bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual-energy CT parameters in correlation to MRI-based apparent diffusion coefficient: evaluation in rectal cancer after radiochemotherapy
Authors: Sauter Andreas P , Kössinger Antonia , Beck Stefanie , Deniffel Dominik , Dapper Hendrik , Combs Stephanie E , Rummeny Ernst J , Pfeiffer Daniela 
Published: September 2020

Background Rectal cancer (RC) is a frequent malignancy for which magnetic resonance imaging (MRI) is the most common and accurate imaging. Iodine concentration (IC) can be quantified with spectral dual-layer computed tomography CT (DL-CT), which could improve imaging of RC, especially for evaluation of response to radiochemotherapy (RCT). Purpose To compare a DL-CT system to MRI as the non-invasive imaging gold standard for imaging of RC to evaluate the possibility of a response evaluation with DL-CT. Material and Methods Eleven patients who received DL-CT as well as MRI before and after RCT of RC were retrospectively included into this study. For each examination, a region of interest (ROI) was placed within the tumor. For MRI, the mean apparent diffusion coefficient (ADC) was assessed. For DL-CT, IC, z-effective, and Hounsfield Units (HU) were measured. IC, z-effective, and HU were normalized to the aorta. ADC was correlated to absolute and relative normalized IC, z-effective, and HU with Spearman’s ρ. Differences before and after treatment were tested with Wilcoxon signed-rank test. Results HU, IC, and Z-effective values in DL-CT images decreased significantly after RCT ( P<0.01 for each comparison). The mean ADC increased significantly after RCT. Spearman’s ρ of the absolute IC difference and the absolute ADC (both before and after RCT) is high and significant (ρ = 0.73; P = 0.01), whereas the ρ-value for z-effective (ρ = 0.56) or HU (ρ = 0.45) to ADC was lower and non-significant. Conclusion Response evaluation of RC after RCT could be possible with DL-CT via the measurement of IC.
Origin of orthopyroxene-bearing felsic gneiss from the perspective of ultrahigh-temperature metamorphism: an example from the Chilka Lake migmatite complex, Eastern Ghats Belt, India
Authors: Bose Sankar , Das Kaushik , Torimoto Junji , Dunkley Daniel 
Published: September 2020

AbstractOrthopyroxene-bearing felsic gneiss occurs as foliation-parallel layers and bands together with aluminous granulite, mafic granulite, and quartzofeldspathic granulite in the Chilka Lake migmatite complex of the Proterozoic Eastern Ghats Belt, India. The rock was classified previously as charnockite which underwent granulite-facies metamorphism. Field and textural features of this rock show evidence of the partial melting of a biotite-bearing greywacke protolith. Orthopyroxene with/without garnet and cordierite were produced with K-feldspar as peritectic phases of incongruent melting of presumed metaluminous sediments. Fluid-inclusion data suggest the presence of high-density CO2-rich fluids during peak metamorphism, which are similar to those found in associated aluminous granulite. Whole-rock major and trace element data show wide variability of the source materials whereas REE distributions show enriched LREE and flat HREE patterns. Zircon grains from representative samples show the presence of inherited cores having spot dates (SHRIMP) in the range c. 1790–3270 Ma. The overgrowth on zircon was formed predominantly during c. 780–730 Ma and sporadically during c. 550–520 Ma. Some neoblastic zircons with c. 780–730 Ma ages are also present. U-rich dark zones surrounding cores appear partially metamictised, but spot ages from this zone vary within c. 1000–900 Ma. The <1000 Ma ages represent metamorphism that mirrors the events in associated aluminous granulite. The sources of metaluminous sediments are speculative as the rock compositions are largely modified under granulite-facies metamorphism and partial melting. Considering the accretionary tectonic setting of the Eastern Ghats Belt during the c. 1000–900 Ma time frame, a greywacke-type protolith for the migmatite complex has been proposed.
Deep amplicon sequencing for culture-free prediction of susceptibility or resistance to 13 anti-tuberculous drugs
Authors: Jouet Agathe , Gaudin Cyril , Badalato Nelly , Allix-Béguec Caroline , Duthoy Stéphanie , Ferré Alice , Diels Maren , Laurent Yannick , Contreras Sandy , Feuerriegel Silke , Niemann Stefan , André Emmanuel , Kaswa Michel K. , Tagliani Elisa , Cabibbe Andrea , Mathys Vanessa , Cirillo Daniela , de Jong Bouke C. , Rigouts Leen , Supply Philip 
Published: September 2020

Conventional molecular tests for detectingMycobacterium tuberculosiscomplex (MTBC) drug resistance on clinical samples cover a limited set of mutations. Whole-genome sequencing (WGS) typically requires culture.Here, we evaluated the Deeplex Myc-TB targeted deep-sequencing assay for prediction of resistance to 13 anti-tuberculous drugs/drug classes, directly applicable on sputum.With MTBC DNA tests, the limit of detection was 100–1000 genome copies for fixed resistance mutations. Deeplex Myc-TB capturedin silico97.1–99.3% of resistance phenotypes correctly predicted by WGS from 3651 MTBC genomes. On 429 isolates, the assay predicted 92.2% of 2369 first- and second-line phenotypes, with a sensitivity of 95.3% and a specificity of 95.0% (95.4% and 97.1%, respectively, when excluding ethionamide). 83 out of 102 (81.4%) residual discrepancies with phenotypic results involved pyrazinamide, ethambutol and ethionamide, and low-level rifampicin or isoniazid resistance mutations, all notoriously prone to phenotypic testing variability. Only two out of 96 (2.1%) resistance phenotypes undetected by Deeplex Myc-TB had known resistance-associated mutations by WGS analysis outside Deeplex Myc-TB targets. Phenotype predictions from Deeplex Myc-TB analysis directly on 109 sputa from a Djibouti survey matched those of MTBSeq/PhyResSE/Mykrobe, fed with WGS data from subsequent cultures, with a sensitivity of 93.5/98.5/93.1% and a specificity of 98.5/97.2/95.3%, respectively. Most residual discordances involved gene deletions/indels and 3–12% heteroresistant calls undetected by WGS analysis or natural pyrazinamide resistance of globally rare “Mycobacterium canettii” strains then unreported by Deeplex Myc-TB. On 1494 arduous sputa from a Democratic Republic of the Congo survey, 14 902 out of 19 422 (76.7%) possible susceptible or resistance phenotypes could be predicted culture-free.Deeplex Myc-TB may enable fast, tailored tuberculosis treatment.
Comparison of ciliary beat frequencies at different temperatures in young adults
Authors: Nikolaizik Wilfried , Hahn Jana , Bauck Monika , Weber Stefanie 
Published: September 2020

RationaleDirect visualisation of ciliary beat pattern (CBP) and ciliary beat frequency (CBF) has been recommended as the first-line diagnostic test in patients suspected of having primary ciliary dyskinesia (PCD). However, the test procedure is not yet completely standardised, and centres measure the CBF at different temperatures.ObjectivesIt was the aim of the study to compare CBF at different temperatures, to establish normative values, to check for age dependency and to measure the temperature on the nasal mucosa of the participants.MethodsHigh-speed video-microscopy analysis with a Sisson-Ammons Video Analysis (SAVA) system was used to determine CBP and CBF in the participants.MeasurementsNasal brushings were taken and CBF was measured in randomised order at three temperatures: 25°C, 32°C and 37°C.Main resultsIn total, 100 healthy young adults (74 female, 26 male), aged 20.2–31.9 years, were included in the study. We found a highly significant difference among the groups: the median CBF was 7.0 Hz at 25°C, 7.6 Hz at 32°C and 8.0 Hz at 37°C. The maximum time periodex vivowas 65 min and did not differ significantly. However, CBF was significantly higher when the cilia were kept at a higher temperature before the measurements were made. We found no correlation between CBF and the age of the participants. The median nasal mucosal temperature in our study participants was 30.2°C (range 24.7–35.8°C) comparable to the 30.2–34.4°C described in the literature.ConclusionsThe most appropriate temperature at which to measure CBF is 32°C. In our study, with 95% confidence for this temperature the CBF was between 6.3 and 9.0 Hz.
Explicit representation of protein activity states significantly improves causal discovery of protein phosphorylation networks
Authors: Liu Jinling , Ma Xiaojun , Cooper Gregory F. , Lu Xinghua 
Published: September 2020

Abstract
Background
Protein phosphorylation networks play an important role in cell signaling. In these networks, phosphorylation of a protein kinase usually leads to its activation, which in turn will phosphorylate its downstream target proteins. A phosphorylation network is essentially a causal network, which can be learned by causal inference algorithms. Prior efforts have applied such algorithms to data measuring protein phosphorylation levels, assuming that the phosphorylation levels represent protein activity states. However, the phosphorylation status of a kinase does not always reflect its activity state, because interventions such as inhibitors or mutations can directly affect its activity state without changing its phosphorylation status. Thus, when cellular systems are subjected to extensive perturbations, the statistical relationships between phosphorylation states of proteins may be disrupted, making it difficult to reconstruct the true protein phosphorylation network. Here, we describe a novel framework to address this challenge.

Results
We have developed a causal discovery framework that explicitly represents the activity state of each protein kinase as an unmeasured variable and developed a novel algorithm called “InferA” to infer the protein activity states, which allows us to incorporate the protein phosphorylation level, pharmacological interventions and prior knowledge. We applied our framework to simulated datasets and to a real-world dataset. The simulation experiments demonstrated that explicit representation of activity states of protein kinases allows one to effectively represent the impact of interventions and thus enabled our framework to accurately recover the ground-truth causal network. Results from the real-world dataset showed that the explicit representation of protein activity states allowed an effective and data-driven integration of the prior knowledge by InferA, which further leads to the recovery of a phosphorylation network that is more consistent with experiment results.

Conclusions
Explicit representation of the protein activity states by our novel framework significantly enhances causal discovery of protein phosphorylation networks.
Global variation of risk thresholds for initiating statins for primary prevention of cardiovascular disease: a benefit-harm balance modelling study
Authors: Yebyo Henock G. , Zappacosta Sofia , Aschmann Hélène E. , Haile Sarah R. , Puhan Milo A. 
Published: September 2020

AbstractBackgroundWe previously showed that the 10-year cardiovascular disease (CVD) risk threshold to initiate statins for primary prevention depends on the baseline CVD risk, age, sex, and the incidence of statin-related harm outcome and competing risk for non-CVD death. As these factors appear to vary across countries, we aimed in this study to determine country-specific thresholds and provide guidelines a quantitative benefit-harm assessment method for local adaptation.MethodsFor each of the 186 countries included, we replicated the benefit-harm balance analysis using an exponential model to determine the thresholds to initiate statin use for populations aged 40 to 75 years, with no history of CVD. The analyses took data inputs from a priori studies, including statin effect estimates (network meta-analysis), patient preferences (survey), and baseline incidence of harm outcomes and competing risk for non-CVD (global burden of disease study). We estimated the risk thresholds above which the benefits of statins were more likely to outweigh the harms using a stochastic approach to account for statistical uncertainty of the input parameters.ResultsThe 5thand 95thpercentiles of the 10-year risk thresholds above which the benefits of statins outweigh the harms across 186 countries ranged between 14 and 20% in men and 19–24% in women, depending on age (i.e., 90% of the country-specific thresholds were in the ranges stated). The median risk thresholds varied from 14 to 18.5% in men and 19 to 22% in women. The between-country variability of the thresholds was slightly attenuated when further adjusted for age resulting, for example, in a 5thand 95thpercentiles of 14–16% for ages 40–44 years and 17–21% for ages 70–74 years in men. Some countries, especially the islands of the Western Pacific Region, had higher thresholds to achieve net benefit of statins at 25–36% 10-year CVD risks.ConclusionsThis extensive benefit-harm analysis modeling shows that a single CVD risk threshold, irrespective of age, sex and country, is not appropriate to initiate statin use globally. Instead, countries need to carefully determine thresholds, considering the national or subnational contexts, to optimize benefits of statins while minimizing related harms and economic burden.
Effect of cholesterol re-supplementation and atorvastatin on plaque composition in the thoracic aorta of New Zealand white rabbits
Authors: Bonaterra G. A. , Bender K. , Wilhelm B. , Schwarzbach H. , Metz S. , Kelber O. , Weiser D. , Metz J. , Kinscherf R. 
Published: September 2020

Abstract
Background
Effects of re-supplementation of a cholesterol-enriched diet (CEDrs) on size, cholesterol content and morphology of already existing plaques are not known to date.

Methods
A group of rabbits received standard chow (SC) for 6 weeks (“negative control”; for plasma lipid measurements only). Group I-IV received 2% CED (induction) for 6 weeks; thereafter, groups II-IV have been fed a SC (= cholesterol withdrawal) for 68 weeks. Afterwards, feeding of groups II-IV was continued as follows: Group II - 10 weeks SC, group III - 4 weeks 0.5% CED (~re-supplementation), afterwards 6 weeks SC (~withdrawal again); group IV - 4 weeks 0.5% CED (re-supplementation) + atorvastatin (2.5 mg/kg body weight/day), afterwards 6 weeks SC (~withdrawal again) + atorvastatin. Plasma lipids, but also plaque size, morphology and cholesterol contents of thoracic aortas were quantified.

Results
After CEDrs, plasma cholesterol levels were increased. However, after withdrawal of CEDrs, plasma cholesterol levels decreased, whereas the cholesterol content of the thoracic aorta was increased in comparison with the group without CEDrs. Plaque size remained unaffected. Atorvastatin application did not change plasma cholesterol level, cholesterol content of the thoracic aorta and plaque size in comparison with the group without drug treatment. However, atorvastatin treatment increased the density of macrophages (MΦ) compared with the group without treatment, with a significant correlation between densities of MΦ (Mac-1+) and apoptotic (TUNEL+; TP53+), antigen-presenting (HLA-DR+) or oxidatively stressed (SOD2+) cells.

Conclusions
In rabbits with already existing plaques, CEDrs affects plaque morphology and cellular composition, but not plaque size. Despite missing effects on plasma cholesterol levels, cholesterol content of the thoracic aorta and size of already existing atherosclerotic plaques, atorvastatin treatment transforms the already existing lesions to a more active form, which may accelerate the remodelling to a more stable plaque.
Prevalence and characteristics of older adults with a persistent death wish without severe illness: a large cross-sectional survey
Authors: Hartog Iris D. , Zomers Margot L. , van Thiel Ghislaine J. M. W. , Leget Carlo , Sachs Alfred P. E. , Uiterwaal Cuno S. P. M. , van den Berg Vera , van Wijngaarden Els 
Published: September 2020

Abstract
Background
Some older persons develop a persistent death wish without being severely ill, often referred to as “completed life” or “tiredness of life”. In the Netherlands and Belgium, the question whether these persons should have legal options for euthanasia or physician-assisted suicide (EAS) is intensely debated. Our main aim was to investigate the prevalence and characteristics of older adults with a persistent death wish without severe illness, as the lack of this knowledge is a crucial problem in de debate.

Methods
We conducted a survey among a representative sample of 32,477 Dutch citizens aged 55+, comprising questions about health, existential issues and the nature of the death wish. Descriptive statistics were used to describe the group with a persistent death wish and no severe illness (PDW-NSI) and several subgroups.

Results
A total of 21,294 respondents completed the questionnaire (response rate 65.6%). We identified 267 respondents (1.25%) as having a persistent death wish and no severe illness (PDW-NSI). PDW-NSI did not only occur among the oldest old. Although qualifying themselves as “not severely ill”, those with PDW-NSI reported considerable health problems. A substantial minority of the PDW-NSI-group reported having had a death wish their whole lives. Within the group PDW-NSI 155 (0.73%) respondents had an active death wish, of which 36 (0.17% of the total response) reported a wish to actually end their lives. Thus, a death wish did not always equal a wish to actually end one’s life. Moreover, the death wishes were often ambiguous. For example, almost half of the PDW-NSI-group (49.1%) indicated finding life worthwhile at this moment.

Conclusions
The identified characteristics challenge the dominant “completed life” or “tiredness of life” image of healthy persons over the age of 75 who, overseeing their lives, reasonably decide they would prefer to die. The results also show that death wishes without severe illness are often ambiguous and do not necessarily signify a wish to end one’s life. It is of great importance to acknowledge these nuances and variety in the debate and in clinical practice, to be able to adequately recognize the persons involved and tailor to their needs.
Enterobacter cloacae colonisation and infection in a neonatal intensive care unit: retrospective investigation of preventive measures implemented after a multiclonal outbreak
Authors: Ferry Alexandrine , Plaisant Frank , Ginevra Christophe , Dumont Yann , Grando Jacqueline , Claris Olivier , Vandenesch François , Butin Marine 
Published: September 2020

Abstract
Background
Enterobacter cloacae species is responsible for nosocomial outbreaks in vulnerable patients in neonatal intensive care units (NICU). The environment can constitute the reservoir and source of infection in NICUs. Herein we report the impact of preventive measures implemented after an Enterobacter cloacae outbreak inside a NICU.

Methods
This retrospective study was conducted in one level 3 NICU in Lyon, France, over a 6 year-period (2012–2018). After an outbreak of Enterobacter cloacae infections in hospitalized neonates in 2013, several measures were implemented including intensive biocleaning and education of medical staff. Clinical and microbiological characteristics of infected patients and evolution of colonization/infection with Enterobacter spp. in this NICU were retrieved. Moreover, whole genome sequencing was performed on 6 outbreak strains.

Results
Enterobacter spp. was isolated in 469 patients and 30 patients developed an infection including 2 meningitis and 12 fatal cases. Preventive measures and education of medical staff were not associated with a significant decrease in patient colonisation but led to a persistent decreased use of cephalosporin in the NICU. Infection strains were genetically diverse, supporting the hypothesis of multiple hygiene defects rather than the diffusion of a single clone.

Conclusions
Grouped cases of infections inside one setting are not necessarily related to a single-clone outbreak and could reveal other environmental and organisational problematics. The fight against implementation and transmission of Enterobacter spp. in NICUs remains a major challenge.
Influences on NHS Health Check behaviours: a systematic review
Authors: Atkins Lou , Stefanidou Chryssa , Chadborn Tim , Thompson Katherine , Michie Susan , Lorencatto Fabi 
Published: September 2020

Abstract
Background
National Health Service Health Checks were introduced in 2009 to reduce cardiovascular disease (CVD) risks and events. Since then, national evaluations have highlighted the need to maximise the programme’s impact by improving coverage and outputs. To address these challenges it is important to understand the extent to which positive behaviours are influenced across the NHS Health Check pathway and encourage the promotion or minimisation of behavioural facilitators and barriers respectively. This study applied behavioural science frameworks to: i) identify behaviours and actors relevant to uptake, delivery and follow up of NHS Health Checks and influences on these behaviours and; ii) signpost to example intervention content.

Methods
A systematic review of studies reporting behaviours related to NHS Health Check-related behaviours of patients, health care professionals (HCPs) and commissioners. Influences on behaviours were coded using theory-based models: COM-B and Theoretical Domains Framework (TDF). Potential intervention types and behaviour change techniques (BCTs) were suggested to target key influences.

Results
We identified 37 studies reporting nine behaviours and influences for eight of these. The most frequently identified influences were physical opportunity including HCPs having space and time to deliver NHS Health Checks and patients having money to adhere to recommendations to change diet and physical activity. Other key influences were motivational, such as beliefs about consequences about the value of NHS Health Checks and behaviour change, and social, such as influences of others on behaviour change. The following techniques are suggested for websites or smartphone apps: Adding objects to the environment, e.g. provide HCPs with electronic schedules to guide timely delivery of Health Checks to target physical opportunity, Social support (unspecified), e.g. include text suggesting patients to ask a colleague to agree in advance to join them in taking the ‘healthy option’ lunch at work; Information about health consequences, e.g. quotes and/or videos from patients talking about the health benefits of changes they have made.

Conclusions
Through the application of behavioural science we identified key behaviours and their influences which informed recommendations for intervention content. To ascertain the extent to which this reflects existing interventions we recommend a review of relevant evidence.