bluuebunny/crossref_metadata_2025 huggingface dataset:
Delivering high quality documentation on operative consent forms: a UK major trauma center Quality Improvement Project
Authors: Hobday Dorian , Chaudhry Zulfiqar , Popova Dardan , Welman Ted , Pahal Gurjinderpal S. , Stodell Matthew
Published: November 2020

Background:

Royal College of Surgeons guidelines exist on the importance of full, accurate and legible completion of consent forms as a key part of the process of gaining informed consent. In addition to this, consent forms serve as an important medico-legal document to protect clinicians and patients should problems arise. It is therefore in all parties’ interests that they are correctly completed.

It was noted that consent forms within the Royal London Hospital Plastic Surgery department were often not correctly completed. A Quality Improvement Project was undertaken to improve the completion of consent forms within the department.

Materials and methods:

Common problem areas on consent forms were identified and Quality Improvement (QI) methodology was used to design the study including selection of appropriate outcome, process and balancing measures. Baseline information on completion of: (1) patient details, (2) consultant details, (3) legibility, (4) use of abbreviations in description of operation/complications, and (5) patient signatures was collected. Four weekly interventions were made which were accompanied by 4 further data collection cycles. A further reaudit took place 4 months following the completion of the project to establish whether improvements had been sustained.

Results:

Over the 5 QI data collection cycles the average completion of the 3 outcome measures rose from 59% to 93% and 4 months later was sustained at 91%. Outcome measure 1 (legibility of documentation) rose from 62% to 100%. Outcome measure 2 (omission of abbreviations) rose from 33% to 79%. Outcome measure 3 (patient signature) rose from 81% to 100%.

Conclusion:

This Quality Improvement Project led to a significant and sustained improvement in quality of completion of consent forms within the department with the most marked improvement in omission of abbreviations. This quality improvement methodology could easily be adapted for other surgical specialities.
Outcomes of Highly Selected Live Donors With a Future Liver Remnant Less Than or Equal to 30%: A Matched Cohort Study
Authors: Zuckerman Jesse , Gorgen Andre , Acuna Sergio A. , Abreu Phillipe , Goldaracena Nicolas , Galvin Zita , Cattral Mark S. , Ghanekar Anand , McGilvray Ian D. , Lilly Les B. , Selzner Nazia , Grant David R. , Sapisochin Gonzalo
Published: November 2020

Background.

The main concern with live donor liver transplantation (LDLT) is the risk to the donor. Given the potential risk of liver insufficiency, most centers will only accept candidates with future liver remnants (FLR) >30%. We aimed to compare postoperative outcomes of donors who underwent LDLT with FLR ≤30% and >30%.

Methods.

Adults who underwent right hepatectomy for LDLT between 2000 and 2018 were analyzed. Remnant liver volumes were estimated using hepatic volumetry. To adjust for between-group differences, donors with FLR ≤30% and >30% were matched 1:2 based on baseline characteristics. Postoperative complications including liver dysfunction were compared between the groups.

Results.

A total of 604 live donors were identified, 28 (4.6%) of whom had a FLR ≤30%. Twenty-eight cases were successfully matched with 56 controls; the matched cohorts were mostly similar in terms of donor and graft characteristics. The calculated median FLR was 29.8 (range, 28.0–30.0) and 35.2 (range, 30.1–68.1) in each respective group. Median follow-up was 36.5 mo (interquartile range, 11.8–66.1). Postoperative outcomes were similar between groups. No difference was observed in overall complication rates (FLR ≤30%: 32.1% versus FLR >30%: 28.6%; odds ratio [OR], 1.22; 95% confidence interval [CI], 0.46-3.27) or major complication rates (FLR ≤30%: 14.3% versus FLR >30%: 14.3%; OR, 1.17; 95% CI, 0.33-4.10). Posthepatectomy liver failure was rare, and no difference was observed (FLR ≤30%: 3.6% versus FLR >30%: 3.6%; OR, 1.09; 95% CI, 0.11-11.1).

Conclusion.

A calculated FLR between 28% and 30% on its own should not represent a formal contraindication for live donation.
Latency of Multifocal Visual Evoked Potential in Multiple Sclerosis: A Visual Pathway Biomarker for Clinical Trials of Remyelinating Therapies
Authors: Klistorner Alexander , Triplett James D. , Barnett Michael H. , Yiannikas Con , Barton Joshua , Parratt John , You Yuyi , Graham Stuart L.
Published: November 2020

Purpose:

Acute focal demyelination is the characteristic feature of multiple sclerosis, with the majority of damaged axons undergoing limited remyelination and forming chronic lesions. Potential remyelinating agents are currently under development and there is therefore an urgent need for reliablein vivobiomarkers of remyelination. This study aimed to investigate potential changes in multifocal visual evoked potentials' (mfVEPs) latency in a cohort of relapsing–remitting multiple sclerosis (RRMS) patients. The potential sample size required for a remyelination-based clinical trial using different treatment effect sizes and the mfVEP latency as an outcome measure was also estimated.

Methods:

A total of 50 RRMS consecutive patients with no previous history of optic neuritis in at least one eye and 15 normal controls of similar age and gender composition were prospectively enrolled. Fifteen patients had a history of unilateral ON more than 12 months earlier, whereas 41 patients demonstrated optic radiations lesions on MRI at baseline. Most patients were on disease modifying therapy. A mfVEP was recorded at baseline and 12 months later.

Results:

At baseline, the mfVEP latency in RRMS patients was delayed compared with normal controls in both optic neuritis and nonoptic neuritis eyes. Latency delay was significantly correlated to optic radiation lesion volume (R2= 0.38,P< 0.001). There was no significant latency change in multiple sclerosis patients' eyes or optic neuritis and nonoptic neuritis eyes over the follow-up period with latency remaining remarkably constant. This was despite the fact that 46 of 50 patients were on disease-modifying therapies, implying current treatments do not affect myelination in chronic RRMS cases. Sample size calculations to evaluate an additional or alternative remyelinating agent, based on a 40% treatment effect, revealed that a relatively small sample size (78 patients) would be required to demonstrate efficacy in future trials of remyelination therapies.

Conclusions:

Given its known sensitivity for latency changes and the stability found in this RRMS population, the mfVEP represents an ideal biomarker to assess the degree of latency recovery that may be achieved by remyelination in multiple sclerosis.
How does level of personality functioning inform clinical management and treatment? Implications for ICD-11 classification of personality disorder severity
Authors: Bach Bo , Simonsen Sebastian
Published: November 2020

Purpose of review

The International Classification of Diseases, 11th Edition (ICD-11) classifies personality disturbance according to levels of severity. This article reviews the literature on levels of personality functioning in relation to clinical management and treatment, and proposes how these findings apply to the ICD-11 classification of personality disorders.

Recent findings

Findings were primarily derived from studies using the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) Level of Personality Functioning Scale (LPFS), Kernberg's Level of Personality Organization, and the general P-factor of personality disorder. Severity of personality dysfunction is related to treatment outcome, risk of dropout, therapeutic alliance, readiness for treatment, risk of harm to self or others, risk of dissociation and psychotic-like breaks, coherence in narrative identity, reflective functioning, and epistemic trust.

The overall level of personality disorder severity indicates risk of negative outcomes and may be used as decision tool for ‘personalized medicine’ and required treatment intensity (e.g., strength of alliance and the need for establishing epistemic trust). Beyond the ICD-11 guidelines for determining personality disorder severity, these implications also apply to practitioners using comparable frameworks such as the DSM-5 LPFS and Kernberg's Level of Personality Organization. Future research should focus on the interaction of severity with trait qualifiers in relation to clinical management.
Body dysmorphic disorder: a treatment synthesis and consensus on behalf of the International College of Obsessive-Compulsive Spectrum Disorders and the Obsessive Compulsive and Related Disorders Network of the European College of Neuropsychopharmacology
Authors: Castle David , Beilharz Francesca , Phillips Katharine A. , Brakoulias Vlasios , Drummond Lynne M. , Hollander Eric , Ioannidis Konstantinos , Pallanti Stefano , Chamberlain Samuel R. , Rossell Susan L. , Veale David , Wilhelm Sabine , Van Ameringen Michael , Dell’Osso Bernardo , Menchon Jose M. , Fineberg Naomi A.
Published: November 2020

Body dysmorphic disorder (BDD) is characterized by a preoccupation with a perceived appearance flaw or flaws that are not observable to others. BDD is associated with distress and impairment of functioning. Psychiatric comorbidities, including depression, social anxiety, and obsessive-compulsive disorder are common and impact treatment. Treatment should encompass psychoeducation, particularly addressing the dangers associated with cosmetic procedures, and may require high doses of selective serotonin reuptake inhibitors* (SSRI*) and protracted periods to establish full benefit. If there is an inadequate response to SSRIs, various adjunctive medications can be employed including atypical antipsychotics*, anxiolytics*, and the anticonvulsant levetiracetam*. However, large-scale randomized controlled trials are lacking and BDD is not an approved indication for these medications. Oxytocin* may have a potential role in treating BDD, but this requires further exploration. Cognitive-behavioural therapy has good evidence for efficacy for BDD, and on-line and telephone-assisted forms of therapy are showing promise. CBT for BDD should be customized to address such issues as mirror use, perturbations of gaze, and misinterpretation of others’ emotions, as well as overvalued ideas about how others view the individual.
Contrasting effects of Miocene and Anthropocene levels of atmospheric CO2on silicon accumulation in a model grass
Authors: Biru Fikadu N. , Cazzonelli Christopher I. , Elbaum Rivka , Johnson Scott N.
Published: November 2020

Grasses are hyper-accumulators of silicon (Si), which they acquire from the soil and deposit in tissues to resist environmental stresses. Given the high metabolic costs of herbivore defensive chemicals and structural constituents (e.g. cellulose), grasses may substitute Si for these components when carbon is limited. Indeed, high Si uptake grasses evolved in the Miocene when atmospheric CO2concentration was much lower than present levels. It is, however, unknown how pre-industrial CO2concentrations affect Si accumulation in grasses. UsingBrachypodium distachyon, we hydroponically manipulated Si-supply (0.0, 0.5, 1, 1.5, 2 mM) and grew plants under Miocene (200 ppm) and Anthropocene levels of CO2comprising ambient (410 ppm) and elevated (640 ppm) CO2concentrations. We showed that regardless of Si treatments, the Miocene CO2levels increased foliar Si concentrations by 47% and 56% relative to plants grown under ambient and elevated CO2, respectively. This is owing to higher accumulation overall, but also the reallocation of Si from the roots into the shoots. Our results suggest that grasses may accumulate high Si concentrations in foliage when carbon is less available (i.e. pre-industrial CO2levels) but this is likely to decline under future climate change scenarios, potentially leaving grasses more susceptible to environmental stresses.
The probability of fusions joining sex chromosomes and autosomes
Authors: Anderson Nathan W. , Hjelmen Carl E. , Blackmon Heath
Published: November 2020

Chromosome fusion and fission are primary mechanisms of karyotype evolution. In particular, the fusion of a sex chromosome and an autosome has been proposed as a mechanism to resolve intralocus sexual antagonism. If sexual antagonism is common throughout the genome, we should expect to see an excess of fusions that join sex chromosomes and autosomes. Here, we present a null model that provides the probability of a sex chromosome autosome fusion, assuming all chromosomes have an equal probability of being involved in a fusion. This closed-form expression is applicable to both male and female heterogametic sex chromosome systems and can accommodate unequal proportions of fusions originating in males and females. We find that over 25% of all chromosomal fusions are expected to join a sex chromosome and an autosome whenever the diploid autosome count is fewer than 16, regardless of the sex chromosome system. We also demonstrate the utility of our model by analysing two contrasting empirical datasets: one from
Drosophila
and one from the jumping spider genus
Habronattus
. We find that in the case of
Habronattus
, there is a significant excess of sex chromosome autosome fusions but that in
Drosophila
there are far fewer sex chromosome autosome fusions than would be expected under our null model.
Biased transformation erases traditions sustained by conformist transmission
Authors: Morgan Thomas J. H. , Thompson Bill
Published: November 2020

Conformist transmission is a cognitively simple decision-making process by which observers are disproportionately likely to follow the majority. It has been studied in multiple species because theory suggests it can create stable cultural variation. However, the current theory assumes that while conformist transmission favours the majority, it is otherwise unbiased and does not systematically transform information, even though such biases are widely documented. Here, we relax this assumption, requiring conformist observers to infer the size of the majority from finite observations of their group mates. Because such inference can be subject to bias, it can lead to the biased transformation of transmitted information. We find that when individuals are biased (even weakly) the capacity of conformist transmission to sustain traditions is reduced and, in many cases, removed entirely. This suggests that the emphasis on conformist transmission as a source of stable cultural variation may be misplaced.
Use of nursery areas by the extinct megatooth shark
Otodus megalodon
(Chondrichthyes: Lamniformes)
Authors: Herraiz Jose L. , Ribé Joan , Botella Héctor , Martínez-Pérez Carlos , Ferrón Humberto G.
Published: November 2020

Nursery areas are fundamental for the success of many marine species, particularly for large, slow-growing taxa with low fecundity and high age of maturity. Here, we examine the population size-class structure of the extinct gigantic shark
Otodus megalodon
in a newly described middle Miocene locality from Northeastern Spain, as well as in eight previously known formations (Temblor, Calvert, Pisco, Gatún, Chucunaque, Bahía Inglesa, Yorktown and Bone Valley). In all cases, body lengths of all individuals were inferred from dental parameters and the size-class structure was estimated from kernel probability density functions and Gaussian mixture models. Our analyses support the presence of five potential nurseries ranging from the Langhian (middle Miocene) to the Zanclean (Pliocene), with higher densities of individuals with estimated body lengths within the typical range of neonates and young juveniles. These results reveal, for the first time, that nursery areas were commonly used by
O. megalodon
over large temporal and spatial scales, reducing early mortality and playing a key role in maintaining viable adult populations. Ultimately, the presumed reliance of
O. megalodon
on the presence of suitable nursery grounds might have also been determinant in the demise of this iconic top predatory shark.
Future climates: Markov blankets and active inference in the biosphere
Authors: Rubin Sergio , Parr Thomas , Da Costa Lancelot , Friston Karl
Published: November 2020

We formalize the Gaia hypothesis about the Earth climate system using advances in theoretical biology based on the minimization of variational free energy. This amounts to the claim that non-equilibrium steady-state dynamics—that underwrite our climate—depend on the Earth system possessing a Markov blanket. Our formalization rests on how the metabolic rates of the biosphere (understood as Markov blanket's internal states) change with respect to solar radiation at the Earth's surface (i.e. external states), through the changes in greenhouse and albedo effects (i.e. active states) and ocean-driven global temperature changes (i.e. sensory states). Describing the interaction between the metabolic rates and solar radiation as climatic states—in a Markov blanket—amounts to describing the dynamics of the internal states as actively inferring external states. This underwrites climatic non-equilibrium steady-state through free energy minimization and thus a form of planetary autopoiesis.
Synchrotron radiation-based X-ray tomography reveals life history in primate cementum incrementation
Authors: Newham Elis , Corfe Ian J. , Brown Kate Robson , Gostling Neil J. , Gill Pamela G. , Schneider Philipp
Published: November 2020

Cementum is a mineralized dental tissue common to mammals that grows throughout life, following a seasonally appositional rhythm. Each year, one thick translucent increment and one thin opaque increment is deposited, offering a near-complete record of an animal's life history. Male and female mammals exhibit significant differences in oral health, due to the contrasting effects of female versus male sex hormones. Oestrogen and progesterone have a range of negative effects on oral health that extends to the periodontium and cementum growth interface. Here, we use synchrotron radiation-based X-ray tomography to image the cementum of a sample of rhesus macaque (
Macaca mulatta
) teeth from individuals of known life history. We found that increased breeding history in females corresponds with increased increment tortuosity and less organized cementum structure, when compared to male and juvenile cementum. We quantified structural differences by measuring the greyscale ‘texture’ of cementum and comparing results using principal components analysis. Adult females and males occupy discrete regions of texture space with no overlap. Females with known pregnancy records also have significantly different cementum when compared with non-breeding and juvenile females. We conclude that several aspects of cementum structure and texture may reflect differences in sexual life history in primates.
Combined computed tomography and position-resolved X-ray diffraction of an intact Roman-era Egyptian portrait mummy
Authors: Stock S. R. , Stock M. K. , Almer J. D.
Published: November 2020

Hawara Portrait Mummy 4, a Roman-era Egyptian portrait mummy, was studied with computed tomography (CT) and with CT-guided synchrotron X-ray diffraction mapping. These are the first X-ray diffraction results obtained non-invasively from objects within a mummy. The CT data showed human remains of a 5-year-old child, consistent with the female (but not the age) depicted on the portrait. Physical trauma was not evident in the skeleton. Diffraction at two different mummy-to-detector separations allowed volumetric mapping of features including wires and inclusions within the wrappings and the skull and femora. The largest uncertainty in origin determination was approximately 1.5 mm along the X-ray beam direction, and diffraction- and CT-determined positions matched. Diffraction showed that the wires were a modern dual-phase steel and showed that the 7 × 5 × 3 mm inclusion ventral of the abdomen was calcite. Tracing the 00.2 and 00.4 carbonated apatite (bone's crystalline phase) reflections back to their origins produced cross-sectional maps of the skull and of femora; these maps agreed with transverse CT slices within approximately 1 mm. Coupling CT and position-resolved X-ray diffraction, therefore, offers considerable promise for non-invasive studies of mummies.
The application of rapid evaporative ionization mass spectrometry in the analysis of
Drosophila
species—a potential new tool in entomology
Authors: Wagner Iris , Koch Natalie I. , Sarsby Joscelyn , White Nicola , Price Tom A. R. , Jones Sam , Hurst Jane L. , Beynon Robert J.
Published: November 2020

There is increasing emphasis on the use of new analytical approaches in subject analysis and classification, particularly in respect to minimal sample preparation. Here, we demonstrate that rapid evaporative ionization mass spectrometry (REIMS), a method that captures metabolite mass spectra after rapid combustive degradation of an intact biological specimen, generates informative mass spectra from several arthropods, and more specifically, is capable of discerning differences between species and sex of several adult
Drosophila
species. A model including five
Drosophila
species, built using pattern recognition, achieves high correct classification rates (over 90%) using test datasets and is able to resolve closely related species. The ease of discrimination of male and female specimens also demonstrates that sex-specific differences reside in the REIMS metabolite patterns, whether analysed across all five species or specifically for
D. melanogaster.
Further, the same approach can correctly discriminate and assign
Drosophila
species at the larval stage, where these are morphologically highly similar or identical. REIMS offers a novel approach to insect typing and analysis, requiring a few seconds of data acquisition per sample and has considerable potential as a new tool for the field biologist.
Understanding and exploiting interactions between cellular proteostasis pathways and infectious prion proteins for therapeutic benefit
Authors: Yakubu Unekwu M. , Catumbela Celso S. G. , Morales Rodrigo , Morano Kevin A.
Published: November 2020

Several neurodegenerative diseases of humans and animals are caused by the misfolded prion protein (PrP
Sc
), a self-propagating protein infectious agent that aggregates into oligomeric, fibrillar structures and leads to cell death by incompletely understood mechanisms. Work in multiple biological model systems, from simple baker's yeast to transgenic mouse lines, as well as
in vitro
studies, has illuminated molecular and cellular modifiers of prion disease. In this review, we focus on intersections between PrP and the proteostasis network, including unfolded protein stress response pathways and roles played by the powerful regulators of protein folding known as protein chaperones. We close with analysis of promising therapeutic avenues for treatment enabled by these studies.
The FBXL family of F-box proteins: variations on a theme
Authors: Mason Bethany , Laman Heike
Published: November 2020

The ubiquitin–proteasome system (UPS) is responsible for the rapid targeting of proteins for degradation at 26S proteasomes and requires the orchestrated action of E1, E2 and E3 enzymes in a well-defined cascade. F-box proteins (FBPs) are substrate-recruiting subunits of Skp1-cullin1-FBP (SCF)-type E3 ubiquitin ligases that determine which proteins are ubiquitinated. To date, around 70 FBPs have been identified in humans and can be subdivided into distinct families, based on the protein-recruiting domains they possess. The FBXL subfamily is defined by the presence of multiple leucine-rich repeat (LRR) protein-binding domains. But how the 22 FBPs of the FBXL family achieve their individual specificities, despite having highly similar structural domains to recruit their substrates, is not clear. Here, we review and explore the FBXL family members in detail highlighting their structural and functional similarities and differences and how they engage their substrates through their LRRs to adopt unique interactomes.
Lawsonella clevelandensis is a rare cause of infected chronic contained rupture of abdominal aortic aneurysm
Authors: Ahmed Wissam , Dewar Simon , Williams Robin , Stansby Gerard , Harris Kathryn , Weiand Daniel
Published: November 2020

Lawsonella clevelandensis

is an anaerobic, partially acid-fast, Gram-positive bacillus associated with abscess formation. We present the case of a 70-year-old male with chronic contained rupture of abdominal aortic aneurysm (CCR-AAA) complicated by intra-abdominal abscess formation. An abdominal computed tomography scan revealed a rim-enhancing retroperitoneal collection tracking into the subcutaneous layer of the left flank and buttock, suggestive of CCR-AAA with infected haematoma. He underwent ultrasound-guided needle aspiration of the intra-abdominal collection. Conventional culture techniques failed to isolate

L. clevelandensis

, and the diagnosis was only confirmed by means of 16S rRNA PCR. The patient underwent branched endovascular repair of his aneurysm, and was commenced on treatment with co-amoxiclav, resulting in significant reduction in the size of the infected collection. This is only the second reported case of infection with

L. clevelandensis

in the UK, and the first reported case of this organism causing infected CCR-AAA.
The role of Meq-vIL8 in regulating Marek’s disease virus pathogenesis
Authors: Liao Yifei , Bajwa Kanika , Al-Mahmood Mohammad , Gimeno Isabel M. , Reddy Sanjay M. , Lupiani Blanca
Published: November 2020

Marek’s disease virus (MDV) is a highly cell-associated oncogenic alphaherpesvirus that causes T cell lymphoma in chickens. MDV-encoded Meq and vIL8 proteins play important roles in transformation and early cytolytic infection, respectively. Previous studies identified a spliced transcript,meq-vIL8, formed by alternative splicing ofmeqandvIL8genes in MDV lymphoblastoid tumour cells. To determine the role of Meq-vIL8 in MDV pathogenesis, we generated a recombinant MDV (MDV-meqΔSD) by mutating the splice donor site in themeqgene to abrogate the expression of Meq-vIL8. As expected, our results show that MDV-meqΔSD virus grows similarly to the parental and revertant viruses in cell culture, suggesting that Meq-vIL8 is dispensable for MDV growthin vitro. We further characterized the pathogenic properties of MDV-meqΔSD virus in chickens. Our results show that lack of Meq-vIL8 did not affect virus replication during the early cytolytic phase, as determined by immunohistochemistry analysis and/or viral genome copy number, but significantly enhanced viral DNA load in the late phase of infection in the spleen and brain of infected chickens. In addition, we observed that abrogation of Meq-vIL8 expression reduced the mean death time and increased the prevalence of persistent neurological disease, common features of highly virulent strains of MDV, in inoculated chickens. In conclusion, our study shows that Meq-vIL8 is an important virulence factor of MDV.
An OregonGreen488-labelled d-amino acid for visualizing peptidoglycan by super-resolution STED nanoscopy
Authors: Söderström Bill , Ruda Alessandro , Widmalm Göran , Daley Daniel O.
Published: November 2020

Fluorescent d-amino acids (FDAAs) are molecular probes that are widely used for labelling the peptidoglycan layer of bacteria. When added to growing cells they are incorporated into the stem peptide by a transpeptidase reaction, allowing the timing and localization of peptidoglycan synthesis to be determined by fluorescence microscopy. Herein we describe the chemical synthesis of an OregonGreen488-labelled FDAA (OGDA). We also demonstrate that OGDA can be efficiently incorporated into the PG of Gram-positive and some Gram-negative bacteria, and imaged by super-resolution stimulated emission depletion (STED) nanoscopy at a resolution well below 100 nm.
Analytical and diagnostic performances of a high-throughput immunoassay for SARS-CoV-2 IgM and IgG
Authors: Padoan Andrea , Cosma Chiara , Zaupa Paolo , Plebani Mario
Published: November 2020

Background

Reliable SARS-CoV-2 serological assays are required for diagnosing infections, for the serosurveillance of past exposures and for assessing the response to future vaccines. In this study, the analytical and clinical performances of a chemiluminescent immunoassays for SARS-CoV-2 IgM and IgG detection (Mindray CL-1200i), targeting Nucleocapsid (N) and receptor binding domain (RBD) portion of the Spike protein, were evaluated.

Methods

Precision and linearity were evaluated using standardized procedures. A total of 157 leftover serum samples from 81 hospitalized confirmed COVID-19 patients (38 with moderate and 43 with severe disease) and 76 SARS-CoV-2 negative subjects (44 healthcare workers, 20 individuals with rheumatic disorders, 12 pregnant women) were included in the study. In an additional series of 44 SARS-CoV-2 positive, IgM and IgG time kinetics were also evaluated in a time-period of 38 days.

Results

Precision was below or equal to 4% for both IgM and IgG, in all the studied levels, whilst a slightly significant deviation from linearity was observed for both assays in the range of values covering the manufacturer’s cut-off. Considering a time frame ≥ 12 days post symptom onset, sensitivity and specificity for IgM were 92.3% (95%CI:79.1%-98.4%) and 92.1% (95%CI:83.6%-97.0%). In the same time frame, sensitivity and specificity for IgG were 100% (95%CI:91.0%-100%) and 93.4% (95%CI:85.3%-97.8%). The assays agreement was 73.9% (Cohen’s kappa of 0.373). Time kinetics showed a substantial overlapping of IgM and IgG response, the latter values being elevated up to 38 days from symptoms onset.

Conclusions

Analytical imprecision is satisfactory as well as the linearity, particularly when taking into account the fact that both assays are claimed to be qualitative. Diagnostic sensitivity of IgG was excellent, especially considering specimens collected ≥12 days post symptom onset. Time kinetics suggest that IgM and IgG are detectable early in the course of infection, but the role of SARS-CoV-2 antibodies in clinical practice still requires further evaluations.
Impact of obstructive sleep apnoea on cardiometabolic health in an ageing population in rural South Africa: Building the case for the treatment of sleep disorders in deprived settings
Authors: Roche Johanna , Rae Dale , Redman Kirsten , Knutson Kristen L , Schantz Malcolm von , Gómez-Olivé F Xavier , Scheuermaier Karine
Published: November 2020

Objectives

The association between obstructive sleep apnoea (OSA) and increased cardiometabolic risk (CMR) has been well documented in higher-income countries. However, OSA and its association with CMR have not yet been investigated, based on objective measures, in Southern Africa. We measured polysomnography (PSG)-derived sleep characteristics, OSA prevalence and its association with cardiometabolic diseases in a rural, low-income, aging African-ancestry population in South Africa.

Methods

Seventy-five participants were recruited. BMI, hypertension, diabetes, dyslipidaemia, and HIV status were determined. A continuous CMR score was calculated using waist circumference (WC), random glucose, HDL-cholesterol, triglycerides, and mean arterial blood pressure. Sleep architecture, arousal index, and apnoea-hypopnea index (AHI) for detection of OSA (AHI≥15) were assessed by home-based PSG. Associations between CMR score and age, sex, socio-economic status (SES), AHI and TST were investigated by multivariable analysis.

Results

In our sample (53 women, 66.1±10.7y, 12 HIV+), 60.7% were overweight/obese, 61.3% hypertensive and 29.3% had undiagnosed OSA. Being older (p=0.02), having a greater BMI (p=0.02) and higher WC (p<0.01) were associated with OSA. AHI severity (ß=0.011p=0.01) and being a woman (ß=0.369, p=0.01) were independently associated with a greater CMR score in SES- and age-adjusted analyses.

Conclusions

In this ageing South African community with obesity and hypertension, OSA prevalence is alarming and associated with CMR. We demonstrate feasibility of detecting OSA in a rural setting using PSG. Our results highlight the necessity for actively promoting health education and systematic screening and treatment of OSA in this population, to prevent future cardiovascular morbidity, especially among women.
Mobile outreach testing for COVID-19 in twenty homeless shelters in Toronto, Canada
Authors: Kiran Tara , Craig-Neil Amy , Das Paul , Lockwood Joel , Wang Ri , Nathanielsz Nikki , Rosenthal Esther , Snider Carolyn , Hwang Stephen W.
Published: November 2020

Background

It is unclear what the best strategy is for detecting COVID-19 among homeless shelter residents and what individual factors are associated with positivity.

Methods

We conducted a retrospective chart audit obtaining repeated cross-sectional data from outreach testing done at homeless shelters between April 1st and July 31st, 2020 in Toronto, Canada. We compared the positivity rate for shelters tested because of an outbreak (at least one known case) versus surveillance (no known cases). A patient-level analysis examined differences in demographic, health, and behavioural characteristics of residents who did and did not test positive for COVID-19.

Findings

One thousand nasopharyngeal swabs were done on 872 unique residents at 20 shelter locations. Among the 504 tests done in outbreak settings, 69 (14%) were positive and 1 (0.2%) was indeterminate. Among the 496 tests done for surveillance, 11 (2%) were positive and none were indeterminate. Shelter residents who tested positive were significantly less likely to have a health insurance card (54% vs 72%, p=0.03) or have visited another shelter in the last 14 days (0% vs 18%, p<0.01) compared to those who tested negative; There was no association between COVID-19 positivity and medical history (p=0.40) or symptoms (p=0.43).

Interpretation

Our findings support testing of asymptomatic shelter residents for COVID-19 when a positive case is identified at the same shelter but suggest limited utility of testing all shelter residents in the absence of a known case. Visiting another shelter in the last 14 days is associated with a decreased risk of COVID-19 positivity.
Inflammatory profile of induced sputum composition in systemic sclerosis: a comparison with healthy volunteers
Authors: Jacquerie P. , Henket M. , André B. , Moermans C. , de Seny D. , Gester F. , Louis R. , Malaise M. , Guiot J.
Published: November 2020

Background

Systemic sclerosis (SSc) is a potentially serious and disabling connective tissue disease specially in case of interstitial lung disease (SSc-ILD). The aim of our study was to evaluate the potential utility of dosing in the induced sputum (IS) and to compare their levels in SSc-ILD and SSc-nonILD patients, as well as in healthy volunteers (HV). IS and sera values were also compared.

Methods

In a prospective cross-sectional analysis, we studied the IS and serum provided from 25 SSc patients, 15 SSc-nonILD and 10 SSc-ILD, compared to 25 HV. We analyzed sputum cell composition and quantified in the supernatant and corresponding serum by commercially available immunoassays: IGFBP-1, IGFBP-2, IGFBP-3, TGF-β, IL-8, TNF-α, YKL-40, MMP-7 and MMP-9. Lung function was studied by the determination of FEV-1 (%), FVC (%), DLCO (%) and KCO (%).

Results

The IS of SSc patients had a lower weight than HV (p<0.01) without any significant difference with regard to the cellularity. IGFBP-1 (p<0.0001), TGF-β (p<0.05), IL-8 (p<0.05), YKL-40 (p<0.0001) and MMP-7 (p<0.01) levels were increased in the IS of SSc patients compared to HV. Only IL-8 serum levels (p<0.001) were increased in SSc patients compared to HV. Neither in IS nor in serum were observed differences between SSc-ILD and SSc-nonILD patients. Correlations were observed between IS IL-8 levels and FEV-1 (%)(r=-0.53, p<0.01), FVC (%) (r=-0.51, p<0.01) and annualized □KCO (%) (r=0.57, p<0.05), between IS TGF-□ levels and annualized □FEV-1 (%) (r=-0.57, p<0.05), between IS IGFBP-2 levels and annualized □KCO (%) (r=0.56, p<0.05).

Conclusion

Our study showed that SSc patients exhibit raised IS levels of IGFBP-1, TGF-β, IL-8, YKL-40 and MMP-7, molecules known to be involved in lung remodeling and fibrotic process, without any significant difference between SSc-ILD and SSc-nonILD patients. IL-8, TGF-□ and IGFBP-2 are correlated with lung function in SSc patients which emphasize clinical relevance. IS analysis represents a new approach to understand lung inflammatory process in SSc patients. A longitudinal study is needed to evaluate their pathophysiological relevance.
“I had made the decision, and no one was going to stop me” —Facilitators of PrEP adherence during pregnancy and postpartum in Cape Town, South Africa
Authors: Davey Dvora L. Joseph , Knight Lucia , Markt-Maloney Jackie , Tsawe Nokwazi , Gomba Yolanda , Mashele Nyiko , Dovel Kathryn , Gorbach Pamina , Bekker Linda-Gail , Coates Thomas J. , Myer Landon
Published: November 2020

Introduction

HIV incidence is high during pregnancy and postpartum in many settings. PrEP is safe and effective but requires adherence during potential HIV exposure, yet the facilitators of high maternal adherence are not well understood in high HIV burden settings.

Methods

We conducted semi-structured interviews with women who reported high adherence (PrEP use ≥ 25 days in last 30-days) within a PrEP service for pregnant and postpartum women located in a large primary care facility in a high-HIV burden township. Topics for interviews included: individual/interpersonal risk, disclosure, anticipated PrEP stigma, safety, side-effects, and facility-level factors effecting adherence. A thematic approach guided an iterative process of coding (reviewed to ensure intercoder reliability) and analysis using NVivo 12.

Results

We interviewed 25 postpartum women with high PrEP adherence who were on PrEP for a median of 9-months, median age 26-years, and median baseline gestational age 24-weeks. Themes identified as key drivers of optimal PrEP use were HIV risk perception – primarily due to partner’s perceived risky sexual behaviors and unknown serosatus—and a strong desire to have a baby free of HIV. Reported disclosure of PrEP use to family, partners and friends facilitated PrEP adherence. Women continued PrEP postpartum because they felt empowered by PrEP and did not want to “go backwards” and increase their HIV risk as before PrEP. Women who reported high adherence all discussed having community support and reminders to take PrEP on time. The primary barriers were anticipated or experienced stigma, which most overcame through education of partners/family about PrEP. Pregnant women experienced transient side effects, but found ways to continue, including taking PrEP at night. Women believed PrEP education and counselling were accessible when integrated into antenatal care which contributed to continued PrEP use.

Conclusions

Facilitators of optimal PrEP use through pregnancy and postpartum included fear of HIV acquisition for self and infant, mostly due to partner sexual behaviors and unknown serostatus, along with PrEP disclosure, and encouragement from partners and family. PrEP programs for pregnant and postpartum women should integrate strategies to assist women with realistic appraisals of risk and teach skills for securing support for significant others.
Integrated Protein Network Analysis of Whole Exome Sequencing of Severe Preeclampsia
Authors: Schuster Jessica , Tollefson George A. , Zarate Valeria , Agudelo Anthony , Stabila Joan , Ragavendran Ashok , Padbury James , Uzun Alper
Published: November 2020

Preeclampsia is a hypertensive disorder of pregnancy, which complicates up to 15 % of US deliveries. It is an idiopathic disorder with complex disease genetics associated with several different phenotypes. We sought to determine if the genetic architecture of preeclampsia can be described by clusters of patients with variants in genes in shared protein interaction networks. We performed a case-control study using whole exome sequencing on early onset preeclamptic mothers with severe features and control mothers with uncomplicated pregnancies. The study was conducted at Women & Infants Hospital of Rhode Island (WIH). A total of 143 patients were enrolled, 61 women with early onset preeclampsia with severe features based on ACOG criteria, and 82 control women at term, matched for race and ethnicity. The main outcomes are variants associated with severe preeclampsia and demonstration of the genetic architecture of preeclampsia. A network analysis and visualization tool, Proteinarium, was used to confirm there are clusters of patients with shared gene networks associated with severe preeclampsia. The majority of the sequenced patients appear in two significant clusters. We identified one case dominant and one control dominant cluster. Thirteen genes were unique to the case dominated cluster. Among these genes, LAMB2, PTK2, RAC1, QSOX1, FN1, and VCAM1 have known associations with the pathogenic mechanisms of preeclampsia. Using the exome-wide sequence variants, combined with these 13 identified network genes, we generated a polygenetic risk score for severe preeclampsia with an AUC of 0.57. Using bioinformatic analysis, we were able to identify subsets of patients with shared protein interaction networks, thus confirming our hypothesis about the genetic architecture of preeclampsia. The unique genes identified in the cluster associated with severe preeclampsia were able to increase the predictive power of the polygenic risk score.
Cell-type Specific Expression Quantitative Trait Loci Associated with Alzheimer Disease in Blood and Brain Tissue
Authors: Patel Devanshi , Zhang Xiaoling , Farrell John J. , Chung Jaeyoon , Stein Thor D. , Lunetta Kathryn L. , Farrer Lindsay A.
Published: November 2020

Because regulation of gene expression is heritable and context-dependent, we investigated AD-related gene expression patterns in cell-types in blood and brain. Cis-expression quantitative trait locus (eQTL) mapping was performed genome-wide in blood from 5,257 Framingham Heart Study (FHS) participants and in brain donated by 475 Religious Orders Study/Memory & Aging Project (ROSMAP) participants. The association of gene expression with genotypes for all cis SNPs within 1Mb of genes was evaluated using linear regression models for unrelated subjects and linear mixed models for related subjects. Cell type-specific eQTL (ct-eQTL) models included an interaction term for expression of “proxy” genes that discriminate particular cell type. Ct-eQTL analysis identified 11,649 and 2,533 additional significant gene-SNP eQTL pairs in brain and blood, respectively, that were not detected in generic eQTL analysis. Of note, 386 unique target eGenes of significant eQTLs shared between blood and brain were enriched in apoptosis and Wnt signaling pathways. Five of these shared genes are established AD loci. The potential importance and relevance to AD of significant results in myeloid cell-types is supported by the observation that a large portion of GWS ct-eQTLs map within 1Mb of established AD loci and 58% (23/40) of the most significant eGenes in these eQTLs have previously been implicated in AD. This study identified cell-type specific expression patterns for established and potentially novel AD genes, found additional evidence for the role of myeloid cells in AD risk, and discovered potential novel blood and brain AD biomarkers that highlight the importance of cell-type specific analysis.
COVID-19: Short term prediction model using daily incidence data
Authors: Zhao Hongwei , Merchant Naveed N , McNulty Alyssa , Radcliff Tiffany A , Cote Murray J , Fischer Rebecca , Sang Huiyan , Ory Marcia G
Published: November 2020

Background

Prediction of the dynamics of new SARS-CoV-2 infections during the current COVID-19 pandemic is critical for public health planning of efficient health care allocation and monitoring the effects of policy interventions. We describe a new approach that forecasts the number of incident cases in the near future given past occurrences using only a small number of assumptions.

Methods

Our approach to forecasting future COVID-19 cases involves 1) modeling the observed incidence cases using a Poisson distribution for the daily incidence number, and a gamma distribution for the series interval; 2) estimating the effective reproduction number assuming its value stays constant during a short time interval; and 3) drawing future incidence cases from their posterior distributions, assuming that the current transmission rate will stay the same, or change by a certain degree.

Results

We apply our method to predicting the number of new COVID-19 cases in a single state in the U.S. and for a subset of counties within the state to demonstrate the utility of this method at varying scales of prediction. Our method produces reasonably accurate results when the effective reproduction number is distributed similarly in the future as in the past. Large deviations from the predicted results can imply that a change in policy or some other factors have occurred that have dramatically altered the disease transmission over time.

Conclusion

We presented a modelling approach that we believe can be easily adopted by others, and immediately useful for local or state planning.
A methodology to generate longitudinally updated ACLF prognostication scores from electronic health record data
Authors: Ge Jin , Najafi Nader , Zhao Wendi , Somsouk Ma , Fang Margaret , Lai Jennifer C.
Published: November 2020

Background and Aims

Queries of electronic health record (EHR) data repositories allow for automated data collection. These techniques have not been utilized in hepatology due to previous inability to capture hepatic encephalopathy (HE) grades, which are inputs for acute-on-chronic liver failure (ACLF) models. Here, we describe a methodology to utilizing EHR data to calculate rolling ACLF scores.

Methods

We examined 239 patient-admissions with end-stage liver disease 7/2014-6/2019. We mapped EHR flowsheet data to determine HE grades and calculated two longitudinally updated ACLF scores. We validated HE grades and ACLF diagnoses via chart review; and calculated sensitivity, specificity, and Cohen’s kappa.

Results

Of 239 patient-admissions analyzed, 37% women, 46% non-Hispanic White, median age 60 years, median MELD-Na at admission. Of the 239, 7% were diagnosed with NACSELD-ACLF at admission, 27% during the hospitalization, and 9% at discharge. Forty percent diagnosed with CLIF-C-ACLF at admission, 51% during the hospitalization, and 34% at discharge.

From chart review of 51 admissions, we found sensitivities and specificities for any HE (grades 1-4) were 92-97% and 76-95%, respectively; for severe HE (grades 3-4) were 100% and 78-98%, respectively. Cohen’s kappa between flowsheet and chart review HE grades ranged 0.55-0.72. Sensitivities and specificities for NACSELD-ACLF diagnoses were 75-100% and 96-100%, respectively; for CLIF-C-ACLF diagnoses were 91-100% and 96-100%, respectively. We generated approximately 28 unique ACLF scores per patient per admission-day.

Conclusion

In this study, we developed an informatics-based methodology for to calculate longitudinally updated ACLF scores. This opens new analytic potentials, such big data methods to develop electronic phenotypes for ACLF patients.