bluuebunny/crossref_metadata_2025 huggingface dataset:
Einleitung
Authors: Behnert Christiane
Published: May 2022

Heutzutage ist das Nutzerverhalten bei der Informationssuche sehr stark durch die Websuche geprägt: Menschen berücksichtigen in der Regel nur die erste Suchergebnisseite und legen ihr Hauptaugenmerk auf die ersten drei Treffer, d. h. sie vertrauen dem Rankingalgorithmus der Websuchmaschine, die für sie relevanten Ergebnisse auf den obersten Positionen anzuzeigen. Aus diesen Studien lässt sich schließen, dass das Relevanzranking die menschliche Relevanzbewertung maßgeblich beeinflusst. Doch nicht nur das Ranking der Suchergebnisse nimmt einen sehr großen Stellenwert bei der Informationssuche und der Auswahl der Suchergebnisse ein; auch deren Darstellung liefert Hinweise darüber, wie diese von informationssuchenden Personen bewertet werden.
Voraussetzungen zur experimentellen Erforschung von Relevanzkriterien
Authors: Behnert Christiane
Published: May 2022

Für die Entwicklung eines experimentellen Studiendesigns müssen die zu untersuchenden Variablen operationalisiert werden. Einer Operationalisierung muss die Definition des Forschungsgegenstands vorangehen. Gegenstand der vorliegenden Arbeit ist der subjektive Prozess der Relevanzbewertung, der von verschiedenen Parametern beeinflusst wird und als aufeinander folgende Anwendung von Relevanzkriterien zu verstehen ist.
Studie zur Untersuchung des Einflusses von Popularitätsdaten auf die Relevanzbewertung von Suchergebnissen in akademischen Suchsystemen
Authors: Behnert Christiane
Published: May 2022

Die Literaturschau zum aktuellen Stand der Forschung hinsichtlich Relevanz und Relevanzkriterien zeigte, dass bisher keine Studien zur Erforschung von Relevanzkriterien veröffentlicht wurden, in denen Teilnehmende Suchergebnisse (Surrogate) mit integrierten Popularitätsdaten bewerteten. Neue Erkenntnisse der Relevanzforschung und im weiteren Sinne der Informationsverhaltensforschung sollten auf Untersuchungen beruhen, in denen Eigenschaften gegenwärtig existierender Suchsysteme mitberücksichtigt werden. Moderne akademische Suchsysteme wie Google Scholar oder die ACM Digital Library integrieren beispielsweise die Anzahl von Downloads oder die Anzahl der Zitationen eines Werkes.
Bulk reconstruction in moduli space holography
Authors: Grimm Thomas W. , Monnee Jeroen , van de Heisteeg Damian
Published: May 2022

Abstract

It was recently suggested that certain UV-completable supersymmetric actions can be characterized by the solutions to an auxiliary non-linear sigma-model with special asymptotic boundary conditions. The space-time of this sigma-model is the scalar field space of these effective theories while the target space is a coset space. We study this sigma-model without any reference to a potentially underlying geometric description. Using a holographic approach reminiscent of the bulk reconstruction in the AdS/CFT correspondence, we then derive its near-boundary solutions for a two-dimensional space-time. Specifying a set ofSl(2,ℝ) boundary data we show that the near-boundary solutions are uniquely fixed after imposing a single bulk-boundary matching condition. The reconstruction exploits an elaborate set of recursion relations introduced by Cattani, Kaplan, and Schmid in the proof of theSl(2)-orbit theorem. We explicitly solve these recursion relations for three sets of simple boundary data and show that they model asymptotic periods of a Calabi-Yau threefold near the conifold point, the large complex structure point, and the Tyurin degeneration.
Nucleolin: a cell portal for viruses, bacteria, and toxins
Authors: Tonello Fiorella , Massimino Maria Lina , Peggion Caterina
Published: May 2022

The main localization of nucleolin is the nucleolus, but this protein is present in multiple subcellular sites, and it is unconventionally secreted. On the cell surface, nucleolin acts as a receptor for various viruses, some bacteria, and some toxins. Aim of this review is to discuss the characteristics that make nucleolin able to act as receptor or co-receptor of so many and different pathogens. The important features that emerge are its multivalence, and its role as a bridge between the cell surface and the nucleus. Multiple domains, short linear motifs and post-translational modifications confer and modulate nucleolin ability to interact with nucleic acids, with proteins, but also with carbohydrates and lipids. This modular multivalence allows nucleolin to participate in different types of biomolecular condensates and to move to various subcellular locations, where it can act as a kind of molecular glue. It moves from the nucleus to the cell surface and can accompany particles in the reverse direction, from the cell surface into the nucleus, which is the destination of several pathogens to manipulate the cell in their favour.
Unintentional drug-related deaths in people with mental illness in NSW Australia, 2012–2016: a retrospective cohort study
Authors: Smith-Merry Jennifer , Fujita Kenji , Chen Tim , Baillie Andrew
Published: May 2022

Purpose

People with mental illness are a vulnerable and stigmatised group with poor health outcomes including greater premature mortality. This study aimed to investigate trends and rates of change in unintentional drug-related deaths for people with mental illness, describe types of medicines involved, and identify populations at risk in a cohort from New South Wales, Australia.

Methods

Features of unintentional drug-related deaths for people with mental illness between 2012 and 2016 were identified in a retrospective review of data from the National Coronial Information System.

Results

A total of 495 unintentional drug-related deaths were identified (1.6 deaths/100,000 population), showing an upward trend (p < 0.01). The most common substance involved was diazepam in both genders (males 135/319, 42%, female 76/176, 43%) and more than one contributory drug was included in 80% of cases. Between 2012 and 2016, amphetamine-related deaths showed the highest increase (3.2-fold), followed by codeine (2.5-fold) and quetiapine (2.5-fold). Males (RR 1.8, 95% CI 1.5–2.2) and people aged 35–44 (RR 1.7, CI 1.3–2.2) were more likely to die from unintentional drug-related deaths compared with the reference (females and people aged 25–34).

Conclusion

This study found that the drugs commonly involved in deaths are also the drugs commonly used by and prescribed to people with mental illness. There were also significant differences between gender, age group, and marital status in the trend and rate of unintentional drug-related deaths for people with mental illness. A multifaceted approach encompassing both pharmaceutical prescribing and targeted public health messaging is required to inform intervention and prevention strategies.
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

Alternative 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

The 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

We 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

Preclinical 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.
Glass-patternable notch-shaped microwave architecture for on-chip spin detection in biological samples
Authors: Oshimi Keisuke , Nishimura Yushi , Matsubara Tsutomu , Tanaka Masuaki , Shikoh Eiji , Zhao Li , Zou Yajuan , Komatsu Naoki , Ikado Yuta , Takezawa Yuka , Kage-Nakadai Eriko , Izutsu Yumi , Yoshizato Katsutoshi , Morita Saho , Tokunaga Masato , Yukawa Hiroshi , Baba Yoshinobu , Teki Yoshio , Fujiwara Masazumi
Published: May 2022

This on-chip device realizes large-area and predictable spin detection of fluorescent nanodiamonds, providing a scalable platform for quantum-sensor-based bioassay.
Lehrende empowern – Netzwerk für betätigungszentrierte Ausbildung
Authors: Bösiger Kathrin , Völler Stefanie , Heizmann Sabrina
Published: May 2022

Eine Gruppe von vier engagierten Ergotherapeutinnen hat sich zusammengeschlossen, um einen Online-Stammtisch für Lehrende ins Leben zu rufen. Das Ziel: ein systematisches Einflechten von betätigungszentrierten Inhalten in die ergotherapeutische Ausbildung.
Flussmetapher erleichtert Therapieeinstieg – Kawa-Modell bei Kindern mit chronischen Schmerzerkrankungen
Authors: Krötz Theresa , Höfel Lea , Georgi Mathias
Published: May 2022

In der interdisziplinären multimodalen Schmerztherapie (IMST) in Garmisch-Partenkirchen kommt das Kawa-Modell in der Therapie mit Kindern und Jugendlichen zum Einsatz. Es erleichtert das Verständnis für die Ausgangssituation, die Planung der Therapieschwerpunkte sowie die Darstellung des Behandlungsprozesses.
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

Fibrous 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

This 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

It 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
Modified hot plate method for synthesizing MoO3 nanoplates
Authors: Zhang Chi , Wei Wei , Pan Jia-qi , Gong Zhong-miao , Chen Yi-gang , Cui Yi
Published: May 2022

Molybdenum trioxide (MoO3 ) with layered structures adopts exotic physical features, which has evoked an extensive interest in electronic and photoelectronic devices. Here, we report a low-cost, simplehandle, atmospheric-pressure, and rapid-synthesis technique for growing large-scale MoO3 crystals, i.e., a modified hot plate method. The growth rate and morphology of the MoO3 crystals were well controlled by changing source temperatures and substrates. Complementary measurements, including optical microscope, atomic force microscope, X-ray diffraction, Raman spectroscope, and scanning near-field optical microscope, were used to investigate the structural and physical properties. The results reveal that large-scale MoO3 crystals with well-defined crystallinity have been obtained. Meanwhile, surface hyperbolic phonon polaritons on as-prepared MoO3 crystal planes have also been observed, which may provide an attractive insight into nanoelectronic and nanophotonic devices.
Influence of vibrating wall on microswimmer migration in a channel
Authors: Ma Tengyang , Qin Fenghua , Cheng Wan , Luo Xisheng
Published: May 2022

The migration of microorganisms or synthetic microscale robots is always affected by the local environment, such as the surrounding fluid or muscular contractions. This paper describes a numerical study and asymptotic analysis of the influence of a moving boundary on the migration of a microswimmer in a channel. The locomotion of a finite swimmer between vibrating walls is simulated with both a beating and motionless flagellum. The swimmer can be propelled by the wall vibration, and this propulsion is independent of the self-propulsion of the beating flagellum. To reveal the influence of the vibrating walls, asymptotic analysis is applied to two models, one with an infinitely long filament placed at the channel center and another with an infinitesimally small swimmer. The results show that the vibrating wall effect depends on the ratio of the distance between the walls to the wavelength. The wall effect functions for the two models are obtained for both two-dimensional and circular channels. The finite swimmer in the two-dimensional channel moves with the velocity of the flow induced by the vibrating wall, rather than the swimming speed of the infinite filament. However, in the circular channel, there is no difference between the migration speeds of the two models, and the range of the wall influence is much larger than in the two-dimensional case.
Effective entropy production and thermodynamic uncertainty relation of active Brownian particles
Authors: Cao Zhiyu , Su Jie , Jiang Huijun , Hou Zhonghuai
Published: May 2022

Understanding stochastic thermodynamics of the active Brownian particles system has been an important topic in very recent years. However, thermodynamic uncertainty relation (TUR), a general inequality describing how the precision of an arbitrary observable current is constraint by energy dissipation, has not been fully studied for a many-body level. Here, we address such an issue in a general model of an active Brownian particles system by introducing an effective Fokker–Planck equation, which allows us to identify a generalized entropy production only by tracking the stochastic trajectory of particles' position, wherein an activity and configuration dependent diffusion coefficient come into play an important role. Within this framework, we are able to analyze the entropic bound as well as TUR associated with any generalized currents in the systems. Furthermore, the effective entropy production has been found to be a reliable measure to quantify the dynamical irreversibility, capturing the interface and defects of motility induced phase separation. We expect the new conceptual quantities proposed here to be broadly used in the context of active matter.
Coulomb-explosion imaging tackles an 11-atom molecule
Authors: Miller Johanna L.
Published: May 2022

Until now, the technique was thought to work only on molecules with no more than about five atoms. A powerful x-ray source leaves that limit in the dust.
ABACC to the future
Authors: Dunlap Christopher
Published: May 2022

At the end of the Cold War, two South American rivals built a system of nuclear safeguards that culminated in the 1991 founding of a bilateral organization, ABACC. Can that nonproliferation regime be exported?
Quantum materials out of equilibrium
Authors: Rodriguez-Vega Martin , Vergniory Maia G. , Fiete Gregory A.
Published: May 2022

Illuminating materials with lasers can create intriguing magnetic and topological states of matter..
Quasicrystals and the birth of the atomic age
Authors: Bindi Luca , Steinhardt Paul J.
Published: May 2022

The first nuclear bomb explosion led to the formation of a novel form of matter, known as a quasicrystal, with an elemental composition that had never been seen before.
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

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

Life 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

Structural 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

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

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

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

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

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 >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

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.
Warburg Effect in Anopheles Mosquito Anti‐Bacterial Immunity
Authors: Moon Alex S. , Xu Jiannong
Published: May 2022

Otto Warburg discovered cancer cells favor increased glycolysis with pyruvate being converted to lactate rather than acetyl‐CoA for the tricarboxylic acid cycle, and this is termed the Warburg effect. Warburg metabolism has been found to occur in mammalian rapidly proliferating cancer and immune cells. Anopheles species mosquitoes, the vectors for malaria, rely on their metabolic system to provide energy and intermediates for their innate immune system, so called immunometabolism. We posited Warburg metabolism is involved in Anopheles sp. mosquito’s immune response. We designed an anti‐bacterial immunity model using intrathoracic inoculations of Escherichia coli K12, avirulent bacterium, and Enterobacter sp. Ag1, virulent bacterium isolated from the Anopheles sp. midgut, to test the immunometabolism response. We found a statistically significant doubling in lactic acid upon Ent sp. immune challenge as compared to injection injury controls using a lactate assay (t‐test, p = 0.0016). This provides evidence to support increased Warburg metabolism in immune challenged mosquitoes. We then fed Anopheles sp. mosquitoes dimethyl fumarate (DMF), a GAPDH inhibitor, and challenged the mosquitoes with E. coli. We found a significant mortality was observed in DMF treated mosquitoes compared to control (Mantel‐Cox, p < 0.001). By inhibiting the utilization of glycolysis and Warburg metabolism, decreased survival related to immune challenge is observed, showing Warburg metabolism is crucial for mosquito immunity. We believe current cancer therapeutics targeting Warburg metabolism can be an effective vector control strategy to prevent mosquito‐borne diseases.
A SUMO‐dependent Pathway for Cytosolic Protein Quality Control
Authors: Wang Wei , Matunis Michael
Published: May 2022

Protein quality control (PQC) maintains proteostasis in cells, whereas PQC dysregulation is found in diseases such as cancers, cardiovascular diseases, and neurodegenerative disorders. Over the past few decades, remarkable progress has been made in understanding compartmentalized PQC pathways that operate inside the nucleus and the endoplasmic reticulum (ER). The small ubiquitin‐related modifiers (SUMOs), for example, were recently found to participate in a nuclear PQC pathway that involves selective sumoylation of misfolded proteins by the SUMO E3 ligase PML, and subsequent recognition and ubiquitylation by the SUMO‐targeted ubiquitin E3 ligase RNF4 (Guo et al., Mol Cell, 2014). Roles of SUMOs in cytoplasmic PQC, however, have not previously been reported. Using yeast mutants and human knockout cell lines, our lab has recently identified a conserved SUMO‐dependent pathway for degradation of a cytosolic, misfolded protein model substrate. The substrate consists of GFP fused to an N‐terminal nuclear export signal (NES) and a C‐terminal hydrophobic degron known as CL1 (NES‐GFP‐CL1). Using protein stability assays, we observed a decrease in the turnover rate of NES‐GFP‐CL1 in a yeast SUMO mutant strain and a human U2OS SUMO1 knockout cell line. Further exploration using nuclear and ER‐localized substrates revealed that this pathway is specific for soluble, cytosolic proteins. In addition, analysis of a U2OS SUMO2 knockout cell line revealed that the observed PQC pathway is specific for the SUMO1 paralogue. This suggests a distinct mechanism from the previously characterized nuclear PML‐SUMO‐RNF4 pathway, which targets misfolded proteins modified by SUMO2/3 polymeric chains. Using cellular fractionation studies, we observed an increase in levels of insoluble NES‐GFP‐CL1 specifically in SUMO1 knockout cells compared to wild type cells. We therefore propose a model where SUMO1 modification of misfolded cytosolic proteins promotes their turnover by enhancing solubility and preventing aggregation. Results from our studies reveal a novel cytosolic PQC regulatory network and provide insights into roles for sumoylation in PQC‐associated diseases.
ALDH2 Deficiency Enhances Mechanical Overload‐Induced Protein Synthesis but Not Muscle Mass
Authors: Jee Eunbin , Tamura Yuki , Kouzaki Karina , Kotani Takaya , Nakazato Koichi
Published: May 2022

Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme of redox homeostasis and ethanol metabolism. Our recent work has indicated an important role for ALDH2 in regulating muscle homeostasis as well. However, the underlying mechanism and adaptability of ALDH2 in skeletal muscle remain highly elusive. We herein examined whether ALDH2 deficiency modifies mechanical overload‐induced muscle hypertrophy and related cellular process. Ten‐week‐old male ALDH2 knockout (background strain: C57BL/6J) and wild‐type littermates were involved in this work. Unilateral synergist ablation (SA; the surgical removal of gastrocnemius and soleus muscles) and sham surgery were performed as an experimental hypertrophy model. Seven days after surgery, plantaris muscles were collected. ALDH2 deficiency augmented SA‐induced activation of mTORC1 (a key regulator of muscle anabolism), based on the increase in phosphorylation of p70S6K at Thr389. Concomitantly, higher amounts of puromycin‐labeled peptides (a marker of protein synthesis rate) were observed in ALDH2 deficit muscle. These observations suggest that ALDH2 deficiency promotes SA‐induced muscle hypertrophy. Unexpectedly, there was no statistical difference in SA‐induced muscle hypertrophy between genotypes. To explore potential mechanisms underlying mismatch between protein synthesis signal and muscle size, we conducted RNA‐seq experiment. However, we couldn’t detect any notable gene potentially affecting muscle mass between genotypes. In conclusion, ALDH2 deficiency enhances mechanical overload‐induced mTORC1 activity and protein synthesis but not muscle mass. Pathways other than protein synthesis and/or post‐transcriptional events may dominantly affect muscle mass in ALDH2 deficit mice.
Multi‐assay profiling of diminazene library reveals predictive bidirectional modulation of MALAT1 triplex stability in vitro
Authors: Zafferani Martina
Published: May 2022

The rapidly increasing characterization of RNA tertiary structures has revealed their pervasiveness and active roles in human diseases. Therefore, small molecule‐mediated modulation of RNA tertiary structures constitutes an attractive avenue for the development of tools for both therapeutically targeting and/or uncovering the pathways associated with these RNA motifs. This potential has been highlighted by preliminary targeting of the triple helix present at the 3’‐end of the non‐coding RNA MALAT1, a transcript implicated in several human diseases. This triplex has been reported to decrease the transcript susceptibility to degradation and, ultimately, promote its cellular accumulation. While small molecules have been shown to bind and impact the stability of the MALAT1 triple helix, the molecular recognition properties behind these structural modulations are not well understood. To elucidate these properties, we designed a focused library utilizing the diminazene scaffold, which is underexplored but precedented for nucleic acid binding, to target the MALAT1 triple helix. To gain a holistic perspective on small molecule recognition, we evaluated this library through a multi‐dimensional approach to assess what parameters, if any, could predict small molecule affinity and effect on triplex stability. We designed and/or optimized competition, calorimetry, and thermal shift assays as well as a novel enzymatic degradation assay, which led to the discovery of bidirectional modulators of triple helix stability within the scaffold‐centric library. Furthermore, employment of quantitative structure activity relationship (QSAR) afforded predictive models for stability‐ and affinity‐based assays. Together, this work provides novel biophysical tools for the evaluation of small molecule: RNA triplex interactions and predictive models that can be applied to small molecule interrogation of the growing body of disease‐associated RNA triple helices.
Asymmetric Control of Food Intake by Left and Right Vagal Sensory Neurons
Authors: de Araujo Alan , Singh Arashdeep , McDougle Molly , Braga Isadora , Leme Gabriel , de Lartigue Guillaume
Published: May 2022

Gut‐innervating vagal sensory neurons residing in the nodose ganglia (NG) conveys meal‐borne signals and control food intake, however, the underlying gut‐brain neurocircuit is unclear. The neuropeptide cocaine‐ and amphetamine‐regulated transcript (CART) is expressed in a subpopulation of vagal sensory neurons (~40%) that innervate the whole length of the gut and its release in the NTS is sufficient for meal termination. Thus, it can be an excellent target to understand the role of sensory neurons in feeding. Emerging evidence suggests that right or left NG (LNG or RNG) neurons recruit different downstream central circuits to control feeding, but the mechanisms remain poorly understood. Our hypothesis is that LNGCART and RNGCART neurons sense different meal‐related signals and are necessary and sufficient to modulate feeding.

Methods

In vivo calcium imaging, viral neuronal tracing, and feeding behaviors were assessed in response to chemo‐ and opto‐genetic stimulation of gut‐innervating vagal sensory neurons using CARTcre mice.

Results

Anatomical tracing revealed that LNGCART and RNGCART neurons innervate different regions of the duodenum (n=3). LNGCART innervate the muscular layer, while RNGCART innervate the villi. Importantly, 2‐photon calcium imaging highlighted real time increased activity in LNGCART in response to stretch, while intraduodenal fat infusions preferentially increased RNGCART neuron activity (n=7/group). Mice with LNGCART neurons ablation consumed higher volumes of liquid meal indicative of attenuated response to gastric and intestinal distension (n=6‐7/group). Furthermore, chemogenetic stimulation of LNGCART, but not RNGCART, caused pronounced and sustained hypophagia (n=7/group). Interestingly, mice with chemogenetic activation of RNGCART, but not LNGCART, increased flavor conditioning (n=7/group), while ablation of RNGCART neurons abolished the conditioned flavor preference that was paired with intragastric fat infusion (n=7/group) supporting their role in reward. In addition, optogenetic stimulation of RNGCART promoted self‐stimulation in a nose poke task (n=4). Lastly, dopaminergic neurons of the substantia nigra increased their firing rate in response to intraduodenal fat infusion, but not duodenal distension (n=2/group).

Conclusion

Left and right vagus nerves provide different sensory information about a meal to the brain. Both anatomical and behavioral feeding studies support the necessity and sufficiency LNGCART neurons as food quantity detectors and RNGCART neurons as food reward mediators ‐ which has less influence on how much is consumed but rather plays a role in the decision‐making process about which foods to consume. Our findings on asymmetrical vagal innervation of the gut provides new mechanistic insight for how feeding decisions are made in response to vast and complex meal‐related signals.