bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammation and neutrophil extracellular traps in cerebral cavernous malformation
Authors: Yau Anthony C. Y. , Globisch Maria Ascencion , Onyeogaziri Favour Chinyere , Conze Lei L. , Smith Ross , Jauhiainen Suvi , Corada Monica , Orsenigo Fabrizio , Huang Hua , Herre Melanie , Olsson Anna-Karin , Malinverno Matteo , Sundell Veronica , Rezai Jahromi Behnam , Niemelä Mika , Laakso Aki , Garlanda Cecilia , Mantovani Alberto , Lampugnani Maria Grazia , Dejana Elisabetta , Magnusson Peetra U. 
Published: March 2022

AbstractCerebral Cavernous Malformation (CCM) is a brain vascular disease with various neurological symptoms. In this study, we describe the inflammatory profile in CCM and show for the first time the formation of neutrophil extracellular traps (NETs) in rodents and humans with CCM. Through RNA-seq analysis of cerebellum endothelial cells from wild-type mice and mice with an endothelial cell-specific ablation of the Ccm3 gene (Ccm3iECKO), we show that endothelial cells from Ccm3iECKO mice have an increased expression of inflammation-related genes. These genes encode proinflammatory cytokines and chemokines, as well as adhesion molecules, which promote recruitment of inflammatory and immune cells. Similarly, immunoassays showed elevated levels of these cytokines and chemokines in the cerebellum of the Ccm3iECKO mice. Consistently, both flow cytometry and immunofluorescence analysis showed infiltration of different subsets of leukocytes into the CCM lesions. Neutrophils, which are known to fight against infection through different strategies, including the formation of NETs, represented the leukocyte subset within the most pronounced increase in CCM. Here, we detected elevated levels of NETs in the blood and the deposition of NETs in the cerebral cavernomas of Ccm3iECKO mice. Degradation of NETs by DNase I treatment improved the vascular barrier. The deposition of NETs in the cavernomas of patients with CCM confirms the clinical relevance of NETs in CCM.
Heterogeneous b-value Distributions Measured Over an Extensive Region from the Northern Okinawa Trough to Southern Kyushu Island, Japan
Authors: Chiba Keita 
Published: March 2022

AbstractSpatiotemporal b-value maps are presented for an extensive region from the northern Okinawa trough to off southern Kyushu Island, Japan. This region shows high seismic activity associated with a tectonic setting characterized by seafloor spreading caused by the opening of a back-arc basin in the Ryukyu arc–trench system and the presence of a left-lateral shear zone on southern Kyushu Island. The obtained spatial and temporal distributions of b-value for the analyzed period are highly heterogeneous, reflecting the influence of the tectonic features and processes of the region. A comparison of the results with other geophysical observations suggests deep fluids associated with mantle upwelling below the seismogenic layer are the dominant control on the observed b-value variations. In addition, the hypocentral area of the largest earthquake (M7.1), which occurred in 2015, corresponds approximately to a region with low b-values (b = 0.5–0.7). Another region with low b-values (b = 0.5–0.7) occurs in the west of the analyzed region off southern Kyushu Island, where the occurrence of large-magnitude events is not clearly recognized. During the analysis period, there were few moderate to large earthquakes in the analyzed region. Furthermore, some active faults that have the potential to generate large earthquakes of ~ M7 are located in those parts of the analyzed region with low b-values. These findings suggest a high likelihood of nucleation of large earthquakes in the focal region.
Pipkin fractures: epidemiology and outcome
Authors: Enocson Anders , Wolf Olof 
Published: March 2022

Abstract
Purpose
To describe the epidemiology of Pipkin fractures including detailed fracture classification and outcome for joint preservation and death.

Methods
We extracted data on all Pipkin fractures in the Swedish Fracture Register from 2013 to 2020 in patients ≥ 18 years. The cohort was cross-matched with the Swedish Hip Arthroplasty Register to obtain data on primary or secondary treatment with arthroplasty. We analysed data on age, sex, injury mechanism, fracture classification, treatment including secondary operative treatment with arthroplasty and mortality. Primary outcome was joint preservation.

Results
In total 47 Pipkin fractures with a median age of 48 years were included. 74% of the fractures were in males. The median follow-up time was 3.5 years. The most common primary treatment was internal fixation (45%), followed by primary arthroplasty (28%), and excision of fragment (15%). Three of the 34 patients with primary non arthroplasty treatment received secondary treatment with arthroplasty. Two patients died within 30 days, and no further deaths occurred up to 1 year after injury.

Conclusion
Three of four fractures occurred in males and more than half of the fractures were due to high energetic injuries. Half of the patients received internal fixation (predominantly younger patients) and 28% were treated with primary arthroplasty (predominantly older patients). The revision rate was low, and after secondary treatment with arthroplasty two thirds of the patients still had a preserved joint.
Patient-specific risk factors for adverse outcomes following geriatric proximal femur fractures
Authors: Becker Nils , Hafner Tobias , Pishnamaz Miguel , Hildebrand Frank , Kobbe Philipp 
Published: March 2022

Abstract
Background
Proximal femur fractures (PFFs) occur frequently among geriatric patients due to diverse risk factors, such as a lower bone mineral density and the increased risk of falls.

Methods
In this review, we focus on recent literature of patient-specific risk factors and their impact on common complications and outcome parameters in patients with PFF.

Results
Patient- and treatment related factors have a significant impact on outcome and are associated with an increased risk of mortality, impairments in functional rehabilitation and complicative courses.

Conclusion
Geriatric patients at high risk for complications are nursing home inhabitants suffering from severe osteoporosis, dementia and sarcopenia. The early and ongoing assessment for these individual risk factors is crucial. Strategies including interdisciplinary approaches, addressing comorbidities and facilitating an optimal risk factor evaluation result in a beneficial outcome. The ongoing ambulant assessment and therapy of complicating factors (e.g., malnutrition, sarcopenia, frailty or osteoporosis) have to be improved.
Controlling the familywise error rate when performing multiple comparisons in a linear latent variable model
Authors: Ozenne Brice , Budtz-Jørgensen Esben , Ebert Sebastian Elgaard 
Published: March 2022

AbstractIn latent variable models (LVMs) it is possible to analyze multiple outcomes and to relate them to several explanatory variables. In this context many parameters are estimated and it is common to perform multiple tests, e.g. to investigate outcome-specific effects using Wald tests or to check the correct specification of the modeled mean and variance using a forward stepwise selection (FSS) procedure based on Score tests. Controlling the family-wise error rate (FWER) at its nominal level involves adjustment of the p-values for multiple testing. Because of the correlation between test statistics, the Bonferroni procedure is often too conservative. In this article, we extend the max-test procedure to the LVM framework for Wald and Score tests. Depending on the correlation between the test statistics, the max-test procedure is equivalent or more powerful than the Bonferroni procedure while also providing, asymptotically, a strong control of the FWER for non-iterative procedures. Using simulation studies, we assess the finite sample behavior of the max-test procedure for Wald and Score tests in LVMs. We apply our procedure to quantify the neuroinflammatory response to mild traumatic brain injury in nine brain regions.
A dictionary learning add-on for spherical downward continuation
Authors: Schneider N. , Michel V. 
Published: March 2022

AbstractWe propose a novel dictionary learning add-on for the Inverse Problem Matching Pursuit (IPMP) algorithms for approximating spherical inverse problems such as the downward continuation of the gravitational potential. With the add-on, we aim to automatize the choice of dictionary and simultaneously reduce the computational costs. The IPMP algorithms iteratively minimize the Tikhonov–Phillips functional in order to construct a weighted linear combination of so-called dictionary elements as a regularized approximation. A dictionary is an intentionally redundant set of trial functions such as spherical harmonics (SHs), Slepian functions (SLs) as well as radial basis functions (RBFs) and wavelets (RBWs). In previous works, this dictionary was chosen manually which resulted in high runtimes and storage demand. Moreover, a possible bias could also not be ruled out. The additional learning technique we present here allows us to work with infinitely many trial functions while reducing the computational costs. This approach may enable a quantification of a possible bias in future research. We explain the general mechanism and provide numerical results that prove its applicability and efficiency.
Theory, strict formula derivation and algorithm development for the computation of a geodesic polygon area
Authors: Nowak Edward , Nowak Da Costa Joanna 
Published: March 2022

AbstractThe paper presents a coherent, original theory and an effective algorithm to calculate the surface area of a geodesic polygon, i.e. the area on an ellipsoid of revolution limited by geodesics, connecting pairs of subsequent vertices of known geographical coordinates. Using the cylindrical coordinate system and introducing an equatorial geodesic triangle, the novel strict recursive formulas were derived for the longitude on the ellipsoid and the distance along the geodesic and the area of a geodesic polygon. The area is determined by constant coefficients, not the values of finite series. The orthodromic properties of geodesics, which led to the detection of bifurcation lines composed of the double solutions of the inverse geodetic problem were analysed. The novel algorithm presented, integrating the problem with geodesic polygon area calculation, is based on the newly proposed parameterisation with two alternative working unknowns and a new formula to obtain the initial value of the geodesic C parameter. It allows solutions for all cases, including near-antipodal or near-vertices, and offers two solutions if bifurcation occurs. The algorithm presented was tested and verified using numerical examples from known publications. The numerical tests proved the accuracy of 1m2 of the computed geodesic area using standard IEEE 754 Double Floating Point PC arithmetic, for geodesic lengths up to ten thousand km.
Toxicology and pharmacology of botulinum and tetanus neurotoxins: an update
Authors: Pirazzini Marco , Montecucco Cesare , Rossetto Ornella 
Published: March 2022

AbstractTetanus and botulinum neurotoxins cause the neuroparalytic syndromes of tetanus and botulism, respectively, by delivering inside different types of neurons, metalloproteases specifically cleaving the SNARE proteins that are essential for the release of neurotransmitters. Research on their mechanism of action is intensively carried out in order to devise improved therapies based on antibodies and chemical drugs. Recently, major results have been obtained with human monoclonal antibodies and with single chain antibodies that have allowed one to neutralize the metalloprotease activity of botulinum neurotoxin type A1 inside neurons. In addition, a method has been devised to induce a rapid molecular evolution of the metalloprotease domain of botulinum neurotoxin followed by selection driven to re-target the metalloprotease activity versus novel targets with respect to the SNARE proteins. At the same time, an intense and wide spectrum clinical research on novel therapeutics based on botulinum neurotoxins is carried out, which are also reviewed here.
Radiation modelling of arbitrary two-dimensional surfaces using the surface-to-surface approach extended with a blocking algorithm
Authors: Büschgens Dominik , Schubert Christian , Pfeifer Herbert 
Published: March 2022

AbstractCalculating the radiation exchange between arbitrary surfaces using view factors is a common practice in the fields of industrial furnaces, climate modelling, solar power, thermal building design and so on. Here, a new model was developed to calculate the view factors of arbitrary two-dimensional geometries. This model is based on Hottel’s crossed strings method paired with an optimized algorithm to efficiently detect shadowing effects between the surfaces. The model’s accuracy and discretization dependency was tested against an analytical view factor calculation method using an example of two concentric, infinitely extended cylinders. The model can be applied to arbitrary linear discretized two-dimensional geometries. In particular, it guarantees the highest possible accuracy within the chosen discretization. The need for developing customized view factor equations of different two-dimensional geometries is therefore no longer necessary, since the convergence of the model with decreasing mesh size on analytical results can be demonstrated. Additionally, the performance and validity of the newly developed shadowing algorithm was tested against a common brute force approach and significant speedups were achieved. Furthermore, the additional application of the net radiation method for the calculation of the heat fluxes exchanged by radiation within those geometries is shown.
Evolutionary Adjustment of tRNA Identity Rules in Bacillariophyta for Recognition by an Aminoacyl-tRNA Synthetase Adds a Facet to the Origin of Diatoms
Authors: Igloi Gabor L. 
Published: March 2022

AbstractError-free protein synthesis relies on the precise recognition by the aminoacyl-tRNA synthetases of their cognate tRNAs in order to attach the corresponding amino acid. A concept of universal tRNA identity elements requires the aminoacyl-tRNA synthetases provided by the genome of an organism to match the identity elements found in the cognate tRNAs in an evolution-independent manner. Identity elements tend to cluster in the tRNA anticodon and acceptor stem regions. However, in the arginine system, in addition to the anticodon, the importance of nucleotide A20 in the tRNA D-loop for cognate enzyme recognition has been a sustained feature for arginyl-tRNA synthetase in archaea, bacteria and in the nuclear-encoded cytosolic form in mammals and plants. However, nuclear-encoded mitochondrial arginyl-tRNA synthetase, which can be distinguished from its cytosolic form by the presence or absence of signature motifs, dispenses with the A20 requirement. An examination of several hundred non-metazoan organisms and their corresponding tRNAArg substrates has confirmed this general concept to a large extent and over numerous phyla. However, some Stramenopiles, and in particular, Diatoms (Bacillariophyta) present a notable exception. Unusually for non-fungal organisms, the nuclear genome encodes tRNAArg isoacceptors with C or U at position 20. In this case one of two nuclear-encoded cytosolic arginyl-tRNA synthetases has evolved to become insensitive to the nature of the D-loop identity element. The other, with a binding pocket that is compatible with tRNAArg-A20 recognition, is targeted to organelles that encode solely such tRNAs.
Risk-related short-term clinical outcomes after transcatheter aortic valve implantation and their impact on early mortality: an analysis of claims-based data from Germany
Authors: Schofer Niklas , Jeschke Elke , Kröger Janine , Baberg Henning , Falk Volkmar , Gummert Jan F. , Hamm Christian W. , Möckel Martin , Goßling Alina , Malzahn Jürgen , Günster Christian , Blankenberg Stefan 
Published: March 2022

Abstract
Objectives
We aimed to define and assess risk-specific adverse outcomes after transcatheter aortic valve implantation (TAVI) in an all-comers patient population based on German administrative claims data.

Methods
Administrative claims data of patients undergoing transvascular TAVI between 2017 and 2019 derived from the largest provider of statutory health-care insurance in Germany were used. Patients’ risk profile was assessed using the established Hospital Frailty Risk (HFR) score and 30-day adverse events were evaluated. Multivariable logistic regression models were applied to investigate the relation of patients’ risk factors to clinical outcomes and, subsequently, of clinical outcomes to mortality.

Results
A total of 21,430 patients were included in the analysis. Of those, 51% were categorized as low-, 37% as intermediate-, and 12% as high-risk TAVI patients according to HFR score. Whereas low-risk TAVI patients showed low rates of periprocedural adverse events, TAVI patients at intermediate or high risk suffered from worse outcomes. An increase in HFR score was associated with an increased risk for all adverse outcome measures. The strongest association of patients’ risk profile and outcome was present for cerebrovascular events and acute renal failure after TAVI. Independent of patients’ risk, the latter showed the strongest relation with early mortality after TAVI.

Conclusions
Differentiated outcomes after TAVI can be assessed using claims-based data and are highly dependent on patients’ risk profile. The present study might be of use to define risk-adjusted outcome margins for TAVI patients in Germany on the basis of health-insurance data.

Graphical abstract
Clusters of anatomical disease-burden patterns in ALS: a data-driven approach confirms radiological subtypes
Authors: Bede Peter , Murad Aizuri , Lope Jasmin , Hardiman Orla , Chang Kai Ming 
Published: March 2022

AbstractAmyotrophic lateral sclerosis (ALS) is associated with considerable clinical heterogeneity spanning from diverse disability profiles, differences in UMN/LMN involvement, divergent progression rates, to variability in frontotemporal dysfunction. A multitude of classification frameworks and staging systems have been proposed based on clinical and neuropsychological characteristics, but disease subtypes are seldom defined based on anatomical patterns of disease burden without a prior clinical stratification. A prospective research study was conducted with a uniform imaging protocol to ascertain disease subtypes based on preferential cerebral involvement. Fifteen brain regions were systematically evaluated in each participant based on a comprehensive panel of cortical, subcortical and white matter integrity metrics. Using min–max scaled composite regional integrity scores, a two-step cluster analysis was conducted. Two radiological clusters were identified; 35.5% of patients belonging to ‘Cluster 1’ and 64.5% of patients segregating to ‘Cluster 2’. Subjects in Cluster 1 exhibited marked frontotemporal change. Predictor ranking revealed the following hierarchy of anatomical regions in decreasing importance: superior lateral temporal, inferior frontal, superior frontal, parietal, limbic, mesial inferior temporal, peri-Sylvian, subcortical, long association fibres, commissural, occipital, ‘sensory’, ‘motor’, cerebellum, and brainstem. While the majority of imaging studies first stratify patients based on clinical criteria or genetic profiles to describe phenotype- and genotype-associated imaging signatures, a data-driven approach may identify distinct disease subtypes without a priori patient categorisation. Our study illustrates that large radiology datasets may be potentially utilised to uncover disease subtypes associated with unique genetic, clinical or prognostic profiles.
From open Ivor Lewis esophagectomy to a hybrid robotic-assisted thoracoscopic approach: a single-center experience over two decades
Authors: Angehrn Fiorenzo V. , Neuschütz Kerstin J. , Fourie Lana , Wilhelm Alexander , Däster Silvio , Ackermann Christoph , von Flüe Markus , Steinemann Daniel C. , Bolli Martin 
Published: March 2022

Abstract
Purpose
Robotic-assisted procedures are increasingly used in esophageal cancer surgery. We compared postoperative complications and early oncological outcomes following hybrid robotic-assisted thoracoscopic esophagectomy (Rob-E) and open Ivor Lewis esophagectomy (Open-E), performed in a single mid-volume center, in the context of evolving preoperative patient and tumor characteristics over two decades.

Methods
We evaluated prospectively collected data from a single center from 1999 to 2020 including 321 patients that underwent Ivor Lewis esophagectomy, 76 underwent Rob-E, and 245 Open-E. To compare perioperative outcomes, a 1:1 case-matched analysis was performed. Endpoints included postoperative morbidity and 30-day mortality.

Results
Preoperative characteristics revealed increased rates of adenocarcinomas and wider use of neoadjuvant treatment over time. A larger number of patients with higher ASA grades were operated with Rob-E. In case-matched cohorts, there were no differences in the overall morbidity (69.7% in Rob-E, 60.5% in Open-E, p value 0.307), highest Clavien-Dindo grade per patient (43.4% vs. 38.2% grade I or II, p value 0.321), comprehensive complication index (median 20.9 in both groups, p value 0.401), and 30-day mortality (2.6% in Rob-E, 3.9% in Open-E, p value 1.000). Similar median numbers of lymph nodes were harvested (24.5 in Rob-E, 23 in Open-E, p value 0.204), and comparable rates of R0-status (96.1% vs. 93.4%, p value 0.463) and distribution of postoperative UICC stages (overall p value 0.616) were observed.

Conclusions
Our study demonstrates similar postoperative complications and early oncological outcomes after Rob-E and Open-E. However, the selection criteria for Rob-E appeared to be less restrictive than those of Open-E surgery.