bluuebunny/crossref_metadata_2025_split huggingface dataset:
Instant improvement in monaural spatial hearing abilities through cognitive feedback
Authors: Arras Tine , Snapp Hillary , Sangen Anouk , Snels Chantal , Kuntz Iris , Theunen Tinne , Kheirkhah Kiana , Zarowski Andrzej , Wesarg Thomas , van Wieringen Astrid , Agterberg Martijn J. H. 
Published: March 2022

AbstractSeveral studies report that sound localization performance of acute and chronic monauralized normal-hearing listeners can improve through training. Typically, training sessions are administered daily for several days or weeks. While this intensive training is effective, it may also be that monaural localization abilities improve instantly after providing explicit top-down information about the direction dependent change in timbre and level. The aim of the present study was to investigate whether cognitive feedback (i.e., top-down information) could instantly improve sound localization in naive acutely monauralized listeners. Forty-three normal-hearing listeners (experimental group), divided over five different centers, were tested. Two control groups, consisting of, respectively, nine and eleven normal-hearing listeners, were tested in one center. Broadband sounds (0.5–20 kHz) were presented from visible loudspeakers, positioned in azimuth (− 90° to 90°). Participants in the experimental group received explicit information about the noticeable difference in timbre and the poor localization in the monauralized listening condition, resulting in an instant improvement in sound localization abilities. With subsequent roving of stimulus level (20 dB), sound localization performance deteriorated immediately. The reported improvement is related to the context of the localization test. The results provide important implications for studies investigating sound localization in a clinical setting, especially during closed-set testing, and indicate the importance of top-down information.
Vitamin D Metabolites: Analytical Challenges and Clinical Relevance
Authors: Alonso N. , Zelzer S. , Eibinger G. , Herrmann M. 
Published: March 2022

AbstractRecent research activities have provided new insights in vitamin D metabolism in various conditions. Furthermore, substantial progress has been made in the analysis of vitamin D metabolites and related biomarkers, such as vitamin D binding protein. Liquid chromatography tandem mass spectrometric (LC–MS/MS) methods are capable of accurately measuring multiple vitamin D metabolites in parallel. Nevertheless, only 25(OH)D and the biologically active form 1,25(OH)2D are routinely measured in clinical practice. While 25(OH)D remains the analyte of choice for the diagnosis of vitamin D deficiency, 1,25(OH)2D is only recommended in a few conditions with a dysregulated D metabolism. 24,25(OH)2D, free and bioavailable 25(OH)D, and the vitamin D metabolite ratio (VMR) have shown promising results, but technical pitfalls in their quantification, limited clinical data and the lack of reference values, impede their use in clinical practice. LC–MS/MS is the preferred method for the measurement of all vitamin D related analytes as it offers high sensitivity and specificity. In particular, 25(OH)D and 24,25(OH)2D can accurately be measured with this technology. When interpreted together, they seem to provide a functional measure of vitamin D metabolism beyond the analysis of 25(OH)D alone. The determination of VDBP, free and bioavailable 25(OH)D is compromised by unresolved analytical issues, lacking reference intervals and insufficient clinical data. Therefore, future research activities should focus on analytical standardization and exploration of their clinical value. This review provides an overview on established and new vitamin D related biomarkers including their pathophysiological role, preanalytical and analytical aspects, expected values, indications and influencing conditions.
Unique TLR9 Activation by Helicobacter pylori Depends on the cag T4SS, But Not on VirD2 Relaxases or VirD4 Coupling Proteins
Authors: Tegtmeyer Nicole , Linz Bodo , Yamaoka Yoshio , Backert Steffen 
Published: March 2022

AbstractThe genomes of the gastric bacterial pathogen Helicobacter pylori harbor multiple type-IV secretion systems (T4SSs). Here we analyzed components of three T4SSs, the cytotoxin-associated genes (cag) T4SS, TFS3 and TFS4. The cag T4SS delivers the effector protein CagA and the LPS-metabolite ADP-heptose into gastric epithelial cells, which plays a pivotal role in chronic infection and development of gastric disease. In addition, the cag T4SS was reported to facilitate conjugative transport of chromosomal bacterial DNA into the host cell cytoplasm, where injected DNA activates intracellular toll-like receptor 9 (TLR9) and triggers anti-inflammatory signaling. Canonical DNA-delivering T4SSs in a variety of bacteria are composed of 11 VirB proteins (VirB1-11) which assemble and engage VirD2 relaxase and VirD4 coupling proteins that mediate DNA processing and guiding of the covalently bound DNA through the T4SS channel. Nevertheless, the role of the latter components in H. pylori is unclear. Here, we utilized isogenic knockout mutants of various virB (virB9 and virB10, corresponding to cagX and cagY), virD2 (rlx1 and rlx2), virD4 (cag5, traG1/2) and xerD recombinase genes in H. pylori laboratory strain P12 and studied their role in TLR9 activation by reporter assays. While inactivation of the structural cag T4SS genes cagX and cagY abolished TLR9 activation, the deletion of rlx1, rlx2, cag5, traG or xerD genes had no effect. The latter mutants activated TLR9 similar to wild-type bacteria, suggesting the presence of a unique non-canonical T4SS-dependent mechanism of TLR9 stimulation by H. pylori that is not mediated by VirD2, VirD4 and XerD proteins. These findings were confirmed by the analysis of TLR9 activation by H. pylori strains of worldwide origin that possess different sets of T4SS genes. The exact mechanism of TLR9 activation should be explored in future studies.
Reproducibility and diagnostic accuracy of pocket-sized ultrasound devices in ruling out compensated cirrhosis of mixed etiology
Authors: Costantino Andrea , Piagnani Alessandra , Nandi Nicoletta , Sciola Valentina , Maggioni Marco , Donato Francesca , Vecchi Maurizio , Lampertico Pietro , Casazza Giovanni , Fraquelli Mirella 
Published: March 2022

Abstract
Objective
Fibrosis is the key prognostic factor in chronic liver disease patients. Liver surface nodularity (LSN) is the ultrasonographic sign with the highest accuracy to detect advanced liver fibrosis. The use of pocket-sized ultrasound devices (PUDs) has been assessed in several clinical settings but never as regards chronic liver disease (CLD) severity. Our study aimed at evaluating the feasibility, reproducibility, and diagnostic accuracy of PUD in LSN identification.

Methods
We enrolled all the consecutive adults referred for percutaneous liver biopsy. Two independent operators evaluated LSN by PUD; one sonographer used standard ultrasound (US). Transient elastography (TE) and liver biopsy were performed on all the patients. PUD reproducibility was evaluated by Cohen’s k statistic. PUD, standard US, and TE results were compared with histology staging.

Results
A total of 104 consecutive patients (aged 54 ± 14 years) with mixed-etiology CLD were studied. Assessment by PUD was feasible in all the patients and showed very good inter-observer agreement with Cohen’s k = 0.87 (95% CI 0.72–0.95). The diagnostic accuracy estimates for PUD in diagnosing compensated cirrhosis (F = 4) were 87.5% sensitivity, 76.8% specificity, positive likelihood ratio (LR) 3.78, and negative likelihood ratio (LR-) 0.16, while those for standard US and TE (> 12.5 kPa) were, respectively, 87.5% sensitivity, 72.6% specificity, LR+ 3.2, and LR- 0.17, and 87.5% sensitivity, 90.5% specificity, LR + 9.2, and LR- 0.13.

Conclusions
PUD reproducibility in assessing LSN was excellent even with operators of different experience. PUD performed very well in excluding advanced CLD. PUD can be used as a first-line tool for screening patients to undergo more invasive techniques, thus shortening the time for clinical decision-making.

Key Points
• PUD is highly reproducible in assessing the sign of liver surface nodularity.
• PUD showed high diagnostic accuracy in excluding the presence of advanced chronic liver disease.
• PUD can be used as a first-line tool for screening patients with CLD who should undergo more invasive techniques.
Developing an understanding of artificial intelligence lung nodule risk prediction using insights from the Brock model
Authors: Chetan Madhurima R. , Dowson Nicholas , Price Noah Waterfield , Ather Sarim , Nicolson Angus , Gleeson Fergus V. 
Published: March 2022

Abstract
Objectives
To determine if predictions of the Lung Cancer Prediction convolutional neural network (LCP-CNN) artificial intelligence (AI) model are analogous to the Brock model.

Methods
In total, 10,485 lung nodules in 4660 participants from the National Lung Screening Trial (NLST) were analysed. Both manual and automated nodule measurements were inputted into the Brock model, and this was compared to LCP-CNN. The performance of an experimental AI model was tested after ablating imaging features in a manner analogous to removing predictors from the Brock model. First, the nodule was ablated leaving lung parenchyma only. Second, a sphere of the same size as the nodule was implanted in the parenchyma. Third, internal texture of both nodule and parenchyma was ablated.

Results
Automated axial diameter (AUC 0.883) and automated equivalent spherical diameter (AUC 0.896) significantly improved the accuracy of Brock when compared to manual measurement (AUC 0.873), although not to the level of the LCP-CNN (AUC 0.936). Ablating nodule and parenchyma texture (AUC 0.915) led to a small drop in AI predictive accuracy, as did implanting a sphere of the same size as the nodule (AUC 0.889). Ablating the nodule leaving parenchyma only led to a large drop in AI performance (AUC 0.717).

Conclusions
Feature ablation is a feasible technique for understanding AI model predictions. Nodule size and morphology play the largest role in AI prediction, with nodule internal texture and background parenchyma playing a limited role. This is broadly analogous to the relative importance of morphological factors over clinical factors within the Brock model.

Key Points
• Brock lung cancer risk prediction accuracy was significantly improved using automated axial or equivalent spherical measurements of lung nodule diameter, when compared to manual measurements.
• Predictive accuracy was further improved by using the Lung Cancer Prediction convolutional neural network, an artificial intelligence-based model which obviates the requirement for nodule measurement.
• Nodule size and morphology are important factors in artificial intelligence lung cancer risk prediction, with nodule texture and background parenchyma contributing a small, but measurable, role.
A common-sense approach to the problem of the itinerary stadion
Authors: Tupikova Irina 
Published: March 2022

AbstractEstimating the length of the Greek stadion remains controversial. This paper highlights the pitfalls of a purely metrological approach to this problem and proposes a formal differentiation between metrologically defined ancient measuring units and other measures used to estimate long distances. The common-sense approach to the problem is strengthened by some cross-over documentary evidence for usage of the so-calleditinerarystadion in antiquity. We discuss the possibility of using statistical analysis methods to estimate the length of the stadion by comparing ancient routes with the actual distances. Simple numerical examples explain the limits of this approach, caused by the low number of data and by their mixed character. A special case of distances which can be calculated with the help of coordinates given in Ptolemy’sGeographyis discussed, and has been shown to lead unavoidably to ambiguous solutions.
Post mortem computed tomography meets radiomics: a case series on fractal analysis of post mortem changes in the brain
Authors: De-Giorgio Fabio , Ciasca Gabriele , Fecondo Gennaro , Mazzini Alberto , Di Santo Riccardo , De Spirito Marco , Pascali Vincenzo L. 
Published: March 2022

AbstractEstimating the post-mortem interval is a fundamental, albeit challenging task in forensic sciences. To this aim, forensic practitioners need to assess post-mortem changes through a plethora of different methods, most of which are inherently qualitative, thus providing broad time intervals rather than precise determinations. This challenging problem is further complicated by the influence of environmental factors, which modify the temporal dynamics of post-mortem changes, sometimes in a rather unpredictable fashion. In this context, the search for quantitative and objective descriptors of post-mortem changes is highly demanded. In this study, we used computed tomography (CT) to assess the post-mortem anatomical modifications occurring in the time interval 0–4 days after death in the brain of four corpses. Our results show that fractal analysis of CT brain slices provides a set of quantitative descriptors able to map post-mortem changes over time throughout the whole brain. Although incapable of producing a direct estimation of the PMI, these descriptors could be used in combination with other more established methods to improve the accuracy and reliability of PMI determination.
Gene fusions and oncogenic mutations in MLH1 deficient and BRAFV600E wild-type colorectal cancers
Authors: Ukkola Iiris , Nummela Pirjo , Kero Mia , Tammio Hanna , Tuominen Jenni , Kairisto Veli , Kallajoki Markku , Haglund Caj , Peltomäki Päivi , Kytölä Soili , Ristimäki Ari 
Published: March 2022

AbstractGene fusions can act as oncogenic drivers and offer targets for cancer therapy. Since fusions are rare in colorectal cancer (CRC), their universal screening seems impractical. Our aim was to investigate gene fusions in 62 CRC cases with deficient MLH1 (dMLH1) and BRAFV600E wild-type (wt) status from a consecutive real-life series of 2079 CRCs. First, gene fusions were analysed using a novel FusionPlex Lung v2 RNA–based next-generation sequencing (NGS) panel, and these results were compared to a novel Idylla GeneFusion assay and pan-TRK immunohistochemistry (IHC). NGS detected seven (7/62, 11%) NTRK1 fusions (TPM3::NTRK1, PLEKHA6::NTRK1 and LMNA::NTRK1, each in two cases, and IRF2BP2::NTRK1 in one case). In addition, two ALK, four RET and seven BRAF fusions were identified. Idylla detected seven NTRK1 expression imbalances, in line with the NGS results (overall agreement 100%). Furthermore, Idylla detected the two NGS–identified ALK rearrangements as one specific ALK fusion and one ALK expression imbalance, whilst only two of the four RET fusions were discovered. However, Idylla detected several expression imbalances of ALK (n = 7) and RET (n = 1) that were found to be fusion negative with the NGS. Pan-TRK IHC showed clearly detectable, fusion partner-dependent staining patterns in the seven NTRK1 fusion cases. Overall agreement for pan-TRK antibody clone EPR17341 was 98% and for A7H6R 100% when compared to the NGS. Of the 62 CRCs, 43 were MLH1 promoter hypermethylated (MLH1ph) and 39 were RASwt. All fusion cases were both MLH1ph and RASwt. Our results show that kinase fusions (20/30, 67%) and most importantly targetable NTRK1 fusions (7/30, 23%) are frequent in CRCs with dMLH1/BRAFV600Ewt/MLH1ph/RASwt. NGS was the most comprehensive method in finding the fusions, of which a subset can be screened by Idylla or IHC, provided that the result is confirmed by NGS.
Psychiatric training in perinatal mental health across Europe
Authors: Casanova Dias Marisa , Sönmez Güngör Ekin , Naughton Sean , Ryland Howard , Gargot Thomas , Pinto da Costa Mariana , Kanellopoulos Athanasios , Baessler Franziska , De Picker Livia 
Published: March 2022

AbstractPerinatal mental illness is associated with considerable maternal and infant morbidity and mortality. However, there are currently no specific guidelines on the standards and structure of postgraduate perinatal psychiatric training in Europe. We describe the characteristics of available and desired specialist perinatal psychiatry training from the perspective of European psychiatrists in training. An online survey was conducted among 34 national psychiatric trainee association representatives of the European Federation of Psychiatric Trainees (EFPT). Participants from the countries in which perinatal psychiatry training was available were invited to participate in in-depth follow-up interviews. Six countries out of 34 (18%) reported that specialist training in perinatal mental health was available (Finland, France, Germany, Ireland, Malta, and the UK). The nature of available training varied in duration, the supervision and assessment model employed, and the training scheme context. Of the 28 countries where specialist perinatal psychiatry training was unavailable, the majority of national representatives (22 countries, 76%) wanted specialist perinatal psychiatry training to be included in their national training curricula. There is a gap between the expected skills and the available training for psychiatrists to meet the mental healthcare needs of women in the perinatal period. Given the prevalence and impact of perinatal mental illness and the expressed desires of trainees themselves for specialist training, this finding should prompt urgent action.
Application of a novel cascade-routing and reinfiltration concept with a Voronoi unstructured grid in MODFLOW 6, for an assessment of surface-water/groundwater interactions in a hard-rock catchment (Sardon, Spain)
Authors: Daoud Mostafa Gomaa , Lubczynski Maciek W. , Vekerdy Zoltan , Francés Alain Pascal 
Published: March 2022

AbstractIntegrated hydrological modelling (IHM) can reliably characterize surface-water/groundwater interactions in complex hydrological systems such as hard-rock systems (HRS), located in water-limited environments (WLE). Such HRS-WLE conditions are represented by Sardon catchment (~80 km2) in Spain, where the MODFLOW 6 modelling environment was tested, applying the following improvements as compared to previous works in that catchment: a new conceptual model, driving forces redefined based on remote sensing data, an unstructured Voronoi grid, and, most importantly, a novel cascade-routing and reinfiltration (CRR) concept. In the standard MODFLOW 6, rejected infiltration and groundwater exfiltration have always been considered as sinks (evaporation). However, in reality, that water can not only evaporate but also reinfiltrate back to the subsurface or move as runoff towards drainage water bodies. The CRR improves surface–unsaturated-zone interactions and also surface-water/groundwater interactions. The standard and new capacities of MODFLOW 6 are presented in the transient model of the Sardon catchment, calibrated using 7 years of daily groundwater heads and streamflows. The results showed: the large spatio-temporal variability of the groundwater fluxes, the substantial role of groundwater exfiltration, the low catchment storage, the fast reaction of the water table and streams to rainfall, and the mosaic character of the net recharge. These characteristics are typical for HRS-WLEs with a shallow water table. MODFLOW 6 has many improvements compared to previous MODFLOW versions, so with the proposed CRR concept (still can be improved), the single-environment MODFLOW 6 has modelling capacity comparable with multienvironment IHMs, while being more flexible and more efficient.
Effects of Body Forces on Turbulent Kinetic Energy Transport in Premixed Flames
Authors: Varma Arun Ravi , Ahmed Umair , Chakraborty Nilanjan 
Published: March 2022

AbstractThe effects of buoyancy on turbulent premixed flames are expected to be strong due to the large changes in density between the unburned and fully burned gases. The present work utilises three-dimensional direct numerical simulations of statistically planar turbulent premixed flames under decaying turbulence to study the influence of buoyancy on the evolution of turbulent kinetic energy within the flame brush. Four sets of turbulence parameters have been studied, with four different values of Froude number for each set. It is found that for a given set of turbulence parameters, flame wrinkling increases with an increase in body force magnitude in the case of unstable stratification, which is also reflected in the increased values of turbulent burning velocity and flame surface area. An increase in body force magnitude in the case of stable stratification acts to reduce the extent of flame wrinkling. Turbulent kinetic energy and its dissipation rate are found to be affected by both the magnitude and direction of the body force. For low turbulence intensities considered here, turbulent kinetic energy increases from the leading edge of the flame brush before decaying eventually towards the product side of the flame brush. For high turbulence intensities, the turbulent kinetic energy is found to decay across the flame brush, and it is also found that the effect of body force on the evolution of turbulent kinetic energy is marginal in the case of high turbulence intensities. The effects of body force magnitude and direction on the statistical behaviours and closures of the various terms of the turbulent kinetic energy transport equation are analysed, and existing models have been modified to account for Froude number effects, where necessary.
Shake table tests of concrete anchors for non-structural components including innovative and alternative anchorage detailing
Authors: Ciurlanti Jonathan , Bianchi Simona , Pürgstaller Andreas , Gallo Patricio Quintana , Bergmeister Konrad , Pampanin Stefano 
Published: March 2022

AbstractIn recent years, the growing need for reducing non-structural damage after earthquakes has stimulated a dedicated effort to develop innovative types of fasteners for anchoring non-structural components (NSCs) to reinforced concrete (RC) host-structures. To contribute to such need, and building on previous research, this paper presents the results of a series of uni-directional shake-table tests of simulated NSCs anchored to concrete via: (1) expansion, and (2) chemical anchors; post-installed into: (a) uncracked, and (b) cracked concrete. Considering different construction details, the experimental investigation focused on traditional anchorage systems, alternative solutions comprising mortar filling into the gap clearance, and a low-damage system relying on supplemental damping devices, capable of reducing the acceleration of the NSCs as well as the force of the anchorage during seismic shakings. The experimental tests provided significant evidence on the beneficial effects of a dissipative anchorage protecting both the non-structural component and the anchorage itself, even during strong earthquakes. Moreover, when construction details allow to close the fixture clearance with a mortar filling, this stiffer solution provide an additional reduction of NSCs seismic accelerations and forces. Therefore, suggestions for further improvements of the adopted low-damage solution are also proposed.