bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophile Dermatosen: ein manchmal unterschätztes Erkrankungsspektrum
Authors: Drach Mathias
Published: April 2022

Neutrophile Dermatosen bilden ein breites Spektrum von Hauterkrankungen ab, welche von sehr häufig bis sehr selten reichen. Generell lässt sich sagen, dass Dermatosen aus diesem Formenkreis klinisch wie auch histologisch recht heterogen sind.
A Systematic Review of Experimental Work on Persuasive Social Robots
Authors: Liu Baisong , Tetteroo Daniel , Markopoulos Panos
Published: April 2022

There is a growing body of work reporting on experimental work on social robotics (SR) used for persuasive purposes. We report a comprehensive review on persuasive social robotics research with the aim to better inform their design, by summarizing literature on factors impacting their persuasiveness. From 54 papers, we extracted the SR’s design features evaluated in the studies and the evidence of their efficacy. We identified five main categories in the factors that were evaluated: modality, interaction, social character, context and persuasive strategies. Our literature review finds generally consistent effects for factors in modality, interaction and context, whereas more mixed results were shown for social character and persuasive strategies. This review further summarizes findings on interaction effects of multiple factors for the persuasiveness of social robots. Finally, based on the analysis of the papers reviewed, suggestions for factor expression design and evaluation, and the potential for using qualitative methods and more longer-term studies are discussed.
Mineral chemistry aspects of radioactive mineralization associated with Zr-, Nb-, and REE-bearing minerals from felsic dikes at Abu Hawis, North Eastern Desert, Egypt
Authors: Gawad Ahmed E. Abdel
Published: April 2022

The exposed rocks in Abu Hawis area, North Eastern Desert (NED), Egypt, consist of tonalite-granodiorite and monzogranite, dissected by post-granite felsic (microgranite and rhyolite) and mafic (basaltic-andesite) dikes. The investigated radioactive minerals and Zr-, Nb-, and REE-bearing minerals were restricted to felsic dikes having E–W and NE–SW trends. Uraninite, uranothorite, and thorite occur as the main radioactive minerals in microgranite dikes, while thorite is represent in rhyolite dikes. Y2O3 and HREE are recorded in zircon crystals from rhyolite dikes whereas HREEs in zircon grains from microgranite dikes are below detection limit. Zircon crystals from microgranite dikes contain high values of HfO2 with up to 9.08 wt % owing to the effect of hydrothermal activity. Columbite from microgranite dikes has Ta/(Ta + Nb) and Mn/(Mn + Fe) ratios ranging between 0.0052–0.0164 and 0.0549–0.7010, respectively, which point to manganocolumbite composition, except for two spots that show a ferrocolumbite composition. Fergusonite is recorded in microgranite dikes, with average values of Nb2O5, Y2O3, and HREE2O3 reaching 50.3, 22.93, and 17.68 wt%, respectively. Monazite is recorded in both microgranite and rhyolite dikes, with marked enrichment of ThO2, which reaches up to 12.52 wt% in the first one, while the total ΣLREE2O3 reached up to 68.5 wt% in the latter. Parisite and chevkinite are confined to rhyolite dikes with clear enrichment in LREE with averages ranging between 53.53 and 43.75 wt% ΣLREE2O3, respectively.
Anti-breast cancer effects of phytochemicals: primary, secondary, and tertiary care
Authors: Mazurakova Alena , Koklesova Lenka , Samec Marek , Kudela Erik , Kajo Karol , Skuciova Veronika , Csizmár Sandra Hurta , Mestanova Veronika , Pec Martin , Adamkov Marian , Al-Ishaq Raghad Khalid , Smejkal Karel , Giordano Frank A. , Büsselberg Dietrich , Biringer Kamil , Golubnitschaja Olga , Kubatka Peter
Published: April 2022

Breast cancer incidence is actually the highest one among all cancers. Overall breast cancer management is associated with challenges considering risk assessment and predictive diagnostics, targeted prevention of metastatic disease, appropriate treatment options, and cost-effectiveness of approaches applied. Accumulated research evidence indicates promising anti-cancer effects of phytochemicals protecting cells against malignant transformation, inhibiting carcinogenesis and metastatic spread, supporting immune system and increasing effectiveness of conventional anti-cancer therapies, among others. Molecular and sub-/cellular mechanisms are highly complex affecting several pathways considered potent targets for advanced diagnostics and cost-effective treatments. Demonstrated anti-cancer affects, therefore, are clinically relevant for improving individual outcomes and might be applicable to the primary (protection against initial cancer development), secondary (protection against potential metastatic disease development), and tertiary (towards cascading complications) care. However, a detailed data analysis is essential to adapt treatment algorithms to individuals’ and patients’ needs. Consequently, advanced concepts of patient stratification, predictive diagnostics, targeted prevention, and treatments tailored to the individualized patient profile are instrumental for the cost-effective application of natural anti-cancer substances to improve overall breast cancer management benefiting affected individuals and the society at large.
Advances in chemistry and bioactivity of the genus Erythroxylum
Authors: Lv Yulian , Tian Tian , Wang Yong-Jiang , Huang Jian-Ping , Huang Sheng-Xiong
Published: April 2022

Erythroxylum P. Browne is the largest and most representative genus of Erythroxylaceae family. It contains approximately 230 species that are mainly distributed in tropical and subtropical regions. Some species in this genus, such as E.monogynum and E.coca, have been used as folk medicines in India or South America for a long history. It is well known that Erythroxylum plants are rich in tropane alkaloids, and the representative member cocaine shows remarkable activity in human central nervous system. However, many other types of active compounds have also been found in Erythroxylum along with the broadening and deepening of phytochemical research. To date, a total of 383 compounds from Erythroxylum have been reported, among which only 186 tropane alkaloids have been reviewed in 2010. In this review, we summarized all remained 197 compounds characterized from 53 Erythroxylum species from 1960 to 2021, which include diterpenes, triterpenes, alkaloids, flavonoids, and other derivates, providing a comprehensive overview of phytoconstituents profile of Erythroxylum plants. In addition, the biological activities of representative phytochemicals and crude extracts were also highlighted.

Graphical Abstract
Rituals, Runaways, and the Haitian Revolution
Authors: Eddins Crystal Nicole
Published: April 2022

The Haitian Revolution was perhaps the most successful slave rebellion in modern history; it created the first and only free and independent Black nation in the Americas. This book tells the story of how enslaved Africans forcibly brought to colonial Haiti through the trans-Atlantic slave trade used their cultural and religious heritages, social networks, and labor and militaristic skills to survive horrific conditions. They built webs of networks between African and 'creole' runaways, slaves, and a small number of free people of color through rituals and marronnage - key aspects to building the racial solidarity that helped make the revolution successful. Analyzing underexplored archival sources and advertisements for fugitives from slavery, Crystal Eddins finds indications of collective consciousness and solidarity, unearthing patterns of resistance. The book fills an important gap in the existing literature on the Haitian Revolution. This title is also available as Open Access on Cambridge Core.
Monotheism, Suffering, and Evil
Authors: Peterson Michael L.
Published: April 2022

Suffering and evil in the world provide the basis for the most difficult challenge to monotheistic belief. This Element discusses how the three great monotheisms – Judaism, Christianity, and Islam – respond to the problem of suffering and evil. Different versions of the problem, types of answers, and recurring themes in philosophical and religious sources are analyzed. Objections to the enterprise of theodicy are also discussed as are additional objections to the monotheistic God more broadly. This treatment culminates in a recommendation for how monotheism can best respond to the most serious formulation of the problem, the argument from gratuitous evil.
Composites Science, Technology, and Engineering
Authors: Jones Frank R.
Published: April 2022

Understand critical principles of composites, such as design of durable structures, choice of fibre, matrix, manufacturing process, and mechanics with this interdisciplinary text. The book features up-to-date coverage of hybrids of fibres and particles and explanation of failure criteria, and includes a comprehensive discussion on choice of fibres, matrices, manufacturing technology, and micromechanics for durable composite structures. It provides the structure and properties of reinforcing fibres, particulates, and matrices together with a discussion of fracture mechanics. This is an essential guide for scientists and engineers wishing to discover the benefits of composite materials for designing strong and durable structures.
Humanising health and social care: What do family members of people with a severe acquired brain injury value most in service provision
Authors: Holloway Mark , Ellis-Hill Caroline
Published: April 2022

Introduction:

Family members living with relatives with severe acquired brain injury (ABI) face many challenges. Although this is recognised, service provision in the UK is poor and needs development.

Method:

In order to support innovative service delivery for family members, we reflect on the research carried out by the first author using a new perspective – a lifeworld humanising approach in order to consider (a) the dehumanising existential challenges facing family members of people living with severe ABI and (b) what family members most value in service delivery presented in humanising terms.

Findings:

Following ABI, family members may enter a parallel lifeworld (feeling separate from ‘usual’ life as it flows by) and face fundamental existential challenges of isolation, loss of agency, dislocation, loss of meaning and loss of personal journey. Family members have reported that service providers who are highly valued are those who act as ‘expert companions’. This role involves supporting families in some, if not all of the following (a) reaching across into the lifeworld of the family member and appreciating and validating what they are facing, (b) helping them make sense of their situation in terms which are meaningful to them and which they can explain to others, (c) through ABI expertise, supporting their relative through knowing their interests and needs and adapting the environment to suit these to help their relative to ‘settle’ and flourish, (d) supporting family members to share their life experiences – developing safe and trusting relationships, (e) having a humane, positive, creative and for some, a humorous approach, (f) being responsive to changing situations, (g) being available to call during times of worry or crisis and (h) help link with others and helpful networks.

Discussion:

It is suggested that the role and approach of companion may help family members regain some sense of their own life and their well-being.
A New Interface to Cope With Unreliable Airspeed	Indications
Authors: Fabre Eve F. , Braca Patrick , Peysakhovich Vsevolod , Dehais Frédéric
Published: April 2022

Abstract. When unreliable airspeed events occur, the pilot flying (PF) is required to fly the aircraft using the thrust and the pitch parameters that are displayed in two distanced locations of the flight deck. The Sycopaero interface was designed to limit the PF’s workload by automatically displaying thrust and pitch values specific to aircraft configuration on the primary flight display. Participants performed a simulated flight scenario in which they lost airspeed information during take-off with and without the Sycopaero interface. Both behavioral and ocular results demonstrate that the Sycopaero interface significantly lowers the mental workload of PFs and improves their monitoring performance. Taken together, these results suggest that the Sycopaero interface may be a suitable solution to safely handle airspeed failures.
Instabilities in the Bottom Boundary Layer Reduce Boundary Layer Arrest and Stir Boundary Layer Water Into the Stratified Interior
Authors: Pringle James M.
Published: April 2022

An along‐isobath current in stratified waters leads to a bottom boundary layer. In models with no alongshore variation, cross‐isobath density transport in this bottom boundary layer reduce the velocity in the bottom boundary layer via thermal wind, and thus the bottom friction experienced by the current above the boundary layer—this is bottom‐boundary‐layer arrest. If, however, alongshore variation of the flow is allowed, the bottom boundary layer is baroclinically unstable. We show with high resolution numerical models that these instabilities reduce this arrest and allow bottom friction to decelerate the flow above the bottom boundary layer when the flow is in the Kelvin wave direction (so that the bottom Ekman transport is downwelling). Both the arrest of the bottom boundary layer and the release from this arrest are asymmetric; the friction experienced by flows in the direction of Kelvin‐wave propagation (downwave) is much greater than flows in the opposite direction. The strength of the near bottom currents, and thus the magnitude of bottom friction, is found to be governed by the destruction of potential vorticity near the bottom balanced by the offshore along‐isopycnal transport of this anomalous potential vorticity. A simple model of this process is created and used to quantify the magnitude of this effect and the resulting reduction of arrest of the bottom boundary layer.
Decadal Observations of Internal Wave Energy, Shear, and Mixing in the Western Arctic Ocean
Authors: Fine Elizabeth C. , Cole Sylvia T.
Published: April 2022

As Arctic sea ice declines, wind energy has increasing access to the upper ocean, with potential consequences for ocean mixing, stratification, and turbulent heat fluxes. Here, we investigate the relationships between internal wave energy, turbulent dissipation, and ice concentration and draft using mooring data collected in the Beaufort Sea during 2003–2018. We focus on the 50–300 m depth range, using velocity and CTD records to estimate near‐inertial shear and energy, a finescale parameterization to infer turbulent dissipation rates, and ice draft observations to characterize the ice cover. All quantities varied widely on monthly and interannual timescales. Seasonally, near‐inertial energy increased when ice concentration and ice draft were low, but shear and dissipation did not. We show that this apparent contradiction occurred due to the vertical scales of internal wave energy, with open water associated with larger vertical scales. These larger vertical scale motions are associated with less shear, and tend to result in less dissipation. This relationship led to a seasonality in the correlation between shear and energy. This correlation was largest in the spring beneath full ice cover and smallest in the summer and fall when the ice had deteriorated. When considering interannually averaged properties, the year‐to‐year variability and the short ice‐free season currently obscure any potential trend. Implications for the future seasonal and interannual evolution of the Arctic Ocean and sea ice cover are discussed.
A 20‐Year Study of Melt Processes Over Larsen C Ice Shelf Using a High‐Resolution Regional Atmospheric Model: 1. Model Configuration and Validation
Authors: Gilbert Ella , Orr Andrew , King John C. , Renfrew Ian A. , Lachlan‐Cope Thomas
Published: April 2022

Following collapses of the neighboring Larsen A and B ice shelves, Larsen C has become a focus of increased attention. Determining how the prevailing meteorological conditions influence its surface melt regime is of paramount importance for understanding the dominant processes causing melt and ultimately for predicting its future. To this end, a new, high‐resolution (4 km grid spacing) Met Office Unified Model (MetUM) hindcast of atmospheric conditions and surface melt processes over the central Antarctic Peninsula is introduced. The hindcast is capable of simulating observed near‐surface meteorology and surface melt conditions over Larsen C. In contrast with previous model simulations, the MetUM captures the observed east‐west gradient in surface melting associated with foehn winds, as well as the interannual variability in melt shown in previous observational studies. As exemplars, we focus on two case studies—the months preceding the collapse of the Larsen B ice shelf in March 2002 and the high foehn, high melt period of March‐May 2016—to test the hindcast's ability to reproduce the atmospheric effects that contributed to considerable melting during those periods. The results suggest that the MetUM hindcast is a useful tool with which to explore the dominant causes of surface melting on Larsen C.
A Sharper Look at the World’s Rivers and Catchments
Authors: Lehner Bernhard , Roth Achim , Huber Martin , Anand Mira , Thieme Michele
Published: April 2022

Digital hydrographic maps have transformed global environmental studies and resource management. A major database update will provide even clearer and more complete views of Earth’s waterways.
KLF6 facilitates differentiation of odontoblasts through modulating the expression of P21 in vitro
Authors: Chen Zhuo , Wu Wenzhi , Zheng Chen , Lan Yanhua , Xie Huizhi , Xie Zhijian
Published: April 2022

Multiple signaling pathways are involved in the regulation of cell proliferation and differentiation in odontogenesis and dental tissue renewal, but the details of these mechanisms remain unknown. Here, we investigated the expression patterns of a transcription factor, Krüppel-like factor 6 (KLF6), during the development of murine tooth germ and its function in odontoblastic differentiation. KLF6 was almost ubiquitously expressed in odontoblasts at various stages, and it was co-expressed with P21 (to varying degrees) in mouse dental germ. To determine the function of Klf6, overexpression and knockdown experiments were performed in a mouse dental papilla cell line (iMDP-3). Klf6 functioned as a promoter of odontoblastic differentiation and inhibited the proliferation and cell cycle progression of iMDP-3 through p21 upregulation. Dual-luciferase reporter assay and chromatin immunoprecipitation showed that Klf6 directly activates p21 transcription. Additionally, the in vivo study showed that KLF6 and P21 were also co-expressed in odontoblasts around the reparative dentin. In conclusion, Klf6 regulates the transcriptional activity of p21, thus promoting the cell proliferation to odontoblastic differentiation transition in vitro. This study provides a theoretical basis for odontoblast differentiation and the formation of reparative dentine regeneration.
CS1 CAR-T targeting the distal domain of CS1 (SLAMF7) shows efficacy in high tumor burden myeloma model despite fratricide of CD8+CS1 expressing CAR-T cells
Authors: O’Neal Julie , Ritchey Julie K. , Cooper Matthew L. , Niswonger Jessica , Sofía González L. , Street Emily , Rettig Michael P. , Gladney Susan W. , Gehrs Leah , Abboud Ramzi , Prior Julie L. , Haas Gabriel J. , Jayasinghe Reyka G. , Ding Li , Ghobadi Armin , Vij Ravi , DiPersio John F.
Published: April 2022

Despite improvement in treatment options for myeloma patients, including targeted immunotherapies, multiple myeloma remains a mostly incurable malignancy. High CS1 (SLAMF7) expression on myeloma cells and limited expression on normal cells makes it a promising target for CAR-T therapy. The CS1 protein has two extracellular domains – the distal Variable (V) domain and the proximal Constant 2 (C2) domain. We generated and tested CS1-CAR-T targeting the V domain of CS1 (Luc90-CS1-CAR-T) and demonstrated anti-myeloma killing in vitro and in vivo using two mouse models. Since fratricide of CD8 + cells occurred during production, we generated fratricide resistant CS1 deficient Luc90- CS1- CAR-T (ΔCS1-Luc90- CS1- CAR-T). This led to protection of CD8 + cells in the CAR-T cultures, but had no impact on efficacy. Our data demonstrate targeting the distal V domain of CS1 could be an effective CAR-T treatment for myeloma patients and deletion of CS1 in clinical production did not provide an added benefit using in vivo immunodeficient NSG preclinical models.
A silent two-photon imaging system for studying in vivo auditory neuronal functions
Authors: Song Xindong , Guo Yueqi , Chen Chenggang , Wang Xiaoqin
Published: April 2022

Two-photon laser-scanning microscopy has become an essential tool for imaging neuronal functions in vivo and has been applied to different parts of the neural system, including the auditory system. However, many components of a two-photon microscope, such as galvanometer-based laser scanners, generate mechanical vibrations and thus acoustic artifacts, making it difficult to interpret auditory responses from recorded neurons. Here, we report the development of a silent two-photon imaging system and its applications in the common marmoset (Callithrix Jacchus), a non-human primate species sharing a similar hearing range with humans. By utilizing an orthogonal pair of acousto-optical deflectors (AODs), full-frame raster scanning at video rate was achieved without introducing mechanical vibrations. Imaging depth can be optically controlled by adjusting the chirping speed on the AODs without any mechanical motion along the Z-axis. Furthermore, all other sound-generating components of the system were acoustically isolated, leaving the noise floor of the working system below the marmoset’s hearing threshold. Imaging with the system in awake marmosets revealed many auditory cortex neurons that exhibited maximal responses at low sound levels, which were not possible to study using traditional two-photon imaging systems. This is the first demonstration of a silent two-photon imaging system that is capable of imaging auditory neuronal functions in vivo without acoustic artifacts. This capacity opens new opportunities for a better understanding of auditory functions in the brain and helps isolate animal behavior from microscope-generated acoustic interference.
Psychosocial functioning in the balance between autism and psychosis: evidence from three populations
Authors: Abu-Akel Ahmad , Wood Stephen J. , Upthegrove Rachel , Chisholm Katharine , Lin Ashleigh , Hansen Peter C. , Gillespie Steven M. , Apperly Ian A. , Montag Christiane
Published: April 2022

Functional impairment is a core feature of both autism and schizophrenia spectrum disorders. While diagnostically independent, they can co-occur in the same individual at both the trait and diagnostic levels. The effect of such co-occurrence is hypothesized to worsen functional impairment. The diametric model, however, suggests that the disorders are etiologically and phenotypically diametrical, representing the extreme of a unidimensional continuum of cognition and behavior. A central prediction of this model is that functional impairment would be attenuated in individuals with mixed symptom expressions or genetic liability to both disorders. We tested this hypothesis in two clinical populations and one healthy population. In individuals with chronic schizophrenia and in individuals with first episode psychosis we evaluated the combined effect of autistic traits and positive psychotic symptoms on psychosocial functioning. In healthy carriers of alleles of copy number variants (CNVs) that confer risk for both autism and schizophrenia, we also evaluated whether variation in psychosocial functioning depended on the combined risk conferred by each CNV. Relative to individuals with biased symptom/CNV risk profiles, results show that functional impairments are attenuated in individuals with relatively equal levels of positive symptoms and autistic traits—and specifically stereotypic behaviors—, and in carriers of CNVs with relatively equal risks for either disorder. However, the pattern of effects along the “balance axis” varied across the groups, with this attenuation being generally less pronounced in individuals with high-high symptom/risk profile in the schizophrenia and CNV groups, and relatively similar for low-low and high-high individuals in the first episode psychosis group. Lower levels of functional impairments in individuals with “balanced” symptom profile or genetic risks would suggest compensation across mechanisms associated with autism and schizophrenia. CNVs that confer equal risks for both disorders may provide an entry point for investigations into such compensatory mechanisms. The co-assessment of autism and schizophrenia may contribute to personalized prognosis and stratification strategies.
Breast cancer in the era of integrating “Omics” approaches
Authors: Rossi Claudia , Cicalini Ilaria , Cufaro Maria Concetta , Consalvo Ada , Upadhyaya Prabin , Sala Gianluca , Antonucci Ivana , Del Boccio Piero , Stuppia Liborio , De Laurenzi Vincenzo
Published: April 2022

Worldwide, breast cancer is the leading cause of cancer-related deaths in women. Breast cancer is a heterogeneous disease characterized by different clinical outcomes in terms of pathological features, response to therapies, and long-term patient survival. Thus, the heterogeneity found in this cancer led to the concept that breast cancer is not a single disease, being very heterogeneous both at the molecular and clinical level, and rather represents a group of distinct neoplastic diseases of the breast and its cells. Indubitably, in the past decades we witnessed a significant development of innovative therapeutic approaches, including targeted and immunotherapies, leading to impressive results in terms of increased survival for breast cancer patients. However, these multimodal treatments fail to prevent recurrence and metastasis. Therefore, it is urgent to improve our understanding of breast tumor and metastasis biology. Over the past few years, high-throughput “omics” technologies through the identification of novel biomarkers and molecular profiling have shown their great potential in generating new insights in the study of breast cancer, also improving diagnosis, prognosis and prediction of response to treatment. In this review, we discuss how the implementation of “omics” strategies and their integration may lead to a better comprehension of the mechanisms underlying breast cancer. In particular, with the aim to investigate the correlation between different “omics” datasets and to define the new important key pathway and upstream regulators in breast cancer, we applied a new integrative meta-analysis method to combine the results obtained from genomics, proteomics and metabolomics approaches in different revised studies.
Decreased thermal niche breadth as a trade-off of antibiotic resistance
Authors: Herren Cristina M , Baym Michael
Published: April 2022

Evolutionary theory predicts that adaptations, including antibiotic resistance, should come with associated fitness costs; yet, many resistance mutations seemingly contradict this prediction by inducing no growth rate deficit. However, most growth assays comparing sensitive and resistant strains have been performed under a narrow range of environmental conditions, which do not reflect the variety of contexts that a pathogenic bacterium might encounter when causing infection. We hypothesized that reduced niche breadth, defined as diminished growth across a diversity of environments, can be a cost of antibiotic resistance. Specifically, we test whether chloramphenicol-resistant Escherichia coli incur disproportionate growth deficits in novel thermal conditions. Here we show that chloramphenicol-resistant bacteria have greater fitness costs at novel temperatures than their antibiotic-sensitive ancestors. In several cases, we observed no resistance cost in growth rate at the historic temperature but saw diminished growth at warmer and colder temperatures. These results were consistent across various genetic mechanisms of resistance. Thus, we propose that decreased thermal niche breadth is an under-documented fitness cost of antibiotic resistance. Furthermore, these results demonstrate that the cost of antibiotic resistance shifts rapidly as the environment changes; these context-dependent resistance costs should select for the rapid gain and loss of resistance as an evolutionary strategy.
Stress-induced pro- and anti-inflammatory cytokine concentrations in female PTSD and depressive patients
Authors: Renner Vanessa , Schellong Julia , Bornstein Stefan , Petrowski Katja
Published: April 2022

Alterations of the hypothalamus pituitary-axis on one hand and heightened rates of somatic diseases and mortality on the other hand are consistently found for PTSD and MDD patients. A possible link between these factors might be the immune system, in particular pro- and anti-inflammatory cytokines. A ‘low-grade inflammation’ in PTSD and MDD patients was found, whereas the influence of acute stress and the role of anti-inflammatory cytokines was rarely examined. In this study, 17 female PTSD patients participated in the Trier social stress test while serum cytokine levels (IL-6, IL-10) were assessed. Cytokine levels of PTSD patients were compared with levels of female depressive patients (n = 18) and female healthy controls (n = 18). Group differences were assessed using a 3 (group) x 8 (time: −15, −1, +1, +10, +20, +30, +45, +60 min) ANCOVA for repeated measures with baseline values as covariates. There was no group difference regarding IL-6 levels (p = 0.920) but PTSD patients showed significantly higher levels of IL-10 compared with depressive patients (p < 0.001, d = 0.16) and healthy controls (p = 0.001, d = 0.38). Under acute stress, PTSD patients did not show the widely found elevated IL-6 levels but showed an increase of anti-inflammatory IL-10. Therefore, acute stress seems to promote an imbalance of pro- and anti-inflammatory cytokine levels in PTSD and might indicate a hyperreactive immune response. This should be considered in future studies to further understand the role of the immune system as a link between stress response and somatic diseases.
Chromosome evolution and the genetic basis of agronomically important traits in greater yam
Authors: Bredeson Jessen V. , Lyons Jessica B. , Oniyinde Ibukun O. , Okereke Nneka R. , Kolade Olufisayo , Nnabue Ikenna , Nwadili Christian O. , Hřibová Eva , Parker Matthew , Nwogha Jeremiah , Shu Shengqiang , Carlson Joseph , Kariba Robert , Muthemba Samuel , Knop Katarzyna , Barton Geoffrey J. , Sherwood Anna V. , Lopez-Montes Antonio , Asiedu Robert , Jamnadass Ramni , Muchugi Alice , Goodstein David , Egesi Chiedozie N. , Featherston Jonathan , Asfaw Asrat , Simpson Gordon G. , Doležel Jaroslav , Hendre Prasad S. , Van Deynze Allen , Kumar Pullikanti Lava , Obidiegwu Jude E. , Bhattacharjee Ranjana , Rokhsar Daniel S.
Published: April 2022

The nutrient-rich tubers of the greater yam,Dioscorea alataL., provide food and income security for millions of people around the world. Despite its global importance, however, greater yam remains an orphan crop. Here, we address this resource gap by presenting a highly contiguous chromosome-scale genome assembly ofD. alatacombined with a dense genetic map derived from African breeding populations. The genome sequence reveals an ancient allotetraploidization in theDioscorealineage, followed by extensive genome-wide reorganization. Using the genomic tools, we find quantitative trait loci for resistance to anthracnose, a damaging fungal pathogen of yam, and several tuber quality traits. Genomic analysis of breeding lines reveals both extensive inbreeding as well as regions of extensive heterozygosity that may represent interspecific introgression during domestication. These tools and insights will enable yam breeders to unlock the potential of this staple crop and take full advantage of its adaptability to varied environments.
The downward spiralling nature of the North Atlantic Subtropical Gyre
Authors: Berglund Sara , Döös Kristofer , Groeskamp Sjoerd , McDougall Trevor J.
Published: April 2022

The Atlantic Meridional Overturning Circulation (AMOC) regulates the heat distribution and climate of Earth. Here we identify a new feature of the circulation within the North Atlantic Subtropical Gyre that is associated with the northward flowing component of the AMOC. We find that 70% of the water that flows northwards as part of the AMOC circulates the Gyre at least once before it can continue northwards. These circuits are needed to achieve an increase of density and depth through a combination of air-sea interaction and interior mixing processes, before water can escape the latitudes of the Gyre and join the northern upper branch of the AMOC. This points towards an important role of the Gyre circulation in determining the strength and variability of the AMOC and the northward heat transport. Understanding this newly identified role of the North Atlantic Subtropical Gyre is needed to properly represent future changes of the AMOC.
Hidden information on protein function in censuses of proteome foldedness
Authors: Cox Dezerae , Ang Ching-Seng , Nillegoda Nadinath B. , Reid Gavin E. , Hatters Danny M.
Published: April 2022

Methods that assay protein foldedness with proteomics have generated censuses of apparent protein folding stabilities in biological milieu. However, different censuses poorly correlate with each other. Here, we show that the reason for this is that methods targeting foldedness through monitoring amino acid sidechain reactivity also detect changes in conformation and ligand binding, which can be a substantial fraction of the data. We show that the reactivity of only one quarter of cysteine or methionine sidechains in proteins in a urea denaturation curve of mammalian cell lysate can be confidently explained by a two-state unfolding isotherm. Contrary to that expected from unfolding, up to one third of the cysteines decreased reactivity. These cysteines were enriched in proteins with functions relating to unfolded protein stress. One protein, chaperone HSPA8, displayed changes arising from ligand and cofactor binding. Unmasking this hidden information using the approaches outlined here should improve efforts to understand both folding and the remodeling of protein function directly in complex biological settings.
Membrane marker selection for segmenting single cell spatial proteomics data
Authors: Dayao Monica T. , Brusko Maigan , Wasserfall Clive , Bar-Joseph Ziv
Published: April 2022

The ability to profile spatial proteomics at the single cell level enables the study of cell types, their spatial distribution, and interactions in several tissues and conditions. Current methods for cell segmentation in such studies rely on known membrane or cell boundary markers. However, for many tissues, an optimal set of markers is not known, and even within a tissue, different cell types may express different markers. Here we present RAMCES, a method that uses a convolutional neural network to learn the optimal markers for a new sample and outputs a weighted combination of the selected markers for segmentation. Testing RAMCES on several existing datasets indicates that it correctly identifies cell boundary markers, improving on methods that rely on a single marker or those that extend nuclei segmentations. Application to new spatial proteomics data demonstrates its usefulness for accurately assigning cell types based on the proteins expressed in segmented cells.
Deep learning enhanced Rydberg multifrequency microwave recognition
Authors: Liu Zong-Kai , Zhang Li-Hua , Liu Bang , Zhang Zheng-Yuan , Guo Guang-Can , Ding Dong-Sheng , Shi Bao-Sen
Published: April 2022

Recognition of multifrequency microwave (MW) electric fields is challenging because of the complex interference of multifrequency fields in practical applications. Rydberg atom-based measurements for multifrequency MW electric fields is promising in MW radar and MW communications. However, Rydberg atoms are sensitive not only to the MW signal but also to noise from atomic collisions and the environment, meaning that solution of the governing Lindblad master equation of light-atom interactions is complicated by the inclusion of noise and high-order terms. Here, we solve these problems by combining Rydberg atoms with deep learning model, demonstrating that this model uses the sensitivity of the Rydberg atoms while also reducing the impact of noise without solving the master equation. As a proof-of-principle demonstration, the deep learning enhanced Rydberg receiver allows direct decoding of the frequency-division multiplexed signal. This type of sensing technology is expected to benefit Rydberg-based MW fields sensing and communication.
Interactive single-cell data analysis using Cellar
Authors: Hasanaj Euxhen , Wang Jingtao , Sarathi Arjun , Ding Jun , Bar-Joseph Ziv
Published: April 2022

Cell type assignment is a major challenge for all types of high throughput single cell data. In many cases such assignment requires the repeated manual use of external and complementary data sources. To improve the ability to uniformly assign cell types across large consortia, platforms and modalities, we developed Cellar, a software tool that provides interactive support to all the different steps involved in the assignment and dataset comparison process. We discuss the different methods implemented by Cellar, how these can be used with different data types, how to combine complementary data types and how to analyze and visualize spatial data. We demonstrate the advantages of Cellar by using it to annotate several HuBMAP datasets from multi-omics single-cell sequencing and spatial proteomics studies. Cellar is open-source and includes several annotated HuBMAP datasets.
CENP-N promotes the compaction of centromeric chromatin
Authors: Zhou Keda , Gebala Magdalena , Woods Dustin , Sundararajan Kousik , Edwards Garrett , Krzizike Dan , Wereszczynski Jeff , Straight Aaron F. , Luger Karolin
Published: April 2022

The histone variant CENP-A is the epigenetic determinant for the centromere, where it is interspersed with canonical H3 to form a specialized chromatin structure that nucleates the kinetochore. How nucleosomes at the centromere arrange into higher order structures is unknown. Here we demonstrate that the human CENP-A-interacting protein CENP-N promotes the stacking of CENP-A-containing mononucleosomes and nucleosomal arrays through a previously undefined interaction between the α6 helix of CENP-N with the DNA of a neighboring nucleosome. We describe the cryo-EM structures and biophysical characterization of such CENP-N-mediated nucleosome stacks and nucleosomal arrays and demonstrate that this interaction is responsible for the formation of densely packed chromatin at the centromere in the cell. Our results provide first evidence that CENP-A, together with CENP-N, promotes specific chromatin higher order structure at the centromere.
Bilateral international migration flow estimates updated and refined by sex
Authors: Abel Guy J. , Cohen Joel E.
Published: April 2022

Females and males often migrate at different rates. Official data on sex-specific international migration flows are missing for most countries, prohibiting comparative measures to identify and address inequalities. Here we use six methods to estimate male and female five-year bilateral migration flows between 200 countries from 1990 to 2020. We validate the estimates from each method through correlations of several migration measures with equivalent reported statistics in countries that collect flow data. We find that the Pseudo-Bayesian demographic accounting method performs consistently better than the other estimation methods for both female and male estimated flows. The estimates from all methods indicate a decline in the share of female migration flows from 1990–1995 to 2005–2010 followed by a recovery over the decade since 2010.
Experimental evidence for snails dispersing tardigrades based on Milnesium inceptum and Cepaea nemoralis species
Authors: Książkiewicz Zofia , Roszkowska Milena
Published: April 2022

Dispersal abilities in animals contribute to their local genetic variability and species persistence. However, the mechanisms facilitating a short-distance migration of small organisms remain underexplored. In this study we experimentally tested the role of land snails for a fine-scale transmission of tardigrades. We also check the ecological relationship between these two groups, by testing the impact of snail's mucus on tardigrades in anhydrobiosis. All the experiments were conducted under laboratory conditions. As model organisms, we used a tardigrade species Milnesium inceptum and a snail species Cepaea nemoralis. The selection of the experimental animals was dictated by their co-occurrence in natural habitats and similar atmospheric conditions required for them to remain active. Results of our experiments support the assumption that snails may transfer active tardigrades for short distances. On the other hand, the effect of the snails mucus on tardigrade recovery to active life after anhydrobiosis was negative. Death rates of tardigrades in anhydrobiosis (tun) were higher when affected by mucus compared to mucus-free tuns.
Computational prediction of the molecular mechanism of statin group of drugs against SARS-CoV-2 pathogenesis
Authors: Ghosh Dipanjan , Ghosh Dastidar Debabrata , Roy Kamalesh , Ghosh Arnab , Mukhopadhyay Debanjan , Sikdar Nilabja , Biswas Nidhan K. , Chakrabarti Gopal , Das Amlan
Published: April 2022

Recently published clinical data from COVID-19 patients indicated that statin therapy is associated with a better clinical outcome and a significant reduction in the risk of mortality. In this study by computational analysis, we have aimed to predict the possible mechanism of the statin group of drugs by which they can inhibit SARS-CoV-2 pathogenesis. Blind docking of the critical structural and functional proteins of SARS-CoV-2 like RNA-dependent RNA polymerase, M-protease of 3-CL-Pro, Helicase, and the Spike proteins ( wild type and mutants from different VOCs) were performed using the Schrodinger docking tool. We observed that fluvastatin and pitavastatin showed fair, binding affinities to RNA polymerase and 3-CL-Pro, whereas fluvastatin showed the strongest binding affinity to the helicase. Fluvastatin also showed the highest affinity for the SpikeDelta and a fair docking score for other spike variants. Additionally, molecular dynamics simulation confirmed the formation of a stable drug-protein complex between Fluvastatin and target proteins. Thus our study shows that of all the statins, fluvastatin can bind to multiple target proteins of SARS-CoV-2, including the spike-mutant proteins. This property might contribute to the potent antiviral efficacy of this drug.
Effect of piezocision procedure in levelling and alignment stage of fixed orthodontic treatment: a randomized clinical trial
Authors: Sultana Sharmin , Ab Rahman Norma , Zainuddin Siti Lailatul Akmar , Ahmad Basaruddin
Published: April 2022

This clinical trial compared the time to complete the levelling and alignment stage with flapless piezocision procedure in the treatment of severe maxillary malocclusion with premolar extraction cases. Two-arm parallel group randomized controlled trial was performed at the Orthodontics Unit of Universiti Sains Malaysia, Malaysia. Sixteen patients with severe anterior maxillary crowding (Little’s irregularity index: 7–9 mm) and required bilateral first premolars extraction was recruited. The participants were randomly assigned to a study group according to a simple randomization method using a sealed envelope mentioned about the group name. Both groups were treated with fixed orthodontic appliance using the 0.022-in. slot of McLaughlin Bennett Trevisi prescription brackets. The piezocision group received flapless piezocision corticotomy about 4–5 mm in length and 3 mm depth on the labial mucogingiva between the roots of six anterior teeth. The number of days since treatment started, Little’s irregularity index, gingival recession, pocket depth, pulp vitality, patient perception of the pain and satisfaction level were recorded before the treatment, at about 1 month and 2 months post-treatment, and at the completion of the levelling and alignment stage. The overall time to complete levelling and alignment stage was significantly shorter in the piezocision group than the control group (mean difference = 31.5 days, 95% CI 6.5, 56.5; p = 0.018). Greater reduction in Little’s irregularity index and faster alignment rate in the first 2 months  were found in the piezocision group compared to the control group (p < 0.05). No changes in the gingival recession, pocket depth, and pulp vitality in both groups were observed. Patients who received piezocision surgery experienced no or mild pain and were satisfied with the treatment. Flapless piezocision corticotomy is an effective adjunct that shortens treatment time during levelling and alignment stage without any adverse effects on the teeth and surrounding tissues. It is also painless, acceptable and satisfactory to the patients.

Trial registration: ACTRN12621001350819.
Co-treatment with Esculin and erythropoietin protects against renal ischemia–reperfusion injury via P2X7 receptor inhibition and PI3K/Akt activation
Authors: El-Maadawy Walaa H. , Hassan Marwa , Hafiz Ehab , Badawy Mohamed H. , Eldahshan Samir , AbuSeada AbdulRahman , El-Shazly Maha A. M. , Ghareeb Mosad A.
Published: April 2022

Renal ischemia/reperfusion (RI/R) is a critical clinical outcome with slightly reported improvement in mortality and morbidity. Effective therapies are still crucially required. Accordingly, the therapeutic effects of esculin (ESC, LCESI-MS/MS-isolated compound from Vachellia farnesiana flowers extract, with reported P2X7 receptor inhibitor activity) alone and in combination with erythropoietin (EPO) were investigated against RI/R injury and the possible underlying mechanisms were delineated. ESC and EPO were administered for 7 days and 30 min prior to RI, respectively. Twenty-four hour following reperfusion, blood and kidney samples were collected. Results revealed that pretreatment with either ESC or EPO reduced serum nephrotoxicity indices, renal oxidative stress, inflammatory, and apoptosis markers. They also ameliorated the renal histopathological injury on both endothelial and tubular epithelial levels. Notably, ESC markedly inhibited P2X7 receptors and NLRP3 inflammasome signaling (downregulated NLRP3 and Caspase-1 gene expressions), whereas EPO significantly upregulated PI3K and Akt gene expressions, also p-PI3K and p-Akt levels in renal tissues. ESC, for the first time, demonstrated effective protection against RI/R-injury and its combination with EPO exerted maximal renoprotection when compared to each monotherapy, thereby representing an effective therapeutic approach via inhibiting oxidative stress, inflammation, renal tubular and endothelial injury, apoptosis, and P2X7 receptors expression, and activating PI3K/Akt pathway.