bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Direct Health Education on the Uptake of Screening by First Degree Relatives of Glaucoma Patients in Nigeria
Authors: Ogunleye Olakunle , Olawoye Olusola , Sarimiye Tarela , Bekibele Charles , Ashaye Adeyinka
Published: December 2020

Précis:

First degree relatives (FDRs) of glaucoma patients are more likely to present for screening when they are directly contacted and educated by health workers on the phone compared with when they are only invited by their relative with glaucoma.

Objective:

The aim was to determine the effect of direct health education by phone calls on the uptake of glaucoma screening among FDRs of primary open angle glaucoma patients as a glaucoma blindness control strategy in an asymptomatic high-risk African population.

Methods:

This was a randomized clinical trial in which 102 primary open angle glaucoma patients (probands) were randomized into control and intervention groups. Both proband groups were educated about glaucoma and requested by the investigator to invite their adult FDR to attend a screening clinic within 1 month. In addition, the FDRs in the intervention group were directly contacted, educated, and invited for examination by phone calls. A total of 560 FDRs were enumerated by the probands. The main outcome measure was proportion of FDR that presented for screening.

Results:

A total of 218 (38.9%) FDRs took up glaucoma screening services. Eighty-nine (30.1%) of the 296 FDRs in the control group and 129 (48.9%) of the 264 FDRs in the intervention group presented for examination. After multivariate analysis, FDRs in the phone call group were 2.506 times [95% confidence interval (CI): 1.695-3.706] more likely to present than FDRs in the no phone call group. Young FDRs were more likely to present [odds ratio (OR)=3.593; 95% CI: 1.613-8.007] than the elderly FDRs, while FDRs living within 200 km of the hospital were also more likely to present (OR=5.200; 95% CI: 2.860-9.456) than those living far (>200 km) away. Probands with moderate to severe visual impairment were significantly more likely (OR=3.073; 95% CI: 1.845-4.352) to have their FDRs present than probands with mild or no visual impairment.

Conclusion:

Direct contact and health education of FDRs through phone calls had a significant positive effect on the uptake of glaucoma screening by FDRs. We recommend direct contact and education of the FDRs of glaucoma patients.
Tenon Cyst Patch Graft for Ahmed Glaucoma Valve Tube Exposure: Case Series Report
Authors: Alvarez-Ascencio Daniela , Lazcano-Gomez Gabriel , Flores-Reyes Elsa , Dueñas-Angeles Karla , Jímenez-Roman Jesús , Kahook Malik Y.
Published: December 2020

Purpose:

To report our experience using a Tenon cyst autograft in the management of tube exposure post Ahmed glaucoma valve (AGV) implantation.

Methods:

This is a retrospective case series.

Results:

Four patients who underwent tube exposure repair using Tenon cyst autograft were identified in our tertiary care center. The duration between initial AGV implantation and tube exposure ranged between 3 and 36 months with a mean of 16 months (±14.35 mo). All patients were followed postoperatively for a range of 4 to 24 months with a mean of 11.75 months (±9.03 o) and all remain exposure free at last follow-up.

Conclusion:

The use of a Tenon cyst autograft for the surgical repair of a tube exposure is valuable, as it involves using autologous scar tissue that is available in eyes that have undergone AGV implantation. The patch autograft is technically easy to harvest, and represents a significantly lower cost when compared with other available options.
Cumulative Efficacy of Longitudinal Repeat Salivary Gland OnabotulinumtoxinA Injection
Authors: Shoval Hannah , Friel Kathleen , Levin Jared , Kim Heakyung
Published: December 2020

Aim

We hypothesized that repeat onabotulinumtoxinA (BTX-A) injections to salivary glands would have a cumulative effect on drooling, leading to prolonged efficacy duration.

Methods

We retrospectively reviewed medical records and conducted a telephone survey of individuals treated with BTX-A to the salivary glands to investigate ongoing efficacy or adverse effects. Outcome measures were duration of decrease in drooling and adverse events. The main independent variable was the number of injections. We identified 52 consecutive individuals (26 females) with cerebral palsy with an average age of 9 yrs, 3 mos ± 5 yrs 2 mos, who had received BTX-A for sialorrhea.

Results

Linear regression analysis showed that each additional injection resulted in the duration of efficacy being 0.68 mos longer (P < 0.001, R
2 = 0.47). Age, sex, Gross Motor Function Classification System level, presence of tube feeding, presence of tracheostomy, gastroesophageal reflex, seizures, and concurrent intramuscular injections seizures were not significant contributors to the association between injection number and efficacy duration (F (6, 45) = 1.01, P = 0.431).

Interpretation

There may be a cumulative effect of BTX-A injections to the salivary glands, resulting in longer periods of efficacy with consecutive injection.
External Devices Among Individuals With Spinal Cord Injury From a Developing Country
Authors: Kumprou Makamas , Thaweewannakij Thiwabhorn , Arayawichanon Preeda , Amatachaya Pipatana , Amatachaya Sugalya
Published: December 2020

Objective

The aim of this study was to explore the proportion, number, and type of external devices (including mobility devices, ambulatory aides, and orthotics) possessed and used by individuals with spinal cord injury (SCI) from a developing country.

Design

This was a cross-sectional study.

Participants

A total of 163 participants with SCI from several rural communities in a developing country participated in the study from June 2018 to August 2019.

Methods

The participants were interviewed and assessed for their SCI characteristics and the external devices (i.e., mobility devices, ambulatory aides, and orthotics) they possessed and used in their daily living.

Results

Most participants (85%), who lived in rural communities with a family income of less than $3167 per year, possessed external devices (one to five types), and 80% of all participants actually used the devices (one to three types) in their daily living. Most participants with motor-complete SCI used a single device, especially a manual wheelchair, whereas those with mild lesion severity used multiple devices for their daily activities, particularly a standard walker.

Conclusion

Owing to budget and environmental constraints, the external devices used by individuals with SCI from a developing country are different from those reported in a developed country. The findings provide particular insights into the management of external devices for these individuals of a developing country.
Rehabilitation Protocol After Hip Arthroscopy
Authors: Bistolfi Alessandro , Guidotti Claudio , Aprato Alessandro , Sabatini Luigi , Artiaco Stefano , Massè Alessandro , Ferracini Riccardo
Published: December 2020

Objective

Although many rehabilitation protocols after hip arthroscopy have been described, there is still significant variability about duration, goals, restrictions, and techniques to apply by the physical therapy after the surgical procedure. The aim of the study was to systematically review rehabilitation after hip arthroscopy.

Design

The data sources were PubMed, Scopus, and Cochrane Library. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for the systematic review. Level I–IV evidence clinical studies and clinical reviews that focused on rehabilitation protocols after hip arthroscopy have been used as study eligibility criteria. Major limitations include the retrospective nature of most of the studies selected (level IV evidence) and the use of different clinical scores to report the outcomes.

Results

This review showed that although a standardized guideline on rehabilitation after hip arthroscopy is still missing, the most recent studies and clinical trials are focusing on a four-phase program, which includes goals, recommendations, and a progression of exercises.

Conclusions

Rehabilitation after hip arthroscopy is strongly suggested, but different authors recommended different rehabilitation programs. There is not a defined program, but as of today, the current standard of care is composed of phase-based programs.
Cancer Patients in the Era of Coronavirus: What to Fear Most?
Authors: Haddad Fady Gh , Kourie Hampig Raphael , Gebara Nicole , Matta Christian , Eid Roland , El Karak Fady , Nasr Fadi , Chahine Georges , Ghosn Marwan , Kattan Joseph
Published: December 2020

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic led to a worldwide medical crisis, affecting mostly immunocompromised patients, such as cancer patients. Various cancer societies have issued recommendations regarding patients care, but few studies addressed the perception of cancer patients regarding this pandemic.

Objective

The aim of the study was to assess the perception of cancer patients regarding their health risks during this pandemic and the preventive measures taken.

Materials and Methods

An anonymous survey was conducted among cancer patients presenting for their treatment, during 10 consecutive working days, at the one-day clinic of Hotel-Dieu de France University hospital in Beirut. We evaluated their state of disease, comorbidities, precautions taken, and their concerns regarding the virus spread.

Results

A total of 216 patients responded with a mean age of 60 years. The majority had a good performance status (performance status = 0–1 in 79.6%), 51.4% had metastatic disease, and chemotherapy was the main therapy used (65.7%). A total of 52.3% of patients considered themselves to be at increased risk of contracting the virus. A total of 55.1% were more worried about the coronavirus rather than their disease. The priority was for the treatment of their cancer in 47.7% of the total patients studied. Of note, only 2.8% of planned one-day clinic reservations were canceled or postponed to avoid COVID-19 exposure.

Conclusions

Although cancer is a disease with a high mortality rate, many patients are more concerned about the actual pandemic rather than their disease. Nevertheless, the absenteeism from their treatment sessions during the COVID-19 atmosphere was minimal.
National and Institutional Trends in Adverse Events Over Time: A Systematic Review and Meta-analysis of Longitudinal Retrospective Patient Record Review Studies
Authors: Connolly Warren , Li Brian , Conroy Ronan , Hickey Anne , Williams David J. , Rafter Natasha
Published: December 2020

Objective

This study aimed to determine if the implementation of large-scale patient safety initiatives have been successful in reducing overall and preventable adverse event rates in hospital inpatients.

Design

The design used in this study was systematic review and meta-analysis.

Data Resources

We followed our published protocol (PROSPERO [CRD42019140058]) and searched the following databases: PubMed, CINAHL, PsycINFO, Cochrane Library, and Embase from inception to February 2020. The reference lists of eligible studies were also searched.

Eligibility

All longitudinal retrospective record review studies that examined adverse event rates before and after the introduction of patient safety initiatives in hospital inpatients were included.

Data Extraction

Data extraction, quality, and risk of bias assessment were carried out by 2 independent reviewers. Information on study design, setting, demographics, interventions, and safety outcome measures was extracted.

Results

A total of 3894 articles were screened, and 7 articles met the eligibility criteria for our systematic review with 5 of these providing sufficient information for inclusion in the meta-analysis. The degree of heterogeneity was high among studies. The meta-analysis demonstrated a minimal risk reduction in overall adverse event rates of 0.017 (95% confidence interval, 0.002–0.032) when the lower-quality studies were excluded, with one adverse event being prevented for every 59 hospital admissions.

Conclusions

These findings are significant when the large numbers of admissions to a hospital every year are considered. Given the low numbers of large-scale implementation studies, there is a need for more research on the effectiveness of patient safety initiatives to further assess the impact of such initiatives on adverse events.
Optimizing Discharge Summaries: A Multispecialty, Multicenter Survey of Primary Care Clinicians
Authors: Silver Aaron M. , Goodman Leigh Anne , Chadha Romil , Higdon Jason , Burton Michael , Palabindala Venkataraman , Jonnalagadda Nageshwar , Thomas Abey , O’Donnell Christopher
Published: December 2020

Background

Patient care in the United States has become increasingly more fragmented, and the discharge summary serves as a critical tool for transmitting information on a patient’s hospital admission to the primary care clinician. Some guidelines regarding how to write discharge summaries exist, but few are focused on prioritizing content that is most important to optimize a patient’s transition of care.

Methods

We conducted a national survey across various medical primary care specialties, including trainees and advanced practice providers, to understand the priorities of primary care clinicians. We distributed the survey to 2184 clinicians affiliated with 8 large academic institutions. Our response rate was 21%.

Results

Hospital course, discharge diagnoses, medication reconciliation, and follow-up sections were ranked as the most important categories with a 95.5% concordance rate among surveyed institutions. The least important sections were contact numbers for inpatient clinicians, ancillary services, weight-bearing status, and wound care. Similar themes were also identified via consensus review of the free-texted comments, adding that discharge summary style was also important. Other identified barriers to high-quality transition of care are both the limited time primary care clinicians can spend reviewing discharge summaries and lack of adequate communication between hospitalists and the outpatient clinician.

Conclusions

High-yield content should be presented at the beginning of the discharge summary and conveyed in a brief, succinct manner to ensure maximal utility of the document as a transition of care tool.
In-depth evaluation of root infection systems with the vascular fungusVerticillium longisporumas soil-borne model pathogen
Authors: Fröschel Christian
Published: December 2020

PREMISE

While leaves are far more accessible for analysing plant defences, roots are hidden in the soil leading to difficulties in studying soil-borne interactions. Literature describes inoculation strategies to infect model plants with model root pathogens, but it remains demanding to obtain a methodological overview. To address this challenge, this study uses the model root pathogenVerticillium longisporumonArabidopsis thalianaand provides recommendations based on evident examples for the selection and management of suitable infection systems to investigate root-microbe interactions.

METHODS AND RESULTS

A novel root infection system is introduced, while two existing ones are precisely described and optimized. Advantages and disadvantages of each are assessed, step-by-step protocols are presented and accompanied by pathogenicity tests, transcriptional analyses of indole-glucosinolate markers and independent confirmations using reporter constructs. The results validate the importance of indole-glucosinolates as secondary metabolites limitingV. longisporumpropagation in hosts.

DISCUSSION

We provide detailed guidelines for studying host responses and defence strategies againstV. longisporum. Furthermore, other soil-borne microorganisms or other model plants, such as economically important oilseed rape, can be used in the infection systems described. Hence, these proven manuals help to find a root infection system for your specific research questions to decipher root-microbe interactions.
A long reads-based de-novo assembly of the genome of the Arlee homozygous line reveals structural genome variation in rainbow trout
Authors: Gao Guangtu , Magadan Susana , Waldbieser Geoffrey C. , Youngblood Ramey C. , Wheeler Paul A. , Scheffler Brian E. , Thorgaard Gary H. , Palti Yniv
Published: December 2020

Currently, there is still a need to improve the contiguity of the rainbow trout reference genome and to use multiple genetic backgrounds that will represent the genetic diversity of this species. The Arlee doubled haploid line was originated from a domesticated hatchery strain that was originally collected from the northern California coast. The Canu pipeline was used to generate the Arlee line genome de-novo assembly from high coverage PacBio long-reads sequence data. The assembly was further improved with Bionano optical maps and Hi-C proximity ligation sequence data to generate 32 major scaffolds corresponding to the karyotype of the Arlee line (2N=64). It is composed of 938 scaffolds with N50 of 39.16 Mb and a total length of 2.33 Gb, of which ∼95% was in 32 chromosome sequences with only 438 gaps between contigs and scaffolds. In rainbow trout the haploid chromosome number can vary from 29 to 32. In the Arlee karyotype the haploid chromosome number is 32 because chromosomes Omy04, 14 and 25 are divided into six acrocentric chromosomes. Additional structural variations that were identified in the Arlee genome included the major inversions on chromosomes Omy05 and Omy20 and additional 15 smaller inversions that will require further validation. This is also the first rainbow trout genome assembly that includes a scaffold with the sex-determination gene (sdY) in the chromosome Y sequence. The utility of this genome assembly is demonstrated through the improved annotation of the duplicated genome loci that harbor the IGH genes on chromosomes Omy12 and Omy13.

Article Summary

A de-novo genome assembly was generated for the Arlee homozygous line of rainbow trout to enable identification and characterization of genome variants towards developing a rainbow trout pan-genome reference. The new assembly was generated using the PacBio sequencing technology and scaffolding with Hi-C contact maps and Bionano optical mapping. A contiguous genome assembly was obtained, with the contig and scaffold N50 over 15.6 Mb and 39 Mb, respectively, and 95% of the assembly in chromosome sequences. The utility of this genome assembly is demonstrated through the improved annotation of the duplicated genome loci that harbor the IGH genes.
Fast end-to-end learning on protein surfaces
Authors: Sverrisson Freyr , Feydy Jean , Correia Bruno E. , Bronstein Michael M.
Published: December 2020

Proteins’ biological functions are defined by the geometric and chemical structure of their 3D molecular surfaces. Recent works have shown that geometric deep learning can be used on mesh-based representations of proteins to identify potential functional sites, such as binding targets for potential drugs. Unfortunately though, the use of meshes as the underlying representation for protein structure has multiple drawbacks including the need to pre-compute the input features and mesh connectivities. This becomes a bottleneck for many important tasks in protein science.

In this paper, we present a new framework for deep learning on protein structures that addresses these limitations. Among the key advantages of our method are the computation and sampling of the molecular surface on-the-fly from the underlying atomic point cloud and a novel efficient geometric convolutional layer. As a result, we are able to process large collections of proteins in an end-to-end fashion, taking as the sole input the raw 3D coordinates and chemical types of their atoms, eliminating the need for any hand-crafted pre-computed features.

To showcase the performance of our approach, we test it on two tasks in the field of protein structural bioinformatics: the identification of interaction sites and the prediction of protein-protein interactions. On both tasks, we achieve state-of-the-art performance with much faster run times and fewer parameters than previous models. These results will considerably ease the deployment of deep learning methods in protein science and open the door for end-to-end differentiable approaches in protein modeling tasks such as function prediction and design.
Statistics or biology: the zero-inflation controversy about scRNA-seq data
Authors: Jiang Ruochen , Sun Tianyi , Song Dongyuan , Li Jingyi Jessica
Published: December 2020

Researchers view vast zeros in single-cell RNA-seq data differently: some regard zeros as biological signals representing no or low gene expression, while others regard zeros as missing data to be corrected. To help address the controversy, here we discuss the sources of biological and non-biological zeros; introduce five mechanisms of adding non-biological zeros in computational benchmarking; evaluate the impacts of non-biological zeros on data analysis; benchmark three input data types: observed counts, imputed counts, and binarized counts; discuss the open questions regarding non-biological zeros; and advocate the importance of transparent analysis.
Epitope-Based Peptide Vaccine against Bombali Ebolavirus Viral Protein 40: An Immunoinformatics Combined with Molecular Docking Studies
Authors: Mustafa Mujahed I. , Shantier Shaza W. , Abdelmageed Miyssa I. , Makhawi Abdelrafie M.
Published: December 2020

Background

Bombali Ebolavirus is RNA viruses belong to the Filoviridae family. They are causing lethal hemorrhagic fever with high mortality rate. Despite having available molecular knowledge of this virus, no approved vaccine or antiviral drugs have been developed yet for the eradication of Bombali Ebolavirus infections in humans.

Objective

the present study described a multi epitope-based peptide vaccine against Bombali Ebolavirus matrix protein VP40, using several immunoinformatics tools.

Materials and Methods

The six strains of Ebolavirus were retrieved from NCBI and Uniprot databases and submitted to VaxiJen to identify the most antigenic protein among all. Then PSIPRED, SOPMA, QMEAN, and PROCHECK tools were used to check the protein quality. T-cell prediction, population coverage, and molecular docking analysis were achieved to select peptides containing multiple Bombali VP40 epitopes showing interaction with multiple HLA molecules for expected immune response across the world.

Result

Bombali Ebola (YP_009513276.1) was found to be the most antigenic protein among all. Which it has been used in all required analysis. For T cell three epitopes showed high affinity to MHC class I (YSFDSTTAA, VQLPQYFTF, and MVNVISGPK) and high population coverage against Africa and the world. Furthermore in MHC class II, six promising epitopes that associated with most common MHC class II alleles.

Conclusion

The above result conclude that, these peptides capable of provoking T-cell response and being interacted with a wide range of HLA molecules have a strong potential to be a vaccine against Bombali Ebolavirus.
Coupled feedback loops involving PAGE4, EMT and Notch signaling can give rise to non-genetic heterogeneity in prostate cancer cells
Authors: Singh Divyoj , Bocci Federico , Kulkarni Prakash , Jolly Mohit Kumar
Published: December 2020

Non-genetic heterogeneity is emerging to be a crucial factor underlying therapy resistance in multiple cancers. However, the design principles of regulatory networks underlying non-genetic heterogeneity in cancer remain poorly understood. Here, we investigate the coupled dynamics of feedback loops involving a) oscillations in androgen receptor (AR) signaling mediated through an intrinsically disordered protein PAGE4, b) multistability in epithelial-mesenchymal transition (EMT), and c) Notch-Delta-Jagged signaling mediated cell-cell communication, each of which can generate non-genetic heterogeneity through multistability and/or oscillations. Our results show how different coupling strengths between AR and EMT signaling can lead to possible bistability in the levels of AR. These results reveal the emergent dynamics of coupled oscillatory and multi-stable systems and unravel mechanisms by which non-genetic heterogeneity in AR levels can be generated, which can act as a barrier to most existing therapies for prostate cancer patients.
Estimation of Kinematics from Inertial Measurement Units Using a Combined Deep Learning and Optimization Framework
Authors: Rapp Eric , Shin Soyong , Thomsen Wolf , Ferber Reed , Halilaj Eni
Published: December 2020

The difficulty of estimating joint kinematics remains a critical barrier toward widespread use of inertial measurement units in biomechanics. Traditional sensor-fusion filters are largely reliant on magnetometer readings, which may be disturbed in uncontrolled environments. Careful sensor-to-segment alignment and calibration strategies are also necessary, which may burden users and lead to further error in uncontrolled settings. We introduce a new framework that combines deep learning and top-down optimization to accurately predict lower extremity joint angles directly from inertial data, without relying on magnetometer readings. We trained deep neural networks on a large set of synthetic inertial data derived from a clinical marker-based motion-tracking database of hundreds of subjects. We used data augmentation techniques and an automated calibration approach to reduce error due to variability in sensor placement and limb alignment. On left-out subjects, lower extremity kinematics could be predicted with a mean (±STD) root mean squared error of less than 1.27 ° (±0.38°) in flexion/extension, less than 2.52°(±0.98 °) in ad/abduction, and less than 3.34°(±1.02°) internal/external rotation, across walking and running trials. Errors decreased exponentially with the amount of training data, confirming the need for large datasets when training deep neural networks. While this framework remains to be validated with true inertial measurement unit (IMU) data, the results presented here are a promising advance toward convenient estimation of gait kinematics in natural environments. Progress in this direction could enable large-scale studies and offer an unprecedented view into disease progression, patient recovery, and sports biomechanics.
Why sensory neurons are tuned to multiple stimulus features
Authors: Macellaio Matthew V. , Liu Bing , Beck Jeffrey M. , Osborne Leslie C.
Published: December 2020

Many sensory neurons encode information about more than one stimulus feature. Multidimensional tuning increases ambiguity in stimulus-response relationships, but we find that it also offers an unexpected computational advantage, allowing the brain to better reconstruct sensory stimuli. From the responses of sensory neurons, populations, and sensory-driven movement behavior, more information can be recovered about a stimulus vector than about its individual components. We term this coding advantage “stimulus synergy” and show that it is distinct from other coding synergies, arising from inseparability of the response-conditioned stimulus distribution along individual stimulus dimensions. From extracellular recordings in motion sensitive cortex and measurements of pursuit eye movements, we demonstrate that stimulus synergy in cortical populations is preserved downstream in the precision of pursuit, and that a common decoding model predicts the level of synergy in pursuit behavior. This suggests that the brain exploits the information advantage afforded by multidimensional sensory tuning.
Defective NET clearance contributes to sustained FXII activation in COVID-19-associated pulmonary thrombo-inflammation
Authors: Englert Hanna , Rangaswamy Chandini , Deppermann Carsten , Sperhake Jan-Peter , Krisp Christoph , Schreier Danny , Gordon Emma , Konrath Sandra , Haddad Munif , Pula Giordano , Mailer Reiner K. , Schlüter Hartmut , Kluge Stefan , Langer Florian , Püschel Klaus , Panousis Kosta , Stavrou Evi X. , Maas Coen , Renné Thomas , Frye Maike
Published: December 2020

Background

Coagulopathy and inflammation are hallmarks of Coronavirus disease 2019 (COVID-19) and are associated with increased mortality. Clinical and experimental data have revealed a role for neutrophil extracellular traps (NETs) in COVID-19 disease. The mechanisms that drive thrombo-inflammation in COVID-19 are poorly understood.

Methods

We performed proteomic analysis and immunostaining of postmortem lung tissues from COVID-19 patients and patients with other lung pathologies. We further compared coagulation factor XII (FXII) and DNase activities in plasma samples from COVID-19 patients and healthy control donors and determined NET-induced Factor XIII (FXII) activation using a chromogenic substrate assay.

Findings

FXII expression and activity were increased in the lung parenchyma, within the pulmonary vasculature and in fibrin-rich alveolar spaces of postmortem lung tissues from COVID-19 patients. In agreement with this, plasma FXII activation (FXIIa) was increased in samples from COVID-19 patients. Furthermore, FXIIa colocalized with NETs in COVID-19 lung tissue indicating that NETs accumulation leads to FXII contact activation in COVID-19. We further showed that an accumulation of NETs is partially due to impaired NET clearance by extracellular DNases as DNase substitution improved NET dissolution and reduced FXII activationin vitro.

Interpretation

Collectively, our study supports that the NETs/FXII axis contributes to the pathogenic chain of procoagulant and proinflammatory responses in COVID-19. Targeting both, NETs and FXIIa, could provide a strategy to mitigate COVID-19-induced thrombo-inflammation.

Funding

This study was supported by the European Union (840189), the Werner Otto Medical Foundation Hamburg (8/95) and the German Research Foundation (FR4239/1-1, A11/SFB877, B08/SFB841 and P06/KFO306).
Indian Red Jungle fowl depicts close genetic relationship with Indian native chicken breeds as evidenced through whole mitochondrial genome intersection
Authors: Kanakachari M. , Chatterjee R.N. , Rajkumar U. , Haunshi S. , Reddy M. R. , Bhattacharya T.K.
Published: December 2020

Native chickens are dispersed in a wide range of geometry and they have influenced hereditary assets that are kept by farmers for various purposes. Mitochondrial DNA (mtDNA) is a widely utilized marker in molecular study because of its quick advancement, matrilineal legacy, and simple molecular structure. In a genomics study, it is important for understanding the origins, history, and adjustment of domestication. In this report, for the first time, we utilized Next-generation sequencing (NGS) to investigate the mitochondrial genomes and to evaluate the hereditary connections, diversity, and measure of gene stream estimation in seven Indian native chicken breeds along with twenty-two Asian native breeds. The absolute length of each mtDNA was 16775bp harboring 4 tRNA genes, 2 rRNA genes, 12 protein-coding genes, and 1 D-loop region. The chicken breeds were genotyped by using the D-loop region and 23 haplotypes were identified. In addition, when compared to only Indian native breeds more haplotypes were identified in the NADH dehydrogenase subunit (ND4 and ND5), Cytochrome c oxidase subunit (COXI and COXII), Cytochrome b, mitochondrial encoded ATP synthase membrane subunit 6, and Ribosomal RNA genes. The phylogenetic examination utilizing N-J computational algorithms indicated that the analyzed all native chicken breeds were divided into six significant clades: A, B, C, D, E, and F. All Indian native breeds are coming under the F clade and it says all Indian breeds are domesticated in India. Besides, the sequencing results effectively distinguished SNPs, INDELs, mutations, and variants in seven Indian native breeds. Additionally, our work affirmed that Indian Red Jungle Fowl is the origin of reference Red Jungle Fowl as well as all Indian breeds, which is reflected in the dendrogram as well as network analysis based on whole mtDNA and D-loop region. Albeit, Indian Red Jungle Fowl is distributed as an outgroup, proposing that this ancestry was reciprocally monophyletic. The seven Indian native chickens of entire mtDNA sequencing and disclosure of variations gave novel insights about adaptation mechanisms and the significance of important mtDNA variations in understanding the maternal lineages of native chickens.
STORM-Net: Simple and Timely Optode Registration Method for Functional Near-Infrared Spectroscopy (fNIRS)
Authors: Erel Yotam , Jaffe-Dax Sagi , Yeshurun Yaara , Bermano Amit H.
Published: December 2020

We introduce a robust video-based method for estimating the positions of fNIRS optodes on the scalp. The method is fast, requires no special hardware, and is intuitive to use with developmental populations. Co-registration is a crucial step for reliable analysis of FNIRS data, yet it still remains an open problem when considering these populations. Existing methods pose motion constraints, require expert annotation, or are only applicable in laboratory conditions. Using novel computer-vision technologies, we implement a fully-automatic appearance-based method that estimates the registration parameters of a mounted cap to the scalp from a raw video of the subject. We validate our method on 10 adult subjects and demonstrate its usability with infants. We compare our method to the standard 3D digitizer, and to other photogrammetry based approaches. We show our method achieves comparable accuracy to current appearance-based methods, while being orders of magnitude faster. Our fast registration facilitates more spatially precise fNIRS analysis with developmental populations even in unconventional environments. The method is implemented as a open-source toolbox athttps://github.com/yoterel/STORM-Net.
Allelic variants of the NLR protein Rpi-chc1 differentially recognise members of thePhytophthora infestansPexRD12/31 effector superfamily through the leucine-rich repeat domain
Authors: Monino-Lopez Daniel , Nijenhuis Maarten , Kodde Linda , Kamoun Sophien , Salehian Hamed , Schentsnyi Kyrylo , Stam Remco , Lokossou Anoma , Abd-El-Haliem Ahmed , Visser Richard GF , Vossen Jack H
Published: December 2020

Phytophthora infestansis a pathogenic oomycete that causes the infamous potato late blight disease. Resistance (R) genes from diverseSolanumspecies encode intracellular receptors that recognizeP. infestansRXLR effector proteins and provide effective defence responses. To deploy theseRgenes in a durable fashion in agriculture, we need to understand the mechanism of effector recognition and the way the pathogen evades recognition.

We cloned sixteen allelic variants of theRpi-chc1gene fromSolanum chacoenseand otherSolanumspecies, and identified the cognateP. infestansRXLR effectors. These tools were used to study receptor-ligand interactions and co-evolution.

Functional and non-functional alleles ofRpi-chc1encode Coiled-Coil-Nucleotide Binding-Leucine-Rich-Repeat (CNL) proteins.Rpi-chc1.1recognised multiple PexRD12 (AVRchc1.1) proteins whileRpi-chc1.2recognised multiple PexRD31 (AVRchc1.2) proteins, both from the PexRD12/31 superfamily. Domain swaps between Rpi-chc1.1 and Rpi-chc1.2 revealed that overlapping subdomains in the LRR were responsible for the difference in effector recognition.

This study showed thatRpi-chc1.1andRpi-chc1.2, evolved to recognize distinct members of the same PexRD12/31 effector family via the LRR domain. The biased distribution of polymorphisms suggests that exchange of LRRs during host-pathogen co-evolution can lead to novel recognition specificities. These insights will help future strategies to breed for durable resistant varieties.
Prolonging the integrated stress response enhances CNS remyelination in an inflammatory environment
Authors: Chen Yanan , Kunjamma Rejani B , Weiner Molly , Chan Jonah R. , Popko Brian
Published: December 2020

The inflammatory environment of demyelinated lesions in multiple sclerosis (MS) patients contributes to remyelination failure. Inflammation activates a cytoprotective pathway, the integrated stress response (ISR), but it remains unclear whether enhancing the ISR can improve remyelination in an inflammatory environment. To examine this possibility, the remyelination stage of experimental autoimmune encephalomyelitis (EAE), as well as a mouse model that incorporates cuprizone-induced demyelination along with CNS delivery of the proinflammatory cytokine IFN-γ were used here. We demonstrate that either genetic or pharmacological ISR enhancement significantly increased the number of remyelinating oligodendrocytes and remyelinated axons in the inflammatory lesions. Moreover, the combined treatment of Sephin1 with the oligodendrocyte differentiation enhancing reagent bazedoxifene increased myelin thickness of remyelinated axons to pre-lesion levels. Taken together, our findings indicate that prolonging the ISR protects remyelinating oligodendrocytes and promotes remyelination in the presence of inflammation, suggesting that ISR enhancement may provide reparative benefit to MS patients.
Rapid expression of COVID-19 proteins by transient expression in tobacco
Authors: Lindsay Penelope , Ackerman Amanda , Jian Yinan , Artz Oliver , Rosado Daniele , Skopelitis Tara , Kitagawa Munenori , Pedmale Ullas V. , Jackson David
Published: December 2020

In 2020 we suffered from a major global pandemic caused by the SARS-CoV-2 coronavirus. Efforts to contain the virus include the development of rapid tests and vaccines, which require a ready supply of viral proteins. Here we report the production of two SARS-CoV-2 proteins by transient transformation of tobacco, leading to high expression within three days, and subsequent purification of the intact proteins. Such efforts may help to develop testing resources to alleviate the major impacts of this global pandemic.
Experimental assessment of K locus effects on the gray wolf response to virus
Authors: Johnston Rachel A. , Rheinwald James G. , vonHoldt Bridgett M. , Stahler Daniel R. , Lowry William , Tung Jenny , Wayne Robert K.
Published: December 2020

In North American gray wolves, black coat color is dominantly inherited via a three base pair coding deletion in thecanine beta defensin 3(CBD103) gene. This three base pair deletion, called theKBallele, was introduced through hybridization with dogs and subsequently underwent a selective sweep that increased its frequency in wild wolves. Despite apparent positive selection,KBBwolves have significantly lower fitness than wolves with theKyBgenotype, even though the two genotypes show no observable differences in black coat color. Thus, theKBallele is thought to have pleiotropic effects on as-yet unknown phenotypes. Given the role of skin-expressedCBD103in innate immunity, we hypothesized that theKBallele influences the gene regulatory response to viral infection. To test this hypothesis, we developed a panel of primary epidermal keratinocyte cell cultures from 24 wild North American gray wolves (bothKyyandKyBgenotypes) and generated immortalizedKyyandCBD103knockout lines. We assessed the transcriptome-wide responses of wolf keratinocytes to polyinosinic:polycytidylic acid (polyI:C), which mimics infection by a double-stranded RNA virus, and to live canine distemper virus. Keratinocytes with theKyBgenotype and with theKyygenotype had similar gene regulatory responses to viral infection, suggesting that this response does not explain pleiotropic effects of theKBallele on fitness. This study supports the feasibility of using cell culture methods to investigate the phenotypic effects of naturally occurring genetic variation in wild mammals.
Structural basis for +1 ribosomal frameshifting during EF-G-catalyzed translocation
Authors: Demo Gabriel , Loveland Anna B. , Svidritskiy Egor , Gamper Howard B. , Hou Ya-Ming , Korostelev Andrei A.
Published: December 2020

Frameshifting of mRNA during translation provides a strategy to expand the coding repertoire of cells and viruses. Where and how in the elongation cycle +1-frameshifting occurs remains poorly understood. We captured six ∼3.5-Å-resolution cryo-EM structures of ribosomal elongation complexes formed with the GTPase elongation factor G (EF-G). Three structures with a +1-frameshifting-prone mRNA reveal that frameshifting takes place during translocation of tRNA and mRNA. Prior to EF-G binding, the pre-translocation complex features an in-frame tRNA-mRNA pairing in the A site. In the partially translocated structure with EF-G, the tRNA shifts to the +1-frame codon near the P site, whereas the freed mRNA base bulges between the P and E sites and stacks on the 16S rRNA nucleotide G926. The ribosome remains frameshifted in the nearly post-translocation state. Our findings demonstrate that the ribosome and EF-G cooperate to induce +1 frameshifting during mRNA translocation.
scRNA-seq-based analysis of skeletal muscle response to denervation reveals selective activation of muscle-resident glial cells and fibroblasts
Authors: Nicoletti C , Wei X , Etxaniz U. , Proietti D , Madaro L. , Puri P.L.
Published: December 2020

Developmental synaptogenesis toward formation of neuromuscular junctions (NMJs) is regulated by the reciprocal exchange of signals derived from nerve or muscle ends, respectively. These signals are re-deployed in adult life to repair NMJ lesions. The emerging heterogeneity of skeletal muscle cellular composition and the functional interplay between different muscle-resident cell types activated in response to homeostatic perturbations challenge the traditional notion that muscle-derived signals uniquely derive from myofibers. We have used single cell RNA sequencing (scRNA-seq) for a longitudinal analysis of gene expression profiles in cells isolated from skeletal muscles subjected to denervation by complete sciatic nerve transection. Our data show that, unlike muscle injury, which massively activates multiple muscle-resident cell types, denervation selectively induced the expansion of two cell types - muscle glial cells and activated fibroblasts. These cells were also identified as putative sources of muscle-derived signals implicated in NMJ repair and extracellular matrix (ECM) remodelling. Pseudo-time analysis of gene expression in muscle glial-derived cells at sequential timepoints post-denervation revealed an initial bifurcation into distinct processes related to either cellular de-differentiation and commitment to specialized cell types, such as Schwann cells, or ECM remodeling. However, at later time points muscle glial-derived cells appear to adopt a more uniform pattern of gene expression, dominated by a reduction of neurogenic signals. Consensual activation of pro-fibrotic and pro-atrophic genes from fibroblasts and other muscle-resident cell types suggests a global conversion of denervated muscles into an environment hostile for NMJ repair, while conductive for progressive development of fibrosis and myofiber atrophy.
Calculative measures of organising and decision-making in developing countries: the case of a quasi-formal organisation in Ghana
Authors: Agyemang Jacob , Jayasinghe Kelum , Adhikari Pawan , Tunyi Abongeh , Carmel Simon
Published: December 2020

Purpose

This paper examines how a “quasi-formal” organisation in a developing country engages in informal means of organising and decision-making through the use of calculative measures.

Design/methodology/approach

The paper presents a case study of a large-scale indigenous manufacturing company in Ghana. Data for the study were collected through the use of semi-structured interviews conducted both onsite and off-site, supplemented by informal conversations and documentary analysis. Weber's notions of rationalities and traditionalism informed the analysis.

Findings

The paper advances knowledge about the practical day-to-day organisation of resources and the associated substantive rational calculative measures used for decision-making in quasi-formal organisations operating in a traditional setting. Instead of formal rational organisational mechanisms such as hierarchical organisational structures, production planning, labour controls and budgetary practices, the organisational mechanisms are found to be shaped by institutional and structural conditions which result from historical, sociocultural and traditional practices of Ghanaian society. These contextual substantive rational calculative measures consist of the native lineage system of inheritance, chieftaincy, trust and the power concealed within historically established sociocultural practices.

Originality/value

This paper is one of a few studies providing evidence of how local and traditional social practices contribute to shaping organising and decision-making activities in indigenous “quasi-formal” organisations. The paper extends our understanding of the nexus between “technical rational” calculative measures and the traditional culture and social practices prevailing in sub-Saharan Africa in general, and Ghana in particular.
Chief marketing officer and internationalization—a resource-based view
Authors: Fong Cher-Min , Chang Hsing-Hua Stella
Published: December 2020

Purpose

This study aims to examine whether the selection of a new outsider chief marketing officer from a developed-country incumbent firm with an established brand can serve as an alternative strategy to the acquisition of developed-country firms in benefiting the internationalization of a postselection emerging-market brand marketer that suffers from late-mover disadvantages.

Design/methodology/approach

A pretest (survey) and two main studies (experiments) were conducted to examine the proposed mediation model of “Chief Marketing Officer background—enhancement of capabilities—brand competitiveness”.

Findings

An emerging-market brand marketer gains enhanced resources and capabilities when a new chief marketing officer is recruited from a developed-country incumbent with a superior reputation, leading to improved brand competitiveness. This positive effect accrues from the new chief marketing officer's background (i.e. prior work organization) spilling over to his/her new emerging-market employer.

Originality/value

This research integrates the research streams of emerging-market firm internationalization, chief marketing officer and executive succession to provide an alternative strategy for emerging-market firms to overcome late-mover disadvantages in global markets.
An improved energy prediction method to predict the fatigue life of laminated rubber-alloy spherical thrust elastomeric bearing under multiaxial loads
Authors: Yi Jianlei , Jin Kunjian , Qin Haiying , Cui Yuhong
Published: December 2020

Purpose

An ideal method for predicting the fatigue life of spherical thrust elastomeric bearings has not been reported, thus far. This paper aims to present a method for predicting the fatigue life of laminated rubber spherical thrust elastomeric bearings.

Design/methodology/approach

First, the mechanical properties of standard rubber samples were tested; the axial stiffness, cocking stiffness, torsional stiffness and fatigue life of several full-size spherical thrust elastomeric bearings were tested. Then, the stiffness results were calculated using the neo-Hookean, Mooney–Rivlin and Yoeh models. Using a modified Mooney–Rivlin constitutive model, this paper proposes an improved method for fatigue life prediction, which considers the laminated characteristics of a spherical thrust elastomeric bearing and loads of multiple multi-axle conditions.

Findings

The Mooney–Rivlin model could accurately describe the stiffness characteristics of the spherical thrust elastomeric bearings. A comparative analysis of experimental results shows that the model can effectively predict the life of a spherical thrust elastomeric bearing within its range of use and the prediction error is within 20%.

Originality/value

The fatigue parameters of elastomeric bearings under multiaxial loads were fitted and corrected using experimental data and an accurate and effective multiaxial fatigue-life prediction expression was obtained. Finally, the software was redeveloped to improve the flexibility and efficiency of modeling and calculation.