bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Age of Data‐Driven Proteomics: How Machine Learning Enables Novel Workflows
Authors: Bouwmeester Robbin , Gabriels Ralf , Van Den Bossche Tim , Martens Lennart , Degroeve Sven 
Published: April 2020

AbstractA lot of energy in the field of proteomics is dedicated to the application of challenging experimental workflows, which include metaproteomics, proteogenomics, data independent acquisition (DIA), non‐specific proteolysis, immunopeptidomics, and open modification searches. These workflows are all challenging because of ambiguity in the identification stage; they either expand the search space and thus increase the ambiguity of identifications, or, in the case of DIA, they generate data that is inherently more ambiguous. In this context, machine learning‐based predictive models are now generating considerable excitement in the field of proteomics because these predictive models hold great potential to drastically reduce the ambiguity in the identification process of the above‐mentioned workflows. Indeed, the field has already produced classical machine learning and deep learning models to predict almost every aspect of a liquid chromatography‐mass spectrometry (LC‐MS) experiment. Yet despite all the excitement, thorough integration of predictive models in these challenging LC‐MS workflows is still limited, and further improvements to the modeling and validation procedures can still be made. Therefore, highly promising recent machine learning developments in proteomics are pointed out in this viewpoint, alongside some of the remaining challenges.
Effect of polymer and ion concentration on mechanical and drug release behavior of gellan hydrogels using factorial design
Authors: Shukla Shashank , Favata Joseph , Srivastava Vikas , Shahbazmohamadi Sina , Tripathi Anubhav , Shukla Anita 
Published: April 2020

AbstractDeveloping optimized hydrogel products requires an in‐depth understanding of the mechanisms that drive hydrogel tunability. Here, we performed a full 4 × 4 factorial design study investigating the impact of gellan, a naturally derived polysaccharide (1%, 2%, 3%, or 4% w/v) and CaCl2concentration (1, 3, 7, or 10 mM) on the viscoelastic, swelling, and drug release behavior of gellan hydrogels containing a model drug, vancomycin. These concentrations were chosen to specifically provide insight into gellan hydrogel behavior for formulations utilizing polymer and salt concentrations expanding beyond those commonly reported by previous studies exploring gellan. With increasing gellan and CaCl2concentration, the hydrogel storage moduli (0.1–100 kPa) followed a power‐law relationship and on average these hydrogels had higher liquid absorption capability and greater total drug release over 6 days. We suggest that the effects of gellan and CaCl2concentration and their interactions on hydrogel properties can be explained by various phenomena that lead to increased swelling and increased resistance to network expansion.
Permafrost research in China related to express highway construction
Authors: Wang Shuangjie , Niu Fujun , Chen Jianbing , Dong Yuanhong 
Published: April 2020

AbstractExpress highways are roads of high speed, large capacity, and transportation flexibility. The network of express highways in China has been developed over the last 30 years to accommodate the needs of a growing population and to facilitate economic development. Part of the network is in permafrost regions, where the construction and maintenance of these roads present significant engineering challenges due to permafrost degradation induced by climate warming and by construction. This paper summarizes the engineering problems encountered in the construction and maintenance of these express highways, and the mitigation techniques used to overcome them on new transportation projects in permafrost regions. Ten types of engineering problems along the Qinghai‐Tibet Highway, the oldest and longest highway in the permafrost regions of China are identified. Their main cause is related to permafrost degradation in the subgrade beneath the road subbase. Settlement of the highway embankment due to thaw consolidation of degrading permafrost is the dominant mechanical distress observed. Mitigation techniques, mainly for enhancing heat convection beneath express highways, are discussed along with their effects. Research in China related to transportation projects may provide a reference for future express highway design and construction in permafrost regions around the world.
Applicability of free drug hypothesis to drugs with good membrane permeability that are not efflux transporter substrates: A microdialysis study in rats
Authors: Chen Chun , Zhou Hongyu , Guan Chi , Zhang Huanhuan , Li Yingying , Jiang Xue , Dong Zheng , Tao Yuanyuan , Du Juan , Wang Shuyao , Zhang Teng , Du Na , Guo Junyang , Wu Yaqiong , Song Zehai , Luan Haofei , Wang Yu , Du Hongwen , Zhang Shaofeng , Li Chen , Chang Hang , Wang Tao 
Published: April 2020

AbstractIn clinical pharmacology, the free drug hypothesis has been widely applied in the interpretation of the relationship between pharmacokinetics and pharmacodynamics (PK/PD). The free drug hypothesis assumes that the unbound drug concentration in blood is the same as that in the site of action at steady state. The objective of this study is to demonstrate whether the free drug hypothesis is universally applicable for all drugs. The unbound concentrations of the 18 compounds in blood and in brain interstitial fluids (ISF) at steady state following constant intravenous infusion were simultaneously monitored up to 6 hours via in vivo microdialysis technique. Based on the permeability and efflux ratio (ER), the test compounds can be divided into two classes. Class I includes the compounds with good membrane permeability that are not substrates of efflux transporters (eg, P‐gp, BCRP, and MRPs), whereas Class II includes the compounds that are substrates of efflux transporters. The steady‐state unbound drug concentrations in blood, brain, and CSF are quantitatively very similar for Class I compounds, whereas the steady‐state unbound concentrations in the brain and CSF are significantly lower than those in blood for Class II compounds. These results strongly suggest that the free drug hypothesis is not universal for all drugs but is only applicable for drugs with good permeability that are not substrates of efflux transporters.
Introducing the γ function in quantum theory
Authors: Surján Péter R. 
Published: April 2020

AbstractThrough a series of postulates, we define a function
γ(x) whose square acts as Dirac's
δ(x) and exhibits several unusual properties. Though the square root of δ cannot be defined among distributions, it appears in quantum theory if one wants to associate a wave function to a (quasi)classical particle having charge distribution
δ(x). The newly defined function
γ(x) serves to describe quasi‐classical particles using part of the quantum formalism (eg, wave functions, operators, expectation values) but exhibiting classical properties. The function
γ(x) appears to be useful to define model wave functions for simple (quasi)quantum systems. In a spherical coordinate system,
γ(r − r0) leads to a quasi‐classical “bubble” model of the hydrogen atom, where the electron is distributed on the surface of a sphere with radius r0, and it provides exact quantum mechanical energies of its total symmetric levels. For other simple quantum systems, it provides approximate but meaningful energies. In particular, exact energy differences for harmonic oscillator levels are obtained, with the zero‐point energy missing.
Selective Catalytic Dehydration of Xylose to Furfural and Fructose and Glucose to 5‐Hydroximethylfurfural (HMF) Using Preyssler Heteropolyacid
Authors: Pardo Cuervo Oscar H. , Romanelli Gustavo P. , Cubillos Jairo A. , Rojas Hugo A. , Martínez José J. 
Published: April 2020

AbstractCatalytic dehydration of xylose to yield furfural was studied by testing different heteropolyacid‐type catalysts. Preyssler heteropolyacid (HPA‐Preyssler) (H14[NaP5W30O110]) was the most efficient. Under the optimal reaction conditions, xylose was dehydrated into furfural with 73% of yield and 95% of selectivity using DMSO as solvent at 140 °C for 4 h. The HPA‐Preyssler catalyst also exhibited good catalytic activity in the dehydration of fructose and glucose to yield 5‐hydroxymethylfurfural (HMF). Thus, from fructose a yield and selectivity to HMF of 97% and 98%, respectively, was obtained in just 10 min, while from glucose, 91% of conversion and 23% of yield were obtained after 9 h. An easy and efficient methodology for the recovery and reuse of HPA‐Preyssler in at least six reaction cycles without appreciable loss of its initial catalytic activity is reported.
TRanscranial AlterNating current Stimulation FOR patients with Mild Alzheimer's Disease (TRANSFORM‐AD study): Protocol for a randomized controlled clinical trial
Authors: Xing Yi , Wei Penghu , Wang Changming , Shan Yi , Yu Yueying , Qiao Yuchen , Xie Beijia , Shi Xinrui , Zhu Zhongfang , Lu Jie , Zhao Guoguang , Jia Jianping , Tang Yi 
Published: April 2020

AbstractIntroductionRecently, transcranial alternating current stimulation (tACS), which can interact with ongoing neuronal activity, has emerged as a potentially effective and promising treatment for Alzheimer's disease (AD), and the 40 Hz gamma frequency was suggested as a suitable stimulation frequency for AD.MethodsThe TRANSFORM‐AD study is a double‐blind, randomized‐controlled trial that will include 40 individuals with mild AD. Eligible patients need to have amyloid β (Aβ) loads examined by Pittsburgh compound B (PiB) positron emission tomography (PET) or decreased Aβ level in cerebrospinal fluid. Participants will be randomized into either a 40 Hz tACS group or a sham stimulation group. Both groups will undergo 30 one‐hour sessions across 3 weeks (21 days). The outcome measures will be assessed at baseline, at the end of the intervention, and 3 months after the first session. The primary outcome is global cognitive function, assessed by the 11‐item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS‐Cog), and the secondary outcomes include changes in other neuropsychological assessments and in PiB‐PET, structural magnetic resonance imaging (MRI), resting electroencephalography (EEG), and simultaneous EEG–functional MRI (EEG‐fMRI) results.ResultsThe trial is currently ongoing, and it is anticipated that recruitment will be completed in June 2021.DiscussionThis trial will evaluate the efficacy and safety of 40 Hz tACS in patients with AD, and further explore the potential mechanisms by analyzing amyloid deposits using PiB‐PET, brain volume and white matter integrity by structural MRI, and neural activity by EEG and EEG‐fMRI.
Efficient and Scalable Universal Circuits
Authors: Alhassan Masaud Y. , Günther Daniel , Kiss Ágnes , Schneider Thomas 
Published: April 2020

AbstractA universal circuit (UC) can be programmed to simulate any circuit up to a given size n by specifying its program inputs. It provides elegant solutions in various application scenarios, e.g., for private function evaluation (PFE) and for improving the flexibility of attribute-based encryption schemes. The asymptotic lower bound for the size of a UC is $$\Omega (n\log n)$$Ω(nlogn), and Valiant (STOC’76) provided two theoretical constructions, the so-called 2-way and 4-way UCs (i.e., recursive constructions with 2 and 4 substructures), with asymptotic sizes $${\sim }\,5n\log _2n$$∼5nlog2n and $${\sim }\,4.75n\log _2n$$∼4.75nlog2n, respectively. In this article, we present and extend our results published in (Kiss and Schneider EUROCRYPT’16) and (Günther et al. ASIACRYPT’17). We validate the practicality of Valiant’s UCs by realizing the 2-way and 4-way UCs in our modular open-source implementation. We also provide an example implementation for PFE using these size-optimized UCs. We propose a 2/4-hybrid approach that combines the 2-way and the 4-way UCs in order to minimize the size of the resulting UC. We realize that the bottleneck in universal circuit generation and programming becomes the memory consumption of the program since the whole structure of size $${\mathcal {O}}(n\log n)$$O(nlogn) is handled by the algorithms in memory. In this work, we overcome this by designing novel scalable algorithms for the UC generation and programming. Both algorithms use only $${\mathcal {O}}(n)$$O(n) memory at any point in time. We prove the practicality of our scalable design with a scalable proof-of-concept implementation for generating Valiant’s 4-way UC. We note that this can be extended to work with optimized building blocks analogously. Moreover, we substantially improve the size of our UCs by including and implementing the recent optimization of Zhao et al. (ASIACRYPT’19) that reduces the asymptotic size of the 4-way UC to $${\sim }\,4.5n\log _2n$$∼4.5nlog2n. Furthermore, we include their optimization in the implementation of our 2/4-hybrid UC which yields the smallest UC construction known so far.
Advances of single-cell genomics and epigenomics in human disease: where are we now?
Authors: Kamies Rizqah , Martinez-Jimenez Celia P. 
Published: April 2020

AbstractCellular heterogeneity is revolutionizing the way to study, monitor and dissect complex diseases. This has been possible with the technological and computational advances associated to single-cell genomics and epigenomics. Deeper understanding of cell-to-cell variation and its impact on tissue function will open new avenues for early disease detection, accurate diagnosis and personalized treatments, all together leading to the next generation of health care. This review focuses on the recent discoveries that single-cell genomics and epigenomics have facilitated in the context of human health. It highlights the potential of single-cell omics to further advance the development of personalized treatments and precision medicine in cancer, diabetes and chronic age-related diseases. The promise of single-cell technologies to generate new insights about the differences in function between individual cells is just emerging, and it is paving the way for identifying biomarkers and novel therapeutic targets to tackle age, complex diseases and understand the effect of life style interventions and environmental factors.
Effect of mixed solvents on polyelectrolyte complexes with salt
Authors: Meng Siqi , Liu Yueming , Yeo Jihyeon , Ting Jeffrey M. , Tirrell Matthew V. 
Published: April 2020

AbstractStrongly interacting polyelectrolyte complexes (PECs) are a versatile class of materials whose physical states can be driven from solids into liquids and ultimately into homogenous solution upon salt addition. However, many of these materials can display high stability using common monovalent salts, leading to difficulties in accessing the entire PEC spectrum. Here, the model system, composed of two styrenic polyelectrolytes, required exceptionally high salt to drive phase transition. We term the amount of salt required to drive these transitions salt resistance. In water, the PEC transferred from solid into liquid at 2.5 M NaBr and never fully dissociated within the studied salt range. We discovered an unconventional approach of weakening salt resistance by switching the solvent to miscible ethylene glycol/water and ethanol/water, allowing us to systematically introduce more hydrophobic constituents. Employing microscopy to determine physical states qualitatively, we found that higher hydrophobicity lowered salt resistance for phase transition and disassembly.
The polymorphisms of IL-6/STAT3 signaling pathway may contribute to cutaneous T-cell lymphomas susceptibility
Authors: Olszewska Berenika , Gleń Jolanta , Zabłotna Monika , Nowicki Roman J. , Sokołowska-Wojdyło Małgorzata 
Published: April 2020

AbstractIL-6/STAT3 signaling pathway has been suggested to play a role in CTCL pathogenesis. Polymorphisms in STAT3 signaling pathway-related genes might be a risk factor for CTCL. However, the exact role of inherited gene polymorphisms of IL-6 and STAT3 in the pathogenesis of CTCL is still not fully understood. The aim was to examine whether IL-6 cytokine and polymorphisms of IL-6 and STAT3 gene are associated with CTCL susceptibility, stage of disease and pruritus intensity. We compared the IL-6 serum level and the frequency of selected single nucleotide polymorphisms of IL-6 and STAT3 in 106 CTCL and 198 control group using polymerase chain reaction with sequence-specific primers method and ELISA. We have found that serum IL-6 level in CTCL patients was significantly higher than in healthy controls (p < 0.05). We also demonstrated that two genotypes, CC of IL-6 and GG of STAT3, were overexpressed in CTCL patients compared to healthy controls, and that they increase the risk of malignancy development (OR = 1.8,p = 0.04 for IL-6 and OR 2.53,p = 0.0064 for STAT3). Moreover, the GG genotype of STAT3 polymorphism seems to be associated with lack of pruritus or mild pruritus in CTCL patients. Our results indicate that IL-6 is involved in pathogenesis of CTCL but not pruritus. Moreover, CC of IL-6 and GG genotype of STAT3 genes might be considered as the risk factor for development of CTCL.
The Development and Feasibility Study of a Multimodal ‘Talking Wall’ to Facilitate the Voice of Young People with Autism and Complex Needs: A Case Study in a Specialist Residential School
Authors: Richards Norah , Crane Laura 
Published: April 2020

AbstractLimited research has examined methods to investigate the views, preferences and experiences of young people with autism and complex needs. The aim of this study, based at a specialist residential school in England, was to develop and pilot an innovative method for this purpose—a ‘Talking Wall’—that was trialled over a 6-month period. Thematic analysis of data from focus groups and semi structured interviews with staff, combined with structured observations of pupils, resulted in three key themes: supporting the expression and evaluation of emotions that underlie preferences; recognising the impact of transitions; and the important role of familiar adults in interpreting communication bids. These positive, initial findings suggest the Talking Wall approach merits further development and evaluation.
Development and Evaluation of an In-line and On-line Monitoring System for Granule Size Distributions in Continuous Roll Compaction/Dry Granulation Based on Laser Diffraction
Authors: Wilms Annika , Meier Robin , Kleinebudde Peter 
Published: April 2020

Abstract
Purpose
Roll compaction/dry granulation is established in manufacturing of solid oral dosage forms and, within the context of continuous manufacturing, it has sparked interest as material is fed, processed, and ejected continuously while also providing large possible throughputs. However, this amount of material has to be adequately controlled in real time to assure quality.

Methods
This research aimed at monitoring the critical quality attribute granule size distribution in continuous roll compaction/dry granulation (QbCon®; L.B. Bohle, Ennigerloh, Germany) using in-line and on-line laser diffraction. The influence of varying process parameters and excipient formulations was studied and evaluated with the prospect of using this technique to develop control loops. For this purpose, residence time parameters were assessed. In- and on-line data was compared with off-line laser diffraction and dynamic image analysis data.

Results
The system successfully monitored the granule size distribution in a variety of process parameters and throughputs (up to 27.5 kg/h). It was sensitive to changes in process parameters and changes in material blends, which could pose a potential threat to the final drug products’ quality. Average event propagation time from the compaction zone to the laser diffraction system of 17.7 s demonstrates the systems’ fast reaction time.

Conclusion
Results highlight laser diffraction as a valuable method of in- and on-line size determination and allow for the development of a control strategy using this principle.
Correlation between the numbers of rotation steps in the ATPase and proton-conducting domains of F- and V-ATPases
Authors: Noji Hiroyuki , Ueno Hiroshi , Kobayashi Ryohei 
Published: April 2020

AbstractThis letter reports the correlation in the number of distinct rotation steps between the F1/V1 and Fo/Vo domains that constitute common rotary F- and V-ATP synthases/ATPases. Recent single-molecule studies on the F1-ATPase revealed differences in the number of discrete steps in rotary catalysis between different organisms—6 steps per turn in bacterial types and mitochondrial F1 from yeast, and 9 steps in the mammalian mitochondrial F1 domains. The number of rotational steps that Fo domain makes is thought to correspond to that of proteolipid subunits within the rotating c-ring present in Fo. Structural studies on Fo and in the whole ATP synthase complex have shown a large diversity in the number of proteolipid subunits. Interestingly, 6 steps in F1 are always paired with 10 steps in Fo, whereas 9 steps in F1 are paired with 8 steps in Fo. The correlation in the number of steps has also been revealed for two types of V-ATPases: one having 6 steps in V1 paired with 10 steps in Vo, and the other one having 3 steps in V1 paired with 12 steps in Vo. Although the abovementioned correlations await further confirmation, the results suggest a clear trend; ATPase motors with more steps have proton-conducting motors with less steps. In addition, ATPases with 6 steps are always paired with proton-conducting domains with 10 steps.
Treatment of fracture-related infection of the lower extremity with antibiotic-eluting ceramic bone substitutes: case series of 35 patients and literature review
Authors: Pesch Sebastian , Hanschen Marc , Greve Frederik , Zyskowski Michael , Seidl Fritz , Kirchhoff Chlodwig , Biberthaler Peter , Huber-Wagner Stefan 
Published: April 2020

Abstract
Introduction
The current treatment concepts of fracture-related infection (FRI) [Consensus Conference (Anti-Infection Task Force (AITF)) on the definition of acute or chronic osteomyelitis (cOM)] are associated with unsolved challenges and problems, underlining the need for ongoing medical research.

Method
Literature review of treatments for FRI and description of own cases.

Results
We could include eight papers with 394 patients reporting treatments and outcome in FRI. The infection was resolved in 92.9% (mean) of all treatments. The mean follow-up was 25 months with a persistent non-union in 7% of the patients. We diagnosed 35 (19f/16m; 56.4 ± 18.6 years) patients with bone infections anatomically allocated to the proximal and distal femur (12×), the pelvis (2×), distal tibia (3×), tibial diaphysis (11×), the ankle joint (4×) and calcaneus (3×). These 35 patients were treated (1) with surgical debridement; (2) with antibiotic-eluting ceramic bone substitutes; (3) bone stabilization (including nail fixation, arthrodesis nails, plates, or external ring fixation), (4) optionally negative pressure wound therapy (NPWT) and (5) optionally soft tissue closure with local or free flaps. The mean follow-up time was 14.9 ± 10.6 months (min/max: 2/40 month). The overall recurrence rate is low (8.5%, 3/35). Prolonged wound secretion was observed in six cases (17.1%, 6/35). The overall number of surgeries was a median of 2.5.

Conclusion
The results in the literature and in our case series are explicitly promising regarding the treatment of posttraumatic fracture-related infection.