bluuebunny/crossref_metadata_2025_split huggingface dataset:
Replacement of animal testing by integrated approaches to testing and assessment (IATA): a call for in vivitrosi
Authors: Caloni Francesca , De Angelis Isabella , Hartung Thomas 
Published: May 2022

AbstractAlternative methods to animal use in toxicology are evolving with new advanced tools and multilevel approaches, to answer from one side to 3Rs requirements, and on the other side offering relevant and valid tests for drugs and chemicals, considering also their combination in test strategies, for a proper risk assessment.While stand-alone methods, have demonstrated to be applicable for some specific toxicological predictions with some limitations, the new strategy for the application of New Approach Methods (NAM), to solve complex toxicological endpoints is addressed by Integrated Approaches for Testing and Assessment (IATA), aka Integrated Testing Strategies (ITS) or Defined Approaches for Testing and Assessment (DA). The central challenge of evidence integration is shared with the needs of risk assessment and systematic reviews of an evidence-based Toxicology. Increasingly, machine learning (aka Artificial Intelligence, AI) lends itself to integrate diverse evidence streams.In this article, we give an overview of the state of the art of alternative methods and IATA in toxicology for regulatory use for various hazards, outlining future orientation and perspectives. We call on leveraging the synergies of integrated approaches and evidence integration from in vivo, in vitro and in silico as true in vivitrosi.
Experiences with Innovation Fund healthcare models in primary care: a qualitative study amongst German general practitioners
Authors: Wangler Julian , Jansky Michael 
Published: May 2022

SummaryThe Innovation Fund was set up in 2015 with the aim of improving medical care in the German statutory health insurance system. Primary care needs to be involved in testing interventions and new forms of care for effectiveness and inclusion in standard care. There has so far been hardly any research on how far Innovation Fund models accommodate the primary care setting, or on the experience general practitioners have had with these models. Between September 2021 and January 2022, 36 semi-standardized individual interviews were performed with general practitioners who had already participated in Innovation Fund projects. Eleven regional physician networks in Rhineland-Palatinate, Hesse, North Rhine-Westphalia, and Schleswig-Holstein were involved in the recruitment process. Most of the interviewees associated the Innovation Fund with potential and opportunity including intensification of application-oriented healthcare research, independent financing, and general healthcare involvement. Even so, many general practitioners were unsure as to how far primary care in particular would stand to benefit from the Innovation Fund in the long term. A mostly positive balance was drawn from participation in care models—benefit of intervention as well as cost–benefit ratio. However, some also reported hurdles and stress factors such as documentation requirements and disruption in everyday office routine. Innovation Fund projects will need to be suitable for general practitioners especially regarding medical decision-making leeway, limits to documentation requirements, preserving established office routine, greater involvement in research planning, and improvements to the primary care setting to encourage willingness to participate in Innovation Fund projects amongst general practitioners.
Condensed matter physics in big discrete time crystals
Authors: Hannaford Peter , Sacha Krzysztof 
Published: May 2022

AbstractWe review the application of discrete time crystals created in a Bose-Einstein condensate (BEC) of ultracold atoms bouncing resonantly on an oscillating atom mirror to the investigation of condensed matter phenomena in the time dimension. Such a bouncing BEC system can exhibit dramatic breaking of time-translation symmetry, allowing the creation of discrete time crystals having up to about 100 temporal lattice sites and suitable for hosting a broad range of temporal condensed matter phenomena. We first consider single-particle condensed matter phenomena in the time dimension which include Anderson localization due to temporal disorder, topological time crystals, and quasi-crystal structures in time. We then discuss many-body temporal condensed matter phenomena including Mott insulator phases in time, many-body localization in time, many-body topological time crystals and time crystals having long-range exotic interactions. We also discuss the construction of two (or three) dimensional time lattices, involving the bouncing of a BEC between two (or three) orthogonal oscillating mirrors and between two oscillating mirrors oriented at 45∘. The latter configuration supports a versatile Möbius strip geometry which can host a variety of two-dimensional time lattices including a honeycomb time lattice and a Lieb square time lattice. Finally, we discuss the construction of a six-dimensional time-space lattice based on periodically driven BECs trapped in a three-dimensional optical lattice.
Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men
Authors: Igarashi Masaki , Nakagawa-Nagahama Yoshiko , Miura Masaomi , Kashiwabara Kosuke , Yaku Keisuke , Sawada Mika , Sekine Rie , Fukamizu Yuichiro , Sato Toshiya , Sakurai Takanobu , Sato Jiro , Ino Kenji , Kubota Naoto , Nakagawa Takashi , Kadowaki Takashi , Yamauchi Toshimasa 
Published: May 2022

AbstractPreclinical studies have revealed that the elevation of nicotinamide adenine dinucleotide (NAD + ) upon the administration of nicotinamide mononucleotide (NMN), an NAD + precursor, can mitigate aging-related disorders; however, human data on this are limited. We investigated whether the chronic oral supplementation of NMN can elevate blood NAD + levels and alter physiological dysfunctions in healthy older participants. We administered 250 mg NMN per day to aged men for 6 or 12 weeks in a placebo-controlled, randomized, double-blind, parallel-group trial. Chronic NMN supplementation was well tolerated and caused no significant deleterious effect. Metabolomic analysis of whole blood samples demonstrated that oral NMN supplementation significantly increased the NAD + and NAD + metabolite concentrations. There were nominally significant improvements in gait speed and performance in the left grip test, which should be validated in larger studies; however, NMN exerted no significant effect on body composition. Therefore, chronic oral NMN supplementation can be an efficient NAD + booster for preventing aging-related muscle dysfunctions in humans.
Bony Cyst in a Ground Glass Matrix: A Rare Case Report of Craniofacial Fibrous Dysplasia with Secondary Aneurysmal Bone Cyst
Authors: Sachar Chandrika , Agarwal Aakanksha , Syed Anjum 
Published: May 2022

AbstractFibrous dysplasia has various ways of presentation including syndromic associations and secondary changes within the lesion. We present a case of a 21-year-old female with craniofacial fibrous dysplasia, presenting with proptosis and intermittent blurring of vision due to focal fibrous dysplasia involving the frontal bone with secondary aneurysmal bone formation that was provisionally diagnosed on imaging and confirmed on histopathology. This case demonstrates the typical imaging findings of fibrous dysplasia with seldom encountered secondary aneurysmal bone cyst formation and also discusses about the pathology and management of the craniofacial fibrous dysplasia.
Comparison of Performance with Wide Dynamic Range Compression and Linear Amplification
Authors: Kam Anna C. S. , Wong Lena L. N. 
Published: May 2022

AbstractThis study compared subject performance and preference using a compression-limiting hearing aid set to linear amplification (program 1) and wide dynamic range compression (WDRC, program 2). The frequency responses of the hearing aid were matched to a 65 dB SPL signal and maximum output to a 90 dB SPL signal. Twenty subjects with moderate to moderately severe sensorineural hearing loss were tested. Speech recognition scores and speech reception thresholds were obtained both in quiet and in noise. Subjective preference for WDRC or linear amplification was measured via a paired-comparison procedure on "loudness appropriateness,” “clarity," and "pleasantness" to continuous discourse presented in quiet and in noise. Results suggested that WDRC yielded better speech intelligibility in quiet for low-level signals and no difference in speech intelligibility in noise compared to linear amplification. Subjects preferred WDRC for loudness to both high- and low-level signals and for pleasantness to high-level signals.
Abbreviations: ANOVA = analysis of variance, AVC = automatic volume control, CL = compression limiting, CVR = consontant-vowel-ratio, HINT = Hearing In Noise Test, Ρ = program, REIG = real-ear insertion gain, REIR = real-ear insertion response, SNR = signal-to-noise ratio, SRS = speech recognition score, SRT = speech reception threshold, WDRC = wide dynamic range compression
Variables Affecting the Use of Prescriptive Formulae to Fit Modern Nonlinear Hearing Aids
Authors: Kuk Francis K. , Ludvigsen Carl 
Published: May 2022

AbstractIt is routine for audiologists to fit nonlinear hearing aids by using one of several current prescriptive formulae. While such an approach might result in acceptable fittings for single-channel analog compression hearing aids, its direct application to fitting current multichannel compression hearing aids may result in less than an optimal fit. In this paper, the effects of filter bandwidth, number of channels, detector type, compression threshold, attack and release times, and distortion on the final output of a nonlinear compression hearing aid are discussed. The subjective results of such effects and its implications on our clinical practice will be explored as well.
Abbreviations: CR = compression ratio, CT = compression threshold, DSL (i/o) = Desired Sensation Level (input/output), FFT = Fast Fourier Transform, HA = hearing aid, IHAFF = Independent Hearing Aid Fitting Forum, I/O = input/output, LGOB = Loudness Growth by Octave Band, RMS = root mean square, UCL = uncomfortable listening level, WDRC = wide dynamic range compression
Medication-Naïve Blood Pressure and Incident Cancers: Analysis of 2 Nationwide Population-Based Databases
Authors: Kaneko Hidehiro , Yano Yuichiro , Lee Hyeok-Hee , Lee Hokyou , Okada Akira , Itoh Hidetaka , Morita Kojiro , Fukui Akira , Fujiu Katsuhito , Suzuki Yuta , Matsuoka Satoshi , Nakamura Sunao , Michihata Nobuaki , Jo Taisuke , Takeda Norifumi , Morita Hiroyuki , Yokoo Takashi , Nishiyama Akira , Node Koichi , Viera Anthony J , Muntner Paul , Oparil Suzanne , Kim Hyeon Chang , Yasunaga Hideo , Komuro Issei 
Published: May 2022

Abstract

BACKGROUND
Results of preceding studies on the relationship between blood pressure (BP) and cancers have been confounded due to individuals taking antihypertensive medications or shared risk factors. We assessed whether medication-naïve high BP is a risk factor for incident cancers.

METHODS
This retrospective observational study included 1,388,331 individuals without a prior history of cancer and not taking antihypertensive medications enrolled in the JMDC Claims Database between 2005 and 2018. The primary outcome was 16 cancers.

RESULTS
The median [interquartile range] age was 45 [40–52] years and 56.2% were men. Mean systolic BP (SBP) and diastolic BP (DBP) were 117.7 ± 15.8 and 72.8 ± 11.6 mm Hg. Multivariate Cox regression analysis demonstrated that SBP per 1-SD was associated with a higher incidence of thyroid (hazard ratio [HR]: 1.09, 95% confidence interval [CI]: 1.03–1.16), esophageal (HR: 1.15, 95% CI: 1.07–1.24), colorectal (HR: 1.04, 95% CI: 1.01–1.07), liver (HR: 1.11, 95% CI: 1.03–1.20), and kidney (HR: 1.22, 95% CI: 1.14–1.31) cancers, but with a lower incidence of stomach cancer (HR: 0.94, 95% CI: 0.91–0.98). These associations remained significant after adjustment for multiple testing. DBP was associated with higher incidences of thyroid, esophageal, colorectal, kidney, and corpus uteri cancers, but with a lower incidence of stomach cancer. The associations between SBP and incidences of thyroid, esophageal, colorectal, liver, and kidney cancers were confirmed in the Korean National Health Insurance Service database.

CONCLUSIONS
Medication-naïve BP was associated with higher incidences of thyroid, esophageal, colorectal, liver, and kidney cancers. Uncovering the underlying mechanisms for our results may help identify novel therapeutic approach for hypertension and cancer.
How to Be A ‘Good Man’: Tracing War’s Imprint Upon the Life Course
Authors: DiPietro Stephanie M , Baker Thomas Owen 
Published: May 2022

AbstractLife course criminologists seldom examine the role of macro-level sociohistorical contexts—particularly those of extreme social ferment (e.g. war and genocide)—in shaping developmental pathways. Such contexts catalyze key life turning points, impose significant constraints on identity resources and shape investments in particular social discourses and practices. To illustrate, we analyze the life history of Omar, a former child soldier from the war and genocide in Bosnia (1992–5), and self-professed violent ‘criminal’. Omar’s life history reveals limited opportunities and identity resources attendant to the war, which prompted his investment in discourses of masculinity that espouse violence as the primary means of proving manhood. These findings enrich our understanding of the link between sociohistorical context and individual adaptation.
White matter microstructural variability linked to differential attentional skills and impulsive behavior in a pediatric population
Authors: Gagnon Anthony , Grenier Gabrielle , Bocti Christian , Gillet Virginie , Lepage Jean-François , Baccarelli Andrea A , Posner Jonathan , Descoteaux Maxime , Takser Larissa 
Published: May 2022

AbstractStructural and functional magnetic resonance imaging (MRI) studies have suggested a neuroanatomical basis that may underly attention-deficit–hyperactivity disorder (ADHD), but the anatomical ground truth remains unknown. In addition, the role of the white matter (WM) microstructure related to attention and impulsivity in a general pediatric population is still not well understood. Using a state-of-the-art structural connectivity pipeline based on the Brainnetome atlas extracting WM connections and its subsections, we applied dimensionality reduction techniques to obtain biologically interpretable WM measures. We selected the top 10 connections-of-interests (located in frontal, parietal, occipital, and basal ganglia regions) with robust anatomical and statistical criteria. We correlated WM measures with psychometric test metrics (Conner’s Continuous Performance Test 3) in 171 children (27 Dx ADHD, 3Dx ASD, 9–13 years old) from the population-based GESTation and Environment cohort. We found that children with lower microstructural complexity and lower axonal density show a higher impulsive behavior on these connections. When segmenting each connection in subsections, we report WM alterations localized in one or both endpoints reflecting a specific localization of WM alterations along each connection. These results provide new insight in understanding the neurophysiology of attention and impulsivity in a general population.
Successful surgical aortic valve replacement in a patient with progeria
Authors: Vukovic Petar , Milacic Petar , Zivkovic Igor , Kosevic Dragana , Micovic Slobodan 
Published: May 2022

Abstract
The progeroid syndrome includes a group of rare, severe genetic disorders clinically characterized by premature physical ageing. Severe aortic stenosis has been described in progeria patients, but no previous surgical aortic valve replacement was reported. We describe a successful surgical aortic valve replacement combined with coronary artery bypass grafting in a progeria patient with severe aortic stenosis and a small aortic annulus.
Solving time-fractional differential equations via rational approximation
Authors: Khristenko Ustim , Wohlmuth Barbara 
Published: May 2022

Abstract
Fractional differential equations (FDEs) describe subdiffusion behavior of dynamical systems. Their nonlocal structure requires taking into account the whole evolution history during the time integration, which then possibly causes additional memory use to store the history, growing in time. An alternative to a quadrature for the history integral is to approximate the fractional kernel with a sum of exponentials, which is equivalent to considering the FDE solution as a sum of solutions to a system of ordinary differential equations. One possibility to construct this system is to approximate the Laplace spectrum of the fractional kernel with a rational function. In this paper we use the adaptive Antoulas–Anderson algorithm for the rational approximation of the kernel spectrum, which yields only a small number of real-valued poles. We propose a numerical scheme based on this idea and study its stability and convergence properties. In addition, we apply the algorithm to a time-fractional Cahn–Hilliard problem.
2,2,6,6-Tetramethylpiperidine-1-oxyl acts as a volatile inhibitor of ferroptosis and neurological injury
Authors: Mizuno Hiroyuki , Kubota Chisato , Takigawa Yuta , Shintoku Ryosuke , Kannari Naokatsu , Muraoka Takako , Obinata Hideru , Yoshimoto Yuhei , Kanazawa Masato , Koshiishi Ichiro , Torii Seiji 
Published: May 2022

Summary
Ferroptosis, a type of oxidative stress cell death, has been implicated in cell injury in several diseases, and treatments with specific inhibitors have been shown to protect cells and tissues. Here we demonstrated that a treatment with the nitroxide radical, 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), prevented the ferroptotic cell death in an airborne manner. Other TEMPO derivatives and lipophilic antioxidants, such as Trolox and ferrostatin-1, also prevented cell death induced by erastin and RSL3; however, only TEMPO exhibited inhibitory activity from a physically distant location. TEMPO vaporized without decomposing and then dissolved again into a nearby water solution. Volatilized TEMPO inhibited glutamate-induced cell death in mouse hippocampal cell lines and also reduced neuronal cell death in a mouse ischemia model. These results suggest that TEMPO is a unique cell protective agent that acts in a volatility-mediated manner.
Evolution and origin of bread wheat
Authors: Levy Avraham A , Feldman Moshe 
Published: May 2022

Abstract
Bread wheat (Triticum aestivum, genome BBAADD) is a young hexaploid species formed only 8,500–9,000 years ago through hybridization between a domesticated free-threshing tetraploid progenitor, genome BBAA, and Aegilops tauschii, the diploid donor of the D subgenome. Very soon after its formation, it spread globally from its cradle in the fertile crescent into new habitats and climates, to become a staple food of humanity. This extraordinary global expansion was probably enabled by allopolyploidy that accelerated genetic novelty through the acquisition of new traits, new intergenomic interactions, and buffering of mutations, and by the attractiveness of bread wheat’s large, tasty, and nutritious grain with high baking quality. New genome sequences suggest that the elusive donor of the B subgenome is a distinct (unknown or extinct) species rather than a mosaic genome. We discuss the origin of the diploid and tetraploid progenitors of bread wheat and the conflicting genetic and archaeological evidence on where it was formed and which species was its free-threshing tetraploid progenitor. Wheat experienced many environmental changes throughout its evolution, therefore, while it might adapt to current climatic changes, efforts are needed to better use and conserve the vast gene pool of wheat biodiversity on which our food security depends.
An Arabidopsis GCMS chemical ionization technique to quantify adaptive responses in central metabolism
Authors: Bergman Matthew E , Evans Sonia E , Davis Benjamin , Hamid Rehma , Bajwa Ibadat , Jayathilake Amreetha , Chahal Anmol Kaur , Phillips Michael A 
Published: May 2022

Abstract
We present a methodology to survey central metabolism in 13CO2-labeled Arabidopsis (Arabidopsis thaliana) rosettes by ammonia positive chemical ionization–gas chromatography–mass spectrometry. This technique preserves the molecular ion cluster of methyloxime/trimethylsilyl-derivatized analytes up to 1 kDa, providing unambiguous nominal mass assignment of &gt;200 central metabolites and 13C incorporation rates into a subset of 111 from the tricarboxylic acid (TCA) cycle, photorespiratory pathway, amino acid metabolism, shikimate pathway, and lipid and sugar metabolism. In short-term labeling assays, we observed plateau labeling of ∼35% for intermediates of the photorespiratory cycle except for glyoxylate, which reached only ∼4% labeling and was also present at molar concentrations several fold lower than other photorespiratory intermediates. This suggests photorespiratory flux may involve alternate intermediate pools besides the generally accepted route through glyoxylate. Untargeted scans showed that in illuminated leaves, noncyclic TCA cycle flux and citrate export to the cytosol revert to a cyclic flux mode following methyl jasmonate (MJ) treatment. MJ also caused a block in the photorespiratory transamination of glyoxylate to glycine. Salicylic acid treatment induced the opposite effects in both cases, indicating the antagonistic relationship of these defense signaling hormones is preserved at the metabolome level. We provide complete chemical ionization spectra for 203 Arabidopsis metabolites from central metabolism, which uniformly feature the unfragmented pseudomolecular ion as the base peak. This unbiased, soft ionization technique is a powerful screening tool to identify adaptive metabolic trends in photosynthetic tissue and represents an important advance in methodology to measure plant metabolic flux.
The impacts of the beneficial owner register on Hungarian asset management foundations, trusts, and hybrid trusts
Authors: Menyhei Ákos 
Published: May 2022

Abstract
The European Union beneficial ownership register regime forces, among others, companies, trusts, and foundations to make publicly available their beneficial owners, even though the definition of a beneficial owner is foreign to many continental jurisdictions due to the Roman law heritage of civil law. This article discusses the functioning of the Beneficial Ownership Register in Hungary with a special focus on the Hungarian asset management foundation, the trust, and the hybrid trust. It also analyzes the impact of the Beneficial Ownership Register and Anti-Money Laundering laws on the privacy of the participants in an asset management foundation, trust, or hybrid trust.