bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Patient Outcomes by Addressing Provider Variation in Emergency Department Asthma Care
Authors: Hartford Emily Altick , Klein Eileen J. , Migita Russell , Richling Stephanie , Chen Jingyang , Rutman Lori E.
Published: December 2020

Introduction:

Asthma exacerbations are frequent in the pediatric emergency department (ED) and result in significant morbidity and costs; standardized treatment improves outcomes. In this study, we aimed to use provider adherence data and the associated patient outcomes as an intervention to change behavior and improve care.

Methods:

We used a retrospective cohort design to analyze 2 years of baseline data for asthma patient encounters. Providers were classified based on guideline adherence. We compared patient outcomes by provider adherence using Mann–Whitney U and Fisher’s exact test. Our intervention included education with data feedback and peer comparison. We then analyzed changes in guideline adherence, the proportion of patients admitted, length of stay (LOS), and costs for this population over time using statistical process control charts.

Results:

In our baseline data analysis, patients seen by less adherent physicians had a higher likelihood of admission (65.1% versus 50.8%, P < 0.001), a longer ED LOS (4.7 versus 4.2 h, P = 0.007), and higher costs ($1,896.20 versus $1,728.50, P < 0.001). Using SPC analysis, there was an improvement in guideline adherence by providers (64%–77%) with a mirrored improvement in patient adherence (76%–84%) associated with our interventions. Admissions decreased 1 year after the intervention; ED LOS and returns remained unchanged.

Conclusion:

In this study, we evaluated patient outcomes according to provider adherence to a clinical guideline and used the results to change provider behavior and improve patient outcomes. Active provision of feedback with peer comparison for providers was associated with improved adherence over time.
CPR during COVID-19: Use of Expert-driven Rapid Cycle Deliberate Practice to Implement PALS Guidelines
Authors: Nichols Blake E. , McMichael Ali B.V. , Volk A. Paige Davis , Bhaskar Priya , Bowens Cindy Darnell
Published: December 2020

Introduction:

The American Heart Association (AHA) and other national institutions have endorsed modifications to resuscitation guidelines given the risk of healthcare workers’ (HCWs) exposure to COVID-19. Institutional implementation of the COVID-19-focused guidelines requires both proof of feasibility and education of HCW. Pediatric critical care medical directors at The University of Texas Southwestern/Children’s Health System of Texas (UTSW/CHST) created a guideline for the resuscitation of COVID-19 patients. The simulation team used in situ simulation to demonstrate guideline feasibility and to create educational materials.

Methods:

A UTSW/CHST guideline incorporated COVID-19-focused AHA and other national organizational recommendations to fit the institutional needs. A high-fidelity in situ simulation helped test the feasibility and optimize the UTSW/CHST guideline. We developed a novel form of rapid cycle deliberate practice (RCDP), expert-driven RCDP, in which all simulation participants are experts, to debrief the simulation.

Results:

In situ simulation with expert-driven RCDP demonstrated guideline feasibility in the resuscitation of a COVID-19 patient while balancing the protection of HCW. Expert-driven RCDP allowed for real-time alterations to the guideline during the simulation event. Video recording and dissemination of the simulation allowed for the education of over 300 staff on the new recommendations.

Conclusions:

High-fidelity in situ simulation with expert-driven RCDP created a rapid consensus among expert critical care providers to develop the UTSW/CHST guideline and quickly adopt the new AHA recommendations. This debriefing method helped minimize the risk of HCW exposure by minimizing the number of required participants and time for simulation. We recommend using this distinctive, expert-driven RCDP debriefing method for expeditious testing of COVID-19-focused processes at other institutions.

Video Abstract available at: [link forthcoming]
Optimizing Professional Practice Evaluation to Enable a Nonpunitive Learning Health System Approach to Peer Review
Authors: Sandborg Christy I. , Hartman Gary E. , Su Felice , Williams Glyn , Teufe Beate , Wixson Nina , Larson David B. , Donnelly Lane F.
Published: December 2020

Purpose:

Healthcare organizations are focused on 2 different and sometimes conflicting tasks; (1) accelerate the improvement of clinical care delivery and (2) collect provider-specific data to determine the competency of providers. We describe creating a process to meet both of these aims while maintaining a culture that fosters improvement and teamwork.

Methods:

We created a new process to sequester activities related to learning and improvement from those focused on individual provider performance. We describe this process, including data on the number and type of cases reviewed and survey results of the participant’s perception of the new process.

Results:

In the new model, professional practice evaluation committees evaluate events purely to identify system issues and human factors related to medical decision-making, resulting in actional improvements. There are separate and sequestered processes that evaluate concerns around an individual provider’s clinical competence or behavior. During the first 5 years of this process, 207 of 217 activities (99.5%) related to system issues rather than issues concerning individual provider competence or behavior. Participants perceived the new process as focused on identifying system errors (4.3/5), nonpunitive (4.2/5), an improvement (4.0/5), and helped with engagement in our system and contributed to wellness (4.0/5).

Conclusion:

We believe this sequestered approach has enabled us to achieve both the oversight mandates to ensure provider competence while enabling a learning health systems approach to build the cultural aspects of trust and teamwork that are essential to driving continuous improvement in our system of care.
A Quality Improvement Learning Collaborative for Human Papillomavirus Vaccination
Authors: Oliver Kristin , Beskin Kera , Noonan Laura , Shah Amy , Perkins Rebecca , Humiston Sharon
Published: December 2020

Introduction:

Many published accounts have shown that quality improvement (QI) initiatives within medical practice settings can increase vaccination rates. Project ECHO is a telementoring platform that uses video conferencing technology to educate and support healthcare professionals through case-based learning and brief lectures. This manuscript explores the results of a learning collaborative focused on combining QI and Project ECHO to increase human papillomavirus (HPV) vaccination rates within pediatric practices.

Methods:

The American Academy of Pediatrics (AAP) recruited 3 AAP chapters that then recruited individual pediatricians and their practices for participation. Participants responded to surveys regarding chapter and pediatrician experience and satisfaction. Impact on HPV immunization rates (HPV initiation, series completion, and missed opportunities to vaccinate during visits) was measured using practice reports of chart reviews to AAP’s data aggregator, which produced run charts.

Results:

Thirty-four pediatricians within 8 practices completed the project; 1 practice withdrew. Physicians self-reported increased confidence in communicating with vaccine-hesitant families and implementing QI activities. We analyzed practice run charts utilizing QI run chart rules and found nonrandom change towards improvement for aggregate missed opportunities to vaccinate but not for HPV vaccine initiation or series completion.

Conclusions:

An HPV QI learning collaborative improved participant confidence in HPV vaccine communication and QI skills and decreased missed opportunities to vaccinate. Future projects should consider a more extended project period or more frequent data collection to reduce data variability to make it easier to spot nonrandom changes.
Improving chromatin-interaction prediction using single-cell open-chromatin profile and making insight about the cis-regulatory landscape of the human brain
Authors: Pandey Neetesh , Chandra Omkar , Mishra Shreya , Kumar Vibhor
Published: December 2020

Single-cell open-chromatin profiles have the potential to reveal the pattern of chromatin-interaction in a cell-type. However, currently available cis-regulatory network prediction methods using single-cell open-chromatin profiles focus more on local chromatin-interactions despite the fact that long-range interaction among genomic sites plays a significant role in gene regulation. Here, we propose a method that predicts both local and long-range interactions among genomic sites using single-cell open chromatin profiles. Using our method’s better sensitivity, we could predict almost 0.7 million interactions among genomic sites across 7 cell-types in the human brain. The chromatin-interactions estimated in the human brain revealed surprising but useful insight about target genes of human-accelerated-elements and disease-associated mutations.
Tailored Graphical Lasso for Data Integration in Gene Network Reconstruction
Authors: Lingjærde Camilla , Lien Tonje G , Borgan Ørnulf , Glad Ingrid K
Published: December 2020

Background

Identifying gene interactions is a topic of great importance in genomics, and approaches based on network models provide a powerful tool for studying these. Assuming a Gaussian graphical model, a gene association network may be estimated from multiomic data based on the non-zero entries of the inverse covariance matrix. Inferring such biological networks is challenging because of the high dimensionality of the problem, making traditional estimators unsuitable. The graphical lasso is constructed for the estimation of sparse inverse covariance matrices in Gaussian graphical models in such situations, usingL1-penalization on the matrix entries. An extension of the graphical lasso is the weighted graphical lasso, in which prior biological information from other (data) sources is integrated into the model through the weights. There are however issues with this approach, as it naïvely forces the prior information into the network estimation, even if it is misleading or does not agree with the data at hand. Further, if an associated network based on other data is used as the prior, weighted graphical lasso often fails to utilize the information effectively.

Results

We propose a novel graphical lasso approach, thetailored graphical lasso, that aims to handle prior information of unknown accuracy more effectively. We provide an R package implementing the method,tailoredGlasso. Applying the method to both simulated and real multiomic data sets, we find that it outperforms the unweighted and weighted graphical lasso in terms of all performance measures we consider. In fact, the graphical lasso and weighted graphical lasso can be considered special cases of the tailored graphical lasso, and a parameter determined by the data measures the usefulness of the prior information. With our method, mRNA data are demonstrated to provide highly useful prior information for protein-protein interaction networks.

Conclusions

The method we introduce utilizes useful prior information more effectively without involving any risk of loss of accuracy should the prior information be misleading.
Analysis of a Mad2 homolog inTrypanosoma bruceiprovides possible hints on the origin of the spindle checkpoint
Authors: Akiyoshi Bungo
Published: December 2020

The spindle checkpoint is a surveillance mechanism that ensures accurate nuclear DNA segregation in eukaryotes. It does so by delaying the onset of anaphase until all kinetochores have established proper attachments to spindle microtubules. The evolutionary origin of the spindle checkpoint remains unclear. The flagellated kinetoplastid parasiteTrypanosoma bruceihas a nucleus that contains the nuclear genome and a kinetoplast that contains the mitochondrial genome. The kinetoplast is physically linked to the basal body of the flagellum and its segregation is driven by the movement of basal bodies. While there is no strong evidence thatT. bruceipossesses a functional spindle checkpoint, it has been suggested that initiation of cytokinesis may be linked to the completion of kinetoplast segregation or basal body separation in this organism. Interestingly, the only identifiable spindle checkpoint component TbMad2 localizes at the basal body area. Here, I report identification of proteins that co-purified with TbMad2. One protein, which I propose to call TbMBP65, localizes at the basal body area and has a putative Mad2-interacting motif. Interestingly, 26S proteasome subunits also co-purified with TbMad2, raising a possibility that TbMad2 might regulate proteasome activity to regulate or monitor the segregation of basal bodies. I speculate that such a function might represent a prototype of the spindle checkpoint. I also show that TbAUK3, one of the three Aurora kinase homologs inT. brucei, localizes at the basal body area from late G1 until the time of kinetoplast separation. Immunoprecipitation of TbAUK3 identified an uncharacterized protein (termed TbABP79) that has a similar localization pattern as TbAUK3. These findings provide a starting point to reveal the function of TbMad2 and TbAUK3 as well as the origin of the spindle checkpoint.
A group refactorization procedure for sleep electroencephalography
Authors: Law Robert G. , Purcell Shaun M.
Published: December 2020

[WORKING DRAFT] In order to relate health and disease to brain state, patterns of activity in the brain must be phenotyped. In this regard, polysomnography datasets present both an opportunity and a challenge, as although sleep data are extensive and multidimensional, features of the sleep EEG are known to correlate with clinical outcomes. Machine learning methods for rank reduction are attractive means for bringing the phenotyping problem to a manageable size. The whole-night power spectrogram is nonnegative, and so applying nonnegative matrix factorization (NMF) to separate spectrograms into time and frequency factors is a natural choice for dimension reduction. However, NMF converges differently depending on initial conditions, and there is no guarantee that factors obtained from one individual will be comparable with those from another, hampering inter-individual analysis.

We therefore reseed time-frequency NMF with group frequency factors obtained from the entire sample. This “refactorization” extends classical frequency bands to frequency factors. The group reseeding procedure coerces factors into equivalence classes, making them comparable across individuals. By comparing frequency factor properties, we illustrate age-related effects on the sleep EEG. The procedure can presumably be adapted to higher resolutions, e.g. to local field potential datasets, for characterizing individual time-frequency events.
Genomic islands of heterozygosity maintained across caribou populations despite inbreeding
Authors: Solmundson Kirsten , Bowman Jeff , Wilson Paul J. , Taylor Rebecca S. , Horn Rebekah L. , Keobouasone Sonesinh , Manseau Micheline
Published: December 2020

Small, isolated populations are prone to inbreeding, increasing the proportion of homozygous sites across the genome that can be quantified as runs of homozygosity (ROH). Caribou (Rangifer tarandus) are declining across their range in Canada; thus, understanding the effects of inbreeding on genetic potential is pertinent for conserving small, isolated populations. We quantified ROH in high-coverage whole genomes of boreal caribou from small, isolated populations in southern Ontario, Canada, in comparison to caribou from the continuous range of Ontario, other caribou ecotypes in Canada, and western Greenland. Sampled populations presented divergent evolutionary histories, differing population sizes, and extents of isolation. We conducted BLAST searches across regions of elevated heterozygosity to identify genes that have maintained variation despite inbreeding. We found caribou from recently isolated populations in Ontario had a large proportion of their genome in long ROH. We observed even larger proportions but shorter ROH in western Greenland, indicating that inbreeding has occurred over a longer period in comparison to other populations. We observed the least inbreeding in barren-ground and eastern migratory caribou, which occur in larger population sizes than boreal caribou. Despite vastly different inbreeding extents, we found regions of high heterozygosity maintained across all populations. Within these islands of heterozygosity, we identified genes associated with immunity, signaling regulation, nucleotide binding, toxin elimination, and feeding behaviour regulation. In this study, we confirm inbreeding in isolated populations of a species at risk, but also uncover high variation in some genes maintained across divergent populations despite inbreeding, suggesting strong balancing selection.
ESR1mutant breast cancers show elevated basal cytokeratins and immune activation
Authors: Li Zheqi , Wu Yang , Bahreini Amir , Priedigkeit Nolan M. , Ding Kai , Sartorius Carol A. , Miller Lori , Rosenzweig Margaret , Wagle Nikhil , Richer Jennifer K. , Muller William J. , Buluwela Laki , Ali Simak , Fang Yusi , Zhu Li , Tseng George C. , Gertz Jason , Atkinson Jennifer M. , Lee Adrian V. , Oesterreich Steffi
Published: December 2020

Estrogen receptor alpha (ER/ESR1) is mutated in 30-40% of endocrine resistant ER-positive (ER+) breast cancer.ESR1mutations cause ligand-independent growth and increased metastasisin vivoandin vitro. Despite the distinct clinical features and changes in therapeutic response associated withESR1mutations, there are no data about their potential role in intrinsic subtype switching. Applying four luminal and basal gene set pairs,ESR1mutant cell models and clinical samples showed a significant enrichment of basal subtype markers. Among them, the six basal cytokeratins (BCKs) were the most enriched genes. Induction of BCKs was independent of ER binding and instead associated with chromatin reprogramming centered around a progesterone receptor-orchestrated topological associated domain at theKRT14/16/17genomic region. Unexpectedly, highBCKexpression in ER+ primary breast cancer is associated with good prognosis, and these tumors show enriched activation of a number of immune pathways, a distinctive feature shared withESR1mutant tumors. S100A8 and S100A9 were among the most highly induced immune mediators shared between high-BCKs ER+ andESR1mutant tumors, and single-cell RNA-seq analysis inferred their involvement in paracrine crosstalk between epithelial and stromal cells. Collectively, these observations demonstrate thatESR1mutant tumors gain basal features with induction of basal cytokeratins via epigenetic mechanisms in rare subpopulation of cells. This is associated with increased immune activation, encouraging additional studies of immune therapeutic vulnerabilities inESR1mutant tumors.
Engineering, production and characterization of Spike and Nucleocapsid structural proteins of SARS–CoV-2 inNicotiana benthamianaas vaccine candidates against COVID-19
Authors: Mamedov Tarlan , Yuksel Damla , Ilgın Merve , Gürbüzaslan İrem , Gulec Burcu , Mammadova Gulshan , Say Deniz , Hasanova Gulnara
Published: December 2020

The COVID-19 pandemic, which is caused by SARS-CoV-2 has rapidly spread to more than 216 countries and has put global public health at high risk. The world urgently needs a cost-effective and safe SARS-CoV-2 coronavirus vaccine, antiviral and therapeutic drugs to control the COVID-19 pandemic. In this study, we engineered the Nucleocapsid (N) and Spike protein (S) variants (Receptor binding domain, RBD and S1 domain) of SARS-CoV-2 genes and produced inNicotiana benthamianaplant. The purification yields were at least 20 mg of pure protein/kg of plant biomass for each target protein. The S protein variants of SARS-CoV-2 showed specific binding to angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 receptor. The purified plant produced N and S variants were recognized by N and S protein specific monoclonal and polyclonal antibodies demonstrating specific reactivity of mAb to plant produced N and S protein variants. In addition, IgG responses of plant produced N and S antigens elicited significantly high titers of antibody in mice. This is the first report demonstrating production of functional active S1 domain and Nucleocapsid protein of SARC-CoV-2 in plants. In addition, in this study, for the first time, we report the co-expression of RBD with N protein to produce a cocktail antigen of SARS-CoV-2, which elicited high-titer antibodies compared to RBD or N proteins. Thus, obtained data support that plant produced N and S antigens, developed in this study, are promising vaccine candidates against COVID-19.
Gait-level analysis of mouse open field behavior using deep learning-based pose estimation
Authors: Sheppard Keith , Gardin Justin , Sabnis Gautam S , Peer Asaf , Darrell Megan , Deats Sean , Geuther Brian , Lutz Cathleen M. , Kumar Vivek
Published: December 2020

1

Gait and whole body posture are sensitive measures of the proper functioning of numerous neural circuits, and are often perturbed in many neurological, neuromuscular, and neuropsychiatric illnesses. Rodents provide a tractable model for elucidating disease mechanisms and interventions, however, studying gait and whole body posture in rodent models requires specialized methods and remains challenging. Here, we develop a simple assay that allows adoption of the commonly used open field apparatus for gait and whole body posture analysis. We leverage modern neural networks to abstract a mouse into keypoints and extract gait and whole body coordination metrics of the animal. Gait-level analysis allows us to detect every step of the animal’s movement and provides high resolution information about the animal’s behavior. We quantitate gait and whole body posture with high precision and accuracy across 62 highly visually diverse strains of mice. We apply our approach to characterize four genetic mutants with known gait deficits. In extended analysis, we demonstrate that multiple autism spectrum disorder (ASD) models show gait and posture deficits, implying this is a general feature of ASD. We conduct a large strain survey of 1898 mice, and find that gait and whole body posture measures are highly heritable in the laboratory mouse, and fall into three classes. Furthermore, the reference mouse strain, C57BL/6J, has a distinctly different gait and posture compared to other standard laboratory and wild-derived strains. We conduct a genome wide association study (GWAS) to define the genetic architecture of mouse movement in the open field. In sum, we describe a simple, sensitive, accurate, scalable, and ethologically relevant method of mouse gait and whole body posture analysis for behavioral neurogenetics. These results provide one of the largest laboratory mouse gait-level data resources for the research community and show the utility of automated machine learning approaches for deriving biological insights.
Dopamine receptors in obesity: a meta-analysis
Authors: Pak Kyoungjune , Lee Myung Jun , Kim Keunyoung , Kim In Joo
Published: December 2020

The brain plays a major role in controlling the desire to eat. This meta-analysis aimed to assess the association between dopamine receptor (DR) availability, measured using positron emission tomography, and obesity. We performed a systematic search of MEDLINE (from inception to June 2019) and EMBASE (from inception to June 2019) for articles published in English using the keywords “dopamine receptor,” “obesity,” and “neuroimaging.” Fitting a locally weighted estimated scatterplot smoothing curve for binding potential (BPND) of the ventral striatum measured by11C-raclopride was performed. Five studies involving 119 subjects were included in this analysis.11C-raclopride was used in four studies, regardless of the ROIs included. The curve of BPNDof the ventral striatum went up and down at BMI of 20–30 kg/m2and became flat after a BMI of >40 kg/m2. Linear regression analysis was performed with BPNDof the striatum from two studies (n = 20). The BPNDof the striatum was negatively associated with BMI. In conclusion, dopamine plays a major role in the reward system with regard to obesity. Compared to normal-weight subjects, overweight and obese subjects had decreased DR availability. However, this tendency should be interpreted carefully with regard to radiopharmaceuticals and ROIs.
Human blood contains circulating cell-free mitochondria, but are they really functional?
Authors: Stier Antoine
Published: December 2020

Dache et al. (2020,FASEB J.15, e2002338–15) recently reported the presence ofrespiratory-competentcell-free mitochondria in human blood (up to 3.7 × 106per mL of blood), providing exciting perspectives on the potential role of these extra-cellular mitochondria. While their evidence for the presence of cell-free mitochondria in human blood is compelling, their conclusion that these cell-free mitochondria are respiratory-competent or functional has to be re-evaluated. To this end, we evaluated the functionality of cell-free mitochondria in human blood using high-resolution respirometry and mitochondria extracted from platelets of the same blood samples as positive controls. While cell-free mitochondria were present in human plasma (i.e. significant MitoTracker Green Fluorescence and complex IV activity), there was no evidence suggesting that their mitochondrial electron transport system (ETS) was functional (i.e. respiration rate not significantly different from 0; no significant responses to ADP, uncoupler or mitochondrial inhibitors oligomycin and antimycin A). Yet,in vitrocomplex IV activity was detectable and even slightly higher than levels found in mitochondria extracted from platelets, suggesting that cell-free mitochondria in human blood are likely to only retain a non-functional part of the electron transport system. Despite being unlikely to be fully functional in the narrow-sense (i.e. capable of oxidative phosphorylation), circulating cell-free mitochondria may have significant physiological roles that remain to be elucidated.
Chromatin Interaction Neural Network (ChINN): A machine learning-based method for predicting chromatin interactions from DNA sequences
Authors: Cao Fan , Zhang Yu , Cai Yichao , Animesh Sambhavi , Zhang Ying , Akincilar Semih , Loh Yan Ping , Chng Wee Joo , Tergaonkar Vinay , Kwoh Chee Keong , Fullwood Melissa J.
Published: December 2020

Chromatin interactions play important roles in regulating gene expression. However, the availability of genome-wide chromatin interaction data is limited. Various computational methods have been developed to predict chromatin interactions. Most of these methods rely on large collections of ChIP-Seq/RNA-Seq/DNase-Seq datasets and predict only enhancer-promoter interactions. Some of the ‘state-of-the-art’ methods have poor experimental designs, leading to over-exaggerated performances and misleading conclusions. Here we developed a computational method, Chromatin Interaction Neural Network (ChINN), to predict chromatin interactions between open chromatin regions by using only DNA sequences of the interacting open chromatin regions. ChINN is able to predict CTCF-, RNA polymerase II- and HiC-associated chromatin interactions between open chromatin regions. ChINN also shows good across-sample performances and captures various sequence features that are predictive of chromatin interactions. To apply our results to clinical patient data, we applied CHINN to predict chromatin interactions in 6 chronic lymphocytic leukemia (CLL) patient samples and a cohort of open chromatin data from 84 CLL samples that was previously published. Our results demonstrated extensive heterogeneity in chromatin interactions in patient samples, and one of the sources of this heterogeneity were the different subtypes of CLL.
Asciminib mitigates DNA damage stress signalling induced by cyclophosphamide in the ovary
Authors: Mattiello Luca , Pucci Giulia , Marchetti Francesco , Diederich Marc , Gonfloni Stefania
Published: December 2020

Cancer treatments often have adverse effects on the quality of life for young women. One of the most relevant negative impacts is the loss of fertility. Cyclophosphamide is one of the most detrimental chemotherapeutic drugs for the ovary. Cyclophosphamide may induce the destruction of dormant follicles while promoting follicle activation and growth. Herein, we demonstrate thein vivoprotective effect of the allosteric Bcr-Abl tyrosine kinase inhibitor Asciminib on signalling pathways activated by cyclophosphamide in mouse ovaries. Besides, we provide evidence that Asciminib did not interfere with the cytotoxic effect of cyclophosphamide in MCF7 breast cancer cells. Our data indicate that concomitant administration of Asciminib mitigates the cyclophosphamide-induced ovarian reserve loss without preventing the anticancer potential of cyclophosphamide. Altogether these observations are relevant for the development of effective ferto-protective adjuvants to preserve the ovarian reserve from the damaging effect of cancer therapies.
Process Development and Scale-up Optimization of the SARS-CoV-2 Receptor Binding Domain-Based Vaccine Candidate, RBD219-N1C1
Authors: Lee Jungsoon , Liu Zhuyun , Chen Wen-Hsiang , Wei Junfei , Kundu Rakhi , Adhikari Rakesh , Rivera Joanne Altieri , Gillespie Portia M. , Strych Ulrich , Zhan Bin , Hotez Peter J. , Bottazzi Maria Elena
Published: December 2020

A SARS-CoV-2 RBD219-N1C1 (RBD219-N1C1) recombinant protein antigen formulated on Alhydrogel®has recently been shown to elicit a robust neutralizing antibody response against SARS-CoV-2 pseudovirus in mice. The antigen has been produced under current good manufacturing practices (cGMP) and is now in clinical testing. Here, we report on process development and scale-up optimization for upstream fermentation and downstream purification of the antigen. This includes production at the 1 and 5 L scale in the yeast,Pichia pastoris,and the comparison of three different chromatographic purification methods. This culminated in the selection of a process to produce RBD219-N1C1 with a yield of >400 mg per liter of fermentation with >92% purity and >39% target product recovery after purification. In addition, we show the results from analytical studies, including SEC-HPLC, DLS, and an ACE2 receptor binding assay that were performed to characterize the purified proteins to select the best purification process. Finally, we propose an optimized upstream fermentation and downstream purification process that generates quality RBD219-N1C1 protein antigen and is fully scalable at a low cost.
Spatio-Temporal Coordination of Transcription Preinitiation Complex Assembly in Live Cells
Authors: Nguyen Vu Q. , Ranjan Anand , Liu Sheng , Tang Xiaona , Ling Yick Hin , Wisniewski Jan , Mizuguchi Gaku , Li Kai Yu , Jou Vivian , Zheng Qinsi , Lavis Luke D. , Lionnet Timothée , Wu Carl
Published: December 2020

Transcription initiation by RNA polymerase II (Pol II) requirespreinitiationcomplex (PIC) assembly at gene promoters. In the dynamic nucleus where thousands of promoters are broadly distributed in chromatin, it is unclear how ten individual components converge on any target to establish the PIC. Here, we use live-cell, single-molecule tracking inS. cerevisiaeto document subdiffusive, constrained exploration of the nucleoplasm by PIC components and Mediator’s key functions in guiding this process. On chromatin, TBP, Mediator, and Pol II instruct assembly of a short-lived PIC, which occurs infrequently but efficiently at an average promoter where initiation-coupled disassembly may occur within a few seconds. Moreover, PIC exclusion by nucleosome encroachment underscores regulated promoter accessibility by chromatin remodeling. Thus, coordinated nuclear exploration and recruitment to accessible targets underlies dynamic PIC establishment in yeast. Collectively, our study provides a global spatio-temporal model for transcription initiation in live cells.
scMomentum: Inference of Cell-Type-Specific Regulatory Networks and Energy Landscapes
Authors: Soto Larisa M. , Bernal-Tamayo Juan P. , Lehmann Robert , Balsamy Subash , Martinez-de-Morentin Xabier , Vilas-Zornoza Amaia , San-Martin Patxi , Prosper Felipe , Gomez-Cabrero David , Kiani Narsis A. , Tegner Jesper
Published: December 2020

Recent progress in single-cell genomics has generated multiple tools for cell clustering, annotation, and trajectory inference; yet, inferring their associated regulatory mechanisms is unresolved. Here we present scMomentum, a model-based data-driven formulation to predict gene regulatory networks and energy landscapes from single-cell transcriptomic data without requiring temporal or perturbation experiments. scMomentum provides significant advantages over existing methods with respect to computational efficiency, scalability, network structure, and biological application.

Availability

scMomentum is available as a Python package athttps://github.com/larisa-msoto/scMomentum.git
COVID-19 and intellectual disability/autism spectrum disorder with high and very high support needs: issues of physical and mental vulnerability
Authors: Buonaguro Elisabetta F. , Bertelli Marco O.
Published: December 2020

Purpose

The COVID-19 outbreak has profoundly plagued the world, and current health efforts are focused on providing prevention and ensuring access to intensive services for people with the most severe symptomatology. Many reports have already described substantial psychological distress in the general population. Nevertheless, disasters tend to affect vulnerable subjects disproportionately, and individuals with intellectual disabilities/autism spectrum disorder with high and very high support needs (PwID/ASD-HSN) seem to be counted among the hardest hit populations. The present paper aims to provide a comprehensive discussion and evaluation of COVID-19 related issues specific to PwID/ASD-HSN.

Design/methodology/approach

Commentary on available literature and analysis of new preliminary data on PwID/ASD-HSN’s physical and psychic vulnerability factors. This knowledge is fundamental to provide families and caregivers special advice to counteract the risks associated with the current pandemic.

Findings

PwID/ASD-HSN represent one of the most vulnerable population to the COVID-19 outbreak and the associated factors of mental distress for several reasons, including multimorbidity, low levels of health literacy, difficulties to understand and communicate, reliance on other people for care, low compliance with complex hygiene rules, the strong need of routine/sameness and low adaptive skills.

Originality/value

In the present work, the authors analyze the specific factors of physical and mental vulnerability in PwID/ASD-HSN, corroborating the dissertation with a discussion on the first data published worldwide and with preliminary data collected on the Italian territory for what concerns prevalence rates of COVID-19 and complications in persons with PwID/ASD-HSN and signs and symptoms of psychic distress during the mass quarantine period.
Drugs, brands and consumer culture: the sign-value of the products sold on the darknet marketplaces
Authors: Craciunescu Nicolae Eduard
Published: December 2020

Purpose

The purpose of this study is to explore drug consumption from a cultural perspective, in the context of the consumer culture. It aims to identify if, through the branding process, cryptomarket vendors are attaching a sign-value to their products to facilitate the process by which consumers will recognize and appreciate it.

Design/methodology/approach

The study was done by performing a qualitative content analysis loosely inspired from semiotics on a sample of 40 seller pages from the Dream Market and samples of their listings, collected in 2018. The vendors who had over 1,000 successful transactions were selected, as they were considered to be the ones who have gained a certain level of trust on the cryptomarket and were considered to having to compete by differentiating their services through their brands of choice.

Findings

The results have shown that the sign-value attached to the drugs sold by the vendors from this sample can be divided in two different types of sign-systems: the popular culture and the drug cultures. The popular culture includes sign-value borrowed from established brands, popular media and media representations of crime worlds. The drug cultures include values from three types of subcultural systems: cannabis, party and psychonaut subculture.

Originality/value

The study is trying to stir the discussions around the regulation of the drug markets by looking at the market forces within them as rather a product of consumer capitalism and not as processes that happen outside the postmodern cultural and societal trends.
Technology-based multi-tiered building diagnosis framework
Authors: Faqih Faisal , Zayed Tarek , Alfalah Ghasan
Published: December 2020

Purpose

A building deteriorates over time due to aging, wear and tear, and inadequate maintenance. Building diagnosis requires a sound knowledge of engineering, building defects, and detection tools to assess the condition of a building. The physical deterioration of a building reduces its ability to perform its intended function, while environmental deterioration influences the comfort and health of building occupants. This study presents a multi-tiered framework for the inspection of building elements and the environmental conditions of a building.

Design/methodology/approach

A three-tiered building inspection framework is proposed in this study, which consists of the following: Tier-I—a preliminary inspection, Tier-II—a detailed inspection, and Tier-III—an expert investigation. Each tier of inspection assesses the severity of building defects using different technologies for different levels of inspection.

Findings

Proposed multi-tier inspection framework is tested and implemented on a case study. Results were promising, with organized data management on a common platform for both physical and environmental condition inspection having the potential to save time.

Originality/value

The application program developed for the implementation of structured multi-tiered building inspection provides better documentation and data management for building inspection data that can save time involved in manual data operations in traditional paper-based processes.
Role of Islamic microfinance in women’s empowerment: evidence from Rural Development Scheme of Islami Bank Bangladesh Limited
Authors: Islam Md. Saiful
Published: December 2020

Purpose

The purpose of this study is to investigate the impact of Islamic microfinance services (IMFS) on women’s empowerment in rural Bangladesh.

Design/methodology/approach

The study is based on a multi-stage sampling technique. The primary data are collected through a face-to-face survey of 389 women respondents who have received IMFS from the Islami Bank Bangladesh Limited. Cronbach’s alpha test is conducted to test the reliability and internal consistency of collected data. Paired-sample tests, logit regression and proportion hypothesis tests are conducted to measure the impact of IMFS on women’s empowerment. Descriptive and inferential statistics are used to interpret the data.

Findings

The study reveals that IMFS have led to structural transformation in the occupation dynamics of the respondents’ families from agriculture to retail businesses. IMFS have had a significant positive impact on household income, savings and expenditure; have improved standard of living and human capital formation; and have enhanced all three dimensions of empowerment, namely, economic empowerment (ECEM), socio-cultural empowerment (SCEM) and familial empowerment (FLEM). Of them, ECEM and SCEM have positively contributed toward overall women’s empowerment, while FLEM has a negative but insignificant impact on overall empowerment. The respondents’ perception also supports the finding that IMFS have benefited rural women and empowered them.

Originality/value

The study is based on primary data. It leads to an inquiry as to whether women are dominant in familial affairs. If so, it may reduce the state of happiness and overall women’s empowerment. There is a clear gap in the existing literature about this inquiry.
Sport events as experiencescapes: the spectator's perspective
Authors: Hallmann Kirstin , Zehrer Anita , Rietz Julia
Published: December 2020

Purpose

Combining sport event tourism and experience economy has led to an experience-based explanation of sport tourists' behavior and the creation of experiencescapes. This study aims to analyze the interdependence of perceived experiences and revisit intention across three events.

Design/methodology/approach

Using a survey, data (n = 986) were collected from spectators at the ice hockey world championships, the table tennis world championships and motorsport events (e.g. German-touring car championship). Entertainment, esthetics, escapism and education served as dimensions defining the experience at sport events and their association with revisit intention. The models were tested using confirmatory factor analyses and structural equation modeling.

Findings

The four dimensions of experience were confirmed. Yet, they differ across the three sport events. For instance, whereas entertainment loaded highest on experience for all events, education had the second-highest factor loading for the table tennis event and esthetics for the ice hockey and motorsports events.

Practical implications

Sport event marketers must understand spectators' experiences and the influence on post-consumption behavior. For motorsports, the promotional material should emphasize the esthetics of an experience, for ice hockey the entertainment, and for table tennis education is at the core of the experience.

Originality/value

This study employed the four realms of experience to a sport event setting, which is new. The results suggested that the three sport events provide distinct experiencescapes for the spectators.
New insights into IFRS and earnings quality: what conclusions to draw from the French experience?
Authors: Benkraiem Ramzi , Ben Saad Itidel , Lakhal Faten
Published: December 2020

Purpose

The purpose of this study is to examine the effect of International Financial Reporting Standards (IFRS) on earnings quality in a continental European context (i.e. France) more than a decade after their mandatory adoption. Furthermore, the authors investigate whether the IFRS effect depends on firm-specific incentives.

Design/methodology/approach

The authors construct an aggregated measure that considers the main qualitative information characteristics: reliability and relevance. They identify accruals quality, earnings smoothing and the degree of conditional conservatism as attributes of reliability and use earnings persistence, predictability, value relevance and timeliness to measure earnings relevance. To test the hypotheses, the authors use a sample of French listed companies. The analyses are based on ordinary least squares (OLS) fixed effects, the Newey–West estimator and the difference-in-difference approach. The authors also use cluster analysis to identify firms with high incentives for earnings quality.

Findings

The results reveal a decrease in earnings quality that persisted for a decade after IFRS adoption. This decrease is mainly due to a decline in earnings relevance, suggesting that the fair value principle worsened earnings volatility. However, the results show that there is an improvement in earnings reliability after IFRS adoption, suggesting that the international standards were able to constrain managerial opportunism. Additionally, the findings reveal that firm-specific incentives can enhance the positive effect of IFRS, but the incentives are not able to substitute for such effect.

Research limitations/implications

The IFRS effect depends on firm-specific incentives.

Practical implications

The authors prove that firm-specific incentives are important to accentuate the positive effect of IFRS on earnings reliability and to mitigate the impact of IFRS on earnings relevance.

Originality/value

This paper makes several contributions to the literature. First, it addresses the relative lack of attention to the main qualitative characteristics in measuring earnings quality, that is, earnings reliability and earning relevance, and uses an aggregate earnings quality measure. Second, this paper uses a cluster analysis to highlight the role of firm-specific incentives in shaping the effect of IFRS on earnings quality.
The COVID-19 pandemic lockdown: a buzz of negativity with a silver lining of social connectedness
Authors: Amoah Anthony , Amoah Benjamin
Published: December 2020

Purpose

Lockdowns are generally characterised by financial depletion, loneliness, stress, depression, loss of jobs and businesses, among others. The effect of the recent lockdown in Ghana as a result of COVID-19 pandemic has not been different. The primary question this study seeks to answer is: are lockdowns only characterised by negativity, or could there be a positive side that has not yet been harnessed?

Design/methodology/approach

To answer this question, the authors rely on a dataset of 879 observations obtained through an online survey administered from 25 April to 3 May 2020. Using a regression approach, the authors applied an ordered probit econometric technique with its associated predicted margins.

Findings

The authors show evidence that in the midst of the negativity surrounding the lockdown, social connectedness is evident, especially in relatively less busy cities. The authors recommend that instead of losing oneself through social isolation and loneliness during lockdowns, people should use lockdowns as an opportunity to build and exhibit social capital and harness the opportunities associated with it. The authors also recommend that during lockdowns, channels of social connectedness should be made easily accessible and cheaper through a well-targeted government subsidy programme for the poor.

Originality/value

To the best of the authors' knowledge, this is a novel study that provides the first empirical evidence on the relationship between coronavirus disease 2019 (COVID-19) pandemic lockdown and social connectedness.
The paradox of being a food artisan entrepreneur: responding to conflicting institutional logics
Authors: Lindbergh Jessica , Schwartz Birgitta
Published: December 2020

Purpose

The aim of this study is to understand how artisanal food entrepreneurs acting as businesses, which are grounded in the logic of profit and growth, navigate the anti-growth constraints of artisanal logic. The study answers the research question of, how and when do the artisanal entrepreneurs respond to tensions between the small-scale craftsmanship logic and the business growth logic?

Design/methodology/approach

This study consists of two cases of artisanal food entrepreneurs situated in rural regions of Sweden. The empirical material is collected through interviews, observations and secondary sources. The analysis consists of two steps: a narrative analysis and a categorization of institutional logics using Pache and Santos (2013) framework.

Findings

Our findings show that the artisanal food entrepreneurs used several types of response to the tensions between the two institutional logics. As businesses grew, business growth logic increasingly penetrated the companies' operations. They responded by combining and blending the two logics and avoided growing too large themselves by collaborating with suppliers and local farmers. In addition, other activities needed to be compartmentalized and hidden since these activities could threaten their business images and their own criteria for small-scale food artisans.

Originality/value

Much work on how different institutional logics affect businesses have been on a structural level. This study answers the call on that more research is needed on an individual level by studying how individuals interpret logics and use them in their business activities.