bluuebunny/crossref_metadata_2025 huggingface dataset:
Connections to Tidal Marsh and Restored Salt Ponds Drive Seasonal and Spatial Variability in Ecosystem Metabolic Rates in Lower South San Francisco Bay
Authors: Roberts Derek , MacVean Lissa , Holleman Rusty , Chelsky Ariella , Art Kristin , Nidzieko Nicholas , Sylvester Zephyr , Senn David
Published: June 2022

We characterized five years of seasonal metabolic patterns in two tidal sloughs in Lower South San Francisco Bay, one surrounded by a broad tidal marsh and the other connected to restored salt ponds (ponds). Despite comparable seasonal dissolved oxygen (DO) patterns, the two sloughs exhibited markedly different seasonal metabolic rates. The in-depth analysis of these small intertidal systems reveals the complexity of processes at work in the fringing habitats of larger estuaries. In the marsh-connected slough, respiration rates peaked in summer (~10 g $${\mathrm{O}}_{2}/{\mathrm{m}}^{2}/\mathrm{d}$$

O
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/

m

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), coincident with highly dynamic net ecosystem production rates (NEP). The peaks in DO consumption were correlated with temperature and tidal elevation. The most negative NEP rates were associated with the highest nighttime tides, when strong over-marsh respiration rates cannot be balanced by production. Thus, the combination of warmer water and the coincidence of higher-high tides with dark hours during summer may largely explain seasonal DO patterns in the marsh-connected slough. In the pond-connected slough, strong net heterotrophy (NEP < -20 g $${\mathrm{O}}_{2}/{\mathrm{m}}^{2}/\mathrm{d}$$

O
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) correlated with peak phytoplankton production and export from the adjacent ponds in spring, consistent with the hypothesis that organic matter exported from the pond exerts oxygen demand in the turbid slough. The impact of the elevated spring respiration rates appears to be offset by the super-oxygen-saturated water entering the slough from the highly productive pond. Oxygen minima in the slough (< 5 $$\mathrm{g}/{\mathrm{m}}^{3})$$

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m

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)

occurred in summer when outflow from the pond was lower in DO, coinciding with weaker, but still very high, in-slough respiration (~ 10 g $${\mathrm{O}}_{2}/{\mathrm{m}}^{2}/\mathrm{d}$$

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).
The Zebrafish model in dermatology: an update for clinicians
Authors: Russo Irene , Sartor Emma , Fagotto Laura , Colombo Anna , Tiso Natascia , Alaibac Mauro
Published: June 2022

Recently, the zebrafish has been established as one of the most important model organisms for medical research. Several studies have proved that there is a high level of similarity between human and zebrafish genomes, which encourages the use of zebrafish as a model for understanding human genetic disorders, including cancer. Interestingly, zebrafish skin shows several similarities to human skin, suggesting that this model organism is particularly suitable for the study of neoplastic and inflammatory skin disorders. This paper appraises the specific characteristics of zebrafish skin and describes the major applications of the zebrafish model in dermatological research.
Switching to Non-daily Pre-exposure Prophylaxis Among Gay and Bisexual Men in Australia: Implications for Improving Knowledge, Safety, and Uptake
Authors: Philpot Steven P. , Murphy Dean , Chan Curtis , Haire Bridget , Fraser Doug , Grulich Andrew E. , Bavinton Benjamin R.
Published: June 2022

Introduction

Preexposure prophylaxis (PrEP) dosing options such as event-driven PrEP hold promise to increase PrEP uptake among gay, bisexual, and queer men (GBQM), but their impacts have not yet been realized and uptake by GBQM suitable for PrEP remains slow in countries where it is only considered an alternative option to daily PrEP.

Methods

We conducted semi-structured interviews between June 2020 and February 2021 with 40 GBQM in Australia to understand PrEP dosing behaviors, knowledge, and preferences.

Results

All participants commenced PrEP daily; 35% had ever switched to non-daily PrEP, mostly taking it event-driven. GBQM who preferred non-daily PrEP had infrequent or predictable sex, were concerned about cost given infrequency of sex, and/or wanted to minimize unnecessary drug exposure. Accurate knowledge of event-driven PrEP was poor. However, reflecting concepts underpinning critical pedagogy, having accurate knowledge was supported by access to consistent messaging across clinical, social, community, and public settings. Several participants who switched to event-driven PrEP had condomless sex events in which they were unable to adhere to pills due to unanticipated sex.

Conclusions and Policy Implications

Implementation of comprehensive and consistent education about correct dosing for event-driven PrEP across multiple settings is needed to ensure increased uptake and safe use. GBQM require messaging about non-condom based HIV prevention strategies when they cannot access daily or event-driven PrEP.
Aquaculture Production and Value Chains in the COVID-19 Pandemic
Authors: Ahmed Nesar , Azra Mohamad N.
Published: June 2022

Purpose of Review

The purpose of this review is to summarize the impacts of the coronavirus disease 2019 (COVID-19) pandemic on aquaculture input supply, production, distribution, and consumption.

Recent Findings

The COVID-19 pandemic–related lockdowns, social distancing, supply chain disruptions, and transport restrictions affect seafood production, distribution, marketing, and consumption. Recommendations are suggested to overcome these challenges.

The COVID-19 has led to disruption of aquaculture practices worldwide. The pandemic has adversely affected the aquaculture input supply of fish stocking and feeding, which, in turn, has impacted aquaculture production. Moreover, the COVID-19 crisis has had adverse effects on value addition to aquaculture products, through the restrictions of seafood marketing and exporting. Aquatic food production is vulnerable to the effects of COVID-19 outbreak; hence, adaptation strategies must be developed to cope with the challenges. There is an urgent need for collaboration among key stakeholders to rebuild the supply chain of inputs and fish marketing for sustainable aquaculture practices. International agencies, donors, government and non-governmental organizations, researchers, and policymakers need to develop policies to support aquaculture production and supply chains.
Overconfidence in the art market: a bargaining pricing model with asymmetric disinformation
Authors: Angelini Francesco , Castellani Massimiliano , Zirulia Lorenzo
Published: June 2022

This paper develops a Nash bargaining model of price formation in the art market. Agents can be naïve, if they are overconfident and either overestimate artistic quality or underestimate their uncertainty of artistic quality, or sophisticated, if they correctly use all the available information. Overconfidence turns out to have a positive impact on both the price and the average quality of the artworks traded in the market. The impact of overconfidence on expected quality is weaker than the corresponding price increase, so sellers overcharge buyers. In addition, the buyer’s (seller’s) overconfidence has a positive (negative) impact on the likelihood of trade. If many pairs of agents may bargain simultaneously, we find that seller’s market power is negatively affected by the number of sellers and positively affected by the number of buyers. If sophisticated and naïve buyers coexist, naïve buyers exert a negative externality on the sophisticated ones, increasing the price the latter pay.
Seeking the real item difficulty: bias-corrected item difficulty and some consequences in Rasch and IRT modeling
Authors: Metsämuuronen Jari
Published: June 2022

When the response pattern in a test item deviates from the deterministic pattern, the percentage of correct answers (p) is shown to be a biased estimator for the latent item difficulty (π). This is specifically true with the items of medium item difficulty. Four elements of impurities in p are formalized in the binary settings and four new estimators of π are proposed and studied. Algebraic reasons and a simulation suggest that, except the case of deterministic item discrimination, the real item difficulty is almost always more extreme than what p indicates. This characteristic of p to be biased toward a medium-leveled item difficulty has a strict consequence to item response theory (IRT) and Rasch modeling. Because the classical estimator of item difficulty p is a biased estimator of the latent difficulty level, the item parameters A and B and the person parameter θ within IRT modeling are, consequently, biased estimators of item discrimination and item difficulty as well as ability levels of the test takers.
Modeling Monetary Economies
Authors: Champ Bruce , Freeman Scott , Haslag Joseph H.
Published: June 2022

Thoroughly updated and expanded with a new chapter on blockchain and increased coverage of cryptocurrency, as well as new data, this established advanced undergraduate textbook approaches the subject via first principles. It builds on a simple, clear monetary model and applies this framework consistently to a variety of monetary questions. Starting with trade being mutually beneficial, the authors demonstrate that money makes people better off, and that government money competes against other means of payments, including other types of government payments. After developing each of these topics, the book tackles the issue of money competing against other stores of value, examining issues associated with trade, finance, and modern banking. From simple economies to modern economies, the authors address the role banks play in making more trade possible, concluding with the information problems plaguing modern banking.
Incidental Jurisdiction in Investment Treaty Arbitration and the Question of Party Consent
Authors: Radović Relja
Published: June 2022

Arbitral tribunals in investment treaty arbitration have not contributed much to the theoretical development of the concept of incidental jurisdiction, even though they have occasionally exercised it in practice. One possible explanation for their apparent reluctance to make explicit and greater use of the concept of incidental jurisdiction is the tendency to adopt a strict approach to jurisdiction governed by party consent. In this essay, I argue that incidental jurisdiction is not in tension with the consensual foundations of international jurisdiction when it is viewed as one inherent power of international courts and tribunals. Key to this argument is that incidental determinations are not binding, and therefore do not need to fall within party-defined jurisdictional limits.
The choanal anatomy of theSebecus icaeorhinusSimpson, 1937 and the variation of the palatine shape in notosuchians (Crocodyliformes, Mesoeucrocodylia)
Authors: Bravo Gonzalo Gabriel , Pol Diego , Armella Matías Alberto , Gómez Kevin
Published: June 2022

Sebecidae is a clade of large carnivorous crocodyliforms that thrived in the Cenozoic and is the only lineage of the diverse and terrestrial group Notosuchia that survived the end-Cretaceous mass extinction event.Sebecus icaeorhinusis the best-known taxon from this clade, both in terms of its cranial and postcranial anatomy (known primarily from the holotype and specimen MPEF-PV 1776, respectively). Additional material represented by a partial skull (MMP 235) is the only specimen that has preserved a complete choanal region. We describe new information from this specimen based on an X-ray computed tomography and identify through comparisons with other taxa a large degree of variability in the palatal anatomy within Sebecidae, in particular in the shape and extension of the palatine (the bone that defines the anterior position and shape of the secondary choana). We quantify variation in the shape of the palatine bone of sebecids through a 2D morphogeometric analysis within the context of notosuchian crocodyliforms. Although traditional accounts of palatal evolution in crocodyliforms linked variation of this structure to the adaptation to the aquatic environment, our analysis allows recognition of eight palatine morphotypes among terrestrial crocodyliforms with very distinct paleoecological traits, including carnivorous, omnivorous, and possibly herbivorous taxa. Furthermore, we show that sebecids had a higher morphological disparity in the choanal region than other terrestrial groups of Notosuchia, underscoring the importance of this region for comparative, morphofunctional, and phylogenetic studies.
The Holocaust Museum of Greece, Thessaloniki: In Whose Memory?
Authors: Karasová Nikola , Králová Kateřina
Published: June 2022

This article explores the political and discursive framing of the emerging project Holocaust Museum of Greece (HMG) based in Thessaloniki (announced in 2013). As an “in situ” Holocaust museum, the HMG could represent an important step toward recognizing Jewish suffering in a country where—compared with the rest of Europe—unprecedentedly high levels of antisemitic attitudes have been recorded over the past decade. Supported by a qualitative media analysis and supplemented with data from our online survey, we explore how HMG stakeholders and potential local visitors reflect on the project. Occurring amid contemporary endeavors in Holocaust commemoration and Greek-German reconciliation, we connect it with their persistence in combating far-right tendencies and antisemitism. Specifically, we investigate whose memory HMG stakeholders aim to display, how they reflect on dominant Greek historical narratives and whether they express a clear memory commitment and a genuine effort to produce a more integrated historical interpretation of the Holocaust in Greece.
Conservation value of vanilla agroecosystems for vertebrate diversity in north-east Madagascar
Authors: Hending Daniel , Andrianiaina Angelo , Rakotomalala Zafimahery , Cotton Sam
Published: June 2022

As a result of increasing global demand for food, large areas of natural habitat are being converted to agroecosystems to accommodate crop cultivation. This agricultural expansion is most prominent in the tropics, where many rural communities are dependent solely on farming income for their livelihoods. Such agricultural land conversion can have severe implications for local fauna. In this study, we compared vertebrate species diversity between natural forest habitat and three types of vanilla plantations maintained under varying management regimes in north-east Madagascar. We used diurnal and nocturnal transects to survey vertebrate diversity. Natural forest habitat contained the greatest vertebrate species diversity, and had proportionally more threatened and endemic species than all vanilla plantation types. However, we observed a greater number of species and a higher inverse Simpson index in minimally managed vanilla plantations located within or near natural forest compared to intensively managed vanilla plantations. These findings are important and encouraging for animal conservation and sustainable crop cultivation in Madagascar, and suggest that newly created vanilla plantations, and already existing plantations, should endeavour to follow the more traditional, minimalistic management approach to improve sustainability and promote higher faunal diversity.
Hidden in plain sight: novel molecular data reveal unexpected genetic diversity among paramphistome parasites (Digenea: Paramphistomoidea) of European water frogs
Authors: Benovics Michal , Mikulíček Peter , Žákovicová Zuzana , Papežík Petr , Pantoja Camila
Published: June 2022

Parasites might represent a helpful tool in understanding the historical dispersion and phylogeography of their hosts. In order to reveal whether the migration routes and diversification of hosts can be traceable in the genetic structures of their parasites, we investigated the diversity of paramphistomoid trematodes of Pelophylax frogs in 2 geographically distant European regions. Water frogs belonging to the genus Pelophylax represent a striking example of a species with a high variety of ecological adaptations and a rich evolutionary history. The parasites were collected from 2 Balkan endemic species, P. epeiroticus and P. kurtmuelleri, and 2 species in Slovakia, P. esculentus and P. ridibundus. While in Slovakia, Pelophylax frogs harboured 2 species, the diplodiscid Diplodiscus subclavatus and the cladorchiid Opisthodiscus diplodiscoides, only the former was recorded in the south-western Balkans. Remarkably high genetic diversity (16 unique mitochondrial cox1 haplotypes, recognized among 60 novel sequences) was observed in D. subclavatus, and subsequent phylogenetic analyses revealed a strong population-genetic structure associated with geographical distribution. We also evidenced the existence of 2 divergent D. subclavatus cox1 haplogroups in the south-western Balkans, which might be associated with the historical diversification of endemic water frogs in the regional glacial microrefugia.
Multi-modal assessment of reward functioning in adolescent anhedonia
Authors: Murray Laura , Israel Elana S. , Balkind Emma G. , Pastro Brianna , Lovell-Smith Nathaniel , Lukas Scott E. , Forbes Erika E. , Pizzagalli Diego A. , Webb Christian A.
Published: June 2022

Background

Anhedonia is a core symptom of depression that predicts worse treatment outcomes. Dysfunction in neural reward circuits is thought to contribute to anhedonia. However, whether laboratory-based assessments of anhedonia and reward-related neural function translate to adolescents' subjective affective experiences in real-world contexts remains unclear.

Methods

We recruited a sample of adolescents (n = 82; ages 12–18; mean = 15.83) who varied in anhedonia and measured the relationships among clinician-rated and self-reported anhedonia, behaviorally assessed reward learning ability, neural response to monetary reward and loss (as assessed with functional magnetic resonance imaging), and repeated ecological momentary assessment (EMA) of positive affect (PA) and negative affect (NA) in daily life.

Results

Anhedonia was associated with lower mean PA and higher mean NA across the 5-day EMA period. Anhedonia was not related to impaired behavioral reward learning, but low PA was associated with reduced nucleus accumbens response during reward anticipation and reduced medial prefrontal cortex (mPFC) response during reward outcome. Greater mean NA was associated with increased mPFC response to loss outcome.

Conclusions

Traditional laboratory-based measures of anhedonia were associated with lower subjective PA and higher subjective NA in youths' daily lives. Lower subjective PA and higher subjective NA were associated with decreased reward-related striatal functioning. Higher NA was also related to increased mPFC activity to loss. Collectively, these findings demonstrate that laboratory-based measures of anhedonia translate to real-world contexts and that subjective ratings of PA and NA may be associated with neural response to reward and loss.
The effect of shade tree species on bird communities in central Kenyan coffee farms
Authors: KAMMERICHS-BERKE DEVEN , LANE FANTER J. , ONG’ONDO FRANK JUMA , MLAMBA EDSON M. , BEAN WILLIAM T. , JEDLICKA JULIE A. , NJOROGE PETER , JOHNSON MATTHEW D.
Published: June 2022

Shade coffee is a well-studied cultivation strategy that creates habitat for tropical birds while also maintaining agricultural yield. Although there is a general consensus that shade coffee is more “bird-friendly” than a sun coffee monoculture, little work has investigated the effects of specific shade tree species on insectivorous bird diversity. This study involved avian foraging observations, mist-netting data, temperature loggers, and arthropod sampling to investigate bottom-up effects of two shade tree taxa - native Cordia sp. and introduced Grevillea robusta - on insectivorous bird communities in central Kenya. Results indicate that foliage-dwelling arthropod abundance, and the richness and overall abundance of foraging birds were all higher on Cordia than on Grevillea. Furthermore, multivariate analyses of the bird community indicate a significant difference in community composition between the canopies of the two tree species, though the communities of birds using the coffee understorey under these shade trees were similar. In addition, both shade trees buffered temperatures in coffee, and temperatures under Cordia were marginally cooler than under Grevillea. These results suggest that native Cordia trees on East African shade coffee farms may be better at mitigating habitat loss and attracting insectivorous birds that could promote ecosystem services. Identifying differences in prey abundance and preferences in bird foraging behaviour not only fills basic gaps in our understanding of the ecology of East African coffee farms, it also aids in developing region-specific information to optimize functional diversity, ecosystem services, and the conservation of birds in agricultural landscapes.
Differential Thermal Analysis Using High Temperature Susceptibility Instruments
Authors: Doctor R. , Feinberg J. M.
Published: June 2022

Measurements of susceptibility as a function of temperature are an important, standard method of quantifying a sample's magnetic mineralogy. These measurements are used to identify the Curie/Néel temperatures of constituent minerals and show evidence of thermally induced oxidation and formation of magnetic minerals. For these reasons, the High Temperature Susceptibility Bridge (HTSB) is a common instrument in paleomagnetism laboratories around the world. Here, we argue that HTSBs can be used to perform simple differential thermal analysis, a technique used to identify phase transitions and exo‐/endothermic reactions by measuring deviations in temperature from a steady heating rate. Because HTSBs are designed to heat samples at a relatively constant rate, the standard susceptibility measurement can be used to obtain similar information, albeit crude, about the phase transitions taking place. For standard samples of vivianite, goethite, and maghemite, we compare the heating curves of the sample and a blank run, to identify DTA‐analogous information. In the case of goethite and vivianite, the reactions identified do not have a corresponding expression in susceptibility, demonstrating that this approach expands the utility of this common piece of equipment. We estimate the minimum enthalpy of reactions detectable and their mass dependence. Additionally, we show that this approach is successful in detecting the dehydration of vivianite in a mixed mineralogy natural sample.
Source Attribution of Atmospheric CO2 Using 14C and 13C as Tracers in Two Chinese Megacities During Winter
Authors: Wang Peng , Zhou Weijian , Xiong Xiaohu , Wu Shugang , Niu Zhenchuan , Yu Yunlong , Liu Jinzhao , Feng Tian , Cheng Peng , Du Hua , Lu Xuefeng , Chen Ning , Hou Yaoyao
Published: June 2022

Identifying the sources of atmospheric Carbon dioxide (CO2) is an important prerequisite for developing effective mitigation strategies. Here we conducted regular observations of the atmospheric CO2 mixing ratio and its carbon isotope compositions (i.e., Δ14C and δ13C) in Xi'an and Beijing during winter, to estimate source contributions of CO2 emissions in Chinese megacities. The results showed that CO2 emissions in both Xi'an and Beijing originated mainly from fossil‐fuel sources, which contributed 65 ± 3% and 82 ± 2% of the total CO2 enhancement, respectively, during the sampling period; the results also revealed a substantial biogenic CO2 contribution during winter. We further separated the fossil‐fuel sources into contributions from coal, oil and natural gas combustions. We found that coal combustion was the dominant anthropogenic source in Xi'an, accounting for 54 ± 4% of the total fossil‐fuel emissions, and oil and natural gas contribute almost equally to the emissions. In contrast, emission from natural‐gas combustion was the main fossil‐fuel source in Beijing, accounting for more than half of the total fossil‐fuel emissions, whereas, coal combustion contributed only 17 ± 10%. These top‐down results are generally consistent with emission inventory when seasonal variations of emissions are considered; some differences between the two methods indicated that the inventory for Xi'an might be underestimating the emissions from oil consumption. This pilot study confirms the potential of direct verification between top‐down and bottom‐up methods from the perspective of source attribution.
Modeling the Dynamic Variability of Sub‐Relativistic Outer Radiation Belt Electron Fluxes Using Machine Learning
Authors: Ma Donglai , Chu Xiangning , Bortnik Jacob , Claudepierre Seth G. , Tobiska W. Kent , Cruz Alfredo , Bouwer S. Dave , Fennell Joseph F. , Blake J. Bernard
Published: June 2022

We present a set of neural network models that reproduce the dynamics of electron fluxes in the range of 50 keV ∼1 MeV in the outer radiation belt. The Outer Radiation belt Electron Neural net model for Medium energy electrons uses only solar wind conditions and geomagnetic indices as input. The models are trained on electron flux data from the Magnetic Electron Ion Spectrometer instrument onboard Van Allen Probes, and they can reproduce the dynamic variations of electron fluxes in different energy channels. The model results show high coefficient of determination (R2 ∼ 0.78–0.92) on the test data set, an out‐of‐sample 30‐day period from 25 February to 25 March in 2017, when a geomagnetic storm took place, as well as an out‐of‐sample one year period after March 2018. In addition, the models are able to capture electron dynamics such as intensifications, decays, dropouts, and the Magnetic Local Time dependence of the lower energy (∼<100 keV) electron fluxes during storms. The models have reliable prediction capability and can be used for a wide range of space weather applications. The general framework of building our model is not limited to radiation belt fluxes and could be used to build machine learning models for a variety of other plasma parameters in the Earth's magnetosphere.
Sex differences in central insulin action: Effect of intranasal insulin on neural food cue reactivity in adults with normal weight and overweight
Authors: Wagner Lore , Veit Ralf , Fritsche Louise , Häring Hans-Ulrich , Fritsche Andreas , Birkenfeld Andreas L. , Heni Martin , Preissl Hubert , Kullmann Stephanie
Published: June 2022

Background/Objectives

Central insulin action influences cognitive processes, peripheral metabolism, and eating behavior. However, the contribution of obesity and sex on central insulin-mediated neural food cue processing still remains unclear.

Subjects/Methods

In a randomized within-participant design, including two visits, 60 participants (30 women, BMI 18–32 kg/m2, age 21–69 years) underwent a functional MRI task measuring blood oxygen level-dependent (BOLD) signal in response to visual food cues after intranasal insulin or placebo spray administration. Central insulin action was defined as the neural BOLD response to food cues after insulin compared to placebo administration. Afterwards, participants were asked to rate the food cues for desire to eat (i.e., wanting rating). For statistical analyses, participants were grouped according to BMI and sex.

Results

Food cue reactivity in the amygdala showed higher BOLD activation in response to central insulin compared to placebo. Furthermore, women with overweight and obesity and men of normal weight showed higher BOLD neural food cue responsivity to central insulin compared to placebo. Higher central insulin action in the insular cortex was associated with better peripheral insulin sensitivity and higher cognitive control. Moreover, central insulin action in the dorsolateral prefrontal cortex (DLPFC) revealed significant sex differences. In response to central insulin compared to placebo, men showed lower DLPFC BOLD activity, whereas women showed higher DLPFC activity in response to highly desired food cues. On behavioral level, central insulin action significantly reduced hunger, whereas the desire to eat, especially for low caloric food cues was significantly higher with central insulin than with placebo.

Conclusions

Obesity and sex influenced the central insulin-mediated neural BOLD activity to visual food cues in brain regions implicated in reward and cognitive control. These findings show that central insulin action regulates food response differentially in men and women, which may have consequences for metabolism and eating behavior.
Three-dimensional Weyl topology in one-dimensional photonic structures
Authors: Tsakmakidis Kosmas L. , Stefański Tomasz P.
Published: June 2022

Topological features, in particular distinct band intersections known as nodal rings, usually requiring three-dimensional structures, have now been demonstrated experimentally in an elegantly simple one-dimensional photonic crystal.
Blood-based liquid biopsies for prostate cancer: clinical opportunities and challenges
Authors: Trujillo Blanca , Wu Anjui , Wetterskog Daniel , Attard Gerhardt
Published: June 2022

Liquid biopsy has been established as a powerful, minimally invasive, tool to detect clinically actionable aberrations across numerous cancer types in real-time. With the development of new therapeutic agents in prostate cancer (PC) including DNA repair targeted therapies, this is especially attractive. However, there is unclarity on how best to screen for PC, improve risk stratification and ultimately how to treat advanced disease. Therefore, there is an urgent need to develop better biomarkers to help guide oncologists’ decisions in these settings. Circulating tumour cells (CTCs), exosomes and cell-free DNA/RNA (cfDNA/cfRNA) analysis, including epigenetic features such as methylation, have all shown potential in prognostication, treatment response assessment and detection of emerging mechanisms of resistance. However, there are still challenges to overcome prior to implementing liquid biopsies in routine clinical practice such as preanalytical considerations including blood collection and storage, the cost of CTC isolation and enrichment, low-circulating tumour content as a limitation for genomic analysis and how to better interpret the sequencing data generated. In this review, we describe an overview of the up-to-date clinical opportunities in the management of PC through blood-based liquid biopsies and the next steps for its implementation in personalised treatment guidance.
Direct observation of significant hot carrier cooling suppression in a two-dimensional silicon phononic crystal
Authors: Yan Wensheng , Long Liyuan , Zang Yue , Yang Gaoyuan , Liang Guijie
Published: June 2022

Finding hot carrier cooling suppression in new material structures is fundamentally important for developing promising technological applications. These phenomenona have not been reported for crystalline silicon phononic crystals. Herein, we experimentally design two-dimensional (2D) silicon samples consisting of airy hole arrays in a crystalline silicon matrix. For reference, the determined hot carrier cooling times were 0.45 ps and 0.37 ps, respectively, at probe wavelengths of 1080 nm and 1100 nm. Surprisingly, when the 2D structured silicon possessed the properties of a phononic crystal, significant suppression of hot carrier cooling was observed. In these cases, the observed hot carrier cooling times were as long as 15.9 ps and 10.7 ps at probe wavelengths of 1080 nm and 1100 nm, respectively, indicating prolongation by orders of magnitude. This remarkable enhancement was also observed with other probe wavelengths. The present work presents experimental evidence for hot carrier cooling suppression in 2D silicon phononic crystals and opens opportunities for promising applications.
Addressing challenges with real-world synthetic control arms to demonstrate the comparative effectiveness of Pralsetinib in non-small cell lung cancer
Authors: Popat Sanjay , Liu Stephen V. , Scheuer Nicolas , Hsu Grace G. , Lockhart Alexandre , Ramagopalan Sreeram V. , Griesinger Frank , Subbiah Vivek
Published: June 2022

As advanced non-small cell lung cancer (aNSCLC) is being increasingly divided into rare oncogene-driven subsets, conducting randomised trials becomes challenging. Using real-world data (RWD) to construct control arms for single-arm trials provides an option for comparative data. However, non-randomised treatment comparisons have the potential to be biased and cause concern for decision-makers. Using the example of pralsetinib from a RET fusion-positive aNSCLC single-arm trial (NCT03037385), we demonstrate a relative survival benefit when compared to pembrolizumab monotherapy and pembrolizumab with chemotherapy RWD cohorts. Quantitative bias analyses show that results for the RWD-trial comparisons are robust to data missingness, potential poorer outcomes in RWD and residual confounding. Overall, the study provides evidence in favour of pralsetinib as a first-line treatment for RET fusion-positive aNSCLC. The quantification of potential bias performed in this study can be used as a template for future studies of this nature.
Topological phonon transport in an optomechanical system
Authors: Ren Hengjiang , Shah Tirth , Pfeifer Hannes , Brendel Christian , Peano Vittorio , Marquardt Florian , Painter Oskar
Published: June 2022

Light is a powerful tool for controlling mechanical motion, as shown by numerous applications in the field of cavity optomechanics. Recently, small scale optomechanical circuits, connecting a few optical and mechanical modes, have been demonstrated in an ongoing push towards multi-mode on-chip optomechanical systems. An ambitious goal driving this trend is to produce topologically protected phonon transport. Once realized, this will unlock the full toolbox of optomechanics for investigations of topological phononics. Here, we report the realization of topological phonon transport in an optomechanical device. Our experiment is based on an innovative multiscale optomechanical crystal design and allows for site-resolved measurements in an array of more than 800 cavities. The sensitivity inherent in our optomechanical read-out allowed us to detect thermal fluctuations traveling along topological edge channels. This represents a major step forward in an ongoing effort to downscale mechanical topological systems.
3D structure and in situ arrangements of CatSper channel in the sperm flagellum
Authors: Zhao Yanhe , Wang Huafeng , Wiesehoefer Caroline , Shah Naman B. , Reetz Evan , Hwang Jae Yeon , Huang Xiaofang , Wang Tse-en , Lishko Polina V. , Davies Karen M. , Wennemuth Gunther , Nicastro Daniela , Chung Jean-Ju
Published: June 2022

The sperm calcium channel CatSper plays a central role in successful fertilization as a primary Ca2+ gateway. Here, we applied cryo-electron tomography to visualize the higher-order organization of the native CatSper complex in intact mammalian sperm. The repeating CatSper units form long zigzag-rows along mouse and human sperm flagella. Above each tetrameric channel pore, most of the extracellular domains form a canopy that interconnects to a zigzag-shaped roof. Murine CatSper contains an additional wing-structure connected to the tetrameric channel. The intracellular domains link two neighboring channels to a diagonal array, suggesting a dimer formation. Fitting of an atomic model of isolated monomeric CatSper to the in situ map reveals supramolecular interactions and assembly of the CatSper complex. Loss of EFCAB9-CATSPERζ alters the architecture and interactions of the channels, resulting in fragmentation and misalignment of the zigzag-rows and disruption of flagellar movement in Efcab9−/− sperm. This work offers unique insights into the structural basis for understanding CatSper regulation of sperm motility.
Comparative parallel multi-omics analysis during the induction of pluripotent and trophectoderm states
Authors: Jaber Mohammad , Radwan Ahmed , Loyfer Netanel , Abdeen Mufeed , Sebban Shulamit , Khatib Areej , Yassen Hazar , Kolb Thorsten , Zapatka Marc , Makedonski Kirill , Ernst Aurelie , Kaplan Tommy , Buganim Yosef
Published: June 2022

Following fertilization, it is only at the 32-64-cell stage when a clear segregation between cells of the inner cell mass and trophectoderm is observed, suggesting a ‘T’-shaped model of specification. Here, we examine whether the acquisition of these two states in vitro, by nuclear reprogramming, share similar dynamics/trajectories. Using a comparative parallel multi-omics analysis (i.e., bulk RNA-seq, scRNA-seq, ATAC-seq, ChIP-seq, RRBS and CNVs) on cells undergoing reprogramming to pluripotency and TSC state we show that each reprogramming system exhibits specific trajectories from the onset of the process, suggesting ‘V’-shaped model. We describe in detail the various trajectories toward the two states and illuminate reprogramming stage-specific markers, blockers, facilitators and TSC subpopulations. Finally, we show that while the acquisition of the TSC state involves the silencing of embryonic programs by DNA methylation, during the acquisition of pluripotency these regions are initially defined but retain inactive by the elimination of H3K27ac.
The chromatin remodeller ATRX facilitates diverse nuclear processes, in a stochastic manner, in both heterochromatin and euchromatin
Authors: Truch Julia , Downes Damien J. , Scott Caroline , Gür E. Ravza , Telenius Jelena M. , Repapi Emmanouela , Schwessinger Ron , Gosden Matthew , Brown Jill M. , Taylor Stephen , Cheong Pak Leng , Hughes Jim R. , Higgs Douglas R. , Gibbons Richard J.
Published: June 2022

The chromatin remodeller ATRX interacts with the histone chaperone DAXX to deposit the histone variant H3.3 at sites of nucleosome turnover. ATRX is known to bind repetitive, heterochromatic regions of the genome including telomeres, ribosomal DNA and pericentric repeats, many of which are putative G-quadruplex forming sequences (PQS). At these sites ATRX plays an ancillary role in a wide range of nuclear processes facilitating replication, chromatin modification and transcription. Here, using an improved protocol for chromatin immunoprecipitation, we show that ATRX also binds active regulatory elements in euchromatin. Mutations in ATRX lead to perturbation of gene expression associated with a reduction in chromatin accessibility, histone modification, transcription factor binding and deposition of H3.3 at the sequences to which it normally binds. In erythroid cells where downregulation of α-globin expression is a hallmark of ATR-X syndrome, perturbation of chromatin accessibility and gene expression occurs in only a subset of cells. The stochastic nature of this process suggests that ATRX acts as a general facilitator of cell specific transcriptional and epigenetic programmes, both in heterochromatin and euchromatin.
ARID1A loss derepresses a group of human endogenous retrovirus-H loci to modulate BRD4-dependent transcription
Authors: Yu Chunhong , Lei Xiaoyun , Chen Fang , Mao Song , Lv Lu , Liu Honglu , Hu Xueying , Wang Runhan , Shen Licong , Zhang Na , Meng Yang , Shen Yunfan , Chen Jiale , Li Pishun , Huang Shi , Lin Changwei , Zhang Zhuohua , Yuan Kai
Published: June 2022

Transposable elements (TEs) through evolutionary exaptation have become an integral part of the human genome, offering ample regulatory sequences and shaping chromatin 3D architecture. While the functional impacts of TE-derived sequences on early embryogenesis have been recognized, their roles in malignancy are only starting to emerge. Here we show that many TEs, especially the pluripotency-related human endogenous retrovirus H (HERVH), are abnormally activated in colorectal cancer (CRC) samples. Transcriptional upregulation of HERVH is associated with mutations of several tumor suppressors, particularly ARID1A. Knockout of ARID1A in CRC cells leads to increased transcription at several HERVH loci, which involves compensatory contribution by ARID1B. Suppression of HERVH in CRC cells and patient-derived organoids impairs tumor growth. Mechanistically, HERVH transcripts colocalize with nuclear BRD4 foci, modulating their dynamics and co-regulating many target genes. Altogether, we uncover a critical role for ARID1A in restraining HERVH, whose abnormal activation can promote tumorigenesis by stimulating BRD4-dependent transcription.
Cryo-EM structure of an amyloid fibril formed by full-length human SOD1 reveals its conformational conversion
Authors: Wang Li-Qiang , Ma Yeyang , Yuan Han-Ye , Zhao Kun , Zhang Mu-Ya , Wang Qiang , Huang Xi , Xu Wen-Chang , Dai Bin , Chen Jie , Li Dan , Zhang Delin , Wang Zhengzhi , Zou Liangyu , Yin Ping , Liu Cong , Liang Yi
Published: June 2022

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. Misfolded Cu, Zn-superoxide dismutase (SOD1) has been linked to both familial and sporadic ALS. SOD1 fibrils formed in vitro share toxic properties with ALS inclusions. Here we produced cytotoxic amyloid fibrils from full-length apo human SOD1 under reducing conditions and determined the atomic structure using cryo-EM. The SOD1 fibril consists of a single protofilament with a left-handed helix. The fibril core exhibits a serpentine fold comprising N-terminal segment (residues 3–55) and C-terminal segment (residues 86–153) with an intrinsic disordered segment. The two segments are zipped up by three salt bridge pairs. By comparison with the structure of apo SOD1 dimer, we propose that eight β-strands (to form a β-barrel) and one α-helix in the subunit of apo SOD1 convert into thirteen β-strands stabilized by five hydrophobic cavities in the SOD1 fibril. Our data provide insights into how SOD1 converts between structurally and functionally distinct states.
BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection
Authors: Cao Yunlong , Yisimayi Ayijiang , Jian Fanchong , Song Weiliang , Xiao Tianhe , Wang Lei , Du Shuo , Wang Jing , Li Qianqian , Chen Xiaosu , Yu Yuanling , Wang Peng , Zhang Zhiying , Liu Pulan , An Ran , Hao Xiaohua , Wang Yao , Wang Jing , Feng Rui , Sun Haiyan , Zhao Lijuan , Zhang Wen , Zhao Dong , Zheng Jiang , Yu Lingling , Li Can , Zhang Na , Wang Rui , Niu Xiao , Yang Sijie , Song Xuetao , Chai Yangyang , Hu Ye , Shi Yansong , Zheng Linlin , Li Zhiqiang , Gu Qingqing , Shao Fei , Huang Weijin , Jin Ronghua , Shen Zhongyang , Wang Youchun , Wang Xiangxi , Xiao Junyu , Xie Xiaoliang Sunney
Published: June 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage1. The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles2, epitope distribution3 and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab4 and cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.
Functional HLA-C expressing trophoblast spheroids as a model to study placental–maternal immune interactions during human implantation
Authors: Alexandrova Marina , Manchorova Diana , You Yuan , Mor Gil , Dimitrova Violeta , Dimova Tanya
Published: June 2022

In healthy couples over half of the conceptions result in failed pregnancy and around 30% of them occur during implantation defining it as a rate-limiting step for the success of native and in vitro fertilization. The understanding of the factors regulating each step of implantation and immune recognition is critical for the pregnancy outcome. Creation of 3D-cell culture models, such as spheroids and organoids, is in the focus of placental tissue engineering in attempt to resemble the in vivo complexity of the maternal-fetal interface and to overcome the need of laboratory animals and human embryos. We constructed stable, reliable, and reproducible trophoblast Sw71 spheroids which are functional independently of the serum level in the culture media. These models resemble the hatched human blastocyst in size, shape and function and are useful for in vitro studies of the in vivo concealed human implantation. Since Sw71 spheroids produce HLA-C, the only classical MHC molecule indispensable for establishment of the immune tolerance and proper human implantation, they are applicable for the evaluation not only of implantation itself but also of maternal-trophoblasts immune interactions. In addition, Sw71-blastocyst-like spheroids are manipulable in low-volume platform, easy to monitor and analyze automatically under treatment with favorable/detrimental factors.
Dissolved oxygen isotope modelling refines metabolic state estimates of stream ecosystems with different land use background
Authors: Piatka David R. , Venkiteswaran Jason J. , Uniyal Bhumika , Kaule Robin , Gilfedder Benjamin , Barth Johannes A. C.
Published: June 2022

Dissolved oxygen (DO) is crucial for aerobic life in streams and rivers and mostly depends on photosynthesis (P), ecosystem respiration (R) and atmospheric gas exchange (G). However, climate and land use changes progressively disrupt metabolic balances in natural streams as sensitive reflectors of their catchments. Comprehensive methods for mapping fundamental ecosystem services become increasingly important in a rapidly changing environment. In this work we tested DO and its stable isotope (18O/16O) ratios as novel tools for the status of stream ecosystems. For this purpose, six diel sampling campaigns were performed at three low-order and mid-latitude European streams with different land use patterns. Modelling of diel DO and its stable isotopes combined with land use analyses showed lowest P rates at forested sites, with a minimum of 17.9 mg m−2 h−1. Due to high R rates between 230 and 341 mg m−2 h−1 five out of six study sites showed a general heterotrophic state with P:R:G ratios between 0.1:1.1:1 and 1:1.9:1. Only one site with agricultural and urban influences showed a high P rate of 417 mg m−2 h−1 with a P:R:G ratio of 1.9:1.5:1. Between all sites gross G rates varied between 148 and 298 mg m−2 h−1. In general, metabolic rates depend on the distance of sampling locations to river sources, light availability, nutrient concentrations and possible exchanges with groundwater. The presented modelling approach introduces a new and powerful tool to study effects of land use on stream health. Such approaches should be integrated into future ecological monitoring.