bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 2b Trial of P2X3 Receptor Antagonist Sivopixant for Refractory or Unexplained Chronic Cough
Authors: McGarvey Lorcan , Smith Jaclyn A. , Morice Alyn , Birring Surinder S. , Chung Kian Fan , Dicpinigaitis Peter V. , Niimi Akio , Benninger Michael S. , Sher Mandel , Matsunaga Yuko , Miyazaki Sayaka , Machida Mitsuaki , Ishihara Hiroyuki , Mahmood Adnan , Gomez Juan-Carlos 
Published: December 2022

Abstract
Introduction
To determine the optimal dose of sivopixant, a highly selective P2X3 receptor antagonist, for refractory or unexplained chronic cough (RCC/UCC).

Methods
In this phase 2b, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial, patients received sivopixant 50, 150, or 300 mg or placebo once daily for 4 weeks. The primary endpoint was a change from baseline in 24-h cough frequency (coughs/h) with sivopixant vs placebo.

Results
Overall, 390/406 randomized patients completed the study. Placebo-adjusted changes in hourly cough count over 24 h were 13.17% (P = 0.3532), − 1.77% (P = 0.8935), and − 12.47% (P = 0.3241) and in cough severity (visual analog scale) were 1.75 mm (P = 0.5854), − 1.21 mm (P = 0.7056), and − 6.55 mm (P = 0.0433) with sivopixant 50, 150, and 300 mg, respectively. Placebo-adjusted changes from baseline in Leicester Cough Questionnaire total scores were − 0.37 (P = 0.4207), − 0.07 (P = 0.8806), and 0.69 (P = 0.1473) with sivopixant 50, 150, and 300 mg, respectively. Additionally, 61.3%, 78.3%, 86.8%, and 71.4% of patients receiving sivopixant 50, 150, and 300 mg and placebo, respectively, reported any improvements in Patient Global Impression of Change. The incidence of treatment-emergent adverse events (TEAEs) was 25.7%, 32.0%, 49.0%, and 20.6% in sivopixant 50, 150, and 300 mg and placebo groups, respectively; all TEAEs in the sivopixant group were mild-to-moderate.

Conclusion
Sivopixant did not demonstrate a statistically significant difference vs placebo in change from baseline in 24-h cough frequency. The dose of 300 mg has potential for RCC/UCC, showing the greatest improvements in cough frequency and patient-reported outcomes and dose-related mild to moderate reversible taste disturbance, although further trials are needed.

Clinical Trial Registration
ClinicalTrials.gov identifier NCT04110054; registered September 26, 2019.
Fatigue trajectories during pediatric ALL therapy are associated with fatigue after treatment: a national longitudinal cohort study
Authors: Irestorm Elin , Steur Lindsay M. H. , Kaspers Gertjan J. L. , Van Eijkelenburg Natasha K. A. , Van der Sluis Inge M. , Dors Natasja , Van den Bos Cor , Tissing Wim J. E. , Grootenhuis Martha A. , Van Litsenburg Raphaele R. L. 
Published: December 2022

Abstract
Objective
Fatigue is one of the most prevalent and distressing symptoms reported by survivors of childhood cancer. There is currently a lack of longitudinal studies on cancer-related fatigue, and especially on the relationship between the course of fatigue during treatment and fatigue at follow-up. The purpose of the current study was therefore to investigate if the course of fatigue during treatment, treatment intensity, serious adverse events, sex, or age at diagnosis are associated with cancer-related fatigue after treatment.

Methods
Participants were 92 children and adolescents diagnosed with acute lymphoblastic leukemia (mean age at diagnosis was 6.26 years). Fatigue was measured with PedsQL multidimensional fatigue scale proxy reports 5 months after diagnosis, 12 months after diagnosis, 24 months after diagnosis, and at follow-up 12 months after end of treatment. The effect of patient and treatment characteristics on fatigue reported at follow-up was tested through logistic regression analyses.

Results
The course of fatigue during treatment significantly predicted fatigue reported at follow-up for general fatigue (p = .038, OR = 9.20), sleep/rest fatigue (p = .011, OR = 15.48), and cognitive fatigue (p < .001, OR = 10.78). None of the other variables were associated with fatigue at follow-up for any of the subscales.

Conclusions
The findings demonstrate that fatigue reported during treatment can predict fatigue at follow-up. These results stress the need for longitudinal assessments. Healthcare professionals need to be aware that pediatric patients who are fatigued during treatment need to receive additional attention and timely interventions since cancer-related fatigue will not resolve by itself in the first year after end of treatment.
Do members of cancer peer support groups know more about cancer than non-members? Results from a cross-sectional study in Germany
Authors: Ziegler Elâ , Klein Jens , Kofahl Christopher 
Published: December 2022

Abstract

Purpose
This study aims to assess whether cancer-specific knowledge (CSK) is associated with membership in a cancer peer support group (PSG) and other factors.

Methods
A cross-sectional study investigated the CSK of 1121 cancer patients of various entities across Germany. CSK was measured with the BCKS-14, a 14-item knowledge instrument which was previously participatory developed with patient representatives and oncologists. Associations between CSK and PSG membership, sociodemographic factors, internet use, and preferences in medical decision-making were analysed with t-tests and multiple linear regressions.

Results
The t-test showed a statistically significant difference in CSK between members and non-members of PSGs. Knowledge for PSG members was on average 0.97 points higher (p < 0.001) and varied between 2 and 14 points compared to 0–14 points for non-members. Regression analysis revealed age, gender, time since diagnosis, education, internet use, and PSG activity to be statistically significant predictors. Younger (β =  − 0.15; p < 0.001), female (β = 0.10; p = 0.001), higher educated patients (β = 0.27; p < 0.001) with and a diagnosis longer ago (β = 0.10; p = 0.002) who use the internet frequently for information seeking (β = 0.20; p ≤ 0.001) and members of cancer PSGs (β = 0.18; p ≤ 0.001) showed a higher CSK.

Conclusion
Overall, CSK of the participants shows a high degree of variance. CSK should be promoted for all patients and especially for older, newly diagnosed patients with low educational levels and PSGs introduced early on as they contribute to improving CSK among other benefits.
CO2 Injection-Induced Shearing and Fracturing in Naturally Fractured Conventional and Superhot Geothermal Environments
Authors: Pramudyo Eko , Goto Ryota , Sakaguchi Kiyotoshi , Nakamura Kengo , Watanabe Noriaki 
Published: December 2022

AbstractThis study elucidates the possibility of CO2 injection-induced formation of a complex cloud-fracture network (CFN) in granite, along with shearing (shear slip) of natural pre-existing fractures under conventional (~ 150–300 °C) and superhot (> ~ 400 °C) geothermal conditions, potentially providing additional connecting flow paths between the stimulated natural fractures. Here, we conduct a set of experiments under triaxial stress states at 150 °C and 450 °C on cylindrical granite samples containing a sawcut (representing a natural fracture) inclined 45° from the sample’s axis. CO2 injection induced dynamic shear slip on the sawcut, with higher slip velocities at 150 °C owing to the higher elasticity of the rock than that at 450 °C. The lower viscosity of CO2 also allowed it to more uniformly pressurize the sawcut, resulting in higher slip velocities and slip displacements compared with those based on water injection in the 150 °C experiments. This implies that under conventional geothermal conditions, CO2 injection can stimulate the same volume of rock as that of water injection at lower injection-well pressures. The CFNs then formed via CO2 injection at pressures similar to those predicted by the Griffith failure criterion as the sawcut shear slip progressed at both experimental temperatures. The experiments also revealed potential challenges associated with CO2 injection in naturally fractured geothermal environments, such as narrow aperture CFNs, owing to decreasing differential stress during their formation; all these factors should be addressed in future research.
Climate change projections of continental-scale streamflow across the Mississippi River Basin
Authors: Lewis James W. , Lytle Sara E. , Tavakoly Ahmad A. 
Published: December 2022

AbstractA large body of scientific research has demonstrated a changing climate, which affects river flow regimes and extreme flood frequencies and magnitudes. The magnitude and frequency of extreme events are of critical importance in the evaluation of river systems to inform flood risk reduction under current and future conditions. The global climate projections from the Coupled Model Intercomparison Project, Phase 5 (CMIP5) datasets were used by the Variable Infiltration Capacity (VIC) land surface model to produce a runoff dataset, implementing a Bias-Correction Spatial Disaggregation (BCSD) approach. The resulting runoff was then used as input to the Routing Application for Parallel computatIon of Discharge (RAPID) river routing model to simulate daily flows within all 1.2 million Mississippi River Basin river reaches for years 1950 through 2099. This research effort analyzed the performance of the models for the historical time period, comparing with the observations at 64 gage locations for 16 different climate models. A recurrence interval analysis was performed to determine the 2-, 5-, 10-, 50-, 100-, 500-, and 1000-year events within both the historical and projected time periods, highlighting the relative changes predicted into the future. Anticipated seasonal changes are demonstrated by comparing monthly average streamflows for three different time periods (1951–2005, 2006–2049, and 2050–2099). Results indicate that the hydrologic conditions of the Lower Mississippi River are not stationary. Based on all 16 models considered in this study, the median of the model projections shows an 8% increase in the 100-year return period discharge at Vicksburg, Mississippi, into the future time period, although the full range of 16 models varies widely from − 11 to + 85% change in the 100-year discharge in the future.
Dye-labeled aromatic azides for multi-photon grafting
Authors: Gallas Katharina , Wohlmuth Dominik , Li Zhiquan , Ajami Aliasghar , Ovsianikov Aleksandr , Liska Robert , Slugovc Christian 
Published: December 2022

AbstractThe synthesis of two dye-labeled azides via de-symmetrization of 2,6-bis(4-azidobenzylidene)-4-methylcyclohexanone (BAC-M) with a copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) using fluorescent dyes is reported. An alkyne functionalized dansyl derivative and an alkyne functionalized perylene diimide derivative were used as the dyes. The photo-physical properties of these dye dyads are described, and their performance in multi-photon grafting onto polyethylene glycol-based hydrogels is investigated. While the dansyl-conjugated BAC derivate is well suited for multi-photon grafting with lasers operating at 800 nm, the perylene diimide-bearing dye does not give the desired result.
Graphical abstract
Gemeinsame Perspektiven Humanistischer Psychotherapien in Covid-Zeiten
Authors: Grillmeier-Rehder Ursula , Hochreiter Karoline , Kisler Ida-Maria , Korunka Christian , Schigl Brigitte 
Published: December 2022

ZusammenfassungDer Beitrag ist ein Versuch, das Spannungsfeld von Unterschieden und Gemeinsamkeiten der fünf großen humanistischen Schulen (Gestalt, Psychodrama, Personzentrierte PT, Logotherapie und Existenzanalyse, Integrative Therapie) in Bezug auf ein relevantes gesellschaftliches Themenfeld auszuloten. Die Covid-19 Pandemie stellt für die gesamte Psychotherapie eine große Herausforderung dar. Viele Menschen leiden unter den zahlreichen Auswirkungen der Pandemie. Aber auch die therapeutische Praxis hat sich dadurch verändert. Wir suchen in diesem Beitrag nach Antworten aus der Sicht der humanistischen Psychotherapieverfahren.Im ersten Teil werden schulenspezifische Zugänge in Bezug auf die Auswirkungen der Pandemie vorgestellt. Hier unterscheiden sich die Schulen in Theorie, Sprache und Schwerpunktsetzungen. Anschließend versuchen wir die Gemeinsamkeiten unserer Ansätze zu erarbeiten. Im zweiten Teil werden Gemeinsamkeiten humanistischer Ansätze in Bezug auf den Umgang mit der Pandemie erarbeitet. Dazu gehören Aspekte des Menschenbildes, philosophische Verankerungen, die Spannungsfelder von Freiheit/Verantwortung und Autonomie/Bezogenheit und die Rolle der therapeutischen Beziehung.
Low-temperature Mössbauer spectroscopy of organs from 57Fe-enriched HFE(−/−) hemochromatosis mice: an iron-dependent threshold for generating hemosiderin
Authors: Vali Shaik Waseem , Lindahl Paul A. 
Published: December 2022

AbstractHereditary hemochromatosis is an iron-overload disease most often arising from a mutation in the Homeostatic Fe regulator (HFE) gene. HFE organs become overloaded with iron which causes damage. Iron-overload is commonly detected by NMR imaging, but the spectroscopic technique is insensitive to diamagnetic iron. Here, we used Mössbauer spectroscopy to examine the iron content of liver, spleen, kidney, heart, and brain of 57Fe-enriched HFE(−/−) mice of ages 3–52 wk. Overall, the iron contents of all investigated HFE organs were similar to the same healthy organ but from an older mouse. Livers and spleens were majorly overloaded, followed by kidneys. Excess iron was generally present as ferritin. Iron–sulfur clusters and low-spin FeII hemes (combined into the central quadrupole doublet) and nonheme high-spin FeII species were also observed. Spectra of young and middle-aged HFE kidneys were dominated by the central quadrupole doublet and were largely devoid of ferritin. Collecting and comparing spectra at 5 and 60 K allowed the presence of hemosiderin, a decomposition product of ferritin, to be quantified, and it also allowed the diamagnetic central doublet to be distinguished from ferritin. Hemosiderin was observed in spleens and livers from HFE mice, and in spleens from controls, but only when iron concentrations exceeded 2–3 mM. Even in those cases, hemosiderin represented only 10–20% of the iron in the sample. NMR imaging can identify iron-overload under non-invasive room-temperature conditions, but Mössbauer spectroscopy of 57Fe-enriched mice can detect all forms of iron and perhaps allow the process of iron-overloading to be probed in greater detail.
Graphical Abstract
Analyzing neural network behavior through deep statistical model checking
Authors: Gros Timo P. , Hermanns Holger , Hoffmann Jörg , Klauck Michaela , Steinmetz Marcel 
Published: December 2022

AbstractNeural networks (NN) are taking over ever more decisions thus far taken by humans, even though verifiable system-level guarantees are far out of reach. Neither is the verification technology available, nor is it even understood what a formal, meaningful, extensible, and scalable testbed might look like for such a technology. The present paper is an attempt to improve on both the above aspects. We present a family of formal models that contain basic features of automated decision-making contexts and which can be extended with further orthogonal features, ultimately encompassing the scope of autonomous driving. Due to the possibility to model random noise in the decision actuation, each model instance induces a Markov decision process (MDP) as verification object. The NN in this context has the duty to actuate (near-optimal) decisions. From the verification perspective, the externally learnt NN serves as a determinizer of the MDP, the result being a Markov chain which as such is amenable to statistical model checking. The combination of an MDP and an NN encoding the action policy is central to what we call “deep statistical model checking” (DSMC). While being a straightforward extension of statistical model checking, it enables to gain deep insight into questions like “how high is the NN-induced safety risk?”, “how good is the NN compared to the optimal policy?” (obtained by model checking the MDP), or “does further training improve the NN?”. We report on an implementation of DSMC inside the ModestToolset in combination with externally learnt NNs, demonstrating the potential of DSMC on various instances of the model family, and illustrating its scalability as a function of instance size as well as other factors like the degree of NN training.
Exploring the benefits and dis-benefits of climate migration as an adaptive strategy along the rural-peri-urban continuum in Namibia
Authors: Thorn Jessica P. R. , Nangolo Penelao , Biancardi Rebeca Aleu , Shackleton Sheona , Marchant Robert A. , Ajala Olayinka , Delgado Guillermo , Mfune John K. E. , Cinderby Steve , Hejnowicz Adam P. 
Published: December 2022

AbstractThe scale of climate migration across the Global South is expected to increase during this century. By 2050, millions of Africans are likely to consider, or be pushed into, migration because of climate hazards contributing to agricultural disruption, water and food scarcity, desertification, flooding, drought, coastal erosion, and heat waves. However, the migration-climate nexus is complex, as is the question of whether migration can be considered a climate change adaptation strategy across both the rural and urban space. Combining data from household surveys, key informant interviews, and secondary sources related to regional disaster, demographic, resource, and economic trends between 1990 and 2020 from north central and central dryland Namibia, we investigate (i) human migration flows and the influence of climate hazards on these flows and (ii) the benefits and dis-benefits of migration in supporting climate change adaptation, from the perspective of migrants (personal factors and intervening obstacles), areas of origin, and areas of destination. Our analysis suggests an increase in climate-related push factors that could be driving rural out-migration from the north central region to peri-urban settlements in the central region of the country. While push factors play a role in rural-urban migration, there are also several pull factors (many of which have been long-term drivers of urban migration) such as perceived higher wages, diversity of livelihoods, water, health and energy provisioning, remittances, better education opportunities, and the exchange of non-marketed products. Migration to peri-urban settlements can reduce some risks (e.g. loss of crops and income due to climate extremes) but amplify others (e.g. heat stress and insecure land tenure). Adaptation at both ends of the rural–urban continuum is supported by deeply embedded linkages in a model of circular rural–urban-rural migration and interdependencies. Results empirically inform current and future policy debates around climate mobilities in Namibia, with wider implications across Africa.
Graphical abstract
Coarse Mesh Superconvergence in Isogeometric Frequency Analysis of Mindlin–Reissner Plates with Reduced Integration and Quadratic Splines
Authors: Xu Xiaolan , Lin Zhiwei , Hou Songyang , Wang Dongdong 
Published: December 2022

AbstractA frequency accuracy study is presented for the isogeometric free vibration analysis of Mindlin–Reissner plates using reduced integration and quadratic splines, which reveals an interesting coarse mesh superconvergence. Firstly, the frequency error estimates for isogeometric discretization of Mindlin–Reissner plates with quadratic splines are rationally derived, where the degeneration to Timoshenko beams is discussed as well. Subsequently, in accordance with these frequency error measures, the shear locking issue corresponding to the full integration isogeometric formulation is elaborated with respect to the frequency accuracy deterioration. On the other hand, the locking-free characteristic for the isogeometric formulation with uniform reduced integration is illustrated by its superior frequency accuracy. Meanwhile, it is found that a frequency superconvergence of sixth order accuracy arises for coarse meshes when the reduced integration is employed for the isogeometric free vibration analysis of shear deformable beams and plates, in comparison with the ultimate fourth order accuracy as the meshes are progressively refined. Furthermore, the mesh size threshold for the coarse mesh superconvergence is provided as well. The proposed theoretical results are consistently proved by numerical experiments.
Habits Over Routines: Remarks on Control Room Practices and Control Room Studies
Authors: Silvast Antti , Virtanen Mikko J. , Abram Simone 
Published: December 2022

AbstractThe evolution of computer tools has had profound impacts on many aspects of control rooms and control room studies. In this paper, we discuss some key assumptions underpinning these studies based on a new case of the electricity distribution control rooms, where the reliability of the electricity infrastructure is managed by a combination of planning and real-time maintenance. Some of these practices have changed remarkably little over the past decades – partially because they have been considered to have been ‘digitalized’ since the 1950s and have continued to amass digital solutions from different periods. Hence, the gradual transformation of control room work demands nuanced attention, both conceptual and empirical. To outline a framework for this work, we provide a conceptualization of organizational routines, habits, and reflectivity and synthesize existing CSCW and control room literature. We then present an empirical study that demonstrates our concepts and shows how they can be applied to study cooperative work. By addressing these aims the paper complements, and advances, the important topics recognized in this special theme issue and hence develops new research openings in CSCW. We address the necessity to avoid implicit determinism when analyzing new digital support tools and suggest focusing on how working habits mediate social changes, distribution, and decentralization in representing the power distribution in control rooms.
Unambiguous Identification of Glucose-Induced Glycation in mAbs and other Proteins by NMR Spectroscopy
Authors: Moises Jennifer E. , Regl Christof , Hinterholzer Arthur , Huber Christian G. , Schubert Mario 
Published: December 2022

Abstract
Objective
Glycation is a non-enzymatic and spontaneous post-translational modification (PTM) generated by the reaction between reducing sugars and primary amine groups within proteins. Because glycation can alter the properties of proteins, it is a critical quality attribute of therapeutic monoclonal antibodies (mAbs) and should therefore be carefully monitored. The most abundant product of glycation is formed by glucose and lysine side chains resulting in fructoselysine after Amadori rearrangement. In proteomics, which routinely uses a combination of chromatography and mass spectrometry to analyze PTMs, there is no straight-forward way to distinguish between glycation products of a reducing monosaccharide and an additional hexose within a glycan, since both lead to a mass difference of 162 Da.

Methods
To verify that the observed mass change is indeed a glycation product, we developed an approach based on 2D NMR spectroscopy spectroscopy and full-length protein samples denatured using high concentrations of deuterated urea.

Results
The dominating β-pyranose form of the Amadori product shows a characteristic chemical shift correlation pattern in 1H-13C HSQC spectra suited to identify glucose-induced glycation. The same pattern was observed in spectra of a variety of artificially glycated proteins, including two mAbs, as well as natural proteins.

Conclusion
Based on this unique correlation pattern, 2D NMR spectroscopy can be used to unambiguously identify glucose-induced glycation in any protein of interest. We provide a robust method that is orthogonal to MS-based methods and can also be used for cross-validation.