bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvements in the Sequencing and Assembly of Plant Genomes
Authors: Sharma Priyanka , Al-Dossary Othman , Alsubaie Bader , Al-Mssallem Ibrahim , Nath Onkar , Mitter Neena , Alves Margarido Gabriel Rodrigues , Topp Bruce , Murigneux Valentine , Masouleh Ardy Kharabian , Furtado Agnelo , Henry Robert J
Published: January 2021

Background

Advances in DNA sequencing have reduced the difficulty of sequencing and assembling plant genomes. A range of methods for long read sequencing and assembly have been recently compared and we now extend the earlier study and report a comparison with more recent methods.

Results

Updated Oxford Nanopore Technology software supported improved assemblies. The use of more accurate sequences produced by repeated sequencing of the same molecule (PacBio HiFi) resulted in much less fragmented assembly of sequencing reads. The use of more data to give increased genome coverage resulted in longer contigs (higher N50) but reduced the total length of the assemblies and improved genome completeness (BUSCO). The original model species, Macadamia jansenii, a basal eudicot, was also compared with the 3 other Macadamia species and with avocado (Persea americana), a magnoliid, and jojoba (Simmondsia chinensis) a core eudicot. In these phylogenetically diverse angiosperms, increasing sequence data volumes also caused a highly linear increase in contig size, decreased assembly length and further improved already high completeness. Differences in genome size and sequence complexity apparently influenced the success of assembly from these different species.

Conclusions

Advances in long read sequencing technology have continued to significantly improve the results of sequencing and assembly of plant genomes. However, results were consistently improved by greater genome coverage (using an increased number of reads) with the amount needed to achieve a particular level of assembly being species dependant.
Measuring gas vesicle dimensions by electron microscopy
Authors: Dutka Przemysław , Malounda Dina , Metskas Lauren Ann , Chen Songye , Hurt Robert C. , Lu George J. , Jensen Grant J. , Shapiro Mikhail G.
Published: January 2021

Gas vesicles (GVs) are cylindrical or spindle-shaped protein nanostructures filled with air and used for flotation by various cyanobacteria, heterotrophic bacteria, and Archaea. Recently, GVs have gained interest in biotechnology applications due to their ability to serve as imaging agents and actuators for ultrasound, magnetic resonance and several optical techniques. The diameter of GVs is a crucial parameter contributing to their mechanical stability, buoyancy function and evolution in host cells, as well as their properties in imaging applications. Despite its importance, reported diameters for the same types of GV differ depending on the method used for its assessment. Here, we provide an explanation for these discrepancies and utilize electron microscopy (EM) techniques to accurately estimate the diameter of the most commonly studied types of GVs. We show that during air drying on the EM grid, GVs flatten, leading to a ~1.5-fold increase in their apparent diameter. We demonstrate that GVs’ diameter can be accurately determined by direct measurements from cryo-EM samples or alternatively indirectly derived from widths of flat collapsed and negatively stained GVs. Our findings help explain the inconsistency in previously reported data and provide accurate methods to measure GV dimensions.
Human embryonic stem cell-derived cardiomyocytes express SARS-CoV-2 host entry proteins: screen to identify inhibitors of infection
Authors: Williams Thomas L. , Colzani Maria T. , Macrae Robyn G.C. , Robinson Emma L. , Bloor Stuart , Greenwood Edward J. D. , Zhan Jun Ru , Strachan Gregory , Kuc Rhoda E. , Nyimanu Duuamene , Maguire Janet J. , Lehner Paul J. , Sinha Sanjay , Davenport Anthony P.
Published: January 2021

Patients with cardiovascular comorbidities are more susceptible to severe infection with SARS-CoV-2, known to directly cause pathological damage to cardiovascular tissue. We outline a screening platform using human embryonic stem cell-derived cardiomyocytes, confirmed to express the protein machinery critical for SARS-CoV-2 infection, and a pseudotyped virus system. The method has allowed us to identify benztropine and DX600 as novel inhibitors of SARS-CoV-2 infection.
Abundant secreted hydrolytic enzymes and secondary metabolite gene clusters in genomes of theBotryosphaeriaceaereflect their role as important plant pathogens
Authors: Nagel JH , Wingfield MJ , Slippers B
Published: January 2021

TheBotryosphaeriaceaeare important plant pathogens, but unique in their ability to establish asymptomatic infections that persist for extended periods in a latent state. In this study, we used comparative analyses to consider elements that might shed light on the genetic basis of the interactions of these fungi with their plant hosts. For this purpose, we characterised secreted hydrolytic enzymes, secondary metabolite biosynthetic gene clusters and considered general trends in genomic architecture using all availableBotryosphaeriaceaegenomes, and selected Dothideomycetes genomes. TheBotryosphaeriaceaegenomes were rich in carbohydrate-active enzymes (CAZymes), proteases, lipases and secondary metabolic biosynthetic gene clusters (BGCs) compared to other Dothideomycete genomes. The genomes ofBotryosphaeria, Macrophomina, LasiodiplodiaandNeofusicoccum, in particular, had gene expansions of the major constituents of the secretome, notably CAZymes involved in plant cell wall degradation. TheBotryosphaeriaceaegenomes were shown to have moderate to high GC contents and most had low levels of repetitive DNA. The genomes were not compartmentalized based on gene and repeat densities, but genes of secreted enzymes were slightly more abundant in gene-sparse regions. The abundance of secreted hydrolytic enzymes and secondary metabolite BGCs in the genomes ofBotryosphaeria, Macrophomina, Lasiodiplodia, andNeofusicoccumwere similar to those in necrotrophic plant pathogens, but also endophytes of woody plants. The results provide a foundation for future comparative genomic analyses and hypothesis to explore the mechanisms underlyingBotryosphaeriaceaehost-plant interactions.
Inspiratory muscle training for enhancing repeated-sprint ability: A pilot study
Authors: Rodriguez Ramón F. , Aughey Robert J. , Billaut François , Townsend Nathan E.
Published: January 2021

This pilot study examined the effect of inspiratory muscle training (IMT) on repeated-sprint ability and vastus lateralis reoxygenation. Ten recreationally trained subjects were randomly divided into two groups to complete 4 weeks of IMT or Sham (placebo) training. Pre- and post-intervention, a repeated-sprint ability (RSA) test was performed in both normoxia and hypoxia (FiO2 ≈ 14.5%). Vastus lateralis reoxygenation (VLreoxy), defined as peak to minimum amplitude deoxyhaemoglobin for each sprint/recovery cycle, was assessed during all trials using near-infrared spectroscopy. For total work performed, power analysis revealed that for small, medium and large effects (Cohen’s f), sample sizes of n = 8, 16 and 90 respectively, are required to achieve a power of 80% at an α level of 0.05. Maximal inspiratory mouth pressure increased in IMT by 36.5%, 95% CI [20.9, 61.6] and by 2.7%, 95% CI [−4.46, 8.8] in Sham. No clear difference in the change of work completed during the sprints between groups were observed in normoxia (Sham −0.805 kJ, 95% CI [−3.92, 0.39]; IMT −2.06 kJ, 95% CI [−11.5, 4.96]; P = 0.802), or hypoxia (Sham −3.09 kJ, 95% CI [−7, 0.396]; IMT 0.354 kJ, 95% CI [−1.49, 2.1]; P = 0.802). VLreoxy in IMT increased by 9.34%, 95% CI [5.15, 13.7] in normoxia only. In conclusion, despite a large increase in IMT, this was only associated with a small effect on RSA in our pilot study cohort. Owing to a potentially relevant impact of training the inspiratory musculature, future studies should include a sample size of at least 16-20 to detect moderate to large effects on RSA.
Historical disturbances to rivers appear to constrain contemporary distribution of a river-dependent frog
Authors: Linnell Mark A. , Davis Raymond J.
Published: January 2021

Frogs dependent on lotic environments are sensitive to disturbances that alter the hydrology (e.g., water impoundments), substrate (e.g., debris torrents), and riparian vegetation (e.g., wildfires) of river ecosystems. Although rivers are often very dynamic, disturbances can push environmental baselines outside of narrowly defined ecological tolerances under which a species evolved. Short-lived lotic-dependent organisms, restricted to movements within the water or the riparian corridor, are at risk of local extirpations owing to such disturbances if they fragment and isolate affected populations from recolonizing source populations. In Oregon, USA, the foothill yellow-legged frog (Rana boylii) is at its northernmost range margin and has experienced an approximately 41% range contraction compared to their historical distribution. To inform conservation and management, we used species distribution models to identify environmentally suitable watersheds based on intrinsic baseline environmental variables, and then examined potential effects of human-caused alterations to rivers, including splash dams used to ferry timber downstream prior to 1957, large water impoundments, and adjacency to agricultural croplands. We used machine-learning in program Maxent and three different river layers that varied in extent and location of mapped rivers but contained distinct information to produce species distribution models which we then combined into a single ensemble model. Stream order, annual precipitation, and precipitation frequency were the highest ranked baseline environmental variables in most models. Watersheds with highly suitable baseline conditions in our ensemble model were negatively correlated with anthropogenic disturbances to rivers. Foothill yellow-legged frogs appeared to be sensitive to human-caused disturbances to rivers, perhaps indicative of their narrow ecological tolerance to in-river conditions. We do not anticipate variables in our model to change much through time. Rather, for conservation we identified potential legacy (spash dams) and ongoing human-caused disturbances that are more likely to change conditions for the species in the short- and long-term.
Succinate Dehydrogenase (SDH)-subunit C regulates muscle oxygen consumption and fatigability in an animal model of pulmonary emphysema
Authors: Balnis Joseph , Drake Lisa A. , Vincent Catherine E. , Korponay Tanner C. , Singer Diane V. , Lacomis David , Lee Chun Geun , Elias Jack A. , Singer Harold A. , Jaitovich Ariel
Published: January 2021

Patients with pulmonary emphysema often develop locomotor muscle dysfunction, which is independently associated with disability and higher mortality in that population. Muscle dysfunction entails reduced force-generation capacity which partially depends on fibers’ oxidative potential, yet very little mechanistic research has focused on muscle respiration in pulmonary emphysema. Using a recently established animal model of pulmonary emphysema-driven skeletal muscle dysfunction, we found downregulation of succinate dehydrogenase (SDH) subunit C in association with lower oxygen consumption and fatigue-tolerance in locomotor muscles. Reduced SDH activity has been previously observed in muscles from patients with pulmonary emphysema and we found that SDHC is required to support respiration in cultured muscle cells. Moreover,in-vivogain of SDH function in emphysema animals muscles resulted in better oxygen consumption rate (OCR) and fatigue tolerance. These changes correlated with a larger number of relatively more oxidative type 2-A and 2X fibers, and a reduced amount of 2B fibers. Our data suggests that SDHC is a key regulator of respiration and fatigability in pulmonary emphysema-driven skeletal muscles, which could be impactful to develop strategies aimed at attenuating this comorbidity.
Prioritizing and characterizing functionally relevant genes across human tissues
Authors: Somepalli Gowthami , Sahoo Sarthak , Singh Arashdeep , Hannenhalli Sridhar
Published: January 2021

Knowledge of genes that are critical to a tissue’s function remains difficult to ascertain and presents a major bottleneck toward a mechanistic understanding of genotype-phenotype links. Here, we present the first machine learning model – FUGUE – combining transcriptional and network features, to predict tissue-relevant genes across 30 human tissues. FUGUE achieves an average cross-validation auROC of 0.86 and auPRC of 0.50 (expected 0.09). In three independent datasets, FUGUE accurately distinguishes tissue or cell type-specific genes, significantly outperforming the conventional metric based on tissue-specific expression alone. Comparison of tissue-relevant transcription factors across tissue recapitulate their developmental relationships. Interestingly, the tissue-relevant genes cluster on the genome within topologically associated domains and furthermore, are highly enriched for differentially expressed genes in the corresponding cancer type. We provide the prioritized gene lists in 30 human tissues and an open-source software to prioritize genes in a novel context given multi-sample transcriptomic data.
Performance of a scalable extraction-free RNA-seq method
Authors: Ghimire Shreya , Stewart Carley G. , Thurman Andrew L. , Pezzulo Alejandro A.
Published: January 2021

RNA sequencing enables high-contents/high-complexity measurements in small molecule screens performed on biological samples. Whereas the costs of DNA sequencing and the complexity of RNA-seq library preparation and analysis have decreased consistently, RNA extraction remains a significant bottleneck for RNA-seq of hundreds of samples in parallel. Direct use of cell lysate for RNA-seq library prep is common in single cell RNA-seq but not in bulk RNA-seq protocols. Recently published protocols suggest that direct lysis is compatible with simplified RNA-seq library prep. Here, we evaluate the performance of a bulk RNA-seq library prep protocol optimized for analysis of many samples of adherent cultured cells in parallel. We combine a low-cost direct lysis buffer compatible with cDNA synthesis (“in-lysate cDNA synthesis”) with Smart-3SEQ and examine the effects of calmidazolium and fludrocortisone-induced perturbation of primary human dermal fibroblasts. We compared this method to normalized purified RNA inputs from matching samples followed by Smart-3SEQ or Illumina TruSeq library prep. Our results show that whereas variable RNA inputs for each sample in the in-lysate cDNA synthesis protocol result in variable sequencing depth, this had minimal effect on data quality, measurement of gene expression patterns, or generation of differentially expressed gene lists. We found that in-lysate cDNA synthesis combined with Smart-3SEQ RNA-seq library prep allows generation of high-quality data when compared to library prep with extracted RNA, or when compared to Illumina TruSeq. Our data show that small molecule screens using RNA-seq are feasible at low reagent and time costs.
Pre-diabetes linked microRNA miR-193b-3p targets PPARGC1A and increases lipid accumulation in hepatocytes: potential biomarker of fatty liver disease
Authors: Mollet Inês Guerra , Macedo Maria Paula
Published: January 2021

Distinct plasma microRNA profiles associate with different disease features. Elevated plasma microRNA hsa-miR-193b-3p has been reported in patients with pre-diabetes where early liver dysmetabolism plays a crucial role. MicroRNA target databases revealed that hsa-miR-193b-3p could potentially target PPARGC1A, a master switch transcriptional co-activator that orchestrates the expression of genes involved in multiple metabolic pathways. In this study we evaluated the effects of hsa-miR-193b-3p in the human HepG2 hepatocyte cell line. We show that hsa-miR-193b-3p targets PPARGC1A/PGC1α mRNA 3’UTR and reduces its expression. Overexpression of hsa-miR-193b-3p under hyperglycemia resulted in increased accumulation of intracellular lipid droplets; and quantitative real-time RT-PCR of a panel of 24 genes revealed significant disruption in the expression of genes coordinating glucose uptake, glycolysis, pyruvate metabolism, fatty acid synthesis, fatty acid oxidation, triglyceride synthesis, VLDL secretion, insulin signalling, and mitochondrial biogenesis, dynamics and function. These results providein vitroevidence that microRNA hsa-miR-193b-3p downregulates PPARGC1A/PGC1α, disrupts downstream metabolic pathways and leads to the accumulation of intracellular lipids in hepatocytes. We propose that microRNA hsa-miR-193b-3p may have potential as a clinically relevant plasma biomarker for metabolic associated fatty liver disease in a pre-diabetic dysglycemic context.
An exceptionally preserved euarthropod with unique feather-like appendages from the Chengjiang biota
Authors: Zhai Dayou , Williams Mark , Siveter David J. , Siveter Derek J. , Harvey Thomas H.P. , Sansom Robert S. , Mai Huijuan , Zhou Runqing , Hou Xianguang
Published: January 2021

Micro-CT scanning of the Cambrian euarthropodChuandianella ovatareveals unprecedented three-dimensional soft-part details. It has an elongate uniramous antennule and a short uniramous second appendage, followed by ten homonomous biramous appendages, each comprising a short paddle-shaped exopod and a unique feather-like endopod with at least 27 podomeres each of which bears a long blade-like endite with a short terminal seta. Based on its carapace and previously known soft-part anatomyC. ovatawas compared with the Burgess Shale mandibulate euarthropodWaptia. However,Waptiahas recently been shown to bear specialized head appendages that are interpreted as a mandible and maxillula, posterior to which are four appendages each with five-segmented endopods. In contrast, we interpretChuandianellaas an ‘upper’ stem-group euarthropod that possessed neither a differentiated mandible nor a maxillula.Chuandianellafurther demonstrates that early Cambrian ‘upper’ stem-group euarthropods were experimenting with a range of different limb arrangements and morphologies.
Bidirectional Associations between Short or Long Sleep Duration and Cognitive Function: the China Health and Retirement Longitudinal Study
Authors: Hua Jianian , Sun Hongpeng , Fang Qi
Published: January 2021

IMPORTANCE

The bidirectional association between sleep duration and cognitive function has not been conclusively demonstrated.

OBJECTIVE

To investigate the longitudinal association between sleep duration and cognitive function among middle-aged and elderly Chinese participants.

Design, SETTING, AND PARTICIPANTS

A national representative and prospective longitudinal study in China. 7984 participants aged 45 years and above were assessed at baseline between June 2011 and March 2012 (wave 1) and 2013 (wave 2), 2015 (wave 3) and 2018 (wave4).

MAIN OUCOMES AND MEASURES

Self-reported nighttime sleep duration was evaluated by interview. Cognitive function was evaluated via assessments of global cognition, which reflected the ability of episodic memory, visuospatial construction, calculation, orientation and attention.

Results

Regarding the 7984 participants in wave 4, the mean (SD) age was 64.7 (8.4), 3862 (48.4) were male, and 6453 (80.7) lived in rural area. There were 14981, 11768 (78.6%), 10192 (68.0%), 7984 (53.3%) participants in the four waves of the study, respectively. Latent growth models showed both sleep duration and global cognition worsen over time. Cross-lagged models indicated that long or short sleep duration in the previous wave was associated lower global cognition in the next wave (standardized β=-0.066; 95%CI: −0.073, −0.059; P<0.001; Wave 1 to 2), and lower global cognition in the previous wave was associated with long or short sleep duration in the next wave (standardized β=-0.106; 95%CI: −0.116, −0.096; P<0.001; Wave 1 to 2). Global cognition was probably the major driver in this reciprocal associations.

CONCLUSIONS AND REVELANCE

There were bidirectional associations between long or short sleep duration and cognitive function. Lower cognitive function had a stronger association with worse cognitive function than the reverse. A moderate sleep duration is always recommended. Moreover, attention should be paid on the declined cognition and cognitive therapy among older adults with short or long sleep duration.
Effect of mutations in the SARS-CoV-2 spike protein on protein stability, cleavage, and cell-cell fusion function
Authors: Barrett Chelsea T. , Neal Hadley E. , Edmonds Kearstin , Moncman Carole L. , Thompson Rachel , Branttie Jean M. , Boggs Kerri Beth , Wu Cheng-Yu , Leung Daisy W. , Dutch Rebecca E.
Published: January 2021

The SARS-CoV-2 spike protein (S) is the sole viral protein responsible for both viral binding to a host cell and the membrane fusion event needed for cell entry. In addition to facilitating fusion needed for viral entry, S can also drive cell-cell fusion, a pathogenic effect observed in the lungs of SARS-CoV-2 infected patients. While several studies have investigated S requirements involved in viral particle entry, examination of S stability and factors involved in S cell-cell fusion remain limited. We demonstrate that S must be processed at the S1/S2 border in order to mediate cell-cell fusion, and that mutations at potential cleavage sites within the S2 subunit alter S processing at the S1/S2 border, thus preventing cell-cell fusion. We also identify residues within the internal fusion peptide and the cytoplasmic tail that modulate S cell-cell fusion. Additionally, we examine S stability and protein cleavage kinetics in a variety of mammalian cell lines, including a bat cell line related to the likely reservoir species for SARS-CoV-2, and provide evidence that proteolytic processing alters the stability of the S trimer. This work therefore offers insight into S stability, proteolytic processing, and factors that mediate S cell-cell fusion, all of which help give a more comprehensive understanding of this highly sought-after therapeutic target.
Polymorphism and surface diversity arising from stress-induced transformations – the case of multicomponent forms of carbamazepine
Authors: Schneider-Rauber Gabriela , Arhangelskis Mihails , Bond Andrew D. , Ho Raimundo , Nere Nandkishor , Bordawekar Shailendra , Sheikh Ahmad Y. , Jones William
Published: January 2021

Stress-induced transformations of labile multicomponent organic solids may have a significant impact on industrial manufacturing processes, for example, in the pharmaceutical field. This study considers 15 carbamazepine (CBZ) multicomponent crystal forms, with the aim of identifying the structural and surface features that drive the outcome of thermal stress-induced transformations. Analysis of the crystal structures, and specifically the degree of similarity with the CBZ polymorphs produced by desolvation-like processes, identifies some degree of correlation between structural features. In particular, mutually exclusive supramolecular motifs identified previously within CBZ crystal structures are frequently (but not invariably) preserved, and thereby provide some indication of the anticipated polymorphic outcome. This is broadly consistent with established models relating reactant and product crystal phases. Some of the CBZ multicomponent materials show surface modifications indicative of the formation of a liquid intermediate phase, which provides an alternative dissolution/recrystallization mechanism and different polymorphic outcomes compared to the direct solid–solid transformation pathway. Other cases show intermediates of varying stoichiometry and instances of chemical decomposition. Hence, the product of thermal decomposition is frequently affected by the physical properties of the coformer, such as boiling point and reactivity. This can lead to a dependence on experimental conditions, especially when events such as recrystallization, chemical decomposition of the coformer, solubilization and peritectic melting occur concomitantly. This study highlights that the overall picture is complex, even within this series of closely related materials.
Drivers of site fidelity in ungulates
Authors: Morrison Thomas A. , Merkle Jerod A. , Hopcraft J. Grant C. , Aikens Ellen O. , Beck Jeffrey L. , Boone Randall B. , Courtemanch Alyson B. , Dwinnell Samantha P. , Fairbanks W. Sue , Griffith Brad , Middleton Arthur D. , Monteith Kevin L. , Oates Brendan , Riotte‐Lambert Louise , Sawyer Hall , Smith Kurt T. , Stabach Jared A. , Taylor Kaitlyn L. , Kauffman Matthew J.
Published: January 2021

While the tendency to return to previously visited locations—termed ‘site fidelity’—is common in animals, the cause of this behaviour is not well understood. One hypothesis is that site fidelity is shaped by an animal's environment, such that animals living in landscapes with predictable resources have stronger site fidelity. Site fidelity may also be conditional on the success of animals’ recent visits to that location, and it may become stronger with age as the animal accumulates experience in their landscape. Finally, differences between species, such as the way memory shapes site attractiveness, may interact with environmental drivers to modulate the strength of site fidelity.

We compared inter‐year site fidelity in 669 individuals across eight ungulate species fitted with GPS collars and occupying a range of environmental conditions in North America and Africa. We used a distance‐based index of site fidelity and tested hypothesized drivers of site fidelity using linear mixed effects models, while accounting for variation in annual range size.

Mule deer Odocoileus hemionus and moose Alces alces exhibited relatively strong site fidelity, while wildebeest Connochaetes taurinus and barren‐ground caribou Rangifer tarandus granti had relatively weak fidelity. Site fidelity was strongest in predictable landscapes where vegetative greening occurred at regular intervals over time (i.e. high temporal contingency). Species differed in their response to spatial heterogeneity in greenness (i.e. spatial constancy). Site fidelity varied seasonally in some species, but remained constant over time in others. Elk employed a ‘win‐stay, lose‐switch’ strategy, in which successful resource tracking in the springtime resulted in strong site fidelity the following spring. Site fidelity did not vary with age in any species tested.

Our results provide support for the environmental hypothesis, particularly that regularity in vegetative phenology shapes the strength of site fidelity at the inter‐annual scale. Large unexplained differences in site fidelity suggest that other factors, possibly species‐specific differences in attraction to known sites, contribute to variation in the expression of this behaviour.

Understanding drivers of variation in site fidelity across groups of organisms living in different environments provides important behavioural context for predicting how animals will respond to environmental change.
Towards a Theory of Network Facilitation: A Microfoundations Perspective on the Antecedents, Practices and Outcomes of Network Facilitation
Authors: Mueller Elisabeth F.
Published: January 2021

Firms cooperate in inter‐firm networks to foster their competitiveness and improve their innovation outcomes. In many cases, network facilitators who are either embedded in a lead firm or a third‐party organization manage the cooperation among the network firms. This qualitative study adopts a microfoundations perspective to investigate the behavioural antecedents of the network facilitators, their facilitation practices and the related network‐level outcomes. Results show that lead‐firm facilitators more strongly invest in trust‐building measures since they are considered deficient in benevolence and integrity. Without these investments, they run the risk that conflicts of interest hinder the stimulation of positive network‐level outcomes. Third‐party facilitators, by contrast, enjoy certain credits of trust and focus on balancing firm interests from the network's activation, but need to invest in enhancing their competencies and skills with regard to the industry the firms operate in. The findings contribute to developing a theory of network facilitation by providing a nuanced understanding of how network‐level outcomes can be reduced to individual‐level factors.
Accounting for uncertainty in policy decision making: Improving access to pediatric dental care
Authors: Curry Stewart , Serban Nicoleta
Published: January 2021

Objective

To introduce a statistical inference framework for policy decision making on access to pediatric dental care.

Data Sources

Secondary data were collected for the state of Colorado for year 2019.

Study Design

The access model was an optimization model, matching the demand (patients) and supply (providers) of dental care. Sampling distributions of model inputs were specified using hierarchical Bayesian models, with hyperparameters informed by prior information derived from multiple data sources. Simultaneous inference was applied to identify areas for access improvement. The model was applied to make inference on the pediatric dental care in Colorado, accounting for financial access, differentiated into public (Medicaid and CHIP), private (commercial and out‐of‐pocket), and without financial access.

Data Collection/Extraction Methods

Multiple data sources informed the access measurement approach including: 2017 American Community Survey, 2019 Colorado Dental Board, and 2019 National Provider Plan and Enumeration System, 2019 InsureKidsNow.gov among others.

Principal Findings

The median access measure (travel distance) was greater than the Colorado access standards in 16.9% and 65.1% of census tracts for children with private financial access and publicly insured, respectively. Accounting for uncertainty (confidence level 99%), these percentages decreased to 14.6% and 25.6%, respectively, with mostly suburban and rural tracts failing to meet the standards. The median disparity for Medicaid and CHIP versus private financial access was greater than 5 miles in 84.5% and 81.6% of census tracts, respectively. Accounting for uncertainty (confidence level 99%), these percentages declined to 19.5% and 10.5%, respectively, with significant disparities around the metropolitan areas.

Conclusions

While many communities failed to meet access standards, when accounting for uncertainty, most urban ones did not fail. Disparities in spatial access between publicly and privately insured were most acute in urban communities. Medicaid insured experienced higher disparities than CHIP insured; those differences were not identified when not accounting for uncertainty.
Upregulation of SIX4 indicates poor clinical outcome and promotes tumor growth and cell metastasis in esophageal squamous cell carcinoma
Authors: Li Yanping , Jiang Xiaomei , Yan Xiaoyan , Wang Yanzheng
Published: January 2021

Background

The role of sine oculis homeobox 4 (SIX4) has been found in some malignant tumors. However, there have been few studies on the function of SIX4 in esophageal squamous cell carcinoma (ESCC). This study aimed to explore the regulatory mechanism of SIX4 in ESCC.

Methods

RT‐qPCR and Western blot analysis were used to measure mRNA and protein expression. The function of SIX4 was investigated using CCK‐8, colony formation, flow cytometry, wound healing and transwell assays. A mouse xenograft tumor assay was designed to perform in vivo experiments.

Results

SIX4 was upregulated in ESCC and indicated poor clinical outcomes in ESCC patients. Functionally, knockdown of SIX4 inhibited cell proliferation and induced apoptosis in ESCC. In addition, the silencing of SIX4 inhibited cell migration, invasion and EMT in ESCC. More importantly, upregulation of SIX4 could activate the PI3K/AKT pathway in ESCC cells and promote tumor growth in vivo.

Conclusions

Upregulation of SIX4 indicates poor clinical outcomes in ESCC patients and promotes tumor growth and cell metastasis in ESCC.
Use and outcome of empiric echinocandins in critically ill patients
Authors: Ylipalosaari Pekka , Ala‐Kokko Tero I. , Koskenkari Juha , Laurila Jouko J. , Ämmälä Sirpa , Syrjälä Hannu
Published: January 2021

Background

Echinocandins are recommended as a first‐line empiric treatment for fungal infections of patients in an intensive care unit (ICU) with critical illness. The primary aim of the study was to compare outcomes among ICU patients treated with empiric anidulafungin (ANI), caspofungin (CASPO), or micafungin (MICA).

Methods

A retrospective cohort study in a mixed adult ICU. Patient demographics, reason for ICU admission, ICU risk scores and organ support therapies were analyzed. Outcome parameters included ICU and hospital stay, 30‐day mortality and 1‐year mortality.

Results

Empiric echinocandin therapy was given to 367 patients (ANI; 73 patients, CASPO; 84 patients, and MICA; 210 patients) with a median duration of 3 days in an ICU. Patient median age was 60.7 years. As a first‐line therapy, 52% of patients received fluconazole. Positive Candida cultures were found in the following samples: blood, 16 (4.4%); central line, 27 (7.4%); deep site, 92 (25.1%). Median ICU stay (ANI 6.4 days, CASPO 5.3 days, MICA 8.1 days), hospital stay (ANI 33 days, CASPO 30 days, MICA 30 days), 30‐day mortality (ANI 27%, CASPO 32%, MICA 32%), and 1‐year mortality (ANI 33%, CASPO 44%, MICA 45%) did not differ between the groups . The cost of antifungal therapy during the ICU period was similar in the three echinocandin groups (ANI; €1 872, CASPO; €1 799, and MICA; €1783).

Conclusion

Our results show that ICU, hospital stay, and mortality (hospital, 30‐day and 1‐year) did not differ among patients with empiric anidulafungin, caspofungin, or micafungin treatment in a mixed adult ICU.
Boat disturbance affects the acoustic behaviour of dolphins engaged in a rare foraging cooperation with fishers
Authors: Pellegrini A. Y. , Romeu B. , Ingram S. N. , Daura‐Jorge F. G.
Published: January 2021

Acoustic behaviour is a key component of specialized foraging tactics for many aquatic species, especially cetaceans. However, in recent decades the natural environment has been increasingly exposed to a variety of anthropogenic noise sources, with the potential to impact natural foraging specializations dependent on acoustic communication. Here we evaluated whether boat noise has the potential to impact a rare foraging tactic used by individuals from a small population of the vulnerable Lahille’s bottlenose dolphin (Tursiops truncatus gephyreus) specialized in cooperation with artisanal fishers in southern Brazil. We tested whether the presence of boats changed the acoustic behaviour of dolphins when engaged in this cooperative foraging. We found that whistles and echolocation click rates were lower when boats were present, suggesting that cooperative foraging may potentially be reduced or interrupted by the presence of boats. Whistle parameters changed in response to the number, type and speed of boats, indicating a behavioural change and acoustic masking. Locally, our results reinforce the need for boat traffic regulations to minimize their impacts on these endangered dolphins and their rare cooperative tactic. From a broad perspective, we demonstrate how nonlethal impacts such as vessel disturbance can manifest subtle changes in animals’ natural behaviour and, in this case, present an insidious threat to a unique foraging specialization.
A continental assessment of diurnality in frog calling behaviour
Authors: Callaghan Corey T. , Rowley Jodi J. L.
Published: January 2021

Acoustic signalling is evolutionarily important, influencing sexual selection and serving as a premating isolation mechanism. There is a strong evolutionary basis for acoustic signalling to occur nocturnally across many terrestrial vertebrate groups including mammals, reptiles and amphibians. Within some of these groups, there is a general assumption that ‘most taxa are nocturnal’ in their acoustic signalling, and this is a particularly strongly held view for most frogs. Here we challenge this well‐accepted notion by quantifying diurnal calling behaviour in Australian frogs, leveraging a continental‐wide citizen science dataset. Of 196 species present in the citizen science dataset, 140 (71%) were recorded at least once during the day. Of the most commonly observed species (i.e. species with at least 150 calls recorded in the database), there were surprisingly high rates of diurnal calling: 14 species had >25% of their calls recorded during the day. We also found that the relative rate of diurnal calling in frogs showed a strong phylogenetic signal, suggesting that the plasticity in calling behaviour as it relates to time of the day is strongly evolutionarily conserved. Our results highlight a suite of ecological and evolutionary questions that are worthy of further investigation.
Quality of recovery scores in deep serratus anterior plane block vs. sham block in ambulatory breast cancer surgery: a randomised controlled trial
Authors: Abdallah F. W. , Patel V. , Madjdpour C. , Cil T. , Brull R.
Published: January 2021

Deep serratus anterior plane block has been widely adopted as an analgesic adjunct for patients undergoing breast surgery, but robust supporting evidence of efficacy is lacking. We randomly allocated 40 patients undergoing simple or partial mastectomy with sentinel node biopsy to receive either a pre‐operative deep serratus anterior plane block (serratus group) or a placebo injection (sham group), in addition to systemic analgesia. The primary outcome measure was the quality of recovery score at discharge, as assessed by the quality of recovery‐15 questionnaire at various time‐points. Secondary analgesic outcomes included: pain severity; postoperative opioid consumption; opioid‐related side‐effects; patient satisfaction up to 7 days postoperatively; and persistent postoperative pain up to 3 months after surgery. All patients who were recruited completed the study. There were no differences in the quality of recovery‐15 scores between patients in the serratus and control groups, with mean (SD) scores of 96 (14) and 102 (20) for the control and serratus groups, respectively. We were also unable to detect differences in any of the secondary analgesic outcomes examined. The addition of a deep serratus anterior plane block to systemic analgesia does not enhance quality of recovery in patients undergoing ambulatory breast cancer surgery.
The #Enzian classification: A comprehensive non‐invasive and surgical description system for endometriosis
Authors: Keckstein Jörg , Saridogan Ertan , Ulrich Uwe A. , Sillem Martin , Oppelt Peter , Schweppe Karl W. , Krentel Harald , Janschek Elisabeth , Exacoustos Caterina , Malzoni Mario , Mueller Michael , Roman Horace , Condous George , Forman Axel , Jansen Frank W. , Bokor Attila , Simedrea Voicu , Hudelist Gernot
Published: January 2021

Advances in preoperative diagnostics as well as in surgical techniques for the treatment of endometriosis, especially for deep endometriosis, call for a classification system, that includes all aspects of the disease such as peritoneal endometriosis, ovarian endometriosis, deep endometriosis, and secondary adhesions. The widely accepted revised American Society for Reproductive Medicine classification (rASRM) has certain limitations because of its incomplete description of deep endometriosis. In contrast, the Enzian classification, which has been implemented in the last decade, has proved to be the most suitable tool for staging deep endometriosis, but does not include peritoneal or ovarian disease or adhesions. To overcome these limitations, a comprehensive classification system for complete mapping of endometriosis, including anatomical location, size of the lesions, adhesions and degree of involvement of the adjacent organs, that can be used with both diagnostic and surgical methods, has been created through a consensus process and will be described in detail—the #Enzian classification.
Heart‐rate agreement between ECG and a new, wireless device during early skin‐to‐skin contact
Authors: Lavizzari Anna , Falgari Roberta , Pesenti Nicola , Colnaghi Mariarosa , Colombo Lorenzo , Zanotta Lidia , Sannino Patrizio , Plevani Laura , Mosca Fabio
Published: January 2021

Aim

To assess the agreement of heart rate (HR) between the new device – a fabric jacket for neonates, with integrated sensors detecting ECG signals and a Bluetooth connection to a computer (ComfTech, HOWDY) – and the clinical reference, ECG, during the skin‐to‐skin contact (SSC) in the first 2 h after birth, for the potential use of early detection of Sudden and Unexpected Postnatal Collapse (SUPC).

Methods

We enrolled newborns ≥35+0 weeks of gestation, with Apgar score >8 at 5 min in a prospective, observational study in the delivery room, excluding infants with need for resuscitation, clinical instability or major malformations. We assessed HR within 20 min after birth by both devices simultaneously: the index test ComfTech HOWDY and the standard ECG (Vita Guard VG 3100, Getemed). We compared HR between the two methods at 0, 15, 30, 45, 60, 90 and 120 min by the Bland–Altman plot.

Results

We included 60 infants. The mean difference between the methods was −1.3 bpm, 95%LoA −12.4 to 9.7 bpm. Spearman rank correlation coefficient ρ = −0.06.

Conclusion

ComfTech HOWDY presents reliable agreement with the ECG and might assist in identifying infants at risk for SUPC.
Geographic variation in female body size and clutch size of the lizard Sceloporus variabilis (Squamata: Phrynosomatidae) in Mexico
Authors: Ramírez‐Bautista Aurelio , Cruz‐Elizalde Raciel , Stephenson Barry P. , Hernández‐Salinas Uriel
Published: January 2021

The body size and reproductive characteristics in populations of the same species is influenced by environmental and ecological factors. In this study, we analysed the relationship of environmental factors, morphological characters (body size and mass) and reproductive traits (clutch size) of females from 13 populations of Sceloporus variabilis. Results showed variation in snout‒vent length (SVL), body mass and clutch size among populations. An ANCOVA between SVL and clutch size showed an increase of the latter in females from Alvarado and Valle Nacional; ANCOVA between body mass and SVL revealed an increase in body mass in most populations. A canonical correlation analysis showed a positive relationship between SVL, body mass, and clutch size with elevation and precipitation, but not with temperature. Future studies should assess the effect of seasonality and food resource availability on reproductive investment among populations of S. variabilis to determine whether these characteristics are a function of differences in key ecological factors (e.g. availability of resources and seasonality) associated with each population, and determine the causes of geographic variation in morphological and life history characteristics among populations.
Poor mobilization of autologous CD34+ peripheral blood stem cells in haematology patients undergoing autologous stem cell transplantation is associated with the presence of variants in genes implicated in clonal haematopoiesis of indeterminant potential
Authors: Gifford Grace , Hesson Luke , Wong Jason W. H. , Carroll Adam , Gabrielli Sara , Bai LiJun , Xia Wei , Stevenson William , Greenwood Matthew
Published: January 2021

Clonal haematopoiesis of indeterminant potential (CHIP) increases in frequency with age. The effect of CHIP on the mobilization of autologous CD34+ peripheral blood stem cells (PBSC) has not been reported. This study uses a DNA‐based targeted candidate gene approach to identify the presence of somatic mutations in ASXL1, DNMT3A, JAK2, SF3B1, TET2 and TP53 in CD34+ haematopoietic progenitor cell‐apheresis products of 96 patients who undergo PBSC mobilization for autologous stem cell transplantation (ASCT). Variants were identified in a significantly greater proportion of patients who experience poor CD34+ PBSC mobilization. A DNA‐based targeted candidate gene array is able to predict poor CD34+ PBSC mobilization and may be deployed pre‐emptively to minimize mobilization and graft failures.
The use of Intensive Interaction within a Positive Behavioural Support framework
Authors: McKim Jules , Samuel Judith
Published: January 2021

Accessible summary

Intensive Interaction is an approach that supports the development of essential communication skills, and social and emotional relationships.

Positive Behavioural Support (PBS) is a framework for developing the quality of life for people who use challenging behaviour.

Intensive Interaction may be used in all the phases within a PBS framework. No previous articles on the use of Intensive Interaction within PBS could be found.

The use of Intensive Interaction in PBS is described for three people.

Background

Positive Behavioural Support (PBS) provides an overarching framework for supporting quality‐of‐life improvements for people who use challenging behaviour. Rapport, or the lack of it, is well understood as a setting factor for some challenging behaviours. Intensive Interaction is an approach that, among other possible outcomes, can develop rapport and feelings of safety, security and connection.

Method

Within an NHS Trust, the Intensive Interaction Service works in partnership with the Intensive Support Team. We present case descriptions of people who used challenging behaviour and received Intensive Interaction support. Changes are described using staff and family interview data. The Intensive Interaction techniques that helped develop rapport at each PBS phase are described.

Results

Intensive Interaction was used in all PBS phases. It played a role in preventing placement breakdown for one individual.

Conclusion

Intensive Interaction should be considered at initial assessment within PBS so that immediate and important improvements can be made to the person's social and communication experience. It is hoped that Intensive Support Services and all PBS practitioners will use it.
Efficient expression of concatenated α1β2δ and α1β3δ GABAA receptors, their pharmacology and stoichiometry
Authors: Liao Vivian Wan Yu , Chebib Mary , Ahring Philip Kiær
Published: January 2021

Background and Purpose

GABAA receptors containing δ‐subunits are notorious for being difficult to study in vitro due to heterogeneity of expressed receptor populations and low GABA‐evoked current amplitudes. Thus, there are some published misconceptions and contradictory conclusions made regarding the pharmacology and stoichiometry of δ‐containing receptors. The aim of this study was to obtain robust homogenous expression of α1βδ receptors for in‐depth investigation.

Experimental Approach

Novel δ‐containing pentameric concatenated constructs were designed. The resulting α1β2δ and α1β3δ GABAA receptor concatemers were investigated by two‐electrode voltage‐clamp electrophysiology using Xenopus laevis oocytes.

Key Results

First, while homogenous α1βδ GABAA receptor pools could not be obtained by manipulating the ratio of injected cRNAs of free α1, β2/3, and δ subunits, concatenated pentameric α1β2δ and α1β3δ constructs resulted in robust expression levels of concatemers. Second, by using optimised constructs that give unidirectional assembly of concatemers, we found that the δ subunit cannot directly participate in GABA binding and receptor activation. Hence, functional δ‐containing receptors are likely to all have a conventional 2α:2β:1δ stoichiometry arranged as βαβαδ when viewed counterclockwise from the extracellular side. Third, α1β2/3δ receptors were found to express efficiently in X. laevis oocytes but have a low estimated open probability of ~0.5% upon GABA activation. Because of this, these receptors are uniquely susceptible to positive allosteric modulation by, for example, neurosteroids.

Conclusion and Implications

Our data answer important outstanding questions regarding the pharmacology and stoichiometry of α1δ‐containing GABAA receptors and pave the way for future analysis and drug discovery efforts.