bluuebunny/crossref_metadata_2025 huggingface dataset:
Referral Patterns of Central Retinal Artery Occlusion to an Academic Center Affiliated With a Stroke Center
Authors: Flowers Alexis M. , Chan Wesley , Meyer Benjamin I. , Bruce Beau B. , Newman Nancy J. , Biousse Valérie
Published: November 2021

Background:

Central retinal artery occlusion (CRAO) is a medical emergency, and patients who present acutely should be immediately referred to the nearest stroke center. We evaluated practice patterns for CRAO management at one academic center over the last decade.

Methods:

This was a retrospective study on all adult patients diagnosed with a CRAO seen at one tertiary hospital and outpatient clinic affiliated with a comprehensive stroke center (“our institution”) from 2010 to 2020. Our electronic medical records were searched for CRAO diagnoses, and patient medical records were reviewed. The exclusion criteria were incorrect diagnosis, unclear diagnosis, historical CRAO, or satellite clinic location. Demographics, distance and time to presentation to our institution, number and type of prior providers seen, diagnostic tests performed, and treatments provided were collected. Summary statistics of median, mean, and frequency were calculated and reported with measures of variance (interquartile range [IQR], ranges). F, Tukey, and Fisher exact tests were used for comparisons.

Results:

We included 181 patients with a diagnosis of CRAO (80 [44.2%] women; median age 69 years [range 20–101]). The median distance from patient's home to our institution was 27.8 miles (IQR 15.5–57.4; range 2.4–930). The median time from visual loss to presentation at our institution was 144 hours (IQR 23–442 hours, range 0.5–2,920) from 2010 to 2013, 72 hours (IQR 10.5–372 hours, range 0–13,140) from 2014 to 2016, and 48 hours (IQR 7–180 hours, range 0–8,030) from 2017 to 2020 (P = 0.07). 91/181 (50%) patients presented to an outpatient provider. 73/181 (40%) presented to an emergency department. Eighty-six percent presented within 1 week of visual loss onset, and rates of comprehensive inpatient evaluation for acute CRAO improved from 44% in 2010–2013 to 82% in 2017–2020 (P < 0.01).

Conclusions:

Patients with CRAO often present late and only after evaluation by multiple outpatient providers. Improvement has occurred over the past decade, but delays underscore the barriers to performing clinical trials evaluating very acute treatments for CRAO. Educational interventions for healthcare providers and patients are necessary.
In situ
polyaniline coating of Prussian blue as cathode material for sodium-ion battery
Authors: luo Yu , Yang Lingxiao , Liu Qing , Yan Youwei
Published: November 2021

Prussian blue (PB) has great potential for use as a sodium cathode material owing to its high working potential and cube frame structure. Herein, this work reports a two-step method to synthesize PB with ascorbic acid as the ball-milling additive, which improves the electrochemical rate performance of PB during the traditional co-precipitation method. The obtained PB sample exhibited a superior specific capability (113.3 mAh g
−1
even at 20 C, 1 C = 170 mA g
−1
) and a specific capacity retention of 84.8% after 100 cycles at 1 C rate. In order to enhance the cycling performance of the PB, an
in situ
polyaniline coating strategy was employed in which aniline was added into the electrolyte and polymerized under electrochemical conditions. The coated anode exhibited a high specific capacity retention of 62.7% after 500 cycles, which is significantly higher than that of the non-coated sample, which only remains 40.1% after 500 cycles. This development has shown a great potential as a low-cost, high-performance and environment-friendly technology for large-scale industrial application of PB.
Simplifying the OpenFlexure microscope software with the web of things
Authors: Collins Joel T. , Knapper Joe , McDermott Samuel J. , Ayazi Filip , Bumke Kaspar E. , Stirling Julian , Bowman Richard W.
Published: November 2021

We present the OpenFlexure Microscope software stack which provides computer control of our open source motorised microscope. Our diverse community of users needs both graphical and script-based interfaces. We split the control code into client and server applications interfaced via a web API conforming to the W3C Web of Things standard. A graphical interface is viewed either in a web browser or in our cross-platform Electron application, and gives basic interactive control including common operations such as Z stack acquisition and tiled scanning. Automated control is possible from Python and M
atlab
, or any language that supports HTTP requests. Network control makes the software stack more robust, allows multiple microscopes to be controlled by one computer, and facilitates sharing of equipment. Graphical and script-based clients can run simultaneously, making it easier to monitor ongoing experiments. We have included an extension mechanism to add functionality, for example controlling additional hardware components or adding automation routines. Using a Web of Things approach has resulted in a user-friendly and extremely versatile software control solution for the OpenFlexure Microscope, and we believe this approach could be generalized in the future to make automated experiments involving several instruments much easier to implement.
Excess dietary sugar impairs colonic epithelial regeneration in response to damage
Authors: Burr Ansen H.P. , Ji Junyi , Ozler Kadir , Eskiocak Onur , Yueh Brian , Menk Ashley V. , Costa Ana S.H. , Rittenhouse Natalie , Marshall Chris W. , Chiaranunt Pailin , Mullinax Lauren , Overacre-Delgoffe Abigail , Cooper Vaughn S. , Poholek Amanda C. , Delgoffe Greg M. , Beyaz Semir , Hand Timothy W.
Published: November 2021

The colonic epithelium requires continuous renewal by intestinal stem cells (ISCs) to restore the barrier after damage and proliferation of epithelial cells is modulated by dietary metabolites. We demonstrate that mice fed a high sugar diet failed to repair colonic barrier damage, resulting in increased intestinal pathology. Culturing ISCs in excess sugar limited murine and human colonoid development, indicating that dietary sugar can directly affect colonic epithelial proliferation. Similarly, in vivo lineage tracing experiments and transcriptomic analysis indicated that dietary sugar impeded the proliferative potential of ISCs. ISCs and their immediate daughter cells predominantly rely on mitochondrial respiration for energy; however, metabolic analysis of colonic crypts revealed that a high sugar diet primed the epithelium for glycolysis without a commensurate increase in aerobic respiration. Colonoids cultured in high-glucose conditions accumulated glycolytic metabolites but not TCA cycle intermediates, indicating that the two metabolic pathways may not be coupled in proliferating intestinal epithelium. Accordingly, biochemically inducing pyruvate flux through the TCA cycle by inhibiting pyruvate dehydrogenase kinase rescued sugar-impaired colonoid development. Our results indicate that excess dietary sugar can directly inhibit epithelial proliferation in response to damage and may inform diets that better support the treatment of acute intestinal injury.
The evolution of color naming reflects pressure for efficiency: Evidence from the recent past
Authors: Zaslavsky Noga , Garvin Karee , Kemp Charles , Tishby Naftali , Regier Terry
Published: November 2021

It has been proposed that semantic systems evolve under pressure for efficiency. This hypothesis has so far been supported largely indirectly, by synchronic cross-language comparison, rather than directly by diachronic data. Here, we directly test this hypothesis in the domain of color naming, by analyzing recent diachronic data from Nafaanra, a language of Ghana and Côte d’Ivoire, and comparing it with quantitative predictions derived from the mathematical theory of efficient data compression. We show that color naming in Nafaanra has changed over the past four decades while remaining near-optimally efficient, and that this outcome would be unlikely under a random drift process that maintains structured color categories without pressure for efficiency. To our knowledge, this finding provides the first direct evidence that color naming evolves under pressure for efficiency, supporting the hypothesis that efficiency shapes the evolution of the lexicon.
BamToCov: an efficient toolkit for sequence coverage calculations
Authors: Birolo Giovanni , Telatin Andrea
Published: November 2021

Many genomics applications requires the calculation of nucleotide coverage of a reference or counting how many reads maps in a reference region.

Here we present BamToCov, a suite of tools for rapid and flexible coverage calculations relying on a memory efficient algorithm and designed for flexible integration in bespoke pipelines. The tools of the suite will process sorted BAM or CRAM files, allowing to extract coverage information using different filtering approaches.

BamToCov tools, unlike existing tools already available, have been developed to require a minimum amount of memory, to be easily integrated in workflows, and to allow for strand-specific coverage analyses. The unique coverage calculation algorithm makes it the ideal choice for the analysis of long reads alignments. The programs and their documentation are freely available at https://github.com/telatin/bamtocov.
Not Quite All in Our Head: Intervention is a Better Predictor of tDCS Mind-Wandering Effects than Subjective Beliefs About Experimental Results
Authors: Gordon Matilda S. , Dux Paul E. , Filmer Hannah L.
Published: November 2021

Background

Establishing adequate blinding for non-invasive brain stimulation research is a topic of extensive debate, especially regarding the efficacy of sham control methods for transcranial direct current stimulation (tDCS) studies. Fassi and Cohen Kadosh [1] assessed the influence of subjective participant belief regarding stimulation type (active or sham) and dosage on behaviour using data from Filmer et al. [2] who applied five stimulation protocols (anodal 1.0mA, cathodal 1.0mA, cathodal 1.5mA, cathodal 2.0mA and sham) to assess the neural substrates of mind wandering. Fassi and Cohen Kadosh [1] concluded that subjective belief drove the pattern of results observed by Filmer et al. [2].

Objective

Fassi and Cohen Kadosh [1] did not assess the key contrast between conditions in Filmer et al. (2019) – 2mA vs sham – rather they examined all stimulation conditions. Here, we consider the relationship between objective and subjective intervention in this key contrast.

Methods

We replicated the analysis and findings of both Filmer et al. [2] and Fassi and Cohen Kadosh [1] before assessing 2mA vs. sham via Bayesian ANOVA on subjective belief regarding stimulation type and dosage.

Results

Our results support objective intervention as the strongest predictor of stimulation effects on mind-wandering when 2mA vs sham was examined, over and above that of subjective intervention.

Conclusions

The conclusions made by Filmer et al. [2] are confirmed. However, it is important to control for and understand the possible effects of subjective beliefs in sham-controlled studies. Best practice to prevent these issues remains the inclusion of active control conditions.
Evaluation of methods for estimating coalescence times using ancestral recombination graphs
Authors: Y C Brandt Debora , Wei Xinzhu , Deng Yun , Vaughn Andrew H. , Nielsen Rasmus
Published: November 2021

The ancestral recombination graph (ARG) is a structure that describes the joint genealogies of sampled DNA sequences along the genome. Recent computational methods have made impressive progress towards scalably estimating whole-genome genealogies. In addition to inferring the ARG, some of these methods can also provide ARGs sampled from a defined posterior distribution. Obtaining good samples of ARGs is crucial for quantifying statistical uncertainty and for estimating population genetic parameters such as effective population size, mutation rate, and allele age. Here, we use standard neutral coalescent simulations to benchmark the estimates of pairwise coalescence times from three popular ARG inference programs: ARGweaver, Relate, and tsinfer+tsdate. We compare 1) the true coalescence times to the inferred times at each locus; 2) the distribution of coalescence times across all loci to the expected exponential distribution; 3) whether the sampled coalescence times have the properties expected of a valid posterior distribution. We find that inferred coalescence times at each locus are most accurate in ARGweaver, and often more accurate in Relate than in tsinfer+tsdate. However, all three methods tend to overestimate small coalescence times and underestimate large ones. Lastly, the posterior distribution of ARGweaver is closer to the expected posterior distribution than Relate's, but this higher accuracy comes at a substantial trade-off in scalability. The best choice of method will depend on the number and length of input sequences and on the goal of downstream analyses, and we provide guidelines for the best practices.
A Novel Ex Vivo Peritoneal Model to Investigate Mechanisms of Peritoneal Metastasis in Gastric Adenocarcinoma
Authors: Ng Deanna , Ali Aiman , Lee Kiera , Eymael Denise , Abe Kento , Luu Shelly , Kazazian Karineh , Brar Savtaj , Conner James , Magalhaes Marco , Swallow Carol J
Published: November 2021

Peritoneal metastases (PM) portend limited survival in patients with Gastric Adenocarcinoma (GCa), and strategies to prevent and/or more effectively treat PM are needed. Existing models are limited in recapitulating key elements of the peritoneal metastatic cascade. To explore the underlying cellular and molecular mechanisms of PM, we have developed an ex vivo human peritoneal explant model. Fresh peritoneal tissue samples were obtained from patients undergoing abdominal surgery and suspended, mesothelial layer down but without direct contact, above a monolayer of red-fluorescent stained AGS human GCa cells for 24hrs, then washed and cultured for a further 3 days. Implantation and invasion of GCa cells within the explant were examined using real-time confocal fluorescence microscopy. Superficial implantation of AGS GCa cells within the mesothelial surface was readily detected, and colonies expanded over 3 days. To investigate the sensitivity of the model to altered GCa cellular implantation, we stably transfected AGS cells with E-Cadherin, restoring the E-Cadherin that they otherwise lack. This markedly suppressed implantation and invasion of AGS cells into the submesothelial mesenchymal layer. Here we show that this ex vivo human peritoneal explant model is responsive to manipulation of genetic factors that regulate peritoneal implantation and invasion by GCa cells, with reproducible results.
A Post-hurricane Quantitative Assessment of the Red-bellied Racer (Alsophis rufiventris) on Saba and Comparison with St. Eustatius
Authors: Madden Hannah , Mielke Lara
Published: November 2021

We estimated occupancy, abundance (lambda), detection probability, density/ha and abundance of a regionally endemic snake in the Colubrid family on the Dutch Caribbean island of Saba in 2021, four years after hurricanes Irma and Maria impacted the island. Line transect surveys were conducted at 74 sites covering 6.7 ha. The proportion of sites occupied was estimated at 0.74 (min 0.48, max 0.90), with occupancy varying between vegetation types and across elevational gradients. Similarly, lambda was estimated at 1.61 (min 0.7, max 3.7) but varied between vegetation types and elevational gradients. Detection probability was estimated at 0.15 (min 0.10, max 0.21). Using Distance sampling, we estimated 10.9 (min 7.3, max 16.2) racers/ha, with a total population estimate of 4,917 (min 2,577, max 6,362) across the entire study region (438.6 ha.) Based on anecdotal observations from Saban residents and prior literature describing the pre-hurricane population as “abundant” (at least 2.0 racers/hour), we posit that the population experienced a hurricane-induced decline but may have since recovered, though not to previous levels (1.28 racers/hour). Nevertheless, our results suggest that racer densities on Saba are currently higher than those on St. Eustatius. Despite this, given the species’ extremely limited extant range and the presence of invasive species on both islands, prevention of local extirpation should be a high conservation priority.
Collective chemotaxis in a Voronoi model for confluent clusters
Authors: Lawson-Keister E. , Manning M. L
Published: November 2021

Collective chemotaxis, where single cells cannot climb a biochemical signaling gradient but clusters of cells can, has been observed in different biological contexts, including confluent tissues where there are no gaps or overlaps between cells. Although particle-based models have been developed that predict important features of collective chemotaxis, the mechanisms in those models depend on particle overlaps, and so it remains unclear if they can explain behavior in confluent systems. Here, we develop an open-source code that couples a 2D Voronoi simulation for confluent cell mechanics to a dynamic chemical signal that can diffuse, advect, and/or degrade, and use the code to study potential mechanisms for collective chemotaxis in cellular monolayers. We first study the impact of advection on collective chemotaxis, and delineate a regime where advective terms are important. Next, we investigate two possible chemotactic mechanisms, contact inhibition of locomotion and heterotypic interfacial tension, and demonstrate that both can drive collective chemotaxis in certain parameter regimes. We further demonstrate that the scaling behavior of cluster motion is well-captured by simple analytic theories.

1

Statement of Significance

The ability of cell collectives to respond to biochemical signals, called collective chemotaxis, is crucial for many important processes including embryonic development and wound healing. We developed an open-source computational model that couples biochemical signaling gradients to confluent cell layers, where there are no gaps between cells. Our model demonstrates that two experimentally observed local cell behaviors – neighbor-induced changes to interfacial tension or a tendency of cells to repel one another after they come into contact – can drive collective chemotaxis. We also highlight a regime in which the motion of migrating cells can alter the gradient.
RNA-guidedAsCas12a- andSpCas9-catalyzed knockout and homology directed repair of theomega-1locus of the human blood fluke,Schistosoma mansoni
Authors: Ittiprasert Wannaporn , Chatupheeraphat Chawalit , Mann Victoria H. , Li Wenhui , Miller André , Ogunbayo Taiwo , Tran Kenny , Alrefaei Yousef , Mentink-Kane Margaret , Brindley Paul J.
Published: November 2021

We compared the efficiency of gene knockout (KO) and precision of insertion (knock-in, KI) of the RNA-guidedAsCas12a nuclease ofAcidaminococcussp. with that ofSpCas9 fromStreptococcus pyogenes, aiming to enhance the functional genomics toolkit forSchistosoma mansoni. Programmed DNA cleavages catalyzed by Cas12a and Cas9 result in staggered and blunt ended strand breaks, respectively. TTTV, the optimal protospacer adjacent motif forAsCas12a would occur frequently within the AT-rich genome of this platyhelminth. We deployed optimized conditions for the ratio of guide RNAs to the nuclease, donor templates, and electroporation parameters, to target a key enzyme termed omega-1 that is secreted by the schistosome egg.AsCas12a was more efficient thanSpCas9 for gene knockout ofomega-1as determined by tracking of indels by decomposition (P< 0.001). Resulting from CRISPREsso2 analysis, most mutations were deletions;SpCas9 induced short deletions of 3 nt in length whereasAsCas12a induced deletions of 2 to 26 nt. Knockout efficiency of both nucleases markedly increased in the presence of short, single stranded oligodeoxynucleotide (ssODN) donor templates. WithAsCas12a, ssODNs representative of both the non-CRISPR target (NT) and target (T) strands of the targeted gene were tested, resulting in KO efficiencies of 15.67, 28.71 and 21.43% in theSpCas9 plus donor ssODN,AsCas12a plus NT-ssODN, andAsCas12a plus T-ssODN groups, respectively.Transcleavage activity against the ssODNs by activatedAsCas12a was not apparentin vitro. ProgrammedSpCas9 editing led to more precise transgene insertion thanAsCas12a, with KI efficiencies of 17.07% for the KI_SpCas9 group, 14.58% for KI_AsCas12a-NT-ssODN and 12.37% for KI_AsCas12a-T-ssODN. AlthoughAsCas12a induced fewer mutations per genome thanSpCas9, the phenotypic impact on transcription and expression of omega-1 was similar for both nucleases. These findings revealed thatAsCas12a andSpCas9 both provide tractable routes for RNA-guided programmed mutation of the genome of the schistosome egg.
Effects of Chronic Intermittent Hypoxia and Chronic Sleep Fragmentation on Gut Microbiome, Serum Metabolome, Liver and Adipose Tissue Morphology
Authors: Wang Fan , Zou Juanjuan , Xu Huajun , Huang Weijun , Zhang Xiaoman , Wei Zhicheng , Li Xinyi , Liu Yupu , Zou Jianyin , Liu Feng , Zhu Huaming , Yi Hongliang , Guan Jian , Yin Shankai
Published: November 2021

Chronic intermittent hypoxia (CIH) and chronic sleep fragmentation (CSF) are two cardinal pathological features of obstructive sleep apnea (OSA). Dietary obesity is a crucial risk intermediator for OSA and metabolic disorders. Gut microbiota affect hepatic and adipose tissue morphology under conditions of CIH or CSF through downstream metabolites. However, the exact relationship is unclear. Herein, chow and high-fat diet (HFD)-fed mice were subjected to CIH or CSF for 10 weeks each and compared to normoxia (NM) or normal sleep (NS) controls. 16S rRNA amplicon sequencing, untargeted liquid chromatography-tandem mass spectrometry, and histological assessment of liver and adipose tissues were used to investigate the correlations between the microbiome, metabolome, and lipid metabolism under CIH or CSF condition. Our results demonstrated that CIH and CSF regulate the abundance of intestinal microbes (such as Akkermansia mucinphila, Clostridium spp., Lactococcus spp., and Bifidobacterium spp.) and functional metabolites, such as tryptophan, free fatty acids, branched amino acids, and bile acids, which influence adipose tissue and hepatic lipid metabolism, and the level of lipid deposition in tissues and peripheral blood. In conclusion, CIH and CSF adversely affect fecal microbiota composition and function, and host metabolism; these findings provide new insight into the independent and synergistic effects of CIH, CSF, and HFD on lipid disorders.
Bacterial LomR Induces the Vibriophage VP882 VqmA-Directed Quorum-Sensing Lysogeny-Lysis Transition
Authors: Sun Jennifer S. , Mashruwala Ameya A. , Fei Chenyi , Bassler Bonnie L.
Published: November 2021

The bacterial cell-cell communication process called quorum sensing enables groups of bacteria to synchronously alter behavior in response to changes in cell population density. Quorum sensing relies on the production, release, accumulation, and detection of extracellular signal molecules called autoinducers. Here, we investigate a mechanism employed by a vibriophage to surveil host quorum sensing and tune its lysogeny-lysis decision to host cell density. The phage possesses a gene called vqmAPhage encoding a quorum-sensing receptor homologous to vibrio VqmA. Both VqmA receptors can detect the host bacteria-produced autoinducer called DPO. DPO-bound VqmAPhage launches the phage lysis process. We discover that the bacterial host produces an inducer of the VqmAPhage-directed quorum-sensing lysogeny-lysis transition. Production of the inducer appears to be widespread among bacteria. A screen of the Escherichia coli Keio collection for mutants impaired for inducer production revealed lomR, located in a prophage, and encoding a poorly understood protein. In the E. coli screening strain, lomR is interrupted by DNA encoding an insertion element. The 3’ domain of this LomR protein is sufficient to induce VqmAPhage-directed lysis. Alanine-scanning mutagenesis showed that substitution at either of two key residues abrogates inducer activity. Full-length LomR is similar to the outer membrane porin OmpX in E. coli and Vibrio parahaemolyticus O3:K6, and OmpT in Vibrio cholerae C6706, and indeed, OmpX and OmpT can induce VqmAPhage-directed activity. Possibly, development of the LomR, OmpX, or OmpT proteins as tools to direct phage lysis of host cells could be used to control bacteria in medical or industrial settings.

ABSTRACT IMPORTANCE

Bacteria communicate with chemical signal molecules using a process called quorum sensing. Quorum sensing allows bacteria to track their cell numbers and orchestrate collective behaviors. Recently, we discovered that a virus that infects and kills bacteria “eavesdrops” on its host’s quorum-sensing process. Specifically, the virus monitors host cell growth by detecting the accumulation of host quorum-sensing signal molecules. In response to the garnered quorum-sensing information, the virus kills the host bacterial cells when the bacterial population has reached a high cell density. This strategy presumably enhances transmission of viruses to new host cells. Here, we discover and characterize three closely-related bacterial host-produced proteins called LomR, OmpX, and OmpT that are capable of inducing the viral quorum-sensing-mediated killing program. Development of this class of inducer proteins as tools to drive “on demand” virus-mediated lysis of pathogenic host bacterial cells could be used to control bacteria in medical or industrial settings.
Disruption of vacuolin microdomains in the host Dictyostelium discoideum increases resistance to Mycobacterium marinum-induced membrane damage and infection
Authors: Bosmani Cristina , Perret Angélique , Leuba Florence , Guého Aurélie , Hanna Nabil , Soldati Thierry
Published: November 2021

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, manipulates the host phagosome maturation pathway to replicate intracellularly. Mycobacterium marinum, a closely-related species, and Dictyostelium discoideum, a social amoeba and alternative phagocytic host, have been used as models to study host-pathogen interactions occurring during mycobacterial infections. Vacuolins, functional homologues of the mammalian flotillins, organize membrane microdomains and play a role in vesicular trafficking. Various pathogens have been reported to manipulate their membrane association and function. During infection of D. discoideum with M. marinum, Vacuolin C was specifically and highly induced and all three vacuolin isoforms were enriched at the mycobacteria-containing-vacuole (MCV). In addition, absence of vacuolins reduced escape from the MCV and conferred resistance to M. marinum infection. Moreover, ESAT-6, the membrane-disrupting virulence factor of M. marinum, was less associated with membranes when vacuolins were absent. Together, these results suggest that vacuolins are important host factors that are manipulated by mycobacteria to inflict membrane damage and escape from their compartment.
Looking for lipases and lipolytic organisms in low-temperature anaerobic reactors treating domestic wastewater
Authors: Bashiri Reihaneh , Allen Ben , Shamurad Burhan , Pabst Martin , Curtis Thomas P. , Ofiţeru Irina D.
Published: November 2021

Poor lipid degradation limits low-temperature anaerobic treatment of domestic wastewater even when psychrophiles are used. We combined metagenomics and metaproteomics to find lipolytic bacteria and their potential, and actual, cold-adapted extracellular lipases in anaerobic membrane bioreactors treating domestic wastewater at 4°C and 15°C. Of the 40 recovered putative lipolytic metagenome-assembled genomes (MAGs), only three (Chlorobium, Desulfobacter, and Mycolicibacterium) were common and abundant (relative abundance ≥ 1%) in all reactors. Notably, some MAGs that represented aerobic autotrophs contained lipases. Therefore, we hypothesised that the lipases we found are not always associated with exogenous lipid degradation and can have other roles such as polyhydroxyalkanoates (PHA) accumulation/degradation and interference with the outer membranes of other bacteria. Metaproteomics did not provide sufficient proteome coverage for relatively lower abundant proteins such as lipases though the expression of fadL genes, long-chain fatty acid transporters, was confirmed for four genera (Dechloromonas, Azoarcus, Aeromonas and Sulfurimonas), none of which were recovered as putative lipolytic MAGs. Metaproteomics also confirmed the presence of 15 relatively abundant (≥1%) genera in all reactors, of which at least 6 can potentially accumulate lipid/polyhydroxyalkanoates. For most putative lipolytic MAGs, there was no statistically significant correlation between the read abundance and reactor conditions such as temperature, phase (biofilm and bulk liquid), and feed type (treated by ultraviolet light or not). Results obtained by metagenomics and metaproteomics did not confirm each other and further work is required to identify the true lipid degraders in these systems.
Host casein kinase 1-mediated phosphorylation modulates phase separation of a rhabdovirus phosphoprotein and virus infection
Authors: Fang Xiao-Dong , Gao Qiang , Zang Ying , Qiao Ji-Hui , Gao Dong-Min , Xu Wen-Ya , Wang Ying , Li Dawei , Wang Xian-Bing
Published: November 2021

Liquid–liquid phase separation (LLPS) plays important roles in forming cellular membraneless organelles. However, how host factors regulate LLPS of viral proteins during negative-sense RNA (NSR) virus infections is largely unknown. Here, we used Barley yellow striate mosaic virus (BYSMV) as a model to demonstrate regulation of host casein kinase 1 in phase separation and infection of NSR viruses. We first found that the BYSMV phosphoprotein (P) formed spherical granules with liquid properties and recruited viral nucleotide (N) and polymerase (L) proteins in vivo. Moreover, the P-formed granules were tethered to the ER/actin network for trafficking and fusion. BYSMV P alone formed droplets and incorporated the N protein and genomic RNA in vitro. Interestingly, phase separation of BYSMV P was inhibited by host casein kinase 1 (CK1)-dependent phosphorylation of an intrinsically disordered P protein region. Genetic assays demonstrated that the unphosphorylated mutant of BYSMV P exhibited condensed phase, which promoted virus replication through concentrating the N, L proteins, and genome RNA into viroplasms. Whereas, the phosphorylation-mimic mutant existed in diffuse phase state leading to enhanced virus transcription. Collectively, our results demonstrate that host CK1 modulates phase separation of viral P protein and virus infection.
Generic Approach For Mathematical Model of Multi-Strain Pandemics
Authors: Lazebnik Teddy , Bunimovich-Mendrazitsky Svetlana ,   with the Lorem Ipsum Consortium
Published: November 2021

Pandemics with multi-strain have become a major concern. We introduce a new model for assessing the connection between multi-strain pandemic and the mortality rate, basic reproduction number, and the maximum of infected individuals. The proposed model provides a general mathematical approach for representing multi-strain pandemics, generalizing for an arbitrary number of strains. We show the proposed model fits well with epidemiological historical data world health over a long period. From a theoretical point of view, we show that the increasing number of strains increases logarithmically the maximum number of infected individuals and the mean mortality rate. Moreover, the mean basic reproduction number is statistically identical to the single, most aggressive strain pandemic for multi-strain pandemics.
Ly-6A-Induced Growth Inhibition and Cell death in a Transformed CD4+T cell line: Role of Tumor Necrosis Factor-α (TNF-α)
Authors: Patel Akshay G. , Moxham Sarah , Bamezai Anil K.
Published: November 2021

Engaging the Ly-6A protein, an inhibitory signaling protein, on CD4+T cell lines triggers apoptosis. Signaling through Ly-6A activates cell-intrinsic apoptotic cell death pathway as indicated by release of cytochrome C, activation of caspase 3 and 9. In addition Ly-6A induces cytokine production and growth inhibition. The mechanism underlying simultaneous distinct cellular responses has remained unknown. To examine the relatedness of distinct responses generated by engaging Ly-6A, we have quantified the secretion of TNFα, TGFβ and a related protein GDF10, the three pro-apoptotic, growth inhibitory and tumor suppressive cytokines. While low levels of TGFβ and GDF10 were detected after engaging Ly-6A, the production of TNF-α was elevated in cell cultures stimulated the Ly-6A protein. Blocking the biological activity of TNFα resulted in reduced apoptosis induced by engaging Ly-6A. In contrast, growth inhibition/apoptosis in response to antigen receptor complex stimulation was not observed. Engaging the antigen receptor through activating the epsilon (ε) chain of CD3 generated high levels of TGF-β and GDF10 while decreasing TNFα. These results suggest that the TNF-α cytokine contributes to the Ly-6A-induced growth inhibitory and pro-apoptotic response in CD4+T cells and provides mechanistic explanation of the observed biologically distinct responses initiated after engaging Ly-6A protein. These findings aid in understanding the inhibitory signaling initiated by Ly-6A protein, especially in the context of its potential immune checkpoint inhibitory role in T cells.
Birnaviridae virus factories show features of liquid-liquid phase separation, and are distinct from paracrystalline arrays of virions observed by electron microscopy
Authors: Reddy Vishwanatha R. A. P. , Campbell Elle A. , Wells Joanna , Simpson Jennifer , Nazki Salik , Hawes Philippa C. , Broadbent Andrew J.
Published: November 2021

To gain more information about the nature of Birnaviridae virus factories (VFs), we used a recombinant infectious bursal disease virus (IBDV) expressing split-GFP11 tagged to the polymerase (VP1) that we have previously shown is a marker for VFs in infected cells expressing GFP1-10. We found that VFs co-localized with 5-ethynyl uridine in the presence of actinomycin D, confirming they were the site of de novo RNA synthesis, and VFs were visible in infected cells that were fixed and permeabilized with digitonin, demonstrating that they were not membrane bound. Fluorescence recovery after photobleaching (FRAP) a region of interest within the VFs occurred rapidly, recovering from approximately 25% to 87% the original intensity over 146 seconds, and VFs were dissolved by 1,6-hexanediol treatment, demonstrating they showed properties consistent with liquid-liquid phase separation. There was a lower co-localization of the VF GFP signal with the capsid protein VP2 (Manders’ coefficient (MC) 0.6), compared to VP3 (MC, 0.9), which prompted us to investigate the VF ultrastructure by transmission electron microscopy (TEM). In infected cells, paracrystalline arrays (PAs) of virions were observed in the cytoplasm, as well as discrete electron dense regions. Using correlative light and electron microscopy (CLEM), we observed that the electron dense regions correlated with the GFP signal of the VFs, which were distinct from the PAs. In summary, Birnaviridae VFs are sites of de novo RNA synthesis, are not bound by a membrane, show properties consistent with liquid-liquid phase separation, and are distinct from the PAs observed by TEM.

Importance

Members of the Birnaviridae infect birds, fish and insects, and are responsible for diseases of significant economic importance to the poultry industry and aquaculture. Despite their importance, how they replicate in cells remains poorly understood. Here, we show that the Birnaviridae virus factories are not membrane bound, demonstrate properties consistent with liquid-liquid phase separation, and are distinct from the paracrystalline arrays of virions observed by transmission electron microscopy, enhancing our fundamental knowledge of virus replication that could be used to develop strategies to control disease, or optimize their therapeutic application.
COVID-19 first and delta waves in relation to ACEI, ARB, Influenza vaccination, and comorbidity in a North Metropolitan Barcelona Health Consortium
Authors: Juanes-González Marta , Calderón-Valdiviezo Ana , Losa-Puig Helena , Valls-Foix Roger , González-Salvador Marta , León-Pérez Marc , Pueyo-Antón Luís , Lozano-Paz Celia , Franco-Romero Maite , Vidal-Alaball Josep , Puigdellívol-Sánchez Anna
Published: November 2021

BACKGROUND

Some authors have reported that angiotensin converter enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) improve clinical outcomes in hypertensive COVID-19 patients, and others have proposed cross-protection for influenza vaccination. This study explores the impact of these variables on the evolution of hospitalized patients, focusing in the first wave and the Delta wave.

METHODS

Hospitalizations (n=1888) from March 1, 2020, to July 31, 2021, in the Hospital of Terrassa, the referral center for the free access Terrassa Health Consortium in the North Metropolitan Barcelona Health Region (population=167,386) were studied. The number of chronic treatments and conditions of patients from the initial outbreak (n=184) and the Delta outbreak (n=158) were recorded.

RESULTS

Of the non-survivors, 96.3% were aged >60 years in the first wave and 100% were aged >70 years in the Delta wave. In non-survival hospitalized patients aged >60 years, the percentage treated with ACEI was similar to general population but was significantly different for ARB treatments of influenza vaccination, although associated to a higher comorbidity and age. In July 2021, the number of hospitalizations for patients aged <50 years was higher than March 2020 and 22% of hospitalized patients without chronic treatments and conditions needed admission to the intensive care unit. Mortality was reduced in the groups with most comorbidities who received influenza and SARS-CoV2 vaccination.

CONCLUSIONS

In COVID-19 infection, age and comorbidity are related to survival, ACEI use is safe. A high proportion of patients without comorbidity require hospitalization and intensive care.
Frequency and phenotype associations of rare variants in five monogenic cerebral small vessel disease genes in 200,000 UK Biobank participants with whole exome sequencing data
Authors: Ferguson Amy C. , Thrippleton Sophie , Henshall David E. , Whittaker Ed , Conway Bryan , MacLeod Malcolm , Malik Rainer , Rawlik Konrad , Tenesa Albert , Sudlow Cathie , Rannikmäe Kristiina
Published: November 2021

Based on previous case reports and disease-based cohorts, a minority of patients with cerebral small vessel disease (cSVD) have a monogenic cause, with many also manifesting extra-cerebral phenotypes. We investigated the frequency, penetrance, and phenotype associations of rare variants in cSVD genes in UK Biobank (UKB), a large population-based study.

We used a systematic review of previous literature and ClinVar to identify putative pathogenic rare variants in CTSA, TREX1, HTRA1, COL4A1/2. We mapped phenotypes previously attributed to these variants (phenotypes-of-interest) to disease coding systems used in UKB’s linked health data from UK hospital admissions, death records and primary care. Among 199,313 exome-sequenced UKB participants, we assessed: the proportion of participants carrying ≥1 variant(s); phenotype-of-interest penetrance; and the association between variant carrier status and phenotypes-of-interest using a binary (any phenotype present/absent) and phenotype burden (linear score of the number of phenotypes a participant possessed) approach.

Among UKB participants, 0.5% had ≥1 variant(s) in studied genes. Using hospital admission and death records, 4-20% of variant carriers per gene had an associated phenotype. This increased to 7-55% when including primary care records. Only COL4A1 variant carrier-status was significantly associated with having ≥1 phenotype-of-interest and a higher phenotype score (OR=1.29, p=0.006).

While putative pathogenic rare variants in monogenic cSVD genes occur in 1:200 people in the UKB population, only around half of variant carriers have a relevant disease phenotype recorded in their linked health data. We could not replicate most previously reported gene-phenotype associations, suggesting lower penetrance rates, overestimated pathogenicity and/or limited statistical power.
Business process nature assessment matrix – a novel approach to the assessment of business process nature
Authors: Berniak-Woźny Justyna , Szelągowski Marek
Published: November 2021

Purpose

The purpose of this study is to give an in-depth understanding of the nature of business processes (BPs) from the perspective of their dynamism and knowledge intensity that will allow for their correct classification and provide practical and useful implications for their more relevant and effective management. A simple and low labor-intensive BP nature assessment approach is proposed that will allow for objective assessment and internal benchmarking of all BPs in a specific context of execution based on their nature.

Design/methodology/approach

The research is divided into two parts. The first comprises a systematic literature review (SLR) based on the resources of the ProQuest, Springer Nature and ScienceDirect full-text databases and the second includes illustrative case studies.

Findings

Building on the SLR, the authors identified and reviewed 3,385 articles and defined a set of criteria by which the nature of BPs can be assessed. Further, the authors proposed a BP nature assessment matrix together with complementary questionnaires for the evaluation of process dynamism and knowledge intensity. To demonstrate the logic of this approach, two illustrative case studies were presented.

Originality/value

The article contributes to the theoretical reflection on the nature of BPs in the knowledge economy. From the practical point of view, a novel approach to the assessment of the nature of BPs is offered. The approach is open and as experience is accumulated it will develop according to the data and recommendations collected.
Principals' intentions and anticipated challenges in implementing nutrition education
Authors: Baloch Fozia Ahmed , Mohamed Ismail Shaik Abdul Malik , Jogezai Nazir Ahmed
Published: November 2021

Purpose

This study aimed to know principals' intentions of implementing nutrition education (NE) and explore the challenges they may anticipate while implementing NE in their respective schools.

Design/methodology/approach

The study employed a sequential mixed-method design using a questionnaire and interviews to collect data. The quantitative data were collected from 378 secondary school principals, while 16 school principals were interviewed.

Findings

The study found principals with positive intentions towards implementing NE. The results also highlighted challenges related to capacity building, resources (both human and physical), policies and plans, roles, and responsibilities of the implementers (teachers and principals), support from higher authorities, community participation and teachers' unions. This study concludes that principals' intentions remain central to the implementation of NE in schools. However, it is necessary to overcome those challenges before its implementation.

Research limitations/implications

The study sought to ascertain principals' intentions rather than their actual behaviour of NE implementation and hence remains limited in this area, which future research may consider. Furthermore, the research is limited to the principals' opinions on the anticipated challenges associated with NE implementation. The study did not solicit the opinions of other stakeholders, such as education managers, policymakers, teachers and communities.

Originality/value

The article is significant in terms of NE being implemented in schools to improve students' physical and academic wellbeing. The critical role of principals has been investigated by determining their intentions and the anticipated challenges associated with implementing NE. The authors declare the originality of the data.
An optimal scheduling policy for upgraded software with updates
Authors: Anand Adarsh , Das Subhrata , Agarwal Mohini , Inoue Shinji
Published: November 2021

Purpose

In the current market scenario, software upgrades and updates have proved to be very handy in improving the reliability of the software in its operational phase. Software upgrades help in reinventing working software through major changes, like functionality addition, feature enhancement, structural changes, etc. In software updates, minor changes are undertaken which help in improving software performance by fixing bugs and security issues in the current version of the software. Through the current proposal, the authors wish to highlight the economic benefits of the combined use of upgrade and update service. A cost analysis model has been proposed for the same.

Design/methodology/approach

The article discusses a cost analysis model highlighting the distinction between launch time and time to end the testing process. The number of bugs which have to be catered in each release has been determined which also consists of the count of latent bugs of previous version. Convolution theory has been utilized to incorporate the joint role of tester and user in bug detection into the model. The cost incurred in debugging process was determined. An optimization model was designed which considers the reliability and budget constraints while minimizing the total debugging cost. This optimization was used to determine the release time and testing stop time.

Findings

The proposal is backed by real-life software bug dataset consisting of four releases. The model was able to successfully determine the ideal software release time and the testing stop time. An increased profit is generated by releasing the software earlier and continues testing long after its release.

Originality/value

The work contributes positively to the field by providing an effective optimization model, which was able to determine the economic benefit of the combined use of upgrade and update service. The model can be used by management to determine their timelines and cost that will be incurred depending on their product and available resources.
Quality 4.0 – a measurement model using the confirmatory factor analysis (CFA) approach
Authors: Sureshchandar G.S.
Published: November 2021

Purpose

The disruptions caused by new-age technologies of Industry 4.0 are posing a formidable challenge to researchers, academicians and practitioners alike. Quality 4.0 that depicts the role of the quality function in the Industry 4.0 scenario must be comprehended so that the rudiments of Quality 4.0 are understood properly, and interventions can be made to embrace the new normal. As the literature on Quality 4.0 is extremely scarce, empirical studies are mandatory to augment the process of theory building.

Design/methodology/approach

The research work identifies 12 axes of the Quality 4.0 revolution based on literature review and insights from experts. Subsequently, a measurement model is formulated and an instrument to measure the level of Quality 4.0 implementation is developed. The measurement model has been checked for model fit, reliability and validity using the confirmatory factor analysis approach.

Findings

The proposed model was found to be adequate, reliable and valid and concludes that though technology plays a significant role in the development of the Quality 4.0 system, aspects of traditional quality are very much apropos to transform to the next frontier of quality.

Research limitations/implications

Implications for future research are provided which would help to further explore the nascent field of Quality 4.0.

Practical implications

This research would help the practitioners better understand the various requirements and measure the degree of implementation of a Quality 4.0 system.

Originality/value

The present research is perhaps the first of its kind in propounding a measurement model, through empirical analysis, for the betterment of the understanding of Quality 4.0 and its associated constituents.