bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological Aging Predicts Vulnerability to COVID-19 Severity in UK Biobank Participants
Authors: Kuo Chia-Ling , Pilling Luke C , Atkins Janice L , Masoli Jane A H , Delgado João , Tignanelli Christopher , Kuchel George A , Melzer David , Beckman Kenneth B , Levine Morgan E
Published: March 2021

Background

Age and disease prevalence are the 2 biggest risk factors for Coronavirus disease 2019 (COVID-19) symptom severity and death. We therefore hypothesized that increased biological age, beyond chronological age, may be driving disease-related trends in COVID-19 severity.

Methods

Using the UK Biobank England data, we tested whether a biological age estimate (PhenoAge) measured more than a decade prior to the COVID-19 pandemic was predictive of 2 COVID-19 severity outcomes (inpatient test positivity and COVID-19-related mortality with inpatient test-confirmed COVID-19). Logistic regression models were used with adjustment for age at the pandemic, sex, ethnicity, baseline assessment centers, and preexisting diseases/conditions.

Results

Six hundred and thirteen participants tested positive at inpatient settings between March 16 and April 27, 2020, 154 of whom succumbed to COVID-19. PhenoAge was associated with increased risks of inpatient test positivity and COVID-19-related mortality (ORMortality = 1.63 per 5 years, 95% CI: 1.43–1.86, p = 4.7 × 10−13) adjusting for demographics including age at the pandemic. Further adjustment for preexisting diseases/conditions at baseline (ORM = 1.50, 95% CI: 1.30–1.73 per 5 years, p = 3.1 × 10−8) and at the early pandemic (ORM = 1.21, 95% CI: 1.04–1.40 per 5 years, p = .011) decreased the association.

Conclusions

PhenoAge measured in 2006–2010 was associated with COVID-19 severity outcomes more than 10 years later. These associations were partly accounted for by prevalent chronic diseases proximate to COVID-19 infection. Overall, our results suggest that aging biomarkers, like PhenoAge may capture long-term vulnerability to diseases like COVID-19, even before the accumulation of age-related comorbid conditions.
Korean Immigrants’ Perception of Mental Well-Being and Help-Seeking Behaviors
Authors: Koh Eun , Choi Ga-Young , Choi Sam , Cho Ji-Young
Published: March 2021

This article describes a study that investigated Korean immigrants’ perception of mental well-being and help-seeking behaviors with particular focus on those with mental illness. Participants with probable diagnoses of anxiety or depression were more likely to recognize their mental health problems and their impact than those without such diagnoses. However, many of them did not acknowledge experiencing mental health problems and did not show high likelihood of seeking professional mental health services. The cultural beliefs and the lack of culturally competent mental health services appeared to contribute to the low levels of recognition of mental health problems and also the low rates of mental health service utilization. The participants listed mental health professionals’ ability to communicate in the language of their preference, confidentiality, and affordability as significant factors in their decision to seek professional help. The study findings emphasize the great need of mental health educational programs within the Korean immigrant community. The findings also suggest that resources and infrastructures be secured for the provision of culturally competent mental health services for this population.
IV and oral fosfomycin pharmacokinetics in neonates with suspected clinical sepsis
Authors: Kane Zoe , Gastine Silke , Obiero Christina , Williams Phoebe , Murunga Sheila , Thitiri Johnstone , Ellis Sally , Correia Erika , Nyaoke Borna , Kipper Karin , van den Anker John , Sharland Mike , Berkley James A , Standing Joseph F
Published: March 2021

Background

Fosfomycin has the potential to be re-purposed as part of a combination therapy to treat neonatal sepsis where resistance to current standard of care (SOC) is common. Limited data exist on neonatal fosfomycin pharmacokinetics and estimates of bioavailability and CSF/plasma ratio in this vulnerable population are lacking.

Objectives

To generate data informing the appropriate dosing of IV and oral fosfomycin in neonates using a population pharmacokinetic analysis of plasma and CSF data.

Methods

The NeoFosfo study (NCT03453177) was a randomized trial that examined the safety and pharmacokinetics of fosfomycin comparing SOC versus SOC plus fosfomycin. Sixty-one neonates received fosfomycin (100 mg/kg IV q12h for 48 h) and then they converted to oral therapy at the same dose. Two plasma pharmacokinetic samples were taken following the first IV and oral doses, sample times were randomized to cover the whole pharmacokinetic profile and opportunistic CSF pharmacokinetic samples were collected. A population pharmacokinetic model was developed in NONMEM and simulations were performed.

Results

In total, 238 plasma and 15 CSF concentrations were collected. A two-compartment disposition model, with an additional CSF compartment and first-order absorption, best described the data. Bioavailability was estimated as 0.48 (95% CI = 0.347–0.775) and the CSF/plasma ratio as 0.32 (95% CI = 0.272–0.409). Allometric weight and postmenstrual age (PMA) scaling was applied; additional covariates included postnatal age (PNA) on clearance and CSF protein on CSF/plasma ratio.

Conclusions

Through this analysis a population pharmacokinetic model has been developed that can be used alongside currently available pharmacodynamic targets to select a neonatal fosfomycin dose based on an infant’s PMA, PNA and weight.
Retrieving reflection arrivals from passive seismic data using Radon correlation
Authors: Hariri Naghadeh Diako , Bean Christopher J , Brenguier Florent , Smith Patrick J
Published: March 2021

Since explosive and impulsive seismic sources such as dynamite, air guns, gas guns or even vibroseis can have a big impact on the environment, some companies have decided to record ambient seismic noise and use it to estimate the physical properties of the subsurface. Big challenges arise when the aim is extracting body waves from recorded passive signals, especially in the presence of strong surface waves. In passive seismic signals, such body waves are usually weak in comparison to surface waves that are much more prominent. To understand the characteristics of passive signals and the effect of natural source locations, three simple synthetic models were created. To extract body waves from simulated passive signals we propose and test a Radon-correlation method. This is a time-spatial correlation of amplitudes with a train of time-shifted Dirac delta functions through different hyperbolic paths. It is tested on a two-layer horizontal model, a three-layer model that includes a dipping layer (with and without lateral heterogeneity) and also on synthetic Marmousi model data sets. Synthetic tests show that the introduced method is able to reconstruct reflection events at the correct time-offset positions that are hidden in results obtained by the general cross-correlation method. Also, a depth migrated section shows a good match between imaged horizons and the true model. It is possible to generate off-end virtual gathers by applying the method to a linear array of receivers and to construct a velocity model by semblance velocity analysis of individually extracted gathers.
On the behavior of functionally graded shape memory polymer composites under thermal coupling
Authors: Liu Bingfei , Yin Kai , Zhang Fangfang , Zhou Rui
Published: March 2021

Shape memory polymer composites (SMPC), which are a type of stimuli-responsive material, show better mechanical properties than pure shape memory polymers. However, different engineering applications have different requirements for the fiber content of SMPC. For example, some parts of the structure require more fibers to enhance strength, while other parts require fewer fibers to maintain deformability. In order to solve this problem, a functionally graded shape memory polymer composite (FG-SMPC) is proposed in this work. The contents of the fibers for the FG-SMPC can be changed along the geometric dimension of the material, enabling different performance requirements to be met in different parts of the structure. Based on the constitutive model of the SMP and the mechanics of composite materials, the mechanical behaviors of the FG-SMPC under thermal loading are discussed. The results show that such materials exhibit gradient behaviors for both the intensity and shape memory effect with different gradient distributions.
Understanding Infants’ In-Home Injuries: Context and Correlates
Authors: Morrongiello Barbara A , Corbett Michael , Bryant Lindsay , Cox Amanda
Published: March 2021

Rationale

Infancy is a time of elevated risk of injury. Past research has focused mostly on the type of injuries, leaving many gaps in knowledge about contextual information that could aid in injury prevention planning.

Methods

In this longitudinal study, a participant-event recording method was used in which mothers tracked their infants’ home injuries through three motor development stages (sitting up independently, crawling, and walking). A contextual analysis elucidated where injuries occurred, their type and severity, the infant’s and parent’s behaviors at the time, if the infant had done the risk behavior before and been injured, the level of supervision, and the nature of any safety precautions parents implemented following these injuries.

Results

Injuries occurred as often in play as in nonplay areas and were due to physically-active nonplay activities more so than play activities; mothers were often doing chores. Bumps and bruises were the most common types of injuries. As infants became more mobile, supervision scores declined and injury severity scores increased. Infants had done the risk behavior leading to injury previously about 60% of the time, with higher scores associated with parents implementing fewer preventive actions in response to injury. When mothers did implement a safety precaution, greater injury severity was associated with more modifications to the environment and increased supervision; teaching about safety was infrequent.

Conclusion

Implications of these results for injury prevention messaging are discussed.
Long-term outcomes of patients with unresectable benign meningioma treated with proton beam therapy
Authors: Sato Hiroshige , Mizumoto Masashi , Okumura Toshiyuki , Sakurai Hideyuki , Sakamoto Noriaki , Akutsu Hiroyoshi , Ishikawa Eiichi , Tsuboi Koji
Published: March 2021

This study aimed to evaluate the long-term efficacy of proton beam therapy (PBT) for unresectable benign meningiomas at the University of Tsukuba, Japan. From 1986–1998, 10 patients were treated at the Particle Radiation Medical Science Center (PRMSC) with a relative biological effectiveness (RBE) value of 1.0 using an accelerator built for physics experiments. The total dose was compensated with an X-ray in three patients. Following that, from 2002–2017, 17 patients were treated with a RBE value of 1.1 at the Proton Medical Research Center (PMRC) which was built for medical use. At the PRMSC, the total dose ranged from 50.4–66 Gy (median: 54 Gy). During the follow-up, which lasted between 3.8 and 31.6 years (median: 25.1 years), the 5-, 10-, 15-, 20- and 30-year local control rates were 100%, and the 5-, 10-, 15-, 20- and 30-year survival rates were 90, 80, 70, 70 and 36%, respectively. One patient died of brainstem radiation necrosis 5.1 years after PBT. At PMRC, the total dose ranged from 45.0–61.2 GyE, with a median of 50.4 GyE. During the follow-up, which lasted between 3 and 17 years with a median of 10.5 years, the 5-, 10- and 15-year local control rates were 94.1%, and the 5-, 10- and 15-year survival rates were 100, 100 and 88.9%, respectively. Neither malignant transformation nor secondary malignancy was observed, indicating that fractionated PBT may be effective and safely control benign unresectable meningioma even for the lifelong period of time.
Digitization Without Digital Evidence: Technology and Sweden’s Asylum System
Authors: Micinski Nicholas R , Jones Will
Published: March 2021

States and asylum seekers are at the centre of rapid digital innovation in surveillance, mobility, welfare and identity. Why do some states rush to digitalize asylum systems, while others do not? Why is the pace and form of digitalization within countries uneven within asylum agencies? In this article, we examine drivers of the digitalization of the Swedish state, in particular uneven digitalization within the Swedish Migration Agency (Migrationsverket). While many processes were swiftly digitalized, we found that Swedish bureaucrats, rather than politicians or activist lawyers, resisted the adoption of digital evidence within the refugee status determination process, despite enthusiastically digitizing elsewhere. We explore these differences by looking at the historical, institutional and cultural bases of Swedish refugee policy. We present evidence from fieldwork in Sweden and find an unequal pace of digitalization that was largely dependent on the bureaucratic risk-aversion, extant legal norms, and perceived vulnerability to fraud.
Digital insights: bridging the phenotype-to-genotype divide
Authors: McCabe Matthew F , Tester Mark
Published: March 2021

This article comments on:

Han R, Wong AJY, Tang Z, Truco MJ, Lavelle DO, Kozik A, Jin Y, Michelmore R. 2021. Drone phenotyping and machine learning enable discovery of loci regulating daily floral opening in lettuce. Journal of Experimental Botany 72,2979–2994.
Dutifully Defying Death: A Right to Life-saving Emergency Treatment
Authors: Lui Edward
Published: March 2021

Article 12 of the International Covenant on Economic, Social and Cultural Rights provides for the right to health. Two questions are considered in this article. Does this right entail a more specific right to life-saving emergency treatment? And if so, should the latter right become justiciable in the domestic courts? Two propositions will be made in this article. First, the right to life-saving emergency treatment is a necessary component of the right to health. Second, the conventional arguments against the justiciability of socio-economic rights do not apply to the right to life-saving emergency treatment. Such a right should be justiciable at the domestic level.
High-sensitivity radio study of the non-thermal stellar bow shock EB27
Authors: Benaglia Paula , del Palacio Santiago , Hales Christopher , Colazo Marcelo E
Published: March 2021

We present a deep radio-polarimetric observation of the stellar bow shock EB27 associated with the massive star BD+43○3654. This is the only stellar bow shock confirmed to have non-thermal radio emission. We used the Jansky Very Large Array in S band (2–4 GHz) to test whether this synchrotron emission is polarized. The unprecedented sensitivity achieved allowed us to map even the fainter regions of the bow shock, revealing that the more diffuse emission is steeper and the bow shock brighter than previously reported. No linear polarization is detected in the bow shock above 0.5 per cent, although we detected polarized emission from two southern sources, probably extragalactic in nature. We modelled the intensity and morphology of the radio emission to better constrain the magnetic field and injected power in relativistic electrons. Finally, we derived a set of more precise parameters for the system EB27–BD+43○3654 using Gaia Early Data Release 3, including the spatial velocity. The new trajectory, back in time, intersects the core of the Cyg OB2 association.
An RNA tagging approach for system-wide RNA-binding proteome profiling and dynamics investigation upon transcription inhibition
Authors: Zhang Zheng , Liu Tong , Dong Hangyan , Li Jian , Sun Haofan , Qian Xiaohong , Qin Weijie
Published: March 2021

RNA-protein interactions play key roles in epigenetic, transcriptional and posttranscriptional regulation. To reveal the regulatory mechanisms of these interactions, global investigation of RNA-binding proteins (RBPs) and monitor their changes under various physiological conditions are needed. Herein, we developed a psoralen probe (PP)-based method for RNA tagging and ribonucleic-protein complex (RNP) enrichment. Isolation of both coding and noncoding RNAs and mapping of 2986 RBPs including 782 unknown candidate RBPs from HeLa cells was achieved by PP enrichment, RNA-sequencing and mass spectrometry analysis. The dynamics study of RNPs by PP enrichment after the inhibition of RNA synthesis provides the first large-scale distribution profile of RBPs bound to RNAs with different decay rates. Furthermore, the remarkably greater decreases in the abundance of the RBPs obtained by PP-enrichment than by global proteome profiling suggest that PP enrichment after transcription inhibition offers a valuable way for large-scale evaluation of the candidate RBPs.
Machine Learning for the Prediction of Molecular Markers in Glioma on Magnetic Resonance Imaging: A Systematic Review and Meta-Analysis
Authors: Jian Anne , Jang Kevin , Manuguerra Maurizio , Liu Sidong , Magnussen John , Di Ieva Antonio
Published: March 2021

BACKGROUND

Molecular characterization of glioma has implications for prognosis, treatment planning, and prediction of treatment response. Current histopathology is limited by intratumoral heterogeneity and variability in detection methods. Advances in computational techniques have led to interest in mining quantitative imaging features to noninvasively detect genetic mutations.

OBJECTIVE

To evaluate the diagnostic accuracy of machine learning (ML) models in molecular subtyping gliomas on preoperative magnetic resonance imaging (MRI).

METHODS

A systematic search was performed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines to identify studies up to April 1, 2020. Methodological quality of studies was assessed using the Quality Assessment for Diagnostic Accuracy Studies (QUADAS)-2. Diagnostic performance estimates were obtained using a bivariate model and heterogeneity was explored using metaregression.

RESULTS

Forty-four original articles were included. The pooled sensitivity and specificity for predicting isocitrate dehydrogenase (IDH) mutation in training datasets were 0.88 (95% CI 0.83-0.91) and 0.86 (95% CI 0.79-0.91), respectively, and 0.83 to 0.85 in validation sets. Use of data augmentation and MRI sequence type were weakly associated with heterogeneity. Both O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation and 1p/19q codeletion could be predicted with a pooled sensitivity and specificity between 0.76 and 0.83 in training datasets.

CONCLUSION

ML application to preoperative MRI demonstrated promising results for predicting IDH mutation, MGMT methylation, and 1p/19q codeletion in glioma. Optimized ML models could lead to a noninvasive, objective tool that captures molecular information important for clinical decision making. Future studies should use multicenter data, external validation and investigate clinical feasibility of ML models.
Symmetry enhancement in a two-logarithm matrix model and the canonical tensor model
Authors: Sasakura Naoki
Published: March 2021

We study a one-matrix model of a real symmetric matrix with a potential which is a sum of two logarithmic functions and a harmonic one. This two-logarithm matrix model is the absolute square norm of a toy wave function which is obtained by replacing the tensor argument of the wave function of the canonical tensor model (CTM) with a matrix. We discuss a symmetry enhancement phenomenon in this matrix model and show that symmetries and dimensions of emergent spaces are stable only in a phase which exists exclusively for the positive cosmological constant case in the sense of CTM. This would imply the importance of the positivity of the cosmological constant in the emergence phenomena in CTM.
Transparency of the national government as key in promoting the rollout of COVID-19 vaccines
Authors: Dela Cruz Moriah Dianne M , Mendoza Abelardo Jose M , Gueco Gevans Ed A , Maghinang C J Mark P , Gopez Jose Ma W
Published: March 2021

A recent correspondence discussed two important attributes of the government officials, namely, public service and common good. These two could possibly help the government in terms of promoting vaccination programs in the Philippines. This paper proposes transparency as the third attribute that could help in gaining trust from the people in promoting vaccination in the country.
Genotypes and prevalence of carbapenemase-producing Enterobacteriaceae and Pseudomonas aeruginosa in a hospital in Saudi Arabia
Authors: Al-Tawfiq Jaffar A , Rabaan Ali A , Saunar Justin V , Bazzi Ali M
Published: March 2021

Background

The molecular epidemiology of resistance of carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas aeruginosa are important in the study of multidrug-resistant bacteria. We evaluate the prevalence of the different mechanisms of CRE in a hospital in Saudi Arabia.

Methods

Carbapenem non-susceptible isolates of Enterobacteriaceae and Pseudomonas aeruginosa were tested by real-time PCR for the detection of genes responsible for beta-lactam resistance.

Results

There were a total of 200 isolates with carbapenem non-susceptibility and these were Klebsiella pneumoniae (n=96, 48%), Escherichia coli (n=51, 25.5%) and Pseudomonas aeruginosa (n=45, 22.5%). The detected carbapenemases were oxacillinase-48 (OXA-48) (n=83, 41.5%), New Delhi metallo-β-lactamase (NDM) (n=19, 2.5%) and both NDM and OXA-48 (n=5, 2.5%). The other carbapenemases were imipenemase (n=1, 0.5%), Verona integrin encoded metallo-β-lactamase (n=6, 3%) and Klebsiella pneumoniae carbapenemase (n=1, 0.5%), but none were detected in 86 isolates (43%).

Conclusion

The most common carbapenemases were OXA-48 and a significant percentage had no detectable genes. These data will help in the selection of new antimicrobial therapies.
Progress and Pitfalls of Bacteriophage Therapy in Critical Care: A Concise Definitive Review
Authors: Valente Luca , Prazak Josef , Que Yok-Ai , Cameron David R.
Published: March 2021

Objective:

Bacterial infections caused by antibiotic-resistant pathogens are a major problem for patients requiring critical care. An approach to combat resistance is the use of bacterial viruses known as “phage therapy.” This review provides a brief “clinicians guide” to phage biology and discusses recent applications in the context of common infections encountered in ICUs.

Data Sources:

Research articles were sourced from PubMed using search term combinations of “bacteriophages” or “phage therapy” with either “lung,” “pneumonia,” “bloodstream,” “abdominal,” “urinary tract,” or “burn wound.”

Study Selection:

Preclinical trials using animal models, case studies detailing compassionate use of phage therapy in humans, and randomized controlled trials were included.

Data Extraction:

We systematically extracted: 1) the infection setting, 2) the causative bacterial pathogen and its antibiotic resistance profile, 3) the nature of the phage therapeutic and how it was administered, 4) outcomes of the therapy, and 5) adverse events.

Data Synthesis:

Phage therapy for the treatment of experimental infections in animal models and in cases of compassionate use in humans has been associated with largely positive outcomes. These findings, however, have failed to translate into positive patient outcomes in the limited number of randomized controlled trails that have been performed to date.

Conclusions:

Widespread clinical implementation of phage therapy depends on success in randomized controlled trials. Additional translational and reverse translational studies aimed at overcoming phage resistance, exploiting phage-antibiotic synergies, and optimizing phage administration will likely improve the design and outcome of future trials.
Recommendations for COVID-19 Vaccination in People with Rheumatic Disease:Developed by the Singapore Chapter of Rheumatologists
Authors: Santosa Amelia , Xu Chuanhui , Arkachaisri Thaschawee , Kong Kok Ooi , Lateef Aisha , Lee Tau Hong , Leong Keng Hong , Low Andrea Hsiu Ling , Sriranganathan Melonie K , Tan Teck Choon , Teng Gim Gee , Thong Bernard Yu-hor , Fong Warren , Lahiri Manjari
Published: March 2021

Aim

People with rheumatic diseases (PRD) remain vulnerable in the era of the COVID-19 pandemic. We formulated recommendations to meet the urgent need for a consensus for vaccination against SARS-CoV-2 in PRD.

Methods

Systematic literature reviews were performed to evaluate (1) outcomes in PRD with COVID-19; (2) efficacy, immunogenicity and safety of COVID-19 vaccination; and (3) published guidelines/recommendations for non-live, non-COVID-19 vaccinations in PRD. Recommendations were formulated based on the evidence and expert opinion according to the Grading of Recommendations Assessment, Development and Evaluation methodology.

Results

The consensus comprises two overarching principles and seven recommendations. Vaccination against SARS-CoV-2 in PRD should be aligned with prevailing national policy and should be individualized through shared decision between the healthcare provider and patient. We strongly recommended that eligible PRD and household contacts be vaccinated against SARS-CoV-2. We conditionally recommended that the COVID-19 vaccine be administered during quiescent disease if possible. Immunomodulatory drugs, other than rituximab, can be continued alongside vaccination. We conditionally recommended that the COVID-19 vaccine be administered prior to commencing rituximab if possible. For patients on rituximab, the vaccine should be administered a minimum of 6 months after the last dose and/or 4 weeks prior to the next dose of rituximab. Post-vaccination antibody titres against SARS-CoV-2 need not be measured. Any of the approved COVID-19 vaccines may be used, with no particular preference.

Conclusion

These recommendations provide guidance for COVID-19 vaccination in PRD. Most recommendations in this consensus are conditional, reflecting a lack of evidence or low-level evidence. (words 247)
De-novo FAIRification via an Electronic Data Capture system by automated transformation of filled electronic Case Report Forms into machine-readable data
Authors: Kersloot Martijn G. , Jacobsen Annika , Groenen Karlijn H.J. , dos Santos Vieira Bruna , Kaliyaperumal Rajaram , Abu-Hanna Ameen , Cornet Ronald , 't Hoen Peter A.C. , Roos Marco , Schultze Kool Leo , Arts Derk L.
Published: March 2021

Introduction
Existing methods to make data Findable, Accessible, Interoperable, and Reusable (FAIR) are usually carried out in a post-hoc manner: after the research project is conducted and data are collected. De-novo FAIRification, on the other hand, incorporates the FAIRification steps in the process of a research project. In medical research, data is often collected and stored via electronic Case Report Forms (eCRFs) in Electronic Data Capture (EDC) systems. By implementing a de-novo FAIRification process in such a system, the reusability and, thus, scalability of FAIRification across research projects can be greatly improved. In this study, we developed and implemented a novel method for de-novo FAIRification via an EDC system. We evaluated our method by applying it to the Registry of Vascular Anomalies (VASCA).

Methods
Our EDC and research project independent method ensures that eCRF data entered into an EDC system can be transformed into machine-readable, FAIR data using a semantic data model (a canonical representation of the data, based on ontology concepts and semantic web standards) and mappings from the model to questions on the eCRF. The FAIRified data are stored in a triple store and can, together with associated metadata, be accessed and queried through a FAIR Data Point. The method was implemented in Castor EDC, an EDC system, through a data transformation application. The FAIRness of the output of the method, the FAIRified data and metadata, was evaluated using the FAIR Evaluation Services.

Results
We successfully applied our FAIRification method to the VASCA registry. Data entered on eCRFs is automatically transformed into machine-readable data and can be accessed and queried using SPARQL queries in the FAIR Data Point. Twenty-one FAIR Evaluator tests pass and one test regarding the metadata persistence policy fails, since this policy is not in place yet.

Conclusion
In this study, we developed a novel method for de-novo FAIRification via an EDC system. Its application in the VASCA registry and the automated FAIR evaluation show that the method can be used to make clinical research data FAIR when they are entered in an eCRF without any intervention from data management and data entry personnel. Due to the generic approach and developed tooling, we believe that our method can be used in other registries and clinical trials as well.
Estimating Causal Treatment Effects of Femoral and Tibial Derotational Osteotomies on Foot Progression in Children with Cerebral Palsy
Authors: Schwartz Michael H. , Kainz Hans , Georgiadis Andrew G.
Published: March 2021

Background

Foot progression deviations are a common and important problem for children with CP. Tibial and femoral derotational osteotomies (TDO, FDO) are used to treat foot progression deviations, but outcomes are unpredictable. The available evidence for the causal effects of TDO and FDO is limited and weak, and thus modeling approaches are needed.

Methods

We queried our clinical database for individuals with a diagnosis of cerebral palsy (CP) who were less than 18 years old and had baseline and follow up gait data collected within a 3-year time span. We then used the Bayesian Causal Forest (BCF) algorithm to estimate the causal treatment effects of TDO and FDO on foot progression deviations (separate models). We examined average treatment effects and heterogeneous treatment effects (HTEs) with respect to clinically relevant covariates.

Results

The TDO and FDO models were able to accurately predict follow-up foot progression (r2 ∼0.7, RMSE ∼8°). The estimated causal effect of TDO was bimodal and exhibited significant heterogeneity with respect to baseline levels of foot progression and tibial torsion as well as changes in tibial torsion at follow-up. The estimated causal effect of FDO was unimodal and largely homogeneous with respect to baseline or change characteristics.

Conclusions

This study demonstrated the potential for causal machine-learning algorithms to impact treatment in children with CP. The causal model is accurate and appears sensible – though no gold-standard exists for validating the causal estimates. The model results can provide guidance for planning surgical corrections, and partly explain unsatisfactory outcomes observed in prior observational clinical studies.
Effect of Eight-Week Online Cognitive Training in Parkinson’s Disease: A Randomized Controlled Trial
Authors: van Balkom Tim D. , Berendse Henk W. , van der Werf Ysbrand D. , Twisk Jos W.R. , Peeters Carel F.W. , Hagen Rob H. , Berk Tanja , van den Heuvel Odile A. , Vriend Chris
Published: March 2021

Background

Cognitive training (CT) has been proposed as a non-pharmacological treatment option for the frequent cognitive impairments occurring in PD.

Objective

Assess the efficacy of CT on cognitive function in PD.

Methods

In this double-blind, randomized controlled trial we enrolled 140 PD patients with significant subjective cognitive complaints. In eight weeks, participants underwent 24 sessions of computerized multi-domain CT or an active control condition for 45 minutes each (n=70 vs. n=70). The primary outcome was the accuracy on a computerized Tower of London task; secondary outcomes included effects on other neuropsychological outcomes and subjective cognitive complaints. Outcomes were assessed before and after training and at six-months follow-up, and were analyzed with multivariate mixed-model analyses.

Results

The intention-to-treat population consisted of 136 participants. Multivariate mixed-model analyses showed no group difference on the Tower of London accuracy corrected for baseline performance: B: −0.06, 95% CI: −0.27 to 0.15, p=0.562. Participants in the CT group were on average 0.30 SD (i.e., 1.5 seconds) faster on the Tower of London, difficulty load 4 (secondary outcome): 95% CI: −0.55 to −0.06, p=0.015. CT had similar positive effects on other processing speed-related executive function tasks, although these did not reach statistical significance. At follow-up, no group differences were present.

Conclusions

The results show tentative but consistent positive effects of CT on processing speed during executive functioning. Future studies should investigate booster sessions to increase durability, optimize training duration, and study different sub-groups of PD patients along the continuum of cognitive decline towards PD dementia.
Estimating the super-spreading rate at workplaces using bluetooth technology
Authors: Vazquez Alexei , Staebler Maximilian , Khanin Alexander , Lichte Daniel , Brucherseifer Eva
Published: March 2021

Workplaces deploy internal guidelines to remain operational during the ongoing COVID-19 pandemic. It is challenging to assess whether those interventions will prevent super-spreading events, where an infected individual transmits the disease to 10 or more secondary cases. Here we provide a model of infectious disease at the level of a workplace to address that problem. We take as input proximity contact records based on bluetooth technology and the infectious disease parameters from the literature. Using proximity contact data for a case-study workplace and an infection transmission model, we estimate the SARS-CoV-2 transmission rate as 0.014 per proximity contact, going up to 0.041 for the SARS-CoV-2 B.1.1.7 variant first detected in the UK. Defining super-spreading as events with 10 or more secondary infections, we obtain a super-spreading event rate of 2.3 per 1000 imported SARS-CoV-2 cases, rising up to 13.7 for SARS-CoV-2 B.1.1.7. This methodology provides the means for workplaces to determine their internal super-spreading rate or other infection related risks.
Detection and genome sequencing of SARS-CoV-2 belonging to the B.1.1.7 lineage in the Philippines
Authors: Tablizo Francis A. , Saloma Cynthia P. , Castro Marc Jerrone R. , Kim Kenneth M. , Yangzon Maria Sofia L. , Lapid Carlo M. , Maralit Benedict A. , Ayes Marc Edsel C. , Yap Jan Michael C. , Llames Jo-Hannah S. , Araiza Shiela Mae M. , Punayan Kris P. , Asin Irish Coleen A. , Tambaoan Candice Francheska B. , Chong Asia Louisa U. , Padilla Karol Sophia Agape R. , Cruz Rianna Patricia S. , Morado El King D. , Dizon Joshua Gregor A. , Cutiongco-de la Paz Eva Maria , de Guzman Alethea R. , Hao Razel Nikka M. , Zamora Arianne A. , Pacial Devon Ray , Magalang Juan Antonio R. , Alejandria Marissa , Carlos Celia , Ong-Lim Anna , Salvaña Edsel Maurice , Wong John Q. , Montoya Jaime C. , Singh-Vergeire Maria Rosario
Published: March 2021

We report the sequencing and detection of 39 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) samples containing lineage-defining mutations specific to viruses belonging to the B.1.1.7 lineage (UK variant) in the Philippines.
SARS-CoV-2-specific T Cell Memory is Sustained in COVID-19 Convalescents for 8 Months with Successful Development of Stem Cell-like Memory T Cells
Authors: Jung Jae Hyung , Rha Min-Seok , Sa Moa , Choi Hee Kyoung , Jeon Ji Hoon , Seok Hyeri , Park Dae Won , Park Su-Hyung , Jeong Hye Won , Choi Won Suk , Shin Eui-Cheol
Published: March 2021

Memory T cells contribute to rapid viral clearance during re-infection, but the longevity and differentiation of SARS-CoV-2-specific memory T cells remain unclear. We conducted direct ex vivo assays to evaluate SARS-CoV-2-specific CD4+ and CD8+ T cell responses in COVID-19 convalescents up to 254 days post-symptom onset (DPSO). Here, we report that memory T cell responses were maintained during the study period. In particular, we observed sustained polyfunctionality and proliferation capacity of SARS-CoV-2-specific T cells. Among SARS-CoV-2-specific CD4+ and CD8+ T cells detected by activation-induced markers, the proportion of stem cell-like memory T (TSCM) cells increased, peaking at approximately 120 DPSO. Development of TSCM cells was confirmed by SARS-CoV-2-specific MHC-I multimer staining. Considering the self-renewal capacity and multipotency of TSCM cells, our data suggest that SARS-CoV-2-specific T cells are long-lasting after recovery from COVID-19. The current study provides insight for establishing an effective vaccination program and epidemiological measurement.
Language disorder in progressive supranuclear palsy and corticobasal syndrome: neural correlates and detection by the MLSE screening tool
Authors: Peterson Katie A. , Jones P. Simon , Patel Nikil , Tsvetanov Kamen A. , Ingram Ruth , Cappa Stefano F. , Ralph Matthew A. Lambon , Patterson Karalyn , Garrard Peter , Rowe James B.
Published: March 2021

Background

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) affect speech and language as well as motor functions. Clinical and neuropathological data indicate a close relationship between these two disorders and the non-fluent variant of primary progressive aphasia (nfvPPA). We use the recently developed Mini Linguistic State Examination tool (MLSE) to study speech and language disorders in patients with PSP, CBS, and nfvPPA, in combination with structural magnetic resonance imaging (MRI).

Methods

Fifty-one patients (PSP N = 13, CBS N = 19, nfvPPA N = 19) and 30 age-matched controls completed the MLSE, the short form of the Boston Diagnostic Aphasia Examination (BDAE), and the Addenbrooke’s Cognitive Examination III. Thirty-eight patients and all controls underwent structural MRI at 3 Tesla, with T1 and T2-weighted images processed by surface-based and subcortical segmentation within FreeSurfer 6.0.0 to extract cortical thickness and subcortical volumes. Morphometric differences were compared between groups and correlated with severity of speech and language impairment.

Results

CBS and PSP patients showed impaired MLSE performance, compared to controls, with a similar language profile to nfvPPA, albeit less severe. All patient groups showed reduced cortical thickness in bilateral frontal regions and striatal volume. PSP and nfvPPA patients also showed reduced superior temporal cortical thickness, with additional thalamic and amygdalo-hippocampal volume reductions in nfvPPA. Multivariate analysis of brain-wide cortical thickness and subcortical volumes with MLSE domain scores revealed associations between performance on multiple speech and language domains with atrophy of left-lateralised fronto-temporal cortex, amygdala, hippocampus, putamen and caudate.

Conclusions

The effect of PSP and CBS on speech and language overlaps with nfvPPA. These three disorders cause a common anatomical pattern of atrophy in the left frontotemporal language network and striatum. The MLSE is a short clinical screening tool that can identify the language disorder of PSP and CBS, facilitating clinical management and patient access to future clinical trials.
Measuring the exposure of Black, Asian and other ethnic groups to Covid-infected neighbourhoods in English towns and cities
Authors: Harris Richard , Brunsdon Chris
Published: March 2021

Drawing on the work of The Doreen Lawrence Review – a report on the disproportionate impact of Covid-19 on Black, Asian and minority ethnic communities in the UK – this paper develops an index of exposure, measuring which ethnic groups have been most exposed to Covid-19 infected residential neighbourhoods during the first and second waves of the pandemic in England. The index is based on a Bayesian Poisson model with a random intercept in the linear predictor, allowing for extra-Poisson variation at neighbourhood and town/city scales. This permits within-city differences to be decoupled from broader regional trends in the disease. The research finds that members of ethnic minority groups tend to be living in areas with higher infection rates but also that the risk of exposure is distributed unevenly across these groups. Initially, in the first wave, the disease disproportionately affected Black residents. As the pandemic has progressed, especially the Pakistani but also the Bangladeshi and Indian groups have had the highest exposure. This higher exposure of the Pakistani group is not straightforwardly a function of neighbourhood deprivation because it is present across a range of average house prices. However, we find evidence to support the view, expressed in The Doreen Lawrence Review, that it is linked to occupational and environmental exposure, particularly residential density.
Predictive Capacity of COVID-19 Test Positivity Rate
Authors: Fenga Livio , Gaspari Mauro
Published: March 2021

COVID-19 infections can spread silently, due to the simultaneous presence of significant numbers of both critical and asymptomatic to mild cases. While for the former reliable data are available (in the form of number of hospitalization and/or beds in intensive care units), this is not the case of the latter. Hence, analytical tools designed to generate reliable forecast and future scenarios, should be implemented to help decision makers planning ahead (e.g. medical structures and equipment). Previous work of one of the authors shows that an alternative formulation of the Test Positivity Rate (TPR), i.e. the proportion of the number of persons tested positive in a given day, exhibits a strong correlation with the number of patients admitted in hospital and intensive care units. In this paper, we investigate the lagged correlation structure between the newly defined TPR and the hospitalized people time series, exploiting a rigorous statistical model, the Seasonal Auto Regressive Moving Average (SARIMA). The rigorous analytical framework chosen, i.e. the stochastic processes theory, allowed for a reliable forecasting about 12 days ahead, of those quantities. The proposed approach would also allow decision makers to forecast the number of beds in hospitals and intensive care units needed 12 days ahead. The obtained results show that a standardized TPR index is a valuable metric to monitor the growth of the COVID-19 epidemic. The index can be computed on daily basis and it is probably one of the best forecasting tools available today for predicting hospital and intensive care units overload, being an optimal compromise between simplicity of calculation and accuracy.
The Impact of the Variation of CT Scanner on the Prediction of human papillomavirus (HPV) Association of Oropharyngeal Cancer (OPC) using Radiomic models
Authors: Reiazi Reza , Arrowsmith Colin , Welch Mattea , Abbas-Aghababazadeh Farnoosh , Eeles Christopher , Tadic Tony , Hope Andrew J. , Bratman Scott V. , Haibe-Kains Benjamin
Published: March 2021

Studies have shown that radiomic features are sensitive to the variability of imaging parameters (e.g., scanner model) and one of the major challenges in these studies lies in improving the robustness of quantitative features against the variations in imaging datasets from multi-center studies. Here, we assess the impact of scanner choice on the computed tomography (CT)-derived radiomic features to predict association of oropharyngeal squamous cell carcinoma with human papillomavirus (HPV). This experiment was performed on CT image datasets acquired with two different scanner manufacturers. We demonstrate strong scanner dependency by developing a machine learning model to classify HPV status from radiological images. These experiments revealed the effect of scanner manufacturers on the robustness of the radiomic features, and the extent of this dependency is reflected on the performance of HPV prediction models. The results of this study highlight the importance of implementing an appropriate approach to reduce the impact of imaging parameters on radiomic features and consequently on the machine learning models.
Polycystic ovary syndrome susceptibility loci inform disease etiological heterogeneity
Authors: Zhang Yanfei , Movva Vani C. , Williams Marc S , Lee Ming Ta Michael
Published: March 2021

Purpose
Polycystic ovary syndrome (PCOS) is a complex disorder with heterogenous phenotypes and unclear etiology. A recent phenotypic clustering study identified metabolic and reproductive subtypes of PCOS. We attempted to deconstruct the PCOS heterogeneity from a genetic perspective.
Methods
We applied k-means clustering to categorize the genome-wide significant PCOS variants into clusters based on their associations with selected quantitative traits that likely reflect PCOS etiological pathways. We evaluated the association of each cluster with PCOS related traits and disease outcomes. We then applied Mendelian randomization to estimate the causal effect of the traits on PCOS and PCOS on disease outcomes.
Results
Clustering analysis suggested three categories of variants: adiposity, insulin resistant, and reproductive. Significant associations were observed for variants in the adiposity cluster with body mass index (BMI), waist circumference and breast cancer, and variants in insulin resistant cluster with fasting insulin and glucose values, and homeostatic model assessment of insulin resistance (HOMA-IR). Sex hormone binding globulin (SHBG) has strong association with all three clusters. Mendelian randomization supported the causal role of BMI and SHBG on PCOS. No causal associations were observed for PCOS on disease outcomes.
Main Conclusions
Our study provides genetic evidence for the heterogeneity in PCOS etiologies, corresponding to the reported phenotypic subtypes. Such studies will improve the current PCOS diagnosis criteria that do not distinguish the heterogeneity. Classification of women with PCOS to inform appropriate treatment will be more accurate in the future with improvements in clustering analysis for PCOS.
Comparative analysis of policies and programs to support families and children during COVID-19
Authors: Kearon Joanne , Cachia Mark , Carsley Sarah , van den Heuvel Meta , Hopkins Jessica
Published: March 2021

Background

Policies and programs that promote positive social environments for young children and their families have the potential to improve early childhood development and long-term health. However, due to the community-wide public health measures implemented to reduce transmission of COVID-19, many families are experiencing health and socio-economic challenges and pre-existing supports and services may no longer be available. In this study, we compared the policies and programs countries have implemented to support maternal and child health during the first wave of COVID-19.

Methods

We compared the policies and programs implemented to support child health and well-being during the first wave of COVID-19 in Australia, Canada, the Netherlands, Singapore, the UK, and the USA. A grey literature review was performed to identify policies, announcements, and guidelines released from governmental and public health organizations within each country related to children, parents, families, early childhood development, adverse childhood experiences, child welfare, pre-school, or daycares. We also performed a manual search of government websites. Both provincial and federal government policies were included for Canada.

Results

The main policies identified were focused on prenatal care, well-baby visit and immunization schedules, financial supports, domestic violence and housing, childcare supports, child protective services, and food security. All of the included countries implemented some of these policies, but there was a large variation in the number, size, and barriers to access these supports. None of the countries implemented supports in all of the potential areas identified.

Conclusion

Political legacy and previous redistributive policies might have influenced the variation in policies and programs introduced by governments. As the COVID-19 pandemic continues, further opportunity for governments to implement supportive programs and policies for children and families exists.