bluuebunny/crossref_metadata_2025 huggingface dataset:
An ST131 clade and a phylogroup A clade bearing an O101-like O-antigen cluster predominate among bloodstream Escherichia coli isolates from South-West Nigeria hospitals
Authors: Afolayan Ayorinde O. , Aboderin A. Oladipo , Oaikhena Anderson O. , Odih Erkison Ewomazino , Ogunleye Veronica O. , Adeyemo Adeyemi T. , Adeyemo Abolaji T. , Bejide Oyeniyi S. , Underwood Anthony , Argimón Silvia , Abrudan Monica , Egwuenu Abiodun , Ihekweazu Chikwe , Aanensen David M. , Okeke Iruka N.
Published: December 2022

Escherichia coli

bloodstream infections are typically attributed to a limited number of lineages that carry virulence factors associated with invasiveness. In Nigeria, the identity of circulating clones is largely unknown and surveillance of their antimicrobial resistance has been limited. We verified and whole-genome sequenced 68 2016–2018 bloodstream

E. coli

isolates from three sentinel sites in South-Western Nigeria and susceptibility tested 67 of them. Resistance to antimicrobials commonly used in Nigeria was high, with 67 (100 %), 62 (92.5 %), 53 (79.1 %) and 37 (55.2 %) showing resistance to trimethoprim, ampicillin, ciprofloxacin and aminoglycosides, respectively. Thirty-five (51 %) isolates carried extended-spectrum β-lactamase genes and 32 (91 %) of these were multidrug resistant. All the isolates were susceptible to carbapenems and colistin. The strain set included globally disseminated high-risk clones from sequence type (ST)12 (2), ST131 (12) and ST648 (4). Twenty-three (33.8 %) of the isolates clustered within two clades. The first of these consisted of ST131 strains, comprising O16:H5 and O25:H4 sub-lineages. The second was an ST10–ST167 complex clade comprising strains carrying O-antigen and capsular genes of likely

Klebsiella

origin, identical to those of avian pathogenic

E. coli

Sanji, and serotyped in silico as O89, O101 or ONovel32, depending on the tool used. Four temporally associated ST90 strains from one sentinel were closely related enough to suggest that at least some of them represented a retrospectively detected outbreak cluster. Our data implicate a broad repertoire of

E. coli

isolates associated with bloodstream infections in South-West Nigeria. Continued genomic surveillance is valuable for tracking clones of importance and for outbreak identification.
One thousand soils for molecular understanding of belowground carbon cycling
Authors: Bowman Maggie M. , Heath Alexis E. , Varga Tamas , Battu Anil K. , Chu Rosalie K. , Toyoda Jason , Cheeke Tanya E. , Porter Stephanie S. , Moffett Kevan , Letendre Brittany , Qafoku Odeta , Bargar John R. , Mans Douglas , Hess Nancy , Graham Emily B.
Published: December 2022

While significant progress has been made in understanding global carbon (C) cycling, the mechanisms regulating belowground C fluxes and storage are still uncertain. New molecular technologies have the power to elucidate these processes, yet we have no widespread standardized implementation of molecular techniques. To address this gap, we introduce the Molecular Observation Network (MONet), a decadal vision from the Environmental Molecular Sciences Laboratory (EMSL), to develop a national network for understanding the molecular composition, physical structure, and hydraulic and biological properties of soil and water. These data are essential for advancing the next generation of multiscale Earth systems models. In this paper, we discuss the 1000 Soils Pilot for MONet, including a description of standardized sampling materials and protocols and a use case to highlight the utility of molecular-level and microstructural measurements for assessing the impacts of wildfire on soil. While the 1000 Soils Pilot generated a plethora of data, we focus on assessments of soil organic matter (SOM) chemistry via Fourier-transform ion cyclotron resonance-mass spectrometry and microstructural properties via X-ray Computed Tomography to highlight the effects of recent fire history in forested ecosystems on belowground C cycling. We observed decreases in soil respiration, microbial biomass, and potential enzyme activity in soils with high frequency burns. Additionally, the nominal oxidation state of carbon in SOM increased with burn frequency in surface soils. This results in a quantifiable shift in the molecular signature of SOM and shows that wildfire may result in oxidation of SOM and structural changes to soil pore networks that persist into deeper soils.
Egg hatching success is significantly influenced by the time of thermal stress in multiple hard tick species
Authors: Ajayi Oluwaseun M. , Oyen Kennan J. , Davies Benjamin , Finch Geoffrey , Piller Benjamin D. , Harmeyer Alison A. , Wendeln Katherine , Perretta Carlie , Rosendale Andrew J. , Benoit Joshua B.
Published: December 2022

Ticks are blood-feeding arthropods responsible for the transmission of disease-causing pathogens to a wide range of vertebrate hosts, including livestock and humans. Tick-borne diseases have been implicated in significant economic losses to livestock production, and this threat will increase as these obligate parasites widen their geographical ranges. Just like in other ectotherms, thermal stress due to changing global temperatures has been shown to influence tick survival and distribution. However, studies on the influence of extreme temperatures in ticks have focused on advanced, mobile stages, ignoring stages that are immobile and cannot move to more favorable microhabitats. In this study, low- and high-temperature regimens were assessed in relation to egg viability for hard tick species -Amblyomma maculatum(Gulf Coast tick),Ixodes scapularis(black-legged tick),Dermacentor variabilis(American dog tick), andRhipicephalus sanguineus(Brown dog tick). Tick eggs exposed early in development were significantly more susceptible to thermal stress when compared with those exposed later in development. In our tested models, treatment was more important for egg hatching than species differences. Lastly, there was evidence of extreme thermal exposure significantly altering the hatching times of tick eggs for specific treatments. These results provide insights into the critical period for tick egg viability and potential tick control strategies as the globe continues to experience climate change.
Effect of Size Variability, Filamentation and Division Dynamics on Escherichia coli Allometry
Authors: Kale Tanvi , Khatri Dhruv , Athale Chaitanya A.
Published: December 2022

The cell surface area (SA) increase with volume (V) for cells is determined by growth and regulation of size and shape. Most studies of the rod-shaped model bacteriumEscherichia colihave focussed on the phenomenology or molecular mechanisms governing such scaling. Here, we proceed to examine the role of population statistics and cell division dynamics in such scaling by a combination of microscopy, image analysis and statistical simulations. We find that while cells sampled from mid-log cultures follow a 2/3 exponent, similar to geometric (Platonic) solids, drug induced filamentous cells have higher exponent values. Modulating the growth rate to change the proportion of filamentous cells, we find SA-V scales with an exponent>2/3, exceeding that predicted by the geometric scaling law. However, since increasing growth rates alter the mean and spread of population cell size distributions, we use statistical modeling to disambiguate between the effect of the mean size and variability. Simulating (i) increasing mean cell length with a constant standard deviation (s.d.) and (ii) a constant mean length with increasing s.d. results in scaling exponents that exceed the 2/3 geometric law, when population variability is included. In order to overcome possible effects of statistical sampling of unsynchronized cell populations, we virtually ‘synchronized’ the estimation of SA-V scaling from single cell growth experiments. We find the exponent depends on the stage with the maximal cell length heterogeneity and scaling exponent observed during the intermediate period between birth (B) and division (D) stages. These results point to a need to consider population statistics and a role for cell growth and division when estimating SA-V scaling of bacterial cells.
Neuroecological selection for musical features through spatial reciprocity in long-term partnerships
Authors: Schruth David M.
Published: December 2022

Chemical sensing via olfaction constitutes a most ancient form of inter-organism communication. But acoustical signaling via tonal and rhythmic patterning is also common among higher vertebrates. Animals that live in well ventilated habitats and move in diasporic ways have further evolved more spectrally varied and discretized call structure. But unlike song in birds, researchers have struggled to locate isolated nucleii specialized for music cognition. The brain stem, midbrain, hindbrain, and forebrain, however, all largely associate with aspects of musical performance, perception, memory, and emotion. I hypothesized that spectral features of musical display evolved as honest signals of spatial cognition for precarious locomotor tasks associated with nurturing and protecting vulnerable offspring. I investigated possible connections between motor, visual, and spatial cognitive areas in relation to both signaler production and receiver processing of acoustical features of musical output. Brain component volume fractions of 42 parts from 48 primates were compiled, from a single source, and compared against a vocal complexity index (ARDI) as well as individual musical feature scores: including tone, interval, repetition, transposition rhythm, and unique syllable count. Structures for spatial and visual perception as well as motor control and emotional processing associated moderately with areas used by species who produce calls with both temporal and spectral musical features. These findings are consistent with a dual (both receiver- and signaler-side) function of musical signals. Associations with spatio-social areas (e.g. schizocortex and insula) support direct selection for a paralimbic-based neighbor orienting [PIANO] sensory modality for mapping and anticipating movement of fellow arboreal cohabitants. Associations with motor areas (e.g. LGN, mid-brain, and thalamus) support the complementary model that signaler capacities for spatio-motive emplacement [ME] are indirectly selected by conspecific receivers. This dual manifestation in low-parity species that locomote in diasporic ways through (arboreally) diffuse habitats, is compatible with musicality serving as courtship signals by long-term mates with consistent and reliable spatial capacities directly relevant to care of vulnerable (arboreal) offspring.
Combination of personalized computational modeling and machine-learning for optimization of left ventricular pacing site in cardiac resynchronization therapy
Authors: Dokuchaev Arsenii , Chumarnaya Tatiana , Bazhutina Anastasia , Khamzin Svyatoslav , Lebedeva Viktoria , Lyubimtseva Tamara , Zubarev Stepan , Lebedev Dmitry , Solovyova Olga
Published: December 2022

Background

The 30-50% non-response rate to cardiac resynchronisation therapy (CRT) calls for improved patient selection and optimized pacing lead placement.

Objective

The study aimed to develop a novel technique using patient-specific cardiac models and machine learning (ML) to predict an optimal left ventricular (LV) pacing site (ML-PS) that maximizes the likelihood of LV ejection fraction (LVEF) improvement in a given CRT candidate. To validate the approach, we evaluated whether the distance DPSbetween the clinical LV pacing site (ref-PS) and ML-PS is associated with improved response rate and magnitude.

Materials and Methods

We reviewed retrospective data for 57 CRT recipients. A positive response was defined as a more than 10% LVEF improvement. Personalized models of ventricular activation and ECG were created from MRI and CT images. The characteristics of ventricular activation during intrinsic rhythm and biventricular (BiV) pacing with ref-PS were derived from the models and used in combination with clinical data to train supervised ML classifiers. The best logistic regression model classified CRT responders with a high accuracy of 0.77 (ROC AUC=0.84). The LR classifier, model simulations and Bayesian optimization with Gaussian process regression were combined to identify an optimal ML-PS that maximizes the ML-score of CRT response over the LV surface in each patient.

Results

The optimal ML-PS improved the ML-score by 17±14% over the ref-PS. Twenty percent of the non-responders were reclassified as positive at ML-PS. Selection of positive patients with a max ML-score >0.5 demonstrated an improved clinical response rate. The distance DPSwas shorter in the responders. The max ML-score and DPSwere found to be strong predictors of CRT response (ROC AUC=0.85). In the group with max ML-score>0.5 and DPS< 30 mm, the response rate was 83% compared to 14% in the rest of the cohort. LVEF improvement in this group was higher than in the other patients (16±8% vs 7±8%).

Conclusion

A new technique combining clinical data, personalized heart modelling and supervised ML demonstrates the potential for use in clinical practice to assist in optimizing patient selection and predicting optimal LV pacing lead position in HF candidates for CRT.
The estimated disease burden of COVID-19 in Japan from 2020 to 2021
Authors: Tsuzuki Shinya , Beutels Philippe
Published: December 2022

Background

To date, it is not fully understood to what extent COVID-19 has burdened society in Japan. This study aimed to estimate the total disease burden due to COVID-19 in Japan during 2020-2021.

Methods

We stratify disease burden estimates by age group and present it as absolute Quality Adjusted Life Years (QALYs) lost and QALYs lost per 100,000 persons. The total estimated value of QALYs lost consists of (1) QALYs lost brought by deaths due to COVID-19, (2) QALYs lost brought by inpatient cases, (3) QALYs lost brought by outpatient cases, and (4) QALYs lost brought by long-COVID.

Findings

QALYs lost due to COVID-19 was estimated as 286,781·7 for two years, 114·0 QALYs per 100,000 population per year. 71·3% of them were explained by the burden derived from deaths. Probabilistic sensitivity analysis showed that the burden of outpatient cases was the most sensitive factor.

Interpretation

The large part of disease burden due to COVID-19 in Japan from the beginning of 2020 to the end of 2021 was derived from Wave 3, 4, and 5 and the proportion of QALYs lost due to morbidity in the total burden increased gradually. The estimated disease burden was smaller than that in other high-income countries. It will be our future challenge to take other indirect factors into consideration.

Fundings

This research was funded by JSPS KAKENHI [Grant number 20K10546]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Crossmodal visual predictions elicit spatially specific early visual cortex activity but later than real visual stimuli
Authors: Stange Liesa , Ossandón José P. , Röder Brigitte
Published: December 2022

Previous studies have indicated that crossmodal visual predictions are instrumental in controlling early visual cortex activity. The exact time course and spatial precision of such crossmodal top-down influences on visual cortex have been unknown. In the present study, participants were exposed to audio-visual combinations comprising one of two sounds and a Gabor patch either in the top left or in the bottom right visual field. Event related potentials (ERP) were recorded to these frequent crossmodal combinations (Standards) as well as to trials in which the visual stimulus was omitted (Omissions) or the visual and auditory stimuli were recombined (Deviants). Standards and Deviants elicited an ERP between 50 and 100 ms of opposite polarity known as a C1 effect commonly associated with retinotopic processing in early visual cortex. In contrast, a C1 effect was not observed in Omission trials. Spatially specific Omission and Mismatch effects (Deviants minus Standards) started only later with a latency of 230 ms and 170 ms, respectively.

These results suggest that crossmodal visual predictions control visual cortex activity in a spatially specific manner. However, visual predictions do not elicit neural responses that mimic stimulus-driven activity but rather seem to affect early visual cortex via distinct neural mechanisms.
Do early indicators of euthyroid sick syndrome predict longer-term post-bariatric weight loss? A hypothesis-generating preliminary study
Authors: Fowler Natasha , Adler Sarah , Najarian Thomas , Rowsemitt Carol N. , Safer Debra L.
Published: December 2022

Background

Despite bariatric surgery’s success for most patients, up to 30% do not experience optimal weight loss outcomes. Reasons remain incompletely understood. Thyroid hormones, due to their role in energy expenditure, have received study. Yet research to date is inconclusive regarding the impact of standard thyroid markers (e.g., thyroid stimulating hormone, or TSH) on weight regulation after bariatric surgery. This prospective observational study investigates whether the early development of euthyroid sick syndrome (ESS) predicts reduced longer-term post-bariatric weight loss. ESS develops during periods of stress (e.g., critical illness, severe infection, famine) and is thought to serve a protective function by suppressing metabolism and conserving weight. Levels of metabolically active free triiodothyronine (FT3) drop, levels of non-catabolic reverse 3,3’,5’-triiodothyronine (rT3) rise, and TSH levels remain euthyroid. Reductions in the ratio of FT3to rT3significantly predict outcomes in critically ill patients with ESS yet have been unexamined in intentional weight loss among post-bariatric patients. Hence this hypothesis-generating preliminary study investigated whether early changes in the FT3:rT3ratio predict weight changes at 1-2 years post-bariatric surgery

Methods

Twenty-three adult patients undergoing Roux-en-Y gastric bypass (n=12) or sleeve gastrectomy (n=11) were recruited from a bariatric surgery clinic. The TSH, FT4, FT3, rT3, and self-reported hypothyroid symptoms were collected 2-weeks pre-surgery and between 2 weeks to 3 months post-surgery. Body mass index was measured pre-surgery and 1-2 years post-surgery.

Results

Reductions in the FT3:rT3ratio from pre- to early post-surgery significantly predicted reduced weight loss at 1 (p= 0.03) and 2 years (p= 0.02) post-surgery. No other thyroid-related markers nor hypothyroid symptoms were predictive.

Conclusions

Although replication with larger samples is needed due to sizeable study attrition, this small exploratory study provides provocative support that early changes in the FT3:rT3ratio associated with ESS predict longer-term reductions in post-bariatric surgery weight loss. Clinical implications are discussed.
Splicing annotation of endometrial cancer GWAS risk loci reveals potentially causal variants and supports a role forNF1andSKAP1as susceptibility genes
Authors: Canson Daffodil M. , O’Mara Tracy A. , Spurdle Amanda B. , Glubb Dylan M.
Published: December 2022

Alternative splicing contributes to cancer development. Indeed, splicing analysis of cancer genome-wide association study (GWAS) risk variants has revealed likely causal variants. To systematically assess GWAS variants for splicing effects, we developed a prioritization workflow using a combination of splicing prediction tools, alternative transcript isoform and splicing quantitative trait locus (sQTL) annotations. Application of this workflow to candidate causal variants from 16 endometrial cancer GWAS risk loci highlighted single nucleotide polymorphisms (SNPs) that were predicted to upregulate alternative transcripts. For two variants, sQTL data supported the predicted impact on splicing. At the 17q11.2 locus, the protective allele for rs7502834 was associated with increased splicing of an exon inNF1alternative transcript encoding a truncated protein in adipose tissue and is consistent with an endometrial cancer transcriptome-wide association study (TWAS) finding in adipose tissue. Notably,NF1haploinsufficiency is protective for obesity, a well-established risk factor for endometrial cancer. At the 17q21.32 locus, the rs2278868 risk allele was predicted to upregulate aSKAP1transcript that is subject to nonsense mediated decay, concordant with a corresponding sQTL in lymphocytes. This is consistent with a TWAS finding that indicates decreasedSKAP1expression in blood increases endometrial cancer risk. As SKAP1 is involved in T-cell immune responses, decreasedSKAP1expression may impact endometrial tumor immunosurveillance. In summary, our analysis has identified potentially causal endometrial cancer GWAS risk variants with plausible biological mechanisms and provides a splicing annotation workflow to aid interpretation of other GWAS datasets.
Understanding the mechanism of the SARS CoV-2 coinfection with other respiratory viruses
Authors: Ponnusamy Kalaiarasan , Srinivasan RadhaKrishnan Venkatraman , Marwal Robin , Datta Meena , Dhar Mahesh Shankar , Chaudhary Urmila , Sharma Uma , Kumari Swati , Sharma Kalpana , Gogia Hema , Madan Preeti , Kabra Sandhya , Rakshit Partha
Published: December 2022

Coinfections have a potential role in increased morbidity and mortality rates during pandemics. Our investigation is aimed at evaluating the viral coinfection prevalence in COVID-19 patients. Rapid diagnostic tests are tools with a paramount impact both on improving patient care. Particularly in the case of respiratory infections, it is of great importance to quickly confirm/exclude the involvement of pathogens. The COVID-19 pandemic has been associated with changes in respiratory virus infections worldwide, which have differed between virus types. In this paper, we systematically searched the percentage of coinfection of various respiratory viruses in COVID-19-positive samples. We included patients of all ages, in all settings. The main outcome was the proportion of patients with viral coinfection. By describing the differences in changes between viral species across different geographies over the course of the COVID-19 pandemic, we may better understand the complex factors involved in the community cocirculation of respiratory viruses.
State-dependency of behavioural traits is a function of the life-stage in a holometabolous insect
Authors: Singh Pragya , Wolthaus Jonas , Schielzeth Holger , Müller Caroline
Published: December 2022

State variables, such as body condition, are important predictors of behavioural traits. Depending on the state of an individual, the costs and benefits associated with different behavioural decisions can vary. An individual’s state could affect its average behavioural response and also the behavioural repeatability. Moreover, even for the same state, different behavioural strategies may be adaptive depending on the individual’s life-stage. Here, we manipulated the body condition in larvae and adults of a holometabolous insect species,Athalia rosae, using starvation. We assessed the effects of starvation on the behavioural traits of post-contact immobility (PCI) and activity levels and tested their repeatability. Our results show state-dependency of behaviour, although the effect varied with life-stage. Starved larvae exhibited shorter PCI duration and higher activity levels, whereas starved adults were less active than non-starved individuals. Moreover, although most behavioural repeatability estimates were significant in both life-stages, we did not find any significant effect of starvation on the estimates. Next, we calculated standardised effect sizes to compare starvation effects across life stages. We found that starvation had a larger and opposite effect in the larval stage than during the adult stage for all behavioural traits. Finally, we conducted microcosm and no-choice bioassay experiments to examine the benefits and costs, respectively, of the behaviour elicited by starvation in the larval stage. We observed that starved larvae located food faster than non-starved larvae but were also attacked sooner by a predator, possibly due to their higher activity levels. Together, our results demonstrate that behavioural state-dependence is a function of the life-stage of an individual. Moreover, the behavioural strategy exhibited can be adaptive for a specific life-stage with respect to certain functions, like foraging, but also carry costs, like risk of predation.
Structure-optimized sgRNA selection with PlatinumCRISPr for efficient Cas9 generation of knock-outs
Authors: Haussmann Irmgard U. , Dix Thomas C. , McQuarrie David W. J. , Dezi Veronica , Hans Abdullah I. , Arnold Roland , Soller Matthias
Published: December 2022

A single guide RNA (sgRNA) directs Cas9 nuclease for gene-specific scission of double-stranded DNA. High Cas9 activity is essential for efficient gene editing to generate gene deletions and gene replacements by homologous recombination. However, cleavage efficiency is below 50% for more than half of randomly selected sgRNA sequences in human cell culture screens or model organisms. We used in vitro assays to determine intrinsic molecular parameters for maximal sgRNA activity including correct folding of sgRNAs and Cas9 structural information. From comparison of over 10 data sets, we find major constraints in sgRNA design originating from defective secondary structure of the sgRNA, sequence context of the seed region, GC context and detrimental motifs, but we also find considerable variation among different prediction tools when applied to different data sets. To aid selection of efficient sgRNAs, we developed web-based PlatinumCRISPr, an sgRNA design tool to evaluate base-pairing and sequence composition parameters for optimal design of highly efficient sgRNAs for Cas9 genome editing named PlatinumCRISPr. We applied this tool to select sgRNAs to efficiently generate gene deletions inDrosophila Ythdc1andYthdf, that bind toN6methylated adenosines (m6A) in mRNA. However, we discovered, that generating small deletions with sgRNAs and Cas9 leads to ectopic reinsertion of the deleted DNA fragment elsewhere in the genome. These insertions can be removed by standard genetic recombination and chromosome exchange. These new insights into sgRNA design and the mechanisms of CRISPR-Cas9 genome editing advances efficient use of this technique for safer applications in humans.
SARS-CoV-2 causes periodontal fibrosis by deregulating mitochondrial β-oxidation
Authors: Gao Yan , Kok Wai Ling , Sharma Vikram , Illsley Charlotte Sara , Hanks Sally , Tredwin Christopher , Hu Bing
Published: December 2022

The global high prevalence of COVID-19 is a major challenge for health professionals and patients. SARS-CoV-2 virus mutate predominantly in the spike proteins, whilst the other key viral components remain stable. Previous studies have shown that the human oral cavity can potentially act as reservoir of the SARS-CoV-2 virus. COVID-19 can cause severe oral mucosa lesions and is likely to be connected with poor periodontal conditions. However, the consequence of SARS-CoV-2 viral infection on human oral health has not been systematically examined. In this research, we aimed to study the pathogenicity of SARS-CoV-2 viral components on human periodontal tissues and cells. We found that by exposing to SARS-CoV-2, especially to the viral envelope and membrane proteins, the human periodontal fibroblasts could develop fibrotic pathogenic phenotypes, including hyperproliferation that was concomitant induced together with increased apoptosis and senescence. The fibrotic degeneration was mediated by a down-regulation of mitochondrial β-oxidation in the fibroblasts. Fatty acid β-oxidation inhibitor, etomoxir treatment could mirror the same pathological consequence on the cells, similar to SARS- CoV-2 infection. Our results therefore provide novel mechanistic insights into how SARS- CoV-2 infection can affect human periodontal health at the cell and molecular level with potential new therapeutic targets for COVID-19 induced fibrosis.
The FMRF-NH2Gated Sodium Channel ofBiomphalaria glabrata: Localization and Expression Following Infection bySchistosoma mansoni
Authors: Vicente-Rodríguez Laura , Torres Amanda , Hernández-Vázquez Anthony , Rosa-Casillas Mariela , Bracho-Rincón Dina P. , de Jesús Paola Méndez , Behra Martine , Rosenthal Joshua J.C. , Miller Mark W.
Published: December 2022

The neglected tropical disease schistosomiasis impacts the lives of over 700 million people globally.Schistosoma mansoni, the trematode parasite that causes the most common type of schistosomiasis, requires planorbid pond snails of the genusBiomphalariato support its larval development and transformation to the form that can infect humans. A greater understanding of neural signaling systems that are specific to theBiomphalariaintermediate host could lead to novel strategies for parasite or snail control. This study characterized aBiomphalaria glabrataneural receptor that is gated by the molluscan neuropeptide FMRF-NH2. TheBiomphalaria glabrataFMRF-NH2gated sodium channel (Bgl-FaNaC) amino acid sequence was highly conserved with FaNaCs found in related gastropods, especially the planorbidPlanorbella trivolvis(91% sequence identity). In common with theP. trivolvisFaNaC, theB. glabratareceptor exhibited a low affinity (EC50: 3 × 10−4M) and high specificity for the FMRF-NH2agonist. Its expression in the central nervous system, detected by immunohistochemistry andin situhybridization, was widespread, with the protein localized mainly to neuronal fibers and the mRNA confined to cell bodies. Colocalization was observed with the FMRF-NH2tetrapeptide precursor in some neurons associated with male mating behavior. At the mRNA level,Bgl-FaNaC expression in the visceral and left parietal ganglia decreased at 20 days post infection byS. mansoniand in the shedding phase. Altered FMRF-NH2signaling could be vital for parasite survival and proliferation in its snail intermediate host.
Cell migration CRISPRi screens in human neutrophils reveal regulators of context-dependent migration and differentiation state
Authors: Belliveau Nathan M. , Footer Matthew J. , Akdogan Emel , van Loon Aaron P. , Collins Sean R. , Theriot Julie A.
Published: December 2022

Neutrophils are the most abundant leukocyte in humans and provide a critical early line of defense as part of our innate immune system. Their exquisite sensitivity to chemical gradients and ability to rapidly migrate make them especially suited to protect against infection. However, their terminal differentiation status and short lifetime (on the order of days) have hindered their study. Furthermore, while modern CRISPR-based gene perturbation strategies now allow comprehensive, genome-scale screens in human cells, their application to complex and dynamic processes like cell migration remain limited. Using HL-60 cells, a leukemia cell line that can be differentiated into neutrophil-like cells, we have developed multiple cell migration screen strategies that provide comprehensive, genome-wide discovery of molecular factors that are critical for directed (chemotaxis), undirected (chemokinesis), and 3D amoeboid cell migration in these fast-moving cells. Combining these assays with additional, pooled, genome-wide CRISPR interference dropout screens of cell proliferation and neutrophil differentiation, we have identified a comprehensive set of genes that are important across the processes of cellular growth, differentiation, and migration. This combined dataset highlights a particular reliance upon mTORC1 signaling that alters neutrophil lifetime, migration phenotype, and sensitivity to chemotactic cues. Across our cell migration screens, we identified several hundred genes important for migration including those with specific roles only in particular migratory contexts. This genome-wide screening strategy, therefore, provides an invaluable approach to the study of neutrophils and provides a resource that will inform future studies of cell migration in these and other rapidly migrating cells.
Advice on describing Bayesian analysis of neutron and X-ray reflectometry
Authors: McCluskey Andrew R. , Caruana Andrew J. , Kinane Christy J. , Armstrong Alexander J. , Arnold Thomas , Cooper Joshaniel F. K. , Cortie David L. , Hughes Arwel V. , Moulin Jean-Francois , Nelson Andrew R. J. , Potrzebowski Wojciech , Starostin Vladimir
Published: December 2022

As a result of the availability of modern software and hardware, Bayesian analysis is becoming more popular in neutron and X-ray reflectometry analysis. The understandability and replicability of these analyses may be harmed by inconsistencies in how the probability distributions central to Bayesian methods are represented in the literature. Herein advice is provided on how to report the results of Bayesian analysis as applied to neutron and X-ray reflectometry. This includes the clear reporting of initial starting conditions, the prior probabilities, the results of any analysis and the posterior probabilities that are the Bayesian equivalent of the error bar, to enable replicability and improve understanding. It is believed that this advice, grounded in the authors' experience working in the field, will enable greater analytical reproducibility in the work of the reflectometry community, and improve the quality and usability of results.
Natural and low‐caloric rebaudioside A as a substitute for dietary sugars: A comprehensive review
Authors: Wang Yang , Luo Xiang , Chen Li , Mustapha Abdullateef Taiye , Yu Xiaojie , Zhou Cunshan , Okonkwo Clinton Emeka
Published: December 2022

For health and safety concerns, traditional high‐calorie sweeteners and artificial sweeteners are gradually replaced in food industries by natural and low‐calorie sweeteners. As a natural and high‐quality sugar substitute, steviol glycosides (SvGls) are continually scrutinized regarding their safety and application. Recently, the cultivation of organic stevia has been increasing in many parts of Europe and Asia, and it is obvious that there is a vast market for sugar substitutes in the future. Rebaudioside A, the main component of SvGls, is gradually accepted by consumers due to its safe, zero calories, clear, and sweet taste with no significant undesirable characteristics. Hence, it can be used in various foods or dietary supplements as a sweetener. In addition, rebaudioside A has been demonstrated to have many physiological functions, such as antihypertension, anti‐diabetes, and anticaries. But so far, there are few comprehensive reviews of rebaudioside A. In this review article, we discuss the physicochemical properties, metabolic process, safety, regulatory, health benefits, and biosynthetic pathway of rebaudioside A and summarize the modification methods and state‐of‐the‐art production and purification techniques of rebaudioside A. Furthermore, the current problems hindering the future production and application of rebaudioside A are analyzed, and suggestions are provided.
FBP1 induced by β‐elemene enhances the sensitivity of gefitinib in lung cancer
Authors: Li Jian , Dai Ping , Sun Jing , Yu Wenyan , Han Wei , Li Kaichun
Published: December 2022

Background

β‐elemene is known to play a critical role in tumorigenesis as well as tyrosine kinase inhibitor (TKI) resistance in lung cancer. However, the biological function and molecular mechanism remain largely unknown.

Methods

In this study, the common genes involved in gefitinib resistance and β‐elemene were identified using bioinformatic analysis. The expression of FBP1 was examined by qRT–PCR and Western blot analysis. Cell proliferation, flow cytometry, clone formation and IC50 assays were performed to assess the effects of β‐elemene and FBP1. Western blot analysis was used to evaluate apoptosis‐related gene expression. Finally, in vivo experiments were conducted to assess the crucial role of FBP1 in gefitinib‐resistant HCC827/GR cells in nude mice.

Results

Screening analysis demonstrated that fructose‐1,6‐bisphosphatase (FBP1) was induced by β‐elemene and downregulated in gefitinib‐resistant lung cells. Functionally, overexpression of FBP1 inhibited proliferation and gefitinib resistance and promoted apoptosis of PC9/GR and HCC827/GR cells in vitro. Mechanistically, FBP1 impeded the nuclear translocation of p‐STAT3. The FBP1/STAT3 axis was required for FBP1‐mediated apoptosis‐related gene expression. In vivo experiments further confirmed the enhanced effects of FBP1 on lung cancer cell sensitivity to gefitinib.

Conclusion

Our research indicated that β‐elemene suppressed proliferation and enhanced sensitivity to gefitinib by inducing apoptosis through the FBP1/STAT3 axis in gefitinib‐resistant lung cancer cells.
How do firms learn? Evidence from corporate cash holdings during the COVID‐19 pandemic
Authors: BC Bishal , Simpson Thuy
Published: December 2022

We examine the impact of COVID‐19 on US corporate cash holdings. Our findings suggest that greater pandemic exposure is associated with higher corporate cash holdings and that firms learn from prior experiences as they manage their cash policies. More specifically, the level of cash holdings in firms that experienced severe financial constraints during the 2008 credit crisis and firms with prior severe acute respiratory syndrome (SARS) and H1N1 exposure is significantly lower than that of firms with no prior epidemic or financial constraints experience. Overall, our findings support the learning behaviour of cash and contribute to corporate cash holdings literature by providing insights on the extent to which firms learn from prior experiences to manage their liquidity.
Long‐term recovery from opioid use disorder: recovery subgroups, transition states and their association with substance use, treatment and quality of life
Authors: Craft William H. , Shin Hwasoo , Tegge Allison N. , Keith Diana R. , Athamneh Liqa N. , Stein Jeffrey S. , Ferreira Marco A. R. , Chilcoat Howard D. , Le Moigne Anne , DeVeaugh‐Geiss Angela , Bickel Warren K.
Published: December 2022

Background and Aims

Limited information exists regarding individual subgroups of recovery from opioid use disorder (OUD) following treatment and how these subgroups may relate to recovery trajectories. We used multi‐dimensional criteria to identify OUD recovery subgroups and longitudinal transitions across subgroups.

Design, Setting and Participants

In a national longitudinal observational study in the United States, individuals who previously participated in a clinical trial for subcutaneous buprenorphine injections for treatment of OUD were enrolled and followed for an average of 4.2 years after participation in the clinical trial.

Measurements

We identified recovery subgroups based on psychosocial outcomes including depression, opioid withdrawal and pain. We compared opioid use, treatment utilization and quality of life among these subgroups.

Findings

Three dimensions of the recovery process were identified: depression, opioid withdrawal and pain. Using these three dimensions, participants were classified into four recovery subgroups: high‐functioning (minimal depression, mild withdrawal and no/mild pain), pain/physical health (minimal depression, mild withdrawal and moderate pain), depression (moderate depression, mild withdrawal and mild/moderate pain) and low‐functioning (moderate/severe withdrawal, moderate depression and moderate/severe pain). Significant differences among subgroups were observed for DSM‐5 criteria (P < 0.001) and remission status (P < 0.001), as well as with opioid use (P < 0.001), treatment utilization (P < 0.001) and quality of life domains (physical health, psychological, environment and social relationships; Ps < 0.001, Cohen’s fs ≥ 0.62). Recovery subgroup assignments were dynamic, with individuals transitioning across subgroups during the observational period. Moreover, the initial recovery subgroup assignment was minimally predictive of long‐term outcomes.

Conclusions

There appear to be four distinct subgroups among individuals in recovery from OUD. Recovery subgroup assignments are dynamic and predictive of contemporaneous, but not long‐term, substance use, substance use treatment utilization or quality of life outcomes.
Effectiveness of probiotics in apical periodontitis progression: A scoping review and implications for research
Authors: La Rosa Giusy Rita Maria , Pedullà Eugenio
Published: December 2022

To synthesise the current knowledge on the effects of probiotics in apical periodontitis progression by a scoping review of animal and human studies. Reporting was based on Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) Extension for Scoping Reviews. The literature search and screening was performed on PubMed and Scopus databases by two independent reviewers selecting human and animal studies that evaluated the effectiveness of probiotics in reducing the severity of apical periodontitis. Two animal studies with 3 publications met the eligibility criteria for qualitative synthesis. The most common probiotics were Lactobacillus rhamnosus and Lactobacillus acidophilus orally administered for gavage in Wistar rats with induced apical periodontitis. Overall, probiotics significantly reduced inflammation and bone resorption with an improvement in the apical periodontitis progression. Although results in animal studies are promising, the use of probiotics in apical periodontitis progression requires caution due to the insufficient available evidence.
Channel impeller design for centrifugal blood pump in hybrid pediatric total artificial heart: Modeling, magnet integration, and hydraulic experiments
Authors: Hirschhorn Matthew , Catucci Nicholas , Day Steven W. , Stevens Randy M. , Tchantchaleishvili Vakhtang , Throckmorton Amy L.
Published: December 2022

Background

The purpose of this research is to address ongoing device shortfalls for pediatric patients by developing a novel pediatric hybrid total artificial heart (TAH). The valveless magnetically‐levitated MCS device (Dragon Heart) has only two moving parts, integrates an axial and centrifugal blood pump into a single device, and will occupy a compact footprint within the chest for the pediatric patient population.

Methods

Prior work on the Dragon Heart focused on the development of pump designs to achieve hemodynamic requirements. The impeller of these pumps was shaft‐driven and thus could not be integrated for testing. The presented research leverages an existing magnetically levitated axial flow pump and focuses on centrifugal pump development. Using the axial pump diameter as a geometric constraint, a shaftless, magnetically supported centrifugal pump was designed for placement circumferentially around the axial pump domain. The new design process included the computational analysis of more than 50 potential centrifugal impeller geometries. The resulting centrifugal pump designs were prototyped and tested for levitation and no‐load rotation, followed by in vitro testing using a blood analog. To meet physiologic demands, target performance goals were pressure rises exceeding 90 mm Hg for flow rates of 1–5 L/min with operating speeds of less than 5000 RPM.

Results

Three puck‐shaped, channel impellers for the centrifugal blood pump were selected based on achieving performance and space requirements for magnetic integration. A quasi‐steady flow analysis revealed that the impeller rotational position led to a pulsatile component in the pressure generation. After prototyping, the centrifugal prototypes (3, 4, and 5 channeled designs) demonstrated levitation and no‐load rotation. Hydraulic experiments established pressure generation capabilities beyond target requirements. The pressure‐flow performance of the prototypes followed expected trends with a dependence on rotational speed. Pulsatile blood flow was observed without pump‐speed modulation due to rotating channel passage frequency.

Conclusion

The results are promising in the advancement of this pediatric TAH. The channeled impeller design creates pressure‐flow curves that are decoupled from the flow rate, a benefit that could reduce the required controller inputs and improve treatment of hypertensive patients.
Adolescent sleep, distress, and technology use: weekday versus weekend
Authors: Reardon Alexander , Lushington Kurt , Agostini Alex
Published: December 2022

Background

In adolescents, technology use at bedtime is linked to disrupted sleep and psychological distress. Adolescents are known to sleep later on weekends compared to weekdays but whether this leads to greater technology use, and, hence, additional psychological distress is not known. At greater risk maybe adolescents with a late compared to early chronotype, that is a preference for late versus early sleep onset and offset times.

Method

Self‐reported measures of sleep timing, chronotype (early, neither early nor late, late), technology medium (social media/texting, TV/streaming, and gaming), and psychological distress (DASS‐21) were collected from 462 students attending one Australian high school.

Results

Technology use at bedtime was greater on weekends and especially in adolescents with a late chronotype. Social media/texting on weekends was predictive of delayed sleep onset times (β = .120), and shorter sleep (β = −.172). Shorter sleep on weekdays but not on weekends was associated with greater psychological distress. Technology medium and chronotype were not predictive of psychological distress.

Conclusions

This study confirmed that technology use and its impact on sleep differed on weekdays compared to weekends and that a late chronotype was associated with greater technology use. However, neither technology medium nor chronotype was found to affect psychological distress. While greater autonomy may be granted to adolescents over the weekend regarding sleep behaviour, young people, parents, and clinicians should be mindful of the link between technology use and sleep.
Health and social characteristics of clients reporting amphetamine type substance use at entry to public alcohol and other drug services in New South Wales, Australia, 2016–2019
Authors: Black Emma , Mammen Kristie , Deacon Rachel M. , Ezard Nadine , Mills Llewellyn , Dunlop Adrian J. , Montebello Mark , Reid David , Childs Steven , Bruno Raimondo , Shakeshaft Anthony , Siefried Krista J. , Farrell Michael , Holmes Jennifer , Lintzeris Nicholas
Published: December 2022

Introduction

Amphetamine type substances (ATS) are commonly used by Australian alcohol and other drug service entrants. We describe demographic characteristics, patterns of ATS and other substance use, health and social conditions among clients entering New South Wales (NSW) public alcohol and other drug services.

Methods

Retrospective cohort of 13,864 records across six health districts (2016–2019) for clients seeking substance use treatment. These districts service approximately 44% of the NSW population aged 15 years and over. Multivariate analysis was conducted on a subsample for whom full data were available (N = 9981). Data included NSW Minimum Data Set for drug and alcohol treatment services and Australian Treatment Outcomes Profile items.

Results

Over the preceding 4 weeks, 77% (n = 10,610) of clients (N = 13,864) reported no recent ATS use, 15% (n = 2109) reported ‘low frequency’ (1–12 days) and 8% (n = 1145) ‘high frequency’ (13–28 days) use. ATS use was most common among people attending for ATS or opioids as primary drug of concern. A multinomial regression (N = 9981) identified that clients reporting recent arrest (aOR 1.74, 95% CI 1.36, 2.24), higher cannabis use frequency (aOR 1.01, 95% CI 1.00, 1.02), lower opioid use frequency (aOR 0.98, 95% CI 0.97, 0.99) and poorer quality of life (aOR 0.91, 95% CI 0.86, 0.97) were more likely to report ‘high frequency’ rather than ‘low frequency’ ATS use.

Discussion and Conclusions

People who use ATS experience health and social issues that may require targeted responses. These should be integrated across all services, not only for clients with ATS as principal drug of concern.