bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunogenicity to Botulinum Toxin Type A: A Systematic Review With Meta-Analysis Across Therapeutic Indications
Authors: Rahman Eqram , Alhitmi Hitmi Khalifa , Mosahebi Afshin
Published: February 2021

Background

Botulinum toxin A (BTX-A) is commonly employed as a neuromodulator in several neurological diseases and aesthetic indications. Formation of neutralizing antibodies (NAbs) after BTX-A injections may be responsible for treatment failure.

Objectives

The authors sought to quantify the prevalence of NAbs following treatment with Abobotulinumtoxin A, Incobotulinumtoxin A, and Onabotulinumtoxin A for therapeutic indications.

Methods

An electronic systematic search (2000-2020) of PubMed, Scopus, Web of Science, and Embase was conducted. Original studies reporting prevalence of NAbs were included. Data analysis was carried out through open meta-analysis softwares.

Results

Forty-three studies involving 8833 patients were included in this meta-analysis. The incidence of NAbs was 1.8% (summary estimate = 0.018, 95% CI [0.012, 0.023]); a meta-regression analysis revealed that BTX-A duration was significantly associated with increased incidence of NAbs (P = 0.007). Patients with dystonia had the highest incidence (7.4%) of NAbs against BTX-A (summary estimate = 0.074, 95% CI = [0.045, 0.103], I2 = 93.%, P < 0.00) followed by patients with spasticity (6.7%) and urological indications (6.2%). Abobotulinumtoxin A was associated with the highest incidence of NAbs (7.4%) (summary estimate = 0.074, 95% CI = [0.053, 0.096], I2 = 97.24%, P < 0.00) by the Incobotulinumtoxin A and Onabotulinumtoxin A 0.3% (summary estimate <0.003%, 95% CI = [−0.001, 0.007], P < 0.003).

Conclusions

Although the overall incidence of NAbs following BTX-A injections is relatively low, patients with secondary nonresponse to BTX-A with no apparent causes should be investigated for NAbs. A consensus needs to be developed for the optimal management of such patients.

Level of Evidence: 2
A model for pH coupling of the SARS-CoV-2 spike protein open/closed equilibrium
Authors: Warwicker Jim
Published: February 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative agent of the coronavirus disease 2019 (COVID-19) pandemic, is thought to release its RNA genome at either the cell surface or within endosomes, the balance being dependent on spike protein stability, and the complement of receptors, co-receptors and proteases. To investigate possible mediators of pH-dependence, pKa calculations have been made on a set of structures for spike protein ectodomain and fragments from SARS-CoV-2 and other coronaviruses. Dominating a heat map of the aggregated predictions, three histidine residues in S2 are consistently predicted as destabilizing in pre-fusion (all three) and post-fusion (two of the three) structures. Other predicted features include the more moderate energetics of surface salt–bridge interactions and sidechain–mainchain interactions. Two aspartic acid residues in partially buried salt-bridges (D290–R273 and R355–D398) have pKas that are calculated to be elevated and destabilizing in more open forms of the spike trimer. These aspartic acids are most stabilized in a tightly closed conformation that has been observed when linoleic acid is bound, and which also affects the interactions of D614. The D614G mutation is known to modulate the balance of closed to open trimer. It is suggested that D398 in particular contributes to a pH-dependence of the open/closed equilibrium, potentially coupled to the effects of linoleic acid binding and D614G mutation, and possibly also A570D mutation. These observations are discussed in the context of SARS-CoV-2 infection, mutagenesis studies, and other human coronaviruses.
An OMICs-based meta-analysis to support infection state stratification
Authors: Myall Ashleigh C , Perkins Simon , Rushton David , David Jonathan , Spencer Phillippa , Jones Andrew R , Antczak Philipp
Published: February 2021

Motivation

A fundamental problem for disease treatment is that while antibiotics are a powerful counter to bacteria, they are ineffective against viruses. Often, bacterial and viral infections are confused due to their similar symptoms and lack of rapid diagnostics. With many clinicians relying primarily on symptoms for diagnosis, overuse and misuse of modern antibiotics are rife, contributing to the growing pool of antibiotic resistance. To ensure an individual receives optimal treatment given their disease state and to reduce over-prescription of antibiotics, the host response can in theory be measured quickly to distinguish between the two states. To establish a predictive biomarker panel of disease state (viral/bacterial/no-infection), we conducted a meta-analysis of human blood infection studies using machine learning.

Results

We focused on publicly available gene expression data from two widely used platforms, Affymetrix and Illumina microarrays as they represented a significant proportion of the available data. We were able to develop multi-class models with high accuracies with our best model predicting 93% of bacterial and 89% viral samples correctly. To compare the selected features in each of the different technologies, we reverse-engineered the underlying molecular regulatory network and explored the neighbourhood of the selected features. The networks highlighted that although on the gene-level the models differed, they contained genes from the same areas of the network. Specifically, this convergence was to pathways including the Type I interferon Signalling Pathway, Chemotaxis, Apoptotic Processes and Inflammatory/Innate Response.

Availability

Data and code are available on the Gene Expression Omnibus and github.

Supplementary information

Supplementary data are available at Bioinformatics online.
orfipy: a fast and flexible tool for extracting ORFs
Authors: Singh Urminder , Wurtele Eve Syrkin
Published: February 2021

Searching for open reading frames is a routine task and a critical step prior to annotating protein coding regions in newly sequenced genomes or de novo transcriptome assemblies. With the tremendous increase in genomic and transcriptomic data, faster tools are needed to handle large input datasets. These tools should be versatile enough to fine-tune search criteria and allow efficient downstream analysis. Here we present a new python based tool, orfipy, which allows the user to flexibly search for open reading frames in genomic and transcriptomic sequences. The search is rapid and is fully customizable, with a choice of FASTA and BED output formats.

Availability and implementation

orfipy is implemented in python and is compatible with python v3.6 and higher. Source code: https://github.com/urmi-21/orfipy. Installation: from the source, or via PyPi (https://pypi.org/project/orfipy) or bioconda (https://anaconda.org/bioconda/orfipy).

Supplementary information

Supplementary data are available at Bioinformatics online.
Mechanical and oral antibiotic bowel preparation versus no bowel preparation in right and left colectomy: subgroup analysis of MOBILE trial
Authors: Koskenvuo L , Lehtonen T , Koskensalo S , Rasilainen S , Klintrup K , Ehrlich A , Pinta T , Scheinin T , Sallinen V
Published: February 2021

Background

In retrospective series, mechanical and oral antibiotic bowel preparation (MOABP) has been reported to reduce surgical-site infections (SSIs) after colectomy compared with no bowel preparation (NBP).

Method

This was a subgroup analysis of a multicentre randomized trial that included patients scheduled for elective colectomy. The MOABP group underwent mechanical bowel preparation, and took 2 g neomycin and 2 g metronidazole orally during the day before surgery. The NBP group did not undergo bowel preparation. Patients were categorized according to the side of resection (right versus left colectomy), and these subgroups compared for postoperative outcomes.

Results

Among 217 patients undergoing right colectomy (106 in MOABP and 111 in NBP group), SSI was detected in seven (7 per cent) and 10 (9 per cent) patients (odds ratio (OR) 0.71, 95 per cent c.i. 0.26 to 1.95; P = 0.510), anastomotic dehiscence in two (2 per cent) and two (2 per cent) patients (OR 1.05, 0.15 to 7.58; P = 1.000), and the mean(s.d.) Comprehensive Complication Index (CCI) score was 9.4(12.9) and 10.5(18.0) (mean difference –1.09; 95 per cent c.i. –5.29 to 3.11; P = 0.608) in the MOABP and NBP groups respectively. Among 164 patients undergoing left colectomy (84 in MOABP and 80 in NBP group), SSI was detected in five (6 per cent) and eight (10 per cent) patients (OR 0.57, 0.18 to 1.82; P = 0.338), anastomotic dehiscence in four (5 per cent) and five (6 per cent) patients (OR 0.75, 0.19 to 2.90; P = 0.742), and the CCI score was 10.2(13.1) and 6.5(11.0) (mean difference 3.68, –0.06 to 7.42; P = 0.053) in the MOABP and NBP groups respectively.

Conclusions

MOABP did not decrease the rate of SSI or complications in patients undergoing either right or left colectomy compared with NBP.
Tracing the origins of hybrids through history: monstrous cultivars and Napoléon Bonaparte’s exiled paper daisies (Asteraceae; Gnaphalieae)
Authors: Collins Timothy L , Bruhl Jeremy J , Schmidt-Lebuhn Alexander N , Telford Ian R H , Andrew Rose L
Published: February 2021

Golden everlasting paper daisies (Xerochrysum, Gnaphalieae, Asteraceae) were some of the earliest Australian native plants to be cultivated in Europe. Reputedly a favourite of Napoléon Bonaparte and Empress Joséphine, X. bracteatum is thought to have been introduced to the island of St Helena in the South Atlantic during Napoléon’s exile there. Colourful cultivars were developed in the 1850s, and there is a widely held view that these were produced by crossing Xerochrysum with African or Asian Helichrysum spp. Recent molecular phylogenetic analyses and subtribal classification of Gnaphalieae cast doubt on this idea. Using single-nucleotide polymorphism (SNP) data, we looked for evidence of gene flow between modern cultivars, naturalized paper daisies from St Helena and four Xerochrysum spp. recorded in Europe in the 1800s. There was strong support for gene flow between cultivars and X. macranthum. Paper daisies from St Helena were genotypically congruent with X. bracteatum and showed no indications of ancestry from other species or from the cultivars, consistent with the continuous occurrence of naturalized paper daisies introduced by Joséphine and Napoléon. We also present new evidence for the origin of colourful Xerochrysum cultivars and hybridization of congeners in Europe from Australian collections.
Diminished antiproteinuric effect of the angiotensin receptor blocker losartan during high potassium intake in patients with CKD
Authors: Wouda Rosa D , Waanders Femke , de Zeeuw Dick , Navis Gerjan , Vogt Liffert ,   the K+ Consortium
Published: February 2021

Background

Angiotensin II type 1 receptor blockers (ARBs) lower blood pressure (BP) and proteinuria and reduce renal disease progression in many—but not all—patients. Reduction of dietary sodium intake improves these effects of ARBs. Dietary potassium intake affects BP and proteinuria. We set out to address the effect of potassium intake on BP and proteinuria response to losartan in non-diabetic proteinuric chronic kidney disease (CKD) patients.

Methods

We performed a post hoc analysis of a placebo-controlled interventional cross-over study in 33 non-diabetic proteinuric patients (baseline mean arterial pressure and proteinuria: 105 mmHg and 3.8 g/day, respectively). Patients were treated for 6 weeks with placebo, losartan and losartan/hydrochlorothiazide (HCT), combined with a habitual (∼200 mmol/day) and low-sodium (LS) diet (<100 mmol/day), in randomized order. To analyse the effects of potassium intake, we categorized patients based on median split of 24-h urinary potassium excretion, reflecting potassium intake.

Results

Mean potassium intake was stable during all six treatment periods. Losartan and losartan/HCT lowered BP and proteinuria in all treatment groups. Patients with high potassium intake showed no difference in the BP effects compared with patients with low potassium intake. The antiproteinuric response to losartan monotherapy and losartan combined with HCT during the habitual sodium diet was significantly diminished in patients with high potassium intake (20% versus 41%, P = 0.011; and 48% versus 64%, P = 0.036). These differences in antiproteinuric response abolished when shifting to the LS diet.

Conclusions

In proteinuric CKD patients, the proteinuria, but not BP-lowering response to losartan during a habitual high-sodium diet was hampered during high potassium intake. Differences disappeared after sodium status change by LS diet.
Risk prediction of COVID-19 incidence and mortality in a large multi-national hemodialysis cohort: implications for management of the pandemic in outpatient hemodialysis settings
Authors: Haarhaus Mathias , Santos Carla , Haase Michael , Mota Veiga Pedro , Lucas Carlos , Macario Fernando
Published: February 2021

Background

Experiences from the first wave of the 2019 coronavirus disease (COVID-19) pandemic can aid in the development of future preventive strategies. To date, risk prediction models for COVID-19-related incidence and outcomes in hemodialysis (HD) patients are missing.

Methods

We developed risk prediction models for COVID-19 incidence and mortality among HD patients. We studied 38 256 HD patients from a multi-national dialysis cohort between 3 March and 3 July 2020. Risk prediction models were developed and validated, based on predictors readily available in outpatient HD units. We compared mortality among patients with and without COVID-19, matched for age, sex and diabetes.

Results

During the observational period, 1259 patients (3.3%) acquired COVID-19. Of these, 62% were hospitalized or died. Mortality was 22% among COVID-19 patients with odds ratios 219.8 [95% confidence interval (CI) 80.6–359] to 342.7 (95% CI 60.6–13 595.1), compared to matched patients without COVID-19. Since the first wave of the pandemic affected most European countries during the study, the risk prediction model for incidence of COVID-19 was developed and validated in European patients only [N = 22 826 area under the ROC curve(AUC)Dev 0.64, AUCVal 0.69]. The model for prediction of mortality was developed in all COVID-19 patients (AUCDev 0.71, AUCVal 0.78). Angiotensin receptor blockers were independently associated with a lower incidence of COVID-19 in European patients.

Conclusions

We identified modifiable risk factors for COVID-19 incidence and outcome in HD patients. Our risk prediction tools can be readily applied in clinical practice. This can aid in the development of preventive strategies for future waves of COVID-19.
CMT: An Efficient Algorithm for Scalable Packet Classification
Authors: Chen Shuhui , Zhong Jincheng , Huang Teng , Wei Ziling , Zhao Shuang
Published: February 2021

Packet classification plays an essential role in diverse network functions such as quality of service, firewall filtering and load balancer. However, implementing an efficient packet classifier is a challenging problem. The problem even gets worse in the era of software-defined network, in which frequent rule updates are performed, and complex flow tables are used. This paper proposes CMT, a new software algorithm named by its novel data structure—common mask tree—to implement an efficient multi-field packet classifier. The core idea of CMT is to combine the strengths of both decision-tree and tuple-space schemes by employing tree-like structures and hash tables simultaneously. The objective of CMT is to achieve both high classification performance and fast rule updates. In the evaluation section, CMT is compared with decision-tree and tuple-space schemes. Compared to the state-of-the-art decision-tree methods, CMT performs rule updates at two orders of magnitude faster. CMT has a stable performance on different rulesets and achieves a 40% improvement in memory access compared to the state-of-the-art tuple-space method.
Strain by speckle tracking echocardiography correlates with electroanatomic scar location and burden in ischaemic cardiomyopathy
Authors: Trivedi Siddharth J , Campbell Timothy , Stefani Luke D , Thomas Liza , Kumar Saurabh
Published: February 2021

Aims

Ventricular tachycardia (VT) in ischaemic cardiomyopathy (ICM) originates from scar, identified as low-voltage areas with invasive high-density electroanatomic mapping (EAM). Abnormal myocardial deformation on speckle tracking strain echocardiography can non-invasively identify scar. We examined if regional and global longitudinal strain (GLS) can localize and quantify low-voltage scar identified with high-density EAM.

Methods and results

We recruited 60 patients, 40 ICM patients undergoing VT ablation and 20 patients undergoing ablation for other arrhythmias as controls. All patients underwent an echocardiogram prior to high-density left ventricular (LV) EAM. Endocardial bipolar and unipolar scar location and percentage were correlated with regional and multilayer GLS. Controls had normal GLS and normal bipolar and unipolar voltages. There was a strong correlation between endocardial and mid-myocardial longitudinal strain and endocardial bipolar scar percentage for all 17 LV segments (r = 0.76–0.87, P < 0.001) in ICM patients. Additionally, indices of myocardial contraction heterogeneity, myocardial dispersion (MD), and delta contraction duration (DCD) correlated with bipolar scar percentage. Endocardial and mid-myocardial GLS correlated with total LV bipolar scar percentage (r = 0.83; 0.82, P < 0.001 respectively), whereas epicardial GLS correlated with epicardial bipolar scar percentage (r = 0.78, P < 0.001). Endocardial GLS −9.3% or worse had 93% sensitivity and 82% specificity for predicting endocardial bipolar scar >46% of LV surface area.

Conclusions

Multilayer strain analysis demonstrated good linear correlations with low-voltage scar by invasive EAM. Validation studies are needed to establish the utility of strain as a non-invasive tool for quantifying scar location and burden, thereby facilitating mapping and ablation of VT.
Development of an international standard set of clinical and patient-reported outcomes for children and adults with congenital heart disease: a report from the International Consortium for Health Outcomes Measurement Congenital Heart Disease Working Group
Authors: Hummel Kevin , Whittaker Sarah , Sillett Nick , Basken Amy , Berghammer Malin , Chalela Tomás , Chauhan Julie , Garcia Luis Antonio , Hasan Babar , Jenkins Kathy , Ladak Laila Akbar , Madsen Nicolas , March Almudena , Pearson Disty , Schwartz Steven M , St Louis James D , van Beynum Ingrid , Verstappen Amy , Williams Roberta , Zheleva Bistra , Hom Lisa , Martin Gerard R
Published: February 2021

Aims

Congenital heart disease (CHD) is the most common congenital malformation. Despite the worldwide burden to patient wellbeing and health system resource utilization, tracking of long-term outcomes is lacking, limiting the delivery and measurement of high-value care. To begin transitioning to value-based healthcare in CHD, the International Consortium for Health Outcomes Measurement aligned an international collaborative of CHD experts, patient representatives, and other stakeholders to construct a standard set of outcomes and risk-adjustment variables that are meaningful to patients.

Methods and results

The primary aim was to identify a minimum standard set of outcomes to be used by health systems worldwide. The methodological process included four key steps: (i) develop a working group representative of all CHD stakeholders; (ii) conduct extensive literature reviews to identify scope, outcomes of interest, tools used to measure outcomes, and case-mix adjustment variables; (iii) create the outcome set using a series of multi-round Delphi processes; and (iv) disseminate set worldwide. The Working Group established a 15-item outcome set, incorporating physical, mental, social, and overall health outcomes accompanied by tools for measurement and case-mix adjustment variables. Patients with any CHD diagnoses of all ages are included. Following an open review process, over 80% of patients and providers surveyed agreed with the set in its final form.

Conclusion

This is the first international development of a stakeholder-informed standard set of outcomes for CHD. It can serve as a first step for a lifespan outcomes measurement approach to guide benchmarking and improvement among health systems.
Farm income in European agriculture: new perspectives on measurement and implications for policy evaluation
Authors: Finger Robert , El Benni Nadja
Published: February 2021

Viable farm households contribute to the resilience of agricultural and food systems. Farm income is a policy-relevant proxy for this viability. Here, we address three key aspects of farm income: first, the income issue, focusing on (average) income levels; second, the variability issue, focusing on income risks faced by farmers; and third, the inequality issue, focusing on the heterogeneity and (in-)equalities of farm incomes. This special issue presents new perspectives on measurement, modelling, development and policies related to the income of farm families in Europe, especially in the light of increasing complexity of farms and policies and risk exposure.
The physical activity paradox in cardiovascular disease and all-cause mortality: the contemporary Copenhagen General Population Study with 104 046 adults
Authors: Holtermann Andreas , Schnohr Peter , Nordestgaard Børge Grønne , Marott Jacob Louis
Published: February 2021

Aims 

Leisure time physical activity associates with reduced risk of cardiovascular disease and all-cause mortality, while these relationships for occupational physical activity are unclear. We tested the hypothesis that leisure time physical activity associates with reduced major adverse cardiovascular events (MACE) and all-cause mortality risk, while occupational physical activity associates with increased risks.

Methods and results 

We studied 104 046 women and men aged 20–100 years in the Copenhagen General Population Study with baseline measurements in 2003–2014 and median 10-year follow-up. Both leisure and occupational physical activity were based on self-report with four response categories. We observed 7913 (7.6%) MACE and 9846 (9.5%) deaths from all causes. Compared to low leisure time physical activity, multivariable adjusted (for lifestyle, health, living conditions, and socioeconomic factors) hazard ratios for MACE were 0.86 (0.78–0.96) for moderate, 0.77 (0.69–0.86) for high, and 0.85 (0.73–0.98) for very high activity; corresponding values for higher occupational physical activity were 1.04 (0.95–1.14), 1.15 (1.04–1.28), and 1.35 (1.14–1.59), respectively. For all-cause mortality, corresponding hazard ratios for higher leisure time physical activity were 0.74 (0.68–0.81), 0.59 (0.54–0.64), and 0.60 (0.52–0.69), and for higher occupational physical activity 1.06 (0.96–1.16), 1.13 (1.01–1.27), and 1.27 (1.05–1.54), respectively. Similar results were found within strata on lifestyle, health, living conditions, and socioeconomic factors, and when excluding individuals dying within the first 5 years of follow-up. Levels of the two domains of physical activity did not interact on risk of MACE (P = 0.40) or all-cause mortality (P = 0.31).

Conclusion 

Higher leisure time physical activity associates with reduced MACE and all-cause mortality risk, while higher occupational physical activity associates with increased risks, independent of each other.
Tillage shapes the soil and rhizosphere microbiome of barley—but not its susceptibility towards Blumeria graminis f. sp. hordei
Authors: Bziuk Nina , Maccario Lorrie , Douchkov Dimitar , Lueck Stefanie , Babin Doreen , Sørensen Søren J , Schikora Adam , Smalla Kornelia
Published: February 2021

Long-term agricultural practices are assumed to shape the rhizosphere microbiome of crops with implications for plant health. In a long-term field experiment, we investigated the effect of different tillage and fertilization practices on soil and barley rhizosphere microbial communities by means of amplicon sequencing of 16S rRNA gene fragments from total community DNA. Differences in the microbial community composition depending on the tillage practice, but not the fertilization intensity were revealed. To examine whether these soil and rhizosphere microbiome differences influence the plant defense response, barley (cultivar Golden Promise) was grown in field or standard potting soil under greenhouse conditions and challenged with Blumeria graminis f. sp. hordei (Bgh). Amplicon sequence analysis showed that preceding tillage practice, but also aboveground Bgh challenge significantly influenced the microbial community composition. Expression of plant defense-related genes PR1b and PR17b was higher in challenged compared to unchallenged plants. The Bgh infection rates were strikingly lower for barley grown in field soil compared to potting soil. Although previous agricultural management shaped the rhizosphere microbiome, no differences in plant health were observed. We propose therefore that the management-independent higher microbial diversity of field soils compared to potting soils contributed to the low infection rates of barley.
Dust-borne microbes affectUlva ohnoi’s growth and physiological state
Authors: Krupnik Nimrod , Asis Dorin Theodora , Belkin Natalia , Rubin-Blum Maxim , Israel Álvaro , Paytan Adina , Meiri David , Herut Barak , Rahav Eyal
Published: February 2021

The marine macroalgae Ulva sp. is considered an ecosystem engineer in rocky shores of temperate waters worldwide. Ulva sp. harbors a rich diversity of associated microbial epibionts, which are known to affect the algae's typical morphological development and ‘health’. We examined the interaction between airborne microbes derived from atmospheric aerosols and Ulva ohnoi growth and physiological state. Specifically, we measured U. ohnoi growth rates and photosynthetic efficiency (Fv/Fm), alongside its microbial epibionts abundance, activity and diversity following dust (containing nutrients and airborne microorganisms) or UV-treated dust (only nutrients) amendments to filtered seawater. Parallel incubations with epibionts-free U. ohnoi (treated with antibiotics that removed the algae epibionts) were also tested to specifically examine if dust-borne microbes can replenish the epibiont community of U. ohnoi. We show that viable airborne microbes can restore U. ohnoi natural microbial epibionts communities, thereby keeping the seaweed alive and ‘healthy’. These results suggest that microbes delivered through atmospheric aerosols can affect epiphyte biodiversity in marine flora, especially in areas subjected to high annual atmospheric dust deposition such as the Mediterranean Sea.
Fungal immunity and pathogenesis in mammals versus the invertebrate model organismGalleria mellonella
Authors: F. Q. Smith Daniel , Casadevall Arturo
Published: February 2021

In recent decades, Galleria mellonella (Lepidoptera: Pyralidae) have emerged as a model system to explore experimental aspects of fungal pathogenesis. The benefits of the G. mellonella model include being faster, cheaper, higher throughput and easier compared with vertebrate models. Additionally, as invertebrates, their use is subject to fewer ethical and regulatory issues. However, for G. mellonella models to provide meaningful insight into fungal pathogenesis, the G. mellonella–fungal interactions must be comparable to mammalian–fungal interactions. Indeed, as discussed in the review, studies suggest that G. mellonella and mammalian immune systems share many similarities, and fungal virulence factors show conserved functions in both hosts. While the moth model has opened novel research areas, many comparisons are superficial and leave large gaps of knowledge that need to be addressed concerning specific mechanisms underlying G. mellonella–fungal interactions. Closing these gaps in understanding will strengthen G. mellonella as a model for fungal virulence in the upcoming years. In this review, we provide comprehensive comparisons between fungal pathogenesis in mammals and G. mellonella from immunological and virulence perspectives. When information on an antifungal immune component is unknown in G. mellonella, we include findings from other well-studied Lepidoptera. We hope that by outlining this information available in related species, we highlight areas of needed research and provide a framework for understanding G. mellonella immunity and fungal interactions.
A short anogenital distance on MRI is a marker of endometriosis
Authors: Crestani A , Abdel Wahab C , Arfi A , Ploteau S , Kolanska K , Breban M , Bendifallah S , Ferrier C , Darai E
Published: February 2021

STUDY QUESTION

Could the anogenital distance (AGD) as assessed by MRI (MRI-AGD) be a diagnostic tool for endometriosis?

SUMMARY ANSWER

A short MRI-AGD is a strong diagnostic marker of endometriosis.

WHAT IS KNOWN ALREADY

A short clinically assessed AGD (C-AGD) is associated with the presence of endometriosis.

STUDY DESIGN, SIZE, DURATION

This study is a re-analysis of previously published data from a case–control study.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Women undergoing pelvic surgery from January 2018 to June 2019 and who had a preoperative pelvic MRI were included. C-AGD was measured at the beginning of the surgery by a different operator who was unaware of the endometriosis status. MRI-AGD was measured retrospectively by a senior radiologist who was blinded to the final diagnosis. Two measurements were made: from the posterior wall of the clitoris to the anterior edge of the anal canal (MRI-AGD-AC), and from the posterior wall of the vagina to the anterior edge of the anal canal (MRI-AGD-AF).

MAIN RESULTS AND THE ROLE OF CHANCE

The study compared MRI-AGD of 67 women with endometriosis to 31 without endometriosis (controls). Average MRI-AGD-AF measurements were 13.3 mm (±3.9) and 21.2 mm (±5.4) in the endometriosis and non-endometriosis groups, respectively (P < 10−5). Average MRI-AGD-AC measurements were 40.4 mm (±7.3) and 51.1 mm (±8.6) for the endometriosis and non-endometriosis groups, respectively (P < 10−5). There was no difference of MRI-AGD in women with and without endometrioma (P = 0.21), or digestive involvement (P = 0.26). Moreover, MRI-AGD values were independent of the revised score of the American Society of Reproductive Medicine and the Enzian score. The diagnosis of endometriosis was negatively associated with both the MRI-AGD-AF (β = −7.79, 95% CI (−9.88; −5.71), P < 0.001) and MRI-AGD-AC (β = −9.51 mm, 95% CI (−12.7; 6.24), P < 0.001) in multivariable analysis. Age (β = +0.31 mm, 95% CI (0.09; 0.53), P = 0.006) and BMI (β = +0.44 mm, 95% CI (0.17; 0.72), P = 0.001) were positively associated with the MRI-AGD-AC measurements in multivariable analysis. MRI-AGD-AF had an AUC of 0.869 (95% CI (0.79; 0.95)) and outperformed C-AGD. Using an optimal cut-off of 20 mm for MRI-AGD-AF, a sensitivity of 97.01% and a specificity of 70.97% were noted.

LIMITATIONS, REASONS FOR CAUTION

This was a retrospective analysis and no adolescents had been included.

WIDER IMPLICATIONS OF THE FINDINGS

This study is consistent with previous works associating a short C-AGD with endometriosis and the absence of correlation with the disease phenotype. MRI-AGD is more accurate than C-AGD in this setting and could be evaluated in the MRI examination of patients with suspected endometriosis.

STUDY FUNDING/COMPETING INTEREST(S)

N/A.

TRIAL REGISTRATION NUMBER

The protocol was approved by the ‘Groupe Nantais d’Ethique dans le Domaine de la Santé’ and registered under reference 02651077.
Isogenies of Elliptic Curves Over Function Fields
Authors: Griffon Richard , Pazuki Fabien
Published: February 2021

We prove two theorems concerning isogenies of elliptic curves over function fields. The first one describes the variation of the height of the $j$-invariant in an isogeny class. The second one is an “isogeny estimate,” providing an explicit bound on the degree of a minimal isogeny between two isogenous elliptic curves. We also give several corollaries of these two results.
Circulating CD4 T Cells Elicited by Endemic Coronaviruses Display Vast Disparities in Abundance and Functional Potential Linked to Antigen Specificity and Age
Authors: Richards Katherine A , Glover Maryah , Crawford Jeremy C , Thomas Paul G , White Chantelle , Sant Andrea J
Published: February 2021

Repeated infections with endemic human coronaviruses (hCoV) are thought to reflect lack of long-lasting protective immunity. We evaluated circulating human CD4 T cells collected prior to 2020 for reactivity towards hCoV spike proteins, probing for the ability to produce interferon-γ, interleukin-2, or granzyme B. We found robust reactivity to spike-derived epitopes, comparable to influenza, but highly variable abundance and functional potential across subjects, depending on age and viral antigen specificity. To explore potential of these memory cells to be recruited in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we examined the subjects for cross-reactive recognition of epitopes from SARS-CoV-2 nucleocapsid, membrane/envelope, and spike. Functional potential of these cross-reactive CD4 T cells was highly variable; nucleocapsid-specific CD4 T cells but not spike-reactive cells showed exceptionally high levels of granzyme production upon stimulation. These results are considered in light of recruitment of hCoV-reactive cells into responses to SARS-CoV infections or vaccinations.
Emergence of a multidrug resistance efflux pump with carbapenem resistance gene blaVIM-2 in a Pseudomonas putida megaplasmid of migratory bird origin
Authors: Li Ruichao , Peng Kai , Xiao Xia , Liu Yuan , Peng Daxin , Wang Zhiqiang
Published: February 2021

Background

Tigecycline and carbapenems are regarded as vital antimicrobials to treat serious bacterial infections. Co-occurrence of resistance genes conferring resistance to both tigecycline and carbapenems in Pseudomonas spp. was not investigated.

Objectives

To characterize a megaplasmid co-harbouring tmexCD1-toprJ1 and blaVIM-2 in Pseudomonas putida of migratory bird origin.

Methods

One tigecycline- and carbapenem-resistant strain was isolated and characterized by antimicrobial susceptibility testing, conjugation assay, WGS and bioinformatics analysis.

Results

The strain P. putida ZXPA-20 resistant to meropenem and tigecycline was positive for blaVIM-2 and tmexCD1-toprJ1 genes. The gene blaVIM-2 was inserted into the backbone of the megaplasmid pZXPA-20 within a Tn5090-like structure. The genetic context of tmexCD1-toprJ1 in the megaplasmid was identical to many chromosomal tmexCD1-toprJ1 of Pseudomonas species. Plasmid-mediated tmexCD1-toprJ1 gene cluster in Pseudomonas spp. was more common than that in Klebsiella pneumoniae. To the best of our knowledge, this is the first report of co-occurrence of blaVIM-2 and tmexCD1-toprJ1 in one plasmid.

Conclusions

Emergence of plasmid-mediated carbapenem and tigecycline resistance genes in P. putida from migratory birds highlighted the importance of surveillance of novel mobile resistance genes in migratory birds, which may play a vital role in global transmission of novel resistance genes.
Could simulation methods solve the curse of sparse data within clinical studies of antibiotic resistance?
Authors: Hurley James C , Brownridge David
Published: February 2021

Infectious disease (ID) physicians and ID pharmacists commonly confront therapeutic questions relating to antibiotic resistance. Randomized controlled trial data are few and meta-analytic-based approaches to develop the evidence-base from several small studies that might relate to an antibiotic resistance question are not simple. The overriding challenge is the sparsity of data which is problematic for traditional frequentist methods, being the paradigm underlying the derivation of ‘P value’ inferential statistics. In other sparse data contexts, simulation methods enable answers to key questions that are meaningful, quantitative and potentially relevant. How these simulation methods ‘work’ and how Bayesian-based methods, being not ‘P value based’, can facilitate simulation are reviewed. These methods are becoming increasingly accessible. This review highlights why sparse data is less of an issue within Bayesian versus frequentist paradigms. A fictional pharmacokinetic study with sparse data illustrates a simplistic application of Bayesian and simulation methods to antibiotic dosing. Whether within epidemiological projections or clinical studies, simulation methods are likely to play an increasing role in antimicrobial resistance research within both hospital and community studies of either rare infectious disease or infections within specific population groups.
Feasibility study of hospital antimicrobial stewardship analytics using electronic health records
Authors: Dutey-Magni P F , Gill M J , McNulty D , Sohal G , Hayward A , Shallcross L , Anderson Niall , Crayton Elise , Forbes Gillian , Jhass Arnoupe , Richardson Emma , Richardson Michelle , Rockenschaub Patrick , Smith Catherine , Sutton Elizabeth , Traina Rosanna , Atkins Lou , Conolly Anne , Denaxas Spiros , Fragaszy Ellen , Horne Rob , Kostkova Patty , Lorencatto Fabiana , Michie Susan , Mindell Jennifer , Robson John , Royston Claire , Tarrant Carolyn , Thomas James , West Jonathan , Williams Haydn , Elsay Nadia , Fuller Chris
Published: February 2021

Background

Hospital antimicrobial stewardship (AMS) programmes are multidisciplinary initiatives to optimize antimicrobial use. Most hospitals depend on time-consuming manual audits to monitor clinicians’ prescribing. But much of the information needed could be sourced from electronic health records (EHRs).

Objectives

To develop an informatics methodology to analyse characteristics of hospital AMS practice using routine electronic prescribing and laboratory records.

Methods

Feasibility study using electronic prescribing, laboratory and clinical coding records from adult patients admitted to six specialities at Queen Elizabeth Hospital, Birmingham, UK (September 2017–August 2018). The study involved: (i) a review of AMS standards of care; (ii) their translation into concepts measurable from commonly available EHRs; and (iii) a pilot application in an EHR cohort study (n = 61679 admissions).

Results

We developed data modelling methods to characterize antimicrobial use (antimicrobial therapy episode linkage methods, therapy table, therapy changes). Prescriptions were linked into antimicrobial therapy episodes (mean 2.4 prescriptions/episode; mean length of therapy 5.8 days), enabling several actionable findings. For example, 22% of therapy episodes for low-severity community-acquired pneumonia were congruent with prescribing guidelines, with a tendency to use broader-spectrum antibiotics. Analysis of therapy changes revealed IV to oral therapy switching was delayed by an average 3.6 days (95% CI: 3.4–3.7). Microbial cultures were performed prior to treatment initiation in just 22% of antibacterial prescriptions. The proposed methods enabled fine-grained monitoring of AMS practice down to specialities, wards and individual clinical teams by case mix, enabling more meaningful peer comparison.

Conclusions

It is feasible to use hospital EHRs to construct rapid, meaningful measures of prescribing quality with potential to support quality improvement interventions (audit/feedback to prescribers), engagement with front-line clinicians on optimizing prescribing, and AMS impact evaluation studies.
PRO: Testing for ESBL production is necessary for ceftriaxone-non-susceptible Enterobacterales: perfect should not be the enemy of progress
Authors: Tamma Pranita D , Humphries Romney M
Published: February 2021

The MERINO trial has seemingly laid to rest the question: ‘Are carbapenems the preferred therapy for ESBL-producing infections?’ It has, however, brought another important question to the forefront: ‘How do we know when we have an ESBL-producing infection?’ A commonly used approach is the interpretation that non-susceptibility to third-generation cephalosporins (e.g. ceftriaxone MICs of ≥2 mg/L) is an accurate proxy for ESBL production. We believe that relying on antibiotic susceptibility results alone to predict ESBL production in clinical isolates is fraught with issues. Rather, we believe accurate molecular assays that detect a comprehensive range of ESBL genes, along with other relevant β-lactamase genes, are well within the reach of existing technology and necessary to optimize patient care. Herein, we elaborate on why the current approach for determining whether an organism is likely to be an ESBL producer (i) is inaccurate; (ii) encourages carbapenem overuse; (iii) ignores the potential for ESBL production in other Enterobacterales species; and (iv) promotes the silent epidemic of ESBL transmission.
Contamination of Wheat, Barley, and Maize Seeds with Toxigenic Fusarium Species and Their Mycotoxins in Tunisia
Authors: Jedidi Ines , Mateo Eva M , Marín Patricia , Jiménez Misericordia , Said Salem , González-Jaén María T
Published: February 2021

Background

Fusarium is a worldwide distributed fungal genus. It includes different species pathogenic to cereals among others crops. Some of these species can also produce toxic compounds toward animals and humans.

Objective

In this work, occurrence of fumonisins B1+B2, zearalenone, type A trichothecenes (T-2 and HT-2 toxins), and type B trichothecenes (deoxynivalenol[DON] and nivalenol[NIV]) was studied in 65 samples of stored and freshly harvested wheat, barley, and maize collected in Tunisia.

Methods

Mycotoxins analyses were performed by using gas chromatography for type B trichothecenes and HPLC for other mycotoxins. Obtained results were compared with the presence of mycotoxigenic species considered responsible for their synthesis by using species-specific polymerase chain reaction (PCR).

Results

Fumonisins occurred in 20.83% of wheat, 40% of barley, and 57.14% of maize samples, at levels exceeding European limits and suggesting a risk in Tunisian cereals, especially maize. Zearalenone, DON, NIV, and T-2+HT-2 toxins were detected at lower values in only wheat and barley samples. PCR protocols showed the predominance of F. verticillioides especially in maize, and occurrence of F. equiseti and F. graminearum in wheat and barley, and F. proliferatum in only two maize samples. A very consistent correlation was found between the detection of F. verticillioides and the contamination by fumonisins, as well as between the presence of F. graminearum and the contamination by zearalenone, DON, and NIV in the analyzed cereals.

Conclusions

Consequently, the detection of Fusarium species with the current PCR assays strategy in wheat, barley, and maize grains may be considered predictive of their potential mycotoxin risk in these matrices.

Highlights

This work is the first to report information on the occurrence of fumonisins, trichothecene, and ZEN, together with their potentially producing Fusarium species in wheat, barley, and maize in Tunisia. The high level of fumonisins in cereals, especially maize, stresses the importance of the control and the regularization of these mycotoxins for food safety.
Functional amino acid supplementation, regardless of dietary protein content, improves growth performance and immune status of weaned pigs challenged with Salmonella Typhimurium
Authors: Rodrigues Lucas A , Wellington Michael O , González-Vega J Caroline , Htoo John K , Van Kessel Andrew G , Columbus Daniel A
Published: February 2021

High dietary protein may increase susceptibility of weaned pigs to enteric pathogens. Dietary supplementation with functional amino acids (FAA) may improve growth performance of pigs during disease challenge. The objective of this study was to evaluate the interactive effects of dietary protein content and FAA supplementation above requirements for growth on performance and immune response of weaned pigs challenged with Salmonella. Sixty-four mixed-sex weanling pigs (13.9 ± 0.82 kg) were randomly assigned to dietary treatments in a 2 × 2 factorial arrangement with low (LP) or high protein (HP) content and basal (AA–) or FAA profile (AA+; Thr, Met, and Trp at 120% of requirements) as factors. After a 7-d adaptation period, pigs were inoculated with either a sterile saline solution (CT) or saline solution containing Salmonella Typhimurium (ST; 3.3 × 109 CFU/mL). Growth performance, body temperature, fecal score, acute-phase proteins, oxidant/antioxidant balance, ST shedding score in feces and intestinal colonization, fecal and digesta myeloperoxidase (MPO), and plasma urea nitrogen (PUN) were measured pre- and postinoculation. There were no dietary effects on any measures pre-inoculation or post-CT inoculation (P > 0.05). Inoculation with ST increased body temperature and fecal score (P < 0.05), serum haptoglobin, plasma superoxide dismutase (SOD), malondialdehyde (MDA), PUN, and fecal MPO, and decreased serum albumin and plasma reduced glutathione (GSH):oxidized glutathione (GSSG) compared with CT pigs (P < 0.05). ST-inoculation reduced average daily gain (ADG) and feed intake (ADFI) vs. CT pigs (P < 0.05) but was increased by AA+ vs. AA– in ST pigs (P < 0.05). Serum albumin and GSH:GSSG were increased while haptoglobin and SOD were decreased in ST-inoculated pigs fed AA+ vs. AA– (P < 0.05). PUN was higher in HP vs. LP-fed pigs postinoculation (P < 0.05). Fecal ST score was increased in ST-inoculated pigs on days 1 and 2 postinoculation and declined by day 6 (P < 0.05) in all pigs while the overall score was reduced in AA+ vs. AA– pigs (P < 0.05). Cecal digesta ST score was higher in HP vs. LP-fed pigs and were lower in AA+ compared with AA– fed pigs in the colon (P < 0.05). Fecal and digesta MPO were reduced in ST pigs fed AA+ vs. AA– (P < 0.05). These results demonstrate a positive effect of FAA supplementation, with minimal effects of dietary protein, on performance and immune status in weaned pigs challenged with Salmonella.
Altmetric Attention Score: Evaluating the Social Media Impact of Burn Research
Authors: Richardson Michelle A , Park Won , Echternacht Scott R , Bell Derek E
Published: February 2021

Traditional measures of scholarly impact (ie, impact factor, citation rate) do not account for the role of social media in knowledge dissemination. The Altmetric Attention Score (AAS) tracks the online sharing activity of articles on platforms such as Twitter and Facebook. All 285 original scientific articles published in Journal of Burn Care & Research and Burns from January to December 2017 were obtained from official journal websites. Article characteristics extracted include AAS; number of Twitter, Facebook, and news outlet mentions; subject of study and study design; number of citations; number of authors and academic institutions; and others. The average AAS for all articles was 6.1 (SD: 48; range: 0 to 611) in which 156 (55%) of those had Twitter mentions. The mean AAS for Journal of Burn Care & Research and Burns were 7.7 (SD: 54; range: 0 to 536) and 5.3 (SD: 45; range: 0 to 611), respectively. There was a weak, positive correlation between AAS and citation count for all articles (ρ = 0.12; P = .049), and this finding was consistent for Journal of Burn Care & Research (ρ = 0.21; P = .039) and Burns (ρ = 0.15; P = .038) individually. The weak correlation between the two metrics supports that AAS and citation count capture the attention of different audiences. In addition, studies discussing skin grafting were associated with higher average AAS (β: 29 [95% CI: 4.2 to 54]; P = .022). Overall, our findings support using both AAS and traditional bibliometrics to assess article impact.