bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infantile‐onset CMT2D/dSMA‐V in a Chinese family with parental germline mosaicism for a novel mutation in the GARS1 gene
Authors: Huang Yufeng , Bi Bo , Zhao Peiwei , Yu Ting , Luo Sukun , Tan Li , Liu Zhisheng , Liu Jie , He Xuelian 
Published: December 2021

AbstractBackground and AimsBoth Charcot‐Marie‐Tooth disease type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA‐V) are GARS1 disease phenotypes involving axonal peripheral neuropathy. Patients often develop clinical symptoms in their teens. Herein, we reported a Chinese family with infantile‐onset CMT2D/dSMA‐V.MethodsClinical evaluation and laboratory examination were performed in our proband, the older sister from this family, and trio exome sequencing (ES) was conducted on the proband and her parents, followed by Sanger sequencing.ResultsA novel GARS1 mutation (c.997G>C, p.E333Q; NM_002047) was identified in this patient and her younger sister but not in her parents; thus, it is presumed that this mutation is inherited from a germline mosaic parent. The younger sister began to exhibit weakness of her hands and feet at the age of 1 year old.ConclusionThis is the first report of infantile CMT2D/dSMA‐V in China. Our study increases the number of infantile‐onset cases, as well as reported pathogenic variants in the GARS1 gene, and highlights the important role of exome sequencing in the clinical diagnosis of disease and enabling subsequent prenatal diagnosis. Our study reminds us to consider the possibility of parent germline mosaicism in the subsequent prenatal genetic diagnosis when identifying a de novo variant.
Technical note: The effect of image annotation with minimal manual interaction for semiautomatic prostate segmentation in CT images using fully convolutional neural networks
Authors: Shahedi Maysam , Dormer James D. , Halicek Martin , Fei Baowei 
Published: December 2021

AbstractPurposeThe goal is to study the performance improvement of a deep learning algorithm in three‐dimensional (3D) image segmentation through incorporating minimal user interaction into a fully convolutional neural network (CNN).MethodsA U‐Net CNN was trained and tested for 3D prostate segmentation in computed tomography (CT) images. To improve the segmentation accuracy, the CNN's input images were annotated with a set of border landmarks to supervise the network for segmenting the prostate. The network was trained and tested again with annotated images after 5, 10, 15, 20, or 30 landmark points were used.ResultsCompared to fully automatic segmentation, the Dice similarity coefficient increased up to 9% when 5–30 sparse landmark points were involved, with the segmentation accuracy improving as more border landmarks were used.ConclusionsWhen a limited number of sparse border landmarks are used on the input image, the CNN performance approaches the interexpert observer difference observed in manual segmentation.
T2 quantification in brain using 3D fast spin‐echo imaging with long echo trains
Authors: Snyder Jeff , McPhee Kelly C. , Wilman Alan H. 
Published: December 2021

AbstractPurposeThree‐dimensional fast spin‐echo (FSE) sequences commonly use very long echo trains (>64 echoes) and severely reduced refocusing angles. They are increasingly used in brain exams due to high, isotropic resolution and reasonable scan time when using long trains and short interecho spacing. In this study, T2 quantification in 3D FSE is investigated to achieve increased resolution when comparing with established 2D (proton‐density dual‐echo and multi‐echo spin‐echo) methods.MethodsThe FSE sequence design was explored to use long echo trains while minimizing T2 fitting error and maintaining typical proton density and T2‐weighted contrasts. Constant and variable flip angle trains were investigated using extended phase graph and Bloch equation simulations. Optimized parameters were analyzed in phantom experiments and validated in vivo in comparison to 2D methods for eight regions of interest in brain, including deep gray‐matter structures and white‐matter tracts.ResultsPhantom and healthy in vivo brain T2 measurements showed that optimized variable echo‐train 3D FSE performs similarly to previous 2D methods, while achieving three‐fold‐higher slice resolution, evident visually in the 3D T2 maps. Optimization resulted in better T2 fitting and compared well with standard multi‐echo spin echo (within the 8‐ms confidence limits defined based on Bland‐Altman analysis).ConclusionT2 mapping using 3D FSE with long echo trains and variable refocusing angles provides T2 accuracy in agreement with 2D methods with additional high‐resolution benefits, allowing isotropic views while avoiding incidental magnetization transfer effects. Consequently, optimized 3D sequences should be considered when choosing T2 mapping methods for high anatomic detail.
Diagnostic and predictive analysis of production and injection‐induced fault activation
Authors: Zhao Xiaoxi , Jha Birendra 
Published: December 2021

AbstractMitigating the hazard of fault reactivation during CO injection and oil production is important for ensuring environmental sustainability of geologic carbon sequestration and hydrocarbon recovery. Currently, we do not know how the Coulomb Failure Stress (CFS), which is a commonly used metric to assess the potential of inducing slip on a fault, evolves differently for gas injection and oil production scenarios. Using high‐resolution simulations of CO injection‐induced and oil production‐induced fault slip and theories of Coulomb failure and poroelasticity, we address this gap in knowledge. We analyze the fault tractions, slip, and reservoir pressure to understand how a fault is destabilized in successive steps, how hypocenter locations are selected, and how these processes differ between injection and production. We extract and summarize the characteristic features of induced fault activation in terms of the dependence of CFS and the Fault Stress Ratio (FSR) on the dimensionless reservoir pressure perturbation caused by injection or production. We apply the framework to the Farnsworth oilfield in Texas, which is undergoing CO injection and oil production, to disambiguate observations related to fault stability. Finally, we discuss how our framework can inform models that aim to forecast fluid flow‐induced slip and mitigate the induced seismicity hazard in oilfields and gas storage sites.
Use of a motion‐based digital therapeutic in women with fecal incontinence: A pilot study
Authors: Weinstein Milena M. , Pulliam Samantha J. , Keyser Laura , Richter Holly E. 
Published: December 2021

AbstractAimsThere is limited data addressing the value of vaginal biofeedback (VBF) on fecal incontinence (FI) symptoms. The objective of this pilot study was to evaluate whether use of a motion‐based VBF device and app was effective for at‐home treatment of women with FI. We hypothesized that VBF would result in improvement in FI symptoms.MethodsA single‐arm 10‐week prospective pilot trial in women with FI was conducted using the VBF device. The primary outcome was change in St. Mark's score from baseline to week 10. Secondary outcomes included change in 2‐week bowel diary and FI quality of life (FIQoL). Statistical analysis included paired t test and Wilcoxon's signed‐rank test.ResultsOf 29 enrolled women, 27 had data available for analysis. Mean (±SD) age was 60.9 (±14.4). 63% (17) subjects were White, 33% (9) were Black. Mean St. Mark's score was 14.6 (±4.4) at baseline and 11.6 (±5.1) at 10‐weeks (p = 0.005). Changes in the total FIQol, and three of four subsets of the FIQoL scores were also significantly improved (p < 0.001). Bowel diary showed decrease in FI episodes, baseline 8.4 (±8.73) to 10 weeks 4.8 (±3.79), (p = 0.052).ConclusionsIn this pilot study, there was significant improvement in FI symptom‐specific severity and quality of life using a vaginal, motion‐based device for biofeedback. A larger study is needed to better understand the value of this device, which may be useful for women who prefer a vaginal device, which can be utilized at home compared with standard anal biofeedback for treatment of FI in the clinical setting.
Multiple‐GPU parallelization of three‐dimensional material point method based on single‐root complex
Authors: Dong Youkou , Cui Lan , Zhang Xue 
Published: December 2021

AbstractAs one of the arbitrary Lagrangian–Eulerian methods, the material point method (MPM) owns intrinsic advantages in simulation of large deformation problems by combining the merits of the Lagrangian and Eulerian approaches. Significant computational intensity is involved in the calculations of the MPM due to its very fine mesh needed to achieve a sufficiently high accuracy. A new multiple‐GPU parallel strategy is developed based on a single‐root complex architecture of the computer purely within a CUDA environment. Peer‐to‐Peer (P2P) communication between the GPUs is performed to exchange the information of the crossing particles and ghost element nodes, which is faster than the heavy send/receive operations between different computers through the infiniBand network. Domain decomposition is performed to split the whole computational task over the GPUs with a number of subdomains. The computations within each subdomain are allocated on a corresponding GPU using an enhanced “Particle‐List” scheme to tackle the data race during the interpolation from associated particles to common nodes. The acceleration effect of the parallelization is evaluated with two benchmarks cases, mini‐slump test after a dam break and cone penetration test in clay, where the maximum speedups with 1 and 8 GPUs are 88 and 604, respectively.
Initiation of quarterly palmitate paliperidone in French clinical practice: Results from the observational, cross‐sectional OPTIMUS study
Authors: Gary Charlotte , Déal Cécile , Boursicot‐Beuzelin Jennifer , Falissard Bruno , Giordana Jean‐Yves , Fakra Eric , Samalin Ludovic , Bouju Sophie 
Published: December 2021

AbstractPurposeLong‐term antipsychotic treatment is key to a positive clinical outcome in schizophrenia. Recent guidelines recommend the prescription of long‐acting antipsychotic formulations (LAIs) as early as the first episode in patients with schizophrenia. The OPTIMUS study evaluated real‐world use of a new three‐monthly paliperidone palmitate formulation (PP3M) in France.MethodsFor this observational cross‐sectional study, all French psychiatrists were invited to enrol patients who had initiated PP3M in the previous 4 months. Snapshot data were collected at a routine consultation, without any modification of clinical practice.ResultsThis population of 350 patients with schizophrenia started on PP3M predominantly included single men, living independently with a diagnosis of schizophrenia for a median of 9.3 years. Demographic characteristics were broadly comparable to those reported in other studies on LAIs. Investigators cited treatment simplification (96.9%) and patient comfort (93.3%) as the most common reasons for switching to PP3M; enhancing adherence was mentioned less often (61.1%) with most patients previously considered as adherent, and a majority of them expressing a positive attitude to their treatment. One‐third of patients accepted the psychiatrist's proposal to initiate PP3M treatment without any discussion, and relatives were involved in the therapeutic decision‐making process in only 23.7% of cases. After initiation, few changes were seen in professional follow‐up frequency or concomitant pharmacological and non‐pharmacological treatment modalities except for a decrease in antipsychotic polytherapy.ConclusionsPP3M is mostly prescribed in adherent patients with fairly stable schizophrenia, and the longer dosing interval does not substantially affect patient care.
Activity and substrate specificity of lytic polysaccharide monooxygenases: An ATR FTIR‐based sensitive assay tested on a novel species from Pseudomonas putida
Authors: Serra Ilenia , Piccinini Daniele , Paradisi Alessandro , Ciano Luisa , Bellei Marzia , Bortolotti Carlo Augusto , Battistuzzi Gianantonio , Sola Marco , Walton Paul H. , Di Rocco Giulia 
Published: December 2021

AbstractPseudomonas putida W619 is a soil Gram‐negative bacterium commonly used in environmental studies thanks to its ability in degrading many aromatic compounds. Its genome contains several putative carbohydrate‐active enzymes such as glycoside hydrolases and lytic polysaccharide monooxygenases (PMOs). In this study, we have heterologously produced in Escherichia coli and characterized a new enzyme belonging to the AA10 family, named PpAA10 (Uniprot: B1J2U9), which contains a chitin‐binding type‐4 module and showed activity toward β‐chitin. The active form of the enzyme was produced in E. coli exploiting the addition of a cleavable N‐terminal His tag which ensured the presence of the copper‐coordinating His as the first residue. Electron paramagnetic resonance spectroscopy showed signal signatures similar to those observed for the copper‐binding site of chitin‐cleaving PMOs. The protein was used to develop a versatile, highly sensitive, cost‐effective and easy‐to‐apply method to detect PMO's activity exploiting attenuated total reflection‐Fourier transform infrared spectroscopy and able to easily discriminate between different substrates.
The Ca2+ response of a smart forisome protein is dependent on polymerization
Authors: Rose Judith , Brand Izabella , Bilstein‐Schloemer Merle , Jachimska Barbara , Twyman Richard M. , Prüfer Dirk , Noll Gundula A. 
Published: December 2021

AbstractForisomes are giant self‐assembling mechanoproteins that undergo reversible structural changes in response to Ca2+ and various other stimuli. Artificial forisomes assembled from the monomer MtSEO‐F1 can be used as smart biomaterials, but the molecular basis of their functionality is not understood. To determine the role of protein polymerization in forisome activity, we tested the Ca2+ association of MtSEO‐F1 dimers (the basic polymerization unit) by circular dichroism spectroscopy and microscale thermophoresis. We found that soluble MtSEO‐F1 dimers neither associate with Ca2+ nor undergo structural changes. However, polarization modulation infrared reflection absorption spectroscopy revealed that aggregated MtSEO‐F1 dimers and fully‐assembled forisomes associate with Ca2+, allowing the hydration of poorly‐hydrated protein areas. A change in the signal profile of complete forisomes indicated that Ca2+ interacts with negatively‐charged regions in the protein complexes that only become available during aggregation. We conclude that aggregation is required to establish the Ca2+ response of forisome polymers.
The performance of filtered leapfrog schemes in benchmark simulations
Authors: Williams Paul D. , Straka Jerry M. , Kanak Katharine M. 
Published: December 2021

AbstractThe stabilisation of the leapfrog time‐stepping scheme provided by the Robert–Asselin filter has enabled decades of atmospheric and oceanic research and weather and climate predictions. The unfortunate concomitant reduction from second‐order accuracy to first‐order accuracy inflicted by the filter has recently ushered in a new generation of leapfrog time filters that preserve the second‐order accuracy, including the Robert–Asselin–Williams (RAW) filter and its variants. These modern filtered leapfrog schemes have previously been shown to improve numerical simulations made using both simple conceptual models and comprehensive general circulation models. However, their performance in standard benchmark experiments has not previously been assessed. Here we evaluate these filtered leapfrog schemes in four classic benchmark experiments: linear scalar advection; a nonlinear density current in the quasi‐compressible equations; a nonlinear rising warm bubble in the fully compressible equations; and the linked behaviour of nonlinear twin tropical cyclones in the rotating shallow‐water equations. For a given time‐step size, the filtered leapfrog schemes are found to compare favourably with the third‐order Runge–Kutta (RK3) scheme. They are also less computationally expensive than RK3, at roughly one‐third to one‐half the cost per time step. For a given computational expenditure, the filtered leapfrog schemes are found to produce smaller errors with respect to the analytical solution (where available) than RK3. Furthermore, the filtered leapfrog schemes are found to be numerically stable, even when the discretisation method splits the slow advection and diffusion modes from the fast acoustic and gravity‐wave modes. Given that implementing filter upgrades requires only minimally invasive changes to an existing computer code, our results provide support for the continued use of filtered leapfrog schemes in atmosphere and ocean models.
Problemstellung
Authors: Jendreck Annekatrin 
Published: December 2021

ZusammenfassungDie Standardsetzung der International Financial Reporting Standards (IFRS) ist durch einen stetigen Wandel gekennzeichnet, der sich unlängst in der Veröffentlichung neuer Rechnungslegungsregeln, etwa zur Bilanzierung von Umsatzerlösen in IFRS 15 Erlöse aus Verträgen mit Kunden in 2014, zur Leasingbilanzierung in IFRS 16 Leasingverhältnisse in 2016 und zur bilanziellen Erfassung von Versicherungsprodukten in IFRS 17 Versicherungsverträge in 2017, sowie in verschiedenen aktuellen Standardsetzungsaktivitäten, wie bspw. dem Primary-Financial-Statements-Projekt, widerspiegelt.
Standardsetzung als rekursiver Prozess
Authors: Jendreck Annekatrin 
Published: December 2021

ZusammenfassungZur Beurteilung des Einflusses der Rechnungslegungspraxis auf die Entstehung von Rechnungslegungsvorschriften bedarf es zunächst einer Auseinandersetzung mit der Rechtsnatur von Bilanzierungsnormen sowie der Frage nach der Normermittlung. Als Erklärungsansätze für die Entwicklung von Rechnungslegungsvorschriften werden zunächst die deduktive und induktive Normermittlungstheorie herangezogen. Anschließend wird der Due Process unter Zuhilfenahme der hermeneutischen Methode als diskursiver Normermittlungsprozess betrachtet.
Analyse des Standardsetzungsprozesses von IFRS 15 anhand von Unternehmensstellungnahmen und Standarddokumenten
Authors: Jendreck Annekatrin 
Published: December 2021

ZusammenfassungFür die Analyse des Einflusses von Unternehmen sowie dem IASB auf die Entwicklung von Rechnungslegungsvorschriften bedarf es einer Prozessbetrachtung, die Aufschluss über den Zusammenhang zwischen dem Entscheidungsprozess – in Form der Begründbarkeit verschiedener Bilanzierungsalternativen und ihrer Umsetzungsmöglichkeiten – sowie dem finalen Standardergebnis ermöglicht. Im Gegensatz zu anderen Forschungsbeiträgen werden hierzu nicht kausale Zusammenhänge der Interessenabwägung, sondern der Standardsetzungsprozess als diskursive Auseinandersetzung untersucht.
Prospects for Development of Induced Pluripotent Stem Cell-Derived CAR-Targeted Immunotherapies
Authors: Mazza Roberta , Maher John 
Published: December 2021

AbstractTechnologies required to generate induced pluripotent stem cells (iPSC) were first described 15 years ago, providing a strong impetus to the field of regenerative medicine. In parallel, immunotherapy has finally emerged as a clinically meaningful modality of cancer therapy. In particular, impressive efficacy has been achieved in patients with selected haematological malignancies using ex vivo expanded autologous T cells engineered to express chimeric antigen receptors (CARs). While solid tumours account for over 90% of human cancer, they currently are largely refractory to this therapeutic approach. Nonetheless, given the considerable innovation taking place worldwide in the CAR field, it is likely that effective solutions for common solid tumours will emerge in the near future. Such a development will create significant new challenges in the scalable delivery of these complex, costly and individualised therapies. CAR-engineered immune cell products that originate from iPSCs offer the potential to generate unlimited numbers of homogeneous, standardised cell products in which multiple defined gene modification events have been introduced to ensure safety, potency and reproducibility. Here, we review some of the emerging strategies in use to engineer CAR-expressing iPSC-derived drug products.
Relaxation of the Boussinesq system and applications to the Rayleigh–Taylor instability
Authors: Gebhard Björn , Kolumbán József J. 
Published: December 2021

AbstractWe consider the evolution of two incompressible fluids with homogeneous densities $$\rho _{-}<\rho _+$$

ρ
-

<

ρ
+

subject to gravity described by the inviscid Boussinesq equations and provide the explicit relaxation of the associated differential inclusion. The existence of a subsolution to the relaxation allows one to conclude the existence of turbulently mixing solutions to the original Boussinesq system. As a specific application we investigate subsolutions emanating from the classical Rayleigh-Taylor initial configuration where the two fluids are separated by a horizontal interface with the heavier fluid being on top of the lighter. It turns out that among all self-similar subsolutions the criterion of maximal initial energy dissipation selects a linear density profile and a quadratic growth of the mixing zone. The subsolution selected this way can be extended in an admissible way to exist for all times. We provide two possible extensions with different long-time limits. The first one corresponds to a total mixture of the two fluids, the second corresponds to a full separation with the lighter fluid on top of the heavier. There is no motion in either of the limit states.
Penalized wavelet estimation and robust denoising for irregular spaced data
Authors: Amato Umberto , Antoniadis Anestis , De Feis Italia , Gijbels Irène 
Published: December 2021

AbstractNonparametric univariate regression via wavelets is usually implemented under the assumptions of dyadic sample size, equally spaced fixed sample points, and i.i.d. normal errors. In this work, we propose, study and compare some wavelet based nonparametric estimation methods designed to recover a one-dimensional regression function for data that not necessary possess the above requirements. These methods use appropriate regularizations by penalizing the decomposition of the unknown regression function on a wavelet basis of functions evaluated on the sampling design. Exploiting the sparsity of wavelet decompositions for signals belonging to homogeneous Besov spaces, we use some efficient proximal gradient descent algorithms, available in recent literature, for computing the estimates with fast computation times. Our wavelet based procedures, in both the standard and the robust regression case have favorable theoretical properties, thanks in large part to the separability nature of the (non convex) regularization they are based on. We establish asymptotic global optimal rates of convergence under weak conditions. It is known that such rates are, in general, unattainable by smoothing splines or other linear nonparametric smoothers. Lastly, we present several experiments to examine the empirical performance of our procedures and their comparisons with other proposals available in the literature. An interesting regression analysis of some real data applications using these procedures unambiguously demonstrate their effectiveness.