Benchmarking table recognition performance on biomedical literature on neurological disorders.

MOTIVATION: Table recognition systems are widely used to extract and structure quantitative information from the vast amount of documents that are increasingly available from different open sources. While many systems already perform well on tables with a simple layout, tables in the biomedical domain are often much more complex. Benchmark and training data for such tables are however very limited. RESULTS: To address this issue, we present a novel, highly curated benchmark dataset based on a hand-curated literature corpus on neurological disorders, which can be used to tune and evaluate table extraction applications for this challenging domain. We evaluate several state-of-the-art table extraction systems based on our proposed benchmark and discuss challenges that emerged during the benchmark creation as well as factors that can impact the performance of recognition methods. For the evaluation procedure, we propose a new metric as well as several improvements that result in a better performance evaluation. AVAILABILITY AND IMPLEMENTATION: The resulting benchmark dataset (https://zenodo.org/record/5549977) as well as the source code to our novel evaluation approach can be openly accessed. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Oxygen saturation targets in infants with bronchiolitis (BIDS): a double-blind, randomised, equivalence trial.

BACKGROUND: The American Academy of Pediatrics recommends a permissive hypoxaemic target for an oxygen saturation of 90% for children with bronchiolitis, which is consistent with the WHO recommendations for targets in children with lower respiratory tract infections. No evidence exists to support this threshold. We aimed to assess whether the 90% or higher target for management of oxygen supplementation was equivalent to a normoxic 94% or higher target for infants admitted to hospital with viral bronchiolitis. METHODS: We did a parallel-group, randomised, controlled, equivalence trial of infants aged 6 weeks to 12 months of age with physician-diagnosed bronchiolitis newly admitted into eight paediatric hospital units in the UK (the Bronchiolitis of Infancy Discharge Study [BIDS]). A central computer randomly allocated (1:1) infants, in varying length blocks of four and six and without stratification, to be clipped to standard oximeters (patients treated with oxygen if pulse oxygen saturation [SpO2] <94%) or modified oximeters (displayed a measured value of 90% as 94%, therefore oxygen not given until SpO2 <90%). All parents, clinical staff, and outcome assessors were masked to allocation. The primary outcome was time to resolution of cough (prespecified equivalence limits of plus or minus 2 days) in the intention-to-treat population. This trial is registered with ISRCTN, number ISRCTN28405428. FINDINGS: Between Oct 3, and March 30, 2012, and Oct 1, and March 29, 2013, we randomly assigned 308 infants to standard oximeters and 307 infants to modified oximeters. Cough resolved by 15·0 days (median) in both groups (95% CI for difference -1 to 2) and so oxygen thresholds were equivalent. We recorded 35 serious adverse events in 32 infants in the standard care group and 25 serious adverse events in 24 infants in the modified care group. In the standard care group, eight infants transferred to a high-dependency unit, 23 were readmitted, and one had a prolonged hospital stay. In the modified care group, 12 infants were transferred to a high-dependency unit and 12 were readmitted to hospital. Recorded adverse events did not differ significantly. INTERPRETATION: Management of infants with bronchiolitis to an oxygen saturation target of 90% or higher is as safe and clinically effective as one of 94% or higher. Future research should assess the benefits and risks of different oxygen saturation targets in acute respiratory infection in older children, particularly in developing nations where resources are scarce. FUNDING: National Institute for Health Research, Health Technology Assessment programme.

Synthetic data generation for a longitudinal cohort study - evaluation, method extension and reproduction of published data analysis results.

Access to individual-level health data is essential for gaining new insights and advancing science. In particular, modern methods based on artificial intelligence rely on the availability of and access to large datasets. In the health sector, access to individual-level data is often challenging due to privacy concerns. A promising alternative is the generation of fully synthetic data, i.e., data generated through a randomised process that have similar statistical properties as the original data, but do not have a one-to-one correspondence with the original individual-level records. In this study, we use a state-of-the-art synthetic data generation method and perform in-depth quality analyses of the generated data for a specific use case in the field of nutrition. We demonstrate the need for careful analyses of synthetic data that go beyond descriptive statistics and provide valuable insights into how to realise the full potential of synthetic datasets. By extending the methods, but also by thoroughly analysing the effects of sampling from a trained model, we are able to largely reproduce significant real-world analysis results in the chosen use case.

Accurate detection of heart rate using in-ear photoplethysmography in a clinical setting.

Background: Recent research has shown that photoplethysmography (PPG) based wearable sensors offer a promising potential for chronic disease monitoring. The aim of the present study was to assess the performance of an in-ear wearable PPG sensor in acquiring valid and reliable heart rate measurements in a clinical setting, with epileptic patients. Methods: Patients undergoing video-electroencephalography (EEG) monitoring with concomitant one-lead electrocardiographic (ECG) recordings were equipped with an in-ear sensor developed by cosinuss°. Results: In total, 2,048 h of recording from 97 patients with simultaneous ECG and in-ear heart rate data were included in the analysis. The comparison of the quality-filtered in-ear heart rate data with the reference ECG resulted in a bias of 0.78 bpm with a standard deviation of ±2.54 bpm; Pearson's Correlation Coefficient PCC = 0.83; Intraclass Correlation Coefficient ICC = 0.81 and mean absolute percentage error MAPE = 2.57. Conclusion: These data confirm that the in-ear wearable PPG sensor provides accurate heart rate measurements in comparison with ECG under realistic clinical conditions, especially with a signal quality indicator. Further research is required to investigate whether this technology is helpful in identifying seizure-related cardiovascular changes.

Minimal-invasive posterior approach for total hip arthroplasty versus standard lateral approach.

In this prospective study we compared clinical and radiological results and rehabilitation progress of 64 patients who underwent total hip arthroplasty using the standard lateral approach with 64 patients operated with a minimal-invasive (MIS) posterior approach. The outcome of our study did not show any significant differences with regard to patient's safety such as complication rate and radiological assessment of the cup position. There was no difference in the duration of surgery, blood loss, hospital stay and postoperative leg length discrepancy. Rehabilitation milestones were achieved earlier by MIS patients and three and six months postoperatively, the Harris Hip Score of the MIS group was significantly higher.

A methodology to establish a database to study gene environment interactions for childhood asthma.

BACKGROUND: Gene-environment interactions are likely to explain some of the heterogeneity in childhood asthma. Here, we describe the methodology and experiences in establishing a database for childhood asthma designed to study gene-environment interactions (PAGES--Paediatric Asthma Gene Environment Study). METHODS: Children with asthma and under the care of a respiratory paediatrician are being recruited from 15 hospitals between 2008 and 2011. An asthma questionnaire is completed and returned by post. At a routine clinic visit saliva is collected for DNA extraction. Detailed phenotyping in a proportion of children includes spirometry, bronchodilator response (BDR), skin prick reactivity, exhaled nitric oxide and salivary cotinine. Dietary and quality of life questionnaires are completed. Data are entered onto a purpose-built database. RESULTS: To date 1045 children have been invited to participate and data collected in 501 (48%). The mean age (SD) of participants is 8.6 (3.9) years, 57% male. DNA has been collected in 436 children. Spirometry has been obtained in 172 children, mean % predicted (SD) FEV1 97% (15) and median (IQR) BDR is 5% (2, 9). There were differences in age, socioeconomic status, severity and %FEV1 between the different centres (p≤0.024). Reasons for non-participation included parents not having time to take part, children not attending clinics and, in a small proportion, refusal to take part. CONCLUSIONS: It is feasible to establish a national database to study gene-environment interactions within an asthmatic paediatric population; there are barriers to participation and some different characteristics in individuals recruited from different centres. Recruitment to our study continues and is anticipated to extend current understanding of asthma heterogeneity.

Total synthesis of the potent anticancer Aglaia metabolites (-)-silvestrol and (-)-episilvestrol and the active analogue (-)-4'-desmethoxyepisilvestrol.

Total synthesis of the anticancer 1,4-dioxane containing natural products silvestrol (1) and episilvestrol (2) is described by an approach based on the proposed biosynthesis of these novel compounds. The key steps included an oxidative rearrangement of the protected d-glucose derivative 11 to afford the 1,4-dioxane 12, which could be elaborated to the coupling partner 5 and a photochemical [3 + 2]-cycloadditon between the 3-hydroxyflavone 27 and methyl cinnamate followed by base-induced alpha-ketol rearrangement and reduction to give the cyclopentabenzofuran core 33. The core (-)-6 and 1,4-dioxane fragment 5 were united by a highly stereoselective Mitsunobu coupling with the modified azodicarboxylate DMEAD to afford the axial coupled product 36. Deprotection then gave episilvestrol (2). Silvestrol (1) was synthesized by a coupling between core (-)-6 and the dioxane 44 followed by deprotection. Compound 1 was also synthesized from episilvestrol (2) by a Mitsunobu inversion. In addition, the analogue 4'-desmethoxyepisilvestrol (46) was synthesized via the same route. It was found that 46 and episilvestrol 2 displayed an unexpected concentration-dependent chemical shift variation for the nonexchangeable dioxane protons. Synthetic compounds 1, 2, 38, 46, and 54 were tested against cancer cells lines, and it was found that the stereochemistry of the core was critical for activity. Synthetic analogue 4'-desmethoxyepisilvestrol (46) was also active against lung and colon cancer cell lines.

Modeling the Optimum Prussian Blue Treatment for Acute Radiation Syndrome Following 137Cs Ingestion.

Accidents or radiological attacks may lead to ingestion of Cs by large numbers of the public. This work models the efficacy of Prussian blue, the medical countermeasure for internal contamination with Cs, to prevent acute radiation syndrome as a function of the duration of treatment and the time that treatment starts after uptake. Risk of acute radiation syndrome is modeled using the International Commission on Radiological Protection's acute radiation hazard model. Dose rates to target organs from Cs ingestion were based on the data published by the US Environmental Protection Agency and the retention of Cs in the reference man. Modeling found that treatment is most effective if begun within 15 d of ingestion, and the course length should be at least 75 d to mitigate cancer risk and 290 d to mitigate fatalities due to acute radiation syndrome. Both of these course lengths are much longer than the minimum Prussian blue treatment regimen of 30 d. Extending the treatment time for contaminated individuals would increase demand for Prussian blue following an accident or attack and in turn, would require a larger stockpile of Prussian blue to meet demand. Not enough data is available to determine if this longer treatment time would lead to adverse medical outcomes due to the toxicity of the treatment itself.

Modeling Cutaneous Radiation Injury from Fallout.

OBJECTIVE: Beta radiation from nuclear weapons fallout could pose a risk of cutaneous radiation injury (CRI) to evacuating populations but has been investigated only cursorily. This work examines 2 components of CRI necessary for estimating the potential public health consequences of exposure to fallout: dose protraction and depth of dose. METHODS: Dose protraction for dry and moist desquamation was examined by adapting the biological effective dose (BED) calculation to a hazard function calculation similar to those recommended by the National Council on Radiation Protection and Measurements for other acute radiation injuries. Depth of burn was examined using Monte Carlo neutral Particle version 5 to model the penetration of beta radiation from fallout to different skin tissues. RESULTS: Nonlinear least squares analysis of the BED calculation estimated the hazard function parameter θ1 (dose rate effectiveness factors) as 25.5 and 74.5 (Gy-eq)2 h-1 for dry and moist desquamation, respectively. Depth of dose models revealed that beta radiation is primarily absorbed in the dead skin layers and basal layer and that dose to underlying tissues is small (<5% of dose to basal layer). CONCLUSIONS: The low relative dose to tissues below the basal layer suggests that radiation-induced necrosis or deep skin burns are unlikely from direct skin contamination with fallout. These results enable future modeling studies to better examine CRI risk and facilitate effectively managing and treating populations with specialized injuries from a nuclear detonation. (Disaster Med Public Health Preparedness. 2019;13:463-469).

Data in support of genetic architecture of glucosinolate variations in Brassica napus.

The transcriptome-based GWAS approach, Associative Transcriptomics (AT), which was employed to uncover the genetic basis controlling quantitative variation of glucosinolates in Brassica napus vegetative tissues is described. This article includes the phenotypic data of leaf and root glucosinolate (GSL) profiles across a diversity panel of 288 B. napus genotypes, as well as information on population structure and levels of GSLs grouped by crop types. Moreover, data on genetic associations of single nucleotide polymorphism (SNP) markers and gene expression markers (GEMs) for the major GSL types are presented in detail, while Manhattan plots and QQ plots for the associations of individual GSLs are also included. Root genetic association are supported by differential expression analysis generated from root RNA-seq. For further interpretation and details, please see the related research article entitled 'Genetic architecture of glucosinolate variation in Brassica napus' (Kittipol et al., 2019).

Genetic architecture of glucosinolate variation in Brassica napus.

The diverse biological activities of glucosinolate (GSL) hydrolysis products play significant biological and economical roles in the defense system and nutritional qualities of Brassica napus (oilseed rape). Yet, genomic-based study of the B. napus GSL regulatory mechanisms are scarce due to the complexity of working with polyploid species. To address these challenges, we used transcriptome-based GWAS approach, Associative Transcriptomics (AT), across a diversity panel of 288 B. napus genotypes to uncover the underlying genetic basis controlling quantitative variation of GSLs in B. napus vegetative tissues. Single nucleotide polymorphism (SNP) markers and gene expression markers (GEMs) associations identify orthologues of MYB28/HAG1 (AT5G61420), specifically the copies on chromosome A9 and C2, to be the key regulators of aliphatic GSL variation in leaves. We show that the positive correlation observed between aliphatic GSLs in seed and leaf is due to the amount synthesized, as controlled by Bna.HAG1.A9 and Bna.HAG1.C2, rather than by variation in the transport processes. In addition, AT and differential expression analysis in root tissues implicate an orthologue of MYB29/HAG3 (AT5G07690), Bna.HAG3.A3, as controlling root aromatic GSL variation. Based on the root expression data we also propose Bna.MAM3.A3 to have a role in controlling phenylalanine chain elongation for aromatic GSL biosynthesis. This work uncovers a regulator of homophenylalanine-derived aromatic GSLs and implicates the shared biosynthetic pathways between aliphatic and aromatic GSLs.

Screening Internal Contamination of Inhaled and Ingested Radionuclides with Hand-held Survey Meters.

During the aftermath of a radiological accident or attack, the rapid identification of individuals who have internalized medically significant amounts of material is paramount to guide medical and public health decisions. This paper explores the utility of hand-held, pancake GM detectors to determine if an individual has inhaled Sr, Cs, Pu, Pu, or Am in quantities requiring treatment. Additionally, ingestion of Sr or Cs was considered. Both Sr and Cs were modeled in equilibrium with their progeny, but the progeny of Pu, Pu, and Am were excluded. Treatment thresholds are defined using the National Council on Radiation Protection & Measurements' (NCRP) clinical decision guides (CDGs). Using Monte Carlo N-Particle (MCNP) modeling software, a human phantom and detector were modeled to determine the activity required to achieve a detector reading of twice background 1, 7, or 30 d post-ingestion or post-inhalation. Modeling found that inhaled Pu, Pu, and Am are detectable only if the contaminated individual inhaled thousands-fold more material than the CDG. This lack of detectability means that hand-held GM detectors are inappropriate for initial screening for americium or plutonium and that more intensive screening is necessary to confirm suspected contamination. Cesium-137, by contrast, could be detected at levels 10- to 100-fold lower than the amount requiring treatment, allowing quick differentiation between contaminated and uncontaminated individuals. Surprisingly, Sr was detectable within a factor of 2 of the amount requiring treatment. Detection of Sr was due primarily to bremsstrahlung radiation from beta interactions with calcium in bone. While rapid screening could identify individuals contaminated by Cs and possibly with Sr, further screening of identified individuals is necessary to establish medical need. However, these contaminated individuals could still be prioritized for further testing and possible presumptive treatment. Based on the findings of this study, concepts of operation for the use of hand-held survey meters should be developed for the screening of individuals potentially internally contaminated with Cs and Sr.

Review of Cases of Occult Radiation Exposure and an Analysis of Time to Diagnosis.

Radiation sickness is challenging to diagnose, and the diagnosis is often based on nonclinical data. In accidents where patients are not aware of their exposure to radiation (so-called "occult exposures"), a correct diagnosis can take weeks or months. The purpose of this study is to review the time to diagnosis of radiation sickness for occult exposures where neither the physician nor the patients are aware of their exposure. We reviewed eight case reports involving occult exposures and examined the factors that contributed to a diagnosis. We found that an average of 23 d after exposure were required for diagnosis, regardless of route of intake. In only one case was radiation injury diagnosed within the first week. Although all but one of these cases occurred in the developing world, the factors confounding diagnosis are common to the U.S. medical system. Therefore, an urgent need exists for properly training physicians on radiation sickness so they can more quickly diagnose and treat radiation exposures when the patients are unaware of the exposure event.

Estimating Risk of Hematopoietic Acute Radiation Syndrome in Children.

Following a radiological terrorist attack or radiation accident, the general public may be exposed to radiation. Historically, modeling efforts have focused on radiation effects on a "reference man"-a 70-kg, 180-cm-tall, 20- to 30-y-old male-which does not adequately reflect radiation hazard to special populations, particularly children. This work examines the radiosensitivity of children with respect to reference man to develop a set of parameters for modeling hematopoetic acute radiation syndrome in children. This analysis was performed using animal studies and the results verified using data from medical studies. Overall, the hematopoietic system in children is much more radiosensitive than that in adults, with the LD50 for children being 56% to 91% of the LD50 of adults, depending on age.

Investigating the effects of reduced size on the properties of ferroelectrics.

A series of experiments has been undertaken to understand more about the fundamental origin of the thickness-induced permittivity collapse often observed in conventional thin film ferroelectric heterostructures. The various experiments are discussed, highlighting the eventual need to examine permittivity collapse in thin film single crystal material. It has been seen that dielectric collapse is not a direct consequence of reduced size, and neither is it a consequence of unavoidable physics associated with the ferroelectric-electrode boundary. Research on three-dimensional shape-constrained ferroelectrics, emphasizing self-assembled structures based on nanoporous alumina templates and on FIB-milled single crystals, is also presented, and appears to represent an exciting area for ongoing research.

Recombinant human zona pellucida proteins ZP1, ZP2 and ZP3 co-expressed in a human cell line.

AIM: To produce biologically active recombinant human (rh) ZP proteins in a human cell for use in sperm function tests. METHODS: The human embryonic kidney cell line 293T was employed to produce rhZP1, rhZP2 and rhZP3 proteins individually and together by co-expression. Presence of these proteins in the culture medium and cell lysate was assessed by Western blotting analysis. The effect of the recombinant proteins on the human AR was assessed. RESULTS: RhZP2 and rhZP3 were secreted into the culture medium, whereas rhZP1 was found only in the cell lysate. Interestingly, when all zona pellucida proteins were co-expressed in the same cells, rhZP1 was also secreted into the culture medium. However, despite the presence of all three ZP proteins in sufficient concentration and evidence of heavy glycosylation on gel electrophoresis, biological activity to induce the AR was not observed. CONCLUSION: RhZP1, rhZP2 and rhZP3 were successfully expressed in the human embryonic kidney cell line 293T. It appears that an interaction amongst these proteins may be required for release of rhZP1 from the cell. Although this approach is not satisfactory for producing active human ZP proteins, it makes a significant contribution to the understanding of the structural and functional characteristics of the ZP proteins.

Taking down the FLAG! How insect cell expression challenges an established tag-system.

In 1988 the preceding journal of Nature Biotechnology, Bio/Technology, reported a work by Hopp and co-workers about a new tag system for the identification and purification of recombinant proteins: the FLAG-tag. Beside the extensively used hexa-his tag system the FLAG-tag has gained broad popularity due to its small size, its high solubility, the presence of an internal Enterokinase cleavage site, and the commercial availability of high-affinity anti-FLAG antibodies. Surprisingly, considering the heavy use of FLAG in numerous laboratories world-wide, we identified in insect cells a post-translational modification (PTM) that abolishes the FLAG-anti-FLAG interaction rendering this tag system ineffectual for secreted proteins. The present publication shows that the tyrosine that is part of the crucial FLAG epitope DYK is highly susceptible to sulfation, a PTM catalysed by the enzyme family of Tyrosylprotein-Sulfo-transferases (TPSTs). We showed that this modification can result in less than 20% of secreted FLAG-tagged protein being accessible for purification questioning the universal applicability of this established tag system.

An automated communication system in a Contact Registry for persons with rare diseases: tools for retaining potential clinical research participants.

Strategies to enhance recruitment are useful in clinical research network settings. Our network data center maintains a Contact Registry of patients who express a willingness to be contacted to enroll in clinical studies. An automated system generates periodic and customized communications to notify registrants of potential studies and network events. The majority of these communications are sent by email, although the system also supports postal communications. A database tracks the sending of all communications and facilitates reports of registry activity.