bluuebunny/crossref_metadata_2025 huggingface dataset:
The TELPERION survey for extended emission regions around active galactic nuclei: a strongly interacting and merging galaxy sample
Authors: Keel William C , Moiseev Alexei , Uklein Roman , Smirnova Aleksandrina
Published: April 2024

We present the results of a search for extended emission-line regions (EELRs) ionized by extant or recently faded active galactic nuclei (AGNs), using [O III] narrow-band imaging and spectroscopic follow-up. The sample includes 198 galaxies in 92 strongly interacting or merging galaxy systems in the range of z = 0.009–0.0285. Among these, three systems have EELRs extended beyond 10 kpc in projection from the nucleus detected in previous studies. We identify a single new distant emission region, projected 35 kpc from UGC 5941. Our optical spectrum does not detect He II, but its strong-line ratios put this in the same class as securely characterized EELR clouds. The nucleus of UGC 5941 is dominated by recent star formation, preventing detection of any weak ongoing AGN. Overall counts of distant EELRs in this and the previous TELPERION samples give incidence 2–5 per cent depending on galaxy and AGN selection, 20–50 times higher than the Galaxy Zoo EELR survey with its higher surface-brightness threshold and much larger input sample. AGNs in interacting and merging systems have an increased detection rate of 12 ± 6 per cent, while none are detected around non-interacting AGNs. Some of these AGNs are at luminosity low enough to require additional X-ray or far-infrared information to tell whether the EELR ionization level suggests long-term fading.
A search for intermediate-mass black holes in compact stellar systems through optical emissions from tidal disruption events
Authors: Pomeroy Richard T , Norris Mark A
Published: April 2024

Intermediate-mass black holes (IMBHs) are expected to exist in globular clusters (GCs) and compact stellar systems (CSSs) in general, but none have been conclusively detected. Tidal disruption events (TDEs), where a star is tidally disrupted by the gravitational field of a black hole, have been observed to occur around the supermassive black holes (SMBHs) found at the centres of galaxies, and should also arise around IMBHs, especially in the dense stellar cores of CSSs. However, to date none have been observed in such environments. Using data from the Zwicky Transient Facility, we search for TDEs associated with CSSs, but none are found. This non-detection allows us to set an upper limit on the TDE rate in CSSs of $n_\text{TDE,Total}\lessapprox 10^{-7} \, \mathrm{ CSS}^{-1}\, \text{yr}^{-1}$, which is 2 dex below the observed TDE rate involving SMBHs interacting with 1 M⊙ main-sequence stars in the nuclei of massive galaxies. We also consider ultracompact dwarfs (UCDs) formed through a tidal stripping process in the surveyed volume. On the assumption that these CSSs contain SMBHs and TDE rates are comparable to current observed optical rates in galactic nuclei ($\approx 3.2 \times 10^{-5}\, \text{gal}^{-1}\, \text{yr}^{-1}$), we determine an upper limit for the number of UCDs formed through a tidal stripping process in the surveyed volume to be NGC,Strip < 1.4 × 104, which we estimate represents $\lt 6~{{\ \rm per\ cent}}$ of the population of GCs >106 M⊙.
Effective mass function of radio meteoroids as a modulating factor in determining atmospheric scale height
Authors: Sarkar Emranul , Ulich Thomas , Lester Mark
Published: April 2024

A long-standing problem in meteor science has been the persistent presence of bias in the measured value of atmospheric scale heights obtained from radio meteor echoes. A common practice of fitting a linear function for bias correction follows the assumption that the systematic bias is devoid of seasonal asymmetry. This would be true if the mass and the velocity distribution of meteoroids remain invariant, both spatially and temporally. But so far no such convincing evidence has been published. On the contrary, fundamental arguments suggest that a universal mass function of radio meteoroids is counterintuitive. This parameter cannot remain invariant due to the intrinsic variability in the meteor response function resulting from the Earth’s motion on the plane of ecliptic. In this paper, we show that an inverse relation exists between the width of meteor height distribution, expressed in unit of atmospheric scale height, and the exponent of the mass function. The overall mean of this exponent for the Sodankylä radar is $1.91 \pm 0.02$, modulated by a seasonal variation from the mean of the order of $\sim \pm 0.1$. The stated inverse relation is applied to correct for the effect of mass distribution on the height distribution. Allowing for variable mass correction effectively removes the non-linear bias in the measured scale heights in the meteor ionization region.
Multiple time-step reversible N-body integrators for close encounters in planetary systems
Authors: Hernandez David M , Dehnen Walter
Published: April 2024

We present new ‘almost’ time-reversible integrators for solution of planetary systems consisting of ‘planets’ and a dominant mass (‘star’). The algorithms can be considered adaptive generalizations of the Wisdom–Holman method, in which all pairs of planets can be assigned time-steps. These time-steps, along with the global time-step, can be adapted time-reversibly, often at no appreciable additional compute cost, without sacrificing any of the long-term error benefits of the Wisdom–Holman method. The method can also be considered a simpler and more flexible version of the symba symplectic code. We perform tests on several challenging problems with close encounters and find the reversible algorithms are up to 2.6 times faster than a code based on symba. The codes presented here are available on Github. We also find adapting a global time-step reversibly and discretely must be done in block-synchronized manner or similar.
Structure-functional characterization of Lactococcus AbiA phage defense system
Authors: Gapińska Marta , Zajko Weronika , Skowronek Krzysztof , Figiel Małgorzata , Krawczyk Paweł S , Egorov Artyom A , Dziembowski Andrzej , Johansson Marcus J O , Nowotny Marcin
Published: April 2024

Bacterial reverse transcriptases (RTs) are a large and diverse enzyme family. AbiA, AbiK and Abi-P2 are abortive infection system (Abi) RTs that mediate defense against bacteriophages. What sets Abi RTs apart from other RT enzymes is their ability to synthesize long DNA products of random sequences in a template- and primer-independent manner. Structures of AbiK and Abi-P2 representatives have recently been determined, but there are no structural data available for AbiA. Here, we report the crystal structure of Lactococcus AbiA polymerase in complex with a single-stranded polymerization product. AbiA comprises three domains: an RT-like domain, a helical domain that is typical for Abi polymerases, and a higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domain that is common for many antiviral proteins. AbiA forms a dimer that distinguishes it from AbiK and Abi-P2, which form trimers/hexamers. We show the DNA polymerase activity of AbiA in an in vitro assay and demonstrate that it requires the presence of the HEPN domain which is enzymatically inactive. We validate our biochemical and structural results in vivo through bacteriophage infection assays. Finally, our in vivo results suggest that AbiA-mediated phage defense may not rely on AbiA-mediated cell death.
ARID1A regulates DNA repair through chromatin organization and its deficiency triggers DNA damage-mediated anti-tumor immune response
Authors: Bakr Ali , Corte Giuditta Della , Veselinov Olivera , Kelekçi Simge , Chen Mei-Ju May , Lin Yu-Yu , Sigismondo Gianluca , Iacovone Marika , Cross Alice , Syed Rabail , Jeong Yunhee , Sollier Etienne , Liu Chun- Shan , Lutsik Pavlo , Krijgsveld Jeroen , Weichenhan Dieter , Plass Christoph , Popanda Odilia , Schmezer Peter
Published: April 2024

AT-rich interaction domain protein 1A (ARID1A), a SWI/SNF chromatin remodeling complex subunit, is frequently mutated across various cancer entities. Loss of ARID1A leads to DNA repair defects. Here, we show that ARID1A plays epigenetic roles to promote both DNA double-strand breaks (DSBs) repair pathways, non-homologous end-joining (NHEJ) and homologous recombination (HR). ARID1A is accumulated at DSBs after DNA damage and regulates chromatin loops formation by recruiting RAD21 and CTCF to DSBs. Simultaneously, ARID1A facilitates transcription silencing at DSBs in transcriptionally active chromatin by recruiting HDAC1 and RSF1 to control the distribution of activating histone marks, chromatin accessibility, and eviction of RNAPII. ARID1A depletion resulted in enhanced accumulation of micronuclei, activation of cGAS-STING pathway, and an increased expression of immunomodulatory cytokines upon ionizing radiation. Furthermore, low ARID1A expression in cancer patients receiving radiotherapy was associated with higher infiltration of several immune cells. The high mutation rate of ARID1A in various cancer types highlights its clinical relevance as a promising biomarker that correlates with the level of immune regulatory cytokines and estimates the levels of tumor-infiltrating immune cells, which can predict the response to the combination of radio- and immunotherapy.
DeepLoc 2.1: multi-label membrane protein type prediction using protein language models
Authors: Ødum Marius Thrane , Teufel Felix , Thumuluri Vineet , Almagro Armenteros José Juan , Johansen Alexander Rosenberg , Winther Ole , Nielsen Henrik
Published: April 2024

DeepLoc 2.0 is a popular web server for the prediction of protein subcellular localization and sorting signals. Here, we introduce DeepLoc 2.1, which additionally classifies the input proteins into the membrane protein types Transmembrane, Peripheral, Lipid-anchored and Soluble. Leveraging pre-trained transformer-based protein language models, the server utilizes a three-stage architecture for sequence-based, multi-label predictions. Comparative evaluations with other established tools on a test set of 4933 eukaryotic protein sequences, constructed following stringent homology partitioning, demonstrate state-of-the-art performance. Notably, DeepLoc 2.1 outperforms existing models, with the larger ProtT5 model exhibiting a marginal advantage over the ESM-1B model. The web server is available at https://services.healthtech.dtu.dk/services/DeepLoc-2.1.
Mutation rate heterogeneity at the sub-gene scale due to local DNA hypomethylation
Authors: Mas-Ponte David , Supek Fran
Published: April 2024

Local mutation rates in human are highly heterogeneous, with known variability at the scale of megabase-sized chromosomal domains, and, on the other extreme, at the scale of oligonucleotides. The intermediate, kilobase-scale heterogeneity in mutation risk is less well characterized. Here, by analyzing thousands of somatic genomes, we studied mutation risk gradients along gene bodies, representing a genomic scale spanning roughly 1–10 kb, hypothesizing that different mutational mechanisms are differently distributed across gene segments. The main heterogeneity concerns several kilobases at the transcription start site and further downstream into 5′ ends of gene bodies; these are commonly hypomutated with several mutational signatures, most prominently the ubiquitous C > T changes at CpG dinucleotides. The width and shape of this mutational coldspot at 5′ gene ends is variable across genes, and corresponds to variable interval of lowered DNA methylation depending on gene activity level and regulation. Such hypomutated loci, at 5′ gene ends or elsewhere, correspond to DNA hypomethylation that can associate with various landmarks, including intragenic enhancers, Polycomb-marked regions, or chromatin loop anchor points. Tissue-specific DNA hypomethylation begets tissue-specific local hypomutation. Of note, direction of mutation risk is inverted for AID/APOBEC3 cytosine deaminase activity, whose signatures are enriched in hypomethylated regions.
MetaboAnalyst 6.0: towards a unified platform for metabolomics data processing, analysis and interpretation
Authors: Pang Zhiqiang , Lu Yao , Zhou Guangyan , Hui Fiona , Xu Lei , Viau Charles , Spigelman Aliya F , MacDonald Patrick E , Wishart David S , Li Shuzhao , Xia Jianguo
Published: April 2024

We introduce MetaboAnalyst version 6.0 as a unified platform for processing, analyzing, and interpreting data from targeted as well as untargeted metabolomics studies using liquid chromatography - mass spectrometry (LC–MS). The two main objectives in developing version 6.0 are to support tandem MS (MS2) data processing and annotation, as well as to support the analysis of data from exposomics studies and related experiments. Key features of MetaboAnalyst 6.0 include: (i) a significantly enhanced Spectra Processing module with support for MS2 data and the asari algorithm; (ii) a MS2 Peak Annotation module based on comprehensive MS2 reference databases with fragment-level annotation; (iii) a new Statistical Analysis module dedicated for handling complex study design with multiple factors or phenotypic descriptors; (iv) a Causal Analysis module for estimating metabolite - phenotype causal relations based on two-sample Mendelian randomization, and (v) a Dose-Response Analysis module for benchmark dose calculations. In addition, we have also improved MetaboAnalyst's visualization functions, updated its compound database and metabolite sets, and significantly expanded its pathway analysis support to around 130 species. MetaboAnalyst 6.0 is freely available at https://www.metaboanalyst.ca.
Assembly of SARS-CoV-2 nucleocapsid protein with nucleic acid
Authors: Zhao Huaying , Syed Abdullah M , Khalid Mir M , Nguyen Ai , Ciling Alison , Wu Di , Yau Wai-Ming , Srinivasan Sanjana , Esposito Dominic , Doudna Jennifer A , Piszczek Grzegorz , Ott Melanie , Schuck Peter
Published: April 2024

The viral genome of SARS-CoV-2 is packaged by the nucleocapsid (N-)protein into ribonucleoprotein particles (RNPs), 38 ± 10 of which are contained in each virion. Their architecture has remained unclear due to the pleomorphism of RNPs, the high flexibility of N-protein intrinsically disordered regions, and highly multivalent interactions between viral RNA and N-protein binding sites in both N-terminal (NTD) and C-terminal domain (CTD). Here we explore critical interaction motifs of RNPs by applying a combination of biophysical techniques to ancestral and mutant proteins binding different nucleic acids in an in vitro assay for RNP formation, and by examining nucleocapsid protein variants in a viral assembly assay. We find that nucleic acid-bound N-protein dimers oligomerize via a recently described protein–protein interface presented by a transient helix in its long disordered linker region between NTD and CTD. The resulting hexameric complexes are stabilized by multivalent protein-nucleic acid interactions that establish crosslinks between dimeric subunits. Assemblies are stabilized by the dimeric CTD of N-protein offering more than one binding site for stem–loop RNA. Our study suggests a model for RNP assembly where N-protein scaffolding at high density on viral RNA is followed by cooperative multimerization through protein–protein interactions in the disordered linker.
RNAhugs web server for customized 3D RNA structure alignment
Authors: Zurkowski Michal , Swiercz Mateusz , Wozny Filip , Antczak Maciej , Szachniuk Marta
Published: April 2024

Alignment of 3D molecular structures involves overlaying their sets of atoms in space in such a way as to minimize the distance between the corresponding atoms. The purpose of this procedure is usually to analyze and assess structural similarity on a global (e.g. evaluating predicted 3D models and clustering structures) or a local level (e.g. searching for common substructures). Although the idea of alignment is simple, combinatorial algorithms that implement it require considerable computational resources, even when processing relatively small structures. In this paper, we introduce RNAhugs, a web server for custom and flexible alignment of 3D RNA structures. Using two efficient heuristics, GEOS and GENS, it finds the longest corresponding fragments within 3D structures that may differ in sizes—given in the PDB or PDBx/mmCIF formats—that manage to align with user-specified accuracy (i.e. with an RMSD not exceeding a cutoff value given as an input parameter). A distinctive advantage of the system lies in its ability to process multi-model files and compare the results of 1–25 alignments in a single task. RNAhugs has an intuitive interface and is publicly available at https://rnahugs.cs.put.poznan.pl/.
Analysis of Candy Tobacco Imitation Products Available Online in the United States
Authors: Bearman Dov S , Sheeran Tadhg J , Kowitt Sarah D , Clark Sonia A , Klein Jonathan D , Goldstein Adam O
Published: April 2024

Introduction

Youth tobacco use remains a critical public health concern, and childhood use of candy tobacco imitation products (CTIP) is associated with cigarette use among youth. However, no research has examined the full extent of CTIP available for purchase in the United States.

Aims and Methods

We conducted a content analysis of CTIP available on English-language, US-based websites. We identified sites that marketed CTIP utilizing Google and candy retail websites, examining each product for product names, the tobacco product being replicated (eg, cigar and cigarette), manufacturer, candy flavor, images, product rating, pack color, and if the product had packaging that may appeal to youth.

Results

We found 66 CTIP available. The most popular CTIP were cigars, with 39 separate products (59%), followed by candy cigarettes—14 products (21%), candy pipes—8 products (12%), and chewing tobacco—5 products (8%). In the 52 products where packaging design was available, 39 (75%) had packaging that may appeal to youth.

Conclusions

CTIP, many of which contain packaging appealing to youth, are widely available for purchase online across the United States. These findings could stimulate policy actions, such as removal of CTIP from popular retail websites, labeling of CTIP as potentially dangerous to youth, or age verification requirements for purchasing CTIP.

Implications

CTIP continues to be sold on the internet despite research indicating candy cigarette product use by youth increases their likelihood of smoking. We conducted research to understand the extent to which CTIP are sold on the internet and whether these products are being marketed to youth. The results provide evidence that some of the largest retail companies in the world continue to sell CTIP, and the majority are sold in packaging that likely appeals to youth. The results suggest that further research into the market for these products is needed, and regulatory measures should be considered to prevent CTIP from leading to youth tobacco use.
The Death and New Life of Law and Religion
Authors: De Girolami Marc O
Published: April 2024

The year 2023 was an end and a beginning. It saw the passing or retirement of many giants in the field of law and religion—scholars who brought their formidable erudition and insight to bear on questions that transcended legal doctrine, venturing upward into the heady realms of political theory, philosophy, history, sociology, and theology.

These and other recent departures from the active world of law and religion are an occasion to reflect on the state of the field. This article begins with a brief history of the field, highlighting the questions that motivated it to emerge in the 1970s and 1980s and the intellectual currents and legal developments against which it was reacting. It then argues that some of the central concerns and inquiries that occupied law and religion as a discrete field of academic study in what it calls the first wave heyday are now at an end. These include the nature of religion and the secular in the law, the division between these concepts, and the implications for law and religion as an independent academic discipline; the concept of state neutrality as to religion and the connected public–private divide as respects what is religious and what is non-religiously political; and the regime of religious exemption for everyone with a sincere objection to a law as the central feature of religious free exercise, in constitutional and statutory law.

This article argues that these are now, or will soon become, dead issues. Of course, they may well continue to be important for lawyers making and opposing claims in litigation, and for judges deciding among them, since the operative textual and doctrinal categories relevant to such claims will continue to depend on clever argumentation concerning some or all of them. And scholars will, no doubt, continue to wrangle over them. But to the extent that they continue to define the field or remain its signature issues, their growing irrelevance signals its death. Intellectual enterprises that survive over generations learn to adapt, and law and religion will need to do so as well. And, in fact, different issues, based on different premises and cultural circumstances, are beginning to emerge that may come to dominate the field and give it new life: the nature of political establishments and how they change; the use of ‘religion’ as a term for a category of political or ideological identity either to re-entrench or subvert political establishment; and the limits of what the so-called religious dissenters (who are now, and in large measure thanks to the first wave, indistinguishable from political or ideological dissenters) from the political establishment may reasonably expect in the way of accommodation from it. If the field is to survive, it will need to reorient itself towards new problems that afflict a very different world from the one in which it came into being.
Genome and clonal hematopoiesis stability contrasts with immune, cfDNA, mitochondrial, and telomere length changes during short duration spaceflight
Authors: Garcia-Medina J Sebastian , Sienkiewicz Karolina , Narayanan S Anand , Overbey Eliah G , Grigorev Kirill , Ryon Krista A , Burke Marissa , Proszynski Jacqueline , Tierney Braden , Schmidt Caleb M , Mencia-Trinchant Nuria , Klotz Remi , Ortiz Veronica , Foox Jonathan , Chin Christopher , Najjar Deena , Matei Irina , Chan Irenaeus , Cruchaga Carlos , Kleinman Ashley , Kim JangKeun , Lucaci Alexander , Loy Conor , Mzava Omary , De Vlaminck Iwijn , Singaraju Anvita , Taylor Lynn E , Schmidt Julian C , Schmidt Michael A , Blease Kelly , Moreno Juan , Boddicker Andrew , Zhao Junhua , Lajoie Bryan , Altomare Andrew , Kruglyak Semyon , Levy Shawn , Yu Min , Hassane Duane C , Bailey Susan M , Bolton Kelly , Mateus Jaime , Mason Christopher E
Published: April 2024

Background

The Inspiration4 (I4) mission, the first all-civilian orbital flight mission, investigated the physiological effects of short-duration spaceflight through a multi-omic approach. Despite advances, there remains much to learn about human adaptation to spaceflight's unique challenges, including microgravity, immune system perturbations, and radiation exposure.

Methods

To provide a detailed genetics analysis of the mission, we collected dried blood spots pre-, during, and post-flight for DNA extraction. Telomere length was measured by quantitative PCR, while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations. A robust bioinformatic pipeline was used for data analysis, including variant calling to assess mutational burden.

Result

Telomere elongation occurred during spaceflight and shortened after return to Earth. Cell-free DNA analysis revealed increased immune cell signatures post-flight. No significant clonal hematopoiesis of indeterminate potential (CHIP) or whole-genome instability was observed. The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight.

Conclusion

Our findings provide valuable insights into the physiological consequences of short-duration spaceflight, with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth. CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts, an understudied phenomenon as previous studies have focused on career astronauts. This study will serve as a reference point for future commercial and non-commercial spaceflight, low Earth orbit (LEO) missions, and deep-space exploration.
K
+
N Elastic Scatterings for Estimation of the In-Medium Quark Condensate with Strange Quarks
Authors: Iizawa Yutaro , Jido Daisuke , Hübsch Stephan
Published: April 2024

We revisit the low-energy K+N elastic scatterings in the context of the in-medium quark condensate with strange quarks. The chiral ward identity connects the in-medium quark condensate to the soft limit value of the pseudoscalar correlation function evaluated in nuclear matter. The in-medium correlation function of the pseudoscalar fields with strangeness describes in-medium kaon propagation and is obtained by kaon–nucleon scattering amplitudes in the low-density approximation. We construct the kaon–nucleon scattering amplitudes in chiral perturbation theory up to the next-to-leading order and add some terms of the next-to-next-to-leading order with the strange quark mass to improve expansion of the strange quark sector. We also consider the effect of a possible broad resonance state around Plab = 600 MeV/c for I = 0 reported in the previous study. The low-energy constants are determined by existing K+N scattering data. We obtain good reproduction of the K+p scattering amplitude by chiral perturbation theory, while the description of the KN amplitude with I = 0 is not so satisfactory due to the lack of low-energy data. Performing analytic continuation of the scattering amplitudes obtained by chiral perturbation theory to the soft limit, we estimate the in-medium strange quark condensate.
The Macroeconomics of Supply Chain Disruptions
Authors: Acemoglu Daron , Tahbaz-Salehi Alireza
Published: April 2024

This paper develops a model to study the macroeconomic implications of supply chain disruptions with three key ingredients: (i) a firm-level network of customized supplier–customer links that generate relationship-specific productivity gains; (ii) bargaining over these relationship-specific surpluses; and (iii) an extensive margin of adjustment, whereby firms decide to form or sever relations with suppliers and customers. We establish equilibrium existence and uniqueness, provide characterization results, and present a number of comparative statics that show how supply chains and aggregate output respond to shocks. We also show that equilibrium supply chains are inefficient and exhibit an inherent fragility: small shocks can lead to discontinuous changes in output, even though the efficient allocation is always continuous in the same shocks. We explore several macroeconomic implications of this fragility.
Hydroxychloroquine-induced pigmentation in rheumatic diseases: prevalence, clinical features and influencing factors
Authors: Yin Zi-Jing , Li Pin , Yu Juan , Zuo Dachen , Fan Hongtao , Li Fayou , Wang Juan , Gao Fei , Zhao Weiqin , Wang Shuya , Ma Sha , Wang Jing
Published: April 2024

Objective

To describe the clinical features of Chinese patients with HCQ-induced pigmentation and analyse the potential risk factors associated with HCQ-induced pigmentation.

Methods

A cross-sectional study was conducted over a duration of 7 months, during which patients who had received HCQ treatment for >6 months were included. Data was collected through a structured questionnaire that encompassed demographic and geographic characteristics, information on HCQ and concomitant medication usage, sun exposure characteristics and hyperpigmentation-related characteristics. Univariate and multivariate analyses were employed to calculate the statistical association between HCQ-induced pigmentation and multiple variables.

Results

Out of 316 patients, 83 (26.3%) patients presented hyperpigmentation during HCQ treatment. Hyperpigmentation was presented after a median duration of HCQ treatment of 12 months (interquartile range, 6.0–30.0 months) with a median cumulative dose of 108 g of HCQ (interquartile range, 36–288 g). The most frequently affected sites of pigmentation were the face (60.2%), lower limbs (36.1%) and hands (20.5%). There was a linear decrease in the incidence of pigmentation with increasing daily sun exposure time (P = 0.030). In the multivariate analysis, variables (cumulative HCQ dose and daily sun exposure time) were included in the final models. The results revealed an independent correlation between HCQ-induced pigmentation and daily sun exposure exceeding 1 h (OR: 0.431; 95% CI: 0.208–0.892; P = 0.023).

Conclusions

The occurrence of HCQ-induced pigmentation is not uncommon, with an incidence rate of 26.3%. Daily sun exposure time exhibited a protective effect against HCQ-induced pigmentation.
Human In Vitro Models of Neuroenergetics and Neurometabolic Disturbances: Current Advances and Clinical Perspectives
Authors: Rogal Julia , Zamproni Laura Nicoleti , Nikolakopoulou Polyxeni , Ygberg Sofia , Wedell Anna , Wredenberg Anna , Herland Anna
Published: April 2024

Neurological conditions conquer the world; they are the leading cause of disability and the second leading cause of death worldwide, and they appear all around the world in every age group, gender, nationality, and socioeconomic class. Despite the growing evidence of an immense impact of perturbations in neuroenergetics on overall brain function, only little is known about the underlying mechanisms. Especially human insights are sparse, owing to a shortage of physiologically relevant model systems. With this perspective, we aim to explore the key steps and considerations involved in developing an advanced human in vitro model for studying neuroenergetics. We discuss biological and technological strategies to meet the requirements of a predictive model, aiming at providing a guide and inspiration for future in vitro models of neuroenergetics.
Transcriptomic analysis reveals the anti-cancer effect of gestational mesenchymal stem cell secretome
Authors: Vaiasicca Salvatore , Melone Gianmarco , James David W , Quintela Marcos , Xiao Jing , Yao Seydou , Finnell Richard H , Conlan Robert S , Francis Lewis W , Corradetti Bruna
Published: April 2024

The environment created during embryogenesis contributes to reducing aberrations that drive structural malformations and tumorigenesis. In this study, we investigate the anti-cancer effect of mesenchymal stem cells (MSCs) derived from 2 different gestational tissues, the amniotic fluid (AF) and the chorionic villi (CV), with emphasis on their secretome. Transcriptomic analysis was performed on patient-derived AF- and CV-MSCs collected during prenatal diagnosis and identified both mRNAs and lncRNAs, involved in tissue homeostasis and inhibiting biological processes associated with the etiology of aggressive cancers while regulating immune pathways shown to be important in chronic disorders. Secretome enrichment analysis also identified soluble moieties involved in target cell regulation, tissue homeostasis, and cancer cell inhibition through the highlighted Wnt, TNF, and TGF-β signaling pathways. Transcriptomic data were experimentally confirmed through in vitro assays, by evaluating the anti-cancer effect of the media conditioned by AF- and CV-MSCs and the exosomes derived from them on ovarian cancer cells, revealing inhibitory effects in 2D (by reducing cell viability and inducing apoptosis) and in 3D conditions (by negatively interfering with spheroid formation). These data provide molecular insights into the potential role of gestational tissues-derived MSCs as source of anti-cancer factors, paving the way for the development of therapeutics to create a pro-regenerative environment for tissue restoration following injury, disease, or against degenerative disorders.
Cell-Cycle–Specific Autoencoding Improves Cluster Analysis of Cycling Cardiomyocytes
Authors: Nguyen Thanh , Nakada Yuji , Wu Yalin , Zhao Jianli , Garry Daniel J , Sadek Hesham , Zhang Jianyi
Published: April 2024

Background

Our previous analyses of cardiomyocyte single-nucleus RNA sequencing (snRNAseq) data from the hearts of fetal pigs and pigs that underwent apical resection surgery on postnatal day (P) 1 (ARP1), myocardial infarction (MI) surgery on P28 (MIP28), both ARP1 and MIP28 (ARP1MIP28), or controls (no surgical procedure or CTL) identified 10 cardiomyocyte subpopulations (clusters), one of which appeared to be primed to proliferate in response to MI. However, the clusters composed of primarily proliferating cardiomyocytes still contained noncycling cells, and we were unable to distinguish between cardiomyocytes in different phases of the cell cycle. Here, we improved the precision of our assessments by conducting similar analyses with snRNAseq data for only the 1646 genes included under the Gene Ontology term “cell cycle.”

Methods

Two cardiac snRNAseq datasets, one from mice (GEO dataset number GSE130699) and one from pigs (GEO dataset number GSE185289), were evaluated via our cell-cycle–specific analytical pipeline. Cycling cells were identified via the co-expression of 5 proliferation markers (AURKB, MKI67, INCENP, CDCA8, and BIRC5).

Results

The cell-cycle–specific autoencoder (CSA) algorithm identified 7 cardiomyocyte clusters in mouse hearts (mCM1 and mCM3-mCM8), including one prominent cluster of cycling cardiomyocytes in animals that underwent MI or Sham surgery on P1. Five cardiomyocyte clusters (pCM1, pCM3-pCM6) were identified in pig hearts, 2 of which (pCM1 and pCM4) displayed evidence of cell cycle activity; pCM4 was found primarily in hearts from fetal pigs, while pCM1 comprised a small proportion of cardiomyocytes in both fetal hearts and hearts from ARP1MIP28 pigs during the 2 weeks after MI induction, but was nearly undetectable in all other experimental groups and at all other time points. Furthermore, pseudotime trajectory analysis of snRNAseq data from fetal pig cardiomyocytes identified a pathway that began at pCM3, passed through pCM2, and ended at pCM1, whereas pCM3 was enriched for the expression of a cell cycle activator that regulates the G1/S phase transition (cyclin D2), pCM2 was enriched for an S-phase regulator (CCNE2), and pCM1 was enriched for the expression of a gene that regulates the G2M phase transition and mitosis (cyclin B2). We also identified 4 transcription factors (E2F8, FOXM1, GLI3, and RAD51) that were more abundantly expressed in cardiomyocytes from regenerative mouse hearts than from nonregenerative mouse hearts, from the hearts of fetal pigs than from CTL pig hearts, and from ARP1MIP28 pig hearts than from MIP28 pig hearts during the 2 weeks after MI induction.

Conclusions

The CSA algorithm improved the precision of our assessments of cell cycle activity in cardiomyocyte subpopulations and enabled us to identify a trajectory across 3 clusters that appeared to track the onset and progression of cell cycle activity in cardiomyocytes from fetal pigs.
Determination of gas flux and animal performance test duration of growing cattle in confined conditions
Authors: Vargas Juan de J , Swenson Maya , Place Sara E
Published: April 2024

Data from three experiments was analyzed to determine the number of visits and days to assess gas flux (CH4, CO2, and O2), dry matter intake (DMI), and average daily gain (ADG) from growing animals under confined conditions. In experiment 1, 213 animals (461 ± 91 kg initial body weight [BW]) were fed a backgrounding diet and evaluated for 60 d. In experiment 2, 169 steers (488 ± 37 kg initial BW) were fed a finishing diet and assessed for 70 d. In experiment 3, 64 steers (514 ± 42 kg initial BW) were fed a finishing diet and evaluated for 80 d. In each experiment, animals were placed in one pen with one Greenfeed and five SmartFeeds to collect gas flux and feed intake simultaneously. Gas flux was analyzed using data from 161 animals from the three experiments with 100 visits for 2 or more min or 3 or more min. Also, metabolic heat production (MHP) was estimated using the individual gas flux. Daily DMI was calculated as the daily feed intake corrected by the dry matter concentration. ADG was computed as the slope of the regression of the shrunk BW (96% BW) throughout each of the experimental periods. The mean gas flux and MHP were estimated for increasing or decreasing 5-visit intervals starting with the first or the last 5 visits and increasing or decreasing until the full 100-visit dataset was utilized, respectively. Intervals of DMI were estimated for increasing or decreasing 5-d intervals starting with the first or the last 5 d and increasing or decreasing until the end of the experimental period, respectively. Intervals of ADG were estimated for increasing or decreasing measurement period intervals until the end of the experimental period, respectively. Pearson and Spearman correlations were computed between the maximum visits or days and each shortened visit or day interval. The minimum number of visits and days was determined when correlations with the total visits were greater than 0.95. The results indicated that the minimum number of visits needed to quantify CO2, O2, and MHP accurately was 40, while CH4 was 60. A visitation length of 2 min or more or 3 min or more did not modify the gas flux determination. Thus, based on the average daily visitation in these experiments, gas flux data could be collected for 25 d. Additionally, the required days to determine DMI was 30, while ADG could not be assessed in a shorter than 60-d period.
An investigation of business calculus students’ covariational reasoning, procedural knowledge and conceptual knowledge in the context of price elasticity of demand
Authors: Mkhatshwa Thembinkosi P
Published: April 2024

Motivated by the paucity of research that has examined students’ covariational reasoning in economic contexts, the study reported in this article investigated business calculus students’ covariational reasoning about the economic concept of price elasticity of demand. Furthermore, the study examined students’ procedural knowledge and conceptual knowledge in the context of explaining what it means for demand to be inelastic, elastic or unit elastic, respectively. Additionally, the study examined students’ calculational knowledge of price elasticity of demand. The analysis of 10 students’ responses to three tasks used in the study revealed that most of the students struggled making sense of what it means for demand to be inelastic, elastic or unit elastic, respectively. A majority of the students only engaged at the lowest levels of covariational reasoning when prompted to reason about the relationship between the concept of price elasticity of demand and its relationship to the economic quantities of price, demand and revenue. Furthermore, showing that maximum revenue occurs when price elasticity of demand is equal to one was particularly challenging for all the students. Overall, findings from this study suggest that the study participants demonstrated a weak understanding of the concept of price elasticity of demand. Directions for future research and implications for instruction are included.
Impacts of Extreme Weather Events on Education Outcomes: A Review of Evidence
Authors: Venegas Marin Sergio , Schwarz Lara , Sabarwal Shwetlena
Published: April 2024

Extreme weather events are increasingly disrupting schooling. Yet, these are underrepresented in the climate change literature. Of 15 review articles on the economic impacts of climate change published since 2010, only three mention the impacts of climate change on education. We review available literature on the effects of weather extremes on education. We outline key pathways through which these events impact education outcomes, as well as the magnitude of those impacts. Evidence implies a significant and adverse relationship between heat and learning. Studies suggest surpassing a high temperature threshold makes learning difficult and results in learning losses. Across studies, each additional day subject to extreme heat reduces learning. Tropical cyclones, floods, and wildfires precipitate school closures, which halt learning. Evidence suggests that one day of school closures leads to one day of learning lost. Weather extremes also negatively impact education outcomes through health, nutrition, poverty, and fragility, among other distal pathways. We discuss the implications of this evidence for policy, including the need to adapt education systems to climate change. Mitigation and adaptation are both urgently needed as extreme weather events become more frequent and severe in the context of climate change.
Putting ‘X’ into Context: The Diversity of ‘Candidatus Phytoplasma pruni’ Strains Associated with the Induction of X-Disease
Authors: Molnar Cody , Shires Madalyn K. , Wright Alice Ann , Hoskins Mason C. , Cowell Sarah J. , Nikolaeva Ekaterina V. , Knier Rachel , Nouri Mohamed Taieb , Black Brent , Harper Scott J.
Published: April 2024

Recurrent epiphytotics of X-disease, caused by ‘Candidatus Phytoplasma pruni,’ have inflicted significant losses on commercial cherry and peach production across North America in the last century. During this period, there have been multiple studies reporting different disease phenotypes and, more recently, identifying different strains through sequencing core genes, but the symptoms have not, to date, been linked with genotype. Therefore, in this study we collected and assessed differing disease phenotypes from multiple U.S. states and conducted multilocus sequence analysis on these strains. We identified a total of five lineages associated with the induction of X-disease on commercial Prunus species and two lineages that were associated with wild P. virginiana. Despite a century of interstate plant movement, there were regional trends in terms of lineages present, and lineage-specific symptoms were observed on P. avium, P. cerasus, and P. virginiana, but not on P. persica. Cumulatively, these data have allowed us to define “true” X-disease–inducing strains of concern to the stone fruit industry across North America, as well as potential sources of infection that exist in the extraorchard environment.
Genetic Diversity and Pathogenicity Characterization of Tomato-Infecting Begomoviruses in Taiwan
Authors: Lai Hsuan-Chun , Neoh Zhuan Yi , Tsai Wen-Shi
Published: April 2024

The tomato yellow leaf curl disease (TYLCD) caused by whitefly (Bemisia tabaci)-transmitted begomoviruses (Geminiviridae) has constrained tomato production in Taiwan since 1981. Lisianthus enation leaf curl virus (LELCV), tomato leaf curl Taiwan virus (ToLCTV), and tomato yellow leaf curl Thailand virus (TYLCTHV) were the major viruses associated with TYLCD. In 2019 to 2020, we investigated TYLCD throughout Taiwan, with a 10 to 100% incidence on tomato fields. Begomovirus sequences were detected in 321 out of 506 collected samples by PCR with primers PAL1v1978B and PAR1c715H. In 2015 to 2016, 59 out of 99 samples collected in Hualien-Taitung areas were also found to have begomovirus sequences. Based on the analysis of 68 viral genomic sequences, six begomoviruses were identified, including LELCV, ToLCTV, TYLCTHV, tomato leaf curl Hsinchu virus, and two new begomoviruses, tentatively named tomato leaf curl Chiayi virus (ToLCCYV) and tomato leaf curl Nantou virus (ToLCNTV). Various isolates of LELCV and TYLCTHV were grouped into four and two strains, respectively. Recombinants were detected in LELCV-A, -C, and -D, ToLCCYV, ToLCNTV, and TYLCTHV-F. Based on virus-specific detection, the majority of TYLCD-associated viruses were mixed-infected by TYLCTHV-B with TYLCTHV-F, LELCV-A, -B, or -D, and/or ToLCTV. Meanwhile, viral DNA-B was mostly associated with TYLCTHV, and all identified DNA-Bs were highly homologous with previous TYLCTHV DNA-B. The pathogenicity of selected begomoviruses was confirmed through agroinfection and whitefly transmission. All tomato plants carrying Ty-1/3 and Ty-2 resistant genes were infected by all LELCV strains and ToLCCYV, although they appeared symptomless, suggesting these viruses could be managed through the use of the resistance pyramid.
Novel Approach to Difficult Spinal Reconstruction: Bilateral Simultaneous Rib and Iliac Crest Vascularized Bone Graft Spinoplastic Surgery
Authors: Shvedova Maria , Abdulwadood Isra , Vernik Daniel M. , Shrout Max A. , Jeger Jonathan L. , Buchanan Dylon C. , Ropper Alexander , Winocour Sebastian , Bohl Michael , Kalani Maziyar A. , Reece Edward M.
Published: April 2024

Pseudoarthrosis is a severe complication of spinal fusion surgery with occurrence rates as high as 35%–40%. Current options of revision surgery to correct pseudoarthrosis frequently carry high failure rates and risk of developing junctional kyphosis. Pedicled vascularized bone grafts (VBGs) are an innovative approach to boost spinal fusion rates via improving structural integrity and increasing the delivery of blood to the donor site. This versatile technique can be performed at different spinal levels without additional skin incisions and with minimal added operative time. Here we present the first bilateral rib and iliac crest VBG spinoplastic surgery performed to augment spinal fusion in a 68-year-old woman with distal junctional kyphosis and severe positive sagittal balance with low back and neck pain and significant difficulty standing upright. The patient had history of multiple spinal operations with preoperative CT imaging demonstrating loosening and pull out of L3 and fracture of L2 screws. She underwent two-stage surgical treatment involving anterior lumbar interbody fusion L3-S1 followed by removal of hardware, T4 to pelvis fusion with L2-3 prone lateral interbody fusion, and T11-S1 posterior column osteotomies. The surgery was augmented by bilateral rib and iliac crest VBGs performed by plastic surgery. At three-month follow-up the patient demonstrated functional improvement, being able to maintain upright posture and walk; was satisfied with the result of the surgery; and demonstrated no graft-related complications. In conclusion, utilization of pedicled VBGs is a novel, promising approach to augment spinal surgery in high risk patients.
Aesthetic Mandibular Angloplasty to Improve Patient Quality of Life in Chronic Recurrent Multifocal Osteomyelitis
Authors: Park Yun Yong , Park Bumjin
Published: April 2024

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoimmune disease that typically develops during adolescence and primarily affects women. CRMO primarily targets the bone in arms and legs, with sporadic occurrences in the mandible. CRMO is typically managed with medical treatment, and the efficacy of surgery remains controversial. Complications of surgery include massive bleeding and potential flare-up of CRMO symptoms. Herein, we report a patient with CRMO who had lesions in the bilateral rami of the mandible treated with aesthetic mandibular angloplasty. This is the first case of aesthetic mandibular angloplasty in a patient with CRMO who had bilateral rami involvement of the mandible. The patient began experiencing jaw pain accompanied by swelling and throbbing discomfort beneath the jawline at the age of 10. A pediatrician diagnosed CRMO, and the symptoms were controlled with nonsteroidal antiinflammatory drugs and immunosuppressants (infliximab, adalimumab). Aesthetic mandibular angloplasty was performed at our center because of mandibular hypertrophy. This procedure necessitated considerable removal of the spongy bone, raising concerns about potential massive intraoperative bleeding. Approximately 1.5 cm of the mandibular body was excised to reveal the cortical bone. Bleeding during surgery was not severe, rendering blood transfusions unnecessary. The patient was satisfied with the surgical results. This case indicates the feasibility of angloplasty for such cases.