bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topographic signatures of progressive glacial landscape transformation
Authors: Liebl Moritz , Robl Jörg , Egholm David Lundbek , Prasicek Günther , Stüwe Kurt , Gradwohl Gerit , Hergarten Stefan 
Published: April 2021

SummaryThe Pleistocene glaciations left a distinct topographic footprint in mountain ranges worldwide. The geometric signature of glacial topography has been quantified in various ways, but the temporal development of landscape metrics has not been traced in a landscape evolution model so far. However, such information is needed to interpret the degree of glacial imprint in terms of the integrated signal of temporal and spatial variations in erosion as a function of glacial occupation time.We apply a surface process model for cold‐climate conditions to an initially fluvial mountain range. By exploring evolving topographic patterns in model time series, we determine locations where topographic changes reach a maximum and where the initial landscape persists. The signal of glacial erosion, expressed by the overdeepening of valleys and the steepening of valley flanks, develops first at the glacier front and migrates upstream with ongoing glacial erosion. This leads to an increase of mean channel slope and its variance. Above steep flanks and head‐walls, however, the observed mean channel slope remains similar to the mean channel slope of the initial fluvial topography. This leads to a characteristic turning point in the channel slope–elevation distribution above the equilibrium line altitude, where a transition from increasing to decreasing channel slope with elevation occurs. We identify this turning point and a high channel slope variance as diagnostic features to quantify glacial imprint.Such features are abundant in glacially imprinted mid‐latitude mountain ranges such as the Eastern Alps. By analysing differently glaciated parts of the mountain range, we observe a decreasing clarity of this diagnostic morphometric property with decreasing glacial occupation. However, catchments of the unglaciated eastern fringe of the Alps also feature turning points in their channel slope–elevation distributions, but in contrast to the glaciated domain, the variance of channel slope is small at all elevation levels.
Assessing the hydrological and geomorphic behaviour of a landscape evolution model within a limits‐of‐acceptability uncertainty analysis framework
Authors: Wong Jefferson S. , Freer Jim E. , Bates Paul D. , Warburton Jeff , Coulthard Tom J. 
Published: April 2021

AbstractLandscape evolution models (LEMs) have the capability to characterize key aspects of geomorphological and hydrological processes. However, their usefulness is hindered by model equifinality and paucity of available calibration data. Estimating uncertainty in the parameter space and resultant model predictions is rarely achieved as this is computationally intensive and the uncertainties inherent in the observed data are large. Therefore, a limits‐of‐acceptability (LoA) uncertainty analysis approach was adopted in this study to assess the value of uncertain hydrological and geomorphic data. These were used to constrain simulations of catchment responses and to explore the parameter uncertainty in model predictions. We applied this approach to the River Derwent and Cocker catchments in the UK using a LEM CAESAR‐Lisflood. Results show that the model was generally able to produce behavioural simulations within the uncertainty limits of the streamflow. Reliability metrics ranged from 24.4% to 41.2% and captured the high‐magnitude low‐frequency sediment events. Since different sets of behavioural simulations were found across different parts of the catchment, evaluating LEM performance, in quantifying and assessing both at‐a‐point behaviour and spatial catchment response, remains a challenge. Our results show that evaluating LEMs within uncertainty analyses framework while taking into account the varying quality of different observations constrains behavioural simulations and parameter distributions and is a step towards a full‐ensemble uncertainty evaluation of such models. We believe that this approach will have benefits for reflecting uncertainties in flooding events where channel morphological changes are occurring and various diverse (and yet often sparse) data have been collected over such events.
Reduced radiotherapy clinical benefit for primary Waldeyer's ring diffuse large B‐cell lymphoma in the rituximab era
Authors: Guan Qingpei , Hong Yuheng , Hu Ge , Zhou Qiqi , Li Lanfang , Qian Zhengzi , Zhou Shiyong , Ren Xiubao , Qiu Lihua , Wang Xianhuo , Zhang Huilai 
Published: April 2021

AbstractThis study aimed to identify the prognostic factors in patients with Waldeyer's ring diffuse large B‐cell lymphoma (WR‐DLBCL), comparing the efficacy of radiotherapy (RT) for the WR‐DLBCL patients in the pre‐rituximab and rituximab eras. We conducted a retrospective analysis of 134 patients diagnosed with WR‐DLBCL. Univariate and multivariate analyses were performed to identify the prognostic factors for WR‐DLBCL. Then, we divided these patients into the rituximab plus chemotherapy group (R‐chemotherapy) (n = 88) and chemotherapy group (n = 46), and the Kaplan–Meier and Cox regression model analyses were applied to investigate the treatment value of RT in both the groups. Multivariate analysis revealed international prognostic index (IPI) ≥ 3 and chemotherapy without rituximab as significant risk factors for the progression‐free survival (PFS, IPI ≥ 3: p = 0.001; chemotherapy without rituximab: p = 0.002) and overall survival (OS, IPI ≥ 3, p < 0.001; chemotherapy without rituximab, p = 0.024). Rituximab combined with chemotherapy significantly improved PFS (p = 0.002) and OS (p = 0.006) in these patients. RT did not significantly contribute to the survival in the overall cohort analysis, whereas in the subgroup analysis, RT significantly improved the PFS (p = 0.025) and OS (p = 0.029) for the patients in the chemotherapy group, but not in the R‐chemotherapy group. In conclusion, the WR‐DLBCL patients could benefit from RT in the pre‐rituximab era, whereas the addition of rituximab to chemotherapy significantly improved the survival of WR‐DLBCL patients, and the clinical benefit of RT was reduced.
Thermal dispersed homogeneous‐heterogeneous reaction within MHD flow of a Jeffrey fluid in the presence of Newtonian cooling and nonlinear thermal radiation
Authors: Sen Satya Subha Shree , Das Mrutyunjay , Shaw Sachin 
Published: April 2021

AbstractThe current study deals with the effects of Newtonian cooling, magnetic field, and nonlinear radiation on the flow of a Jeffrey fluid along with thermal dispersion and homogeneous‐heterogeneous reaction towards a stagnation point. The developed governing equations are transformed into nondimensional equations employing suitable similarity transformations along with their related boundary conditions. To solve and analyze these equations, the BVP4C solver of MATLAB has been used. The various properties of the fluid flow such as velocity, temperature, and concentration are represented in their respective graphs. The values obtained for skin friction and Nusselt number are expressed in the form of a table. The important outcomes of the present study are that the velocity declines as we increase the melting parameter, magnetic parameter, and Prandtl number. The temperature profile increases with radiation parameter, heat source, and magnetic number. An inclination is seen in the concentration of the fluid with a rise in Schmidt number whereas declination is seen with a rise in the homogeneous reaction parameter. Also, a comparison Table 1 has been made with the previous work under limited conditions. The table shows that the current work justifies the previous work system under those conditions. The present model can be utilized for many industrial purposes. Large‐scale industries like plastic and food processing industries can utilize these results to enhance their productivity.
Stability of a chemically reacting double‐diffusive fluid layer in a porous medium
Authors: Mahajan Amit , Tripathi Vinit K. 
Published: April 2021

AbstractIn the present study, double‐diffusive convection with chemical reaction in a Darcy–Brinkman porous layer, heated and salted below, has been investigated. Linear analysis is performed with the help of the normal mode technique, and nonlinear analysis is performed with the help of the energy method. The effect of the thermal contribution of the chemical reaction is found to be more effective on the convective instability in comparison with the solutal contribution of the chemical reaction. The reaction parameters enhance the onset of convection in the stationary mode, however, in oscillatory mode, the onset of convection is seen to be delayed. The effect of solute Rayleigh number , Darcy number , is depicted graphically.
Efficient generation of osteoclasts from human induced pluripotent stem cells and functional investigations of lethal CLCN7-related osteopetrosis
Authors: Rössler Uta , Hennig Anna Floriane , Stelzer Nina , Bose Shroddha , Kopp Johannes , Søe Kent , Cyganek Lukas , Zifarelli Giovanni , Ali Salaheddine , von der Hagen Maja , Strässler Elisabeth Tamara , Hahn Gabriele , Pusch Michael , Stauber Tobias , Izsvák Zsuzsanna , Gossen Manfred , Stachelscheid Harald , Kornak Uwe 
Published: April 2021

ABSTRACTHuman induced pluripotent stem cells (hiPSCs) hold great potential for modeling human diseases and the development of innovative therapeutic approaches. Here, we report on a novel, simplified differentiation method for forming functional osteoclasts from hiPSCs. The three-step protocol starts with embryoid body formation, followed by hematopoietic specification, and finally osteoclast differentiation. We observed continuous production of monocyte-like cells over a period of up to 9 weeks, generating sufficient material for several osteoclast differentiations. The analysis of stage-specific gene and surface marker expression proved mesodermal priming, the presence of monocyte-like cells, and of terminally differentiated multinucleated osteoclasts, able to form resorption pits and trenches on bone and dentine in vitro. In comparison to peripheral blood mononuclear cell (PBMC)-derived osteoclasts hiPSC-derived osteoclasts were larger and contained a higher number of nuclei. Detailed functional studies on the resorption behavior of hiPSC-osteoclasts indicated a trend towards forming more trenches than pits and an increase in pseudoresorption. We used hiPSCs from an autosomal recessive osteopetrosis (ARO) patient (BIHi002-A, ARO hiPSCs) with compound heterozygous missense mutations p.(G292E) and p.(R403Q) in CLCN7, coding for the Cl−/H+-exchanger ClC-7, for functional investigations. The patient's leading clinical feature was a brain malformation due to defective neuronal migration. Mutant ClC-7 displayed residual expression and retained lysosomal co-localization with OSTM1, the gene coding for the osteopetrosis-associated transmembrane protein 1, but only ClC-7 harboring the mutation p.(R403Q) gave strongly reduced ion currents. An increased autophagic flux in spite of unchanged lysosomal pH was evident in undifferentiated ARO hiPSCs. ARO hiPSC-derived osteoclasts showed an increased size compared to hiPSCs of healthy donors. They were not able to resorb bone, underlining a loss-of-function effect of the mutations. In summary, we developed a highly reproducible, straightforward hiPSC-osteoclast differentiation protocol. We demonstrated that osteoclasts differentiated from ARO hiPSCs can be used as a disease model for ARO and potentially also other osteoclast-related diseases. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Germline Saturation Mutagenesis Induces Skeletal Phenotypes in Mice
Authors: Rios Jonathan J , Denton Kristin , Russell Jamie , Kozlitina Julia , Ferreira Carlos R , Lewanda Amy F , Mayfield Joshua E , Moresco Eva , Ludwig Sara , Tang Miao , Li Xiaohong , Lyon Stephen , Khanshour Anas , Paria Nandina , Khalid Aysha , Li Yang , Xie Xudong , Feng Jian Q , Xu Qian , Lu Yongbo , Hammer Robert E , Wise Carol A , Beutler Bruce 
Published: April 2021

ABSTRACT
Proper embryonic and postnatal skeletal development require coordination of myriad complex molecular mechanisms. Disruption of these processes, through genetic mutation, contributes to variation in skeletal development. We developed a high-throughput N-ethyl-N-nitrosourea (ENU)-induced saturation mutagenesis skeletal screening approach in mice to identify genes required for proper skeletal development. Here, we report initial results from live-animal X-ray and dual-energy X-ray absorptiometry (DXA) imaging of 27,607 G3 mice from 806 pedigrees, testing the effects of 32,198 coding/splicing mutations in 13,020 genes. A total of 39.7% of all autosomal genes were severely damaged or destroyed by mutations tested twice or more in the homozygous state. Results from our study demonstrate the feasibility of in vivo mutagenesis to identify mouse models of skeletal disease. Furthermore, our study demonstrates how ENU mutagenesis provides opportunities to create and characterize putative hypomorphic mutations in developmentally essential genes. Finally, we present a viable mouse model and case report of recessive skeletal disease caused by mutations in FAM20B. Results from this study, including engineered mouse models, are made publicly available via the online Mutagenetix database. © 2021 American Society for Bone and Mineral Research (ASBMR).
Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent
Authors: Nguyen Ashley , Chow Diana S‐L. , Wu Lei , Teng Yang (Angela) , Sarkar Mahua , Toups Elizabeth G. , Harrop James S. , Schmitt Karl M. , Johnson Michele M. , Guest James D. , Aarabi Bizhan , Shaffrey Christopher I. , Boakye Maxwell , Frankowski Ralph F. , Fehlings Michael G. , Grossman Robert G. 
Published: April 2021

AbstractRiluzole, a benzothiazole sodium channel blocker that received US Food and Drug Administration approval to attenuate neurodegeneration in amyotrophic lateral sclerosis in 1995, was found to be safe and potentially efficacious in a spinal cord injury (SCI) population, as evident in a phase I clinical trial. The acute and progressive nature of traumatic SCI and the complexity of secondary injury processes can alter the pharmacokinetics of therapeutics. A 1‐compartment with first‐order elimination population pharmacokinetic model for riluzole incorporating time‐dependent clearance and volume of distribution was developed from combined data of the phase 1 and the ongoing phase 2/3 trials. This change in therapeutic exposure may lead to a biased estimate of the exposure‐response relationship when evaluating therapeutic effects. With the developed model, a rational, optimal dosing scheme can be designed with time‐dependent modification that preserves the required therapeutic exposure of riluzole.
Pharmacological Predictors of Morbidity and Mortality in COVID‐19
Authors: Oddy Christopher , McCaul James , Keeling Polly , Allington Jonathan , Senn Dhanuja , Soni Neesha , Morrison Hannah , Mawella Ruwani , Samuel Thomas , Dixon John 
Published: April 2021

AbstractThe interaction of coronavirus disease (COVID‐19) with the majority of common prescriptions is broadly unknown. The purpose of this study is to identify medications associated with altered disease outcomes in COVID‐19. A retrospective cohort composed of all adult inpatient admissions to our center with COVID‐19 was analyzed. Data concerning all antecedent prescriptions were collected and agents brought forward for analysis if prescribed to at least 20 patients in our cohort. Forty‐two medications and 22 classes of medication were examined. Groups were propensity score matched and analyzed by logistic and linear regression. The majority of medications did not show a statistically significant relationship with altered disease outcomes. Lower mortality was associated with use of pregabalin (hazard ratio [HR], 0.10; 95% confidence interval [CI], 0.01‐0.92; P = .049) and inhalers of any type (HR, 0.33; 95%CI, 0.14‐0.80; P = .015), specifically beclomethasone (HR, 0.10; 95%CI, 0.01‐0.82; P = .032), tiotropium (HR, 0.07; 95%CI, 0.01‐0.83; P = .035), and steroid‐containing inhalers (HR, 0.35; 95%CI, 0.15‐0.79; P = .013). Gliclazide (HR, 4.37; 95%CI, 1.26‐15.18; P = .020) and proton pump inhibitor (HR, 1.72; 95%CI, 1.06‐2.79; P = .028) use was associated with greater mortality. Diuretic (HR, 0.07; 95%CI, 0.01‐0.37; P = .002) and statin (HR, 0.35; 95%CI, 0.17‐0.73; P = .006) use was associated with lower rates of critical care admission. Our data lends confidence to observing usual practice in patients with COVID‐19 by continuing antecedent prescriptions in the absence of an alternative acute contraindication. We highlight potential benefits in investigation of diuretics, inhalers, pregabalin, and statins as therapeutic agents for COVID‐19 and support further assessment of the safety of gliclazide and proton pump inhibitors in the acute illness.
Relationship Between Apparent Systemic Clearance of Vemurafenib and Toxicity in Patients With Melanoma
Authors: Kichenadasse Ganessan , Hughes Jim Henry , Fahmy Alia , Rowland Andrew , Sorich Michael J. , Hopkins Ashley H. 
Published: April 2021

AbstractVemurafenib, a B rapidly accelerated fibrosarcoma inhibitor, is commonly used in combination of cobimetinib for the treatment of melanoma. In the current study, we evaluated the relationship between vemurafenib exposure, as measured by the estimated apparent clearance (CLB) at steady state and any grade ≥3 toxicity, grade ≥3 skin rash, or toxicity requiring dose modification using pooled data from 3 prospective clinical trials involving 898 patients. A total of 69% had any grade ≥3 toxicity; grade ≥3 skin rash in 15% and 47% had a dose reduction/interruption or cessation. The median vemurafenib CLB was 1.35 L/h (interquartile range, 1.15‐1.65 L/h). Lower vemurafenib CLB was significantly associated with an increased risk of grade ≥3 toxicity (hazard ratio [HR], 0.62; P < .001), grade ≥3 rash (HR, 0.29; P < .001), and adverse events requiring vemurafenib dose reduction/interruption or cessation (HR, 0.5; P < .001). When the patients were divided into 3 groups based on the vemurafenib CLB thresholds, those with low CLB (<1.22 L/h) had significantly increased incidence of any grade ≥3 toxicity or skin rash or dose adjustment, interruption, or cessation at 12 months and at day 28 when compared to those with medium (≥1.22 and <1.55 L/h) or high (>1.55 L/h) vemurafenib CLB. In conclusion, the estimated CLB of vemurafenib is associated with severe toxicities and dose adjustment or cessation, suggesting that an early estimation of vemurafenib exposure may be useful in identifying patients at risk of experiencing toxicity.
Evaluation of heavy metals effects on morpho‐anatomical alterations of wheat (Triticum aestivum L.) seedlings
Authors: Nazir Abdul , Rafique Faiza , Ahmed Khalid , Khan Sabaz Ali , Khan Nadeem , Akbar Muhammad , Zafar Muhammad 
Published: April 2021

AbstractThe present study aimed to evaluate the effects of Cd and Cr as separate and in combinations in hydroponically grown seedlings of FA‐08 and SH‐13 cultivars of wheat (Triticum aestivum L.). The concentrations of heavy metals were higher in the root as compared to shoot and were more pronounced in SH‐13 than FA‐08 cultivar. The decrease in the seedling length and biomass was observed when the metals were applied in combined form (Cd–Cr 80–120, Cd–Cr 100–120, Cr–Cd 140–80, and Cr–Cd 140–100). There were more declines in root length in the cultivar SH‐13 as compared to the shoot length, as the concentration of HMs increased. The root at level Cr‐140 and shoot at level Cd‐100 showed more reduction in SH‐13 than FA‐08. The high concentration of Cd and Cr affected the root epidermis, the cortical cells, and the xylem vessel. The size and number of stomata, length of long cells and short cells, and trichome were reduced at the concentration Cd‐100 and Cr‐140. The present study showed that the higher concentration of Cd and Cr affects the morpho‐anatomical features of both selected wheat cultivar moderately.
Analysis of adsorption energy distribution in selected hydrophilic‐interaction chromatography systems with amide, amine, and zwitterionic stationary phases
Authors: Ziobrowski Piotr , Chutkowski Marcin , Przywara Mateusz , Zapała Lidia , Kosińska‐Pezda Małgorzata , Zapała Wojciech 
Published: April 2021

AbstractAdsorption mechanisms of caffeine, quercetin, and phenol as test substances in various chromatographic systems have been analyzed. The investigations were conducted using three different chromatographic columns packed with polar bonded stationary phases, that is, amide, amine, and zwitterionic. Methanol–water and acetonitrile–water systems with different organic solvent contents have been used as mobile phases. On the basis of adsorption isotherms obtained for the tested systems, Scatchard plots and adsorption energy distributions have been determined. The most likely retention mechanisms have been discussed. The results of investigations indicate that (i) the surfaces of tested adsorbents are energetically heterogeneous, and (ii) the main role in sorption mechanism is played by low‐energy sites.
In Situ Synthesis of Incompatible Polymers within Hollow Porous Organic Nanosphere Networks for Cascade Reactions
Authors: Zhang Li , Yu Haitao , Gao Shengguang , Wang Huaqing , He Zhiwei , Huang Kun 
Published: April 2021

AbstractIn the paper, the novel hollow porous organic nanosphere networks (H‐PONNs) with remaining Z‐type chain transfer agent (CTA) inside the cavity are synthesized via a hypercrosslinking mediated self‐assembly method using the polystyrene‐b‐polylactide as precursors. The resultant Z‐type CTA functionalized H‐PONNs can be utilized to mediate reversible addition‐fragmentation chain transfer polymerization and the acidic or basic monomer (phenyl 4‐vinylbenzene sulfonate (PVBS) , 4‐N‐(4‐vinylbenzyl)‐N‐methylaminopyridine (VBMAP)) can be in situ polymerized in the cavity of nanospheres to produce acid/base‐functionalized hollow porous organic nanosphere networks (poly(phenyl 4‐vinylbenzene sulfonate) (PPVBS)/H‐PONNs and poly(4‐N‐(4‐vinylbenzyl)‐N‐methylaminopyridine) (PVBMAP)/H‐PONNs). These PPVBS/H‐PONNs and PVBMAP/H‐PONNs possess the large surface area, hierarchically porous structure, and robust organic framework, which exhibit the excellent catalytic performance for acid–base cascade reactions. Furthermore, the turnover frequency is up to 51 h−1 that shows the catalysts have a great advantage over other similar materials for one‐pot reactions.