HFRCP for renal protection.

METHODS

From 2009 to 2021, 28 consecutive neonates and infants who underwent aortic arch reconstruction with HFRCP were enrolled. The median age of the patients was 27 days; the median body weight was 3.0 kg. In HFRCP, perfusion flow was targeted at approximately 80–100 mL/kg/min and then lowered corresponding to brain rSO2 levels and blood gas data. Isosorbide dinitrate and chlorpromazine were administered to enhance peripheral perfusion flow. Regional oxygen saturation of the forehead and thighs were monitored. The stage of acute kidney injury (AKI) was classified based on the Kidney Disease Improving Global Outcomes criteria.

RESULTS

No patients had neurological events and peritoneal dialysis after surgery. The incidence of AKI was 39.3% with only three patients having greater than stage 2 AKI. The maximum postoperative serum creatinine concentration was negatively associated with the lowest rSO2T during HFRCP. The rSO2T during HFRCP was a predictive factor for postoperative creatinine increase of ≧0.3 mg/dL. The area under receiver operating characteristic curve was 0.78 with the cutoff value of 48% for rSO2T.

CONCLUSIONS

The rSO2T during HFRCP is a potential predictor of postoperative renal function. To prevent AKI, the rSO2T should be preserved more than 48% by increasing HFRCP flow.
Second-Generation Human Immunodeficiency Virus Integrase Inhibitors Induce Differentiation Dysregulation and Exert Toxic Effects in Human Embryonic Stem Cell and Mouse Models
Authors: Smith Marie-Soleil R , Mohan Haneesha , Ajaykumar Abhinav , Hsieh Anthony Y Y , Martineau Lou , Patel Ronil , Gadawska Izabella , Sherwood Christopher , Serghides Lena , Piret James M , Côté Hélène C F
Published: September 2022

Background

Each year, approximately 1.1 million children are exposed in utero to human immunodeficiency virus antiretrovirals, yet their safety is often not well characterized during pregnancy. The Tsepamo study reported a neural tube defect signal in infants exposed to the integrase strand transfer inhibitor (InSTI) dolutegravir from conception, suggesting that exposure during early fetal development may be detrimental

Methods

The effects of InSTIs on 2 human embryonic stem cell (hESC) lines were characterized with respect to markers of pluripotency, early differentiation, and cellular health. In addition, fetal resorptions after exposure to InSTIs from conception were analyzed in pregnant mice.

Results

At subtherapeutic concentrations, second-generation InSTIs bictegravir, cabotegravir, and dolutegravir decreased hESC counts and pluripotency and induced dysregulation of genes involved in early differentiation. At therapeutic concentrations, bictegravir induced substantial hESC death and fetal resorptions. It is notable that first-generation InSTI raltegravir did not induce any hESC toxicity or differentiation, at any concentration tested.

Conclusions

Exposure to some InSTIs, even at subtherapeutic concentrations, can induce adverse effects in hESCs and pregnant mice. Given the increasingly prevalent use of second-generation InSTIs, including in women of reproductive age, it is imperative to further elucidate the effect of InSTIs on embryonic development, as well as their long-term safety after in utero exposure.
Localizing the International Relations Classroom: Evaluation of Academic Partnerships with City Government
Authors: Baer Madeline , Haddad Heidi Nichols
Published: September 2022

As the world becomes increasingly “smaller,” global governance too shifts beyond states and formal agreements to include norms and actors at all levels of government and society. Cities, in particular, are emergent actors in global affairs. This paper examines a new type of experiential learning model for this burgeoning local–global governance: academic partnerships with city governments for undergraduate international relations courses. Occidental College and Pomona College have partnered with the Los Angeles Mayor's Office to localize and adopt the United Nations Sustainable Development Goals (SDGs). This study focuses on two Spring 2021 Task Force courses, where students worked in consultation with the Mayor's Office to conduct policy research on local implementation of SDG 5 on gender equality. It analyzes the pedagogical value of the Task Force courses with a focus on student learning outcomes and challenges. Through qualitative content analysis of student reflection papers, we find that the courses generate substantial student learning, particularly in higher forms of learning, including development of research and professional skills and metacognitive reflection on “doing theory,” or praxis, within the international relations discipline. Further, these partnerships also benefit the city, as they generate valuable data that inform policymaking.
Rock physics model for shale gas reservoirs with nanopore adsorption
Authors: Yin Linjie , Yin Xingyao , Li Kun
Published: September 2022

Shale gas is primarily concentrated in nanopores extensively distributed in shale. The elastic properties of nanopores are significantly different from those of pores of larger sizes due to surface effects. How nanopores and adsorbed fluids affect the overall elastic properties of rock is rarely studied. Based on a recently developed nano-elasticity theory, a new method for calculating elastic modulus of nanoporous media considering adsorption is proposed by performing a detailed analysis on the relationship of surface adsorption with surface effects. The surface parameters of nanopores (pore radius, surface elastic moduli) are converted to adsorbed gas ratio and adsorbed gas elastic moduli. The proposed method is then used in rock physics modeling to estimate the elastic properties of nanoporous shale. The quantitative relationships of the effective velocities with adsorbed gas ratio, adsorbed gas elastic modulus and porosity of the shale are established, respectively. An important finding is that the elastic properties of nanoporous shale can be enhanced by increasing adsorbed gas ratio and adsorbed gas elastic moduli. A comparison between the theoretical model with laboratory data and the well data is performed and the results indicate that they are in good agreement. The results in this paper may provide certain insights on rock physics for the quantitative characterization of elastic properties of shale.
Diagnosing and managing a giant primary cutaneous malignant melanoma of the lower limb
Authors: Faderani Ryan , Ali Stephen R , Nijran Amit , Dobbs Thomas D , Karoo Richard
Published: September 2022

We present a woman who was referred to our plastic surgery unit with a suspected squamous cell carcinoma following a 3-year history of an enlarging mass on her thigh. Surprisingly, histopathological assessment confirmed the diagnosis of nodular malignant melanoma measuring 77×77×54 mm with a Breslow thickness of 52 mm, making it the largest recorded lower limb primary cutaneous malignant melanoma in the UK.
Temperature-induced changes in Arabidopsis Rubisco activity and isoform expression
Authors: Cavanagh Amanda P , Slattery Rebecca , Kubien David S
Published: September 2022

In many plant species, expression of the nuclear encoded Rubisco small subunit (SSu) varies with environmental changes, but the functional role of any changes in expression remains unclear. In this study, we investigated the impact of differential expression of Rubisco SSu isoforms on carbon assimilation in Arabidopsis. Using plants grown at contrasting temperatures (10 °C and 30 °C), we confirm the previously reported temperature response of the four RbcS genes and extend this to protein expression, finding that warm-grown plants produce Rubisco containing ~65% SSu-B and cold-grown plants produce Rubisco with ~65% SSu-A as a proportion of the total pool of subunits. We find that these changes in isoform concentration are associated with kinetic changes to Rubisco in vitro: warm-grown plants produce a Rubisco having greater CO2 affinity (i.e. higher SC/O and lower KC) but lower kcatCO2 at warm measurement temperatures. Although warm-grown plants produce 38% less Rubisco than cold-grown plants on a leaf area basis, warm-grown plants can maintain similar rates of photosynthesis to cold-grown plants at ambient CO2 and 30 °C, indicating that the carboxylation capacity of warm-grown Rubisco is enhanced at warmer measurement temperatures, and is able to compensate for the lower Rubisco content in warm-grown plants. This association between SSu isoform expression and maintenance of Rubisco activity at high temperature suggests that SSu isoform expression could impact the temperature response of C3 photosynthesis.
Five Influential Factors for Clinical Team Performance in Urgent, Emergency Care Contexts
Authors: Andreatta Pamela B , Graybill John Christopher , Renninger Christopher H , Armstrong Robert K , Bowyer Mark W , Gurney Jennifer M
Published: September 2022

Introduction

In deployed contexts, military medical care is provided through the coordinated efforts of multiple interdisciplinary teams that work across and between a continuum of widely distributed role theaters. The forms these teams take, and functional demands, vary by roles of care, location, and mission requirements. Understanding the requirements for optimal performance of these teams to provide emergency, urgent, and trauma care for multiple patients simultaneously is critical. A team’s collective ability to function is dependent on the clinical expertise (knowledge and skills), authority, experience, and affective management capabilities of the team members. Identifying the relative impacts of multiple performance factors on the accuracy of care provided by interdisciplinary clinical teams will inform targeted development requirements.

Materials and Methods

A regression study design determined the extent to which factors known to influence team performance impacted the effectiveness of small, six to eight people, interdisciplinary teams tasked with concurrently caring for multiple patients with urgent, emergency care needs. Linear regression analysis was used to distinguish which of the 11 identified predictors individually and collectively contributed to the clinical accuracy of team performance in simulated emergency care contexts.

Results

All data met the assumptions for regression analyses. Stepwise linear regression analysis of the 11 predictors on team performance yielded a model of five predictors accounting for 82.30% of the variance. The five predictors of team performance include (1) clinical skills, (2) team size, (3) authority profile, (4) clinical knowledge, and (5) familiarity with team members. The analysis of variance confirmed a significant linear relationship between team performance and the five predictors, F(5, 240) = 218.34, P < .001.

Conclusions

The outcomes of this study demonstrate that the collective knowledge, skills, and abilities within an urgent, emergency care team must be developed to the extent that each team member is able to competently perform their role functions and that smaller teams benefit by being composed of clinical authorities who are familiar with each other. Ideally, smaller, forward-deployed military teams will be an expert team of individual experts, with the collective expertise and abilities required for their patients. This expertise and familiarity are advantageous for collective consideration of significant clinical details, potential alternatives for treatment, decision-making, and effective implementation of clinical skills during patient care. Identifying the most influential team performance factors narrows the focus of team development strategies to precisely what is needed for a team to optimally perform.
P006 Resistance of Aspergillus flavus clinical isolates and associated fitness-cost
Authors: Djenontin Elie , Debourgogne Anne , Bergui Imane , Costa Jean-Marc , Mousavi Bita , Ait-Ammar Nawel , Guillot Jacques , Botterel Françoise , Dannaoui Eric
Published: September 2022

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

 

Objectives

Aspergillus flavus and closely related species could be pathogenic for humans, animals, and plants and could also produce mycotoxins. The members of the Flavi section are morphologically quite similar making precise identification to the species level difficult. In this study, we present the antifungal susceptibility profiles of French clinical isolates belonging to the Flavi section. Isolates have been characterized by molecular methods and the potential fitness-cost associated with azole-resistance has been determined.

Methods

A total of 120 isolates phenotypically identified as A. flavus were included in the study. These clinical isolates were recovered over a 15-year period (2001-2015). For all isolates, specific identification was confirmed by sequencing a part of the β-tubulin and calmodulin genes. The isolates were first screened for their susceptibility to azoles antifungal agents by using 3-sectors agar plates containing itraconazole, voriconazole, and a drug-free control. Susceptibility to six antifungal drugs was further determined by using the EUCAST reference microdilution broth technique. Fitness cost was evaluated by growth curve kinetics in RPMI and by evaluation of virulence in a Galleria mellonella invertebrate animal model.

Results

Out of 120 isolates, molecular analysis of the partial β-tubulin and calmodulin sequences showed that 117 isolates were A. flavus sensu stricto and the three remaining corresponded to A. parasiticus, A. nomius, and A. tamarii. Two isolates were azole-resistant by the screening test. For the A. flavus sensu stricto isolates, the geometric mean MIC values (range) of amphotericin B, itraconazole, voriconazole, posaconazole, isavuconazole, and caspofungin were 1.84 (0.25-16), 0.29 (0.125-2), 0.82 (0.5-8), 0.27 (0.06-2), 1.15 (0.25-8), and 0.061 (0.03-0.125) μg/ml, respectively. For A. parasiticus, A. nomius, and A. tamarii, MICs were in the same range. Two A. flavus sensu stricto isolates (AfR1 and AfR2) had voriconazole and isavuconazole MICs at 8 μg/ml. Compared to susceptible isolates, these two azole-resistant isolates had a delayed growth in RPMI liquid medium. In the G. mellonella model, the mortality was 100% for susceptible isolates. In contrast, the Galleria infected by AfR1 and AfR2 showed a significantly lower mortality rate.

Conclusion

Antifungal susceptibility to six drugs was determined on a large collection of clinical isolates belonging to Aspergillus Flavi section. Most of the isolates were identified as A. flavus sensu stricto and most of them were susceptible to antifungal drugs. Nevertheless, the occurrence of two resistant isolates highlights the need for susceptibility testing for A. flavus. It seems that azole-resistance is associated with a fitness-cost including a lower growth rate and a lower virulence.
P013 Green synthesis of silver nanoparticles using Trillium govanianum and its antifungal potential against Candida auris
Authors: Negi Preeti , Raj Khem , Verma Nandini , Riyaz Mohammad
Published: September 2022

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

 

Objective

This study aimed to evaluate the antifungal and anti-biofilm activities of silver nanoparticles synthesized using Trillium govanianum, a trans-Himalayan medicinal plant extract, against multidrug-resistant Candida auris.

Methods

Silver nanoparticles (AgNPs) were synthesized by adopting a green approach. Optimization and characterization of TG-AgNPs were carried out using UV-VIS spectroscopy, TEM, and FTIR. Minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and antibiofilm activity of the crude extract, as well as TG-nanoparticles, were evaluated. Furthermore, their effect on cell morphology and cell permeability was also analyzed using FESEM.

Results

Crude extracts of roots of T. govanianum exerted remarkable antifungal activity against multiple strains of Candida auris. The incorporation of silver nanoparticles to plant extract significantly improved the antifungal and antibiofilm activities against the tested strains in a synergistic manner.

Conclusion

Silver nanoparticles synthesized using Trillium govanianum extract provide eco-friendly, biocompatible nanostructures with antifungal activity and have the potential for use as a therapeutic/nutraceutical agent.
P014 Prevalence and antifungal susceptibility of Wickerhamomyces anomalus in a tertiary care center
Authors: Pandey Abhishek , Paul Raees , Kaur Harsimran , Ghosh Anup , Chakrabarti Arunaloke , Rudramurthy Shivaprakash
Published: September 2022

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

 

Objectives

The spectrum of yeast species causing fungemia has been expanding with emergence of many unusual pathogenic species. One such species is Wickerhamomyces anomalus which has been recognized as an important cause of nosocomial fungemia in neonates and pediatric patients. We evaluated antifungal susceptibility and the burden of antifungal resistance in W. anomalus.

Methods

Species identification of the isolates was performed using MALDI-TOF MS. Antifungal susceptibility testing was done according to the CLSI broth microdilution method following the M27- A3 protocol. C. parapsilosis ATCC22019 and C. krusei ATCC6258 were used as quality control strains. The lowest azole or echinocandin concentration inhibiting 50% visible growth and for amphotericin B, 100% growth-inhibition was taken as minimum inhibitory concentration (MIC). As species-specific breakpoints for resistance are not available for W. anomalus, the susceptibility data was interpreted using CLSI breakpoints (M60 1st edition) as surrogate markers of resistance.

Results

A total of 633 W. anomalous isolated over a 5-year study period from January 2016, through December 2019 at our center, were evaluated for susceptibility to amphotericin B, fluconazole, voriconazole, caspofungin, anidulafungin, and micafungin. The majority of W. anomalus was isolated from neonates (57.1%) followed by other pediatric patients (40.1%). Antifungal therapy was administered in 21% of the patients with fluconazole as the commonest antifungal agent (67.3%) followed by amphotericin B, 31.2%, and voriconazole (1.4%). For amphotericin B, 99.6% (602/604) of the isolates exhibited MIC ≤ 2 mg/l. For fluconazole, 81% of the isolates were susceptible while 19% of the isolates exhibited reduced susceptibility of which 3% were resistant, and 16% exhibited susceptible dose-dependent phenotype. Of all the fluconazole-resistant isolates, two (0.3%) isolates were cross-resistant to voriconazole. Among echinocandins, the resistant rate of 2.8%, 1.2%, and 1.6% wase noted in caspofungin, anidulafungin, and micafungin, respectively.

Conclusions

Wickerhamomyces anomalus exhibited intrinsic susceptibility to all the antifungal agents evaluated. A substantial resistance to fluconazole was noted in this species while resistance to echinocandins was low.
P030 Highly slow-release antifungal wound dressing for chronic dermatophytosis
Authors: Asghari-paskiabi Farnoush , Bonakdar Shahin , Razzaghi-Abyaneh Mehdi
Published: September 2022

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

 

Objectives

The aim of this research was to make a biocompatible and affordable nanofibrous wound dressing that is able to release terbinafine at the site of chronic superficial fungal infection over time.

Methods

Polymer solution (10%) of poly (caprolactone) (PCL) was prepared in hexafluoroisopropanol (HFIP). Terbinafine hydrochloride (TFH) was added equal to 5% of PCL weight for drug-loaded samples. Electrospinning was performed with a 27-G-needle equipped syringe at a distance of 15 cm which the injection flow rate of the solution was 0.2 ml/h and a 30 kV voltage was applied. The measurements of drug release were performed with HPLC. Antifungal tests were done on three different fungal species and MTT assay was done based on ISO-10993 on 24 h L929 cells. The drug release was monitored for 144 h in a human body simulated system (incubation at 37°C, shaking by 30 rpm, and passing the drug through a wet Whatman filter into PBS).

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Results

The mean diameter of fibers was obtained at 1262 nm for PCL nanofibers without TFH and 249 nm for PCL nanofibers with TFH. The drug loading for PCL was 83.4%. Antifungal activity of PCL fibers was examined against a dermatophyte (Trichophyton mentagrophytes), a saprophyte (Aspergillus fumigatus), and a yeast (Candida albicans). The terbinafine hydrochloride-contained electrospun PCL fibers inhibited the growth of T. Mentagrophytes and A. Fumigatus but did not inhibit C. albicans growth. None of the samples showed cytotoxic effects after 24 h and 2 weeks.

Conclusions

The diameter of PCL nanofibers with TFH apparently decreased by fives times (P >.05). PCL nanofibers successfully inhibited two important fungal species while no toxicity was observed in MTT assay for its extraction of 2 weeks. They were able to release TFH slowly over time which makes them suitable for the treatment of chronic superficial fungal infections.
P033 Genomic epidemiology of the antifungal-resistant dermatophytosis epidemic, India, 2017-2019
Authors: Bagal Ujwal , Gade Lalitha , Le Ngoc , Bentz Meghan , Berkow Elizabeth , Hurst Steven , Lockhart Shawn , Litvintseva Anastasia , Min Brian , Sexton Joseph , Uhrlaß Silke , Jackson Brendan , Chow Nancy , Chiller Tom , Nenoff Pietro , Verma Shyam
Published: September 2022

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

 

Objective

The epidemic of antifungal-resistant dermatophytosis in India has been reported. These infections are associated with severe morbidity, resistance to oral itraconazole and terbinafine, and the widespread misuse of topical steroids. Trichophyton indotineae has emerged as the predominant causative agent. In this study, we investigated 162 dermatophytosis infections from eight Indian states using genomic sequencing. The primary objective was to determine whether a clonal outbreak strain is responsible for the current epidemic.

Methods

A total of 161 T. indotineae and one T. rubrum isolates from skin scrapings collected from India in 2017-2019 and previously reported were sent to the U.S. Centers for Disease Control and Prevention (CDC) for genomic analysis. After species identification, genomic DNA was extracted and sequenced using Illumina NovaSeq. Single-nucleotide (SNP) analysis was performed using the portable workflow MycoSNP (v0.21). Briefly, MycoSNP prepared the reference genome, performed pre-processing, aligned sample reads to the reference using the BWA (v 0.7.17) alignment algorithm, and called variants using GATK (v4.1.4.1). High-quality SNPs were used for constructing phylogenetic trees using neighbor-joining (NJ) and maximum likelihood (ML) methods. Further, to understand if infections are genetically clustered by state or region, multi-dimensional scaling (MDS) was applied using the ML tree in R.

Result

SNP analysis identified 1259 450 variant sites which were used to construct an NJ and ML tree. The tree topology from both NJ and ML methods showed consensus. All 161 T. indotineae isolates from India clustered together forming a large, well-supported clade. SNP differences between the samples varied from 0-160 SNPs. Historical isolates available at CDC were included as controls and clustered over 40 000 SNPs from the clade comprising isolates from India. The MDS plot revealed that isolates did not cluster by state or region.

Conclusion

Antifungal-resistant dermatophytosis is an emerging threat with cases of chronic, recurrent infection reported from several countries including India. Additionally, the rapid spread of infections involves person-to-person spread. Our results suggest that a clonal outbreak of a T. indotineae strain is circulating in multiple states in India. Current plans are to expand the geographic scope of the study by including over 10 countries from Europe, Middle East, and the Americas. This work will allow the public health community to better understand the emergence and transmission of antifungal-resistant dermatophytosis worldwide.
P044 Demonstration of the yeasticidal efficacy of povidone-iodine-based commercial antiseptic solutions against Candida auris
Authors: Chesnay Adélaïde , Bailly Eric , Evplanov Victor , Favalli Filippo , Desoubeaux Guillaume
Published: September 2022

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

 

Objectives

Candida auris is an emerging yeast pathogen with worldwide distribution and a great propensity for nosocomial spread. Recent reports have warned of the significant emergence of C. auris in several healthcare facilities. In order to stop its nosocomial transmission, use of antiseptics constitutes the first-line lever of action in fighting against C. auris skin colonization. However, little is known about the efficacy of these products, and moreover, no antiseptics are currently registered for use against C. auris.

Material and Methods

This study investigated the in vitro yeasticidal activity of povidone-iodine (Betadine®) against C. auris, and compared the findings to C. albicans and C. glabrata.

Results

In all the samples, the fungal load was substantially reduced by ≥4.2 Log10 colony-forming units, according to the EN standard 1275:2005. Moreover, even when largely diluted, povidone-iodine products still allowed a sustainable decrease of the yeast viability below 0.1%.

Conclusion

Overall, these results support the use of such commercial antiseptics in the context of colonization with this yeast.
P048 Antifungal susceptibility and mechanism of azole resistance in Candida albicans clinical isolates from oropharyngeal candidiasis patients in Iran
Authors: Jahanshiri Zahra
Published: September 2022

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

 

Objectives

Oropharyngeal candidiasis (OPC) is the most frequent opportunistic fungal infection in head and neck cancer patients. This study was done to investigate the azole susceptibility of Candida albicans (C. albicans) from oropharyngeal candidiasis (OPC) patients and to determine the relationship between ERG11 gene mutations in these isolates and azole resistance.

Methods

A total of 324 clinical isolates of Candida species were collected. Identification of the oral clinical samples was determined by culturing on CHROMagar, carbohydrate assimilation and ITS sequencing methods. Azole susceptibility was tested in vitro in microdilution studies. The ERG11 genes of 42 isolates of C. albicans were amplified and sequenced.

Results

Of the 324 isolates collected, 44.75% (145 isolates) were C. albicans. ERG11 gene was sequenced in 42 isolates. In total, 14 missense mutations were detected in ERG11 genes from 42 isolates. Among them, A945C and T495A substitutions were most prevalent and were known to cause fluconazole resistance.

Conclusions

A total of 14 mutations in the ERG11 gene were identified in azole-resistant C. albicans isolates, which indicated a possible relation with the increase in resistance to azole drugs and the recurrence of oropharyngeal candidiasis. Finding more mutations and relevance requires studies with a higher number of samples.