bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and activity of varlilumab, a novel and first-in-class agonist anti-CD27 antibody, for hematologic malignancies
Authors: Ansell Stephen M. , Flinn Ian , Taylor Matthew H. , Sikic Branimir I. , Brody Joshua , Nemunaitis John , Feldman Andrew , Hawthorne Thomas R. , Rawls Tracey , Keler Tibor , Yellin Michael J.
Published: May 2020

CD27, a costimulatory molecule on T cells, induces intracellular signals mediating cellular activation, proliferation, effector function, and cell survival on binding to its ligand, CD70. Varlilumab, a novel, first-in-class, agonist immunoglobulin G1 anti-CD27 antibody, mediates antitumor immunity and direct killing of CD27+ tumor cells in animal models. This first-in-human, dose-escalation, and expansion study evaluated varlilumab in patients with hematologic malignancies. Primary objectives were to assess safety and the maximum tolerated and optimal biologic doses of varlilumab. Secondary objectives were to evaluate pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. In a 3 + 3 dose-escalation design, 30 patients with B-cell (n = 25) or T-cell (n = 5) malignancies received varlilumab (0.1, 0.3, 1, 3, or 10 mg/kg IV) as a single dose with a 28-day observation period, followed by weekly dosing (4 doses per cycle, up to 5 cycles, depending on tumor response). In an expansion cohort, 4 additional patients with Hodgkin lymphoma received varlilumab at 0.3 mg/kg every 3 weeks (4 doses per cycle, up to 5 cycles). No dose-limiting toxicities were observed. Treatment-related adverse events, generally grade 1 to 2, included fatigue, decreased appetite, anemia, diarrhea, and headache. Exposure was linear and dose-proportional across dose groups and resulted in increases in proinflammatory cytokines and soluble CD27. One patient with stage IV Hodgkin lymphoma experienced a complete response and remained in remission at >33 months with no further anticancer therapy. These data support further investigation of varlilumab for hematologic malignancies, particularly in combination approaches targeting nonredundant immune regulating pathways. This trial was registered at www.clinicaltrials.gov as #NCT01460134.
Artificial intelligence techniques in asthma: a systematic review and critical appraisal of the existing literature
Authors: Exarchos Konstantinos P. , Beltsiou Maria , Votti Chainti-Antonella , Kostikas Konstantinos
Published: May 2020

Artificial intelligence (AI) when coupled with large amounts of well characterised data can yield models that are expected to facilitate clinical practice and contribute to the delivery of better care, especially in chronic diseases such as asthma.

The purpose of this paper is to review the utilisation of AI techniques in all aspects of asthma research,i.e.from asthma screening and diagnosis, to patient classification and the overall asthma management and treatment, in order to identify trends, draw conclusions and discover potential gaps in the literature.

We conducted a systematic review of the literature using PubMed and DBLP from 1988 up to 2019, yielding 425 articles; after removing duplicate and irrelevant articles, 98 were further selected for detailed review.

The resulting articles were organised in four categories, and subsequently compared based on a set of qualitative and quantitative factors. Overall, we observed an increasing adoption of AI techniques for asthma research, especially within the last decade.

AI is a scientific field that is in the spotlight, especially the last decade. In asthma there are already numerous studies; however, there are certain unmet needs that need to be further elucidated.
Hydrogen peroxide and disease: towards a unified system of pathogenesis and therapeutics
Authors: Pravda Jay
Published: May 2020

Although the immune response has a prominent role in the pathophysiology of ulcerative colitis, sepsis, and systemic lupus erythematosus, a primary immune causation has not been established to explain the pathogenesis of these diseases. However, studies have reported significantly elevated levels of colonic epithelial hydrogen peroxide (a known colitic agent) in ulcerative colitis prior to the appearance of colitis. And patients with sepsis are reported to have toxic levels of blood hydrogen peroxide, whose pathologic effects mirror the laboratory and clinical abnormalities observed in sepsis. More recently, evidence supports a causal role for cellular hydrogen peroxide (a potent apoptotic agent) in the enhanced apoptosis believed to be the driving force behind auto-antigenic exposure and chronic immune activation in systemic lupus erythematosus. The different biological properties of hydrogen peroxide exert distinct pathologic effects depending on the site of accumulation within the body resulting in a unique disease patho-phenotype. On a cellular level, the build-up of hydrogen peroxide triggers apoptosis resulting in systemic lupus erythematosus, on a tissue level (colonic epithelium) excess hydrogen peroxide leads to inflammation and ulcerative colitis, and on a systemic level the pathologic effects of toxic concentrations of blood hydrogen peroxide result in bioenergetic failure and microangiopathic dysfunction leading to multiple organ failure and circulatory shock, characteristic of advanced sepsis. The aim of this paper is to provide a unified evidence-based common causal role for hydrogen peroxide in the pathogenesis of ulcerative colitis, sepsis, and systemic lupus erythematosus. Based on this new theory of pathogenesis, a novel evidence-based treatment of sepsis is also discussed.
Extracellular HMGB1: a therapeutic target in severe pulmonary inflammation including COVID-19?
Authors: Andersson Ulf , Ottestad William , Tracey Kevin J.
Published: May 2020

Background

The 2019 novel coronavirus disease (COVID-19) causes for unresolved reasons acute respiratory distress syndrome in vulnerable individuals. There is a need to identify key pathogenic molecules in COVID-19-associated inflammation attainable to target with existing therapeutic compounds.

The endogenous damage-associated molecular pattern (DAMP) molecule HMGB1 initiates inflammation via two separate pathways. Disulfide-HMGB1 triggers TLR4 receptors generating pro-inflammatory cytokine release. Extracellular HMGB1, released from dying cells or secreted by activated innate immunity cells, forms complexes with extracellular DNA, RNA and other DAMP or pathogen-associated molecular (DAMP) molecules released after lytic cell death.

These complexes are endocytosed via RAGE, constitutively expressed at high levels in the lungs only, and transported to the endolysosomal system, which is disrupted by HMGB1 at high concentrations. Danger molecules thus get access to cytosolic proinflammatory receptors instigating inflammasome activation. It is conceivable that extracellular SARS-CoV-2 RNA may reach the cellular cytosol via HMGB1-assisted transfer combined with lysosome leakage.

Extracellular HMGB1 generally exists in vivo bound to other molecules, including PAMPs and DAMPs. It is plausible that these complexes are specifically removed in the lungs revealed by a 40% reduction of HMGB1 plasma levels in arterial versus venous blood. Abundant pulmonary RAGE expression enables endocytosis of danger molecules to be destroyed in the lysosomes at physiological HMGB1 levels, but causing detrimental inflammasome activation at high levels. Stress induces apoptosis in pulmonary endothelial cells from females but necrosis in cells from males.

Conclusion

Based on these observations we propose extracellular HMGB1 to be considered as a therapeutic target for COVID-19.
Sensory processing patterns affect headache severity among adolescents with migraine
Authors: Genizi Jacob , Halevy Ayelet , Schertz Mitchell , Osman Khaled , Assaf Nurit , Segal Idan , Srugo Isaac , Kessel Aharon , Engel-Yeger Batya
Published: May 2020

Objective

To evaluate the relationship between pain catastrophizing level, sensory processing patterns, and headache severity among adolescents with episodic migraine.

Background

Catastrophizing about pain is a critical variable in how we understand adjustment to pain and has a unique contribution in predicting pain intensity. Recent reports found that migraine is also related to enhanced sensory sensitivity. However, the relationship between pain severity, pain catastrophizing level and sensory sensitivity requires greater study especially among adolescents.

Methods

Participants were 92 adolescents aged 13–18 years, 40 with episodic migraine and 52 healthy controls. The migraine patients were prospectively recruited from outpatient pediatric neurology clinics. All participants completed the Adolescent/Adult Sensory Profile (AASP), and the Pain Catastrophizing Scale for children (PCS-ch). The migraine groups also completed the PedMIDAS, which measures Headache related disability.

Results

Adolescents with migraine had significantly lower tendency to seek sensory input than healthy controls. Elevated rumination and helplessness correlated with higher migraine pain severity. Tendency to avoid sensory input predicted the migraine related disability level. They also significantly higher pain catastrophizing level than healthy controls, as seen in enhanced rumination (p ≤ 0.001) and helplessness (p ≤ 0.05).

Conclusions

Sensory processing difficulties are common among adolescents with episodic migraine. Sensory avoidance may be related to pain experience, and pain catastrophizing and disability level.
Downregulation of miR-637 promotes vascular smooth muscle cell proliferation and migration via regulation of insulin-like growth factor-2
Authors: Yang Ning , Dong Bo , Song Yanqiu , Li Yang , Kou Lu , Yang Jingyu , Qin Qin
Published: May 2020

Background

Dysregulation of the proliferation and migration of vascular smooth muscle cells (VSMCs) is a crucial cause of atherosclerosis. MiR-637 exerts an antiproliferative effect on multiple human cells. Its impact on atherosclerosis remains largely unexplored.

Methods

Real-time PCR was used to determine miR-637 expression in samples from atherosclerosis patients and animal models. Its expression in VSMC dysfunction models (induced by ox-LDL) was also measured. The proliferation and migration of VSMCs were respectively tested using CCK-8 and Transwell assays, and apoptosis was measured using flow cytometry. The Targetscan database was used to predict the target genes of miR-637. Interaction between miR-637 and the potential target gene was validated via real-time PCR, western blotting and a luciferase reporter assay.

Results

MiR-637 expression was significantly lower in atherosclerosis patient and animal model samples. It also decreased in a dose- and time-dependent manner in animal models with ox-LDL-induced atherosclerosis. Transfection with miR-637 mimics suppressed the proliferation and migration of VSMCs while promoting apoptosis, while transfection with miR-637 inhibitors had the opposite effects. We also validated that insulin-like growth factor-2 (IGF-2), a crucial factor in the pathogenesis of atherosclerosis, serves as a target gene for miR-637.

Conclusion

MiR-637 targeting IGF-2 contributes to atherosclerosis inhibition and could be a potential target for this disease.
Effects of Post Annealing on Electrical Performance of Polycrystalline Ga2O3 Photodetector on Sapphire
Authors: Hu Haodong , Liu Yuchen , Han Genquan , Fang Cizhe , Zhang Yanfang , Liu Huan , Wang Yibo , Liu Yan , Ye Jiandong , Hao Yue
Published: May 2020

Effects of post annealing on the physical and electrical properties of solar-blind polycrystalline gallium oxide (Ga2O3) ultraviolet photodetectors on the sapphire substrate are investigated. The grain size of poly-Ga2O3 becomes larger with the post annealing temperature (PAT) increasing from 800 °C to 1000 °C, but it gets smaller with further raising PAT to 1100 °C. A blue shift is observed at the absorption edge of the transmittance spectra of Ga2O3 on sapphire as increasing PAT, due to the incorporation of Al from the sapphire substrate into Ga2O3 to form (AlxGa1–x)2O3. The high-resolution X-ray diffraction and transmittance spectra measurement indicate that the substitutional Al composition and bandgap of (AlxGa1–x)2O3 annealed at 1100 °C can be above 0.30 and 5.10 eV, respectively. The Rmax of the sample annealed at 1000 °C increases about 500% compared to the as-deposited device, and the sample annealed at 1000 °C has short rise time and decay time of 0.148 s and 0.067 s, respectively. This work may pave a way for the fabrication of poly-Ga2O3 ultraviolet photodetector and find a method to improve responsivity and speed of response.
A coarse-graining, ultrametric approach to resolve the phylogeny of prokaryotic strains with frequent homologous recombination
Authors: Pang Tin Yau
Published: May 2020

Background

A frequent event in the evolution of prokaryotic genomes is homologous recombination, where a foreign DNA stretch replaces a genomic region similar in sequence. Recombination can affect the relative position of two genomes in a phylogenetic reconstruction in two different ways: (i) one genome can recombine with a DNA stretch that is similar to the other genome, thereby reducing their pairwise sequence divergence; (ii) one genome can recombine with a DNA stretch from an outgroup genome, increasing the pairwise divergence. While several recombination-aware phylogenetic algorithms exist, many of these cannot account for both types of recombination; some algorithms can, but do so inefficiently. Moreover, many of them reconstruct the ancestral recombination graph (ARG) to help infer the genome tree, and require that a substantial portion of each genome has not been affected by recombination, a sometimes unrealistic assumption.

Methods

Here, we propose a Coarse-Graining approach for Phylogenetic reconstruction (CGP), which is recombination-aware but forgoes ARG reconstruction. It accounts for the tendency of a higher effective recombination rate between genomes with a lower phylogenetic distance. It is applicable even if all genomic regions have experienced substantial amounts of recombination, and can be used on both nucleotide and amino acid sequences. CGP considers the local density of substitutions along pairwise genome alignments, fitting a model to the empirical distribution of substitution density to infer the pairwise coalescent time. Given all pairwise coalescent times, CGP reconstructs an ultrametric tree representing vertical inheritance.

Results

Based on simulations, we show that the proposed approach can reconstruct ultrametric trees with accurate topology, branch lengths, and root positioning. Applied to a set of E. coli strains, the reconstructed trees are most consistent with gene distributions when inferred from amino acid sequences, a data type that cannot be utilized by many alternative approaches.

Conclusions

The CGP algorithm is more accurate than alternative recombination-aware methods for ultrametric phylogenetic reconstructions.
A life-history perspective on sexual selection in a polygamous species
Authors: Gao Ke , van Wijk Michiel , Clement Zoe , Egas Martijn , Groot Astrid T.
Published: May 2020

Background

Ever since Darwin, evolutionary biologists have studied sexual selection driving differences in appearance and behaviour between males and females. An unchallenged paradigm in such studies is that one sex (usually the male) signals its quality as a mate to the other sex (usually the female), who is choosy in accepting a partner. Here, we hypothesize that in polygamous species these roles change dynamically with the mating status of males and females, depending on direct reproductive costs and benefits of multiple matings, and on sperm competition. We test this hypothesis by assessing fitness costs and benefits of multiple matings in both males and females in a polygamous moth species, as in moths not males but females are the signalers and males are the responders.

Results

We found that multiple matings confer fitness costs and benefits for both sexes. Specifically, the number of matings did not affect the longevity of males or females, but only 67% of the males and 14% of the females mated successfully in all five nights. In addition, the female’s reproductive output increased with multiple matings, although when paired with a new virgin male every night, more than 3 matings decreased her reproductive output, so that the Bateman gradient for females fit a quadratic model better than a linear model. The male’s reproductive success was positively affected by the number of matings and a linear regression line best fit the data. Simulations of the effect of sperm competition showed that increasing last-male paternity increases the steepness of the male Bateman gradient and thus the male’s relative fitness gain from additional mating. Irrespective of last-male paternity value, the female Bateman gradient is steeper than the male one for up to three matings.

Conclusion

Our results suggest that choosiness in moths may well change throughout the mating season, with males being more choosy early in the season and females being more choosy after having mated at least three times. This life-history perspective on the costs and benefits of multiple matings for both sexes sheds new light on sexual selection forces acting on sexual signals and responses.
Differential expression pattern of the proteome in response to cadmium stress based on proteomics analysis of wheat roots
Authors: Jian Mingyang , Zhang Dazhong , Wang Xiaoying , Wei Shuwei , Zhao Yue , Ding Qin , Han Yucui , Ma Lingjian
Published: May 2020

Background

Heavy metal cadmium (Cd) is a common environmental pollutant in soils, which has an negative impacts on crop growth and development. At present, cadmium has become a major soil and water heavy metal pollutant, which not only causes permanent and irreversible health problems for humans, but also causes a significant reduction in crop yields.

Results

This study examined the chemical forms of Cd in the roots of two wheat varieties (M1019 and Xinong20) by continuous extraction and analyzed differences in distribution characteristics of Cd in the root cell wall, cytoplasm, and organelles by elemental content determination and subcellular separation. Furthermore, we conducted proteomics analysis of the roots of the two varieties under Cd pollution using mass spectrometry quantitative proteomics techniques. A total of 11,651 proteins were identified, of which 10,532 proteins contained quantitative information. In addition, the differentially expressed proteins in the two varieties were related to DNA replication and repair, protein metabolism, and the glutathione metabolism pathway.

Conclusion

The results of this study improve our understanding of the mechanism of plant responses to Cd stress.
Correction to: The International Conference on Intelligent Biology and Medicine 2019 (ICIBM 2019): conference summary and innovations in genomics
Authors: Mathé Ewy , Zhang Chi , Wang Kai , Ning Xia , Guo Yan , Zhao Zhongming
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Bifidobacterium mongoliense genome seems particularly adapted to milk oligosaccharide digestion leading to production of antivirulent metabolites
Authors: Bondue Pauline , Milani Christian , Arnould Emilie , Ventura Marco , Daube Georges , LaPointe Gisèle , Delcenserie Véronique
Published: May 2020

Background

Human milk oligosaccharides (HMO) could promote the growth of bifidobacteria, improving young children’s health. In addition, fermentation of carbohydrates by bifidobacteria can result in the production of metabolites presenting an antivirulent activity against intestinal pathogens. Bovine milk oligosaccharides (BMO), structurally similar to HMO, are found at high concentration in cow whey. This is particularly observed for 3′-sialyllactose (3′SL). This study focused on enzymes and transport systems involved in HMO/BMO metabolism contained in B. crudilactis and B. mongoliense genomes, two species from bovine milk origin. The ability of B. mongoliense to grow in media supplemented with whey or 3′SL was assessed. Next, the effects of cell-free spent media (CFSM) were tested against the virulence expression of Escherichia coli O157:H7 and Salmonella enterica serovar Typhimurium.

Results

Due to the presence of genes encoding β-galactosidases, β-hexosaminidases, α-sialidases and α-fucosidases, B. mongoliense presents a genome more sophisticated and more adapted to the digestion of BMO/HMO than B. crudilactis (which contains only β-galactosidases). In addition, HMO/BMO digestion involves genes encoding oligosaccharide transport systems found in B. mongoliense but not in B. crudilactis. B. mongoliense seemed able to grow on media supplemented with whey or 3′SL as main source of carbon (8.3 ± 1.0 and 6.7 ± 0.3 log cfu/mL, respectively). CFSM obtained from whey resulted in a significant under-expression of ler, fliC, luxS, stx1 and qseA genes (− 2.2, − 5.3, − 2.4, − 2.5 and − 4.8, respectively; P < 0.05) of E. coli O157:H7. CFSM from 3′SL resulted in a significant up-regulation of luxS (2.0; P < 0.05) gene and a down-regulation of fliC (− 5.0; P < 0.05) gene. CFSM obtained from whey resulted in significant up-regulations of sopD and hil genes (2.9 and 3.5, respectively; P < 0.05) of S. Typhimurium, while CFSM obtained from 3′SL fermentation down-regulated hil and sopD genes (− 2.7 and − 4.2, respectively; P < 0.05).

Conclusion

From enzymes and transporters highlighted in the genome of B. mongoliense and its potential ability to metabolise 3′SL and whey, B. mongoliense seems well able to digest HMO/BMO. The exact nature of the metabolites contained in CFSM has to be identified still. These results suggest that BMO associated with B. mongoliense could be an interesting synbiotic formulation to maintain or restore intestinal health of young children.
Genome-wide association mapping of Sclerotinia sclerotiorum resistance in soybean using whole-genome resequencing data
Authors: Boudhrioua Chiheb , Bastien Maxime , Torkamaneh Davoud , Belzile François
Published: May 2020

Background

Sclerotinia stem rot (SSR), caused by Sclerotinia sclerotiorum (Lib.) de Bary, is an important cause of yield loss in soybean. Although many papers have reported different loci contributing to partial resistance, few of these were proved to reproduce the same phenotypic impact in different populations.

Results

In this study, we identified a major quantitative trait loci (QTL) associated with resistance to SSR progression on the main stem by using a genome-wide association mapping (GWAM). A population of 127 soybean accessions was genotyped with 1.5 M SNPs derived from genotyping-by-sequencing (GBS) and whole-genome sequencing (WGS) ensuring an extensive genome coverage and phenotyped for SSR resistance. SNP-trait association led to discovery of a new QTL on chromosome 1 (Chr01) where resistant lines had shorter lesions on the stem by 29 mm. A single gene (Glyma.01 g048000) resided in the same LD block as the peak SNP, but it is of unknown function. The impact of this QTL was even more significant in the descendants of a cross between two lines carrying contrasted alleles for Chr01. Individuals carrying the resistance allele developed lesions almost 50% shorter than those bearing the sensitivity allele.

Conclusion

These results suggest that the new region on chromosome 1 harbors a promising resistance QTL to SSR that can be used in soybean breeding program.
Genetic mapping and genomic selection for maize stalk strength
Authors: Liu Xiaogang , Hu Xiaojiao , Li Kun , Liu Zhifang , Wu Yujin , Wang Hongwu , Huang Changling
Published: May 2020

Background

Maize is one of the most important staple crops and is widely grown throughout the world. Stalk lodging can cause enormous yield losses in maize production. However, rind penetrometer resistance (RPR), which is recognized as a reliable measurement to evaluate stalk strength, has been shown to be efficient and useful for improving stalk lodging-resistance. Linkage mapping is an acknowledged approach for exploring the genetic architecture of target traits. In addition, genomic selection (GS) using whole genome markers enhances selection efficiency for genetically complex traits. In the present study, two recombinant inbred line (RIL) populations were utilized to dissect the genetic basis of RPR, which was evaluated in seven growth stages.

Results

The optimal stages to measure stalk strength are the silking phase and stages after silking. A total of 66 and 45 quantitative trait loci (QTL) were identified in each RIL population. Several potential candidate genes were predicted according to the maize gene annotation database and were closely associated with the biosynthesis of cell wall components. Moreover, analysis of gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway further indicated that genes related to cell wall formation were involved in the determination of RPR. In addition, a multivariate model of genomic selection efficiently improved the prediction accuracy relative to a univariate model and a model considering RPR-relevant loci as fixed effects.

Conclusions

The genetic architecture of RPR is highly genetically complex. Multiple minor effect QTL are jointly involved in controlling phenotypic variation in RPR. Several pleiotropic QTL identified in multiple stages may contain reliable genes and can be used to develop functional markers for improving the selection efficiency of stalk strength. The application of genomic selection to RPR may be a promising approach to accelerate breeding process for improving stalk strength and enhancing lodging-resistance.
Association of intraoperative hyperglycemia and postoperative outcomes in patients undergoing non-cardiac surgery: a multicenter retrospective study
Authors: Shah Nirav J. , Leis Aleda , Kheterpal Sachin , Englesbe Michael J. , Kumar Sathish S.
Published: May 2020

Background

While pre and postoperative hyperglycemia is associated with increased risk of surgical site infection, myocardial infarction, stroke and risk of death, there are no multicenter data regarding the association of intraoperative blood glucose levels and outcomes for the non-cardiac surgical population.

Methods

We conducted a retrospective cohort study from the Michigan Surgical Quality Collaborative, a network of 64 hospitals that prospectively collects validated data on surgical patients for the purpose of quality improvement. We included data for adult general, vascular, endocrine, hepatobiliary, and gastrointestinal operations between 2013 and 2015. We assessed the risk-adjusted, independent relationship between intraoperative hyperglycemia (glucose > 180) and the primary outcome of 30-day morbidity/mortality and secondary outcome of infectious complications using multivariable logistic regression modelling. Post hoc sensitivity analysis to assess the association between blood glucose values ≥250 mg/dL and outcomes was also performed.

Results

Ninety-two thousand seven hundred fifty-one patients underwent surgery between 2013 and 2015 and 5014 (5.4%) had glucose testing intra-operatively. Of these patients, 1647 patients (32.9%) experienced the primary outcome, and 909 (18.1%) the secondary outcome. After controlling for patient comorbidities and surgical factors, peak intraoperative glucose > 180 mg/dL was not an independent predictor of 30-day mortality/morbidity (adjusted OR 1.05, 95%CI:0.86 to 1.28; p-value 0.623; model c-statistic of 0.720) or 30-day infectious complications (adjusted OR 0.93, 95%CI:0.74,1.16; p 0.502; model c-statistic of 0.709). Subgroup analysis for patients with or without diabetes yielded similar results. Sensitivity analysis demonstrated blood glucose of 250 mg/dL was a predictor of 30-day mortality/morbidity (adjusted OR: 1.59, 95% CI: 1.24, 2.05; p < 0.001).

Conclusions

Among more than 5000 patients across 64 hospitals who had glucose measurements during surgery, there was no difference in postoperative outcomes between patients who had intraoperative glucose > 180 mg/ dL compared to patients with glucose values ≤180 mg/ dL.
Correlation and variation of cuff inflating volumes and pressures in different adult models of laryngeal mask: a prospective randomized trial
Authors: Ruananukun Narut , Watcharotayangul Jittiya , Jeeranukosol Suchaya , Komonhirun Rojnarin
Published: May 2020

Background

Hyperinflation of laryngeal mask cuffs may carry the risk of airway complications. The manufacturer recommends inflating cuff until the intracuff pressure reaches 60 cmH2O, or inflate with the volume of air to not exceed the maximum recommended volume. We prospectively assessed the correlation of cuff inflating volumes and pressures, and the appropriated the cuff inflating volumes to generate an intracuff pressure of 60 cmH2O in the adult laryngeal masks from different manufacturers.

Methods

Two groups of 80 patients requiring laryngeal mask size 3 and 4 during general anesthesia were randomized into 4 subgroups for each size of the laryngeal mask: Soft Seal® (Portex®), AuraOnce™ (Ambu®), LMA-Classic™ (Teleflex®) and LMA-ProSeal™ (Teleflex®). After insertion, the cuff was inflated with 5-ml increments of air up to the maximum recommended volume. After each 5-ml intracuff pressure was measured, the volume of air that generated the intracuff pressure of 60 cmH2O was recorded.

Results

Mean (SD) volume of air required to achieve the intracuff pressure of 60 cmH2O in Soft Seal®, AuraOnce™, LMA-Classic™, LMA-ProSeal™ laryngeal mask size 3 were 11.80(1.88), 9.20(1.88), 8.95(1.50) and 13.50(2.48) ml, respectively, and these volumes in laryngeal mask size 4 were 14.45(4.12), 12.55(1.85), 11.30(1.95) and 18.20(3.47) ml, respectively. The maximum recommended volume resulted in high intracuff pressures (> 60 cmH2O) in all laryngeal mask types and sizes studied.

Conclusion

Pressure-volume curves of adult laryngeal masks are all in sigmoidal shape. Cuff designs and materials can effect pressure and volume correlation. Approximately half of the maximum recommended volume is required to achieve the intracuff pressure of 60 cmH2O except LMA-ProSeal™ which required two-thirds of the maximum recommended volume.

Trial registration

Thai Clinical Trials Registry, TCTR20150602001, May 28, 2015.
Which interactions matter in economic evaluations? A systematic review and simulation study
Authors: Dakin Helen , Gray Alastair
Published: May 2020

Background

We aimed to assess the magnitude of interactions in costs, quality-adjusted life-years (QALYs) and net benefits within a sample of published economic evaluations of factorial randomised controlled trials (RCTs), evaluate the impact that different analytical methods would have had on the results and compare the performance of different criteria for identifying which interactions should be taken into account.

Methods

We conducted a systematic review of full economic evaluations conducted alongside factorial RCTs and reviewed the methods used in different studies, as well as the incidence, magnitude, statistical significance, and type of interactions observed within the trials. We developed the interaction-effect ratio as a measure of the magnitude of interactions relative to main effects. For those studies reporting sufficient data, we assessed whether changing the form of analysis to ignore or include interactions would have changed the conclusions. We evaluated how well different criteria for identifying which interactions should be taken into account in the analysis would perform in practice, using simulated data generated to match the summary statistics of the studies identified in the review.

Results

Large interactions for economic endpoints occurred frequently within the 40 studies identified in the review, although interactions rarely changed the conclusions.

Conclusions

Simulation work demonstrated that in analyses of factorial RCTs, taking account of all interactions or including interactions above a certain size (regardless of statistical significance) minimised the opportunity cost from adopting treatments that do not in fact have the highest true net benefit.
Experts’ perceptions on the use of visual analytics for complex mental healthcare planning: an exploratory study
Authors: Walsh Erin I. , Chung Younjin , Cherbuin Nicolas , Salvador-Carulla Luis
Published: May 2020

Background

Health experts including planners and policy-makers face complex decisions in diverse and constantly changing healthcare systems. Visual analytics may play a critical role in supporting analysis of complex healthcare data and decision-making. The purpose of this study was to examine the real-world experience that experts in mental healthcare planning have with visual analytics tools, investigate how well current visualisation techniques meet their needs, and suggest priorities for the future development of visual analytics tools of practical benefit to mental healthcare policy and decision-making.

Methods

Health expert experience was assessed by an online exploratory survey consisting of a mix of multiple choice and open-ended questions. Health experts were sampled from an international pool of policy-makers, health agency directors, and researchers with extensive and direct experience of using visual analytics tools for complex mental healthcare systems planning. We invited them to the survey, and the experts’ responses were analysed using statistical and text mining approaches.

Results

The forty respondents who took part in the study recognised the complexity of healthcare systems data, but had most experience with and preference for relatively simple and familiar visualisations such as bar charts, scatter plots, and geographical maps. Sixty-five percent rated visual analytics as important to their field for evidence-informed decision-making processes. Fifty-five percent indicated that more advanced visual analytics tools were needed for their data analysis, and 67.5% stated their willingness to learn new tools. This was reflected in text mining and qualitative synthesis of open-ended responses.

Conclusions

This exploratory research provides readers with the first self-report insight into expert experience with visual analytics in mental healthcare systems research and policy. In spite of the awareness of their importance for complex healthcare planning, the majority of experts use simple, readily available visualisation tools. We conclude that co-creation and co-development strategies will be required to support advanced visual analytics tools and skills, which will become essential in the future of healthcare.

Graphical abstract
Adherence in chronic hepatitis B: associations between medication possession ratio and adverse viral outcomes
Authors: Allard Nicole L. , MacLachlan Jennifer H. , Dev Anouk , Dwyer James , Srivatsa Geeta , Spelman Timothy , Thompson Alexander J. , Cowie Benjamin C.
Published: May 2020

Background

Antiviral therapy for chronic hepatitis B (CHB) is effective and can substantially reduce the risk of progressive liver disease and hepatocellular carcinoma but is often administered for an indefinite duration. Adherence has been shown in clinical trials to maximize the benefit of therapy and prevent the development of resistance, however the optimal threshold for predicting clinical outcomes has not been identified. The aim of this study was to analyse adherence using the medication possession ration (MPR) and its relation to virological outcomes in a large multi-centre hospital outpatient population, and guide development of an evidence-based threshold for optimal adherence.

Methods

Pharmacy and pathology records of patients dispensed CHB antiviral therapy from 4 major hospitals in Melbourne between 2010 and 2013 were extracted and analysed to determine their MPR and identify instances of unfavourable viral outcomes. Viral outcomes were classified categorically, with unfavourable outcomes including HBV DNA remaining detectable after 2 years treatment or experiencing viral breakthrough. The association between MPR and unfavourable outcomes was assessed according to various thresholds using ROC analysis and time-to-event regression.

Results

Six hundred forty-two individuals were included in the analysis. Median age was 46.6 years, 68% were male, 77% were born in Asia, and the median time on treatment was 27.5 months. The majority had favourable viral outcomes (91.06%), with most having undetectable HBV DNA at the end of the study period. The most common unfavourable outcome was a rise of < 1 log in HBV DNA (6.54% of the total), while 2.49% of participants experienced viral breakthrough. Adherence was linearly associated with favourable outcomes, with increasing risk of virological breakthrough as MPR fell. Decreasing the value of MPR, at which a cut-point was taken, was associated with a progressively larger reduction in the rate of unfavourable event; from a 60% reduction under a cut-point of 1.00 to a 79% reduction when the MPR cut-point was set at 0.8.

Conclusion

Lower adherence as measured using the MPR was strongly associated with unfavourable therapeutic outcomes, including virological failure. Optimising adherence is therefore important for preventing viral rebound and potential complications such as antiviral resistance. The evidence of dose-response highlights the need for nuanced interventions.
Nurse-patient interaction and self-transcendence: assets for a meaningful life in nursing home residents?
Authors: Haugan Gørill , Kuven Britt Moene , Eide Wenche Mjanger , Taasen Siv Eriksen , Rinnan Eva , Xi Wu Vivien , Drageset Jorunn , André Beate
Published: May 2020

Background

Due to the shift to an older population worldwide and an increased need for 24-h care, finding new and alternative approaches to increase wellbeing among nursing home (NH) residents is highly warranted. To guide clinical practice in boosting wellbeing among NH residents, knowledge about nurse-patient interaction (NPI), inter- (ST1) and intra-personal (ST2) self-transcendence and meaning-in-life (PIL) seems vital. This study tests six hypotheses of the relationships between NPI, ST1, ST2 and PIL among cognitively intact NH residents.

Methods

In a cross-sectional design, 188 (92% response rate) out of 204 long-term NH residents representing 27 NHs responded to NPI, ST, and the PIL scales. Inclusion criteria were: (1) municipality authority’s decision of long-term NH care; (2) residential time 3 months or longer; (3) informed consent competency recognized by responsible doctor and nurse; and (4) capable of being interviewed. The hypothesized relations between the latent constructs were tested through structural equation modeling (SEM) using Stata 15.1.

Results

The SEM-model yielded a good fit (χ2 = 146.824, p = 0.021, df = 114, χ2/df = 1.29 RMSEA = 0.040, p-close 0.811, CFI = 0.97, TLI = 0.96, and SRMR = 0.063), supporting five of the six hypothesized relationships between the constructs of NPI, ST1, ST2 and PIL.

Conclusion

NPI significantly relates to both ST1, ST2 and PIL in NH residents. ST revealed a fundamental influence on perceived PIL, while NPI demonstrated a significant indirect influence on PIL, mediated by ST.
Reducing physical restraints by older adults in home care: development of an evidence-based guideline
Authors: Scheepmans Kristien , Dierckx de Casterlé Bernadette , Paquay Louis , Van Gansbeke Hendrik , Milisen Koen
Published: May 2020

Background

Restraint use is a complex and challenging issue in home care. Due to socio-demographic trends, worldwide home healthcare providers are faced with an increasing demand for restraint use from informal caregivers, patients and healthcare providers, resulting in the use of various types of restraints in home care. Awareness and knowledge of restraint use in home care, its implications and the ethical challenges surrounding it are of crucial importance to its reduction. This research aimed to describe the development process of an evidence-based practice guideline to support caregivers to optimize home care.

Method

The practice guideline was developed according to the framework of the Belgian Centre for Evidence-Based Medicine and AGREE II. The guideline was developed over several stages: (1) determination of the target population and scope, (2) literature search, (3) drafting and (4) validation. A multidisciplinary working group determined the proposed purpose, target group, and six clinical questions for the guideline. A consensus procedure and consultation by experts were used to develop the guideline.

Results

The guideline provides an answer to six clinical questions and contains ten key recommendations based on the classification of GRADE, with the objective of increasing healthcare providers’ awareness, knowledge and competence to adequately deal with situations or questions related to restraint use. The guideline also includes a flowchart for dealing with complex situations where the use of restraints is requested, already present or considered.

Conclusions

The guideline was validated by the Belgian Centre for Evidence-Based Medicine. Increasing competence, awareness and knowledge related to restraint use are key objectives of the guideline for reducing restraint use in home care. A multicomponent intervention to support healthcare workers in implementing the guideline in clinical practice needs to be developed.
Francisella tularensis as the cause of protracted fever
Authors: Antonitsch Lukas , Weidinger Gerhard , Stanek Gerold , Markowicz Mateusz
Published: May 2020

Background

Tularemia, a re-emerging, potential life threatening infectious disease, can present itself with nonspecific clinical symptoms including fever, chills and malaise. Taking a detailed history of exposure and a highly raised index of clinical suspicion are necessary to take the appropriate diagnostic and therapeutic steps in this setting. Here, a case report of typhoid tularaemia is presented.

Case presentation

A 53-year old male forester and farmer with protracted fever, abdominal pain, diarrhoea and loss of weight, who experienced productive cough and a pulmonary infiltrate later in the course of disease, was admitted for further investigation. Tularaemia was suspected only owing to history and confirmed by serologic testing more than three weeks after the beginning of the symptoms. The initial antibiotic therapy with ceftriaxone/doxycycline was switched to ciprofloxacin, resulting in the resolution of fever and symptoms.

Conclusion

Tularaemia has to be considered as a differential diagnosis in febrile patients, even more in cases with protracted fever. Since tularaemia is expanding geographically, involving more animal hosts and causing larger outbreaks, clinicians have to be aware of this potentially fatal disease.
A novel nonsense variant in SLC24A4 causing a rare form of amelogenesis imperfecta in a Pakistani family
Authors: Khan Sher Alam , Khan Muhammad Adnan , Muhammad Nazif , Bashir Hina , Khan Niamat , Muhammad Noor , Yilmaz Rüstem , Khan Saadullah , Wasif Naveed
Published: May 2020

Background

Amelogenesis imperfecta (AI) is a highly heterogeneous group of hereditary developmental abnormalities which mainly affects the dental enamel during tooth development in terms of its thickness, structure, and composition. It appears both in syndromic as well as non-syndromic forms. In the affected individuals, the enamel is usually thin, soft, rough, brittle, pitted, chipped, and abraded, having reduced functional ability and aesthetics. It leads to severe complications in the patient, like early tooth loss, severe discomfort, pain, dental caries, chewing difficulties, and discoloration of teeth from yellow to yellowish-brown or creamy type. The study aimed to identify the disease-causing variant in a consanguineous family.

Methods

We recruited a consanguineous Pashtun family of Pakistani origin. Exome sequencing analysis was followed by Sanger sequencing to identify the pathogenic variant in this family.

Results

Clinical analysis revealed hypomaturation AI having generalized yellow-brown or creamy type of discoloration in affected members. We identified a novel nonsense sequence variant c.1192C > T (p.Gln398*) in exon-12 of SLC24A4 by using exome sequencing. Later, its co-segregation within the family was confirmed by Sanger sequencing. The human gene mutation database (HGMD, 2019) has a record of five pathogenic variants in SLC24A4, causing AI phenotype.

Conclusion

This nonsense sequence variant c.1192C > T (p.Gln398*) is the sixth disease-causing variant in SLC24A4, which extends its mutation spectrum and confirms the role of this gene in the morphogenesis of human tooth enamel. The identified variant highlights the critical role of SLC24A4 in causing a rare AI type in humans.
Defining preconception: exploring the concept of a preconception population
Authors: Hill Briony , Hall Jennifer , Skouteris Helen , Currie Sinéad
Published: May 2020

Background

Health prior to conception can significantly impact offspring health, however, a clear definition of the attributes of the preconception population is currently lacking. We aimed to use existing literature to explore the concept and attributes of a preconception population by: [1] identifying characteristics and research recruitment methods; and [2] generating an attribute-based working definition of a preconception population.

Methods

A rapid review of current literature using CINAHL and the subject heading ‘pre-pregnancy care’ was conducted (Stage 1). Data extracted included definitions of preconception, participant inclusion/exclusion criteria, participant characteristics, and recruitment methods. Stage 2 involved a wider search of relevant publications beyond peer-reviewed literature followed by a concept analysis of the phrase “preconception population” applying Walker and Avant’s framework (Stage 2).

Results

Twenty-three papers (19 studies) were included in Stage 1. “Preconception” was explicitly defined in one study. Twelve studies specified participants must be planning a pregnancy. Stage 2 included 33 publications. Four key perspectives for the concept of the preconception population were derived: [1] intentional; [2] potential; [3] public health; and [4] life course.

Conclusions

Adopting these perspectives may allow researchers to accurately define, identify and recruit preconception populations and to develop interventions that are appropriately broad or tailored depending on population needs. We hope the definitions will facilitate research with this population and will subsequently improve the wellbeing of preconception men and women, which is essential to ensuring the health of future generations.
Symptom continuum reported by affective disorder patients through a structure-validated questionnaire
Authors: Guo Fanjia , Cai Jingyi , Jia Yanli , Wang Jiawei , Jakšić Nenad , Kövi Zsuzsanna , Šagud Marina , Wang Wei
Published: May 2020

Background

Affective disorders, such as major depressive (MDD), bipolar I (BD I) and II (BD II) disorders, are overlapped at a continuum, but their exact loci are not clear. The self-reports from patients with affective disorders might help to clarify this issue.

Methods

We invited 738 healthy volunteers, 207 individuals with BD I, 265 BD II, and 192 MDD to answer a 79 item-MATRIX about on-going affective states.

Results

In study 1, all 1402 participants were divided random-evenly and gender-balanced into two subsamples; one subsample was used for exploratory factor analysis, and another for confirmatory factor analysis. A structure-validated inventory with six domains of Overactivation, Psychomotor Acceleration, Distraction/ Impulsivity, Hopelessness, Retardation, and Suicide Tendency, was developed. In study 2, among the four groups, MDD scored the highest on Retardation, Hopelessness and Suicide Tendency, whereas BD I on Distraction/ Impulsivity and Overactivation.

Conclusion

Our patients confirmed the affective continuum from Suicide Tendency to Overactivation, and described the different loci of MDD, BD I and BD II on this continuum.