bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Sclerectomy With Intrascleral Versus Suprachoroidal Collagen Implant: A Randomized Control Trial
Authors: Mitwally Rany , Aref Amr , Shaarawy Tarek
Published: January 2021

Précis:

Deep sclerectomy with intrascleral collagen implant (DSCI) was less effective in lowering intraocular pressure (IOP) than with suprachoroidal implantation. Further studies are needed to establish the potency and safety of deep sclerectomy with suprachoroidal collagen implant (DSSCI).

Purpose:

The purpose of this study was to analyze the safety and IOP-lowering effect of DSSCI in comparison with DSCI.

Setting:

Geneva University Hospitals, Geneva, Switzerland.

Methods:

This is a prospective, randomized, controlled study involving 13 patients (26 phakic eyes) with bilateral medically uncontrolled primary or secondary open-angle glaucoma. Bilateral deep sclerectomy was performed with each patient being randomly assigned to receive a collagen implant in the intrascleral space in one eye, and a suprachoroidal collagen implant in the other. Follow-up visits were performed at day 1; at week 1; and at months 6, 9, 12, 18, 30, 48, 54, and 60.

Results:

Mean preoperative IOP was 24.1±4.2 mm Hg for DSCI group and 25.3±5.3 mm Hg for DSSCI group (P=0.1). The mean postoperative IOP was 14.8±4.0 mm Hg (DSCI) versus 9.8±3.7 mm Hg (DSSCI) at month 60 (P=0.01). Mean preoperative best-corrected visual acuity for the DSCI group was 0.76±0.22 and 0.74±0.23 for the DSSCI group (P=0.001), while the mean postoperative best-corrected visual acuity was 0.82±0.17 (DSCI) and 0.80±0.17 (DSSCI) at month 60 (P=0.004).

Conclusions:

DSSCI demonstrated a greater IOP-lowering effect than deep sclerectomy with intrascleral implantation. The safety profile of both methods was similar. More patients with a longer follow-up are required to comprehensively assess the safety and efficacy of this new approach.
Prediction of ambulatory visits for itching diseases using Google Trends data
Authors: Muddasani Suraj , Fleischer Alan B.
Published: January 2021

It would provide insight to know if Google queries for “itch” relate to the probability of a patient visit for common itching diseases in the National Ambulatory Medical Care Survey. There was a negative predictive value of visits for vaginitis, vulvitis, and vulvovaginitis [odds ratio 0.983 (95% confidence interval 0.977, 0.989)], psoriasis [0.986 (0.980, 0.992)], and dermatitis [0.983 (0.979, 0.986)] with increased normalized search interest (P<0.0001). There was no relationship between search interest and visits for urticaria [0.997 (0.986, 1.01), P=0.5] or atopic dermatitis [1.02 (0.994, 1.01), P=0.9]. This demonstrates that internet search behavior can affect real world patient visits.
A Literature Review on the Benefits for an Interprofessional Educational Program to Increase Novice Nurse Awareness of Case Management in Heart Failure
Authors: Trefethen Emily Prieto
Published: January 2021

Purpose/Objectives:

The purpose of this literature review is to examine the potential value for an interprofessional education program to increase novice nurse awareness of case management in heart failure (HF).

Primary Practice Setting:

Acute care health care settings involving novice nurses.

Findings/Conclusions:

Evidence demonstrates that interprofessional collaboration on transitional care interventions for HF patients reduces 30-day readmissions. Implementation of an interprofessional education program for novice nurses can be an effective intervention to decrease readmissions by increasing knowledge of the nurse case manager role and development of interprofessional relationships.

Implications for Case Management Practice:

Increased awareness of HF case management is important for novice nurses. Understanding the nurse case manager role and early interprofessional collaboration can improve patient health outcomes among the HF population. Therefore, an education program to build confidence and strengthen interprofessional partnership in HF case management for the novice nurse is warranted.
Left Ventricular Dysfunction and Depression in Hospitalized Patients with Heart Failure
Authors: Freedland Kenneth E. , Carney Robert M. , Steinmeyer Brian C. , Skala Judith A. , Rich Michael W.
Published: January 2021

Objective

This study examined whether the severity of left ventricular systolic dysfunction is associated with depression in patients with heart failure (HF). Other factors were also studied to identify independent correlates of depression in HF.

Methods

The sample consisted of 400 hospitalized patients with HF. Left ventricular ejection fraction and other medical data were obtained from medical records. Depression and other psychosocial characteristics were assessed by an interview and questionnaires. Proportional odds models were used to test the relationships of these characteristics to Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) depressive disorders, and analysis of covariance was used to test relationships with continuous measures of depression in secondary models.

Results

The models produced no evidence of an association between left ventricular ejection fraction and depression. The adjusted odds ratio (95% confidence interval) was 1.00 (0.98–1.01; p = .87) for depression diagnosis. Analysis of covariance estimates (standard errors) were −0.01 (0.02; p = .54) for the Hamilton Rating Scale for Depression and −0.01 (0.01; p = .59) for the Patient Health Questionnaire. The odds of depression were higher in African American patients and in those with high levels of anxiety or stress. Other characteristics that have been associated with depression in previous studies, including sex and age, were not consistently associated with depression in this study.

Conclusions

There is no relationship between the severity of left ventricular systolic dysfunction and depression in hospitalized patients with HF. In contrast, African American patients and those with a high level of anxiety or perceived stress are more likely than other patients to have a comorbid depressive disorder.
Tools for Assessing the Performance of Pediatric Perioperative Teams During Simulated Crises: A Psychometric Analysis of Clinician Raters' Scores
Authors: Watkins Scott C. , de Oliveira Filho Getulio R. , Furse Cory M. , Muffly Matthew K. , Ramamurthi R. J. , Redding Amanda T. , Maass Birgit , McEvoy Matthew D.
Published: January 2021

Introduction

The pediatric perioperative setting is a dynamic clinical environment where multidisciplinary interprofessional teams interact to deliver complex care to patients. This environment requires clinical teams to possess high levels of complex technical and nontechnical skills. For perioperative teams to identify and maintain clinical competency, well-developed and easy-to-use measures of competency are needed.

Methods

Tools for measuring the technical and nontechnical performance of perioperative teams were developed and/or identified, and a group of raters were trained to use the instruments. The trained raters used the tools to assess pediatric teams managing simulated emergencies. A psychometric analysis of the trained raters' scores using the different instruments was performed and the agreement between the trained raters' scores and a reference score was determined.

Results

Five raters were trained and scored 96 recordings of perioperative teams managing simulated emergencies. Scores from both technical skills assessment tools demonstrated significant reliability within and between ratings with the scenario-specific performance checklist tool demonstrating greater interrater agreement than scores from the global rating scale. Scores from both technical skills assessment tools correlated well with the other and with the reference standard scores. Scores from the Team Emergency Assessment Measure nontechnical assessment tool were more reliable within and between raters and correlated better with the reference standard than scores from the BARS tool.

Conclusions

The clinicians trained in this study were able to use the technical performance assessment tools with reliable results that correlated well with reference scores. There was more variability between the raters' scores and less correlation with the reference standard when the raters used the nontechnical assessment tools. The global rating scale used in this study was able to measure the performance of teams across a variety of scenarios and may be generalizable for assessing teams in other clinical scenarios. The Team Emergency Assessment Measure tool demonstrated reliable measures when used to assess interprofessional perioperative teams in this study.
A stable, unified model for resonant Faraday cages
Authors: Delourme B. , Lunéville E. , Marigo J.-J. , Maurel A. , Mercier J.-F. , Pham K.
Published: January 2021

We study some effective transmission conditions able to reproduce the effect of a periodic array of Dirichlet wires on wave propagation, in particular when the array delimits an acoustic Faraday cage able to resonate. In the study of Hewett & Hewitt (2016
Proc. R. Soc. A
472
, 20160062 (
doi:10.1098/rspa.2016.0062
)) different transmission conditions emerge from the asymptotic analysis whose validity depends on the frequency, specifically the distance to a resonance frequency of the cage. In practice, dealing with such conditions is difficult, especially if the problem is set in the time domain. In the present study, we demonstrate the validity of a simpler
unified
model derived in Marigo & Maurel (2016
Proc. R. Soc. A
472
, 20160068 (
doi:10.1098/rspa.2016.0068
)), where
unified
means valid whatever the distance to the resonance frequencies. The effectiveness of the model is discussed in the harmonic regime owing to explicit solutions. It is also exemplified in the time domain, where a formulation guaranteeing the stability of the numerical scheme has been implemented.
Haltere and visual inputs sum linearly to predict wing (but not gaze) motor output in tethered flying
Drosophila
Authors: Rauscher Michael J. , Fox Jessica L.
Published: January 2021

In the true flies (Diptera), the hind wings have evolved into specialized mechanosensory organs known as halteres, which are sensitive to gyroscopic and other inertial forces. Together with the fly's visual system, the halteres direct head and wing movements through a suite of equilibrium reflexes that are crucial to the fly's ability to maintain stable flight. As in other animals (including humans), this presents challenges to the nervous system as equilibrium reflexes driven by the inertial sensory system must be integrated with those driven by the visual system in order to control an overlapping pool of motor outputs shared between the two of them. Here, we introduce an experimental paradigm for reproducibly altering haltere stroke kinematics and use it to quantify multisensory integration of wing and gaze equilibrium reflexes. We show that multisensory wing-steering responses reflect a linear superposition of haltere-driven and visually driven responses, but that multisensory gaze responses are not well predicted by this framework. These models, based on populations, extend also to the responses of individual flies.
Maternally derived hormones, neurosteroids and the development of behaviour
Authors: Mouton James C. , Duckworth Renée A.
Published: January 2021

In a wide range of taxa, there is evidence that mothers adaptively shape the development of offspring behaviour by exposing them to steroids. These maternal effects have major implications for fitness because, by shaping early development, they can permanently alter how offspring interact with their environment. However, theory on parent–offspring conflict and recent physiological studies showing that embryos rapidly metabolize maternal steroids have placed doubt on the adaptive significance of these hormone-mediated maternal effects. Reconciling these disparate perspectives requires a mechanistic understanding of the pathways by which maternal steroids can influence neural development. Here, we highlight recent advances in developmental neurobiology and psychiatric pharmacology to show that maternal steroid metabolites can have direct neuro-modulatory effects potentially shaping the development of neural circuitry underlying ecologically relevant behavioural traits. The recognition that maternal steroids can act through a neurosteroid pathway has critical implications for our understanding of the ecology and evolution of steroid-based maternal effects. Overall, compared to the classic view, a neurosteroid mechanism may reduce the evolutionary lability of hormone-mediated maternal effects owing to increased pleiotropic constraints and frequently influence long-term behavioural phenotypes in offspring.
Ancient mitochondrial genomes from Chinese cave hyenas provide insights into the evolutionary history of the genusCrocuta
Authors: Hu Jiaming , Westbury Michael V. , Yuan Junxia , Zhang Zhen , Chen Shungang , Xiao Bo , Hou Xindong , Ji Hailong , Lai Xulong , Hofreiter Michael , Sheng Guilian
Published: January 2021

Cave hyenas (genusCrocuta) are extinct bone-cracking carnivores from the family Hyaenidae and are generally split into two taxa that correspond to a European/Eurasian and an (East) Asian lineage. They are close relatives of the extant African spotted hyenas, the only extant member of the genusCrocuta. Cave hyenas inhabited a wide range across Eurasia during the Pleistocene, but became extinct at the end of the Late Pleistocene. Using genetic and genomic datasets, previous studies have proposed different scenarios about the evolutionary history ofCrocuta.However, causes of the extinction of cave hyenas are widely speculative and samples from China are severely understudied. In this study, we assembled near-complete mitochondrial genomes from two cave hyenas from northeastern China dating to 20 240 and 20 253 calBP, representing the youngest directly dated fossils ofCrocutain Asia. Phylogenetic analyses suggest a monophyletic clade of these two samples within a deeply diverging mitochondrial haplogroup ofCrocuta. Bayesian analyses suggest that the split of this Asian cave hyena mitochondrial lineage from their European and African relatives occurred approximately 1.85 Ma (95% CI 1.62–2.09 Ma), which is broadly concordant with the earliest EurasianCrocutafossil dating to approximately 2 Ma. Comparisons of mean genetic distance indicate that cave hyenas harboured higher genetic diversity than extant spotted hyenas, brown hyenas and aardwolves, but this is probably at least partially due to the fact that their mitochondrial lineages do not represent a monophyletic group, although this is also true for extant spotted hyenas. Moreover, the joint female effective population size ofCrocuta(both cave hyenas and extant spotted hyenas) has sustained two declines during the Late Pleistocene. Combining this mitochondrial phylogeny, previous nuclear findings and fossil records, we discuss the possible relationship of fossilCrocutain China and the extinction of cave hyenas.
Factors affecting the production and measurement of hydrogen peroxide in honey samples
Authors: Guttentag Annabel , Krishnakumar Krishothman , Cokcetin Nural , Harry Elizabeth , Carter Dee
Published: January 2021

Many Australian native honeys possess significant antimicrobial properties due to the production of hydrogen peroxide (H2O2) by glucose oxidase, an enzyme derived from the honeybee. The level of H2O2 produced in different honey samples is highly variable, and factors governing its production and stability are not well understood. In this study, highly active Australian honeys that had been stored for >10 years lost up to 54 % of their antibacterial activity, although almost all retained sufficient activity to be considered potentially therapeutically useful. We used a simple colourimetric assay to quantify H2O2 production. Although we found a significant correlation between H2O2 production and antibacterial activity across diverse honey samples, variation in H2O2 only explained 47 % of the variation observed in activity, limiting the assay as a screening tool and highlighting the complexity of the relationship between H2O2 and the killing power of honey. To further examine this, we tested whether H2O2 detection in honey was being inhibited by pigmented compounds and if H2O2 might be directly degraded in some honey samples. We found no correlation between H2O2 detection and honey colour. Some honey samples rapidly lost endogenous and spiked H2O2, suggesting that components in honey, such as catalase or antioxidant polyphenols, may degrade or quench H2O2. Despite this rapid loss of H2O2, these honeys had significant peroxide-based antibacterial activity, indicating a complex relationship between H2O2 and other honey components that may act synergistically to augment activity.
Lentzea alba sp. nov., a novel actinobacterium isolated from soil
Authors: Sun Xiujun , Zhao Junwei , Luo Xianxian , Hou Wenyu , Xiang Wensheng , Song Jia , Wang Xiangjing
Published: January 2021

A novel actinobacterium, designated strain NEAU-D13T, was isolated from soil collected from Aohan Banner, Chifeng, Inner Mongolia Autonomous Region, China and characterized using a polyphasic approach. On the basis of 16S rRNA gene sequence analysis, strain NEAU-D13T belonged to the genus

Lentzea

and shared the highest sequence similarity with

Lentzea kentuckyensis

JCM 14913
T (99.17 %). Morphological and chemotaxonomic characteristics of the strain also supported its assignment to the genus

Lentzea

. Cell walls contained meso-diaminopimelic acid as the diagnostic diamino acid and the whole-cell sugars were ribose and mannose. The phospholipid profile contained diphosphatidylglycerol, phosphatidylethanolamine, hydroxyphosphatidylethanolamine and phosphatidylinositol. The menaquinone was only MK-9(H4). The major fatty acids were iso-C16:0, C16:0, anteiso-C17:0, iso-C15:0 and anteiso-C15:0. DNA G+C content was 68.71 mol%. Phylogenetic analysis using the 16S rRNA gene sequences showed that the strain formed a stable clade with

L. kentuckyensis

JCM 14913
T in the genus

Lentzea

. Meanwhile, a combination of digital DNA–DNA hybridization results and some phenotypic characteristics demonstrated that strain NEAU-D13T could be distinguished from its closely related strain. Therefore, it is concluded that strain NEAU-D13T represents a novel species of the genus

Lentzea

, for which the name Lentzea alba sp. nov. is proposed, with NEAU-D13T (=CCTCC AA 2019089T=JCM 33970T) as the type strain.
Ex vivo potential of a quinoline-derivative nail lacquer as a new alternative for dermatophytic onychomycosis treatment
Authors: Machado Gabriella da Rosa Monte , Pippi Bruna , Berlitz Simone , Diedrich Denise , Defferrari Diego , Lopes William , Gnoatto Simone Cristina Baggio , Kulkamp-Guerreiro Irene Clemes , Vainstein Marilene Henning , Jean Mickael , Van de Weghe Pierre , de Andrade Saulo Fernandes , Fuentefria Alexandre Meneghello
Published: January 2021

Introduction. Onychomycosis infections currently show a significant increase, affecting about 10 % of the world population. Trichophyton rubrum is the main agent responsible for about 80 % of the reported infections. The clinical cure for onychomycosis is extremely difficult and effective new antifungal therapy is needed.

Hypothesis/Gap Statement.
Ex vivo onychomycosis models using porcine hooves can be an excellent alternative for evaluating the efficacy of new anti-dermatophytic agents in a nail lacquer.

Aim. Evaluation of the effectiveness of a nail lacquer containing a quinoline derivative on an ex vivo onychomycosis model using porcine hooves, as well as the proposal of a plausible antifungal mechanism of this derivative against dermatophytic strains.

Methodology. The action mechanism of a quinoline derivative was evaluated through the sorbitol protection assay, exogenous ergosterol binding, and the determination of the dose-response curves by time-kill assay. Scanning electron microscopy evaluated the effect of the derivative in the fungal cells. The efficacy of a quinoline-derivative nail lacquer on an ex vivo onychomycosis model using porcine hooves was evaluated as well.

Results. The quinoline derivative showed a time-dependent fungicidal effect, demonstrating reduction and damage in the morphology of dermatophytic hyphae. In addition, the ex vivo onychomycosis model was effective in the establishment of infection by T. rubrum.

Conclusion. Treatment with the quinoline-derivative lacquer showed a significant inhibitory effect on T. rubrum strain in this infection model. Finally, the compound presents high potential for application in a formulation such as nail lacquer as a possible treatment for dermatophytic onychomycosis.
A mutagenic screen reveals NspS residues important for regulation of Vibrio cholerae biofilm formation
Authors: Young Erin C. , Baumgartner Jackson T. , Karatan Ece , Kuhn Misty L.
Published: January 2021

Biofilm formation in the human intestinal pathogen

Vibrio cholerae

is in part regulated by norspermidine, spermidine and spermine.

V. cholerae

senses these polyamines through a signalling pathway consisting of the periplasmic protein, NspS, and the integral membrane c-di-GMP phosphodiesterase MbaA. NspS and MbaA belong to a proposed class of novel signalling systems composed of periplasmic ligand-binding proteins and membrane-bound c-di-GMP phosphodiesterases containing both GGDEF and EAL domains. In this signal transduction pathway, NspS is hypothesized to interact with MbaA in the periplasm to regulate its phosphodiesterase activity. Polyamine binding to NspS likely alters this interaction, leading to the activation or inhibition of biofilm formation depending on the polyamine. The purpose of this study was to determine the amino acids important for NspS function. We performed random mutagenesis of the nspS gene, identified mutant clones deficient in biofilm formation, determined their responsiveness to norspermidine and mapped the location of these residues onto NspS homology models. Single mutants clustered on two lobes of the NspS model, but the majority were found on a single lobe that appeared to be more mobile upon norspermidine binding. We also identified residues in the putative ligand-binding site that may be important for norspermidine binding and interactions with MbaA. Ultimately, our results provide new insights into this novel signalling pathway in

V. cholerae

and highlight differences between periplasmic binding proteins involved in transport versus signal transduction.
The competition dynamics of resistant and sensitive infections
Authors: Lee T. E. , Bonhoeffer S. , Penny M. A.
Published: January 2021

Antimicrobial resistance is a major health problem with complex dynamics. Resistance may occur in an area because treated infections mutated and developed resistance, and the proportion of infections in a population may then increase. We developed a novel and flexible model that captures several features of resistance dynamics and competition. The model is able to account for many antimicrobials and thus can generally explore competition dynamics and their impact on pathogens and bacteria.

Unlike simpler models, our nested model allows the population of resistant pathogen to smoothly increase or decrease. Time dependent dynamics are incorporated into difference equations which examines the effects of 12 parameters. This enables us to explicitly include three key competition dynamics: the transmission cost of resistance that occurs between hosts, the fitness cost of resistance that occurs within untreated hosts, and the release of this competition (from the fitness cost) that occurs once a host is treated. For malaria, our results suggest that without competitive release, drug resistance does not emerge. However, once emerged, competitive release has little effect, and the best way to mitigate the spread is to ensure that treatment is very effective.
Switches, stability and reversals: the evolutionary history of sexual systems in fish
Authors: Pla Susanna , Benvenuto Chiara , Capellini Isabella , Piferrer Francesc
Published: January 2021

Sexual systems are highly diverse and have profound consequences for population dynamics and resilience. Yet, little is known about how they evolved. Using phylogenetic Bayesian modelling and a sample of 4614 species, we show that gonochorism is the likely ancestral condition in teleost fish. While all hermaphroditic forms revert quickly to gonochorism, protogyny and simultaneous hermaphroditism are evolutionarily more stable than protandry. In line with theoretical expectations, simultaneous hermaphroditism does not evolve directly from gonochorism but can evolve slowly from sequential hermaphroditism, particularly protandry. We find support for the predictions from life history theory that protogynous, but not protandrous, species live longer than gonochoristic species and invest the least in male gonad mass. The distribution of teleosts’ sexual systems on the tree of life does not seem to reflect just adaptive predictions, suggesting that adaptations alone may not fully explain why some sexual forms evolve in some taxa but not others (Williams’ paradox). We propose that future studies should incorporate mating systems, spawning behaviours, and the diversity of sex determining mechanisms. Some of the latter might constrain the evolution of hermaphroditism, while the non-duality of the embryological origin of teleost gonads might explain why protogyny predominates over protandry in teleosts.
Transcranial direct current stimulation does not improve performance in a whole-body movement task
Authors: Caesley Harriet , Sewell Isabella , Gogineni Nikita , Javadi Amir-Homayoun
Published: January 2021

Research has investigated the use of non-invasive brain interventions, such as transcranial direct current stimulation (tDCS), to enhance motor learning and rehabilitation. Much research has shown that tDCS improves motor learning and that bilateral tDCS is more beneficial than unilateral tDCS in improving motor learning. However, past research has primarily utilised simple motor tasks in measuring motor skill learning. These are not ecologically reliable as whole-body movement is required for everyday activities. This study involved two experiments. Each experiment involved participants learning 12 Ballroom and Latin dance moves whilst undergoing tDCS. All participants underwent three sessions of tDCS, (unilateral, bilateral and sham), over three consecutive days. Participants in the first experiment (n=30) had stimulation to the primary motor cortex (PMC) and those in the second experiment (n=31) had stimulation to the dorsolateral prefrontal cortex (DLPFC). In each experiment, a baseline was taken before the training sessions and two outcome measures were taken; a day after the last training session and two weeks later. In each testing session participants’ dance ability was measured. Our results showed that bilateral tDCS impaired performance in both experiments. Unilateral stimulation impaired performance in the first experiment, and did not significantly improve performance any better than the sham stimulation in the second experiment. These results suggest that task complexity plays a crucial role when tDCS procedures are used to modulate motor performance and highlights possible limitations of tDCS in practice.
New distributional data for the northern forestfly,Lednia borealisBaumann and Kondratieff, 2010 (Plecoptera: Nemouridae), Washington, USA
Authors: Fallon Candace E. , Blevins Emilie , Blackburn Michele , Cotten Taylor B. , Stinson Derek W.
Published: January 2021

The northern forestfly,Lednia borealis(Plecoptera: Nemouridae) is a rare montane stonefly believed to be endemic to Washington. The species, first recognized as a valid taxon in 2010, is the only member of the genusLedniaknown from the state. Like other species in its genus, it is found in mid- to high-elevation cold water habitat, including lakes, glacial-fed streams, and rheocrenes (channelized springs).Ledniaspecies in general appear to be rare or at least rarely collected. Because of their reliance on alpine and subalpine habitat,Ledniamay be especially vulnerable to threats associated with climate change. However, relatively little is known about this species, and distribution data are scarce. From 2015 to 2019, 94 sites were surveyed in order to document unmapped populations ofLednia borealisto improve range and distributional information from montane areas of Washington State. In this paper, we share locations ofL. borealisdocumented to date, including collections from eight newly documentedLedniasites in the Mt. Baker and Glacier Peak Wildernesses in the Cascade Mountains of Washington, and report recent COI barcoding results. We also provide updated details on the species’ distribution, highlight a confirmed habitat association with glacial edge meltwater, and provide recommendations for future surveys.
Hybrid Clustering of Long and Short-read for Improved Metagenome Assembly
Authors: Lu Yakang , Shi Lizhen , Van Goethem Marc W. , Sevim Volkan , Mascagni Michael , Deng Li , Wang Zhong
Published: January 2021

Next-generation sequencing has enabled metagenomics, the study of the genomes of microorganisms sampled directly from the environment without cultivation. We previously developed a proof-of-concept, scalable metagenome clustering algorithm based on Apache Spark to cluster sequence reads according to their species of origin. To overcome its under-clustering problem on short-read sequences, in this study we developed a new, two-step Label Propagation Algorithm (LPA) that first forms clusters of long reads and then recruits short reads to these clusters. Compared to alternative label propagation strategies, this hybrid clustering algorithm (hybrid-LPA) yields significantly larger read clusters without compromising cluster purity. We show that adding an extra clustering step before assembly leads to improved metagenome assemblies, predicting more complete genomes or gene clusters from a synthetic metagenome dataset and a real-world metagenome dataset, respectively. These results suggest that hybrid-LPA is a good alternative to current metagenome assembly practice by providing benefits in both scalability and accuracy on large metagenome datasets.

Availability and implementation

https://bitbucket.org/zhong_wang/hybridlpa/src/master/.

Contact

zhongwang@lbl.gov
Induction of Antioxidant and Detoxifying Enzymes via the Nrf2-ARE Pathway by Oriental Bezoar
Authors: Tsubonoya Tomoe , Inoue Eiji , Sudo Keiichi , Shimizu Yasuharu
Published: January 2021

Objectives

Oriental bezoar, a gallstone formed in the gall sac ofBos taurusLinné var.domesticusGmelin (Bovidae), has been used as a crude drug in oriental medicine for stroke, convulsion, epilepsy, swelling and pain in the throat, and high fever. Despite reports on the antioxidative effect of oriental bezoar-containing drugs,in vitro-cultured calculus bovis (a substitute for oriental bezoar), and its components (namely, bilirubin and biliverdin), the intracellular mechanism of the antioxidative action of oriental bezoar remains unclear. Therefore, we studied the effect of oriental bezoar on the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, which transcriptionally regulates genes encoding antioxidant and detoxifying enzymes, such as heme oxygenase-1 (HO-1), glutathione-S-transferase alpha 1 (GSTA1), and quinone oxidoreductase 1 (NQO1), to elucidate its antioxidative effect.

Methods

ARE promoter activity and mRNA expression (HO-1, GSTA1, andNQO1) in HepG2 cells supplemented with test drugs were examinedin vitroby luciferase reporter assay and real-time PCR, respectively.

Results

Oriental bezoar induced ARE promoter activity and increased the mRNA expression level ofHO-1, GSTA1, andNQO1. Its components, namely, bilirubin and biliverdin, also increased the ARE promoter activity.

Conclusion

These results suggest that oriental bezoar can induce antioxidative and detoxification effects via the Nrf2-ARE pathway.
Commercial porcine gastric mucin contributes to variation in production of small molecule virulence factors byPseudomonas aeruginosawhen cultured in different formulations of artificial sputum medium
Authors: Neve Rachel L. , Carrillo Brent D. , Phelan Vanessa V.
Published: January 2021

Site-specificin vitroculture media are being developed to investigate microbial pathogenicity and ecology in nutrient environments that are more reflective of disease. For microbial ecology research in cystic fibrosis (CF), different artificial sputum media (ASM) formulations have been created to recapitulate the nutrient availability of the CF lung environment. However, these ASM formulations vary in concentration of amino acids, mucin, and other niche-specific compounds. Here, we measured the differential production of small molecule virulence factors byPseudomonas aeruginosa, the predominant pathogen in CF pulmonary infections, cultured in nine different ASM formulations via liquid chromatography tandem mass spectrometry (LC-MS/MS) and molecular networking. We show that different ASM formulations lead to different phenotypes and metabolic profiles ofP. aeruginosaand commercial porcine gastric mucin (PGM) contains a myriad of contaminants, including iron, which affectP. aeruginosaphysiology.

IMPORTANCE

Different media formulations aiming to replicatein vivoinfection environments contain different nutrients, which affects interpretation of experimental results. Inclusion of undefined components, such as commercial porcine gastric mucin (PGM), in an otherwise chemically defined medium can alter the nutrient content of the medium in unexpected ways and influence experimental outcomes.
Water, sanitation, and hygiene practices and challenges during the COVID-19 pandemic: a cross-sectional study in rural Odisha, India
Authors: Bauza Valerie , Sclar Gloria D. , Bisoyi Alokananda , Majorin Fiona , Ghugey Apurva , Clasen Thomas
Published: January 2021

Water, sanitation, and hygiene (WASH) practices emerged as a critical component to controlling and preventing the spread of the COVID-19 pandemic. We conducted 131 semi-structured phone interviews with households in rural Odisha, India to understand behavior changes made in WASH practices as a result of the pandemic and challenges that would prevent best practices. Interviews were conducted from May-July 2020 with 73 heads of household, 37 caregivers of children less than five years old, and 21 members of village water and sanitation committees in villages with community-level piped water and high levels of latrine ownership. The majority of respondents (86%, N=104) reported a change in their handwashing practice due to COVID-19 or the related government lockdown, typically describing an increase in handwashing frequency, more thorough washing method, and/or use of soap. These improved handwashing practices remained in place a few months after the pandemic began and were often described as a new consistent practice after additional daily actions (such as returning home), suggesting new habit formation. Few participants (13%) reported barriers to handwashing. Some respondents also detailed improvements in other WASH behaviors including village-level cleaning of water tanks and/or treatment of piped water (48% of villages), household water treatment and storage (17% of respondents), and household cleaning (41% of respondents). However, there was minimal change in latrine use and child feces management practices as a result of the pandemic. We provide detailed thematic summaries of qualitative responses to allow for richer insights into these WASH behavior changes, or lack thereof, during the pandemic. The results also highlight the importance of ensuring communities have adequate WASH infrastructure to enable the practice of safe behaviors and strengthen resilience during a large-scale health crisis.
The genetic architecture of obsessive-compulsive disorder: alleles across the frequency spectrum contribute liability to OCD
Authors: Mahjani Behrang , Klei Lambertus , Mattheisen Manuel , Halvorsen Matthew W. , Reichenberg Abraham , Roeder Kathryn , Pedersen Nancy L. , Boberg Julia , de Schipper Elles , Bulik Cynthia M. , Landén Mikael , Fundín Bengt , Mataix-Cols David , Sandin Sven , Hultman Christina M. , Crowley James J. , Buxbaum Joseph D. , Rück Christian , Devlin Bernie , Grice Dorothy E.
Published: January 2021

Objective

Obsessive-compulsive disorder (OCD) is known to be substantially heritable; however, the contribution of common genetic variation across the allele frequency spectrum to this heritability remains uncertain. We use two new, homogenous cohorts to estimate heritability of OCD from common genetic variation and contrast results with prior studies.

Methods

The sample consisted of 2096 Swedish-born individuals diagnosed with OCD and 4609 controls, all genotyped for common genetic variants, specifically >400,000 single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) ≥ 0.01. Using genotypes of these SNPs to estimate distant familial relationships among individuals, we estimated heritability of OCD, both overall and partitioned according to MAF bins.

Results

We estimated narrow-sense heritability of 28% (SE=4%). The estimate was robust, varying only modestly under different models. Contrary to an earlier study, however, SNPs with MAF between 0.01 and 0.05 accounted for 8% of heritability and estimated heritability per bin roughly follows expectations based on a simple model for SNP-based heritability.

Conclusions

These results indicate that common inherited risk variation (MAF ≥ 0.01) accounts for most of the heritable variation in OCD. SNPs with low MAF contribute meaningfully to the heritability of OCD and the results are consistent with expectation under the “infinitesimal model,” where risk is influenced by a large number of loci across the genome and across MAF bins.
Outcomes of Ivermectin in the treatment of COVID-19: a systematic review and meta-analysis
Authors: Castañeda-Sabogal Alex , Chambergo-Michilot Diego , Toro-Huamanchumo Carlos J. , Silva-Rengifo Christian , Gonzales-Zamora José , Barboza Joshuan J.
Published: January 2021

Background

To assess the outcomes of ivermectin in ambulatory and hospitalized patients with COVID-19.

Methods

Five databases and websites for preprints were searched until January 2021 for randomized controlled trials (RCTs) and retrospective cohorts assessing ivermectin versus control in ambulatory and hospitalized participants. The primary outcome was overall mortality. Secondary outcome was recovered patients. For meta-analysis, random-effects and inverse variance meta-analyses with logarithmic transformation were performed. ROBINS-I for cohort studies, and the Cochrane Risk of Bias 2.0 tool for trials were used. The strength of evidence was assessed using GRADE.

Results

After the selection, twelve studies (five retrospective cohort studies, six randomized clinical trials and one case series), were included. In total, 7412 participants were reported, the mean age was 47.5 (SD 9.5) years, and 4283 (58%) were male. Ivermectin was not associated with reduced mortality (logRR: 0.89, 95% CI 0.09 to 1.70, p = 0.04, I2= 84.7%), or reduced patient recovery (logRR 5.52, 95% CI -24.36 to 35.4, p = 0.51, I2= 92.6%). All studies had a high risk of bias, and showed a very low certainty of the evidence.

Conclusions

There insufficient certainty and quality of evidence to recommend the use of ivermectin to prevent or treat ambulatory or hospitalized patients with COVID-19.
Heterogeneous recruitment abilities to RNA polymerases generate nonlinear scaling of gene expression with cell volume
Authors: Wang Qirun , Lin Jie
Published: January 2021

While most genes’ expression levels are proportional to cell volumes, some genes exhibit nonlinear scaling between their expression levels and cell volume. Therefore, their mRNA and protein concentrations change as the cell volume increases, which often have crucial biological functions such as cell-cycle regulation. However, the biophysical mechanism underlying the nonlinear scaling between gene expression and cell volume is still unclear. In this work, we show that the nonlinear scaling is a direct consequence of the heterogeneous recruitment abilities of promoters to RNA polymerases based on a gene expression model at the whole-cell level. Those genes with weaker (stronger) recruitment abilities than the average ability spontaneously exhibit superlinear (sublinear) scaling with cell volume. Analysis of the promoter sequences and the nonlinear scaling ofSaccharomyces cerevisiae’s mRNA levels shows that motifs associated with transcription regulation are indeed enriched in genes exhibiting nonlinear scaling, in concert with our model.
Unsupervised discovery of dynamic cell phenotypic states from transmitted light movies
Authors: Nguyen Phuc H.B. , Chien Sylvia , Dai Jin , Monnat Raymond J. , Becker Pamela S , Kueh Hao Yuan
Published: January 2021

Identification of cell phenotypic states within heterogeneous populations, along with elucidation of their switching dynamics, is a central challenge in modern biology. Conventional single-cell analysis methods typically provide only indirect, static phenotypic readouts. Transmitted light images, on the other hand, provide direct morphological readouts and can be acquired over time to provide a rich data source for dynamic cell phenotypic state identification. Here, we describe an end-to-end deep learning platform, UPSIDE (for Unsupervised Phenotypic State IDEntification), for discovering cell states and their dynamics from transmitted light movies.

UPSIDE uses the variational auto-encoder architecture to learn latent cell representations, that are then clustered for state identification, decoded for feature interpretation, and linked across movie frames for transition rate inference. Using UPSIDE, we identified distinct blood cell types in a heterogeneous dataset. From acute myeloid leukemia cell movies, we then identified stem-cell associated morphological states and their inter-conversion rates. UPSIDE opens up use of transmitted light movies for systematic exploration of cell state heterogeneity and dynamics in biology and medicine.
Molecular mechanism of a parasite kinesin motor and implications for its inhibition
Authors: Cook Alexander D. , Roberts Anthony , Atherton Joseph , Tewari Rita , Topf Maya , Moores Carolyn A.
Published: January 2021

Plasmodiumparasites cause malaria and are responsible annually for hundreds of thousands of deaths. They have a complex life cycle in which distinct stages are transmitted between, and reproduce in, human and mosquito hosts. In the light of emerging resistance to current therapies, components of the parasite replicative machinery are potentially important targets for anti-parasite drugs. Members of the superfamily of kinesin motors play important roles in the microtubule-based replicative spindle machinery, and kinesin-5 motors are established anti-mitotic targets in other disease contexts. We therefore studied kinesin-5 fromPlasmodium falciparum(PfK5) and characterised the biochemical properties and structure of thePfK5 motor domain. We found that thePfK5 motor domain is an ATPase with microtubule plus-end directed motility. We used cryo-EM to determine the motor’s microtubule-bound structure in no nucleotide and AMPPNP-bound states. Despite significant sequence divergence in this motor, these structures reveal that this parasite motor exhibits classical kinesin mechanochemistry. This includes ATP-induced neck-linker docking to the motor domain, which is consistent with the motor’s plus-ended directed motility. Crucially, we also observed that a large insertion in loop5 of thePfK5 motor domain creates a dramatically different chemical environment in the well characterised human kinesin-5 drug-binding site. Our data thereby reveal the possibility for selective inhibition ofPfK5 and can be used to inform future exploration ofPlasmodiumkinesins as anti-parasite targets.
Phenotypic plasticity is aligned with phenological adaptation on both micro- and macroevolutionary timescales
Authors: De Lisle Stephen P. , Mäenpää Maarit I. , Svensson Erik I.
Published: January 2021

In seasonally-variable environments, phenotypic plasticity in phenology may be critical for adaptation to fluctuating environmental (temperature) conditions. Using an 18-generation longitudinal dataset from natural insect (damselfly) populations, we show that phenology has strongly advanced. Individual fitness data suggest this is likely an adaptive response towards a thermally-dependent fitness optimum. A laboratory experiment revealed that developmental plasticity qualitatively matches environmental-dependence of selection, partially explaining observed phenological advance. Expanding our analysis to the macroevolutionary level, we use a database of over 1-million occurrence records and spatiotemporally-matched temperature data from 49 Swedish Odonate species to infer macroevolutionary dynamics of phenology. Phenological plasticity was more closely aligned with adaptation for species that have recently colonized northern latitudes, with more phenological mismatch at lower latitudes. Our results show that phenological plasticity plays a key role in microevolutionary dynamics within a single species, and such plasticity may have facilitated post-Pleistocene range expansion in this insect clade.
Novel method for quantifying AhR-ligand binding affinities using Microscale Thermophoresis
Authors: Stinn Anne , Furkert Jens , Kaufmann Stefan H.E. , Moura-Alves Pedro , Kolbe Michael
Published: January 2021

The aryl hydrocarbon receptor (AhR) is a highly conserved cellular sensor of a variety of environmental pollutants and dietary-, cell- and microbiota-derived metabolites with important roles in fundamental biological processes. Deregulation of the AhR pathway is implicated in several diseases, including autoimmune diseases and cancer, rendering AhR a promising target for drug development and host-directed therapy. The pharmacological intervention of AhR processes requires detailed information about the ligand binding properties to allow specific targeting of a particular signalling process without affecting the remaining. Here, we present a novel microscale thermophoresis-based approach to monitoring the binding of purified recombinant human AhR to its natural ligands in a cell-free system. This approach facilitates a precise identification and characterization of unknown AhR ligands and represents a screening strategy for the discovery of potential selective AhR modulators.