bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of embryo density on cell number of day 3 embryos cultured in a 30-μl drop: a retrospective cohort study
Authors: Shi Cheng , Sun Tie Cheng , Chen Shu Wen , Wang Ping , Liang Rong , Duan Sheng Nan , Han Hong Jing , Shen Huan , Chen Xi
Published: March 2022

For individual cultures, findings on regulating embryo density by changing the microdrop volume are contradictory. The aim of this study was to investigate the relationship between embryo density and the developmental outcome of day 3 embryos after adjusting covariates. In total, 1196 embryos from 206 couples who had undergonein vitrofertilization treatment were analyzed retrospectively. Three embryo densities were used routinely, i.e. one embryo in a drop (30 μl/embryo), two embryos in a drop (15 μl/embryo) and three embryos in a drop (10 μl/embryo). Embryo quality on day 3 was evaluated, both the cell number of day 3 embryos and the proportion of successful implantations served as endpoints. Maternal age, paternal age, antral follicles and level of anti-Müllerian hormone, type of infertility, controlled ovarian stimulation protocol, length of stimulation, number of retrieved oocytes, number of zygotes (two pronuclei) and insemination type were covariates and adjusted. After adjusting fully for all covariates, the cell number of day 3 embryos was significantly increased by 0.40 (95% CI 0.00, 0.79;P= 0.048) and 0.78 (95% CI 0.02, 1.54;P= 0.044) in the 15 μl/embryo and 10 μl/embryo group separately, compared with the 30 μl/embryo group. The proportions of implanted embryos were 42.1%, 48.7% and 0.0% in the 30 μl/embryo, 15 μl/embryo and 10 μl/embryo groups respectively. There was no statistical significance (P= 0.22) between the 30 μl/embryo group and the 15 μl/embryo group. After adjusting for confounders that were significant in univariate analysis, embryo density was still not associated with day 3 embryo implantation potential (P> 0.05). In a 30-μl microdrop, culturing embryos with an embryo density of both 15 and 10 μl/embryo increased the cell number of day 3 embryos, which did not benefit embryo implanting potential, compared with individual culture of 30 μl/embryo.
The French RevolutionNow; or, Carlyle's Eternal Return
Authors: Allison Mark
Published: March 2022

This essay utilizes the publication of the first scholarly edition ofThe French Revolution: A History(1837) as an occasion to reassess this thoroughgoingly radical—and puzzlingly neglected—masterpiece. It explores how Thomas Carlyle's maverick conceptions of sympathy and affect, the relationship of the individual and the collective, and narrative itself underlie the audacious stylistic innovations that characterize this singular text. Moreover, this paper interprets Carlyle's history as a chronicle of inverted utopianism; that is, an apocalyptic manifestation of what is nevertheless a properly utopian longing for heaven on earth. Thus read, The French Revolution offers perspective on our own volatile times as well as a promise—or perhaps a warning—that the insurrectionary struggle for Liberty, Equality, and Fraternity is not over.
The normative grounds for NICE decision-making: a narrative cross-disciplinary review of empirical studies
Authors: Charlton Victoria
Published: March 2022

The National Institute for Health and Care Excellence (NICE) is the UK's primary health care priority-setter, responsible for advising the National Health Service on its adoption of health technologies. The normative basis for NICE's advice has long been the subject of public and academic interest, but the existing literature does not include any comprehensive summary of the factors observed to have substantively shaped NICE's recommendations. The current review addresses this gap by bringing together 29 studies that have explored NICE decision-making from different disciplinary perspectives, using a range of quantitative and qualitative methods. It finds that although cost-effectiveness has historically played a central role in NICE decision-making, 10 other factors (uncertainty, budget impact, clinical need, innovation, rarity, age, cause of disease, wider societal impacts, stakeholder influence and process factors) are also demonstrably influential and interact with one another in ways that are not well understood. The review also highlights an over-representation in the literature of appraisals conducted prior to 2009, according to methods that have since been superseded. It suggests that this may present a misleading view of the importance of allocative efficiency to NICE's current approach and illustrates the need for further up-to-date research into the normative grounds for NICE's decisions.
“Cheerful Nonchalance” as an Affective Response to Precarity: Refusing Safety Measures in Eastern Siberia
Authors: Orlova Vasilina
Published: March 2022

This article is building on the analysis of affective responses to precarious conditions to argue that one such response can be described as “cheerful nonchalance.” The village of Anosovo emerged in 1961 after the construction of the Bratsk dam on the Angara River. Many villagers were certain Anosovo was a temporary settlement from the beginning. Yet more than half a century later, Anosovo is still there, even as its population diminishes. When not only the state gives up on a place, but people also adopt a kind of blasé attitude to the risks of daily life, the affect of cheerful nonchalance comes to life to help with the living. Various affective attitudes toward precarity and uncertainty in post-Soviet realities and beyond have been described as nostalgia, “patriotism of despair,” and “cruel optimism” in post-Soviet realities and beyond. Nonchalance has been overlooked, even though it is doing the work of making life possible in a place enduring socio-economic disenfranchisement. With the use of ethnographic methods, this article shows how mundane events—such as the implementation of a polygraph test by a timber harvesting firm or a refusal to abide by safety measures like wearing seat belts—are the expressions of the affect of nonchalance.
The Thaw's Provincial Margins: Place, Community and Canon in Pages from Tarusa
Authors: Jones Polly
Published: March 2022

This article offers a comprehensive examination of the editing, publication, reception, and after-effects of the almanac Pages from Tarusa (1961), a major, but little-analyzed, Soviet publication of the Thaw. Drawing on a wide range of memoir and local archive material, it argues that Pages was crucially shaped by Tarusa's position astride dacha territory and the “101st kilometer”, the borders of the metropolitan zone from which Gulag and exile returnees were banned. Pages’ diverse and flexible cohort, and its editing practices, were shaped by the migration, residency, and socializing practices associated with both these territories. The almanac's concern with cultural and social (re-)inclusion and innovation was visible both in its content (especially its overlooked documentary texts) and in the “emotional style” of its cohort and their activities in Tarusa. The almanac's production, as well as its content, epitomized key elements of Thaw sensibility and sociability that had hitherto largely been confined to private kompanii, and more inchoate. In concluding, the article outlines the subsequent development of these Thaw agendas and behaviors in the “Tarusa fraternity” and in Tarusa itself, including the emergence of samizdat and dissidence, as well as the “provincialization” of the local Soviet literary scene.
MDS mit Deletion 5q
Authors: Wilk Christian Matthias , Goede Jeroen Simon
Published: March 2022

Zusammenfassung. Die Deletion des langen Arms des Chromosoms 5, del(5q), ist eine bei Myelodysplastischen Syndromen rekurrent auftretende Veränderung, die diese Erkrankungen nicht nur pathopysiologisch sondern auch hinsichtlich ihrer Therapie von anderen myelodysplastischen Syndromen unterscheidet. Die isoliert auftretende del(5q) ist mit einem günstigen Risikoprofil assoziiert und kann seit der Zulassung von Lenalidomid für diese Entität auch gezielt therapiert werden. Zu unterscheiden von der isoliert auftretenden del(5q) sind Veränderungen am langen Arm von Chromosom 5 in Verbindung mit mehr als einer anderen Mutationen, die diese Formen des MDS zu Hochrisikoerkrankungen machen.
Wenn die Dysplasie und die Proliferation zusammen kommen: MDS/MPN
Authors: Benz Rudolf
Published: March 2022

Zusammenfassung. Myelodysplastische/myeloproliferative Neoplasien sind nicht selten diagnostische und therapeutische Herausforderungen. Da Entzündungen gehäuft bei diesen Störungen gesehen werden können und zu ähnlichen Blutbildveränderungen führen, kann eine gesicherte Diagnose nicht selten erst im Verlauf gestellt werden. Aus therapeutischer Sicht stehen sich das Bremsen der Proliferation und die Stimulation der Zytopenie bei Dysplasie konträr gegenüber. Hypomethylinisierende Substanzen sind daher eine typische Therapie bei diesen Krankheitsbildern.
Freude durch Sport und Bewegung bei psychischen Erkrankungen
Authors: Kreppke Jan-Niklas , Cody Robyn , Faude Oliver , Gerber Markus
Published: March 2022

Zusammenfassung. Die Sport- und Bewegungstherapie ist eine effektive Ergänzung in der Therapie der Major Depression. Die Empfehlungen von mind. 150 Minuten moderater oder 75 Minuten intensiver körperlicher Aktivität pro Woche sollten erfüllt werden, damit positive Effekte durch körperliche Aktivität erreicht werden. Zudem sollten individuelle Bedürfnisse und der körperliche Gesundheitszustand in die Planung und Durchführung mit einbezogen werden, damit die Patientinnen und Patienten auch langfristig Freude an der Bewegung haben.
The Three-Level Curriculum Sports Psychiatry and an Evaluation of the First Course “Basic Health Care in Sports Psychiatry”
Authors: Hofmann Carlos Gonzalez , Claussen Malte Christian
Published: March 2022

Abstract. Due to scientific progress and diversification in medicine and psychiatry, there is a need for specialization in sports psychiatry. Therefore, the SSSPP has been developing a curriculum on sports psychiatry. Different backgrounds and approaches within the above-mentioned areas are presented here since they have influenced the development of the three-level curriculum. The structure of the three-level curriculum, which contains theory, practical experience, and supervision, encompassing 80 hours of additional training, will also be explained. Within this curriculum, basic knowledge in sports medicine, sports psychology, sports science, and applied sports theory will also be taught. Other subjects include sports and exercise on mental disorders, mental disorders in competitive sports, sports as a coping strategy, and other contents. Moreover, different contents and key topics of the curriculum’s three levels will be presented.
Gewalt und Missbrauch im Leistungssport
Authors: Raas Marcel I. , Schneeberger Andres Ricardo , Karunaharamoorthy Achudhan , Sinsel Daniela , Schmidt Ralph Erich , Hofmann Carlos Gonzalez , Imboden Christian , Hemmeter Ulrich Michael , Seifritz Erich , Claussen Malte Christian
Published: March 2022

Zusammenfassung. Gewalt und Missbrauch im Leistungssport, wie physische und psychische Misshandlungen, Vernachlässigungen sowie sexueller Missbrauch betreffen Kinder, Jugendliche und Erwachsene. Daraus folgen oft schwerwiegende körperliche, psychische und soziale Konsequenzen. In den gegenwärtigen medizinischen und pädagogischen Versorgungskonzepten von Sportlerinnen und Sportlern fehlt die konsequente Einbindung (sport-)psychiatrisch-psychotherapeutischer, klinisch-psychologischer und -psychotherapeutischer, entwicklungspädiatrischer und entwicklungspsychologischer Expertisen. Problemfelder ergeben sich durch die fliessenden Übergänge zwischen Belästigung, nicht-körperlicher und körperlicher Gewalt. Das vorliegende Positionspapier enthält Empfehlungen zur Entwicklung eines Konzepts für den Schutz psychischer Gesundheit im Leistungssport und für den Umgang mit psychischen Belastungen und Erkrankungen durch qualifizierte medizinische Fachleute für die psychische Gesundheit, d.h. Kinder-, Jugend- und Erwachsenenpsychiater_innen und -psychotherapeut_innen mit einer spezifischen Expertise im Leistungssport: Sportpsychiater_innen und -psychotherapeut_innen. Gemäss den Empfehlungen sollten Fachleute ausserdem weitere Kompetenzen mitbringen und entwickeln, insbesondere in Fragen der Ethik, des Kinderschutzes, des Schutzes vor Gewalt und Missbrauch im Leistungssport, des Bewusstseins für und des Umgangs mit Grenzverletzungen, der Kindesentwicklung sowie der Transparenz in Trainingsstrukturen und -beziehungen.
A Shallow and Left‐Lateral Rupture Event of the 2021 Mw 5.3 Baicheng Earthquake: Implications for the Diffuse Deformation of Southern Tianshan
Authors: Yao Yuan , Wen Shaoyan , Yang Liao , Wu Chuanyong , Sun Xiaolin , Wang Lili , Zhang Zhibin
Published: March 2022

On 24 March 2021, an Mw 5.3 earthquake struck northwest Baicheng, located in the Kuqa fold‐and‐thrust belt (FTB), northwest China. In the current study, interferometric synthetic aperture radar (InSAR) data were used to investigate the associated fault rupture solution (dip, dip direction, and slip sense), to determine the geometry of the seismogenic structure; the high‐resolution images of the surface rupture were obtained using an unmanned aerial vehicle (UAV). This geometric model, along with the co‐seismic slip distribution from the InSAR data, and deformation characteristics of co‐seismic surface rupture revealed that: (a) it was a shallow event, the focal depth was 0.5–2 km, and the co‐seismic slip was distributed in the 0–7 km range with high dip angles (66°, 70°). (b) A 4‐km long surface rupture with obvious left‐lateral strike‐slip was distributed on the surface, and the maximum strike‐slip displacement and width were 0.79 and 0.7 m, respectively. This left‐lateral strike‐slip event indicates that the relative motion between the Tianshan and Tarim blocks is a continuous and diffuse deformation process. The study shows that, when evaluating the earthquake risk of the Kuqa FTB, we should consider both the front position of the fault outburst and the internal compressional salt‐related structures, which can also produce moderate to strong earthquakes.
An Alternative Incoming Correction for Cosmic‐Ray Neutron Sensing Observations Using Local Muon Measurement
Authors: Stevanato L. , Baroni G. , Oswald S. E. , Lunardon M. , Mares V. , Marinello F. , Moretto S. , Polo M. , Sartori P. , Schattan P. , Ruehm W.
Published: March 2022

Measuring the variability of incoming neutrons locally would be usefull for the cosmic‐ray neutron sensing (CRNS) method. As the measurement of high energy neutrons is not so easy, alternative particles can be considered for such purpose. Among them, muons are particles created from the same cascade of primary cosmic‐ray fluxes that generate neutrons at the ground. In addition, they can be easily detected by small and relatively inexpensive detectors. For these reasons they could provide a suitable local alternative to incoming corrections based on remote neutron monitor data. The reported measurements demonstrated that muon detection system can detect incoming cosmic‐ray variations locally. Furthermore the precision of this measurement technique is considered adequate for many CRNS applications.
Modeling the Dynamics of Salt Marsh Development in Coastal Land Reclamation
Authors: Xu Yiyang , Kalra Tarandeep S. , Ganju Neil K. , Fagherazzi Sergio
Published: March 2022

The valuable ecosystem services of salt marshes are spurring marsh restoration projects around the world. However, it is difficult to determine the final vegetated area based on physical drivers. Herein, we use a 3D fully coupled vegetation‐hydrodynamic‐morphological modeling system to simulate the final vegetation cover and the timescale to reach it under various forcing conditions. Marsh development in our simulations can be divided in three distinctive phases: A preparation phase characterized by sediment accumulation in the absence of vegetation, an encroachment phase in which the vegetated area grows, and an adjustment phase in which the vegetated area remains relatively constant while marsh accretes vertically to compensate for sea level rise. Sediment concentration, settling velocity, sea level rise, and tidal range each comparably affect equilibrium coverage and timescale in different ways. Our simulations show that the Unvegetated‐Vegetated Ratio also relates to sediment budget in marsh development under most conditions.
Experimentally Mapping Water Surface Elevation, Velocity, and Pressure Fields of an Open Channel Flow Around a Stalk
Authors: Moreto Jose Roberto , Reeder William Jeff , Budwig Ralph , Tonina Daniele , Liu Xiaofeng
Published: March 2022

Quantification of velocity and pressure fields over streambeds is important for predicting sediment mobility, benthic and hyporheic habitat qualities, and hyporheic exchange. Here, we report the first experimental investigation of reconstructed water surface elevations and three‐dimensional time‐averaged velocity and pressure fields quantified with non‐invasive image techniques for a three‐dimensional free surface flow around a barely submerged vertical cylinder over a plane bed of coarse granular sediment in a full‐scale flume experiment. Stereo particle image velocimetry coupled with a refractive index‐matched fluid measured velocity data at multiple closely‐spaced parallel and aligned planes. The time‐averaged pressure field was reconstructed using the Rotating Parallel Ray Omni‐Directional integration method to integrate the pressure gradient terms obtained by the balance of all the Reynolds‐Averaged Navier‐Stokes equation terms, which were evaluated with stereo particle image velocimetry. The detailed pressure field allows deriving the water surface profile deformed by the cylinder and hyporheic flows induced by the cylinder.
Sensitivity of a Coarse‐Resolution Global Ocean Model to a Spatially Variable Neutral Diffusivity
Authors: Holmes R. M. , Groeskamp S. , Stewart K. D. , McDougall T. J.
Published: March 2022

Motivated by recent advances in mapping mesoscale eddy tracer mixing in the ocean we evaluate the sensitivity of a coarse‐resolution global ocean model to a spatially variable neutral diffusion coefficient κn(x, y, z). We gradually introduce physically motivated models for the horizontal (mixing length theory) and vertical (surface mode theory) structure of κn along with suppression of mixing by mean flows. Each structural feature influences the ocean's hydrography and circulation to varying extents, with the suppression of mixing by mean flows being the most important factor and the vertical structure being relatively unimportant. When utilizing the full theory (experiment “FULL”) the interhemispheric overturning cell is strengthened by 2 Sv at 26°N (a ∼20% increase), bringing it into better agreement with observations. Zonal mean tracer biases are also reduced in FULL. Neutral diffusion impacts circulation through surface temperature‐induced changes in surface buoyancy fluxes and nonlinear equation of state effects. Surface buoyancy forcing anomalies are largest in the Southern Ocean where a decreased neutral diffusivity in FULL leads to surface cooling and enhanced dense‐to‐light surface water mass transformation, reinforced by reductions in cabbeling and thermobaricity. The increased water mass transformation leads to enhanced midlatitude stratification and interhemispheric overturning. The spatial structure for κn in FULL is important as it enhances the interhemispheric cell without degrading the Antarctic bottom water cell, unlike a spatially uniform reduction in κn. These results highlight the sensitivity of modeled circulation to κn and motivate the use of physics‐based models for its structure.
Genetics of glutamate and its receptors in autism spectrum disorder
Authors: Nisar Sabah , Bhat Ajaz A. , Masoodi Tariq , Hashem Sheema , Akhtar Sabah , Ali Tayyiba Akbar , Amjad Sara , Chawla Sanjeev , Bagga Puneet , Frenneaux Michael P. , Reddy Ravinder , Fakhro Khalid , Haris Mohammad
Published: March 2022

Autism spectrum disorder (ASD) is a neurodevelopmental impairment characterized by deficits in social interaction skills, impaired communication, and repetitive and restricted behaviors that are thought to be due to altered neurotransmission processes. The amino acid glutamate is an essential excitatory neurotransmitter in the human brain that regulates cognitive functions such as learning and memory, which are usually impaired in ASD. Over the last several years, increasing evidence from genetics, neuroimaging, protein expression, and animal model studies supporting the notion of altered glutamate metabolism has heightened the interest in evaluating glutamatergic dysfunction in ASD. Numerous pharmacological, behavioral, and imaging studies have demonstrated the imbalance in excitatory and inhibitory neurotransmitters, thus revealing the involvement of the glutamatergic system in ASD pathology. Here, we review the effects of genetic alterations on glutamate and its receptors in ASD and the role of non-invasive imaging modalities in detecting these changes. We also highlight the potential therapeutic targets associated with impaired glutamatergic pathways.
Reduced cerebellar cortical thickness in World Trade Center responders with cognitive impairment
Authors: Clouston Sean A. P. , Kritikos Minos , Huang Chuan , Kuan Pei-Fen , Vaska Paul , Pellecchia Alison C. , Santiago-Michels Stephanie , Carr Melissa A. , Gandy Sam , Sano Mary , Bromet Evelyn J. , Lucchini Roberto G. , Luft Benjamin J.
Published: March 2022

Prior research has demonstrated high levels of cognitive and physical functional impairments in World Trade Center (WTC) responders. A follow-up neuroimaging study identified changes to white matter connectivity within the cerebellum in responders with cognitive impairment (CI). In the first study to examine cerebellar cortical thickness in WTC responders with CI, we fielded a structural magnetic resonance imaging protocol. WTC responders (N = 99) participated in a structural magnetic resonance imaging (MRI) study, of whom 48 had CI. Participants with CI did not differ demographically or by intracranial volume when compared to cognitively unimpaired participants. MRIs were processed using the CERES imaging pipeline; bilateral cortical thickness in 12 cerebellar lobules was reported. Analyses were completed comparing mean cerebellar cortical thickness across groups. Lobules were examined to determine the location and functional correlates of reduced cerebellar cortical thickness. Multivariable-adjusted analyses accounted for the false discovery rate. Mean cerebellar cortical thickness was reduced by 0.17 mm in responders with CI. Decrements in cerebellar cortical thickness were symmetric and located in the Cerebellar Crus (I and II), and in Lobules IV, VI, VIIb, VIIIa, VIIIb, and IX. Cerebellar cortical thickness was associated with episodic memory, response speed, and tandem balance. WTC responders with CI had evidence of reduced cerebellar cortical thickness that was present across lobules in a pattern unique to this cohort.
Versatile subtypes of pericytes and their roles in spinal cord injury repair, bone development and repair
Authors: Zhu Sipin , Chen Min , Ying Yibo , Wu Qiuji , Huang Zhiyang , Ni Wenfei , Wang Xiangyang , Xu Huazi , Bennett Samuel , Xiao Jian , Xu Jiake
Published: March 2022

Vascular regeneration is a challenging topic in tissue repair. As one of the important components of the neurovascular unit (NVU), pericytes play an essential role in the maintenance of the vascular network of the spinal cord. To date, subtypes of pericytes have been identified by various markers, namely the PDGFR-β, Desmin, CD146, and NG2, each of which is involved with spinal cord injury (SCI) repair. In addition, pericytes may act as a stem cell source that is important for bone development and regeneration, whilst specific subtypes of pericyte could facilitate bone fracture and defect repair. One of the major challenges of pericyte biology is to determine the specific markers that would clearly distinguish the different subtypes of pericytes, and to develop efficient approaches to isolate and propagate pericytes. In this review, we discuss the biology and roles of pericytes, their markers for identification, and cell differentiation capacity with a focus on the potential application in the treatment of SCI and bone diseases in orthopedics.
The possible involvement of circRNA DMNT1/p53/JAK/STAT in gestational diabetes mellitus and preeclampsia
Authors: Bao Dongqin , Zhuang Chaohui , Jiao Yan , Yang Li
Published: March 2022

Circular RNA (circRNA) plays an important role in biological processes of gestational diabetes mellitus (GDM) and preeclampsia (PE). However, the mechanisms for circRNA DMNT1 (circ-DMNT1) in GDM and PE remain unclarified. The expression levels of circ-DMNT1 and p53 in GDM and PE were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. When the expression of circ-DMNT1 or p53 was abnormal, cell counting kit-8 (CCK-8) assay, bromodeoxyuridine (BrdU) staining, flow cytometry, cell scratch, and Transwell assays were used to assess cell viability, proliferation, cell cycle, apoptosis, migration, and invasion of trophoblast cells, respectively. Subsequently, the binding relationship between circ-DMNT1 and p53 was verified by RNA pull-down and RIP analysis, followed by the determination of JAK/STAT pathway-related protein expression levels using western blot analysis. Both circ-DMNT1 and p53 were highly expressed in GDM and PE. Upregulation of circ-DMNT1 or p53 inhibited trophoblast cell viability, proliferation, migration, and invasion, meanwhile promoting cell apoptosis but blocking cell cycle progression. However, downregulation of circ-DMNT1 or p53 induced trophoblast cell survival. In GDM and PE, circ-DMNT1 activated the JAK/STAT pathway by binding to p53, which resulted in increased expression levels of p-JAK and p-STAT. The results suggested that circ-DMNT1 was involved in the deterioration of GDM and PE, possibly through inducing p53 expression and activating the JAK/STAT signaling pathway.
Machine learning discovery of missing links that mediate alternative branches to plant alkaloids
Authors: Vavricka Christopher J. , Takahashi Shunsuke , Watanabe Naoki , Takenaka Musashi , Matsuda Mami , Yoshida Takanobu , Suzuki Ryo , Kiyota Hiromasa , Li Jianyong , Minami Hiromichi , Ishii Jun , Tsuge Kenji , Araki Michihiro , Kondo Akihiko , Hasunuma Tomohisa
Published: March 2022

Engineering the microbial production of secondary metabolites is limited by the known reactions of correctly annotated enzymes. Therefore, the machine learning discovery of specialized enzymes offers great potential to expand the range of biosynthesis pathways. Benzylisoquinoline alkaloid production is a model example of metabolic engineering with potential to revolutionize the paradigm of sustainable biomanufacturing. Existing bacterial studies utilize a norlaudanosoline pathway, whereas plants contain a more stable norcoclaurine pathway, which is exploited in yeast. However, committed aromatic precursors are still produced using microbial enzymes that remain elusive in plants, and additional downstream missing links remain hidden within highly duplicated plant gene families. In the current study, machine learning is applied to predict and select plant missing link enzymes from homologous candidate sequences. Metabolomics-based characterization of the selected sequences reveals potential aromatic acetaldehyde synthases and phenylpyruvate decarboxylases in reconstructed plant gene-only benzylisoquinoline alkaloid pathways from tyrosine. Synergistic application of the aryl acetaldehyde producing enzymes results in enhanced benzylisoquinoline alkaloid production through hybrid norcoclaurine and norlaudanosoline pathways.
Generation of a μ-1,2-hydroperoxo FeIIIFeIII and a μ-1,2-peroxo FeIVFeIII Complex
Authors: Walleck Stephan , Zimmermann Thomas Philipp , Hachmeister Henning , Pilger Christian , Huser Thomas , Katz Sagie , Hildebrandt Peter , Stammler Anja , Bögge Hartmut , Bill Eckhard , Glaser Thorsten
Published: March 2022

μ-1,2-Peroxo-diferric intermediates (P) of non-heme diiron enzymes are proposed to convert upon protonation either to high-valent active species or to activated P′ intermediates via hydroperoxo-diferric intermediates. Protonation of synthetic μ-1,2-peroxo model complexes occurred at the μ-oxo and not at the μ-1,2-peroxo bridge. Here we report a stable μ-1,2-peroxo complex {FeIII(μ-O)(μ-1,2-O2)FeIII} using a dinucleating ligand and study its reactivity. The reversible oxidation and protonation of the μ-1,2-peroxo-diferric complex provide μ-1,2-peroxo FeIVFeIII and μ-1,2-hydroperoxo-diferric species, respectively. Neither the oxidation nor the protonation induces a strong electrophilic reactivity. Hence, the observed intramolecular C-H hydroxylation of preorganized methyl groups of the parent μ-1,2-peroxo-diferric complex should occur via conversion to a more electrophilic high-valent species. The thorough characterization of these species provides structure-spectroscopy correlations allowing insights into the formation and reactivities of hydroperoxo intermediates in diiron enzymes and their conversion to activated P′ or high-valent intermediates.
Impaired bidirectional communication between interneurons and oligodendrocyte precursor cells affects social cognitive behavior
Authors: Fang Li-Pao , Zhao Na , Caudal Laura C. , Chang Hsin-Fang , Zhao Renping , Lin Ching-Hsin , Hainz Nadine , Meier Carola , Bettler Bernhard , Huang Wenhui , Scheller Anja , Kirchhoff Frank , Bai Xianshu
Published: March 2022

Cortical neural circuits are complex but very precise networks of balanced excitation and inhibition. Yet, the molecular and cellular mechanisms that form the balance are just beginning to emerge. Here, using conditional γ-aminobutyric acid receptor B1- deficient mice we identify a γ-aminobutyric acid/tumor necrosis factor superfamily member 12-mediated bidirectional communication pathway between parvalbumin-positive fast spiking interneurons and oligodendrocyte precursor cells that determines the density and function of interneurons in the developing medial prefrontal cortex. Interruption of the GABAergic signaling to oligodendrocyte precursor cells results in reduced myelination and hypoactivity of interneurons, strong changes of cortical network activities and impaired social cognitive behavior. In conclusion, glial transmitter receptors are pivotal elements in finetuning distinct brain functions.
Unbiasing fermionic quantum Monte Carlo with a quantum computer
Authors: Huggins William J. , O’Gorman Bryan A. , Rubin Nicholas C. , Reichman David R. , Babbush Ryan , Lee Joonho
Published: March 2022

Interacting many-electron problems pose some of the greatest computational challenges in science, with essential applications across many fields. The solutions to these problems will offer accurate predictions of chemical reactivity and kinetics, and other properties of quantum systems1–4. Fermionic quantum Monte Carlo (QMC) methods5,6, which use a statistical sampling of the ground state, are among the most powerful approaches to these problems. Controlling the fermionic sign problem with constraints ensures the efficiency of QMC at the expense of potentially significant biases owing to the limited flexibility of classical computation. Here we propose an approach that combines constrained QMC with quantum computation to reduce such biases. We implement our scheme experimentally using up to 16 qubits to unbias constrained QMC calculations performed on chemical systems with as many as 120 orbitals. These experiments represent the largest chemistry simulations performed with the help of quantum computers, while achieving accuracy that is competitive with state-of-the-art classical methods without burdensome error mitigation. Compared with the popular variational quantum eigensolver7,8, our hybrid quantum-classical computational model offers an alternative path towards achieving a practical quantum advantage for the electronic structure problem without demanding exceedingly accurate preparation and measurement of the ground-state wavefunction.
High-resolution laser resonances of antiprotonic helium in superfluid 4He
Authors: Sótér Anna , Aghai-Khozani Hossein , Barna Dániel , Dax Andreas , Venturelli Luca , Hori Masaki
Published: March 2022

When atoms are placed into liquids, their optical spectral lines corresponding to the electronic transitions are greatly broadened compared to those of single, isolated atoms. This linewidth increase can often reach a factor of more than a million, obscuring spectroscopic structures and preventing high-resolution spectroscopy, even when superfluid helium, which is the most transparent, cold and chemically inert liquid, is used as the host material1–6. Here we show that when an exotic helium atom with a constituent antiproton7–9 is embedded into superfluid helium, its visible-wavelength spectral line retains a sub-gigahertz linewidth. An abrupt reduction in the linewidth of the antiprotonic laser resonance was observed when the liquid surrounding the atom transitioned into the superfluid phase. This resolved the hyperfine structure arising from the spin–spin interaction between the electron and antiproton with a relative spectral resolution of two parts in 106, even though the antiprotonic helium resided in a dense matrix of normal matter atoms. The electron shell of the antiprotonic atom retains a small radius of approximately 40 picometres during the laser excitation7. This implies that other helium atoms containing antinuclei, as well as negatively charged mesons and hyperons that include strange quarks formed in superfluid helium, may be studied by laser spectroscopy with a high spectral resolution, enabling the determination of the particle masses9. The sharp spectral lines may enable the detection of cosmic-ray antiprotons10,11 or searches for antideuterons12 that come to rest in liquid helium targets.
Tumor cell identification and classification in esophageal adenocarcinoma specimens by hyperspectral imaging
Authors: Maktabi Marianne , Wichmann Yannis , Köhler Hannes , Ahle Henning , Lorenz Dietmar , Bange Michael , Braun Susanne , Gockel Ines , Chalopin Claire , Thieme René
Published: March 2022

Esophageal cancer is the sixth leading cause of cancer-related death worldwide. Histopathological confirmation is a key step in tumor diagnosis. Therefore, simplification in decision-making by discrimination between malignant and non-malignant cells of histological specimens can be provided by combination of new imaging technology and artificial intelligence (AI). In this work, hyperspectral imaging (HSI) data from 95 patients were used to classify three different histopathological features (squamous epithelium cells, esophageal adenocarcinoma (EAC) cells, and tumor stroma cells), based on a multi-layer perceptron with two hidden layers. We achieved an accuracy of 78% for EAC and stroma cells, and 80% for squamous epithelium. HSI combined with machine learning algorithms is a promising and innovative technique, which allows image acquisition beyond Red–Green–Blue (RGB) images. Further method validation and standardization will be necessary, before automated tumor cell identification algorithms can be used in daily clinical practice.
Caller ID for Risso’s and Pacific White-sided dolphins
Authors: Al-Badrawi Mahdi H. , Liang Yue , Seger Kerri D. , Foster Christopher M. , Kirsch Nicholas J.
Published: March 2022

Tracking species with expanding ranges is crucial to conservation efforts and some typically temperate marine species are spreading northward into the Arctic Ocean. Risso’s (Gg) and Pacific white-sided (Lo) dolphins have been documented spreading poleward. Further, they make very similar sounds, so it is difficult for both human analysts and classification algorithms to tell them apart. Using automatic detectors and classifiers on large acoustic datasets would improve the efficiency of monitoring these species. variational mode decomposition (VMD) provides both an easier visualization tool for human analysts and exhibited robustness to background noise while extracting features in pulsed signals with very similar spectral properties. The goal of this work was to develop a new visualization tool using VMD and a statistics-based classification algorithm to differentiate similar pulsed signals. The proposed VMD method achieved 81% accuracy, even when using audio files with low SNR that did not have concurrent visual survey data. While many dolphins whistle, pulsed signals are one of the more useful vocalizations to use in detection and classification because of their species-specific acoustic features. Automating the VMD method and expanding it to other dolphin species that have very similar pulsed signals would complement current detection and classification methods and lead to a more complete understanding of ecosystem dynamics under a changing climate.
Sleep phase and pre-sleep arousal predicted co-developmental trajectories of pain and insomnia within adolescence
Authors: Arnison Tor , Schrooten Martien G. S. , Bauducco Serena , Jansson-Fröjmark Markus , Persson Jonas
Published: March 2022

The onset of both chronic pain and insomnia is high during adolescence. Although a bidirectional relationship between pain and insomnia has support, how pain and sleep co-develop throughout adolescence remains unknown. Sleep–wake patterns, pre-sleep behavior and pre-sleep arousal may influence the co-development of pain and insomnia. Four waves of longitudinal self-report data were used (Nbaseline = 2767, Agebaseline M = 13.65 years, SD = 0.65). Multidimensional growth mixture modeling was used to identify four subgroups of adolescents with different concurrent trajectories of pain and insomnia. The trajectories followed each other across time in all classes: one class of consistently low pain and insomnia (68.7%), one class with persistent high symptoms (4.9%), as well as one class of increasing (13.9%), and one of decreasing (12.5%), trajectories. Later sleep–wake patterns and more pre-sleep cognitive-emotional arousal predicted both increasing and decreasing trajectories of concurrent pain and insomnia. The current study showed that developmental trajectories of pain and insomnia follow each other within adolescents and across adolescence. Both sleep-phase focused interventions as well as psychological interventions that focus on pre-sleep cognitive-emotional arousal may prove beneficial for adolescents with comorbid pain and insomnia.
Looking beyond community structure leads to the discovery of dynamical communities in weighted networks
Authors: Nathe Chad , Gambuzza Lucia Valentina , Frasca Mattia , Sorrentino Francesco
Published: March 2022

A fundamental question is whether groups of nodes of a complex network can possibly display long-term cluster-synchronized behavior. While this question has been addressed for the restricted classes of unweighted and labeled graphs, it remains an open problem for the more general class of weighted networks. The emergence of coordinated motion of nodes in natural and technological networks is directly related to the network structure through the concept of an equitable partition, which determines which nodes can show long-term synchronized behavior and which nodes cannot. We provide a method to detect the presence of nearly equitable partitions in weighted networks, based on minimal information about the network structure. With this approach we are able to discover the presence of dynamical communities in both synthetic and real technological, biological, and social networks, to a statistically significant level. We show that our approach based on dynamical communities is better at predicting the emergence of synchronized behavior than existing methods to detect community structure.
The surgical outcome of multilevel anterior cervical discectomy and fusion in myelopathic elderly and younger patients
Authors: Luo Chi-An , Lim Austin Samuel , Lu Meng-Ling , Chiu Ping-Yeh , Lai Po-Liang , Niu Chi-Chien
Published: March 2022

The elderly population has an increased risk of degenerative cervical myelopathy due to multilevel disease, causing motor and sensory dysfunctions and a poor quality of life. Multilevel anterior cervical discectomy and fusion (ACDF) is an alternative surgical treatment option, but has a perceived higher risk of complications. The goal of this study is to report the outcome. We retrospectively reviewed patients from 2006 to 2019 undergoing multilevel ACDF for degenerative cervical myelopathy and compared outcomes and complications between elder patients (aged 70 and above) and younger patients (below 70). The patients’ comorbidities, and postoperative complications, radiographic parameters such as C2–C7 Cobb angle, C2–C7 sagittal vertical axis, inter-body height of surgical levels and fusion rate were recorded. Japanese Orthopaedic Association (JOA) score and modified Odom’s score were collected. Included were 18 elderly (mean age 74, range 70–87) and 45 young patients (mean age 56, range 43–65) with a follow-up of 43.8 and 55.5 months respectively. Three-level ACDF was the most common. The ratios of ASA class III patients were 94.4% and 48.9% (p < 0.001). The Charlson comorbidity indexes were 4.3 ± 1.03 and 2.1 ± 1.11 (p < 0.001). The average lengths of hospital stays were 4.9 and 4.6 days. Eleven patients (61.1%) in the elderly group experienced at least one short-term complication, compared with 16 patients (35.6%) in the younger group (p < 0.05). The middle-term complications were comparable (22.2% and 20.0%). The JOA score, recovery rate and modified Odom score showed comparable result between groups. Despite its extensiveness, multilevel ACDF is feasible for the elder patients with good clinical outcome and fusion rate. When compared to younger cohort, there is a trend of lower preoperative JOA score and recovery rate. The short-term complication rate is higher in the elderly group.
Generalized ComBat harmonization methods for radiomic features with multi-modal distributions and multiple batch effects
Authors: Horng Hannah , Singh Apurva , Yousefi Bardia , Cohen Eric A. , Haghighi Babak , Katz Sharyn , Noël Peter B. , Shinohara Russell T. , Kontos Despina
Published: March 2022

Radiomic features have a wide range of clinical applications, but variability due to image acquisition factors can affect their performance. The harmonization tool ComBat is a promising solution but is limited by inability to harmonize multimodal distributions, unknown imaging parameters, and multiple imaging parameters. In this study, we propose two methods for addressing these limitations. We propose a sequential method that allows for harmonization of radiomic features by multiple imaging parameters (Nested ComBat). We also employ a Gaussian Mixture Model (GMM)-based method (GMM ComBat) where scans are split into groupings based on the shape of the distribution used for harmonization as a batch effect and subsequent harmonization by a known imaging parameter. These two methods were evaluated on features extracted with CapTK and PyRadiomics from two public lung computed tomography datasets. We found that Nested ComBat exhibited similar performance to standard ComBat in reducing the percentage of features with statistically significant differences in distribution attributable to imaging parameters. GMM ComBat improved harmonization performance over standard ComBat (− 11%, − 10% for Lung3/CAPTK, Lung3/PyRadiomics harmonizing by kernel resolution). Features harmonized with a variant of the Nested method and the GMM split method demonstrated similar c-statistics and Kaplan–Meier curves when used in survival analyses.
Ingroup favoritism overrides fairness when resources are limited
Authors: Chae Jihwan , Kim Kunil , Kim Yuri , Lim Gahyun , Kim Daeeun , Kim Hackjin
Published: March 2022

Ingroup favoritism and fairness are two potentially competing motives guiding intergroup behaviors in human. Here, we investigate if and how limited resources can modulate the way these two motives affect individuals’ decisions in intergroup situation. In the present study, participants (N = 58) were asked to accept or reject three types of resource allocation proposals generated by a computer: the ingroup advantageous condition, outgroup advantageous condition, and neutral condition. In general, participants were more willing to accept the proposals in the ingroup advantageous condition than the outgroup advantageous or the neutral conditions, and also in the moderate inequality than the extreme inequality condition. This may indicate that people sought a careful balance between ingroup favoritism and fairness, although we also found marked individual differences in their preferences for ingroup favoritism or fairness. Importantly, as predicted, participants were more likely to show ingroup favoritism only when limited resources affect the well-being of ingroup members. The present study provides novel insights into the situational and personality factors affecting human intergroup behaviors, shedding light on motives underlying intergroup conflicts prevalent in human societies.
Expanding the clinical spectrum of COL2A1 related disorders by a mass like phenotype
Authors: Demal Till Joscha , Scholz Tasja , Schüler Helke , Olfe Jakob , Fröhlich Anja , Speth Fabian , von Kodolitsch Yskert , Mir Thomas S. , Reichenspurner Hermann , Kubisch Christian , Hempel Maja , Rosenberger Georg
Published: March 2022

MASS phenotype is a connective tissue disorder clinically overlapping with Marfan syndrome and caused by pathogenic variants in FBN1. We report four patients from three families presenting with a MASS-like phenotype consisting of tall stature, arachnodactyly, spinal deformations, dural ectasia, pectus and/or feet deformations, osteoarthritis, and/or high arched palate. Gene panel sequencing was negative for FBN1 variants. However, it revealed likely pathogenic missense variants in three individuals [c.3936G > T p.(Lys1312Asn), c.193G > A p.(Asp65Asn)] and a missense variant of unknown significance in the fourth patient [c.4013G > A p.(Ser1338Asn)] in propeptide coding regions of COL2A1. Pathogenic COL2A1 variants are associated with type II collagenopathies comprising a remarkable clinical variablility. Main features include skeletal dysplasia, ocular anomalies, and auditory defects. A MASS-like phenotype has not been associated with COL2A1 variants before. Thus, the identification of likely pathogenic COL2A1 variants in our patients expands the phenotypic spectrum of type II collagenopathies and suggests that a MASS-like phenotype can be assigned to various hereditary disorders of connective tissue. We compare the phenotypes of our patients with related disorders of connective tissue and discuss possible pathomechanisms and genotype–phenotype correlations for the identified COL2A1 variants. Our data recommend COL2A1 sequencing in FBN1-negative patients suggestive for MASS/Marfan-like phenotype (without aortopathy).
The role of the right prefrontal cortex in the retrieval of weak representations
Authors: Yi Kyongmyon , Heo Juyeon , Hong Jiyun , Kim Chobok
Published: March 2022

Although recent studies have shown the importance of control in creative problem solving, the neural mechanisms of control processes engaged in retrieval of weak representations, which is closely linked to creative problem solving, remain unclear. The current study aimed to examine the neural mechanisms associated with retrieval of weak representations using functional magnetic resonance imaging and their potential relationships with creativity task performance. For this purpose, participants performed an experimental task that enabled us to directly compare between retrieval of previously unattended-and-weak representations and attended-and-strong representations. Imaging results indicated that the right anterior dorsolateral prefrontal cortex (aDLPFC) was selectively engaged in retrieval of weak representations. Moreover, the right aDLPFC activations were positively correlated with individuals’ creativity task performance but independent of attention-demanding task performance. We therefore suggest that the right aDLPFC plays a key role in retrieval of weak representations and may support creative problem solving.