bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination therapy of capecitabine, irinotecan, oxaliplatin, and bevacizumab as a first‐line treatment for metastatic colorectal cancer: Safety lead‐in results from the QUATTRO-II study
Authors: Kotani Daisuke , Yoshino Takayuki , Kotaka Masahito , Kawazoe Akihito , Masuishi Toshiki , Taniguchi Hiroya , Yamazaki Kentaro , Yamanaka Takeharu , Oki Eiji , Muro Kei , Komatsu Yoshito , Bando Hideaki , Satake Hironaga , Kato Takeshi , Tsuji Akihito 
Published: May 2021

SummaryBackground FOLFOXIRI plus bevacizumab is the first-line treatment for metastatic colorectal cancer (mCRC) but demonstrates high neutropenia incidence among Asian patients. Hence, we conducted the randomized phase II QUATTRO-II study (ClinicalTrials.gov identifier: NCT04097444; Japan Registry of Clinical Trials identifier: jRTCs041190072) to evaluate the safety and efficacy of capecitabine, oxaliplatin, and irinotecan (CAPOXIRI) combination plus bevacizumab versus FOLFOXIRI plus bevacizumab, expecting a lower incidence of neutropenia without compromising the efficacy. Methods We investigated the recommended doses (RD) of oxaliplatin and irinotecan as a safety lead-in portion of Step 1 before initiating the randomized portion as Step 2. Four dose levels of CAPOXIRI (fixed dose of capecitabine, 1600 mg/m2; escalated/de-escalated doses of oxaliplatin and irinotecan) plus bevacizumab (7.5 mg/kg) were investigated in a 3 + 3 manner. A dose level of ≤ 2/6 of dose-limiting toxicity (DLT) cases was expected as the RD. Results In Step 1, we included nine patients (three and six in levels 0 and + 1, respectively). Level 0 (irinotecan, 200 mg/m2; oxaliplatin, 100 mg/m2) did not demonstrate DLTs. In level + 1 (irinotecan, 200 mg/m2; oxaliplatin, 130 mg/m2), although one patient experienced grade 4 febrile neutropenia, no further safety concerns were observed. As a preliminary efficacy result, the objective response rate in all nine patients was 89 % (100 and 83 % in levels 0 and + 1, respectively). Conclusions The RD of CAPOXIRI plus bevacizumab was 200, 130, and 1600 mg/m2 for irinotecan, oxaliplatin, and capecitabine, respectively, and 7.5 mg/kg for bevacizumab. The randomized portion is still ongoing.
Quantum Polar Duality and the Symplectic Camel: A New Geometric Approach to Quantization
Authors: Gosson Maurice A. de 
Published: May 2021

AbstractWe define and study the notion of quantum polarity, which is a kind of geometric Fourier transform between sets of positions and sets of momenta. Extending previous work of ours, we show that the orthogonal projections of the covariance ellipsoid of a quantum state on the configuration and momentum spaces form what we call a dual quantum pair. We thereafter show that quantum polarity allows solving the Pauli reconstruction problem for Gaussian wavefunctions. The notion of quantum polarity exhibits a strong interplay between the uncertainty principle and symplectic and convex geometry and our approach could therefore pave the way for a geometric and topological version of quantum indeterminacy. We relate our results to the Blaschke–Santaló inequality and to the Mahler conjecture. We also discuss the Hardy uncertainty principle and the less-known Donoho–Stark principle from the point of view of quantum polarity.
Fast screening of covariates in population models empowered by machine learning
Authors: Sibieude Emeric , Khandelwal Akash , Hesthaven Jan S. , Girard Pascal , Terranova Nadia 
Published: May 2021

AbstractOne of the objectives of Pharmacometry (PMX) population modeling is the identification of significant and clinically relevant relationships between parameters and covariates. Here, we demonstrate how this complex selection task could benefit from supervised learning algorithms using importance scores. We compare various classical methods with three machine learning (ML) methods applied to NONMEM empirical Bayes estimates: random forest, neural networks (NNs), and support vector regression (SVR). The performance of the ML models is assessed using receiver operating characteristic (ROC) curves. The F1 score, which measures test accuracy, is used to compare ML and PMX approaches. Methods are applied to different scenarios of covariate influence based on simulated pharmacokinetics data. ML achieved similar or better F1 scores than stepwise covariate modeling (SCM) and conditional sampling for stepwise approach based on correlation tests (COSSAC). Correlations between covariates and the number of false covariates does not affect the performance of any method, but effect size has an impact. Methods are not equivalent with respect to computational speed; SCM is 30 and 100-times slower than NN and SVR, respectively. The results are validated in an additional scenario involving 100 covariates. Taken together, the results indicate that ML methods can greatly increase the efficiency of population covariate model building in the case of large datasets or complex models that require long run-times. This can provide fast initial covariate screening, which can be followed by more conventional PMX approaches to assess the clinical relevance of selected covariates and build the final model.
Use of WetSEM® capsules for convenient multimodal scanning electron microscopy, energy dispersive X-ray analysis, and micro Raman spectroscopy characterisation of technetium oxides
Authors: Bailey D. J. , Stennett M. C. , Heo J. , Hyatt N. C. 
Published: May 2021

AbstractSEM–EDX and Raman spectroscopy analysis of radioactive compounds is often restricted to dedicated instrumentation, within radiological working areas, to manage the hazard and risk of contamination. Here, we demonstrate application of WetSEM® capsules for containment of technetium powder materials, enabling routine multimodal characterisation with general user instrumentation, outside of a controlled radiological working area. The electron transparent membrane of WetSEM® capsules enables SEM imaging of submicron non-conducting technetium powders and acquisition of Tc Lα X-ray emission, using a low cost desktop SEM–EDX system, as well as acquisition of good quality μ-Raman spectra using a 532 nm laser.
Dynamic light scattering distributions by any means
Authors: Farkas Natalia , Kramar John A. 
Published: May 2021

AbstractDynamic light scattering (DLS) is an essential technique for nanoparticle size analysis and has been employed extensively for decades, but despite its long history and popularity, the choice of weighting and mean of the size distribution often appears to be picked ad hoc to bring the results into agreement with other methods and expectations by any means necessary. Here, we critically discuss the application of DLS for nanoparticle characterization and provide much-needed clarification for ambiguities in the mean-value practice of commercial DLS software and documentary standards. We address the misleading way DLS size distributions are often presented, that is, as a logarithmically scaled histogram of measured relative quantities. Central values obtained incautiously from this representation often lead to significant interpretation errors. Through the measurement of monomodal nanoparticle samples having an extensive range of sizes (5 to 250 nm) and polydispersity, we similarly demonstrate that the default outputs of a frequently used DLS inversion method are ill chosen, as they are regularizer-dependent and significantly deviate from the cumulant z-average size. The resulting discrepancies are typically larger than 15% depending on the polydispersity index of the samples. We explicitly identify and validate the harmonic mean as the central value of the intensity-weighted DLS size distribution that expresses the inversion results consistently with the cumulant results. We also investigate the extent to which the DLS polydispersity descriptors are representative of the distributional quality and find them to be unreliable and misleading, both for monodisperse reference materials and broad-distribution biomedical nanoparticles. These results overall are intended to bring essential improvements and to stimulate reexamination of the metrological capabilities and role of DLS in nanoparticle characterization.
Germination and early establishment of dryland grasses and shrubs on intact and wind-eroded soils under greenhouse conditions
Authors: Niu Furong , Pierce Nathan A. , Archer Steven R. , Okin Gregory S. 
Published: May 2021

Abstract
Aims
Grassland-to-shrubland transition is a common form of land degradation in drylands worldwide. It is often attributed to changes in disturbance regimes, particularly overgrazing. A myriad of direct and indirect effects (e.g., accelerated soil erosion) of grazing may favor shrubs over grasses, but their relative importance is unclear. We tested the hypothesis that topsoil “winnowing” by wind erosion would differentially affect grass and shrub seedling establishment to promote shrub recruitment over that of grass.

Methods
We monitored germination and seedling growth of contrasting perennial grass (Bouteloua eriopoda, Sporobolus airoides, and Aristida purpurea) and shrub (Prosopis glandulosa, Atriplex canescens, and Larrea tridentata) functional groups on field-collected non-winnowed and winnowed soils under well-watered greenhouse conditions.

Results
Non-winnowed soils were finer-textured and had higher nutrient contents than winnowed soils, but based on desorption curves, winnowed soils had more plant-available moisture. Contrary to expectations, seed germination and seedling growth on winnowed and non-winnowed soils were comparable within a given species. The N2-fixing deciduous shrub P. glandulosa was first to emerge and complete germination, and had the greatest biomass accumulation of all species.

Conclusions
Germination and early seedling growth of grasses and shrubs on winnowed soils were not adversely nor differentially affected comparing with that observed on non-winnowed soils under well-watered greenhouse conditions. Early germination and rapid growth may give P. glandulosa a competitive advantage over grasses and other shrub species at the establishment stage in grazed grasslands. Field establishment experiments are needed to confirm our findings in these controlled environment trials.
Prospects and challenges of gender neutralization in Russian
Authors: Kirey-Sitnikova Yana 
Published: May 2021

AbstractFeminist linguistic activism has gained prominence among Western feminists as a way to eliminate sexism in language and everyday life. In Russian, gender specification (known asfeminitivy) represents the mainstream approach practiced by grassroots feminist reformers. However, alternative approaches aimed at gender neutralization proliferate. The paper examines the prospects and challenges of gender neutralization both in writing and oral speech. Results of a survey documenting attitudes of Russian-speaking feminist and LGBTQI communities to language reform attempts are presented, with a special focus on comparison between gender specification and gender neutralization.
Should one trust experts?
Authors: Duijf Hein 
Published: May 2021

AbstractShould one trust experts? My answer to this question is a qualified ‘no’ (and a qualified ‘yes’). In this paper I explore the conditions under which it is rational to trust and defer to experts, and those under which it may be rational to refrain from doing so. I draw on two important factors for an actor’s trust in a partner: trust depends on the partner’s competence and on the partner’s interests (and benevolence). I propose that the conditions under which it is rational to trust and defer to experts depend on the competences of the layperson and the expert, and the degree of interest alignment. I present a model that demonstrates that it can be practically infeasible and even logically impossible to determine the expert’s level of competence and the degree of interest alignment. Although it may sound pessimistic that one can rationally refrain from trusting experts, I will also explore some more optimistic conclusions.
Screening for venous thromboembolism in patients with COVID-19
Authors: Vandenbriele Christophe , Gorog Diana A. 
Published: May 2021

AbstractPulmonary thromboembolism and deep venous thrombosis occur frequently in hospitalised patients with COVID-19, the prevalence increases on the intensive care unit (ICU) and is very high in patients on extracorporeal membrane oxygenation (ECMO). We undertook a literature review to assess the usefulness of screening for peripheral venous thrombosis or pulmonary thrombosis in patients admitted with COVID-19. Outside of the ICU setting, D-dimer elevation on presentation or marked increase from baseline should alert the need for doppler ultrasound scan of the lower limbs. In the ICU setting, consideration should be given to routine screening with doppler ultrasound, given the high prevalence of thrombosis in this cohort despite standard anticoagulant thromboprophylaxis. However, absence of lower limb thrombosis on ultrasound does not exclude pulmonary venous thrombosis. Screening with CT pulmonary angiography (CTPA) is not justified in patients on the general wards, unless there are clinical features and/or marked elevations in markers of COVID-19-associated coagulopathy. However, the risk of pulmonary embolism or pulmonary thrombosis in ICU patients is very high, especially in patients on ECMO, where studies that employed routine screening for thrombosis with CT scanning have uncovered up to 100% incidence of pulmonary thrombosis despite standard anticoagulant thromboprophylaxis. Therefore, in patients at low bleeding risk and high clinical suspicion of venous thromboembolism, therapeutic anticoagulation should be considered even before screening, Our review highlights the need for increased vigilance for VTE, with a low threshold for doppler ultrasound and CTPA in high risk in-patient cohorts, where clinical features and D-dimer levels may not accurately reflect the occurrence of pulmonary thromboembolism.
Distribution of Gaps and Adhesive Interaction Between Contacting Rough Surfaces
Authors: Monti Joseph M. , Sanner Antoine , Pastewka Lars 
Published: May 2021

AbstractUnderstanding the distribution of interfacial separations between contacting rough surfaces is integral for providing quantitative estimates for adhesive forces between them. Assuming non-adhesive, frictionless contact of self-affine surfaces, we derive the distribution of separations between surfaces near the contact edge. The distribution exhibits a power-law divergence for small gaps, and we use numerical simulations with fine resolution to confirm the scaling. The characteristic length scale over which the power-law regime persists is given by the product of the rms surface slope and the mean diameter of contacting regions. We show that these results remain valid for weakly adhesive contacts and connect these observations to recent theories for adhesion between rough surfaces.
Differences in attitudes, behaviours and beliefs towards eating between female bodybuilding athletes and non-athletes, and the implications for eating disorders and disordered eating
Authors: Money-Taylor Eleanor , Dobbin Nick , Gregg Rebecca , Matthews Joseph J. , Esen Ozcan 
Published: May 2021

AbstractBackgroundFemale athletes participating in sports emphasising aesthetics are potentially more prone to developing disordered eating (DE) and eating disorders (EDs) than non-athletes, males, and those participating in sports with less emphasis on leanness. Despite this, female bodybuilding athletes have received little attention.AimTo investigate differences in eating attitudes, behaviours and beliefs in female bodybuilding athletes and a non-athlete group.MethodsA cross-sectional study design was used with the eating attitude test-26 (EAT-26) distributed to 75 women (49.3% bodybuilding athletes; 50.7% non-athletes) and the female athlete screening tool (FAST) distributed to the female bodybuilding group only.ResultsDemographic characteristics revealed no significant difference in age, stature or body mass index (P = 0.106 to 0.173), though differences in body mass were evident (P = 0.0001 to 0.042). Bodybuilding athletes scored significantly higher (P = 0.001) than non-athletes on the EAT-26 questionnaire, with significantly more athletes (56.8%) being labelled as ‘at risk’ of an ED than non-athletes (23.7%,P = 0.001). Responses to the FAST questionnaire indicated female bodybuilding athletes have high preoccupation with their body mass; engage in exercise to alter their body mass; and disclosed negative perceptions of themselves.ConclusionIn all, female bodybuilding athletes demonstrate behaviours associated with DE and EDs as well as a preoccupation with nutrition intake, exercise, and strategies to alter their appearance. These findings have important implications for those managing female bodybuilding athletes such as strength and conditioning coaches, athletic trainers, nutritionist and dietitians with respect to detecting DE and EDs as well as minimising the risk factors.
A Low-Dimensional Network Model for an SIS Epidemic: Analysis of the Super Compact Pairwise Model
Authors: Corcoran Carl , Hastings Alan 
Published: May 2021

AbstractNetwork-based models of epidemic spread have become increasingly popular in recent decades. Despite a rich foundation of such models, few low-dimensional systems for modeling SIS-type diseases have been proposed that manage to capture the complex dynamics induced by the network structure. We analyze one recently introduced model and derive important epidemiological quantities for the system. We derive the epidemic threshold and analyze the bifurcation that occurs, and we use asymptotic techniques to derive an approximation for the endemic equilibrium when it exists. We consider the sensitivity of this approximation to network parameters, and the implications for disease control measures are found to be in line with the results of existing studies.
On the Comparison of Incompatibility of Split Systems Across Different Numbers of Taxa
Authors: Hendriksen Michael , Kapust Nils 
Published: May 2021

AbstractWe consider the problem of the minimum number of phylogenetic trees it would take to display all splits in a given set, a problem related tok-compatibility. A set of trees that displays every single possible split is termed auniversal tree set. In this note, we find the universal incompatibilityU(n), the minimal size of a universal tree set forntaxa. By normalising incompatibility usingU(n), one can then compare incompatibility of split systems across different numbers of taxa. We demonstrate this application by comparing two SplitsTree networks derived from archaeal genomes, with different numbers of taxa.
Screening for extremely rare pathogenic variants of monogenic diabetes using targeted panel sequencing
Authors: Płoszaj Tomasz , Antosik Karolina , Jakiel Paulina , Zmysłowska Agnieszka , Borowiec Maciej 
Published: May 2021

Abstract
Aims
Maturity‐onset diabetes of the young (MODY) is one of the rare monogenic forms of diabetes. To date, about 12 genes in the scientific literature are closely related to the occurrence of the disease phenotype. However, there is still a high prevalence of undiagnosed cases of so-called MODY-X whose genetic background is still unknown.

Methods
We performed tNGS for 523 patients with suspected MODY. Next 357 selected patients, in whom no damaging variants were found in 12 major genes causing MODY, were screened for the presence of pathogenic variants in four candidate genes (MNX1, RFX6, NKX2.2, and NKX6.1). All data were generated in one tNGS sequencing reaction and confirmed by Sanger sequencing.

Results
In total, we selected five potentially damaging variants, in eight patients, in RFX6, NKX2.2, and NKX6.1 genes. Four of them have never been described in literature before. The frequency of occurrence of two of them in the RFX6 gene significantly differed in relation to the healthy population. The analysis of segregation in the family did not reveal that they were the only cause of the disease phenotype.

Conclusions
The very-rare variants indicated in this study show that this type of research on large population groups may help in the future for better understanding and more accurate diagnostics of extremely rare forms of MODY.
The differential activation of cardiovascular hormones across distinct stages of portal hypertension predicts clinical outcomes
Authors: Hartl Lukas , Jachs Mathias , Desbalmes Christopher , Schaufler Dunja , Simbrunner Benedikt , Paternostro Rafael , Schwabl Philipp , Bauer David Josef Maria , Semmler Georg , Scheiner Bernhard , Bucsics Theresa , Eigenbauer Ernst , Marculescu Rodrig , Szekeres Thomas , Peck-Radosavljevic Markus , Kastl Stefan , Trauner Michael , Mandorfer Mattias , Reiberger Thomas 
Published: May 2021

Abstract
Background and aims
The cardiovascular hormones renin/angiotensin/aldosterone (RAA), brain-type natriuretic peptide (BNP)and arginine-vasopressin (AVP) are key regulators of systemic circulatory homeostasis in portal hypertension (PH). We assessed (i) the activation of renin, BNP and AVP across distinct stages of PH and (ii) whether activation of these hormones correlates with clinical outcomes.

Methods
Plasma levels of renin, proBNP and copeptin (AVP biomarker) were determined in 663 patients with advanced chronic liver disease (ACLD) undergoing hepatic venous pressure gradient (HVPG) measurement at the Vienna General Hospital between 11/2011 and 02/2019. We stratified for Child stage (A–C), HVPG (6–9 mmHg, 10–15 mmHg, ≥ 16 mmHg) and compensated vs. decompensated ACLD.

Results
With increasing PH, hyperdynamic state was indicated by higher heart rates (6–9 mmHg: median 71.0 [IQR 18.0] bpm, 10–15 mmHg: 76.0 [19.0] bpm, ≥ 16 mmHg: 80.0 [22.0] bpm; p < 0.001), lower mean arterial pressure (6–9 mmHg: 103.0 [13.5] mmHg, 10–15 mmHg: 101.0 [19.5] mmHg, ≥ 16 mmHg: 99.0 [21.0] mmHg; p = 0.032) and lower serum sodium (6–9 mmHg: 139.0 [3.0] mmol/L, 10–15 mmHg: 138.0 [4.0] mmol/L, ≥ 16 mmHg: 138.0 [5.0] mmol/L; p < 0.001). Across HVPG strata (6–9 mmHg vs. 10–15 mmHg vs ≥ 16 mmHg), median plasma levels of renin (21.0 [50.5] vs. 25.1 [70.9] vs. 65.4 [219.6] µIU/mL; p < 0.001), proBNP (86.1 [134.0] vs. 63.6 [118.0], vs. 132.2 [208.9] pg/mL; p = 0.002) and copeptin (7.8 [7.7] vs. 5.6 [8.0] vs. 10.7 [18.6] pmol/L; p = 0.024) increased with severity of PH. Elevated renin levels independently predicted first hepatic decompensation (adjusted hazard ratio [aHR]: 1.69; 95% confidence interval [95% CI] 1.07–2.68; p = 0.025) and mortality in compensated patients (aHR: 3.15; 95% CI 1.70–5.84; p < 0.001) and the overall cohort aHR: 1.42; 95% CI 1.01–2.01; p = 0.046). Elevated copeptin levels predicted mortality in decompensated patients (aHR: 5.77; 95% CI 1.27–26.33; p = 0.024) and in the overall cohort (aHR: 3.29; 95% CI 1.36–7.95; p = 0.008). ProBNP levels did not predict clinical outcomes.

Conclusions
The cardiovascular hormones renin, proBNP and AVP are activated with progression of ACLD and PH. Renin activation is a risk factor for hepatic decompensation and mortality, especially in compensated patients. Increased plasma copeptin is a risk factor for mortality, in particular in decompensated patients.