bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-Talk between Mucosal-Associated Invariant T, Natural Killer, and Natural Killer T Cell Populations is Implicated in the Pathogenesis of Placenta Accreta Spectrum
Authors: El-Badawy Omnia , Abbas Ahmed M. , Radwan Eman , Makboul Rania , Khamis Areej A. , Ali Maha , Elkabsh Mai M. , Bakr Marwa H. , Zahran Asmaa M.
Published: March 2023

The study included 32 women with PAS and 20 with normally implanted placenta as a control group. Vascular endothelial cell growth factor (VEGF), Soluble FMS Like Tyrosine Kinase (sFLT-1/sVEGFR1), and Endoglin (ENG) were measured in placenta tissue by ELISA. Granzyme B (GrzB) expression in trophoblastic and stromal mesenchymal cells was evaluated by immunohistochemistry. MAIT, NK, and NKT cells were assessed in blood and placenta by flow cytometry. Alterations were observed in levels of MAIT cells, NK cell subsets, and NKT cells in patients compared with controls. Several significant correlations were detected between these cells and GrzB scores, VEGF, ENG, and sFLT-1 levels. This is the first study analysing these cells in PAS patients and correlating their levels with changes in some angiogenic and antiangiogenic factors implicated in trophoblast invasion and with GrzB distribution in trophoblast and stroma. Interrelation between these cells probably plays an important role in pathogenesis of PAS.
Academic Stress, Academic Self-efficacy, and Psychological Distress: A Moderated Mediation of Within-person Effects
Authors: Kristensen Sara Madeleine , Larsen Torill Marie Bogsnes , Urke Helga Bjørnøy , Danielsen Anne Grete
Published: March 2023

Previous research has largely failed to separate the between- and within-person effects in the longitudinal associations between academic stress, academic self-efficacy, and psychological distress (symptoms of anxiety and depression). Filling this research gap, this study investigated if academic self-efficacy mediated the relationship between academic stress and psychological distress at the intraindividual level during 3 years of upper secondary school. Gender moderation was also examined in the hypothesised model. The present sample consisted of 1508 Norwegian adolescents (baseline M age = 16.42; 52.9% high perceived family wealth; 70.6% Norwegian-born). The random intercept cross-lagged panel model results indicated (1) positive and time-invariant direct effects from academic stress to psychological distress, (2) academic self-efficacy partially mediated these effects, and (3) psychological distress impacted later academic stress. Academic stress was more strongly related to academic self-efficacy and psychological distress at the interpersonal level for boys, while the intraindividual impact of academic stress on psychological distress was stronger for girls. The study findings might have implications for school-based implementation strategies and theoretical development.
Ethical and practical considerations related to data sharing when collecting patient-reported outcomes in care-based child health research
Authors: Vanderhout Shelley , Potter Beth K. , Smith Maureen , Butcher Nancy J. , Vaters Jordan , Chakraborty Pranesh , Adams John , Inbar-Feigenberg Michal , Offringa Martin , Speechley Kathy , Trakadis Yannis , Binik Ariella
Published: March 2023

Purpose

The collection and use of patient reported outcomes (PROs) in care-based child health research raises challenging ethical and logistical questions. This paper offers an analysis of two questions related to PROs in child health research: (1) Is it ethically obligatory, desirable or preferable to share PRO data collected for research with children, families, and health care providers? And if so, (2) What are the characteristics of a model best suited to guide the collection, monitoring, and sharing of these data?

Methods

A multidisciplinary team of researchers, providers, patient and family partners, and ethicists examined the literature and identified a need for focus on PRO sharing in pediatric care-based research. We constructed and analyzed three models for managing pediatric PRO data in care-based research, drawing on ethical principles, logistics, and opportunities to engage with children and families.

Results

We argue that it is preferable to share pediatric PRO data with providers, but to manage expectations and balance the risks and benefits of research, this requires a justifiable data sharing model. We argue that a successful PRO data sharing model will allow children and families to have access to and control over their own PRO data and be engaged in decision-making around how PROs collected for research may be integrated into care, but require support from providers.

Conclusion

We propose a PRO data sharing model that can be used across diverse research settings and contributes to improved transparency, communication, and patient-centered care and research.
The Normative Challenges of AI in Outer Space: Law, Ethics, and the Realignment of Terrestrial Standards
Authors: Pagallo Ugo , Bassi Eleonora , Durante Massimo
Published: March 2023

The paper examines the open problems that experts of space law shall increasingly address over the next few years, according to four different sets of legal issues. Such differentiation sheds light on what is old and what is new with today’s troubles of space law, e.g., the privatization of space, vis-à-vis the challenges that AI raises in this field. Some AI challenges depend on its unique features, e.g., autonomy and opacity, and how they affect pillars of the law, whether on Earth or in space missions. The paper insists on a further class of legal issues that AI systems raise, however, only in outer space. We shall never overlook the constraints of a hazardous and hostile environment, such as on a mission between Mars and the Moon. The aim of this paper is to illustrate what is still mostly unexplored or in its infancy in this kind of research, namely, the fourfold ways in which the uniqueness of AI and that of outer space impact both ethical and legal standards. Such standards shall provide for thresholds of evaluation according to which courts and legislators evaluate the pros and cons of technology. Our claim is that a new generation of sui generis standards of space law, stricter or more flexible standards for AI systems in outer space, down to the “principle of equality” between human standards and robotic standards, will follow as a result of this twofold uniqueness of AI and of outer space.
Development of polymer blend electrolytes for battery systems: recent progress, challenges, and future outlook
Authors: Yazie Negese , Worku Delele , Gabbiye Nigus , Alemayehu Addisu , Getahun Zerihun , Dagnew Mehary
Published: March 2023

Nowadays, addressing the drawbacks of liquid electrolyte-based batteries is a hot and challenging issue, which is supposed to be fulfilled through solid electrolyte systems such as polymer electrolytes. Polymer blend electrolytes (PBEs) are widely investigated as viable options to solve the undesired characteristics of their liquid counterparts and also the poor ionic conductivity of homopolymer-based electrolytes. Even though PBEs outperform homopolymer-based electrolytes in terms of performance, the conductivity of pristine PBEs is quite low for practical applications (i.e. below 10–3 S/cm at room temperature). A very promising approach to solve this limitation is to incorporate additives into the electrolyte systems, to select suitable polymeric materials and to employ the desired synthesizing techniques as the performance of PBEs is strongly dependent on the selection of polymeric materials (i.e. on the inherent properties of polymers), the nature and amount of salts and other additives, and also the techniques employed to synthesize the polymer blend hosts and/or polymer blend electrolytes, determining the functionality, amorphousness, dielectric constant, dimensional stability, and, ultimately, the electrochemical performances of the system. This paper reviews the different factors affecting the miscibility of polymer blends, PBEs synthesizing techniques, the thermal, chemical, mechanical and electrochemical characteristics of PBEs, and also the challenges and opportunities of PBEs. Moreover, the paper presents the current progress of polymer blend electrolytes as well as future prospects for advancing polymer blend electrolytes in the energy storage sectors.
Fluorinated graphene quantum dots with long-term lubrication for visual drug loading and joint inflammation therapy
Authors: Gong Peiwei , Qi Changmin , Wang Dandan , Chao Mianran , Liu Jianxi , Cai Meirong , Liu Weimin
Published: March 2023

Osteoarthritis (OA) treatment mainly relies on developing new drugs or nanocarriers, while little attention is paid to building novel remedial mode and improving drug loading efficiency. This work reports an integrated nanosystem that not only realizes visual drug loading and release, but also achieves enhanced lubrication and effective joint inflammation therapy based on fluorinated graphene quantum dots (FGQDs). Oxygen introduction promotes FGQDs outstanding water-stability for months, and layered nano-sized structure further guarantees excellent lubricating properties in biomimetic synovial fluid. The special design of chemistry and structure endows FGQDs robust fluorescence in a wide range of pH conditions. Also, the excitation spectrum of FGQDs well overlaps the absorption spectrum of drugs, which further constructs a new concept of internal filtering system to visually monitor drug loading by naked eyes. More importantly, extraordinary long-term lubrication performance is reported, which is the first experimental demonstration of concentration-dependent mutations of coefficient of friction (COF). Cell incubation experiments indicate that drug-loaded FGQDs have good biocompatibility, tracking property of cellular uptake and drug release, which show efficient anti-inflammation potential for H2O2-induced chondrocyte degradation by up-regulated cartilage anabolic genes. This study establishes a promising OA treatment strategy that enables to monitor drug loading and release, to enhance long-time lubricating property, and to show effective anti-inflammatory potential for cartilage protection.
Review on Chemical Stability of Lead Halide Perovskite Solar Cells
Authors: Zhuang Jing , Wang Jizheng , Yan Feng
Published: March 2023

Lead halide perovskite solar cells (PSCs) have become a promising next-generation photovoltaic technology due to their skyrocketed power conversion efficiency. However, the device stability issues may restrict their commercial applications, which are dominated by various chemical reactions of perovskite layers. Hence, a comprehensive illustration on the stability of perovskite films in PSCs is urgently needed. In this review article, chemical reactions of perovskite films under different environmental conditions (e.g., moisture, oxygen, light) and with charge transfer materials and metal electrodes are systematically elucidated. Effective strategies for suppressing the degradation reactions of perovskites, such as buffer layer introduction and additives engineering, are specified. Finally, conclusions and outlooks for this field are proposed. The comprehensive review will provide a guideline on the material engineering and device design for PSCs.
The Problem of Hard and Easy Problems
Authors: Baetu Tudor M.
Published: March 2023

David Chalmers advocates the view that the phenomenon of consciousness is fundamentally different from all other phenomena studied in the life sciences, positing a uniquely hard problem that precludes the possibility of a mechanistic explanation. In this paper, I evaluate three demarcation criteria for dividing phenomena into hard and easy problems: functional definability, the puzzle of the accompanying phenomenon, and the first-person data of subjective experience. I argue that none of the proposed criteria can accurately discriminate between the phenomenon of consciousness and mechanistically explainable phenomena.
Near-field evolution and scaling of shear layer instabilities in a reacting jet in crossflow
Authors: Nair Vedanth , Sirignano Matthew , Emerson Benjamin L. , Lieuwen Timothy C.
Published: March 2023

This study analyses the stability characteristics of the shear layer vortices (SLV) in a reacting jet in crossflow, analysing effects of flame position, momentum flux ratio (

$J$

) and density ratio (

$S$

). It utilizes 40 kHz particle image velocimetry to characterize the dominant SLV frequencies, streamwise evolution and convective/global stability characteristics for three different canonical configurations, one non-reacting and two reacting (‘R1’ and ‘R2’). In the non-reacting case, both convective and global instability is observed, depending upon

$S$

and

$J$

. Qualitatively similar

$S$

dependencies occur for the R1 reacting case where the radial flame position lies outside the jet shear layer, albeit with slower SLV growth rates. When the flame lies inside the jet shear layer, the R2 reacting case, a qualitatively different behaviour is observed, as vorticity concentration in the shear layers is suppressed almost completely. Finally, we show that frequency and stability characteristics of the non-reacting and R1 cases can be scaled in a unified manner using a counter-current shear layer model. This model relates these SLV behaviours to a vorticity layer thickness, a velocity scale and an effective density ratio (noting that there are three distinct densities associated with the jet, the crossflow and the burned gases). These parameters were extracted from the data and used to collapse the frequency scaling, and to explain the transition to self-excited oscillatory behaviour.
Multilevel Calibration Weighting for Survey Data
Authors: Ben-Michael Eli , Feller Avi , Hartman Erin
Published: March 2023

In the November 2016 U.S. presidential election, many state-level public opinion polls, particularly in the Upper Midwest, incorrectly predicted the winning candidate. One leading explanation for this polling miss is that the precipitous decline in traditional polling response rates led to greater reliance on statistical methods to adjust for the corresponding bias—and that these methods failed to adjust for important interactions between key variables like educational attainment, race, and geographic region. Finding calibration weights that account for important interactions remains challenging with traditional survey methods: raking typically balances the margins alone, while post-stratification, which exactly balances all interactions, is only feasible for a small number of variables. In this paper, we propose multilevel calibration weighting, which enforces tight balance constraints for marginal balance and looser constraints for higher-order interactions. This incorporates some of the benefits of post-stratification while retaining the guarantees of raking. We then correct for the bias due to the relaxed constraints via a flexible outcome model; we call this approach “double regression with post-stratification.” We use these tools to re-assess a large-scale survey of voter intention in the 2016 U.S. presidential election, finding meaningful gains from the proposed methods. The approach is available in the multical R package.
A geometric interpretation of Ranicki duality
Authors: Connolly Frank
Published: March 2023

Consider a commutative ring

$R$

and a simplicial map,

$X\mathop {\longrightarrow }\limits ^{\pi }K,$

of finite simplicial complexes. The simplicial cochain complex of

$X$

with

$R$

coefficients,

$\Delta ^*X,$

then has the structure of an

$(R,K)$

chain complex, in the sense of Ranicki . Therefore it has a Ranicki-dual

$(R,K)$

chain complex,

$T \Delta ^*X$

. This (contravariant) duality functor

$T:\mathcal {B} R_K\to \mathcal {B} R_K$

was defined algebraically on the category of

$(R,K)$

chain complexes and

$(R,K)$

chain maps.

Our main theorem, 8.1, provides a natural

$(R,K)$

chain isomorphism:

\[ T\Delta^*X\cong C(X_K) \]

where

$C(X_K)$

is the cellular chain complex of a CW complex

$X_K$

. The complex

$X_K$

is a (nonsimplicial) subdivision of the complex

$X$

. The

$(R,K)$

structure on

$C(X_K)$

arises geometrically.
Putting Morals into Economics: From Value Neutrality to the Moral Economy and the Economization of Morality
Authors: Kanitsar Georg
Published: March 2023

The economic discipline plays a performative role in constructing the moral order of market society. Yet, little attention has been paid to what economists explicitly regard as moral or how they conceive of morality. This article reflects a recent attempt to put morals into economics, that is, to introduce morality as a research topic in behavioural and experimental economics. It maps three research programs that theorize the moral economy. The programs emphasize the moral foundations of market society, the moral limits of market expansion, and the moral consequences of market trading and, thus, appear irreconcilable with classifications of economists as market enthusiasts or moral agnostics. At the same time, however, the literature centres on an “economized” form of morality that is corrective to market inefficiencies, attributed to the responsibility of the individual, and expressed in rational terms. In doing so, this literature contributes to redefining moral problems in economic terms.
The Segregation Effect: How Residential Isolation Shapes Ethnic Minority Representation in England
Authors: Campion Selene
Published: March 2023

Extant literature argues that ethnic minority representation in plurality systems will benefit from the presence of sizable co-ethnic populations. I argue that the threshold for election depends not only on a minority population's group size but a district's level of segregation. I show that residential segregation can facilitate the increased representation of ethnic minority populations. Contrary to the prevailing literature, however, I find that increased segregation levels in cities with sizable minority populations decrease the percentage of co-ethnics elected to office. I support this argument with evidence from an original dataset on the local representation outcomes of Muslims in England between 2011 and 2021, which covers 434 district council elections. Using threshold modelling, I introduce the concept of the population threshold, above which increases in segregation level decrease Muslim representation. This article contributes to the electoral geography literature on ethnic minority representation.
J’va share mon étude sur les anglicismes avec vous autres!: A sociolinguistic approach to the use of morphologically unintegrated English-origin verbs in Quebec French
Authors: Bouchard Marie-Eve
Published: March 2023

This study explores variation in the use of English-origin verbs in Quebec French. These lexical borrowings are usually integrated grammatically into the receiving language (Poplack, 2018), as inil vacrasherandelle m’aghostéin Quebec French. However, a new lexical insertion strategy for English-origin verbs has been observed in the past few years: verbal borrowings can lack overt morphological integration, as inil vacrashandelle m’aghost.This article examines the use of English-origin verbs in Quebec French from a variationist perspective by focusing on 1) possible correlations between speakers and how they evaluate the different lexical insertion strategies, and 2) the social factors that constrain the use of morphologically unintegrated English-origin verbs. Results from quantitative analyses based on 675 participants indicate that young Quebecers from Montreal with a high level of proficiency in English are the ones who use this morphologically unintegrated form the most and evaluate it more positively. This unintegrated form poses a theoretical problem according to Poplack’s (2018) theory, for which nonce borrowings are morphologically and syntactically integrated into the receiving language.
Re-expansion pulmonary edema after minimally invasive cardiac surgery in children
Authors: Kimura Naritaka , Yamashita Kentaro , Shimizu Hideyuki
Published: March 2023

Re-expansion pulmonary edema is a serious complication that can occur after minimally invasive cardiac surgery through a right mini-thoracotomy. Herein, we describe two paediatric cases where re-expansion pulmonary edema was observed after simple atrial septal defect closure through a right mini-thoracotomy. This is the first case report of re-expansion pulmonary edema after a paediatric cardiac surgery.
Pacific Decadal Oscillation Influences Tropical Oxygen Minimum Zone Extent and Obscures Anthropogenic Changes
Authors: Poupon Mathieu A. , Resplandy Laure , Lévy Marina , Bopp Laurent
Published: March 2023

Observations suggest that the tropical Pacific Ocean has lost oxygen since the 1960s leading to the expansion of its oxygen minimum zone (OMZ). Attribution to anthropogenic forcing is, however, difficult because of limited data availability and the large natural variability introduced by the Pacific Decadal Oscillation (PDO). Here, we evaluate the PDO influence on oxygen dynamics and OMZ extent using observations and hindcast simulations from two global ocean circulation models (NEMO‐PISCES, MOM6‐COBALT). In both models, the tropical Pacific oxygen content decreases by about 30 Tmol.decade−1 and the OMZ volume expands by 1.3 × 105 km3.decade−1 during PDO positive phases, while variations of similar magnitude but opposite sign are simulated during negative phases. Changes in equatorial advective oxygen supply, partially offset by biological demand, control the oxygen response to PDO. Observations which cover 39% of the tropical Pacific volume only partially capture spatio‐temporal variability, hindering the separation of anthropogenic trend from natural variations.
Highly Unradiogenic Pb Isotopes Revealed by Plagioclase‐Hosted Melt Inclusions in E‐MORB From the South China Sea
Authors: Wu Tao , Zhang Wen , Wilde Simon A. , Lu Jianggu , Zhang Guoliang , Li Chunfeng , Chen Xuegang , Chen Shuangshuang
Published: March 2023

Mid‐ocean ridge basalts (MORBs) can record heterogeneity of the upper mantle. Early crystallized minerals and their melt inclusions commonly record greater isotopic variability than whole‐rocks and are powerful tools to investigate the mantle source. In this study, we develop a new in situ Pb analytical protocol for Pb‐poor materials (sub‐ppm level) and apply it to the plagioclase‐hosted melt‐inclusions from IODP Expedition 349 Site U1433, South China Sea (SCS). Together with element mapping, in situ major and trace element analyzes and in situ Sr isotopes of plagioclase phenocrysts, we show that unlike the low and uniform whole‐rock 87Sr/86Sr ratios, the plagioclase phenocrysts record extreme Sr isotopic heterogeneity. Strontium isotopic heterogeneity is observed between crystals even in a single thin section. Based on the high an contents of plagioclase phenocrysts and high Mg# values of their melt inclusions, we propose they crystallized early in the magma chamber and were most likely formed in different batches of mantle‐derived melts. The plagioclase‐hosted melt inclusions show highly variable Pb isotopes, exhibiting a typical linear variation in 207Pb/204Pb versus 206Pb/204Pb. Such a mixing trend indicates an end‐member with highly unradiogenic Pb isotopes. The LREE enrichment and negative correlations between La/Sm and Pb isotopes of the melt inclusions, indicate that ancient cratonic lower continent crustal materials, with low time‐integrated U/Pb ratios, are likely present in the sub‐ridge mantle of the southwest Sub‐basin, SCS.
Influence of Melt‐Peridotite Interactions on Deformation and Seismic Properties of the Upper Mantle Beneath a Destroyed Craton: A Case Study of the Damaping Peridotites From the North China Craton
Authors: Wen Da‐Peng , Wang Yong‐Feng , Zhang Jun‐Feng
Published: March 2023

Extensive melt‐peridotite interactions had been documented in the lithospheric mantle beneath the North China Craton (NCC), a prime example of destroyed cratons in the world. Yet the impacts of melt‐peridotite interactions on the deformation and seismic anisotropy of the NCC upper mantle remain unclear. Here we studied in detail the microstructure, crystallographic preferred orientation (CPO) of minerals, and seismic properties of 26 peridotite xenoliths from the Damaping area of the NCC. The studied samples can be classified into two groups: weakly to nonfoliated and strongly foliated. Petrographic and microstructural observations suggest that multiple melt‐peridotite interactions and at least two stages of deformation had influenced samples from both microstructural groups. Dislocation creep in response to a transpression deformation led to the [010]‐fiber type olivine CPOs in most samples. Variable degrees of annealing followed the last stage of deformation. Due to a higher degree of melt‐peridotite interactions, which had promoted nondislocation creep, and more extensive annealing, olivine and pyroxene in the strongly foliated samples developed weaker CPOs. This in turn leads to weaker maximum P wave propagation anisotropy and S wave polarization anisotropy for this microstructural group. Our data, therefore, cast light on a strong control of intensity of melt‐peridotite interactions on deformation and seismic properties of the upper mantle beneath the NCC. If foliation and lineation are vertical and horizontal, respectively, the measured SKS splitting parameters can be well explained by the “fossil” anisotropy frozen in the lithospheric mantle, with no need to invoke asthenospheric flow as a source of the anisotropy.
Spatially resolved multimarker evaluation of CD274 (PD-L1)/PDCD1 (PD-1) immune checkpoint expression and macrophage polarisation in colorectal cancer
Authors: Elomaa Hanna , Ahtiainen Maarit , Väyrynen Sara A. , Ogino Shuji , Nowak Jonathan A. , Lau Mai Chan , Helminen Olli , Wirta Erkki-Ville , Seppälä Toni T. , Böhm Jan , Mecklin Jukka-Pekka , Kuopio Teijo , Väyrynen Juha P.
Published: March 2023

Background

The CD274 (PD-L1)/PDCD1 (PD-1) immune checkpoint interaction may promote cancer progression, but the expression patterns and prognostic significance of PD-L1 and PD-1 in the colorectal cancer microenvironment are inadequately characterised.

Methods

We used a custom 9-plex immunohistochemistry assay to quantify the expression patterns of PD-L1 and PD-1 in macrophages, T cells, and tumour cells in 910 colorectal cancer patients. We evaluated cancer-specific mortality according to immune cell subset densities using multivariable Cox regression models.

Results

Compared to PD-L1– macrophages, PD-L1+ macrophages were more likely M1-polarised than M2-polarised and located closer to tumour cells. PD-L1+ macrophage density in the invasive margin associated with longer cancer-specific survival [Ptrend = 0.0004, HR for the highest vs. lowest quartile, 0.52; 95% CI: 0.34–0.78]. T cell densities associated with longer cancer-specific survival regardless of PD-1 expression (Ptrend < 0.005 for both PD-1+ and PD-1– subsets). Higher densities of PD-1+ T cell/PD-L1+ macrophage clusters associated with longer cancer-specific survival (Ptrend < 0.005).

Conclusions

PD-L1+ macrophages show distinct polarisation profiles (more M1-like), spatial features (greater co-localisation with tumour cells and PD-1+ T cells), and associations with favourable clinical outcome. Our comprehensive multimarker assessment could enhance the understanding of immune checkpoints in the tumour microenvironment and promote the development of improved immunotherapies.
Immortal data: a qualitative exploration of patients’ understandings of genomic data
Authors: Lyle Kate , Weller Susie , Horton Rachel , Lucassen Anneke
Published: March 2023

As ambitions to ‘mainstream’ genetic and genomic medicine in the UK advance, patients are increasingly exposed to information about genomic data. Unlike the results of many other medical investigations which are linked to the time of sample collection, genomic testing provides immortal data that do not change across time, and may have relevance for relatives and generations far beyond the patient’s own lifespan. This immortality raises new ethical challenges for healthcare professionals, patients and families alike, such as ensuring consent for possible future interpretations; determining when genomic data are best sought (at birth, on illness etc) and reinterpreted; and balancing the confidentiality of patients and duties of care towards others. This paper reports on qualitative work exploring the perspectives of patients and relatives participating in genomic testing, and suggests that their engagements with this immortality are shaped by: the contrast between the simplicity of sample provision and information gathered; understandings of heritability; and notions of genomic data as a collective resource. We discuss the implications this holds for practice and argue that the immortality of genomic data must take a more prominent position in patient and healthcare professional interactions.
Genome-wide tiled detection of circulating Mycobacterium tuberculosis cell-free DNA using Cas13
Authors: Thakku Sri Gowtham , Lirette Jackson , Murugesan Kanagavel , Chen Julie , Theron Grant , Banaei Niaz , Blainey Paul C. , Gomez James , Wong Sharon Y. , Hung Deborah T.
Published: March 2023

Detection of microbial cell-free DNA (cfDNA) circulating in the bloodstream has emerged as a promising new approach for diagnosing infection. Microbial diagnostics based on cfDNA require assays that can detect rare and highly fragmented pathogen nucleic acids. We now report WATSON (Whole-genome Assay using Tiled Surveillance Of Nucleic acids), a method to detect low amounts of pathogen cfDNA that couples pooled amplification of genomic targets tiled across the genome with pooled CRISPR/Cas13-based detection of these targets. We demonstrate that this strategy of tiling improves cfDNA detection compared to amplification and detection of a single targeted locus. WATSON can detect cfDNA from Mycobacterium tuberculosis in plasma of patients with active pulmonary tuberculosis, a disease that urgently needs accurate, minimally-invasive, field-deployable diagnostics. We thus demonstrate the potential for translating WATSON to a lateral flow platform. WATSON demonstrates the ability to capitalize on the strengths of targeting microbial cfDNA to address the need for point-of-care diagnostic tests for infectious diseases.
Quantum decoherence of dark pulses in optical microresonators
Authors: Lao Chenghao , Jin Xing , Chang Lin , Wang Heming , Lv Zhe , Xie Weiqiang , Shu Haowen , Wang Xingjun , Bowers John E. , Yang Qi-Fan
Published: March 2023

Quantum fluctuations disrupt the cyclic motions of dissipative Kerr solitons (DKSs) in nonlinear optical microresonators and consequently cause timing jitter of the emitted pulse trains. This problem is translated to the performance of several applications that employ DKSs as compact frequency comb sources. Recently, device manufacturing and noise reduction technologies have advanced to unveil the quantum properties of DKSs. Here we investigate the quantum decoherence of DKSs existing in normal-dispersion microresonators known as dark pulses. By virtue of the very large material nonlinearity, we directly observe the quantum decoherence of dark pulses in an AlGaAs-on-insulator microresonator, and the underlying dynamical processes are resolved by injecting stochastic photons into the microresonators. Moreover, phase correlation measurements show that the uniformity of comb spacing of quantum-limited dark pulses is better than 1.2 × 10−16 and 2.5 × 10−13 when normalized to the optical carrier frequencies and repetition frequencies, respectively. Comparing DKSs generated in different material platforms explicitly confirms the advantages of dark pulses over bright solitons in terms of quantum-limited coherence. Our work establishes a critical performance assessment of DKSs, providing guidelines for coherence engineering of chip-scale optical frequency combs.
Mutation in glutamate transporter homologue GltTk provides insights into pathologic mechanism of episodic ataxia 6
Authors: Colucci Emanuela , Anshari Zaid R. , Patiño-Ruiz Miyer F. , Nemchinova Mariia , Whittaker Jacob , Slotboom Dirk J. , Guskov Albert
Published: March 2023

Episodic ataxias (EAs) are rare neurological conditions affecting the nervous system and typically leading to motor impairment. EA6 is linked to the mutation of a highly conserved proline into an arginine in the glutamate transporter EAAT1. In vitro studies showed that this mutation leads to a reduction in the substrates transport and an increase in the anion conductance. It was hypothesised that the structural basis of these opposed functional effects might be the straightening of transmembrane helix 5, which is kinked in the wild-type protein. In this study, we present the functional and structural implications of the mutation P208R in the archaeal homologue of glutamate transporters GltTk. We show that also in GltTk the P208R mutation leads to reduced aspartate transport activity and increased anion conductance, however a cryo-EM structure reveals that the kink is preserved. The arginine side chain of the mutant points towards the lipidic environment, where it may engage in interactions with the phospholipids, thereby potentially interfering with the transport cycle and contributing to stabilisation of an anion conducting state.
Emission of coherent THz magnons in an antiferromagnetic insulator triggered by ultrafast spin–phonon interactions
Authors: Rongione E. , Gueckstock O. , Mattern M. , Gomonay O. , Meer H. , Schmitt C. , Ramos R. , Kikkawa T. , Mičica M. , Saitoh E. , Sinova J. , Jaffrès H. , Mangeney J. , Goennenwein S. T. B. , Geprägs S. , Kampfrath T. , Kläui M. , Bargheer M. , Seifert T. S. , Dhillon S. , Lebrun R.
Published: March 2023

Antiferromagnetic materials have been proposed as new types of narrowband THz spintronic devices owing to their ultrafast spin dynamics. Manipulating coherently their spin dynamics, however, remains a key challenge that is envisioned to be accomplished by spin-orbit torques or direct optical excitations. Here, we demonstrate the combined generation of broadband THz (incoherent) magnons and narrowband (coherent) magnons at 1 THz in low damping thin films of NiO/Pt. We evidence, experimentally and through modeling, two excitation processes of spin dynamics in NiO: an off-resonant instantaneous optical spin torque in (111) oriented films and a strain-wave-induced THz torque induced by ultrafast Pt excitation in (001) oriented films. Both phenomena lead to the emission of a THz signal through the inverse spin Hall effect in the adjacent heavy metal layer. We unravel the characteristic timescales of the two excitation processes found to be < 50 fs and > 300 fs, respectively, and thus open new routes towards the development of fast opto-spintronic devices based on antiferromagnetic materials.
Bacterial detoxification of plant defence secondary metabolites mediates the interaction between a shrub and frugivorous birds
Authors: Trabelcy Beny , Shteindel Nimrod , Lalzar Maya , Izhaki Ido , Gerchman Yoram
Published: March 2023

Many plants produce fleshy fruits, attracting fruit-eating animals that disperse the seeds in their droppings. Such seed dispersal results in a conflict between the plant and the animal, as digestion of seeds can be highly beneficial to the animal but reduces plant fitness. The plant Ochradenus baccatus uses the myrosinase-glucosinolates system to protect its seeds. We show that hydrolysis of the O. baccatus fruit glucosinolates by the myrosinase enzyme inhibited digestive enzymes and hampered digestion in naïve individuals of the bird Pycnonotus xanthopygos. However, digestion in birds regularly feeding on O. baccatus fruits was unaffected. We find that Pantoea bacteria, dominating the gut of these experienced birds as well as the fruits, thrive on glucosinolates hydrolysis products in culture. Augmentation of Pantoea protects both naïve birds and plant seedlings from the effects of glucosinolates hydrolysis products. Our findings demonstrate a tripartite interaction, where the plant-bird mutually beneficial interactions are mediated by a communal bacterial tenant.
Aging reduces calreticulin expression and alters spontaneous calcium signals in astrocytic endfeet of the mouse dorsolateral striatum
Authors: Zarate Sara M. , Huntington Taylor E. , Bagher Pooneh , Srinivasan Rahul
Published: March 2023

Aging-related impairment of the blood brain barrier (BBB) and neurovascular unit (NVU) increases the risk for neurodegeneration. Among various cells that participate in BBB and NVU function, calcium signals in astrocytic endfeet are crucial for maintaining BBB and NVU integrity. To assess if aging is associated with altered calcium signals within astrocytic endfeet of the dorsolateral striatum (DLS), we expressed GCaMP6f in DLS astrocytes of young (3–4 months), middle-aged (12–15 months) and aging (20–30 months) mice. Compared to endfeet in young mice, DLS endfeet in aging mice demonstrated decreased calreticulin expression, and alterations to both spontaneous membrane-associated and mitochondrial calcium signals. While young mice required both extracellular and endoplasmic reticulum calcium sources for endfoot signals, middle-aged and aging mice showed heavy dependence on endoplasmic reticulum calcium. Thus, astrocytic endfeet show significant changes in calcium buffering and sources throughout the lifespan, which is important for understanding mechanisms by which aging impairs the BBB and NVU.
Twitter misogyny associated with Hillary Clinton increased throughout the 2016 U.S. election campaign
Authors: Weaving Morgan , Alshaabi Thayer , Arnold Michael V. , Blake Khandis , Danforth Christopher M. , Dodds Peter S. , Haslam Nick , Fine Cordelia
Published: March 2023

Online misogyny has become a fixture in female politicians’ lives. Backlash theory suggests that it may represent a threat response prompted by female politicians’ counterstereotypical, power-seeking behaviors. We investigated this hypothesis by analyzing Twitter references to Hillary Clinton before, during, and after her presidential campaign. We collected a corpus of over 9 million tweets from 2014 to 2018 that referred to Hillary Clinton, and employed an interrupted time series analysis on the relative frequency of misogynistic language within the corpus. Prior to 2015, the level of misogyny associated with Clinton decreased over time, but this trend reversed when she announced her presidential campaign. During the campaign, misogyny steadily increased and only plateaued after the election, when the threat of her electoral success had subsided. These findings are consistent with the notion that online misogyny towards female political nominees is a form of backlash prompted by their ambition for power in the political arena.
The role of cognitive flexibility in moderating the effect of school-related stress exposure
Authors: Harel Orly , Hemi Alla , Levy-Gigi Einat
Published: March 2023

Educators are exposed to various stressful events as part of their ongoing work, including violence, sexual assaults, suicidal behavior, and loss or illness of students or their family members. Previous studies revealed an increased risk of developing PTSD symptoms in healthcare and supportive professionals exposed to repeated stress as part of their work. Cognitive flexibility might be a protective factor against the negative effect of such stress. The current study aimed to examine the interactive effects of school-related stress exposure and cognitive flexibility on the tendency to develop Post Traumatic Stress Disorder (PTSD) symptoms and the coping abilities of educators. One hundred and fifty educators (86.5% female; Mage = 43.08, Mteaching_experience= 12.90) volunteered to participate in this study. They completed questionnaires measuring levels of stress exposure, cognitive flexibility, coping ability, and PTSD symptoms. Analyses revealed that cognitive flexibility moderated the relationship between school-related stress exposure and both PTSD symptoms severity and maladaptive coping. Specifically, whereas educators with low cognitive flexibility exhibited positive associations between continuous stress exposure and both levels of PTSD symptoms and maladaptive coping, no such association was found among educators with high cognitive flexibility. The results highlight the importance of cognitive flexibility as a protective factor against the harmful effects of possible stress exposure in school environments. Awareness of the crucial role of cognitive flexibility as a protective factor for educators can be a breakthrough in improving educators' well-being and adaptive functioning.
RNA-binding proteins that lack canonical RNA-binding domains are rarely sequence-specific
Authors: Ray Debashish , Laverty Kaitlin U. , Jolma Arttu , Nie Kate , Samson Reuben , Pour Sara E. , Tam Cyrus L. , von Krosigk Niklas , Nabeel-Shah Syed , Albu Mihai , Zheng Hong , Perron Gabrielle , Lee Hyunmin , Najafabadi Hamed , Blencowe Benjamin , Greenblatt Jack , Morris Quaid , Hughes Timothy R.
Published: March 2023

Thousands of RNA-binding proteins (RBPs) crosslink to cellular mRNA. Among these are numerous unconventional RBPs (ucRBPs)—proteins that associate with RNA but lack known RNA-binding domains (RBDs). The vast majority of ucRBPs have uncharacterized RNA-binding specificities. We analyzed 492 human ucRBPs for intrinsic RNA-binding in vitro and identified 23 that bind specific RNA sequences. Most (17/23), including 8 ribosomal proteins, were previously associated with RNA-related function. We identified the RBDs responsible for sequence-specific RNA-binding for several of these 23 ucRBPs and surveyed whether corresponding domains from homologous proteins also display RNA sequence specificity. CCHC-zf domains from seven human proteins recognized specific RNA motifs, indicating that this is a major class of RBD. For Nudix, HABP4, TPR, RanBP2-zf, and L7Ae domains, however, only isolated members or closely related homologs yielded motifs, consistent with RNA-binding as a derived function. The lack of sequence specificity for most ucRBPs is striking, and we suggest that many may function analogously to chromatin factors, which often crosslink efficiently to cellular DNA, presumably via indirect recruitment. Finally, we show that ucRBPs tend to be highly abundant proteins and suggest their identification in RNA interactome capture studies could also result from weak nonspecific interactions with RNA.
Agent-based null models for examining experimental social interaction networks
Authors: Fennell Susan C. , Gleeson James P. , Quayle Michael , Durrheim Kevin , Burke Kevin
Published: March 2023

We consider the analysis of temporal data arising from online interactive social experiments, which is complicated by the fact that classical independence assumptions about the observations are not satisfied. Therefore, we propose an approach that compares the output of a fitted (linear) model from the observed interaction data to that generated by an assumed agent-based null model. This allows us to discover, for example, the extent to which the structure of social interactions differs from that of random interactions. Moreover, we provide network visualisations that identify the extent of ingroup favouritism and reciprocity as well as particular individuals whose behaviour differs markedly from the norm. We specifically consider experimental data collected via the novel Virtual Interaction APPLication (VIAPPL). We find that ingroup favouritism and reciprocity are present in social interactions observed on this platform, and that these behaviours strengthen over time. Note that, while our proposed methodology was developed with VIAPPL in mind, its potential usage extends to any type of social interaction data.
Suicidal risk associated with finasteride versus dutasteride among men treated for benign prostatic hyperplasia: nationwide cohort study
Authors: Laanani Moussa , Weill Alain , Jollant Fabrice , Zureik Mahmoud , Dray-Spira Rosemary
Published: March 2023

Finasteride, a 5α-reductase inhibitor used in benign prostatic hyperplasia and androgenetic alopecia, has been associated with an increased suicidal risk, whereas it is unclear whether such risk is similar to that for another 5α-reductase inhibitor, dutasteride. We aimed to assess the risk of suicidal behaviours with finasteride relative to dutasteride. A nationwide cohort study was conducted using the French National Health Data System (SNDS). Men aged 50 years or older initiating finasteride 5 mg or dutasteride 0.5 mg in France between 01-01-2012 and 30-06-2016 were included and followed until outcome (suicide death identified from death certificate or self-harm hospitalisation), treatment discontinuation or switch, death, or 31-12-2016. Self-harm by violent means or resulting in admission to an intensive care unit were also examined. Cox proportional hazards models controlled for age and psychiatric and non-psychiatric conditions by inverse probability of treatment weighting (IPTW). Analyses were stratified according to psychiatric history. The study compared 69,786 finasteride new users to 217,577 dutasteride new users (median age: 72.0 years [Q1–Q3 = 64.5–80.2] vs. 71.1 [Q1–Q3 = 65.0–79.2]). During follow-up, 18 suicide deaths (0.57/1000 person-years) and 34 self-harm hospitalisations (1.08/1000) occurred among finasteride users versus 47 deaths (0.43/1000) and 87 hospitalisations (0.79/1000) among dutasteride users. Overall, finasteride was not associated with an increased risk of any suicidal outcome (IPTW-adjusted Hazard Ratio = 1.21 [95% Confidence Interval  .87–1.67]), suicide death or self-harm hospitalisation. However, among individuals with a history of mood disorders, finasteride was associated with an increased risk of any suicidal outcome (25 versus 46 events; HR = 1.64 [95% CI 1.00–2.68]), suicide death (8 versus 10 events; HR = 2.71 [95% CI 1.07–6.91]), self-harm by violent means (6 versus 6 events; HR = 3.11 [95% CI 1.01–9.61]), and self-harm with admission to an intensive care unit (7 versus 5 events; HR = 3.97 [95% CI 1.26–12.5]). None of these risks was significantly increased among individuals without a psychiatric history. These findings do not support an increased risk of suicide with finasteride used in the treatment of benign prostatic hyperplasia. However, an increased risk cannot be excluded among men with a history of mood disorder, but this result based on a limited number of events should be interpreted with caution.
Complete genome analysis of African swine fever virus genotypes II, IX and XV from domestic pigs in Tanzania
Authors: Hakizimana Jean N. , Yona Clara , Makange Mariam R. , Kasisi Ester A. , Netherton Christopher L. , Nauwynck Hans , Misinzo Gerald
Published: March 2023

African swine fever (ASF) caused by ASF virus (ASFV) is an infectious transboundary animal disease notifiable to the World Organization for Animal Health causing high mortality in domestic pigs and wild boars threatening the global domestic pig industry. To date, twenty-four ASFV genotypes have been described and currently genotypes II, IX, X, XV and XVI are known to be circulating in Tanzania. Despite the endemic status of ASF in Tanzania, only one complete genome of ASFV from the country has been described. This study describes the first complete genome sequence of ASFV genotype XV. In addition, the first Tanzanian complete genome of ASFV genotype IX and three ASFV strains belonging to genotype II collected during ASF outbreaks in domestic pigs in Tanzania were determined in this study using Illumina sequencing and comparative genomics analysis. The generated ASFV complete genome sequences ranged from 171,004 to 184,521 base pairs in length with an average GC content of 38.53% and encoded 152 to 187 open reading frames. The results of this study provide insights into the genomic structure of ASFV and can be used to monitor changes within the ASFV genome and improve our understanding of ASF transmission dynamics.