bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor DNA‐methylome derived epigenetic fingerprint identifies HPV‐negative head and neck patients at risk for locoregional recurrence after postoperative radiochemotherapy
Authors: Tawk Bouchra , Wirkner Ute , Schwager Christian , Rein Katrin , Zaoui Karim , Federspil Philippe A. , Adeberg Sebastian , Linge Annett , Ganswindt Ute , Hess Julia , Unger Kristian , Tinhofer Ingeborg , Budach Volker , Lohaus Fabian , Krause Mechthild , Guberina Maja , Stuschke Martin , Balermpas Panagiotis , Rödel Claus , Grosu Anca L. , Schäfer Henning , Zips Daniel , Combs Stephanie E. , Pigorsch Steffi , Zitzelsberger Horst , Baumeister Philipp , Kirchner Thomas , Bewerunge‐Hudler Melanie , Weichert Wilko , Hess Jochen , Herpel Esther , Belka Claus , Baumann Michael , Debus Jürgen , Abdollahi Amir ,   For the DKTK‐ROG
Published: October 2021

AbstractBiomarkers with relevance for loco‐regional therapy are needed in human papillomavirus negative aka HPV(−) head and neck squamous cell carcinoma (HNSCC). Based on the premise that DNA methylation pattern is highly conserved, we sought to develop a reliable and robust methylome‐based classifier identifying HPV(−) HNSCC patients at risk for loco‐regional recurrence (LR) and all‐event progression after postoperative radiochemotherapy (PORT‐C). The training cohort consisted of HPV‐DNA negative HNSCC patients (n = 128) homogeneously treated with PORT‐C in frame of the German Cancer Consortium—Radiation Oncology Group (DKTK‐ROG) multicenter biomarker trial. DNA Methylation analysis was performed using Illumina 450 K and 850 K‐EPIC microarray technology. The performance of the classifier was integrated with a series of biomarkers studied in the training set namely hypoxia‐, 5‐microRNA (5‐miR), stem‐cell gene‐expression signatures and immunohistochemistry (IHC)‐based immunological characterization of tumors (CD3/CD8/PD‐L1/PD1). Validation occurred in an independent cohort of HPV(−) HNSCC patients, pooled from two German centers (n = 125). We identified a 38‐methylation probe‐based HPV(−) Independent Classifier of disease Recurrence (HICR) with high prognostic value for LR, distant metastasis and overall survival (P < 10−9). HICR remained significant after multivariate analysis adjusting for anatomical site, lymph node extracapsular extension (ECE) and size (T‐stage). HICR high‐risk tumors were enriched for younger patients with hypoxic tumors (15‐gene signature) and elevated 5‐miR score. After adjustment for hypoxia and 5‐miR covariates, HICR maintained predicting all endpoints. HICR provides a novel mean for assessing the risk of LR in HPV(−) HNSCC patients treated with PORT‐C and opens a new opportunity for biomarker‐assisted stratification and therapy adaptation in these patients.
Liver tumor segmentation using a new asymmetrical dilated convolutional semantic segmentation network in CT images
Authors: Arulappan Anisha , Thankaraj Ajith Bosco Raj 
Published: October 2021

AbstractLiver cancer has become one of the commonly occurring cancers in men and women. The segmented computed tomography (CT) image of the tumor is the major source for a doctor to diagnose liver diseases. This article proposes a fully automatic system based on an asymmetric dilated convolutional encoder–decoder neural (ADCEDN) network for the problem of accurately extracting the liver and tumor from abdominal CT slices. Specifically, two ADCEDN networks are used in a cascaded form to perform both liver and liver abnormality segmentation. We enrich the encoder module by incorporating the multiscale contextual information through dilated convolutions that enhance the capacity and efficiency of the network. Hybrid dilated convolution across depths perform depth‐wise separable convolution by providing a less steep increase in dilation rate and thus denser sampling that can reduce the computation cost and several metrics while maintaining better performance. Also, the encoder–decoder network is made asymmetric, thereby making the network less complex and more generalizable. The suggested method produced an average dice similarity coefficient score of 96.54% and 76.16% for liver segmentation and liver abnormality segmentation on the 3D Image Reconstruction for Comparison of Algorithm Database data set and 96.42% and 75.7% on the Liver Tumor Segmentation data set. The test outcomes show that the proposed ADCEDN attains state‐of‐the‐art performance in both segmentation of liver and tumors.
An overview of current alternative models in the context of ocular surface toxicity
Authors: Bonneau Noémie , Baudouin Christophe , Réaux‐Le Goazigo Annabelle , Brignole‐Baudouin Françoise 
Published: October 2021

AbstractThe 21st century has seen a steadily increasing social awareness of animal suffering, with increased attention to ethical considerations. Developing new integrated approaches to testing and assessment (IATA) strategies is an Organisation for Economic Co‐operation and Development (OECD) goal to reduce animal testing. Currently, there is a lack of alternative models to test for ocular surface toxicity (aside from irritation) in lieu of the Draize eye irritation test (OECD guideline No. 405) performed in rabbits. Five alternative in vitro or ex vivo methods have been validated to replace this reference test, but only in combination. However, pathologies like Toxicity‐Induced Dry Eye (TIDE), cataract, glaucoma, and neuropathic pain can occur after exposure to a pharmaceutical product or chemical and therefore need to be anticipated. To do so, new models of lacrimal glands, lens, and neurons innervating epithelia are required. These models must take into account real‐life exposure (dose, time, and tear film clearance). The scientific community is working hard to develop new, robust, alternative, in silico, and in vitro models, while attempting to balance ethics and availability of biological materials. This review provides a broad overview of the validated methods for analyzing ocular irritation and those still used by some industries, as well as promising models that need to be optimized according to the OECD. Finally, we give an overview of recently developed innovative models, which could become new tools in the evaluation of ocular surface toxicity within the scope of IATAs.
Enhanced neural differentiation of human‐induced pluripotent stem cells on aligned laminin‐functionalized polyethersulfone nanofibers; a comparison between aligned and random fibers on neurogenesis
Authors: Ghollasi Marzieh , Poormoghadam Delaram 
Published: October 2021

AbstractDespite the numerous attempts in nerve tissue engineering, no ideal strategy has been translated into effective therapy for neuronal regeneration yet. Here, we designed a novel nerve regeneration scaffold combining aligned laminin‐immobilized polyethersulfone (PES) nanofibers and human‐induced pluripotent stem cells (hiPSCs) for transplantation strategies. Aligned and random PES nanofibers were fabricated by electrospinning method with a diameter of 95–500 nm and were then modified with covalent laminin bounding subsequent to O2 plasma treatment. PES‐functionalized fibers found to induce a remarkable higher rate of neuronal genes expression as compared to nontreated group. In addition, hiPSCs cultured on aligned pure fibers exhibited the extension of neurites along with fibers direction and an exponentially elevated expression of neuron specific enolase (early neuroectoderm marker), Tuj‐1 (axonal marker), and microtubule‐associated protein 2 (dendritic marker) in comparison with random pure fibers. The concomitant of increased hydrophilicity and biocompatibility along with exploiting topographical cues and directional guidance make aligned PES‐plasma‐laminin a versatile scaffold for adhesion, proliferation, spreading, and differentiation of hiPSCs into nerve cells.
Oriented homo‐epitaxial crystallization of polylactic acid displaying a biomimetic structure and improved blood compatibility
Authors: Li Zhengqiu , Wu Ting , Chen Yueling , Gao Xiaoyan , Ye Jingbiao , Jin Ying , Chen Baoshu 
Published: October 2021

AbstractEpitaxial crystallization and solid hot‐drawing technology were employed to fabricate oriented homo‐epitaxial crystallization of polylactic acid (PLA) with nano‐topography to enhance its blood compatibility and mechanical characteristics as blood‐contacting medical devices. The process involved solid hot stretching the PLA plates. A PLA nutrient solution was then used to immerse the oriented plates to dissolve some of the PLA solutes, ensuring plate integrity. Consequently, the drawing process exponentially enhanced the modulus and tensile strength of the PLA. Orientation and epitaxial crystallization could substantially enhance blood compatibility of PLA by prolonging clotting time and decreasing hemolysis rate, protein adsorption, and platelet activation. The oriented homo‐epitaxial crystallization of PLA exhibited a nano‐topography and fibrous structure similar to the intimal layer of a blood vessel, and this biomimetic structure was advantageous in decreasing the activation and/or adhesion of platelets.
Hemispheric cortical atrophy and chronic microglial activation following mild focal ischemic stroke in adult male rats
Authors: Ermine Charlotte M. , Nithianantharajah Jess , O’Brien Katrina , Kauhausen Jessica A. , Frausin Stefano , Oman Alexander , Parsons Mark W. , Brait Vanessa H. , Brodtmann Amy , Thompson Lachlan H. 
Published: October 2021

AbstractAnimal modeling has played an important role in our understanding of the pathobiology of stroke. The vast majority of this research has focused on the acute phase following severe forms of stroke that result in clear behavioral deficits. Human stroke, however, can vary widely in severity and clinical outcome. There is a rapidly building body of work suggesting that milder ischemic insults can precipitate functional impairment, including cognitive decline, that continues through the chronic phase after injury. Here we show that a small infarction localized to the frontal motor cortex of rats following injection of endothelin‐1 results in an essentially asymptomatic state based on motor and cognitive testing, and yet produces significant histopathological change including remote atrophy and inflammation that persists up to 1 year. While there is understandably a major focus in stroke research on mitigating the acute consequences of primary infarction, these results point to progressive atrophy and chronic inflammation as additional targets for intervention in the chronic phase after injury. The present rodent model provides an important platform for further work in this area.
Expression of degQ gene and its effect on lipopeptide production as well as formation of secretory proteases in Bacillus subtilis strains
Authors: Lilge Lars , Vahidinasab Maliheh , Adiek Isabel , Becker Philipp , Kuppusamy Nesamani Chanthiya , Treinen Chantal , Hoffmann Mareen , Morabbi Heravi Kambiz , Henkel Marius , Hausmann Rudolf 
Published: October 2021

AbstractBacillus subtilis is described as a promising production strain for lipopeptides. In the case of B. subtilis strains JABs24 and DSM10T, surfactin and plipastatin are produced. Lipopeptide formation is controlled, among others, by the DegU response regulator. The activating phospho‐transfer by the DegS sensor kinase is stimulated by the pleiotropic regulator DegQ, resulting in enhanced DegU activation. In B. subtilis 168, a point mutation in the degQ promoter region leads to a reduction in gene expression. Corresponding reporter strains showed a 14‐fold reduced expression. This effect on degQ expression and the associated impact on lipopeptide formation was examined for B. subtilis JABs24, a lipopeptide‐producing derivative of strain 168, and B. subtilis wild‐type strain DSM10T, which has a native degQ expression. Based on the stimulatory effects of the DegU regulator on secretory protease formation, the impact of degQ expression on extracellular protease activity was additionally investigated. To follow the impact of degQ, a deletion mutant was constructed for DSM10T, while a natively expressed degQ version was integrated into strain JABs24. This allowed strain‐specific quantification of the stimulatory effect of degQ expression on plipastatin and the negative effect on surfactin production in strains JABs24 and DSM10T. While an unaffected degQ expression reduced surfactin production in JABs24 by about 25%, a sixfold increase in plipastatin was observed. In contrast, degQ deletion in DSM10T increased surfactin titer by threefold but decreased plipastatin production by fivefold. In addition, although significant differences in extracellular protease activity were detected, no decrease in plipastatin and surfactin produced during cultivation was observed.
Intergenerational polygenic obesity risk throughout adolescence in a cross‐sectional study design: The HUNT study, Norway
Authors: Næss Marit , Sund Erik R. , Vie Gunnhild Å. , Bjørngaard Johan H. , Åsvold Bjørn Olav , Holmen Turid Lingaas , Kvaløy Kirsti 
Published: October 2021

AbstractObjectiveThis study examined the relationship between parental obesity polygenic risk and children’s BMI throughout adolescence. Additionally, from a smaller subsample, the objective was to assess whether parental polygenic risk score (PRS) may act as a proxy for offspring PRS in studies lacking offspring genetic data.MethodsA total of 8,561 parent‐offspring (age 13‐19 years) trios from the Trøndelag Health Study (the HUNT Study) were included, of which, 1,286 adolescents had available genetic data. Weighted parental PRSs from 900 single‐nucleotide polymorphisms robustly associated with adult BMI were constructed and applied in linear mixed‐effects models.ResultsA positive association between parental PRS and offspring sex‐ and age‐adjusted BMI (iso‐BMI) throughout adolescence was identified. The estimated marginal effects per standard deviation increase in parental PRS were 0.26 (95% CI: 0.18‐0.33), 0.36 (95% CI: 0.29‐0.43), and 0.62 kg/m2 (95% CI: 0.51‐0.72) for maternal, paternal, and combined parental PRS, respectively. In subsample analyses, the magnitude of association of the parental PRS versus offspring PRS with iso‐BMI in adolescents was similar.ConclusionsParental PRS was consistently associated with offspring iso‐BMI throughout adolescence. Results from subsample analyses support the use of parental PRS of obesity as a proxy for adolescent PRS in the absence of offspring genetic data.
Synthesis, Characterization and Photocatalytic Behavior of SiO2@nitrized‐TiO2 Nanocomposites Obtained by a Straightforward Novel Approach
Authors: Gulino Antonino , Papanikolaou Georgia , Lanzafame Paola , Aaliti Abdellatif , Primerano Patrizia , Spitaleri Luca , Triolo Claudia , Dahrouch Zainab , Khaskhoussi Amani , Lo Schiavo Sandra 
Published: October 2021

AbstractWe report on the facile synthesis of SiO2@nitrized‐TiO2 nanocomposite (NST) by calcination of TiO2 xerogel with OctaAmmonium POSS® (N‐POSS; POSS=polyhedral oligomeric silsesquioxanes). The as‐obtained nanoporous mixed oxide is constituted by uniformly distributed SiO2 and nitrized‐TiO2, where the silica component is present in an amorphous state and TiO2 in an anatase/rutile mixed phase (92.1 % vs. 7.9 %, respectively) with very small anatase crystallites (3.7 nm). The TiO2 lattice is nitrized both at interstitial and substitutional positions. NST features a negatively charged surface with a remarkable surface area (406 m2 g−1), endowed with special adsorption capabilities towards cationic dyes. Its photocatalytic behavior was tested by following the degradation of standard aqueous methylene blue and methyl orange solutions under UV and visible light irradiation, according to ISO 10678:2010. For comparison, analogous investigations were carried out on a silica‐free N−TiO2, obtained by using NH4Cl as nitrogen source.
Efficacy and toxicity of high‐risk therapy of the Dutch Childhood Oncology Group in childhood acute lymphoblastic leukemia
Authors: van Binsbergen Annelien L. , de Haas Valérie , van der Velden Vincent H.J. , de Groot‐Kruseman Hester A. , Fiocco Marta F. , Pieters Rob 
Published: October 2021

AbstractBackgroundChildren with acute lymphoblastic leukemia (ALL) and high‐risk (HR) features have a poor outcome and are treated with HR blocks, often followed by allogenic stem cell transplantation (SCT).ProcedureThis article analyses the outcomes of children treated with HR blocks between 2004 and 2017 according to DCOG ALL10/11 protocols. 1297 patients with newly diagnosed ALL were consecutively enrolled, of which 107 met the HR criteria (no complete remission; minimal residual disease (MRD) > 10–3 after consolidation; “MLL‐AF4” translocation and in ALL‐10 also poor prednisone response). Patients were treated with one induction and consolidation course followed by three HR chemotherapy blocks, after which they received either SCT or further chemotherapy. MRD levels were measured at end of induction, consolidation, and after each HR block.ResultsAt five years, the event‐free survival was 72.8% (95% CI, 64.6‐82.0), and the cumulative incidence of relapse was 13.0% (95% CI, 6.3‐19.8). Patients with only negative or low‐positive MRD levels during HR blocks had a significantly lower five‐year cumulative incidence of relapse (CIR) of 2.2% (95% CI, 0‐6.6) compared with patients with one or more high‐positive MRD levels (CIR 15.4%; 95% CI, 3.9‐26.9). During the entire treatment protocol, 11.2% of patients died due to toxicity.ConclusionsThe high survival with HR blocks seems favorable compared with other studies. However, the limit of treatment intensification might have been reached as the number of patients dying from leukemia relapse is about equal as the number of patients dying from toxicity. Patients with negative or low MRD levels during HR blocks have lower relapse rates.
Application advances of deep learning methods for de novo drug design and molecular dynamics simulation
Authors: Bai Qifeng , Liu Shuo , Tian Yanan , Xu Tingyang , Banegas‐Luna Antonio Jesús , Pérez‐Sánchez Horacio , Huang Junzhou , Liu Huanxiang , Yao Xiaojun 
Published: October 2021

AbstractDe novo drug design is a stationary way to build novel ligands in the confined pocket of receptor by assembling the atoms or fragments, while molecular dynamics (MD) simulation is a dynamical way to study the interaction mechanism between the ligands and receptors based on the molecular force field. De novo drug design and MD simulation are effective tools for novel drug discovery. With the development of technology, deep learning methods, and interpretable machine learning (IML) have emerged in the research area of drug design. Deep learning methods and IML can be used further to improve the efficiency and accuracy of de novo drug design and MD simulations. The application summary of deep learning methods for de novo drug design, MD simulations, and IML can further promote the technical development of drug discovery. In this article, two major workflow methods and the related components of classical algorithm and deep learning are described for de novo drug design from a new perspective. The application progress of deep learning is also summarized for MD simulations. Furthermore, IML is introduced for the deep learning model interpretability of de novo drug design and MD simulations. Our paper deals with an interesting topic about deep learning applications of de novo drug design and MD simulations for the scientific community.This article is categorized under:Data Science > ChemoinformaticsData Science > Artificial Intelligence/Machine Learning
Toward situational awareness in threat detection. A survey
Authors: Rendall Kieran , Mylonas Alexios , Vidalis Stilianos 
Published: October 2021

AbstractThe pervasiveness of the Internet did not come without security risk. The current threat landscape is characterized by the rise of sophisticated cyber attacks, which target user devices and corporate infrastructure. To tackle the risk of compromise, data‐driven detection strategies have become increasingly mainstream. The relevant literature includes many works that leverage open‐source datasets, supervised learning or, less commonly, unsupervised learning. However, advanced network attacks' spatial and temporal characteristics prove standalone threat detection systems inadequate, especially for detecting a multi‐stage attack and often stealthy techniques. Moreover, attackers have been demonstrating adversarial effects that are caused by deception and contaminating data‐driven methods with adversarial learning. For these reasons, recent research in threat detection is moving away from commonly, and often obsolete, datasets as well as adopting more multi‐layered decision strategies. As such, this article provides a comprehensive review of decision strategies. We also examine their ability to support cyber situational awareness (CSA), providing to security analysts CSA properties such as situation assessment and system refinement.This article is categorized under:
Digital and Multimedia Science > Cyber Threat Intelligence
Inelastic dark matter, small scale problems, and the XENON1T excess
Authors: Baek Seungwon 
Published: October 2021

Abstract
We study a generic model in which the dark sector is composed of a Majorana dark matter χ1, its excited state χ2, both at the electroweak scale, and a light dark photon Z′ with mz′ ∼ 10−4 eV. The light Z′ enhances the self-scattering elastic cross section χ1χ1 → χ1χ1 enough to solve the small scale problems in the N-body simulations with the cold dark matter. The dark matter communicates with the SM via kinetic mixing parameterized by ϵ. The inelastic scattering process χ1χ1 → χ2χ2 followed by the prompt decay χ2 → χ1Z′ generates energetic Z′. By setting δ ≡ mχ2− mχ1 ≃ 2.8 keV and ϵ ∼ 10−10 the excess in the electron-recoil data at the XENON1T experiment can be explained by the dark-photoelectric effect. The relic abundance of the dark matter can also be accommodated by the thermal freeze-out mechanism via the annihilation χ1χ1(χ2χ2) → Z′Z′ with the dark gauge coupling constant αX ∼ 10−3.
Support Vector Machine-based Spontaneous Intracranial Hypotension Detection on Brain MRI
Authors: Arnold Philipp G. , Kaya Emre , Reisert Marco , Lützen Niklas , Dovi-Akué Philippe , Fung Christian , Beck Jürgen , Urbach Horst 
Published: October 2021

Abstract
Background and Purpose
To develop a fully automatic algorithm for the magnetic resonance imaging (MRI) identification of patients with spontaneous intracranial hypotension (SIH).

Material and Methods
A support vector machine (SVM) was trained with structured reports of 140 patients with clinically suspected SIH. Venous sinuses and basal cisterns were segmented on contrast-enhanced T1-weighted MPRAGE (Magnetization Prepared-Rapid Gradient Echo) sequences using a convolutional neural network (CNN). For the segmented sinuses and cisterns, 56 radiomic features were extracted, which served as input data for the SVM. The algorithm was validated with an independent cohort of 34 patients with proven cerebrospinal fluid (CSF) leaks and 27 patients who had MPRAGE scans for unrelated reasons.

Results
The venous sinuses and the suprasellar cistern had the best discriminative power to separate SIH and non-SIH patients. On a combined score with 2 points, mean SVM score was 1.41 (±0.60) for the SIH and 0.30 (±0.53) for the non-SIH patients (p < 0.001). Area under the curve (AUC) was 0.91.

Conclusion
A fully automatic algorithm analyzing a single MRI sequence separates SIH and non-SIH patients with a high diagnostic accuracy. It may help to consider the need of invasive diagnostics and transfer to a SIH center.