bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Supervised Representation Learning of Protein Tertiary Structures (PtsRep) and Its Implications for Protein Engineering
Authors: Luo Junwen , Cai Yi , Wu Jialin , Cai Hongmin , Yang Xiaofeng , Lin Zhanglin
Published: December 2020

In recent years, deep learning has been increasingly used to decipher the relationships among protein sequence, structure, and function. Thus far these applications of deep learning have been mostly based on primary sequence information, while the vast amount of tertiary structure information remains untapped. In this study, we devised a self-supervised representation learning framework (PtsRep) to extract the fundamental features of unlabeled protein tertiary structures deposited in the PDB, a total of 35,568 structures. The learned embeddings were challenged with two commonly recognized protein engineering tasks: the prediction of protein stability and prediction of the fluorescence brightness of green fluorescent protein (GFP) variants, with training datasets of 16,431 and 26,198 proteins or variants, respectively. On both tasks, PtsRep outperformed the two benchmark methods UniRep and TAPE-BERT, which were pre-trained on two much larger sets of data of 24 and 32 million protein sequences, respectively. Protein clustering analyses demonstrated that PtsRep can capture the structural signatures of proteins. Further testing of the GFP dataset revealed two important implications for protein engineering: (1) a reduced and experimentally manageable training dataset (20%, or 5,239 variants) yielded a satisfactory prediction performance for PtsRep, achieving a recall rate of 70% for the top 26 brightest variants with 795 variants in the testing dataset retrieved; (2) counter-intuitively, when only the bright variants were used for training, the performances of PtsRep and the benchmarks not only did not worsen but they actually slightly improved. This study provides a new avenue for learning and exploring general protein structural representations for protein engineering.
Functional analysis of caspase cleavable proteoforms from theDrosophilaGSK-3 geneshaggy
Authors: Korona Dagmara , Nightingale Daniel , Fabre Bertrand , Nelson Michael , Fischer Bettina , Johnson Glynnis , Hubbard Simon , Lilley Kathryn , Russell Steven
Published: December 2020

TheDrosophila shaggy(sgg) gene encodes the major fly orthologue of Glycogen Synthase Kinase −3 (GSK-3), a key highly conserved kinase at the heart of many signalling pathways. Thesgglocus is complex, encoding multiple protein isoforms that are expressed in distinct temporal and tissue-specific patterns across development. Its isoforms predominantly differ at the carboxy and amino termini due to the use of different transcriptional start sites and alternative splicing events that include internal and terminal exons. One interesting class of proteins isoforms is represented by the Sgg-PD class (Sgg46), three proteoforms that contain a large 582 amino acid N-terminal domain which contains recognition sites for caspase-mediated cleavage. Regulated cleavage at these sites by non-apoptotic caspases has previously been implicated in the regulation of Sgg activity in adult bristle development. Here, we take a genome engineering approach to introduce specific tags into this unique Sgg-PD exon and utilise these for localisation and protein interaction studies. We also generated new loss of function alleles and specific mutations in the caspase cleavage motifs. We find that loss of functions Sgg-PD class alleles are viable and fertile, but exhibit adult locomotor and bristle defects. Expression analysis of lines carrying tags on both sides of the caspase cleavage sites indicates that the cleavage is developmentally regulated during embryogenesis. Surprisingly, we found that in some cells, particularly embryonic hemocytes, the N-terminal domain released by caspase cleavage is retained while the polypeptide containing the conserved kinase domain is apparently lost. Transcriptomic analysis of embryos homozygous for the new caspase-insensitive allele indicates a role for Sgg-PD in the regulation of cytoskeletal and cell junction functions, which is supported by proteomics analysis using specific in locus tags to identify common and unique protein interaction partners with N- and C-terminal domains. Taken together, our work identifies new activities for the Sgg protein and uncovers unexpected roles for caspase cleavage in Sgg biology.
Wild animal oral microbiomes reflect the history of human antibiotics use
Authors: Brealey Jaelle C. , Leitão Henrique G. , Hofstede Thijs , Kalthoff Daniela C. , Guschanski Katerina
Published: December 2020

Following the advent of industrial-scale antibiotics production in the 1940s, antimicrobial resistance (AMR) has been on the rise and now poses a major global health threat. Because AMR can be exchanged between humans, livestock and wildlife, evaluating the potential of wild animals to act as AMR reservoirs is essential. We used shotgun metagenomics sequencing of dental calculus, the calcified form of the oral microbial biofilm, to determine the abundance and repertoire of AMR genes in the oral microbiome of Swedish brown bears from museum specimens collected over the last 200 years. Our temporal metagenomics approach allowed us to establish a baseline of natural AMR in the pre-antibiotics era and to quantify a significant increase in total AMR load and diversity of AMR genes that is correlated with human antibiotics use. We also demonstrated that Swedish public health policies were effective in limiting AMR spillover into wildlife.
TSA-seq reveals a largely conserved genome organization relative to nuclear speckles with small position changes tightly correlated with gene expression changes
Authors: Zhang Liguo , Zhang Yang , Chen Yu , Gholamalamdari Omid , Wang Yuchuan , Ma Jian , Belmont Andrew S.
Published: December 2020

TSA-seq mapping suggests that gene distance to nuclear speckles is more deterministic and predictive of gene expression levels than gene radial positioning. Gene expression correlates inversely with distance to nuclear speckles, with chromosome regions of unusually high expression located at the apex of chromosome loops protruding from the nuclear periphery into the interior. Genomic distances to the nearest lamina-associated domain are larger for loop apexes mapping closest to nuclear speckles, suggesting the possibility of conservation of speckle-associated regions. To facilitate comparison of genome organization by TSA-seq, we reduced required cell numbers 10- to 20-fold for TSA-seq by deliberately saturating protein-labeling while preserving distance mapping by the still unsaturated DNA-labeling. Only ∼10% of the genome shows statistically significant shifts in relative nuclear speckle distances in pair-wise comparisons between human cell lines (H1, HFF, HCT116, K562); however, these moderate shifts in nuclear speckle distances tightly correlate with changes in cell type–specific gene expression. Similarly, half of heat shock-induced gene loci already preposition very close to nuclear speckles, with the remaining positioned near or at intermediate distance (HSPH1) to nuclear speckles but shifting even closer with transcriptional induction. Speckle association together with chromatin decondensation correlates with expression amplification upon HSPH1 activation. Our results demonstrate a largely “hardwired” genome organization with specific genes moving small mean distances relative to speckles during cell differentiation or a physiological transition, suggesting an important role of nuclear speckles in gene expression regulation.
Profiling neural editomes reveals a molecular mechanism to regulate RNA editing during development
Authors: Rajendren Suba , Dhakal Alfa , Vadlamani Pranathi , Townsend Jack , Deffit Sarah N. , Hundley Heather A.
Published: December 2020

Adenosine (A) to inosine (I) RNA editing contributes to transcript diversity and modulates gene expression in a dynamic, cell type–specific manner. During mammalian brain development, editing of specific adenosines increases, whereas the expression of A-to-I editing enzymes remains unchanged, suggesting molecular mechanisms that mediate spatiotemporal regulation of RNA editing exist. Herein, by using a combination of biochemical and genomic approaches, we uncover a molecular mechanism that regulates RNA editing in a neural- and development-specific manner. Comparing editomes during development led to the identification of neural transcripts that were edited only in one life stage. The stage-specific editing is largely regulated by differential gene expression during neural development. Proper expression of nearly one-third of the neurodevelopmentally regulated genes is dependent on adr-2, the sole A-to-I editing enzyme in C. elegans. However, we also identified a subset of neural transcripts that are edited and expressed throughout development. Despite a neural-specific down-regulation of adr-2 during development, the majority of these sites show increased editing in adult neural cells. Biochemical data suggest that ADR-1, a deaminase-deficient member of the adenosine deaminase acting on RNA (ADAR) family, is competing with ADR-2 for binding to specific transcripts early in development. Our data suggest a model in which during neural development, ADR-2 levels overcome ADR-1 repression, resulting in increased ADR-2 binding and editing of specific transcripts. Together, our findings reveal tissue- and development-specific regulation of RNA editing and identify a molecular mechanism that regulates ADAR substrate recognition and editing efficiency.
Financial leverage and corporate innovation in Chinese public-listed firms
Authors: Iqbal Najaf , Xu Ju Feng , Fareed Zeeshan , Wan Guangcai , Ma Lina
Published: December 2020

Purpose

This study attempts to document the impact of financial leverage on corporate innovation in the Chinese nonfinancial public firms listed on Shenzhen and Shanghai stock exchanges.

Design/methodology/approach

The firm-level data are collected from CSMAR database for ten years, ranging from 2007 to 2016. The authors have employed the panel fixed effects model and further system GMM approach for analysis. The sample is segregated on the basis of state (SOE) and nonstate ownership (NSOE) to check for the diverse effects. In total, three different proxies of financial leverage are used to unearth the varying impact of short-time and long-term leverage separately. Further, corporate innovation is divided into input innovation (R&D/Sales and R&D/Assets) and output innovation (patents and inventions).

Findings

The results suggest that financial leverage is detrimental to the input innovation while conducive for the output innovation when measured by the number of patents. Contrarily, leverage has a negative influence over the output innovation when measured by the number of inventions. This implies that leverage is more damaging for the highest form of innovativeness (inventions) in China. Input innovation is more sensitive to the changes in long-term leverage versus short-term leverage. Further, the authors find that innovation in SOEs is more sensitive to the changes in the leverage as compared to the NSOEs. The results are free from the threat of endogeneity and identification problems, as reported by the system GMM model.

Research limitations/implications

The authors did not segregate the sample on the basis of industry/sector.

Practical implications

The firms pursuing a strategy of radical innovation should try to keep their debt levels lower in order to achieve a higher innovation performance. Although, a rise in the leverage may mean an increased access to finance for a firm but such an access comes at a cost in the form of damage to the corporate innovation. However, increased debt financing may not be so bad for the firms that want to achieve a moderate and not the highest level of innovation. Such firms can produce recurring and synergic effects with debt financing and moderate innovation, once they achieve a level of innovation performance that satisfies their financiers.

Originality/value

To the best of authors’ knowledge, this is probably the first study to check the impact of firm-level financial leverage on both input and output innovation in the Chinese public-listed nonfinancial firms' panel data perspective till now.
Availability modeling and estimation of Fluid Catalytic Cracking Unit using generalized Stochastic Petri Nets
Authors: Gurunathan Thangamani
Published: December 2020

Purpose

The purpose of this paper to present a practical and systematic approach to estimate the availability of a process plant using generalized stochastic Petri nets (GSPNs). The actual live problem at a fluid catalytic cracking unit (FCCU) of a refinery is used to demonstrate this approach.

Design/methodology/approach

A majority of models used for estimation of availability of a complex system are based on the assumptions that the failure of the system is associated with only a few states, and the system does not face different operating conditions, repair actions and common-cause failures. In reality, this is often not the case. Therefore, it is necessary to construct more sophisticated models without such assumptions. In this paper, an attempt has been made to model interaction of component failures, partial failures of components and common-cause failures.

Findings

The superiority of this approach over other modeling approaches such as fault tree and Markov analysis is demonstrated. The proposed GSPN is a promising tool that can be conveniently used to model and analyze any complex systems.

Practical implications

GSPN was used to model the reactor-regenerator section of FCCU, which is quite a large system, which shows the strength of modeling capability. The use of Petri nets (PNs) for modeling complex systems for the purpose of availability assessment is demonstrated in this paper. Sensitivity analysis was also carried out for various subsystem/components.

Originality/value

No similar work has been conducted for FCCU using GSPN as per literature incorporating different operating conditions and common-cause failures. The understanding and usage of PNs require a steep learning curve for the practitioners, and this paper provides an approach to estimate availability measures for the complex system.
Facilitation of information literacy through a multilingual MOOC considering cultural aspects
Authors: Dreisiebner Stefan , Polzer Anna Katharina , Robinson Lyn , Libbrecht Paul , Boté-Vericad Juan-José , Urbano Cristóbal , Mandl Thomas , Vilar Polona , Žumer Maja , Juric Mate , Pehar Franjo , Stričević Ivanka
Published: December 2020

Purpose

The purpose of this paper is to demonstrate the rationale, technical framework, content creation workflow and evaluation for a multilingual massive open online course (MOOC) to facilitate information literacy (IL) considering cultural aspects.

Design/methodology/approach

A good practice analysis built the basis for the technical and content framework. The evaluation approach consisted of three phases: first, the students were asked to fill out a short self-assessment questionnaire and a shortened adapted version of a standardized IL test. Second, they completed the full version of the IL MOOC. Third, they were asked to fill out the full version of a standardized IL test and a user experience questionnaire.

Findings

The results show that first the designed workflow was suitable in practice and led to the implementation of a full-grown MOOC. Second, the implementation itself provides implications for future projects developing multilingual educational resources. Third, the evaluation results show that participants achieved significantly higher results in a standardized IL test after attending the MOOC as mandatory coursework. Variations between the different student groups in the participating countries were observed. Fourth, self-motivation to complete the MOOC showed to be a challenge for students asked to attend the MOOC as nonmandatory out-of-classroom task. It seems that multilingual facilitation alone is not sufficient to increase active MOOC participation.

Originality/value

This paper presents an innovative approach of developing multilingual IL teaching resources and is one of the first works to evaluate the impact of an IL MOOC on learners' experience and learning outcomes in an international evaluation study.
Behavioral routes to loyalty across gender on m-banking usage
Authors: Windasari Nila Armelia , Albashrawi Mousa
Published: December 2020

Purpose

Despite merely comparing constructs on male vs female, this study aims to explore how customer usage behavior to loyalty journey is generated by both service providers and the individual factors.

Design/methodology/approach

The authors survey 516 m-banking customers and test the hypotheses using partial least squares structural equation modeling. Structural equation modeling analysis was used because of its capability to handle several exogenous and endogenous variables. All variables were adapted from established constructs in information systems literature.

Findings

The results show different routes of loyalty between male vs female. Males emphasize system and information qualities to shape expectancies as well as facilitating conditions that in turn affect males’ loyalty. While in females, service quality plays a big role in shaping their satisfaction, and in turn affects female customer loyalty.

Originality/value

The study of gender and technology usage has been growing since decades. With higher technological advancement, people always demand for higher service experience and customer behavior evolves accordingly. Although earlier studies on technology adoption models have received considerable empirical validation, most of the studies did not consider different routes across gender.
Mimicking Behçet's disease: GM-CSF gain of function mutation in a family suffering from a Behçet's disease-like disorder marked by extreme pathergy
Authors: Rösler B , Heinhuis B , Wang X , Silvestre R , Joosten L A B , Netea M G , Arts P , Mantere T , Lefeber D J , Hoischen A , Veerdonk F L
Published: December 2020

Behçet's disease (BD) is an inflammatory disease mainly affecting men along the ancient Silk Route. In the present study we describe a Dutch family suffering from BD-like disease with extreme pathergic responses, but without systemic inflammation. Genetic assessment revealed a combination of the human leukocyte antigen (HLA)-B*51 risk-allele together with a rare heterozygous variant in the CSF2 gene (c.130A>C, p.N44H) encoding for granulocyte–macrophage colony-stimulating factor (GM-CSF) found by whole exome sequencing. We utilized an over-expression vector system in a human hepatocyte cell line to produce the aberrant variant of GM-CSF. Biological activity of the protein was measured by signal transducer and activator of transcription 5 (STAT-5) phosphorylation, a downstream molecule of the GM-CSF receptor, in wild-type peripheral mononuclear cells (PBMCs) using flow cytometry. Increased STAT-5 phosphorylation was observed in response to mutated GM-CSF when compared to the wild-type or recombinant protein. CSF2 p.N44H results in disruption of one of the protein's two N-glycosylation sites. Enzymatically deglycosylated wild-type GM-CSF also enhanced STAT-5 phosphorylation. The patient responded well to anti-tumor necrosis factor (TNF)-α treatment, which may be linked to the capacity of TNF-α to induce GM-CSF in phorbol 12-myristate 13-acetate (PMA)-treated PBMCs, while GM-CSF itself only induced dose-dependent interleukin (IL)-1Ra production. The identified CSF2 pathway could provide novel insights into the pathergic response of BD-like disease and offer new opportunities for personalized treatment.
An analysis of the prevalence of osteoporosis and osteopenia in patients with epidermolysis bullosa: A cross‐sectional study
Authors: Kang Mina , Chen Jessica S. C. , Radjenovic Melissa , Yang Anes , Feng Grant H. Y. , Murrell Dedee F.
Published: December 2020

Background

Epidermolysis bullosa (EB) patients have multiple risk factors for osteoporosis. There is limited literature describing the prevalence of bone health in EB, particularly in adults and less severe EB types.

Objectives

To investigate the prevalence of osteopenia or osteoporosis in EB patients from the Australasian Epidermolysis Bullosa Registry (AEBR).

Methods

Of 417 AEBR patients, 72 underwent a dual energy X‐ray absorptiometry scan. Bone mineral density (BMD) T and Z‐scores, EB Disease Activity and Scarring Index (EBDASI), and Quality of Life in EB (QOLEB) scores were obtained.

Results

T‐scores of RDEB patients were significantly lower than the diagnostic cut‐off value for osteopenia. EBDASI and QOLEB scores were inversely correlated with Z‐scores. The prevalence of osteoporosis in adults was 75% in severe EB types (RDEB and JEB). In adults with less severe types (EBS and DDEB), the prevalence of osteopenia was 50% and 33%, respectively.

Conclusions

This is the largest study of osteoporosis in EB to date and the first to include adult patients with EBS. The high prevalence of osteoporosis and osteopenia identified in these patients warrants larger, collaborative international studies. Nevertheless, EB patients with high disease severity and QOL scores, irrespective of type, should receive early osteoporosis screening and prophylaxis.
The multi‐functional RNA‐binding protein G3BP1 and its potential implication in neurodegenerative disease
Authors: Sidibé Hadjara , Dubinski Alicia , Vande Velde Christine
Published: December 2020

Ras‐GTPase‐activating protein (GAP)‐binding protein 1 (G3BP1) is a multi‐functional protein that is best known for its role in the assembly and dynamics of stress granules. Recent studies have highlighted that G3BP1 also has other functions related to RNA metabolism. In the context of disease, G3BP1 has been therapeutically targeted in cancers because its over‐expression is correlated with proliferation of cancerous cells and metastasis. However, evidence suggests that G3BP1 is essential for neuronal development and possibly neuronal maintenance. In this review, we will examine the many functions that are carried out by G3BP1 in the context of neurons and speculate how these functions are critical to the progression of neurodegenerative diseases. Additionally, we will highlight the similarities and differences between G3BP1 and the closely related protein G3BP2, which is frequently overlooked. Although G3BP1 and G3BP2 have both been deemed important for stress granule assembly, their roles may differ in other cellular pathways, some of which are specific to the CNS, and presents an opportunity for further exploration.

image
Comparing risk factors associated with the late detection of critical congenital heart disease at different facility levels
Authors: Sotodate Genichiro , Oyama Kotaro , Saiki Hirofumi , Matsumoto Atsushi , Konishi Yu , Toya Yukiko , Takashimizu Nao , Tsuchiya Shigekuni
Published: December 2020

Aims

Critical congenital heart disease (CCHD) requires surgery or catheter intervention within the first year of life; delayed diagnoses result in worsened outcomes. In Japan, there are few reports of delayed CCHD diagnosis. We investigated the diagnoses and factors associated with the late detection of CCHD.

Methods

This retrospective cohort study evaluated 88 CCHD infants admitted to a level IV facility. We compared the late detection rates across facility levels of neonatal care and CCHD characteristics.

Results

Critical congenital heart disease was identified prenatally in 46 (52%) infants: early (≤3 days postnatally) in 29 (33%) and late (≥4 days postnatally) in 13 (15%). The oxygen saturation of 27 of 29 infants with early detection and 7 of 13 infants with late detection was measured using pulse oximetry within 3 days postnatally. Factors associated with the late detection of CCHD were lack of clinical recognition of symptoms in five infants, referral to higher‐level facilities after discharge in four infants, and definitive diagnosis not confirmed using echocardiography in four infants. The most common factors associated with late detection were referral to higher‐level facilities after discharge in level I facilities and definitive diagnosis not confirmed using echocardiography in level II facilities.

Conclusion

Critical congenital heart disease may require advanced knowledge and echocardiographic techniques for diagnosis. Pulse oximetry and telemedicine should also be incorporated in the diagnostic algorithm. Improvement in these factors might contribute to reducing the late detection of CCHD.
Inter‐ and intra‐individual coupling between pupillary, electrophysiological, and behavioral responses in a visual oddball task
Authors: LoTemplio Sara , Silcox Jack , Federmeier Kara D. , Payne Brennan R.
Published: December 2020

Although the P3b component of the event‐related brain potential is one of the most widely studied components, its underlying generators are not currently well understood. Recent theories have suggested that the P3b is triggered by phasic activation of the locus‐coeruleus norepinephrine (LC‐NE) system, an important control center implicated in facilitating optimal task‐relevant behavior. Previous research has reported strong correlations between pupil dilation and LC activity, suggesting that pupil diameter is a useful indicator for ongoing LC‐NE activity. Given the strong relationship between LC activity and pupil dilation, if the P3b is driven by phasic LC activity, there should be a robust trial‐to‐trial relationship with the phasic pupillary dilation response (PDR). However, previous work examining relationships between concurrently recorded pupillary and P3b responses has not supported this. One possibility is that the relationship between the measures might be carried primarily by either inter‐individual (i.e., between‐participant) or intra‐individual (i.e., within‐participant) contributions to coupling, and prior work has not systematically delineated these relationships. Doing so in the current study, we do not find evidence for either inter‐individual or intra‐individual relationships between the PDR and P3b responses. However, baseline pupil dilation did predict the P3b. Interestingly, both the PDR and P3b independently predicted inter‐individual and intra‐individual variability in decision response time. Implications for the LC‐P3b hypothesis are discussed.
Prevalence, patterns and beliefs about the use of herbal medicinal products in Ghana: a multi‐centre community‐based cross‐sectional study
Authors: Kretchy Irene A. , Koduah Augustina , Opuni Kwabena F. M. , Agyabeng Kofi , Ohene‐Agyei Thelma , Boafo Eugene A. , Ntow Prisca O.
Published: December 2020

Objective

Worldwide, herbal medicinal products (HMPs) play key roles in healthcare systems, especially in developing countries, yet there is inconsistent evidence about their prevalence and patterns of use in Ghana. This study therefore sought to determine the prevalence, patterns and beliefs about the use of HMPs in Ghana.

Methods

A descriptive community‐based cross‐sectional survey was conducted using a researcher‐administered questionnaire on 1364 adults, selected from five communities for each of the ecological zones in Ghana using a multi‐stage sampling procedure. The study was conducted between December 2019 and March 2020.

Results

The prevalence of ever use of HMPs was 76.5% with 73.0% of respondents using these products within the past year. Almost 60% of respondents reported using HMPs that were registered by the Ghana Food and Drugs Authority. About 56.7% used these products to cure diseases. All the sociodemographic characteristics (age, religion, marital status, educational level and employment status) except for sex were significantly associated with the use of HMPs (P < 0.001). For beliefs about HMPs, the proportion of respondents classified to be accepting, ambivalent, indifferent and sceptical was 14.3%, 25.2%, 47.5% and 13.07%, respectively. About 62.2% of study participants had plans to use HMPs in the future, and 69.1% were willing to encourage others to use such products. However, 51.6% of the participants did not perceive HMPs as more effective and safe compared with orthodox products.

Conclusion

The prevalence of use of HMPs in Ghana is high, thus suggesting an appropriate public health policy to improve the regulation of these products and also provide basis for the integration of HMPs into the healthcare system in Ghana.
An Assessment on the Plastic Capacity of Pipe-in-Pipe Systems Under Damage Progression Effect
Authors: Davaripour Farhad , Quinton Bruce W.T. , Pike Kenton
Published: December 2020

In recent years, pipe-in-pipe (PiP) systems have been employed in an increasing number of subsea projects. According to the previous studies, the external pressure required to develop the initial local buckle on the PiP system is significantly higher than the pressure required to propagate the buckle along the system. In this respect, it is reasonable to investigate a novel topic where the propagation of buckle is induced by a lateral interference load instead of external pressure (e.g., diagonal fishing gear impact). On this subject, the recent studies showed the progression of plastic damage along a single-walled pipe, which is induced by a lateral load, could significantly lower the load-carrying capacity of the pipe. The present study investigates this finding for a PiP solution under a two-phase loading condition: in phase 1, the PiP solution is subject to 75 mm perpendicular indentation, and in phase 2, the resulting plastic damage in phase 1 is translated and induced longitudinally along the PiP system. Furthermore, using finite element analyses, the effect of combined loading (axial and lateral load) on the load-carrying capacity of the PiP specimen is investigated. The test results show that upon the initiation of damage progression, the load-carrying capacity of the PiP specimen (against the lateral indentation) declines by 10%. Also, the numerical results show that the structural resistance of a PiP specimen against a lateral indentation drops significantly when the inner pipe is subject to axial compression.
Posture-Invariant Three Dimensional Human Hand Statistical Shape Model
Authors: Yang Yusheng , Yuan Tianyun , Huysmans Toon , Elkhuizen Willemijn S. , Tajdari Farzam , Song Yu
Published: December 2020

A high-fidelity digital representation of (part of) the human body is a key enabler for integrating humans in a digital twin. Among different parts of human body, building the model of the hand can be a challenging task due to the posture deviations among collected scans. In this article, we proposed a posture invariant statistical shape model (SSM) of the human hand based on 59 3D scans of human hands. First, the 3D scans were spatially aligned using a Möbius sphere-based algorithm. An articulated skeleton, which contains 20 bone segments and 16 joints, was embedded for each 3D scan. Then, all scans were aligned to the same posture using the skeleton and the linear blend skinning (LBS) algorithm. Three methods, i.e., principal component analysis (PCA), kernel-PCA (KPCA) with different kernel functions, and independent component analysis (ICA), were evaluated in the construction of the SSMs regarding the compactness, the generalization ability, and the specificity. The PCA-based SSM was selected, where 20 principal components were used as parameters for the model. Results of the leave-one-out validation indicate that the proposed model was able to fit a given 3D scan of the human hand at an accuracy of 1.21 ± 0.14 mm. Experiment results also indicated that the proposed SSM outperforms the SSM that was built on the scans without posture correction. It is concluded that the proposed posture correction approach can effectively improve the accuracy of the hand SSM and therefore enables its wide usage in human-integrated digital twin applications.
Supplemental Material: Suprasubduction zone ophiolite fragments in the central Appalachian orogen: Evidence for mantle and Moho in the Baltimore Mafic Complex (Maryland, USA)
Authors: Guice G.L. , al. et
Published: December 2020

Excel file containing bulk-rock and mineral chemical data, including standard data and precision calculations.
New screening approach to detecting congenital syphilis in China: a retrospective cohort study
Authors: Hu Fang , Guo Shuai-Jun , Lu Jian-Jun , Hua Ning-Xuan , Song Yan-Yan , Lin Sui-Fang , Zhu Sui
Published: December 2020

Background

Diagnosis of congenital syphilis (CS) is not straightforward and can be challenging. This study aimed to evaluate the validity of an algorithm using timing of maternal antisyphilis treatment and titres of non-treponemal antibody as predictors of CS.

Methods

Confirmed CS cases and those where CS was excluded were obtained from the Guangzhou Prevention of Mother-to-Child Transmission of syphilis programme between 2011 and 2019. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) using receiver operating characteristics (ROC) in two situations: (1) receiving antisyphilis treatment or no-treatment during pregnancy and (2) initiating treatment before 28 gestational weeks (GWs), initiating after 28 GWs or receiving no treatment for syphilis seropositive women.

Results

Among 1558 syphilis-exposed children, 39 had confirmed CS. Area under the curve, sensitivity and specificity of maternal non-treponemal titres before treatment and treatment during pregnancy were 0.80, 76.9%, 78.7% and 0.79, 69.2%, 88.7%, respectively, for children with CS. For the algorithm, ROC results showed that PPV and NPV for predicting CS were 37.3% and 96.4% (non-treponemal titres cut-off value 1:8 and no antisyphilis treatment), 9.4% and 100% (non-treponemal titres cut-off value 1:16 and treatment after 28 GWs), 4.2% and 99.5% (non-treponemal titres cut-off value 1:32 and treatment before 28 GWs), respectively.

Conclusions

An algorithm using maternal non-treponemal titres and timing of treatment during pregnancy could be an effective strategy to diagnose or rule out CS, especially when the rate of loss to follow-up is high or there are no straightforward diagnostic tools.
Systematic review of reviews of symptoms and signs of COVID-19 in children and adolescents
Authors: Viner Russell M , Ward Joseph Lloyd , Hudson Lee D , Ashe Melissa , Patel Sanjay Valabh , Hargreaves Dougal , Whittaker Elizabeth
Published: December 2020

Objective

To undertake a systematic review of reviews of the prevalence of symptoms and signs of COVID-19 in those aged under 20 years.

Design

Narrative systematic review of reviews. PubMed, medRxiv, Europe PMC and COVID-19 Living Evidence Database were searched on 9 October 2020.

Setting

All settings, including hospitalised and community settings.

Patients

Children and young people (CYP) under age 20 years with laboratory-proven COVID-19.

Study review, data extraction and quality

Potentially eligible articles were reviewed on title and abstract by one reviewer. Quality was assessed using the modified AMSTARS criteria and data were extracted from included studies by two reviewers.

Main outcome measures

Prevalence of symptoms and signs of COVID-19.

Results

1325 studies were identified and 18 reviews were included. Eight were high quality, 7 medium and 3 low quality. All reviews were dominated by studies of hospitalised children. The proportion of asymptomatic CYP ranged from 14.6% to 42%. Fever and cough were the the most common symptoms; proportions with fever ranged from 46% to 64.2% and with cough from 32% to 55.9%. All other symptoms or signs including rhinorrhoea, sore throat, headache, fatigue/myalgia and gastrointestinal symptoms including diarrhoea and vomiting were infrequent, occurring in less than 10%–20%.

Conclusions

Fever and cough are the most common symptoms in CYP with COVID-19, with other symptoms infrequent. Further research on symptoms in community samples are needed to inform pragmatic identification and testing programmes for CYP.
Lafora body disease: a case of progressive myoclonic epilepsy
Authors: Kaur Ranjot , Balaini Neeraj , Sharma Sudhir , Sharma Sudarshan Kumar
Published: December 2020

Progressive myoclonic epilepsy (PME) is a progressive neurological disorder. Unfortunately, until now, no definitive curative treatment exists; however, it is of utmost importance to identify patients with PME. The underlying aetiology can be pinpointed if methodological clinical evaluation is performed, followed by subsequent genetic testing. We report a case of PME that was diagnosed as Lafora body disease. This case emphasises that, suspecting and identifying PME is important so as to start appropriate treatment and reduce the probability of morbidity and prognosticate the family.
Irish National Diabetic RetinaScreen Programme: report on five rounds of retinopathy screening and screen-positive referrals. (INDEAR study report no. 1)
Authors: Pandey Rajiv , Morgan Margaret M , Murphy Colette , Kavanagh Helen , Acheson Robert , Cahill Mark , McGettrick Patricia , O’Toole Louise , Hamroush Fatima , Mooney Therese , Byrne Helen , Fitzpatrick Patricia , Keegan David J
Published: December 2020

Objective

To study the uptake of annual diabetic retinopathy screening and study the 5-year trends in the detection of screen-positive diabetic retinopathy and non-diabetes-related eye disease in a cohort of annually screened individuals.

Design

Retrospective retinopathy screening attendance and retinopathy grading analysis.

Setting

Community-based retinopathy screening centres for the Diabetic RetinaScreen Programme.

Participants

171 557 were identified by the screening programme to be eligible for annual diabetic retinopathy screening. 120 048 individuals over the age of 12 consented to and attended at least one screening appointment between February 2013 to December 2018.

Main Outcome Measures

Detection rate per 100 000 of any retinopathy, screen-positive referrable retinopathy and nondiabetic eye disease.

Results

Uptake of screening had reached 67.2% in the fifth round of screening. Detection rate of screen-positive retinopathy reduced from 13 229 to 4237 per 100 000 screened over five rounds. Detection of proliferative disease had reduced from 2898 to 713 per 100 000 screened. Non-diabetic eye disease detection and referral to treatment centres increased almost eightfold from 393 in round 1 to 3225 per 100 000 screened. The majority of individuals referred to treatment centres for ophthalmologist assessment are over the age of 50 years.

Conclusions

Screening programme has seen a reduced detection rate both screen-positive retinopathy referral in Ireland over five rounds of screening. Management of nondiabetic eye diseases poses a significant challenge in improving visual outcomes of people living with diabetes in Ireland.
Plexus-specific retinal capillary avascular area in exudative age-related macular degeneration with projection-resolved OCT angiography
Authors: Gao Liqin , Wang Jie , You Qisheng , Guo Yukun , Flaxel Christina J , Hwang Thomas S , Huang David , Jia Yali , Bailey Steven T
Published: December 2020

Objective

To detect the plexus-specific retinal capillary avascular area in exudative age-related macular degeneration (EAMD) with projection-resolved optical coherence tomography angiography (PR-OCTA).

Methods and analysis

In this prospective cross-sectional single centre study, eyes with treatment-naïve EAMD underwent macular 3×3 mm OCTA with AngioVue system. OCTA scans were analysed and processed including three-dimensional projection artefact removal, retinal layer semi-automated segmentation and en face angiogram generation. Automated quantification of extrafoveal (excluding the central 1 mm circle) avascular area (EAA) were calculated on projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP) and deep capillary plexus (DCP), respectively.

Results

Nineteen eyes with EAMD and 19 age-matched healthy control eyes were included. There was no significant difference between the EAMD and control eyes in terms of age, sex, axial length and mean ocular perfusion pressure (all p>0.05). Compared with control eyes, EAMD eyes had significantly larger EAA in SVC (median 0.125 vs 0.059 mm2, p=0.006), ICP (0.016 vs 0.000 mm2, p=0.004) and DCP (0.033 vs 0.000 mm2, p＜0.001).

Conclusion

PR-OCTA showed that EAMD is associated with focal avascular area in all the three retinal vascular plexuses.
Peripapillary sclera exhibits a v-shaped configuration that is more pronounced in glaucoma eyes
Authors: Wang Xiaofei , Tun Tin A , Nongpiur Monisha Esther , Htoon Hla M , Tham Yih Chung , Strouthidis Nicholas G , Aung Tin , Cheng Ching-Yu , Girard Michael JA
Published: December 2020

Aims

To compare the shape of the anterior surface of the peripapillary sclera (PPS) between glaucoma and healthy subjects.

Methods

88 primary open angle glaucoma (POAG), 98 primary angle closure glaucoma (PACG) and 372 age-matched and gender-matched healthy controls were recruited in this study. The optic nerve head of one randomly selected eye of each subject was imaged with spectral domain optical coherence tomography. The shape of the PPS was measured through an angle defined between a line parallel to the nasal anterior PPS boundary and one parallel to the temporal side. A negative value indicated that the PPS followed an inverted v-shaped configuration (peak pointing towards the vitreous), whereas a positive value indicated that it followed a v-shaped configuration.

Results

The mean PPS angle in normal controls (4.56±5.99°) was significantly smaller than that in POAG (6.60±6.37°, p=0.011) and PACG (7.90±6.87°, p<0.001). The v-shaped PPS was significantly associated with older age (β=1.79, p<0.001), poorer best-corrected visual acuity (β=3.31, p=0.047), central corneal thickness (β=−0.28, p=0.001), peripapillary choroidal thickness (β=−0.21, p<0.001) and presence of POAG (β=1.94, p<0.009) and PACG (β=2.96, p<0.001). The v-shaped configuration of the PPS significantly increased by 1.46° (p=0.001) in healthy controls for every 10-year increase in age, but not in glaucoma groups.

Conclusions

The v-shaped configuration of the PPS was more pronounced in glaucoma eyes than in healthy eyes. This posterior bowing of the PPS may have an impact on the biomechanical environment of the optic nerve head.
Do smartphone applications and activity trackers increase physical activity in adults? Systematic review, meta-analysis and metaregression
Authors: Laranjo Liliana , Ding Ding , Heleno Bruno , Kocaballi Baki , Quiroz Juan C , Tong Huong Ly , Chahwan Bahia , Neves Ana Luisa , Gabarron Elia , Dao Kim Phuong , Rodrigues David , Neves Gisela Costa , Antunes Maria L , Coiera Enrico , Bates David W
Published: December 2020

Objective

To determine the effectiveness of physical activity interventions involving mobile applications (apps) or trackers with automated and continuous self-monitoring and feedback.

Design

Systematic review and meta-analysis.

Data sources

PubMed and seven additional databases, from 2007 to 2020.

Study selection

Randomised controlled trials in adults (18–65 years old) without chronic illness, testing a mobile app or an activity tracker, with any comparison, where the main outcome was a physical activity measure. Independent screening was conducted.

Data extraction and synthesis

We conducted random effects meta-analysis and all effect sizes were transformed into standardised difference in means (SDM). We conducted exploratory metaregression with continuous and discrete moderators identified as statistically significant in subgroup analyses.

Main outcome measures

Physical activity: daily step counts, min/week of moderate-to-vigorous physical activity, weekly days exercised, min/week of total physical activity, metabolic equivalents.

Results

Thirty-five studies met inclusion criteria and 28 were included in the meta-analysis (n=7454 participants, 28% women). The meta-analysis showed a small-to-moderate positive effect on physical activity measures (SDM 0.350, 95% CI 0.236 to 0.465, I2=69%,T2=0.051) corresponding to 1850 steps per day (95% CI 1247 to 2457). Interventions including text-messaging and personalisation features were significantly more effective in subgroup analyses and metaregression.

Conclusion

Interventions using apps or trackers seem to be effective in promoting physical activity. Longer studies are needed to assess the impact of different intervention components on long-term engagement and effectiveness.
Time-efficient intervention to improve older adolescents’ cardiorespiratory fitness: findings from the ‘Burn 2 Learn’ cluster randomised controlled trial
Authors: Lubans David R , Smith Jordan J , Eather Narelle , Leahy Angus A , Morgan Philip J , Lonsdale Chris , Plotnikoff Ronald C , Nilsson Michael , Kennedy Sarah G , Holliday Elizabeth G , Weaver Natasha , Noetel Michael , Shigeta Tatsuya T , Mavilidi Myrto F , Valkenborghs Sarah R , Gyawali Prajwal , Walker Frederick R , Costigan Sarah A , Hillman Charles H
Published: December 2020

Background

Cardiorespiratory fitness (CRF) is an important marker of current and future health status. The primary aim of our study was to evaluate the impact of a time-efficient school-based intervention on older adolescents’ CRF.

Methods

Two-arm cluster randomised controlled trial conducted in two cohorts (February 2018 to February 2019 and February 2019 to February 2020) in New South Wales, Australia. Participants (N=670, 44.6% women, 16.0±0.43 years) from 20 secondary schools: 10 schools (337 participants) were randomised to the Burn 2 Learn (B2L) intervention and 10 schools (333 participants) to the control. Teachers in schools allocated to the B2L intervention were provided with training, resources, and support to facilitate the delivery of high-intensity interval training (HIIT) activity breaks during curriculum time. Teachers and students in the control group continued their usual practice. The primary outcome was CRF (20 m multi-stage fitness test). Secondary outcomes were muscular fitness, physical activity, hair cortisol concentrations, mental health and cognitive function. Outcomes were assessed at baseline, 6 months (primary end-point) and 12 months. Effects were estimated using mixed models accounting for clustering.

Results

We observed a group-by-time effect for CRF (difference=4.1 laps, 95% CI 1.8 to 6.4) at the primary end-point (6 months), but not at 12 months. At 6 months, group-by-time effects were found for muscular fitness, steps during school hours and cortisol.

Conclusions

Implementing HIIT during curricular time improved adolescents’ CRF and several secondary outcomes. Our findings suggest B2L is unlikely to be an effective approach unless teachers embed sessions within the school day.

Trial registration number

Australian New Zealand Clinical Trials Registry (ACTRN12618000293268).