bluuebunny/crossref_metadata_2025 huggingface dataset:
So your patient is a gamer: an exploration of benefits and harms
Authors: Lamar Luke , Craig James T. , Shubkin Catherine D.
Published: August 2021

Purpose of review

The appropriate amount and type of screen time for children remains a persistent topic of discussion between parents and pediatricians. During the COVID-19 pandemic, screen time has considerably increased. The need to quarantine and utilize remote learning prompted our review of the basis for current screen time recommendations and more recent research.

Recent findings

The broad stroke of recent research points to an association of increased video game screen time with sedentary lifestyle and its related harms. However, there also are specific instances where video games have been found to be therapeutically useful for certain populations.

In light of these findings, it is prudent for the pediatrician to explore more of the ‘why’ of video game use as opposed to purely the ‘how much’. Given the future beneficial therapeutic uses of some video games, clinicians should keep their eyes on this space for its continued development.
“First in Man” Total Percutaneous Aortic Arch Repair With 3-Inner-branch Endografts
Authors: Mougin Justine , Azogui Ron , Guihaire Julien , Tyrrell Mark R. , Oderich Gustavo S. , Fabre Dominique , Haulon Stéphan
Published: August 2021

Summary Background Data:

Aneurysms of the arch are a complex clinical problem and a technical challenge. Currently, over 40% of patients are considered unfit for conventional open surgery, requiring a cardiopulmonary bypass and hypothermic circulatory arrest. In experienced hands and appropriate anatomic conditions, arch-branched graft technology has shown to be a safe and effective alternative to open conventional surgery to patients that historically have had no surgical options.

Objectives:

This report summarizes the first in man implant of a three-vessel arch branch stent graft using a total percutaneous approach without the need for exposure of the cervical arteries—a surgical step with inherent problems and risks.

Methods:

This approach was performed in two consecutive patients, a 66-year-old woman with a chronic post type A dissection 60 mm diameter aneurysm of the aortic arch, and a 72-year-old man with a 70 mm saccular degenerative atheromatous aortic arch aneurysm.

Results:

Technical success was obtained in both cases. The patients were extubated in the operating theatre. Neither suffered any pre- or postoperative neurological deficits. Both were discharged home after remarkably uneventful hospital stays. There were no access complications. Postoperative computerized tomography scans and ultra-sound confirmed patent supra-aortic branches and completely excluded aneurysms.

Conclusions:

Our new truly minimally invasive approach demonstrates that it is possible to manage one of the most challenging treatments of aortic pathologies without any surgical incision. Further, evaluation and experience are required to confirm these promising results.
Opioid Use After Gastric Bypass, Sleeve Gastrectomy or Intensive Lifestyle Intervention
Authors: Wallén Stefan , Bruze Gustaf , Ottosson Johan , Marcus Claude , Sundström Johan , Szabo Eva , Olbers Torsten , Palmetun-Ekbäck Maria , Näslund Ingmar , Neovius Martin
Published: August 2021

Objective:

To compare opioid use in patients with obesity treated with bariatric surgery versus adults with obesity who underwent intensive lifestyle modification.

Summary of Background Data:

Previous studies of opioid use after bariatric surgery have been limited by small sample sizes, short follow-up, and lack of control groups.

Methods:

Nationwide matched cohort study including individuals from the Scandinavian Obesity Surgery Registry and the Itrim health database with individuals undergoing structured intensive lifestyle modification, between August 1, 2007 and September 30, 2015. Participants were matched on Body Mass Index, age, sex, education, previous opioid use, diabetes, cardiovascular disease, and psychiatric status (n = 30,359:21,356). Dispensed opioids were retrieved from the Swedish Prescribed Drug Register from 2 years before to up to 8 years after intervention.

Results:

During the 2-year period before treatment, prevalence of individuals receiving ≥1 opioid prescription was identical in the surgery and lifestyle group. At 3 years, the prevalence of opioid prescriptions was 14.7% versus 8.9% in the surgery and lifestyle groups (mean difference 5.9%, 95% confidence interval 5.3–6.4) and at 8 years 16.9% versus 9.0% (7.9%, 6.8–9.0). The difference in mean daily dose also increased over time and was 3.55 mg in the surgery group versus 1.17 mg in the lifestyle group at 8 years (mean difference [adjusted for baseline dose] 2.30 mg, 95% confidence interval 1.61–2.98).

Conclusions:

Bariatric surgery was associated with a higher proportion of opioid users and larger total opioid dose, compared to actively treated obese individuals. These trends were especially evident in patients who received additional surgery during follow-up.
Chronic Pain After Groin Hernia Surgery in Women
Authors: Jakobsson Ebbe , Lundström Karl-Johan , Holmberg Henrik , de la Croix Hanna , Nordin Pär
Published: August 2021

Objective:

The aim of this study was to evaluate chronic pain 1 year after surgery, and risk factors for chronic pain after groin hernia repair in women.

Background:

Groin hernia surgery in women is less frequently studied than in men. Chronic pain is common after groin hernia surgery and remains an important area with room for improvement. Previous studies are small or inconclusive. Guidelines recommend timely repair of all female groin hernias.

Methods:

From the Swedish Hernia Register 4021 female and 37,542 male patients operated between September 1, 2012 and August 30, 2017 responded to a patient-reported outcome questionnaire (response rate 70.0%) 1 year after primary groin hernia surgery. Multivariable analysis was performed to compare chronic postoperative pain in women with men as a control group, and to evaluate risk factors for chronic pain in women.

Results:

Among women operated for groin hernia, 18% suffered chronic postoperative pain. The risk for chronic pain was significantly higher for women [odds ratio 1.3 (95% confidence interval 1.16–1.46). Three risk factors for chronic pain in women were found: high body mass index, high American Society of Anesthesiologists classification, and femoral hernia. No differences in chronic pain in women were seen when comparing surgical methods or emergency versus elective surgery.

Conclusions:

Almost one-fifth of women suffered of chronic pain affecting daily activity after groin hernia repair. Chronic pain was more common for women than men. In view of the high-rate chronic postoperative pain, further research on management strategies in female groin hernia is warranted.
Surgical Performance Anxiety and Wellbeing Among Surgeons
Authors: Miller Robert , Hotton Matthew , Williamon Aaron , Kneebone Roger , Goodacre Tim , O’Leary Denis , Chan James K. K.
Published: August 2021

Objective:

This national cross-sectional study aims to establish the prevalence and potential impact of performance anxiety among surgeons and investigate its association with psychological traits and wellbeing.

Summary and Background Data:

Despite a growing awareness that human factors, non-technical skills and wellbeing in healthcare affect patient outcomes, an area that has remained unexplored is surgical performance anxiety (SPA).

Methods:

A prospectively registered, cross-sectional study using mixed methods was conducted across the United Kingdom. Data captured included demographics, surgical specialty, trait anxiety, trait perfectionism, SPA, and surgical perfectionism scores. Wellbeing was assessed using The Short Warwick-Edinburgh Mental Wellbeing Scale, whereas qualitative data were collected regarding surgeons’ experiences of SPA.

Results:

A total of 631 responses were collected. Mean age was 41·2 years and mean surgical experience 15·3 years. A total of 62% were male and 52% of consultant/attending grade. A total of 100% felt that SPA affected surgeons, with 87% having experienced it themselves. A total of 65% reported SPA negatively impacted surgical performance and 96% felt SPA negatively impacted surgeons’ wellbeing. Male surgeons reported significantly better wellbeing than female surgeons. Surgeons with SPA reported significantly worse wellbeing compared with surgeons who did not experience SPA. Surgeons in general experienced significantly lower mental wellbeing compared with population norms. Thematic analysis highlighted a reticence to share SPA openly and need for cultural change.

Conclusions:

Surgical performance anxiety is a very common and significant challenge among surgeons across all specialties at all levels of experience in the United Kingdom. It is perceived by surgeons to affect surgical performance adversely and is associated with worse psychological wellbeing. A more open culture of sharing and acknowledgment has been identified to be beneficial.
Effect of Pregnancy on eGFR After Kidney Transplantation: A National Cohort Study
Authors: van Buren Marleen C. , Gosselink Margriet , Groen Henk , van Hamersvelt Henk , de Jong Margriet , de Borst Martin H. , Zietse Robert , van de Wetering Jacqueline , Lely A. Titia ,   on behalf of the PARTOUT working group
Published: August 2021

Background.

The effect of pregnancy on the course of estimated glomerular filtration rate (eGFR) is unknown in kidney transplant recipients (KTRs).

Methods.

We conducted a nationwide multicenter cohort study in KTRs with pregnancy (>20 wk) after kidney transplantation (KT). Annual eGFRs after KT until death or graft loss and additional eGFRs before each pregnancy were collected according to protocol. Changes in eGFR slope before and after each pregnancy were analyzed by generalized estimating equations multilevel analysis adjusted for transplant vintage.

Results.

We included 3194 eGFR measurements before and after pregnancy in 109 (55%) KTRs with 1, 78 (40%) with 2, and 10 (5%) with 3 pregnancies after KT. Median follow-up after first delivery post-KT was 14 y (interquartile range, 18 y). Adjusted mean eGFR prepregnancy was 59 mL/min/1.73 m2 (SEM [standard error of the mean] 1.72; 95% confidence interval [CI], 56-63), after the first pregnancy 56 mL/min/1.73 m2 (SEM 1.70; 95% CI, 53-60), after the second pregnancy 56 mL/min/1.73 m2 (SEM 2.19; 95% CI, 51-60), and after the third pregnancy 55 mL/min/1.73 m2 (SEM 8.63; 95% CI, 38–72). Overall eGFR slope after the first, second, and third pregnancies was not significantly worse than prepregnancy (P = 0.28). However, adjusted mean eGFR after the first pregnancy was 2.8 mL/min/1.73 m2 (P = 0.08) lower than prepregnancy.

Conclusions.

The first pregnancy has a small, but insignificant, effect on eGFR slope in KTRs. Midterm hyperfiltration, a marker for renal reserve capacity, was associated with better eGFR and death-censored graft survival. In this KTR cohort with long-term follow-up, no significant effect of pregnancy on kidney function was detected.
Impact of Red Blood Cells on Function and Metabolism of Porcine Deceased Donor Kidneys During Normothermic Machine Perfusion
Authors: Venema Leonie H. , van Leeuwen L. Leonie , Posma Rene A. , van Goor Harry , Ploeg Rutger J. , Hannaert Patrick , Hauet Thierry , Minor Thomas , Leuvenink Henri G.D. ,   on behalf of the COPE Consortium
Published: August 2021

Background.

Normothermic machine perfusion (NMP) protocols using blood-based solutions are commonly used in the assessment of kidneys before transplantation. This procedure is, nevertheless, limited by blood availability and warrants the search for alternatives. We compared a blood-based solution with a serum-like preservation solution (Aqix) enriched with colloids with and without red blood cells (RBCs).

Methods.

Porcine kidneys retrieved from an abattoir were subjected to 30 min of warm ischemia, followed by 3 h of hypothermic oxygenated machine perfusion at 4 °C. Subsequently, kidneys (n = 6 per group) were evaluated with NMP for 4 h with 5 different solutions: diluted blood, Aqix with BSA ± RBCs, or Aqix with dextran 40 ± RBCs.

Results.

Throughout NMP, markers of renal function and tubular metabolism were favorable in groups with RBCs. The addition of RBCs resulted in 4- to 6-fold higher oxygen consumption rates. Controls had significantly higher ATP levels post-NMP, exhibited decreased production of oxidative stress markers, and had the highest creatinine clearance. In conclusion, this study shows that the addition of RBCs during NMP reduced renal injury, improved function, and was associated with increased renal metabolism.

Conclusions.

Although the RBC-BSA–supplemented Aqix solution was also able to support metabolism and renal function, a blood-based perfusion solution remains superior.
Lattice Boltzmann simulations on the tumbling to tank-treading transition: effects of membrane viscosity
Authors: Guglietta Fabio , Behr Marek , Biferale Luca , Falcucci Giacomo , Sbragaglia Mauro
Published: August 2021

The tumbling to tank-treading (TB-TT) transition for red blood cells (RBCs) has been widely investigated, with a main focus on the effects of the viscosity ratio

λ

(i.e., the ratio between the viscosities of the fluids inside and outside the membrane) and the shear rate

γ
˙

applied to the RBC. However, the membrane viscosity

μ

m

plays a major role in a realistic description of RBC dynamics, and only a few works have systematically focused on its effects on the TB-TT transition. In this work, we provide a parametric investigation on the effect of membrane viscosity

μ

m

on the TB-TT transition for a single RBC. It is found that, at fixed viscosity ratios

λ

, larger values of

μ

m

lead to an increased range of values of capillary number at which the TB-TT transition occurs; moreover, we found that increasing

λ

or increasing

μ

m

results in a qualitatively but not quantitatively similar behaviour. All results are obtained by means of mesoscale numerical simulations based on the lattice Boltzmann models.

This article is part of the theme issue ‘Progress in mesoscale methods for fluid dynamics simulation’.
Lattice Boltzmann simulations of drying suspensions of soft particles
Authors: Wouters M. , Aouane O. , Sega M. , Harting J.
Published: August 2021

The ordering of particles in the drying process of a colloidal suspension is crucial in determining the properties of the resulting film. For example, microscopic inhomogeneities can lead to the formation of cracks and defects that can deteriorate the quality of the film considerably. This type of problem is inherently multiscale and here we study it numerically, using our recently developed method for the simulation of soft polymeric capsules in multicomponent fluids. We focus on the effect of the particle softness on the film microstructure during the drying phase and how it relates to the formation of defects. We quantify the order of the particles by measuring both the Voronoi entropy and the isotropic order parameter. Surprisingly, both observables exhibit a non-monotonic behaviour when the softness of the particles is increased. We further investigate the correlation between the interparticle interaction and the change in the microstructure during the evaporation phase. We observe that the rigid particles form chain-like structures that tend to scatter into small clusters when the particle softness is increased.

This article is part of the theme issue ‘Progress in mesoscale methods for fluid dynamics simulation’.
A lattice Boltzmann model for reactive mixtures
Authors: Sawant N. , Dorschner B. , Karlin I. V.
Published: August 2021

A new lattice Boltzmann model for reactive ideal gas mixtures is presented. The model is an extension to reactive flows of the recently proposed multi-component lattice Boltzmann model for compressible ideal gas mixtures with Stefan–Maxwell diffusion for species interaction. First, the kinetic model for the Stefan–Maxwell diffusion is enhanced to accommodate a source term accounting for the change in the mixture composition due to chemical reaction. Second, by including the heat of formation in the energy equation, the thermodynamic consistency of the underlying compressible lattice Boltzmann model for momentum and energy allows a realization of the energy and temperature change due to chemical reactions. This obviates the need for ad-hoc modelling with source terms for temperature or heat. Both parts remain consistently coupled through mixture composition, momentum, pressure, energy and enthalpy. The proposed model uses the standard three-dimensional lattices and is validated with a set of benchmarks including laminar burning speed in the hydrogen–air mixture and circular expanding premixed flame.

This article is part of the theme issue ‘Progress in mesoscale methods for fluid dynamics simulation’.
Comprehensive analysis of the immunogenomic landscape and clinical features in cervical cancer
Authors: Fan Xinyue , He Chunbo
Published: August 2021

Immunotherapy has changed the standard of treatment for many cancers. However, the same treatments showed disappointing outcomes in cervical cancer so far. Thus, understanding the mechanisms that support the immune tolerance of cervical cancer will provide a way to design new strategies to enhance immunotherapies. Here, we characterized cellular compositions of the immune infiltrates in cervical cancer and investigated if the tumor immune landscape is a predictor for patient prognosis. The fraction of ten immune infiltrates of cervical and other cancers were analyzed by using QuanTIseq software base on the bulk mRNA sequencing data from The Cancer Genome Atlas Program (TCGA). Cervical cancer is one of the cancers that had the lowest percentage of total immune infiltrates, but it had the highest ratio for CD8 T cells to all immune infiltrates among all solid cancers. Both the principal components (PCA) analysis and heatmap with dendrogram analysis showed that cervical cancer had a similar immune infiltrated microenvironment with other squamous cell carcinomas, such as head and neck cancer and lung squamous cell cancer. The PCA and heatmap with dendrogram analysis showed that cervical cancer and HPV positive head and neck cancers were clustered more closer and partially separated with HPV negative head and neck cancer. Further analysis showed that HPV-positive cervical and head and neck cancers had a significantly higher level of CD8 T cells and M1-liked macrophages, but a lower level of M2 macrophages. The survival analysis showed that a higher level of CD8 T cells was associated with a better patient prognosis. However, immuno-suppressive immune infiltrates including M2 macrophages and Treg cells that are known to suppress anti-tumor immunity also demonstrated positive patient overall survival. Our study provided a conceptual framework to understand the tumor immune microenvironment of cervical cancer. Our results also demonstrated that the immune infiltrates can be a prognosis marker for cervical cancer.

Simple Summary

Cervical cancer is the most common gynecologic cancer and the fourth leading cause of cancer-related death in women worldwide. There are relatively limited treatment options for late-stage cervical cancer. Immunotherapy is a new therapeutic treatment developed with great success in treating many cancers, but the same treatment has not been producing satisfactory results in many cases of cervical cancer. In the present study, we provided a comprehensive immune characterization specifically for cervical cancer. We determined the prognostic value of a specific subtype of tumor-infiltrating immune cells for clinical outcomes and demonstrated that HPV infection affected the immune cell infiltration and induce pro-inflammatory phenotypes. Our study provides a systematic insight into the tumor immune microenvironment of cervical cancers and offers a conceptual framework for the future design of rational combination treatment strategies to improve immunotherapy outcomes.
Metabolic regulation of species-specific developmental rates
Authors: Diaz-Cuadros Margarete , Miettinen Teemu P , Sheedy Dylan , Diaz-Garcia Carlos Manlio , Gapon Svetlana , Hubaud Alexis , Yellen Gary , Manalis Scott R , Oldham William , Pourquie Olivier
Published: August 2021

Animals display significant inter-specific variation in the rate of embryonic development despite broad conservation of the overall sequence of developmental events. Differences in biochemical reaction speeds, including the rates of protein production and degradation, are thought to be responsible for distinct species-specific rates of development. However, the cause of differential biochemical reaction speeds between species remains unknown. Using pluripotent stem cells, we have established an in vitro system that recapitulates the two-fold difference in developmental rate between early mouse and human embryos. This system provides a quantitative measure of developmental speed as revealed by the period of the segmentation clock, a molecular oscillator associated with the rhythmic production of vertebral precursors. Using this system, we showed that mass-specific metabolic rates scale with developmental rate and are therefore elevated in mouse cells compared to human cells. We further showed that reducing these metabolic rates by pharmacologically inhibiting the electron transport chain slows down the segmentation clock. The effect of the electron transport chain on the segmentation clock is mediated by the cellular NAD+/NADH redox balance independent of ATP production and, further downstream, by the global rate of protein synthesis. These findings represent a starting point for the manipulation of developmental rate, which would find multiple translational applications including the acceleration of human pluripotent stem cell differentiation for disease modeling and cell-based therapies.
The Need for Transfer Learning in CRISPR-Cas Off-Target Scoring
Authors: Kota Pavan K. , Pan Yidan , Vu Hoang-Anh , Cao Mingming , Baraniuk Richard G. , Bao Gang
Published: August 2021

Motivation

The scalable design of safe guide RNA sequences for CRISPR gene editing depends on the computational “scoring” of DNA locations that may be edited. As there is no widely accepted benchmark dataset to compare scoring models, we present a curated “TrueOT” dataset that contains thoroughly validated datapoints to best reflect the properties of in vivo editing. Many existing models are trained on data from high throughput assays. We hypothesize that such models may suboptimally transfer to the low throughput data in TrueOT due to fundamental biological differences between proxy assays and in vivo behavior. We developed new Siamese convolutional neural networks, trained them on a proxy dataset, and compared their performance against existing models on TrueOT.

Results

Our simplest model with a single convolutional and pooling layer surprisingly exhibits state-of-the-art performance on TrueOT. Adding subsequent layers improved performance on a proxy dataset while compromising performance on TrueOT. We demonstrate improved generalization on TrueOT with a Siamese model of higher complexity when we apply transfer learning techniques. These results suggest an urgent need for the CRISPR community to agree upon a benchmark dataset such as TrueOT and highlight that various sources of CRISPR data cannot be assumed to be equivalent.

Availability and Implementation

Our code base and datasets are available on GitHub at github.com/baolab-rice/CRISPR_OT_scoring.
Forecasting Preventive Dental Quality Measures
Authors: Nagarajan Radhakrishnan , Panny Aloksagar , Ryan Megan , Murphy Scott , Vujicic Marko , Nycz Gregory
Published: August 2021

Dental quality measures objectively measure the efficiency and performance of dental providers and organizations. While these measures in conjunction with established benchmarks are used routinely for self-assessment, forecasting them ahead of time in a data-driven and evidence-based manner has the potential to assist in assessing future dental treatment needs, oral disease burden, care utilization patterns, and strategic decision making for sustained performance improvement complementing traditional descriptive visualization dashboards. The present study modeled the temporal trends of four key preventive dental quality measures related to caries prevention (Adult New Caries, Sealants (6-9yrs.), Sealants (12-15yrs.), Fluoride Varnish) sampled monthly from (Dec. 2010 to July 2017) averaged across ten Family Health Center Dental Centers (FQHC), Wisconsin, using auto-regressive integrated moving average time series models. Five-month ahead forecasts along with their 95% confidence levels and mean absolute percentage error were determined across the four measures (Adult New Caries: 1.8%, Sealants (6-9yrs.): 0.90%, Sealants (12-15yrs.): 0.30%, Fluoride Varnish: 0.15%). Model diagnostics revealed auto-regressive integrated moving average models to sufficiently capture the temporal patterns of these measures and the forecast estimates of Adult New Caries and Sealants (12-15yrs.) revealed the need for increased efforts for improved preventive care utilization. Forecasting preventive dental quality measures can provide insights into expected treatment needs ahead of time and can assist in optimal resource and staff allocation with potential to prescribe suitable interventions to shift the trajectory from predicted outcomes to desired outcomes in a targeted manner. While the present study investigated organization level preventive dental quality measures, the time series approach presented is as such generic and expected to translate across similar settings.
Predicting the impact of low influenza activity in 2020 on population immunity and future influenza season in the United States
Authors: Lee Kyueun , Jalal Hawre , Raviotta Jonathan M. , Krauland Mary G. , Zimmerman Richard K. , Burke Donald S. , Roberts Mark S.
Published: August 2021

Backgrounds

The influenza season of 2020-21 was remarkably low, likely due to implementation of public health preventive measures such as social distancing, mask-wearing, and school closure and due to decreased international travel. This leads to a key public health question: what will happen in the 2021-22 influenza season? To answer this, we developed a multi-season influenza model that accounted for residual immunity from prior infection.

Method

We built a multi-strain, non-age structured compartmental model that captures immunity over multiple influenza seasons. By the end of the influenza season, we sorted the population based on their experience of natural infection and/or vaccination, which determines the susceptibility to influenza infection in the following season. Because the exact parameters of transmission rates and immunity are unknown, we implemented Bayesian calibration against the observed influenza epidemics (influenza hospitalization rates from 2012 to 2020 in the US) to estimate those parameters. In forward projections, we simulated low influenza activity in 2020-21 season by lowering transmission rate by 20%. Compared to the counterfactual case, in which influenza activity remained at the normal level in 2020-21, we estimated the change in the number of hospitalizations in the following seasons with varying level of vaccine uptake and effectiveness. We measured the change in population immunity over time by varying the number of seasons with low influenza activity.

Result

With the low influenza activity in 2020-21, the model estimated 102,000 [95% CI: 57,000-152,000] additional hospitalizations in 2021-22, without change in vaccine uptake and effectiveness. The expected change in hospitalization varied depending on the level of vaccine uptake and effectiveness in the following year. Achieving 50% increase in one of two measures (1.5X vaccine uptake with 1X vaccine efficacy or 1.5X vaccine efficacy with 1X vaccine uptake) was necessary to avert the expected increase in hospitalization in the next influenza season. Otherwise, increases in both measures by 25% averted the expected increase in influenza-hospitalization. If the low influenza activity seasons continue, population immunity would remain low during those seasons, with 48% the population susceptible to influneza infection.

Conclusion

We predicted a large compensatory influenza season in 2021-2 due to a light season in 2020-21. However, higher influenza vaccine uptake would reduce this projected increase in influenza.
Identifying SNP associations and predicting disease risk from Genome-wide association studies using LassoNet
Authors: Sajwani Hussain M. , Feng Samuel F.
Published: August 2021

In this paper, we show that under certain conditions LassoNet [1] should outperform threshold of significance (P-value) methods for identifying multi-SNP disease associations and predicting disease risk using data from Genome Wide Association Studies. To demonstrate this, we built a genotype-phenotype simulation to comprehensively benchmark each method’s performance in variant selection and in predicting disease risk. Our results suggest that LassoNet, with its ease of implementation, should be added to the biomedical informatician’s toolkit. We release code to replicate our results.
Adding context to the pneumococcal core genes – a bioinformatic analysis of the intergenic pangenome of Streptococcus pneumoniae
Authors: Nielsen Flemming Damgaard , Møller-Jensen Jakob , Jørgensen Mikkel Girke
Published: August 2021

Whole genome sequencing offers great opportunities for linking genotypes to phenotypes aiding in our understanding of human disease and bacterial pathogenicity. However, these analyses often overlook non-coding intergenic regions (IGRs). By disregarding the IGRs, crucial information is lost, as genes have little biological function without expression. In this study, we present the first complete pangenome of the important human pathogen Streptococcus pneumoniae (pneumococcus), spanning both the genes and IGRs. We show that the pneumococcus species retains a small core genome of IGRs that are present across all isolates. Gene expression is highly dependent on these core IGRs, and often several copies of these core IGRs are found across each genome. Core genes and core IGRs show a clear linkage as 81% of core genes are associated with core IGRs. Additionally, we identify a single IGR within the core genome that is always occupied by one of two highly distinct sequences, scattered across the phylogenetic tree. Their distribution indicates that this IGR is transferred between isolates through horizontal regulatory transfer independent of the flanking genes and that each type likely serves different regulatory roles depending on their genetic context.
Interactions between RNA m6A modification, alternative splicing, and poly(A) tail revealed by MePAIso-seq2
Authors: Liu Yusheng , Zhang Yiwei , Lu Falong , Wang Jiaqiang
Published: August 2021

RNA post-transcriptional regulation involves 5′-end capping, 3′ poly(A) tailing (including polyadenylation sites, tail length, and non-A residues1, 2), alternative splicing, and chemical modifications including N6-methyladenosine (m6A)3. Studying the interplay of m6A, alternative splicing, alternative polyadenylation sites, poly(A) tail length, and non-A residues in poly(A) tails requires monitoring them simultaneously on one transcript, however strategies to achieve this are lacking. Therefore, we developed a new method, combining m6A-specific methylated RNA immunoprecipitation and the PacBio-based, tail-included, full-length RNA sequencing approach PAIso-seq2, which we’ve named m6A and poly(A) inclusive RNA isoform sequencing 2 (MePAIso-seq2). Using MePAIso-seq2, we revealed that m6A promotes and inhibits a similar number of alternative splicing events in mouse cell lines, showing that m6A does affect alternative splicing. In contrast, no correlation was detected between m6A and alternative polyadenylation sites choice. Surprisingly, we found that m6A-modified RNAs possess longer poly(A) tails and a lower proportion of poly(A) tails containing non-A residues, especially in mouse embryonic stem cells. Together, we developed a new method to detect full-length m6A-modified RNAs to comprehensively study the relationships between m6A, alternative splicing, and poly(A) tailing, laying a foundation for further exploration of the functional coordination of different RNA post-transcriptional modifications.
The OPAQUE1/DISCORDIA2 myosin XI is required for phragmoplast guidance during asymmetric cell division in maize
Authors: Nan Qiong , Liang Hong , Mendoza Janette , Liu Le , Fulzele Amit , Wright Amanda , Bennett Eric J , Rasmussen Carolyn G. , Facette Michelle R
Published: August 2021

Formative asymmetric divisions produce cells with different fates and are critical for development. We show the myosin XI protein, OPAQUE1 (O1), is necessary for asymmetric divisions during maize stomatal development. We analyzed stomatal precursor cells prior to and during asymmetric division to determine why o1 mutants have abnormal division planes. Cell polarization and nuclear positioning occur normally in the o1 mutant, and the future site of division is correctly specified. The defect in o1 occurs during late cytokinesis, when the phragmoplast forms the nascent cell plate. Initial phragmoplast guidance in o1 is correct; however, as phragmoplast expansion continues o1 phragmoplasts become misguided. To understand how O1 contributes to phragmoplast guidance, we identified O1-interacting proteins. Maize kinesins related to the Arabidopsis thaliana division site markers PHRAGMOPLAST ORIENTING KINESINs (POKs), which are also required for correct phragmoplast guidance, physically interact with O1. We propose that different myosins are important at multiple steps of phragmoplast expansion, and the O1 actin motor and POK-like microtubule motors work together to ensure correct late-stage phragmoplast guidance.
Leveraging epigenomes and three-dimensional genome organization for interpreting regulatory variation
Authors: Baur Brittany , Schreiber Jacob , Shin Junha , Zhang Shilu , Zhang Yi , Manjunath Mohith , Song Jun S. , Noble William Stafford , Roy Sushmita
Published: August 2021

Understanding the impact of regulatory variants on complex phenotypes is a significant challenge because the genes and pathways that are targeted by such variants are typically unknown. Furthermore, a regulatory variant might influence a particular gene’s expression in a cell type or tissue-specific manner. Cell-type specific long-range regulatory interactions that occur between a distal regulatory sequence and a gene offers a powerful framework for understanding the impact of regulatory variants on complex phenotypes. However, high-resolution maps of such long-range interactions are available only for a handful of model cell lines. To address this challenge, we have developed L-HiC-Reg, a Random Forests based regression method to predict high- resolution contact counts in new cell lines, and a network-based framework to identify candidate cell line-specific gene networks targeted by a set of variants from a Genome-wide association study (GWAS). We applied our approach to predict interactions in 55 Roadmap Epigenome Consortium cell lines, which we used to interpret regulatory SNPs in the NHGRI GWAS catalogue. Using our approach, we performed an in-depth characterization of fifteen different phenotypes including Schizophrenia, Coronary Artery Disease (CAD) and Crohn’s disease. In CAD, we found differentially wired subnetworks consisting of known as well as novel gene targets of regulatory SNPs. Taken together, our compendium of interactions and associated network-based analysis pipeline offers a powerful resource to leverage long-range regulatory interactions to examine the context-specific impact of regulatory variation in complex phenotypes.
Endothelial integration of mechanosensory signals by the spectrin cytoskeleton
Authors: Mylvaganam Sivakami , Yusuf Bushra , Li Ren , Lu Chien-Yi , Robinson Lisa A. , Freeman Spencer A. , Grinstein Sergio
Published: August 2021

Physiological blood flow induces the secretion of vasoactive compounds, notably NO, and promotes endothelial cell elongation and reorientation parallel to the direction of applied shear. How shear is sensed and relayed to intracellular effectors is incompletely understood. We demonstrate that an apical spectrin network is essential to convey the force imposed by shear to endothelial mechanosensors. By anchoring CD44, spectrin modulates the cell surface density of hyaluronan, which senses and translates shear into changes in plasma membrane tension. Spectrins also regulate the stability of apical caveolae, where the mechanosensitive Piezo1 channels are thought to reside. Accordingly, shear-induced Piezo1 activation and the associated calcium influx were absent in spectrin-deficient cells. As a result, cell realignment and flow-induced eNOS stimulation were similarly dependent on spectrin. We concluded that the apical spectrin network is not only required for shear sensing, but transmits and distributes the resulting tensile forces to mechanosensors that elicit protective and vasoactive responses.
A novel regulatory gene promotes novel cell fate by suppressing ancestral fate in the sea anemone Nematostella vectensis
Authors: Babonis Leslie S , Enjolras Camille , Ryan Joseph F , Martindale Mark Q
Published: August 2021

Cnidocytes (“stinging cells”) are an unequivocally novel cell type used by cnidarians (corals, jellyfish, and their kin) to immobilize prey. Although they are known to share a common evolutionary origin with neurons, the developmental program that promoted the emergence of cnidocyte fate is not known. Using functional genomics in the sea anemone, Nematostella vectensis, we show that cnidocytes evolved by suppression of neural fate in a subset of neurons expressing RFamide. We further show that a single regulatory gene, a C2H2-type zinc finger transcription factor (ZNF845), coordinates both the gain of novel (cnidocyte-specific) traits and the inhibition of ancestral (neural) traits during cnidocyte development and that this gene arose by domain shuffling in the stem cnidarian. Thus, we uncover a mechanism by which a truly novel regulatory gene (ZNF845) promoted the origin of a truly novel cell type (cnidocyte) through duplication of an ancestral cell lineage (neuron) and inhibition of its ancestral identity (RFamide).

Significance

In this study, we demonstrate how new cell types can arise in animals through duplication of an ancestral (old) cell type followed by functional divergence of the new daughter cell. Specifically, we show that stinging cells in cnidarians (jellyfish and corals) evolved by duplication of an ancestral neuron followed by inhibition of the RFamide neuropeptide it once secreted. This is the first evidence that stinging cells evolved from a specific subtype of neurons and suggests some neurons may be easier to co-opt for novel functions than others.
Alternative Covid-19 mitigation measures in school classrooms: analysis using an agent-based model of SARS-CoV-2 transmission
Authors: Woodhouse M. J. , Aspinall W. P. , Sparks R. S. J. , Pollock E. Brooks , Relton C.
Published: August 2021

1.

The SARS-CoV-2 epidemic continues to have major impacts on children’s education, with schools required to implement infection control measures that have led to long periods of absence and classroom closures. We have developed an agent-based epidemiological model of SARS-CoV-2 transmission that allows us to quantify projected infection patterns within primary school classrooms, and related uncertainties; the basis of our approach is a contact model constructed using random networks, informed by structured expert judgement. The effectiveness of mitigation strategies are considered in terms of effectiveness at supressing infection outbreaks and limiting pupil absence. Covid-19 infections in schools in the UK in Autumn 2020 are re-examined and the model used for forecasting infection levels in autumn 2021, as the more infectious Delta-variant was emerging and school transmission thought likely to play a major role in an incipient new wave of the epidemic. Our results were in good agreement with available data. These findings indicate that testing-based surveillance of infections in the classroom population with isolation of positive cases is a more effective mitigation measure than bubble quarantine, both for reducing transmission in primary schools and for avoiding pupil absence, even accounting for insensitivity of self-administered tests. Bubble quarantine entails large numbers of pupils being absent from school, with only modest impact on classroom infection levels. However, maintaining reduced contact rates within the classroom can have a major beneficial impact for managing Covid-19 in school settings.
Impact of information and communication technologies (ICT) on student’s learning: a case from university of the Punjab, Pakistan
Authors: Ahmad Toqeer , Sheikh Arslan
Published: August 2021

Purpose

This study aims to investigate the impact of information and communication technologies (ICT) on student’s learning primarily concentrating on the following factors: including availability, accessibility and user-ability of using ICT resources. This investigation will highlight the role of ICT in the pedagogical activities of students, especially in their learning.

Design/methodology/approach

A questionnaire was designed to comprehend the questions related to the objectives and a sample of 275 students through convenience sampling technique was selected that was enrolled in various degree programs of the University of the Punjab, Pakistan. Primarily the descriptive analysis was made and data were presented in tabulated form. However, for inferential analysis, the Pearson correlation test was applied to determine the relationship among the dependent and independent variables including (availability, accessibility user-ability and student’s learning) and to test the hypotheses of the study.

Findings

The findings disclose that students at the University of the Punjab have access to various kinds of ICT applications and resources. Moreover, they have an adequate number of ICT equipment available for their use and they are familiar with various kinds of ICT applications and resources which they use in various educational tasks during their studies. A strong positive linear correlation exists between availability, accessibility and user-ability of using ICT resources and the student’s educational learning. This confirms that ICT plays a significant role in the student’s educational accomplishments. It helps students in searching, retrieving and consulting various types of information sources. It also helps them in completing their educational tasks in a quick manner. Students at all levels also see it as a matter of great importance to acquire ICT-related skills as this can help them to be more productive in their educational accomplishments.

Originality/value

This study concludes that availability, accessibility, adequacy and user ability to use the ICT resources positively impact students learning. Therefore, it is highly recommended for students to learn ICT-related skills and to make the best use of the different communication technologies in their pedagogical activities. Moreover, if academic institutions in Pakistan give more emphasis on developing ICT-based infrastructure and ICT skilled manpower then this can also bring fruitful results in the learning process of student’s educational endeavors.
Celebrity CEOs’ credibility, image of their brands and consumer materialism
Authors: Huaman-Ramirez Richard , Merunka Dwight
Published: August 2021

Purpose

This paper aims to model and estimate how celebrity chief executive officers (CEOs) credibility (i.e. expertise, trustworthiness, attractiveness) is related to their brand image (i.e. functional, sensory/visual). This paper further examines the effects of consumer materialism on both celebrity CEOs’ credibility and the image of their brand.

Design/methodology/approach

A total of 260 participants knowledgeable of CEOs and their corresponding brands completed an online questionnaire in a cross-sectional study. The data were analyzed through covariance-based structural equation modeling.

Findings

Celebrity CEOs’ expertise and attractiveness are positively related to both functional and sensory/visual images of their brands. Results also demonstrate the positive effect of materialism on both celebrity CEOs’ credibility and brand image.

Research limitations/implications

The research was conducted in one country (France) using a cross-sectional design. Additional studies in other settings or countries should be carried out to establish the generalizability of results and strengthen causality inferences.

Practical implications

CEOs need to understand and manage their key role as celebrities, given the direct influence they may have on consumer brand perceptions and behavior.

Originality/value

This study refines the relationship between celebrity CEOs’ credibility and brand image. It is the first to introduce and validate the effect of consumer materialism on the perception of celebrity CEOs.
Exploring the application of property graph model in visualizing COBie data
Authors: Kumar Vishal , Teo Evelyn Ai Lin Evelyn
Published: August 2021

Purpose

The usability aspect of the construction operations building information exchange (COBie) datasheet has been largely overlooked. Users find it difficult to find relevant data inside COBie and understand the dependencies of information. This research study is a part of a more comprehensive research study to identify the usability issues associated with COBie and propose solutions to deal with them. This paper aims to discuss the challenges associated with the visualization aspect of COBie and proposes a solution to mitigate them.

Design/methodology/approach

This paper is based on design thinking and waterfall methodology. While the design thinking methodology is used to explore the issues associated with the visualization aspect of COBie, the waterfall methodology is used to develop a working prototype of the visualizer for the COBie datasheet using a spreadsheet format.

Findings

The paper demonstrates that the property graph model based on a node-link diagram can be effectively used to represent the COBie datasheet. This will help in storing data in a visually connected manner and looking at links more dynamically. Moreover, converting and storing data into an appropriate database will help reach data directly rather than navigate multiple workbooks. This database can also help get the history of data inside the COBie datasheet as it develops throughout the project.

Originality/value

This research proposes a novel approach to visualize the COBie datasheet interactively using the property graph model, a type of node-link diagram. Using the property graph model will help users see data in a connected way, which is currently missing in the spreadsheet representation of COBie data. Moreover, this research also highlights that storing historical changes in COBie data can help understand how data has evolved throughout the construction. Additionally, structured storage of data in relationship format can help users to access the end of connected data directly through the efficient search.