bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissecting the contribution of common variants to risk of rare neurodevelopmental conditions
Authors: Huang Qin Qin , Wigdor Emilie M , Campbell Patrick , Malawsky Daniel S , Samocha Kaitlin E , Chundru V Kartik , Danecek Petr , Lindsay Sarah , Marchant Thomas , Musa Mahmoud Koko , Amanat Sana , Bonifanti Davide , Sheridan Eamonn , Radford Elizabeth J , Barrett Jeffrey C , Wright Caroline F , Firth Helen V , Warrier Varun , Young Alexander Strudwick , Hurles Matthew E , Martin Hilary C
Published: March 2024

Although rare neurodevelopmental conditions have a large Mendelian component, common genetic variants also contribute to risk. However, little is known about how this polygenic risk is distributed among patients with these conditions and their parents, its interplay with rare variants, and whether parents’ polygenic background contributes to their children’s risk beyond the direct effect of variants transmitted to the child (i.e. via indirect genetic effects potentially mediated through the prenatal environment or ‘genetic nurture’). Here, we addressed these questions using genetic data from 11,573 patients with rare neurodevelopmental conditions, 9,128 of their parents and 26,869 controls. Common variants explained ∼10% of variance in overall risk. Patients with a monogenic diagnosis had significantly less polygenic risk than those without, supporting a liability threshold model, while both genetically undiagnosed patients and diagnosed patients with affected parents had significantly more risk than controls. In a trio-based model, using a polygenic score for neurodevelopmental conditions, the transmitted but not the non-transmitted parental alleles were associated with risk, indicating a direct genetic effect. In contrast, we observed no direct genetic effect of polygenic scores for educational attainment and cognitive performance, but saw a significant correlation between the child’s risk and non-transmitted alleles in the parents, potentially due to indirect genetic effects and/or parental assortment for these traits. Indeed, as expected under parental assortment, we show that common variant predisposition for neurodevelopmental conditions is correlated with the rare variant component of risk. Our findings thus suggest that future studies should investigate the possible role and nature of indirect genetic effects on rare neurodevelopmental conditions, and consider the contribution of common and rare variants simultaneously when studying cognition-related phenotypes.
Cause-Specific Excess Mortality in the US During the COVID-19 Pandemic
Authors: Degtiareva Ekaterina , Tilstra Andrea M. , Schöley Jonas , Kashyap Ridhi , Dowd Jennifer B.
Published: March 2024

The COVID-19 pandemic was a significant shock to United States mortality, and it is important to understand how the pandemic impacted other causes of death. We estimated monthly excess mortality in the US by cause of death, age, and sex, for official deaths at ages 15 and older. Data come from the CDC Wonder Multiple Cause of Death database. We used a compositionally robust Generalized Additive Model (GAM) to estimate expected mortality counts in March 2020-December 2022 for eight causes of death: accidents, cardiovascular diseases, cancer, diabetes, influenza and pneumonia, substance-related (drugs and alcohol), suicide, and residual (including COVID-19 related deaths). Analyses were stratified by sex and 15-year age groups from 15-29 to 75+. Excess mortality was calculated as observed deaths minus expected deaths. From March 2020 to December 2022, we estimated 1 298 763 total excess deaths (95% CI: 1 226 542 to 1 370 804). While there were fewer deaths than expected due to some causes like flu/pneumonia and suicide, the largest number of excess deaths, excluding COVID-19, were attributed to cardiovascular diseases (115 765 deaths, 95% CI: 98 697 to 133 783) and substance use (86 637 deaths, 95% CI: 79 273 to 93 690). Percent excess substance-related mortality was high across all ages, while percent excess from cardiovascular diseases was highest at midlife ages. Some of these excess cardiovascular deaths were likely due to undercounted COVID-19 deaths, but others may reflect indirect impacts of the pandemic on healthcare utilization or longer-term effects of COVID-19 infections.

SIGNIFICANCE STATEMENT

The COVID-19 pandemic increased mortality directly due to COVID-19 deaths, but also changed the pattern of deaths due to other causes in the United States. We estimated excess cause-specific mortality in the US and present several findings. We estimated nearly 1.3 million total excess deaths in the US from March 2020 to December 2022. Deaths from suicide and influenza and pneumonia were lower than expected based on previous trends, but deaths due to cardiovascular diseases, diabetes, accidents, and substance-related causes (drug and alcohol) were higher. Cancer deaths were generally unchanged. By quantifying both the direct and indirect effects of the COVID-19 pandemic on US mortality, we highlight areas of on-going vulnerability in the US.
The emerging H3K9me3 chromatin landscape during zebrafish embryogenesis
Authors: Duval Katherine L. , Artis Ashley R. , Goll Mary G.
Published: March 2024

The structural organization of eukaryotic genomes is contingent upon the fractionation of DNA into transcriptionally permissive euchromatin and repressive heterochromatin. However, we have a limited understanding of how these distinct states are first established during animal embryogenesis. Histone 3 lysine 9 trimethylation (H3K9me3) is critical to heterochromatin formation and bulk establishment of this mark is thought to help drive large-scale remodeling of an initially naive chromatin state during animal embryogenesis. However, a detailed understanding of this process is lacking. Here, we leverage CUT&RUN to define the emerging H3K9me3 landscape of the zebrafish embryo with high sensitivity and temporal resolution. Despite the prevalence of DNA transposons in the zebrafish genome, we found that LTR transposons are preferentially targeted for embryonic H3K9me3 deposition, with different families exhibiting distinct establishment timelines. High signal-to-noise ratios afforded by CUT&RUN revealed new, emerging sites of low-amplitude H3K9me3 that initiated before the major wave of zygotic genome activation (ZGA). Early sites of establishment predominated at specific subsets of transposons and were particularly enriched for transposon sequences with maternal piRNAs and pericentromeric localization. Notably, the number of H3K9me3 enriched sites increased linearly across blastula development, while quantitative comparison revealed a >10-fold genome-wide increase in H3K9me3 signal at established sites over just 30 minutes at the onset of ZGA. Continued maturation of the H3K9me3 landscape was observed beyond the initial wave of bulk establishment.

Article Summary

Eukaryotic genomes are organized into transcriptionally permissive euchromatin and repressive heterochromatin. However, we have a limited understanding of how these distinct states are first established during animal embryogenesis. Here, we define the emerging landscape of the heterochromatic histone tail modification H3K9me3 across zebrafish embryogenesis. Our results uncover distinct kinetics of H3K9me3 establishment and growth, define unique characteristics associated with initial sites of H3K9me3, and demonstrate additional maturation of the H3K9me3 landscape beyond the window of bulk H3K9me3 deposition.
Picoplankton nitrogen guilds in the tropical and subtropical oceans: from the surface to the deep
Authors: Rivas-Santisteban Juan , Fernández-González Nuria , Laso-Pérez Rafael , Tamames Javier , Pedrós-Alió Carlos
Published: March 2024

Ecological guilds quantify the incidence and extent of resource transformation functions, irrespective of the species involved. Therefore, tackling the microbial nitrogen guilds is key to our understanding of the oceanic nitrogen cycle, but quantitative estimates of guild contribution across varying depths and under specific environmental conditions have yet to be accomplished. In this study, we examine the main picoplankton guilds participating in nitrogen cycling within the low and mid-latitude ocean ecosystems, from the surface down to 4000 m, using data obtained from 75 samples belonging to 11 stations in the Malaspina (MP) dataset. In particular, we used a quantitative approach to investigate the stability of nitrogen acquisition and nitrogen-redox guilds separately. Our results showed that nitrogen acquisition guilds are more stable and redundant than nitrogen-redox guilds across depths and site specific conditions. For example, differential conditions such as nitrogen depletion and oxygen availability affected the two groups of guilds in different ways. These findings have implications for the understanding of global nitrogen fluxes and the biosphere’s functional diversification.
The latent stage ofToxoplasma gondiiis targeted by the immune response and host protective
Authors: Shallberg Lindsey A. , Eberhard Julia N. , Winn Aaron , Chandrasekaran Sambamurthy , Giuliano Christopher J. , Merritt Emily F. , Willis Elinor , Christian David A. , Aldridge Daniel L. , Bunkofske Molly , Jacquet Maxime , Dzierszinski Florence , Katifori Eleni , Lourido Sebastian , Koshy Anita A. , Hunter Christopher A.
Published: March 2024

Latency is a microbial strategy for persistence. ForToxoplasma gondiithe ability of the bradyzoite stage to form long-lived cysts is critical for transmission, while their presence in neurons is considered important for immune evasion. Development of a mathematical model highlighted that immune pressure on bradyzoites should contribute to dynamics of cyst formation and reactivation. Experimental data demonstrated that a cyst-derived antigen was recognized by CD8+T cells and that IFN-γ signaling in neurons contributes to cyst control. In addition, modeling and the use of a parasite strain unable to form bradyzoites revealed that this stage was not required for long-term persistence, but the absence of cyst formation resulted in increased tachyzoite replication in the CNS with associated tissue damage and mortality. Thus, the latent form ofT. gondiiis under immune pressure, mitigates infection-induced damage, and promotes survival of host and parasite.
Bacteroidesvesicles promote functional alterations in gut microbiota composition
Authors: Shagaleeva Olga Yu. , Kashatnikova Daria A. , Kardonsky Dmitry A. , Efimov Boris A. , Ivanov Viktor A. , Evsiev Suleiman S. , Zubkov Eugene A. , Abramova Olga V. , Zorkina Yana A. , Morozova Anna Y. , Vorobeva Elizaveta A. , Silantiev Artemiy S. , Kolesnikova Irina V. , Markelova Maria I. , Olekhnovich Evgenii I. , Morozov Maxim D. , Zoruk Polina Y. , Boldyreva Daria I. , Vanyushkina Anna A. , Chaplin Andrei V. , Grigoryeva Tatiana V. , Zakharzhevskaya Natalya B.
Published: March 2024

Inflammatory bowel diseases are characterized by chronic intestinal inflammation and alterations of gut microbiota composition.Bacteroides fragilis, which secretes outer membrane vesicles (OMVs) with polysaccharide A (PSA), can moderate inflammatory response and possibly alter microbiota composition. In this research, we created a murine model of chronic DSS- induced intestinal colitis and treated it withBacteroides fragilisOMVs. We monitored the efficiency of OMVs therapy by determining the disease activity index (DAI) and histological examination (HE) of the intestine before and after vesicles exposure. We also analyzed the microbiota composition using 16S rRNA gene sequencing. Finally, we evaluated the volatile compounds composition in animals’ stools by HS-GC/MS to assess the functional activity of the microbiota. As a result, we observed a more effective intestine repair after OMVs treatment according to DAI and HE. The metabolomic study also indicated the microbiota functional activity change, showing a predominance of phenol and pentanoic acid in the control group compared to the group treated with DSS (DSS) and the group treated with OMVs (DSS OMV). We also observed a positive correlation of these metabolites withSaccharibacteriaandHungatei Clostridiumin the control group, whereas in the DSS group there was a negative correlation of phenol and pentanoic acid withLactococcusandRomboutsia. According to metabolome and sequencing data, the microbiota composition of the DSS OMV group was intermediate between the control and DSS groups. It can be concluded that OMVs not only have an anti-inflammatory effect, but also contribute to the recovery of the microbiota composition.
High-Throughput Phenotyping of Seed Quality Traits Using Imaging and Deep Learning in Dry Pea
Authors: Morales Mario Andres , Worral Hannah , Piche Lisa , Adeniyi Atanda Sikiru , Dariva Francoise , Ramos Catalina , Hoang Khang , Yan Changhui , Flores Paulo , Bandillo Nonoy
Published: March 2024

Seed traits, such as seed color and seed size, directly impact seed quality, affecting the marketability and value of dry peas [1]. Assessing seed quality is integral to a plant breeding programs to ensure optimal seed standards. This research introduced a phenotyping tool to assess seed quality traits specifically tailored for pulse crops, which integrates image processing with cutting-edge deep learning models. The proposed method is designed for automation, seamlessly processing a sequence of images while minimizing human intervention. The pipeline standardized red-green-blue (RGB) images captured from a color light box and used deep learning models to segment and detect seed features. Our method extracted up to 86 distinct seed characteristics, ranging from basic size metrics to intricate texture details and color nuances. Compared to traditional methods, our pipeline demonstrated a 95 percent similarity in seed quality assessment and increased time efficiency (from 2 weeks to 30 minutes for processing time). Specifically, we observed an improvement in the accuracy of seed trait identification by simply using an RGB value instead of a categorical, non-standard description, which allowed for an increase in the range of detectable seed quality characteristics. By integrating conventional image processing techniques with foundational deep learning models, this approach emerges as a pivotal instrument in pulse breeding programs, guaranteeing the maintenance of superior seed quality standards.
Seasonal patterns of exometabolites depend on microbial functions in the oligotrophic ocean
Authors: McParland Erin L , Wittmers Fabian , Bolanos Luis M , Carlson Craig A , Curry Ruth , Giovannoni Stephen J , Michelsen Michelle , Parsons Rachel J , Kido Soule Melissa C , Swarr Gretchen J , Temperton Ben , Vergin Kevin , Worden Alexandra Z , Longnecker Krista , Kujawinski Elizabeth B
Published: March 2024

Predictions of how the biogeochemical reservoir of marine dissolved organic matter (DOM) will respond to future ocean changes require an improved understanding of the thousands of individual microbe-molecule interactions which regulate the transformation and fate of DOM. Bulk characterizations of organic matter can mask this complex network of interactions comprised of rich chemical and taxonomic diversity. Here, we present a three-year, depth-resolved time-series of the seasonal dynamics of the exometabolome and the bacterioplankton community at the Bermuda Atlantic Time-series Study (BATS) site. We find both time-series to be highly structured and compositionally distinct across sampling depths. Putative exometabolite identifications (gonyol, glucose 6-sulfate, succinate, and trehalose) indicate that at least a portion of the exometabolome contains rapidly remineralized, labile molecules. We hypothesize that apparent seasonal accumulation of these labile molecules could result from environmental conditions that alter community composition on a seasonal timescale and thus shift the relative proportions of microbial functions that produce and consume the substrates. Critically, we found the composition of seasonal DOM features was more stable interannually than the microbial community structure. By estimating redundancy of metabolic functions responsible for cycling these molecules in BATS metagenomes, we propose a paradigm whereby core microbial metabolisms, either those utilized by all or by a subset of marine microbes, are better predictors of DOM composition than microbial taxonomies. The molecular-level characterization of DOM achieved herein highlights the metabolic imprint of microbial activity in DOM composition and greatly enhances our understanding of the dynamics regulating the largest reservoir of organic carbon on Earth.
Aurora B controls microtubule stability to regulate abscission dynamics in stem cells
Authors: Kodba Snježana , Öztop Amber , van Berkum Eri , Iwanski Malina K. , Nijenhuis Wilco , Kapitein Lukas C. , Chaigne Agathe
Published: March 2024

Abscission is the last step of cell division leading to the complete separation of the two sister cells and consists of the cutting of a cytoplasmic bridge. Abscission is mediated by the ESCRT membrane remodeling machinery which also triggers the severing of a thick bundle of microtubules that needs to be cleared prior to abscission. Here, we show that rather than being passive actors in abscission, microtubules control abscission speed. Using mouse embryonic stem cells, which transition from slow to fast abscission during exit from naïve pluripotency, we investigate the molecular mechanism for the regulation of abscission dynamics and identify a feedback loop between the activity of Aurora B and microtubule stability. We demonstrate that naïve stem cells maintain high Aurora B activity after cytokinesis. This high Aurora B activity leads to transient microtubule stabilization that delays abscission. In turn, stable microtubules promote the activity of Aurora B. When cells exit naïve pluripotency, a decrease in Wnt signaling leads to a decrease in the activity of Aurora B, less stable microtubules, and a faster abscission. Overall, our data demonstrate that Aurora B-dependent microtubule stability controls abscission dynamics.
P
-wave states
Tbb−
from diquarks
Authors: Lin Zu-Hang , An Chun-Sheng , Deng Cheng-Rong
Published: March 2024

We investigate the P-wave states Tbb− in the isospin singlet and three excited modes [excitation occurring in the diquark [bb]c1s1 (ρ-mode), antidiquark [u¯d¯]c2s2 (r-mode), or between them (λ-mode)] from diquarks in a quark model. We analyze the dynamical behaviors of the diquark [bb]c1s1, antidiquark [u¯d¯]c2s2, and their correlations in the states Tbb− by decomposing the interactions from various sources in the model. The absolute dominant color-spin configuration, more than 99%, in the ρ-mode with 1P11 is [bb]3¯0[u¯d¯]30. Its energy is lower by about 18 MeV than the threshold B¯B¯ so that it can establish a compact bound state. The chromomagnetic and meson-exchange interactions in the antidiquark [u¯d¯]30 are responsible for its binding mechanism. Two other excited modes are higher than their respective threshold. The color configuration 6⊗6¯ need to be handled discreetly in the tetraquark states.

Published by the American Physical Society
2024
Lorentz invariance violation and the
CPT
-odd electromagnetic response of a tilted anisotropic Weyl semimetal
Authors: Gómez Andrés , von Dossow R. Martínez , Martín-Ruiz A. , Urrutia Luis F.
Published: March 2024

We derive the electromagnetic response of a particular fermionic sector in the minimal QED contribution to the Standard Model Extension (SME), which can be physically realized in terms of a model describing a tilted and anisotropic Weyl semimetal (WSM). The contact is made through the identification of the Dirac-like Hamiltonian resulting from the SME with that corresponding to the WSM in the linearized tight-binding approximation. We first calculate the effective action by computing the nonperturbative vacuum polarization tensor using thermal field theory techniques, focusing upon the corrections at finite chemical potential and zero temperature. Next, we confirm our results by a direct calculation of the anomalous Hall current within a chiral kinetic theory approach. In an ideal Dirac cone picture of the WSM (isotropic and nontilted) such response is known to be governed by axion electrodynamics, with the space-time dependent axion angle Θ(r,t)=2(b·r−b0t), being 2b and 2b0 the separation of the Weyl nodes in momentum and energy, respectively. In this paper we demonstrate that the node tilting and the anisotropies induce novel corrections at a finite density which however preserve the structure of the axionic field theory. We apply our results to the ideal Weyl semimetal

EuCd

2

As

2

and to the highly anisotropic and tilted monopnictide TaAs.

Published by the American Physical Society
2024
Strongly interacting photonic quantum walk using single atom beamsplitters
Authors: Zheng Xinyuan , Waks Edo
Published: March 2024

Photonics provide an efficient way to implement quantum walks, the quantum analog of classical random walks, which demonstrate rich physics with potential applications. However, most photonic quantum walks do not involve photon interactions, which limits their potential to explore strongly correlated many-body physics of light. We propose a strongly interacting discrete-time photonic quantum walk using a network of single atom beamsplitters. We calculate output statistics of the quantum walk for the case of two photons, which reveals the strongly correlated transport of photons. Particularly, the walk can exhibit either bosonlike or fermionlike statistics which is tunable by postselecting the two-photon detection time interval. Also, the walk can sort different types of two-photon bound states into distinct pairs of output ports under certain conditions. These unique phenomena show that our quantum walk is an intriguing platform to explore strongly correlated quantum many-body states of light. Finally, we propose an experimental realization based on time-multiplexed synthetic dimensions.

Published by the American Physical Society
2024
Dualities in One-Dimensional Quantum Lattice Models: Topological Sectors
Authors: Lootens Laurens , Delcamp Clement , Verstraete Frank
Published: March 2024

It has been a long-standing open problem to construct a general framework for relating the spectra of dual theories to each other. Here, we solve this problem for the case of one-dimensional quantum lattice models with symmetry-twisted boundary conditions. In Ref. [PRX Quantum 4, 020357], dualities are defined between (categorically) symmetric models that only differ in a choice of module category. Using matrix product operators, we construct from the data of module functors explicit symmetry operators preserving boundary conditions as well as intertwiners mapping topological sectors of dual models onto one another. We illustrate our construction with a family of examples that are in the duality class of the spin-12 Heisenberg XXZ model. One model has symmetry operators forming the fusion category Rep(S3) of representations of the group

S

3

. We find that the mapping between its topological sectors and those of the XXZ model is associated with the nontrivial braided autoequivalence of the Drinfel’d center of Rep(S3).

Published by the American Physical Society
2024
Identifying the push and pull factors for migration patterns vis-à-vis smart cities’ context
Authors: Naval Naveen , Alexopoulos Charalampos , Rizun Nina , Saxena Stuti
Published: March 2024

Purpose

While the causes of migration across a range of diverse societies have been studied in the extant literature, a systematic study encapsulating the extant literature pertaining to the push and pull factors for the phenomenon of migration has not been conducted so far. The purpose of this study is to present a gist of the push and pull factors that are responsible for migration patterns across different contexts.

Design/methodology/approach

Inferences from the literature review and documentary analysis show that, on the one hand, the push factors for migration entail the enforced reasons like natural causes, wars, health and the like; the pull factors are, by and large, the affirmative ones related to better job opportunities, anticipation of improved well-being, etc.

Findings

It may also be deduced that both the categories of migration causes are analyzed at the individual, group, societal as well as regional levels.

Originality/value

Hitherto, the migration research has focused on understanding the antecedents and consequences of migration in temporal–spatial context, but a syncretic understanding of the push and pull factors behind migration vis-à-vis smart cities is required. The present study seeks to fill this gap. Besides contributing toward the mainstream literature on migration in general, the present study also adds to the literature pertaining to the specific factors responsible for migration patterns.
N‐glycosylation of the SARS‐CoV‐2 spike protein at Asn331 and Asn343 is involved in spike‐ACE2 binding, virus entry, and regulation of IL‐6
Authors: Das Tuhin , Luo Shuhong , Tang Hao , Fang Jianmin , Mao Yinging , Yen Haw‐Han , Dash Sabyasachi , Shajahan Asif , Pepi Lauren , Huang Steven , Jones Valerie S. , Xie Shehuo , Huang Gordon F. , Lu Jinqiao , Anderson Blake , Zhang Benyue , Azadi Parastoo , Huang Ruo‐Pan
Published: March 2024

The coronavirus disease 2019 (COVID‐19) pandemic is an ongoing global public health crisis. The causative agent, the SARS‐CoV‐2 virus, enters host cells via molecular interactions between the viral spike protein and the host cell ACE2 surface protein. The SARS‐CoV‐2 spike protein is extensively decorated with up to 66 N‐linked glycans. Glycosylation of viral proteins is known to function in immune evasion strategies but may also function in the molecular events of viral entry into host cells. Here, we show that N‐glycosylation at Asn331 and Asn343 of SARS‐CoV‐2 spike protein is required for it to bind to ACE2 and for the entry of pseudovirus harboring the SARS‐CoV‐2 spike protein into cells. Interestingly, high‐content glycan binding screening data have shown that N‐glycosylation of Asn331 and Asn343 of the RBD is important for binding to the specific glycan molecule G4GN (Galβ−1,4 GlcNAc), which is critical for spike‐RBD‐ACE2 binding. Furthermore, IL‐6 was identified through antibody array analysis of conditioned media of the corresponding pseudovirus assay. Mutation of N‐glycosylation of Asn331 and Asn343 sites of the spike receptor‐binding domain (RBD) significantly reduced the transcriptional upregulation of pro‐inflammatory signaling molecule IL‐6. In addition, IL‐6 levels correlated with spike protein levels in COVID‐19 patients' serum. These findings establish the importance of RBD glycosylation in SARS‐CoV‐2 pathogenesis, which can be exploited for the development of novel therapeutics for COVID‐19.
How Does Management Voluntary Disclosure Behavior Influence Auditors’ Judgments?
Authors: HILLISON SEAN M. , VITTORI KAMBER D.
Published: March 2024

Forward‐looking information, often used by auditors to evaluate complex estimates and form conclusions about going‐concern audit report modifications, is commonly disclosed voluntarily by U.S. public companies. We experimentally examine how this disclosure behavior affects auditors’ skepticism toward such information. Prior research has shown that investors and analysts frequently interpret voluntarily disclosed forward‐looking information as credible. We demonstrate that auditors, in contrast, exhibit greater skepticism toward forecasted information that has been voluntarily disclosed (vs. mandatorily disclosed or held privately) because of their reduced trust in management, even when the forecasts align with prior year trends (vs. being more optimistic). Our results suggest that a manager's decision to disclose, rather than the disclosure content itself, leads to increased auditor skepticism. Our findings have implications not only for audit outcomes, but also for manager disclosure behavior, as increased auditor scrutiny could discourage future voluntary disclosure.
All the News That Is Fit to Steal: Charles Gildon, Ferrante Pallavicino, and the Geopolitics of Rifled Mailbag Fiction
Authors: Beebee Thomas O.
Published: March 2024

Charles Gildon (1665–1724) is known today as the ultimate hack writer of Restoration England. Nonetheless, his two fiction collections in the ‘rifled mailbag’ genre — The Post‐Boy Rob'd of His Mail (1692) and The Post‐Man Robb'd of His Mail (1719) — contain insights concerning the structures and practices of information gathering in early modern Europe. This essay places these fictions by Gildon in their historical and literary contexts, including his repurposing of the Italian Il Corriero svaligiato by Ferrante Pallavicino, the relation to John Dunton's Athenian Mercury, and the use of addresses and occupations of letters to describe the geopolitics of Restoration London and its surround.
Bacterial symbionts of the precious coral Corallium rubrum are differentially distributed across colony‐specific compartments and differ among colormorphs
Authors: van de Water Jeroen A. J. M. , Allemand Denis , Ferrier‐Pagès Christine
Published: March 2024

Corals engage in symbioses with micro‐organisms that provide nutrients and protect the host. Where the prokaryotic microbes perform their symbiotic functions within a coral is, however, poorly understood. Here, we studied the tissue‐specific microbiota of the coral Corallium rubrum by dissecting its tissues from the skeleton and separating the white polyps from the red‐coloured coenenchyme, followed by 16S rRNA gene metabarcoding of the three fractions. Dissection was facilitated by incubating coral fragments in RNAlater, which caused tissues to detach from the skeleton. Our results show compartmentalisation of the microbiota. Specifically, Endozoicomonas, Parcubacteria and a Gammaproteobacteria were primarily located in polyps, whereas Nitrincolaceae and one Spirochaeta phylotype were found mainly in the coenenchyme. The skeleton‐associated microbiota was distinct from the microbiota in the tissues. Given the difference in tissue colour and microbiota of the polyps and coenenchyme, we analysed the microbiota of three colormorphs of C. rubrum (red, pink, white), finding that the main difference was a very low abundance of Spirochaeta in white colormorphs. While the functions of C. rubrum's symbionts are unknown, their localisation within the colony suggests that microhabitats exist, and the presence of Spirochaeta appears to be linked to the colour of C. rubrum.
High‐dose methotrexate pharmacokinetics and its impact on prognosis of paediatric acute lymphoblastic leukaemia patients: A population pharmacokinetic study
Authors: Chen Xiaoxiao , Li Jing , Yu Liting , Hu Wenting , Cai Jiaoyang , Wang Zhuo , Chen Changcheng , Zhang Xin , Xie Yangyang , Wu Kefei , Mo Yixiao , Chen Jihui , Shen Shuhong
Published: March 2024

This study delivers a comprehensive evaluation of the efficacy and pharmacokinetics of high‐dose methotrexate (HDMTX) in a large cohort of Chinese paediatric acute lymphoblastic leukaemia patients. A total of 533 patients were included in the prognostic analysis. An association was observed between lower steady‐state MTX concentrations (<56 μmol/L) and poorer outcomes in intermediate‐/high‐risk (IR/HR) patients. Subgroup analysis further revealed that this relationship between concentrations and prognosis was even more pronounced in patients with MLL rearrangements. In contrast, such an association did not emerge within the low‐risk patient group. Additionally, utilizing population pharmacokinetic modelling (6051 concentrations from 815 patients), we identified the significant impact of physiological maturation, estimated glomerular filtration rate, sex and concurrent dasatinib administration on MTX pharmacokinetics. Simulation‐based recommendations include a reduced dosage regimen for those with renal insufficiency and a specific 200 mg/kg dosage for infants under 1 year. The findings underscore the critical role of HDMTX in treating IR/HR populations and call for a reassessment of its application in lower‐risk groups. An individualized pharmacokinetic dosage regimen could achieve the most optimal results, ensuring the largest proportion of steady‐state concentrations within the optimal range.
Cells flowing to attain functionality
Authors: Bellino Martín G.
Published: March 2024

Unraveling the fundamental biological processes underpinning cell functions and behavior remains a key challenge. Researchers working on cell biological processes might want to take a look at microscale cell flow as functionality genesis. This Commentary provides an outlook on how cell‐microcirculation interplay promises to lead to exciting insights into the cell biology complexity.
Curcumin activates the JNK signaling pathway to promote ferroptosis in colon cancer cells
Authors: Xin Wei , Zhang Yong
Published: March 2024

Recent evidence has proved that curcumin as a natural polyphenol have a great anticancer and anti‐proliferative effects in cancer cells. Ferroptosis, a new form of regulated cell death, plays a vital role in the pathogenesis and therapy of cancers. In this study, we aimed to examine the effects of curcumin in ferroptosis of human colorectal cancer cells and its underlying molecular mechanisms. SW‐480 colorectal cancer cells were treated by curcumin with different concentrations. Cell viability was determined by using MTT assay. The concentrations of reactive oxygen species (ROS) and intracellular iron were measured using specific related kits. Real‐time PCR and Western blot analysis were used to determine the expression of ferroptosis‐related proteins including ACSL4, GPx4 and FTH1 and activation of JNK protein. Curcumin suppressed SW‐480 cancer cells viability in dose‐dependent manner. Cell treatment with curcumin led to accumulation of ROS and iron within cells and increase in the intracellular levels of lipid peroxidation. In addition, curcumin modulated the mRNA and protein expression levels of ferroptosis‐related proteins including ACSL4, GPx4 and FTH1 and suppression of JNK signaling. Curcumin may exhibit its anticancer effect on colorectal cancer by downregulating JNK signaling to induce ferroptosis in SW‐480 cells.
Caffeic acid‐grafted chitooligosaccharides downregulate MAPK and NF‐kB in RAW264.7 cells
Authors: Bui Van‐Hoai , Vo Hong‐Tham N. , Kim Se‐Kwon , Ngo Dai‐Nghiep
Published: March 2024

Chitooligosaccharide (COS) is a derivative of chitosan, which is a natural macromolecular compound. COS has been shown effects in an inflammatory response. Recent reports show that COS derivatives have enhanced anti‐inflammatory activity by inhibiting intracellular signals. Evaluation of the anti‐inflammatory effect of caffeic acid conjugated COS chain (CA‐COS) was performed in this study. The effects of CA‐COS on the inflammatory response were demonstrated in lipopolysaccharide‐stimulated RAW264.7 macrophages. The results showed that CA‐COS inhibited nitric oxide (NO) production and downregulated the gene expression of nitric oxide synthase (iNOS), and cytokines such as tumor necrosis factor‐alpha (TNF‐α), IL‐1β, and IL‐6 without cytotoxic effect. In addition, western blot analysis showed that CA‐COS inhibits the protein expression of iNOS and nuclear factor kappa B (NF‐kB), including p50 and p65, and mitogen‐activated protein kinase (MAPK) signaling pathways. Collectively, these results provide clear evidence for the anti‐inflammatory mechanism of CA‐COS that show great potential as a novel agent for the prevention and therapy of inflammatory diseases.
Being a sibling of a youth with a neurodisability: A qualitative study about the roles and responsibilities during the transition to adulthood
Authors: Nguyen Linda , Jack Susan M. , Davis Hanae , Bellefeuille Samantha , Arafeh Dana , Di Rezze Briano , Ketelaar Marjolijn , Gorter Jan Willem
Published: March 2024

Background

During the transition to adulthood, a common challenge that youth with a neurodisability may experience is learning how to navigate services in the adult care system. During this transition youth may rely on their families, including siblings, for support. However, delineation of sibling roles and responsibilities during this transition period are unclear. This study aims to identify the roles and responsibilities that siblings perceive to have with their sibling with a neurodisability during the transition to adulthood, and describe the decision‐making process of how siblings chose these roles.

Methods

In this descriptive qualitative case study, siblings were eligible to participate if they were between 14 to 40 years old, had a sibling between 14 to 21 years with a childhood‐onset neurodisability and spoke English. Semi‐structured interviews augmented by techniques of photo elicitation and relational maps were conducted. Reflexive thematic analysis was applied to identify sibling roles, as well as the emotional and decision‐making process associated with these roles. Our team partnered with siblings with lived experience in all study phases.

Results

Nineteen participants (median age = 19 years, range = 14 to 33 years) from 16 unique families were interviewed. Six unique roles were described: friend, role model/mentor, protector, advocate, supporter, or caregiver. The emotions that siblings experienced with each role, also known as emotional responsibility, were categorized into levels of low, medium or high. Siblings also described a four‐phase decision‐making process for their roles: (1) acquiring knowledge; (2) preparing plans; (3) making adjustments; and (4) seeking support. Intrapersonal characteristics, including personal identity, values and experiences, influenced roles assumed by siblings.

Conclusions

Siblings identified needing support as they process their decisions and emotional responsibility in their roles when their sibling with a neurodisability is transitioning to adulthood. Resources should be developed or further enhanced to support siblings.
Risk of major birth defects after first‐trimester exposure to carbocisteine and ambroxol: A multicenter prospective cohort study using counseling data for drug safety during pregnancy
Authors: Usuda Mariko , Jwa Seung Chik , Goto Mikako , Kobayashi Mizuki , Nagano Hiroyuki , Yakuwa Naho , Yamane Ritsuko , Murashima Atsuko , Makabe Hideki
Published: March 2024

To assess the risk of major birth defects after first‐trimester exposure to carbocisteine and ambroxol during pregnancy, we conducted a prospective cohort study using counseling data for drug use during pregnancy provided by the Japan Drug Information Institute in Pregnancy and Toranomon Hospital. Counseling information, including drug usage and participants' demographic information, was collected between April 1988 and December 2017. Pregnancy outcome data, including major birth defects, were obtained using a questionnaire administered 1 month after delivery. The risks of major birth defects after first‐trimester exposure to carbocisteine (n = 588) and ambroxol (n = 341) were compared with those of nonteratogenic drug use during the first trimester (n = 1525). The adjusted odds ratio (aORs) for major birth defects was calculated using a multiple logistic regression analysis adjusted for confounders. The incidence of major birth defects was 1.2% (7/588) and 2.1% (7/341) in the carbocisteine and ambroxol groups, respectively, which was comparable to the control group (26/1525, 1.7%). Results of multiple logistic regression demonstrated similar nonsignificant risks for both carbocisteine (aOR: 0.66, 95% confidence interval [CI]: 0.40–1.1, p = 0.11) and ambroxol (aOR: 1.1, 95% CI: 0.18–7.2, p = 0.88). No specific major birth defects were reported in the carbocisteine or ambroxol groups. This study demonstrated that carbocisteine and ambroxol exposure during the first trimester was not associated with an increased risk of major birth defects. These results could help in counseling for the use of these drugs during pregnancy and further alleviate anxiety in patients.
Prediction of colour strength in environmentally‐friendly dyeing of polyester fabric with madder using supercritical carbon dioxide
Authors: Haji Aminoddin , Vadood Morteza , Öztürk Merve , Yigit İdil , Eren Semiha , Eren Hüseyin Aksel
Published: March 2024

The textile industry is one of the significant reasons for global water pollution, with dyeing processes being particularly environmentally detrimental. Researchers have explored alternative approaches to address this issue, such as using natural dyes, supercritical fluids and so forth. In addition to environment‐friendly approaches, reducing the number of experiments in studies, accurate production straightaway and using artificial intelligence (AI), one of the technologies of the present and the future that will provide significant support. Reaching clearer results with AI technology will not necessarily contribute to environment‐friendly technologies. However, AI techniques, including artificial neural networks (ANNs) and adaptive neuro fuzzy interface system (ANFIS) were employed to predict the colour strength (K/S) of the dyed fabric based on process parameters. A comprehensive experimental design involving pressure, temperature, and time variations was conducted, and the results were analysed using multi‐factor analysis of variance (MANOVA). The study demonstrates that supercritical carbon dioxide (scCO2) dyeing with madder on polyester fabric is a promising and environmentally friendly approach. Additionally, the optimised ANN and ANFIS models, aided by genetic algorithms (GAs), exhibit high predictive accuracy (less than 3%), providing insights into the impact of process parameters on colour strength. This research underscores the potential of AI‐driven automation in textile dyeing, offering solutions for dye formula prediction, colour matching, and defect detection, reducing the need for human intervention in these processes.
Single center utilization and post‐transplant outcomes of thoracoabdominal normothermic regional perfusion deceased cardiac donor organs
Authors: Motter Jennifer D. , Jaffe Ian S. , Moazami Nader , Smith Deane E. , Kon Zachary N. , Piper Greta L. , Sommer Philip M. , Reyentovich Alex , Chang Stephanie H. , Aljabban Imad , Montgomery Robert A. , Segev Dorry L. , Massie Allan B. , Lonze Bonnie E.
Published: March 2024

Introduction

Thoracoabdominal normothermic regional perfusion (TA‐NRP) following cardiac death is an emerging multivisceral organ procurement technique. Recent national studies on outcomes of presumptive TA‐NRP‐procured organs are limited by potential misclassification since TA‐NRP is not differentiated from donation after cardiac death (DCD) in registry data.

Methods

We studied 22 donors whose designees consented to TA‐NRP and organ procurement performed at our institution between January 20, 2020 and July 3, 2022. We identified these donors in SRTR to describe organ utilization and recipient outcomes and compared them to recipients of traditional DCD (tDCD) and donation after brain death (DBD) organs during the same timeframe.

Results

All 22 donors progressed to cardiac arrest and underwent TA‐NRP followed by heart, lung, kidney, and/or liver procurement. Median donor age was 41 years, 55% had anoxic brain injury, 45% were hypertensive, 0% were diabetic, and median kidney donor profile index was 40%. TA‐NRP utilization was high across all organ types (88%–100%), with a higher percentage of kidneys procured via TA‐NRP compared to tDCD (88% vs. 72%, p = .02). Recipient and graft survival ranged from 89% to 100% and were comparable to tDCD and DBD recipients (p ≥ .2). Delayed graft function was lower for kidneys procured from TA‐NRP compared to tDCD donors (27% vs. 44%, p = .045).

Conclusion

Procurement from TA‐NRP donors yielded high organ utilization, with outcomes comparable to tDCD and DBD recipients across organ types. Further large‐scale study of TA‐NRP donors, facilitated by its capture in the national registry, will be critical to fully understand its impact as an organ procurement technique.
Seasonal distribution patterns and conservation gaps of blue sharks in the Indo‐Western Pacific Ocean
Authors: Zhang Yuewen , Lian Peng , Zhang Xiong
Published: March 2024

Aim

Oceanic sharks play an important role in maintaining the stability and biodiversity of marine ecosystems, and yet they are among the most threatened taxa worldwide. Currently, large spatial‐scale distribution patterns and conservation gaps are poorly known for most species since they are challenging to study. To address the problem, we here use an integrated approach with an illustration with the blue shark (Prionace glauca), a common bycatch oceanic species.

Location

Indo‐Western Pacific Ocean (IWPO).

Methods

We first collated decades of species occurrences and marine environmental datasets from open‐access sources. We then applied ensembled species distribution models (SDMs) to predict its seasonal distributions and evaluated the model performance using true skill statistic (TSS) and area under the receiver‐operating characteristic curve (AUC). We finally conducted spatial analyses (e.g. bivariate hotspot analyses) to identify conservation gaps/opportunities based on the predicted distribution maps and two additional datasets, namely, marine protected areas (MPAs) and fishing effort.

Results

(1) Both seasonal SDMs performed well (mean TSS > 0.8, AUC > 0.95), and the results suggested that blue sharks were widely distributed in the IWPO with some seasonal differences in ecological niches and distributions (mainly in the West Indian Ocean and the Northwest Pacific Ocean); (2) large MPAs and shark sanctuaries covered comparable, small portions (4%–9%) of blue shark habitats, but these locations (in MPAs and sanctuaries) varied between seasons; (3) fishery‐shark conflict hotspots also varied between seasons with some located in or close to large MPAs and sanctuaries.

Main conclusions

We provide seasonal (cold vs. warm) distribution maps of blue sharks across the IWPO to advance their conservation and management. We highlight the importance of strengthening management both in and near large MPAs and shark sanctuaries. Our study contributes a feasible integrated approach to reveal seasonal distribution patterns and conservation opportunities for oceanic sharks.
Targeting of neuroblastoma cells through Kynurenine‐AHR pathway inhibition
Authors: dos Santos Igor Lopes , Mitchell Michael , Nogueira Pedro A. S. , Lafita‐Navarro M. Carmen , Perez‐Castro Lizbeth , Eriom Joyane , Kilgore Jessica A. , Williams Noelle S. , Guo Lei , Xu Lin , Conacci‐Sorrell Maralice
Published: March 2024

Neuroblastoma poses significant challenges in clinical management. Despite its relatively low incidence, this malignancy contributes disproportionately to cancer‐related childhood mortality. Tailoring treatments based on risk stratification, including MYCN oncogene amplification, remains crucial, yet high‐risk cases often confront therapeutic resistance and relapse. Here, we explore the aryl hydrocarbon receptor (AHR), a versatile transcription factor implicated in diverse physiological functions such as xenobiotic response, immune modulation, and cell growth. Despite its varying roles in malignancies, AHR's involvement in neuroblastoma remains elusive. Our study investigates the interplay between AHR and its ligand kynurenine (Kyn) in neuroblastoma cells. Kyn is generated from tryptophan (Trp) by the activity of the enzymes indoleamine 2,3‐dioxygenase 1 (IDO1) and tryptophan 2,3‐dioxygenase (TDO2). We found that neuroblastoma cells displayed sensitivity to the TDO2 inhibitor 680C91, exposing potential vulnerabilities. Furthermore, combining TDO2 inhibition with retinoic acid or irinotecan (two chemotherapeutic agents used to treat neuroblastoma patients) revealed synergistic effects in select cell lines. Importantly, clinical correlation analysis using patient data established a link between elevated expression of Kyn‐AHR pathway genes and adverse prognosis, particularly in older children. These findings underscore the significance of the Kyn‐AHR pathway in neuroblastoma progression, emphasizing its potential role as a therapeutic target.