bluuebunny/crossref_metadata_2025 huggingface dataset:
A late-glacial lake-effect climate regime and abundant tamarack in the Great Lakes Region, North America
Authors: Griggs Carol B. , Lewis C.F. Michael , Kristovich David A.
Published: May 2022

A unique regional climate progression, ca 14.2–11.5 cal ka BP, in the eastern Great Lakes region of North America is suggested by subfossil logs, high-resolution14C dates, and established proxy records in New York, USA. The progression began with a northern boreal-type climate ca. 14.2–13.1 ka coeval with the expansion of Lake Iroquois, a transition to a southern boreal-type climate ~13.1–12.9 ka that coincided with the transition of Lake Iroquois into progressively lower lake levels, and a continuation of the southern boreal-type climate ~12.9–11.5 ka. These conditions and changes are evident in the tree rings and relative dominance of tamarack (Larix laricina) and spruce species (Piceaspp.) plus the presence of black ash (Fraxinus nigra) as the only thermophilous species. Together they suggest variations in atmospheric moisture levels, surface winds, temperature extremes, and/or an enhanced seasonality over time. Here we propose that the evolution of the glacial Great Lakes and their interactions with ice sheets, meltwater, winds, and regional topography created a regional glacial lake-effect climate, 14.2–11.5 cal ka BP, that was opposite to the established warming Bølling-Allerød–cold Younger Dryas climate progression.
Canvassing the Gatekeepers: A Field Experiment to Increase Women Voters’ Turnout in Pakistan
Authors: CHEEMA ALI , KHAN SARAH , LIAQAT ASAD , MOHMAND SHANDANA KHAN
Published: May 2022

How can we close persistent gender gaps in political participation? We develop a theory highlighting the role of male household members as “gatekeepers” of women’s participation in patriarchal settings and argue that the answer involves targeting these men. We conduct a field experiment in Pakistan and find that targeting women with a nonpartisan get-out-the-vote campaign has no effect on their turnout in a national election. However, women’s turnout increases substantially when male household members are canvassed to support women’s participation. Households where both men and women are canvassed see the largest increases in women’s turnout and additional increases in political discussion and men’s practical support to help women vote. Using a costly behavioral measure, we also demonstrate lasting effects on men’s supportive behavior in these households two months after the election. Our results address the importance, and tangible benefits, of engaging men to ease constraints that hinder equal participation.
Record of three specimens of megamouth sharks – Megachasma pelagios – in tropical tuna purse seine fisheries in the Atlantic and Indian Oceans
Authors: Diez Guzman , Ruiz Jon , Salgado Alex
Published: May 2022

The observer programme onboard the Spanish tropical tuna purse seine fleet recorded the incidental catch of one adult megamouth shark Megachasma pelagios in December 2005 and two juvenile megamouth sharks in the eastern Atlantic in July 2016 and August 2018, respectively. The same fleet also bycaught an adult individual in December 2005 in the western Indian Ocean. The juveniles were caught relatively near to the coast, while the adult was caught in oceanic waters. The companion species in the fishing sets were elasmobranchs, tuna and billfish.
Risk for midlife psychosis in women: critical gaps and opportunities in exploring perimenopause and ovarian hormones as mechanisms of risk
Authors: Culbert Kristen M. , Thakkar Katharine N. , Klump Kelly L.
Published: May 2022

Women show a heightened risk for psychosis in midlife that is not observed in men. The menopausal transition (i.e. perimenopause) and accompanying changes in ovarian hormones are theorized to account for this midlife increase in risk. This narrative review aims to empirically examine these theories by reviewing studies of midlife and perimenopausal psychosis risk in women and potential ovarian hormone mechanisms of effects. Clinical and pre-clinical studies examining the effects of midlife age, menopausal stage, and ovarian hormones across adulthood on psychosis risk were identified. Synthesis of this body of work revealed that the peak ages of midlife psychosis risk in women overlap with the age range of key menopausal stages (especially the perimenopausal transition), although studies directly assessing menopausal stage are lacking. Studies examining ovarian hormone effects have almost exclusively focused on earlier developmental stages and events (e.g. pregnancy, the menstrual cycle) and show increases in psychotic symptoms in women and female rats during periods of lower estradiol levels. Estrogen treatment also tends to enhance the effects of neuroleptics in females across species at various reproductive phases. Initial data are promising in suggesting a role for menopausal stage and ovarian hormones in psychosis risk. However, critical gaps in our knowledge base remain, as there is a tendency to rely on indirect and proxy measures of menopausal status and hormones. Opportunities for future research are discussed with the goal of increasing research in this critical area of women's health.
Urbanization impacts water quality and the use of microhabitats by fish in subtropical agricultural streams
Authors: Barrios Margenny , Teixeira de Mello Franco
Published: May 2022

Land-use changes have negative effects on stream conditions and fish assemblages, but their effects on water quality and the use of microhabitats by fish in subtropical lowland streams are unclear. We evaluated the effects of urban patches (two urban streams) in an agricultural matrix (two ‘agricultural’ streams) on water quality, microhabitat diversity and fish assemblages, as well as the selection of microhabitat types by fish in the Arroyo Colorado basin (Uruguay). Physicochemical water parameters were measured, the fish sampled using electrofishing, microhabitat diversity, occupancy of microhabitats by fish and the most important microhabitat types for fish species were analysed. Agricultural streams presented higher water quality and microhabitat diversity, and most of the microhabitats were occupied by fish. Microhabitats with medium substrate sizes and running water prevailed in urban streams, while the presence of macrophytes, shallow waters and different substrate sizes were common in agricultural streams. The most important microhabitats used by fish species were not the most abundant, highlighting the fragility of streams resulting from the loss of appropriate conditions. Understanding how different degrees of deterioration in streams affect water quality and microhabitat–fish interactions is essential for the designing of effective monitoring and restoration programmes.
Prevalence of SARS-CoV-2 antibodies during phased access to vaccination: results from a population-based survey in New York City, September 2020–March 2021
Authors: Parrott Jannae C. , Annibale Ariana Maleki , Osahan Sukhminder , Alroy Karen , Caton Jo-Anne , Chernov Claudia , Dumas Sarah , Fowler Randal C. , Hermosi Gabriella , Hsin Yusyin , Perlman Sharon , Wu Jing , Hughes Scott , Gould L. Hannah , Schuster Anne
Published: May 2022

Repeated serosurveys are an important tool for understanding trends in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination. During 1 September 2020–20 March 2021, the NYC Health Department conducted a population-based SARS-CoV-2 antibody prevalence survey of 2096 NYC adults who either provided a blood specimen or self-reported the results of a previous antibody test. The serosurvey, the second in a series of surveys conducted by the NYC Health Department, aimed to estimate SARS-CoV-2 antibody prevalence across the city and for different groups at higher risk for adverse health outcomes. Weighted citywide prevalence was 23.5% overall (95% confidence interval (CI) 20.1–27.4) and increased from 19.2% (95% CI 14.7–24.6) before coronavirus disease 2019 vaccines were available to 31.3% (95% CI 24.5–39.0) during the early phases of vaccine roll-out. We found no differences in antibody prevalence by age, race/ethnicity, borough, education, marital status, sex, health insurance coverage, self-reported general health or neighbourhood poverty. These results show an overall increase in population-level seropositivity in NYC following the introduction of SARS-CoV-2 vaccines and highlight the importance of repeated serosurveys in understanding the pandemic's progression.
Outbreak of STEC O157:H7 linked to a milk pasteurisation failure at a dairy farm in England, 2019
Authors: Jenkins Claire , Bird Philippa K. , Wensley Adrian , Wilkinson Jarrod , Aird Heather , Mackintosh Adrienne , Greig David R. , Simpson Alex , Byrne Lisa , Wilkinson Rachel , Godbole Gauri , Arunachalam Nachi , Hughes Gareth J.
Published: May 2022

In November 2019, an outbreak of Shiga toxin-producing Escherichia coli O157:H7 was detected in South Yorkshire, England. Initial investigations established consumption of milk from a local dairy as a common exposure. A sample of pasteurised milk tested the next day failed the phosphatase test, indicating contamination of the pasteurised milk by unpasteurised (raw) milk. The dairy owner agreed to immediately cease production and initiate a recall. Inspection of the pasteuriser revealed a damaged seal on the flow divert valve. Ultimately, there were 21 confirmed cases linked to the outbreak, of which 11 (52%) were female, and 12/21 (57%) were either <15 or >65 years of age. Twelve (57%) patients were treated in hospital, and three cases developed haemolytic uraemic syndrome. Although the outbreak strain was not detected in the milk samples, it was detected in faecal samples from the cattle on the farm. Outbreaks of gastrointestinal disease caused by milk pasteurisation failures are rare in the UK. However, such outbreaks are a major public health concern as, unlike unpasteurised milk, pasteurised milk is marketed as ‘safe to drink’ and sold to a larger, and more dispersed, population. The rapid, co-ordinated multi-agency investigation initiated in response to this outbreak undoubtedly prevented further cases.
Successful treatment of re-coarctation of the aorta with percutaneous stent placement via axillary artery access in a young patient
Authors: Çınar Ayşegül Aslan , Yücel İlker Kemal , Çelebi Ahmet
Published: May 2022

In patients with critical coarctation of the aorta, percutaneous balloon angioplasty and/or stent placement is usually performed via the femoral route. When femoral access is not suitable for intervention, the trans-axillary approach can be chosen as an alternative access. We hereby present the first case of a patient who had a successful percutaneous stent placement via trans-axillary access in our institution.
Integration Law – An Independent Legal System
Authors: Iskakova Zhanna , Karazhan Bekmyrza , Seidesh Bakizhan , Karabayev Fazylzhan , Zukay Zhanerke
Published: May 2022

Economic integration has become a general trend in the development of cooperation between states. At the initial stages of integration construction, integration associations are a special kind of international organization. Later, the legal complexes of integration formations stand out and represent separate, independent legal systems (both from international law and from the national (domestic) law of the member states). This article attempts to theoretically generalize, synthesize and develop scientific provisions on integration associations and the legal systems created in them, accumulated in domestic and foreign legal science. The purpose of this study was the formation of a balanced, reasoned position, which fitted modern realities, on the existence of integration law. The methodological basis of the research was formed by a complex of general scientific and special methods for studying legal concepts, institutions and processes in the field of integration law: comparative legal, systemic and structural. Thanks to their application, it becomes possible to identify the general, specific and singular in the activities of integration associations. We managed to substantiate the concept of the formation within the framework of integration associations of our own institutional and legal systems (integration law), which have a close genetic link with international and national law. In our opinion, integration law (or ‘the law of integration formations’) acts as a system that presupposes a single internal structure, hierarchy and mutual consistency of its constituent parts.
Coping with demographic change: macroeconomic performance and welfare inequality effects of public pension reform
Authors: Devriendt Willem , Heylen Freddy , Jacobs Arthur
Published: May 2022

This paper evaluates alternative reforms of the public pension system in an overlapping generations model for an open economy facing demographic change. We make progress compared to existing literature on pension reform by modelling individuals with heterogeneous innate ability and endogenous human capital, and by putting (the reduction of) welfare inequality effects of reform at the centre. Frequently adopted reforms such as an increase of the normal retirement age or a decrease of the pension benefit can guarantee financial sustainability, but they fail when the objective is also to avoid intergenerational or intragenerational welfare inequality. Our results prefer a reform which combines an increase of the retirement age with an intelligent linkage between the pension benefit and earlier labour earnings. First, this design conditions pension benefits on past individual labour income, with a high weight on labour income earned when older and a low weight on labour income earned when young. Second, this linkage is complemented by a strong rise in the benefit replacement rate for low ability individuals (and a reduction for high ability individuals).
Genetic diversity and phylogeny analysis of 3-hydroxy 3-methylglutaryl-CoA reductase gene (SmHMGR) in Danshen (Salvia miltiorrhiza Bunge)
Authors: Ren Ruihua , Liao Fang , Kong Deying , Yin Yanyan , Liu Wei , Teng Shaona , Feng Jie , Li Guanrong
Published: May 2022

HMGR, 3-hydroxy-3-methylglutaryl-CoA reductase, is a major rate-limiting enzyme in mevalonate (MVA) pathway for isoprenoids and subsequent tanshinone biosynthesis in the Chinese traditional bulk herbal medicine Danshen, Salvia miltiorrhiza, mainly for cardiovascular disorders. In this paper, the genomic SmHMGR genes of 38 cultivated populations of S. miltiorrhiza collected in China were for the first time sequenced to reveal the genetic diversity and phylogeny. The SmHMGR gene was shown to be intron-free, 1650~1659 bp in complete CDS with the majority being 1656 bp, and two unique populations (W-FJLY-V-1 and W-SCHY-W-1) being 1659 and 1650 bp respectively. A total of 103 SNP variation sites were detected with a variation rate of 6.22%, most of which occurred in S. miltiorrhiza f. alba population W-SCHY-W-1; a total of 25 amino acid variation sites were found, of which 19 was in W-SCHY-W-1. The same four populations, W-SCHY-W-1, V-HBAG-V-1, V-JLCC-V-1 and S-NM-V-1 could be discriminated from the remaining 34 by both the SNP fingerprints and the deduced amino acid variation sites. Other or composite DNA markers are needed for better identification. The SmHMGR gene of white flower S. miltiorrhiza f. alba population W-SCHY-W-1 is especially rich in variations and worthy of further studies. Phylogenetic trees based on both the gene and the deduced amino acid sequences showed a very similar two-clade topological structure. This research enriched the content and the genetic means for the molecular identification, genetic diversity and phylogenetic studies of the cultivated S. miltiorrhiza populations, and laid a solid foundation for further related and in-depth investigations.
Morbus Behçet
Authors: Mahr Alfred
Published: May 2022

Zusammenfassung. In der ärztlichen Praxis stellt der Morbus Behçet (MB) eine diagnostische und therapeutische Herausforderung dar. Wegen der Seltenheit des MB und des heterogenen Krankheitsbilds ist es schwierig, einen guten Erfahrungsschatz über diese Erkrankung zu gewinnen. Ausserdem beruht die Diagnosestellung in den allermeisten Fällen auf dem klinischen Bild und therapeutische Entscheidungen müssen sich an den Daten von relativ wenigen Therapiestudien orientieren. Diese kurze Übersicht behandelt einige Grundlagen der Diagnostik und Behandlung des MB.
Kutane Vaskulitiden
Authors: Bircher Andreas J. , Pelloni Lorenzo , Terrani Isabella , Spoerl David , Beltraminelli Helmut
Published: May 2022

Zusammenfassung. Vaskulitiden sind eine heterogene Gruppe von Erkrankungen, die unterschiedlich klassifiziert werden, zum Beispiel nach der Grösse des betroffenen Gefässes oder nach primärer und sekundärer Ätiologie. Die Haut ist am häufigsten betroffen ist, sie kann sowohl isoliert als auch im Rahmen von systemischen Formen involviert sein. Die Kombination der Hautläsionen, deren anatomischer Lokalisation und Informationen zum Zeitablauf geben Hinweise für die Differenzialdiagnose. Purpura, Blasen, Nekrosen, Ulzerationen und allenfalls eine Livedo sind charakteristische Manifestationen. Konstitutionelle Symptome wie Gewichtsverlust, Abgeschlagenheit, Fieber und Arthralgien sind hinweisend auf eine systemische Form. Wichtig ist die differenzialdiagnostische Abgrenzung von Vaskulopathien, die sich ähnlich manifestieren können. Am häufigsten beim Erwachsenen ist die kutane leukozytoklastische Angiitis, beim Kind die IgA-Vaskulitis (Purpura Schönlein-Henoch). Bei diesen kommen diverse Auslöser in Frage: Infektionen, Medikamente, Autoimmunerkrankungen und Malignome, wobei bis zu 50% ätiologisch ungeklärt bleiben. Hautbiopsien und Laborparameter, allenfalls ergänzt durch Bildgebung, sind wichtige Schritte im Abklärungsprozedere. Die Behandlung richtet sich primär auf die Elimination einer möglichen Ursache. Die idiopathische kutane Form bildet sich meistens spontan zurück, die Behandlung ist symptomatisch. Bei schwererem Verlauf werden primär topisch Kortikosteroide oder Calcineurinantagonisten angewandt. Bei Therapieresistenz werden systemische Immunsuppressiva eingesetzt.
Primäre ZNS-Vaskulitis
Authors: Hammer Helly , Kamber Nicole , Friedli Christoph , Hoepner Robert , Diem Lara , Chan Andrew , Salmen Anke
Published: May 2022

Zusammenfassung. Die zerebralen Vaskulitiden, insbesondere die primäre Vaskulitis des Zentralnervensystems (primäre ZNS-Vaskulitis), sind seltene entzündliche Erkrankungen der kleinen und mittelgrossen Gefässe des ZNS. Klinisch präsentiert sich die primäre ZNS-Vaskulitis heterogen mit Leitsymptomen wie Kopfschmerzen, Gedächtnisstörungen und anderen neurologischen Defiziten. Die Pathogenese der primären ZNS-Vaskulitis ist unklar. Vermutet wird eine infektgetriggerte Aktivierung des Immunsystems mit daraus resultierender Inflammation der Blutgefässe des ZNS. Die breite differentialdiagnostische Abklärung vor Therapieeinleitung spielt eine entscheidende Rolle. Die Behandlung besteht aus einer Immuntherapie (Puls- und Erhaltungstherapie) und bedarf aufgrund des erhöhten Rezidivrisikos der Erkrankung einer langfristigen neurologischen Anbindung und Therapie.
A Statistical Study of Pancake Pitch Angle Distribution of Low‐Energy Protons and Their Correlation With Magnetosonic Waves
Authors: Wu Z. , Teng S. , Ma Q. , Tao X.
Published: May 2022

We performed a statistical study of the proton pancake pitch angle distributions (PADs) at the energy from 10 to 300 eV with the Helium Oxygen Proton Electron instrument on board the Van Allen Probes. The occurrence rate of low energy proton pancake PADs and their dependence on the energy, L shell, magnetic local time (MLT) and AL* index are analyzed. The results indicate that: (a) the occurrence rate of pancake PADs decreases as the proton energy increases; (b) under active geomagnetic activities (AL* < −300 nT), pancake PADs preferentially occur in the dayside; (c) under weak geomagnetic activities (AL* > −100 nT), the occurrence rate of pancake PADs has little dependence on MLT. We further discuss the contribution of magnetosonic (MS) waves on the formation of proton pancake PADs at low energy. The strong correlation between the occurrence of pancake PADs and the appearance of MS waves indicates that MS waves contribute to the formation of low energy proton pancake PADs. Moreover, the proton diffusion coefficients caused by MS waves suggest that MS waves can cause the proton heating at low energies in high density regions.
The Levels and Sources of Nitrous Acid (HONO) in Winter of Beijing and Sanmenxia
Authors: Zhang Xinran , Tong Shengrui , Jia Chenhui , Zhang Wenqian , Li Jie , Wang Weigang , Sun Yele , Wang Xuan , Wang Lingling , Ji Dongsheng , Wang Lili , Zhao Pusheng , Tang Guiqian , Xin Jinyuan , Li Ang , Ge Maofa
Published: May 2022

HONO concentrations in Beijing (BJ) and Sanmenxia (SMX) were simultaneously measured in winter with a duration of 1 month, and the sources and sinks of HONO in the two cities were comparably analyzed. BJ and SMX had different pollution characteristics. Direct vehicle emission made a contribution to observed HONO of about 28% in BJ, whereas it contributed to HONO only about 12% in SMX. Additionally, direct emission from coal combustion in SMX also made a significant contribution to atmospheric HONO, which could achieve to be 13%. In BJ, nighttime NO2 conversion on the aerosol and ground surfaces contributed to HONO sources of 15% and 27%, respectively. In SMX, nighttime NO2 conversion on the aerosol and ground surfaces contributed to HONO sources of 40% and 30%, respectively. Daytime NO2 heterogeneous conversion (including photo‐enhanced conversion) on the aerosol and ground surfaces was important in SMX. Daytime NO3− photolysis contributed 9% HONO in SMX and 4% in BJ. The primary OH production rates from photolysis of daytime HONO in both BJ and SMX were three orders of magnitude faster than those from photolysis of O3, revealing the dominant role of HONO in local atmospheric chemistry of the two cities in winter.
Climatic Control on Spatial Distribution of Water Storage at the Catchment Scale: A Framework for Unifying Saturation Excess Runoff Models
Authors: Yao Lili , Wang Dingbao
Published: May 2022

This paper aims to investigate the connection between TOPography‐based hydrological model (TOPMODEL) and Variable Infiltration Capacity (VIC) model through virtual experiments from the perspective of water table and storage at the catchment scale. A simple finite‐difference groundwater flow model was built for a hypothetical catchment forced by a sequence of recharges. A steady‐state water table under a low recharge rate is used as the climatic lower limit, above which the pore space is considered as the maximum storage capacity. When the water table is shallow, the land surface is a good proxy of the water table as assumed in the original TOPMODEL, and the underlying water storage distribution curve is similar as the maximum storage capacity distribution curve. When the water table is deep, the climatic lower limit is a good proxy of water table, and the storage is approximately spatially uniform over the unsaturated area as assumed in the VIC model. The systematic variation of water table and storage distribution potentially provides a framework for unifying the TOPMODEL and VIC model.
Evaluating Multiple Canopy‐Snow Unloading Parameterizations in SUMMA With Time‐Lapse Photography Characterized by Citizen Scientists
Authors: Lumbrazo Cassie , Bennett Andrew , Currier William Ryan , Nijssen Bart , Lundquist Jessica
Published: May 2022

Canopy‐snow unloading is the complex physical process of snow unloading from the canopy through meltwater drip, sublimation to the atmosphere, or solid snow unloading to the snowpack below. This process is difficult to parameterize due to limited observations. Time‐lapse photographs of snow in the canopy were characterized by citizen scientists to create a data set of snow interception observations at multiple locations across the western United States. This novel interception data set was used to evaluate three snow unloading parameterizations in the Structure for Unifying Multiple Modeling Alternatives (SUMMA) modular hydrologic modeling framework. SUMMA was modified to include a third snow unloading parameterization, termed Wind‐Temperature (Roesch et al., 2001, https://doi.org/10.1007/s003820100153), which includes wind‐dependent and temperature‐dependent unloading functions. It was compared to a meltwater drip unloading parameterization, termed Melt (Andreadis et al., 2009, https://doi.org/10.1029/2008wr007042), and a time‐dependent unloading parameterization, termed Exponential‐Decay (Hedstrom & Pomeroy, 1998, https://doi.org/10.1002/(SICI)1099-1085(199808/09)12:10/11<1611::AID-HYP684>3.0.CO;2-4). Wind‐Temperature performed well without calibration across sites, specifically in cold climates, where wind dominates unloading and rime accretion is low. At rime prone sites, Wind‐Temperature should be calibrated to account for longer interception events with less sensitivity to wind, otherwise Melt can be used without calibration. The absence of model physics in Exponential‐Decay requires local calibration that can only be transferred to sites with similar unloading patterns. The choice of unloading parameterization can result in 20% difference in SWE on the ground below the canopy and 10% difference in estimated average winter canopy albedo. These novel observations shed light on processes that are often overlooked in hydrology.
Pediatric T-ALL type-1 and type-2 relapses develop along distinct pathways of clonal evolution
Authors: Richter-Pechańska Paulina , Kunz Joachim B. , Rausch Tobias , Erarslan-Uysal Büşra , Bornhauser Beat , Frismantas Viktoras , Assenov Yassen , Zimmermann Martin , Happich Margit , von Knebel-Doeberitz Caroline , von Neuhoff Nils , Köhler Rolf , Stanulla Martin , Schrappe Martin , Cario Gunnar , Escherich Gabriele , Kirschner-Schwabe Renate , Eckert Cornelia , Avigad Smadar , Pfister Stefan M. , Muckenthaler Martina U. , Bourquin Jean-Pierre , Korbel Jan O. , Kulozik Andreas E.
Published: May 2022

The mechanisms underlying T-ALL relapse remain essentially unknown. Multilevel-omics in 38 matched pairs of initial and relapsed T-ALL revealed 18 (47%) type-1 (defined by being derived from the major ancestral clone) and 20 (53%) type-2 relapses (derived from a minor ancestral clone). In both types of relapse, we observed known and novel drivers of multidrug resistance including MDR1 and MVP, NT5C2 and JAK-STAT activators. Patients with type-1 relapses were specifically characterized by IL7R upregulation. In remarkable contrast, type-2 relapses demonstrated (1) enrichment of constitutional cancer predisposition gene mutations, (2) divergent genetic and epigenetic remodeling, and (3) enrichment of somatic hypermutator phenotypes, related to BLM, BUB1B/PMS2 and TP53 mutations. T-ALLs that later progressed to type-2 relapses exhibited a complex subclonal architecture, unexpectedly, already at the time of initial diagnosis. Deconvolution analysis of ATAC-Seq profiles showed that T-ALLs later developing into type-1 relapses resembled a predominant immature thymic T-cell population, whereas T-ALLs developing into type-2 relapses resembled a mixture of normal T-cell precursors. In sum, our analyses revealed fundamentally different mechanisms driving either type-1 or type-2 T-ALL relapse and indicate that differential capacities of disease evolution are already inherent to the molecular setup of the initial leukemia.
The laws of physics do not prohibit counterfactual communication
Authors: Salih Hatim , McCutcheon Will , Hance Jonte R. , Rarity John
Published: May 2022

It has been conjectured that counterfactual communication is impossible, even for post-selected quantum particles. We strongly challenge this by proposing precisely such a counterfactual scheme where—unambiguously—none of Alice’s photons that correctly contribute to her information about Bob’s message have been to Bob. We demonstrate counterfactuality experimentally by means of weak measurements, and conceptually using consistent histories—thus simultaneously satisfying both criteria without loopholes. Importantly, the fidelity of Alice learning Bob’s bit can be made arbitrarily close to unity.
The mosaic oat genome gives insights into a uniquely healthy cereal crop
Authors: Kamal Nadia , Tsardakas Renhuldt Nikos , Bentzer Johan , Gundlach Heidrun , Haberer Georg , Juhász Angéla , Lux Thomas , Bose Utpal , Tye-Din Jason A. , Lang Daniel , van Gessel Nico , Reski Ralf , Fu Yong-Bi , Spégel Peter , Ceplitis Alf , Himmelbach Axel , Waters Amanda J. , Bekele Wubishet A. , Colgrave Michelle L. , Hansson Mats , Stein Nils , Mayer Klaus F. X. , Jellen Eric N. , Maughan Peter J. , Tinker Nicholas A. , Mascher Martin , Olsson Olof , Spannagl Manuel , Sirijovski Nick
Published: May 2022

Cultivated oat (Avena sativa L.) is an allohexaploid (AACCDD, 2n = 6x = 42) thought to have been domesticated more than 3,000 years ago while growing as a weed in wheat, emmer and barley fields in Anatolia1,2. Oat has a low carbon footprint, substantial health benefits and the potential to replace animal-based food products. However, the lack of a fully annotated reference genome has hampered efforts to deconvolute its complex evolutionary history and functional gene dynamics. Here we present a high-quality reference genome of A. sativa and close relatives of its diploid (Avena longiglumis, AA, 2n = 14) and tetraploid (Avena insularis, CCDD, 2n = 4x = 28) progenitors. We reveal the mosaic structure of the oat genome, trace large-scale genomic reorganizations in the polyploidization history of oat and illustrate a breeding barrier associated with the genome architecture of oat. We showcase detailed analyses of gene families implicated in human health and nutrition, which adds to the evidence supporting oat safety in gluten-free diets, and we perform mapping-by-sequencing of an agronomic trait related to water-use efficiency. This resource for the Avena genus will help to leverage knowledge from other cereal genomes, improve understanding of basic oat biology and accelerate genomics-assisted breeding and reanalysis of quantitative trait studies.
Quantum imaging with a photon counting camera
Authors: Wolley Osian , Gregory Thomas , Beer Sebastian , Higuchi Takafumi , Padgett Miles
Published: May 2022

Classical light sources emit a randomly-timed stream of individual photons, the spatial distribution of which can be detected with a camera to form an image. Quantum light sources, based on parametric down conversion, emit photons as correlated photon-pairs. The spatial correlations between the photons enables imaging systems where the preferential selection of photon-pairs allows for enhancements in the noise performance over what is possible using classical light sources. However, until now the technical challenge of measuring, and correlating both photons has led to system complexity. Here we show that a camera capable of resolving the number of individual photons in each pixel of the detector array can be used to record an image formed from these photon-pair events and hence achieve a greater contrast than possible using a classical light source. We achieve an enhancement in the ratio of two-photon events compared to one-photon events using spatially correlated SPDC light compared to uncorrelated illumination by a LED. These results indicate the potential advantages of using photon counting cameras in quantum imaging schemes and these advantages will further increase as the technology is developed. Operating in photon sparse regimes such systems have potential applications in low-light microscopy and covert imaging.
Genome-wide DNA methylation and gene expression patterns of androgenetic haploid tiger pufferfish (Takifugu rubripes) provide insights into haploid syndrome
Authors: Zhou He , Wang Qian , Zhou Zi-Yu , Li Xin , Sun Yu-Qing , Shan Gu , Zheng Xin-Yi , Chen Qi , Liu Hai-Jin , Wang Wei , Shao Chang-Wei
Published: May 2022

Androgenesis is an important chromosome set manipulation technique used in sex control in aquaculture. Haploid embryos exhibit haploid syndrome with body abnormalities and even die during early embryonic development. In this study, we used whole genome bisulfite sequencing (WGBS) to investigate the genome-wide DNA methylation profiles in haploid females (1n-X) and males (1n-Y), and diploid females (2n-XX) and males (2n-XY) of tiger pufferfish (Takifugu rubripes), an economically important fish in China. A total of 96.32 Gb clean data was produced. Differentially methylated regions (DMRs) were found between haploids and diploids, which may be related to abnormal development and early embryonic death in haploids. There were 3,641 hyper-methylated differentially methylated genes (DMGs) and 2,179 hypo-methylated DMGs in haploid vs. diploid comparisons in both females and males. These DMGs were mainly related to genomic stability maintenance and cell cycle regulation.slf1,actr8,gas2, andpbrm1genes were selected to validate the methylation sequencing. After combining the methylation data with the corresponding transcriptome data, we identified several genes, includingguca2a,myoc,fezf2,rprml,telo2,s100a1, andmarveld1,which exhibited differential expression levels modulated by DNA methylation. In conclusion, our study revealed different methylation and expression profiles between haploid and diploidT.rubripes for the first time. Several DMGs were identified between different ploidy levels, which may be related to haploid syndrome formation. The results expand the understanding of the effects of ploidy on the early development of teleosts and provide knowledge about target genes and networks to improve the survival rate of haploids.
Obesity and accelerated epigenetic aging in a high-risk cohort of children
Authors: Etzel Laura , Hastings Waylon J. , Hall Molly A. , Heim Christine M. , Meaney Michael J. , Noll Jennie G. , O’Donnell Kieran J. , Pokhvisneva Irina , Rose Emma J. , Schreier Hannah M. C. , Shenk Chad E. , Shalev Idan
Published: May 2022

New insights into mechanisms linking obesity to poor health outcomes suggest a role for cellular aging pathways, casting obesity as a disease of accelerated biological aging. Although obesity has been linked to accelerated epigenetic aging in middle-aged adults, the impact during childhood remains unclear. We tested the association between body mass index (BMI) and accelerated epigenetic aging in a cohort of high-risk children. Participants were children (N = 273, aged 8 to 14 years, 82% investigated for maltreatment) recruited to the Child Health Study, an ongoing prospective study of youth investigated for maltreatment and a comparison youth. BMI was measured as a continuous variable. Accelerated epigenetic aging of blood leukocytes was defined as the age-adjusted residuals of several established epigenetic aging clocks (Horvath, Hannum, GrimAge, PhenoAge) along with a newer algorithm, the DunedinPoAm, developed to quantify the pace-of-aging. Hypotheses were tested with generalized linear models. Higher age-and sex- adjusted z-scored BMI was significantly correlated with household income, blood cell counts, and three of the accelerated epigenetic aging measures: GrimAge (r = 0.31, P < .0001), PhenoAge (r = 0.24, P < .0001), and DunedinPoAm (r = 0.38, P < .0001). In fully adjusted models, GrimAge (β = 0.07; P = .0009) and DunedinPoAm (β = 0.0017; P < .0001) remained significantly associated with higher age- and sex-adjusted z-scored BMI. Maltreatment-status was not associated with accelerated epigenetic aging. In a high-risk cohort of children, higher BMI predicted epigenetic aging as assessed by two epigenetic aging clocks. These results suggest the association between obesity and accelerated epigenetic aging begins in early life, with implications for future morbidity and mortality risk.
Enhanced anticancer potency with reduced nephrotoxicity of newly synthesized platin-based complexes compared with cisplatin
Authors: Salehi Roya , Abyar Selda , Ramazani Fatemeh , Khandar Ali Akbar , Hosseini-Yazdi Seyed Abolfazl , White Jonathan M. , Edalati Mahdi , Kahroba Houman , Talebi Mehdi
Published: May 2022

As a platinum-containing anticancer drug, cisplatin is the keystone for treating many malignancies. Nephrotoxicity is the main dose-limiting toxicity, and several hydration therapies and supplementary strategies are utilized to reduce cisplatin-induced kidney damage, so the discovery and development of effective and safe antitumor drugs are still on the path of human health. Herein, a new four-coordinated Pt complex [Pt(TSC)Cl] using N(4)-phenyl-2-formylpyridine thiosemicarbazone (HTSC) was synthesized and characterized by single-crystal X-ray diffraction, 1HNMR, FT-IR, LC/MS and CHN elemental analysis. The Pt(TSC)Cl complex revealed antiproliferative activity against A549, MCF-7 and Caco-2 cell lines with a low micromolar IC50 (200–1.75 µM). Specifically, the Pt(TSC)Cl complex displayed more selectivity in Caco-2 cells (IC50 = 2.3 µM) than cisplatin (IC50 = 107 µM) after 48 h of treatment. Moreover, compared with cisplatin, a known nephrotoxic drug, the Pt(TSC)Cl complex exhibited lower nephrotoxicity against Hek293 normal cells. We also found that the Pt(TSC)Cl complex can effectively prevent cancer cell propagation in sub-G1 and S phases and induce apoptosis (more than 90%). Real time PCR and western analysis demonstrated that the expression pattern of apoptotic genes and proteins is according to the intrinsic apoptosis pathway through the Bax/Bcl-2-Casp9-Casp3/Casp7 axis. Collectively, our findings indicated that the Pt(TSC)Cl complex triggers apoptosis in Caco-2 cell lines, while low nephrotoxicity was shown and may be considered a useful anticancer drug candidate for colorectal cancers for further optimization and growth.
Ciliary neurotrophic factor is increased in the plasma of patients with obesity and its levels correlate with diabetes and inflammation indices
Authors: Perugini Jessica , Di Mercurio Eleonora , Giuliani Angelica , Sabbatinelli Jacopo , Bonfigli Anna Rita , Tortato Elena , Severi Ilenia , Cinti Saverio , Olivieri Fabiola , le Roux Carel W. , Gesuita Rosaria , Giordano Antonio
Published: May 2022

To establish whether obesity involves activation of endogenous ciliary neurotrophic factor (CNTF) signalling, we evaluated its plasma levels in patients with obesity and correlated its values with the major clinical and haematological indices of obesity, insulin resistance and systemic inflammation. This study involved 118 subjects: 39 healthy controls (19 men), 39 subjects with obesity (19 men) and 40 subjects with obesity and diabetes (20 men). Plasma CNTF and CNTF receptor α (CNTFRα) were measured using commercial ELISA kits. The results showed that plasma CNTF was significantly higher in males and females with obesity with and without diabetes than in healthy subjects. Women consistently exhibited higher levels of circulating CNTF. In both genders, CNTF levels correlated significantly and positively with obesity (BMI, WHR, leptin), diabetes (fasting insulin, HOMA index and HbA1c) and inflammation (IL-6 and hsCRP) indices. Circulating CNTFRα and the CNTF/CNTFRα molar ratio tended to be higher in the patient groups than in controls. In conclusion, endogenous CNTF signalling is activated in human obesity and may help counteract some adverse effects of obesity. Studies involving a higher number of selected patients may reveal circulating CNTF and/or CNTFRα as potential novel diagnostic and/or prognostic markers of obesity, diabetes and associated diseases.
Tension experience induced by tonal and melodic shift at music phrase boundaries
Authors: Zhang Ning , Sun Lijun , Wu Qiong , Yang Yufang
Published: May 2022

Music tension is a link between music structures and emotions. As music unfolds, developmental patterns induce various emotional experiences, but the relationship between developmental patterns and tension experience remains unclear. The present study compared two developmental patterns of two successive phrases (tonal shift and melodic shift) with repetition condition to investigate the relationship with tension experience. Professional musicians rated on-line felt tension and EEG responses were recorded while listening to music sequences. Behavioral results showed that tension ratings under tonal and melodic shift conditions were higher than those under repetition conditions. ERP results showed larger potentials at early P300 and late positive component (LPC) time windows under tonal shift condition, and early right anterior negativity (ERAN) and LPC under melodic shift condition. ERSP results showed early beta and late gamma power increased under tonal shift condition, theta power decreased and alpha power increased under melodic shift condition. Our findings suggest that developmental patterns play a vital role in tension experiences; tonal shift affects tension by tonal shift detection and integration, while melodic shift affects tension by attentional processing and working memory integration. From the perspective of Event Structure Processing Model, solid evidence was given to specify the time-span segmentation and reduction.
Targeting the translational machinery in gastrointestinal stromal tumors (GIST): a new therapeutic vulnerability
Authors: Lee Donna M. , Sun Angela , Patil Sneha S. , Liu Lijun , Rao Aparna V. , Trent Parker T. , Ali Areej A. , Liu Catherine , Rausch Jessica L. , Presutti Laura D. , Kaczorowski Adam , Schneider Felix , Amankulor Nduka M. , Shuda Masahiro , Duensing Anette
Published: May 2022

Although KIT-mutant GISTs can be effectively treated with tyrosine kinase inhibitors (TKIs), many patients develop resistance to imatinib mesylate (IM) as well as the FDA-approved later-line agents sunitinib, regorafenib and ripretinib. Resistance mechanisms mainly involve secondary mutations in the KIT receptor tyrosine kinase gene indicating continued dependency on the KIT signaling pathway. The fact that the type of secondary mutation confers either sensitivity or resistance towards TKIs and the notion that secondary mutations exhibit intra- and intertumoral heterogeneity complicates the optimal choice of treatment in the imatinib-resistant setting. Therefore, new strategies that target KIT independently of its underlying mutations are urgently needed. Homoharringtonine (HHT) is a first-in-class inhibitor of protein biosynthesis and is FDA-approved for the treatment of chronic myeloid leukemia (CML) that is resistant to at least two TKIs. HHT has also shown activity in KIT-mutant mastocytosis models, which are intrinsically resistant to imatinib and most other TKIs. We hypothesized that HHT could be effective in GIST through downregulation of KIT expression and subsequent decrease of KIT activation and downstream signaling. Testing several GIST cell line models, HHT led to a significant reduction in nascent protein synthesis and was highly effective in the nanomolar range in IM-sensitive and IM-resistant GIST cell lines. HHT treatment resulted in a rapid and complete abolishment of KIT expression and activation, while KIT mRNA levels were minimally affected. The response to HHT involved induction of apoptosis as well as cell cycle arrest. The antitumor activity of HHT was confirmed in a GIST xenograft model. Taken together, inhibition of protein biosynthesis is a promising strategy to overcome TKI resistance in GIST.
Age-related changes in visuo-proprioceptive processing in perceived body position
Authors: Teramoto Wataru
Published: May 2022

This study investigated age-related change in visuo-proprioceptive processing in the perceived body position using mirror hand/foot illusions, focusing on its temporal characteristics, its dependency on body parts, and its association with older adults’ fall risk. Either immediately or 15 s after the exposure to the mirror-induced inconsistency of visuo-proprioceptive signals regarding the right hand or foot position, participants performed a reaching task using the unseen, illusion-affected hand or foot. Results showed clear age group differences. Specifically, older adults exhibited larger reaching errors than younger adults in the hand condition, and after the 15 s delay in the foot condition. Further, the reaching errors were constant across time for older adults but decreased after the delay in young adults, regardless of the tested body part. Particularly, older adults’ risk of falling, which was assessed by the timed up-and-go test, was negatively correlated with the reduction of reaching error across time. This suggests that older adults, especially those with a high risk of falling, face difficulties in appropriately processing visual and proprioceptive information for body perception in accordance with their external environment.
Spanish cross-cultural adaptation and validation of the Australian Pelvic Floor Questionnaire in running women
Authors: Molina-Torres Guadalupe , Guallar-Bouloc Marina , Galán-Mercant Alejandro , Kasper-Jędrzejewska Martyna , Merchán-Baeza José Antonio , Gonzalez-Sanchez Manuel
Published: May 2022

Pelvic floor dysfunctions are a wide range of disorders in the gynaecological, lower urinary and gastrointestinal tracts that affect the structure and/or function of the pelvic organs. The objective of this study was to carry out a cross-cultural adaptation and a psychometric analysis of the Spanish version of the Australian Pelvic Floor Questionnaire. Observational study divided into two main phases: (1) translation and cross-cultural adaptation and (2) psychometric tests. Women runners from all over the Spanish territory, from different federations, clubs and levels were recruited. Participants: 424 female runners, native Spanish, over 18 years of age and who had been practicing running for more than 6 months. The instruments used in this study were the Australian Pelvic Floor Questionnaire, Female Sexual Function Index, King Health Questionnaire, Quality of Life SF-12 and EuroQoL 5-D. The Spanish version of Australian Pelvic Floor Questionnaire has proven to be an understandable and easy-to-use tool. The general internal consistency of the questionnaire was 0.972 and the intraclass correlation coefficient ranged between ICC 0.596–0.960. The Spanish version of Australian Pelvic Floor Questionnaire is a valid and reliable measure that can be used clinically to assess pelvic floor dysfunctions among the female Spanish population.
Graph Ricci curvatures reveal atypical functional connectivity in autism spectrum disorder
Authors: Elumalai Pavithra , Yadav Yasharth , Williams Nitin , Saucan Emil , Jost Jürgen , Samal Areejit
Published: May 2022

While standard graph-theoretic measures have been widely used to characterize atypical resting-state functional connectivity in autism spectrum disorder (ASD), geometry-inspired network measures have not been applied. In this study, we apply Forman–Ricci and Ollivier–Ricci curvatures to compare networks of ASD and typically developing individuals (N = 1112) from the Autism Brain Imaging Data Exchange I (ABIDE-I) dataset. We find brain-wide and region-specific ASD-related differences for both Forman–Ricci and Ollivier–Ricci curvatures, with region-specific differences concentrated in Default Mode, Somatomotor and Ventral Attention networks for Forman–Ricci curvature. We use meta-analysis decoding to demonstrate that brain regions with curvature differences are associated to those cognitive domains known to be impaired in ASD. Further, we show that brain regions with curvature differences overlap with those brain regions whose non-invasive stimulation improves ASD-related symptoms. These results suggest the utility of graph Ricci curvatures in characterizing atypical connectivity of clinically relevant regions in ASD and other neurodevelopmental disorders.