bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tracking of progressing human DNA polymerase δ holoenzymes reveals distributions of DNA lesion bypass activities
Authors: Dannenberg Rachel L , Cardina Joseph A , Pytko Kara G , Hedglin Mark 
Published: September 2022

Abstract
During DNA replication, DNA lesions in lagging strand templates are initially encountered by DNA polymerase δ (pol δ) holoenzymes comprised of pol δ and the PCNA processivity sliding clamp. These encounters are thought to stall replication of an afflicted template before the lesion, activating DNA damage tolerance (DDT) pathways that replicate the lesion and adjacent DNA sequence, allowing pol δ to resume. However, qualitative studies observed that human pol δ can replicate various DNA lesions, albeit with unknown proficiencies, which raises issues regarding the role of DDT in replicating DNA lesions. To address these issues, we re-constituted human lagging strand replication to quantitatively characterize initial encounters of pol δ holoenzymes with DNA lesions. The results indicate pol δ holoenzymes support dNTP incorporation opposite and beyond multiple lesions and the extent of these activities depends on the lesion and pol δ proofreading. Furthermore, after encountering a given DNA lesion, subsequent dissociation of pol δ is distributed around the lesion and a portion does not dissociate. The distributions of these events are dependent on the lesion and pol δ proofreading. Collectively, these results reveal complexity and heterogeneity in the replication of lagging strand DNA lesions, significantly advancing our understanding of human DDT.
Plant mitochondrial RNA editing factors can perform targeted C-to-U editing of nuclear transcripts in human cells
Authors: Lesch Elena , Schilling Maximilian T , Brenner Sarah , Yang Yingying , Gruss Oliver J , Knoop Volker , Schallenberg-Rüdinger Mareike 
Published: September 2022

Abstract
RNA editing processes are strikingly different in animals and plants. Up to thousands of specific cytidines are converted into uridines in plant chloroplasts and mitochondria whereas up to millions of adenosines are converted into inosines in animal nucleo-cytosolic RNAs. It is unknown whether these two different RNA editing machineries are mutually incompatible. RNA-binding pentatricopeptide repeat (PPR) proteins are the key factors of plant organelle cytidine-to-uridine RNA editing. The complete absence of PPR mediated editing of cytosolic RNAs might be due to a yet unknown barrier that prevents its activity in the cytosol. Here, we transferred two plant mitochondrial PPR-type editing factors into human cell lines to explore whether they could operate in the nucleo-cytosolic environment. PPR56 and PPR65 not only faithfully edited their native, co-transcribed targets but also different sets of off-targets in the human background transcriptome. More than 900 of such off-targets with editing efficiencies up to 91%, largely explained by known PPR-RNA binding properties, were identified for PPR56. Engineering two crucial amino acid positions in its PPR array led to predictable shifts in target recognition. We conclude that plant PPR editing factors can operate in the entirely different genetic environment of the human nucleo-cytosol and can be intentionally re-engineered towards new targets.
Widespread autogenous mRNA–protein interactions detected by CLIP-seq
Authors: Kapral Thomas H , Farnhammer Fiona , Zhao Weihao , Lu Zhi J , Zagrovic Bojan 
Published: September 2022

Abstract
Autogenous interactions between mRNAs and the proteins they encode are implicated in cellular feedback-loop regulation, but their extent and mechanistic foundation are unclear. It was recently hypothesized that such interactions may be common, reflecting the role of intrinsic nucleobase–amino acid affinities in shaping the genetic code's structure. Here we analyze a comprehensive set of CLIP-seq experiments involving multiple protocols and report on widespread autogenous interactions across different organisms. Specifically, 230 of 341 (67%) studied RNA-binding proteins (RBPs) interact with their own mRNAs, with a heavy enrichment among high-confidence hits and a preference for coding sequence binding. We account for different confounding variables, including physical (overexpression and proximity during translation), methodological (difference in CLIP protocols, peak callers and cell types) and statistical (treatment of null backgrounds). In particular, we demonstrate a high statistical significance of autogenous interactions by sampling null distributions of fixed-margin interaction matrices. Furthermore, we study the dependence of autogenous binding on the presence of RNA-binding motifs and structured domains in RBPs. Finally, we show that intrinsic nucleobase–amino acid affinities favor co-aligned binding between mRNA coding regions and the proteins they encode. Our results suggest a central role for autogenous interactions in RBP regulation and support the possibility of a fundamental connection between coding and binding.
Human Thg1 displays tRNA-inducible GTPase activity
Authors: Antika Titi Rindi , Nazilah Kun Rohmatan , Lee Yi-Hsueh , Lo Ya-Ting , Yeh Chung-Shu , Yeh Fu-Lung , Chang Tien-Hsien , Wang Tzu-Ling , Wang Chien-Chia 
Published: September 2022

Abstract
tRNAHis guanylyltransferase (Thg1) catalyzes the 3′-5′ incorporation of guanosine into position -1 (G-1) of tRNAHis. G-1 is unique to tRNAHis and is crucial for recognition by histidyl-tRNA synthetase (HisRS). Yeast Thg1 requires ATP for G-1 addition to tRNAHis opposite A73, whereas archaeal Thg1 requires either ATP or GTP for G-1 addition to tRNAHis opposite C73. Paradoxically, human Thg1 (HsThg1) can add G-1 to tRNAsHis with A73 (cytoplasmic) and C73 (mitochondrial). As N73 is immediately followed by a CCA end (positions 74–76), how HsThg1 prevents successive 3′-5′ incorporation of G-1/G-2/G-3 into mitochondrial tRNAHis (tRNAmHis) through a template-dependent mechanism remains a puzzle. We showed herein that mature native human tRNAmHis indeed contains only G-1. ATP was absolutely required for G-1 addition to tRNAmHis by HsThg1. Although HsThg1 could incorporate more than one GTP into tRNAmHisin vitro, a single-GTP incorporation prevailed when the relative GTP level was low. Surprisingly, HsThg1 possessed a tRNA-inducible GTPase activity, which could be inhibited by ATP. Similar activity was found in other high-eukaryotic dual-functional Thg1 enzymes, but not in yeast Thg1. This study suggests that HsThg1 may downregulate the level of GTP through its GTPase activity to prevent multiple-GTP incorporation into tRNAmHis.
EventPointer 3.0: flexible and accurate splicing analysis that includes studying the differential usage of protein-domains
Authors: Ferrer-Bonsoms Juan A , Gimeno Marian , Olaverri Danel , Sacristan Pablo , Lobato César , Castilla Carlos , Carazo Fernando , Rubio Angel 
Published: September 2022

Abstract
Alternative splicing (AS) plays a key role in cancer: all its hallmarks have been associated with different mechanisms of abnormal AS. The improvement of the human transcriptome annotation and the availability of fast and accurate software to estimate isoform concentrations has boosted the analysis of transcriptome profiling from RNA-seq. The statistical analysis of AS is a challenging problem not yet fully solved. We have included in EventPointer (EP), a Bioconductor package, a novel statistical method that can use the bootstrap of the pseudoaligners. We compared it with other state-of-the-art algorithms to analyze AS. Its performance is outstanding for shallow sequencing conditions. The statistical framework is very flexible since it is based on design and contrast matrices. EP now includes a convenient tool to find the primers to validate the discoveries using PCR. We also added a statistical module to study alteration in protein domain related to AS. Applying it to 9514 patients from TCGA and TARGET in 19 different tumor types resulted in two conclusions: i) aberrant alternative splicing alters the relative presence of Protein domains and, ii) the number of enriched domains is strongly correlated with the age of the patients.
SPROUT: spectral sparsification helps restore the spatial structure at single-cell resolution
Authors: Wang Jingwan , Li Shiying , Chen Lingxi , Li Shuai Cheng 
Published: September 2022

AbstractSingle-cell RNA sequencing thoroughly quantifies the individual cell transcriptomes but renounces the spatial structure. Conversely, recently emerged spatial transcriptomics technologies capture the cellular spatial structure but skimp cell or gene resolutions. Ligand-receptor interactions reveal the potential of cell proximity since they are spatially constrained. Cell–cell affinity values estimated by ligand–receptor interaction can partially represent the structure of cells but falsely include the pseudo affinities between distant or indirectly interacting cells. Here, we develop a software package, SPROUT, to reconstruct the single-cell resolution spatial structure from the transcriptomics data through diminished pseudo ligand–receptor affinities. For spatial data, SPROUT first curates the representative single-cell profiles for each spatial spot from a candidate library, then reduces the pseudo affinities in the intercellular affinity matrix by partial correlation, spectral graph sparsification, and spatial coordinates refinement. SPROUT embeds the estimated interactions into a low-dimensional space with the cross-entropy objective to restore the intercellular structures, which facilitates the discovery of dominant ligand–receptor pairs between neighboring cells at single-cell resolution. SPROUT reconstructed structures achieved shape Pearson correlations ranging from 0.91 to 0.97 on the mouse hippocampus and human organ tumor microenvironment datasets. Furthermore, SPROUT can solely de novo reconstruct the structures at single-cell resolution, i.e., reaching the cell-type proximity correlations of 0.68 and 0.89 between reconstructed and immunohistochemistry-informed spatial structures on a human developing heart dataset and a tumor microenvironment dataset, respectively.
Computational identification of signals predictive for nuclear RNA exosome degradation pathway targeting
Authors: Wu Mengjun , Schmid Manfred , Jensen Torben Heick , Sandelin Albin 
Published: September 2022

Abstract
The RNA exosome degrades transcripts in the nucleoplasm of mammalian cells. Its substrate specificity is mediated by two adaptors: the ‘nuclear exosome targeting (NEXT)’ complex and the ‘poly(A) exosome targeting (PAXT)’ connection. Previous studies have revealed some DNA/RNA elements that differ between the two pathways, but how informative these features are for distinguishing pathway targeting, or whether additional genomic features that are informative for such classifications exist, is unknown. Here, we leverage the wealth of available genomic data and develop machine learning models that predict exosome targets and subsequently rank the features the models use by their predictive power. As expected, features around transcript end sites were most predictive; specifically, the lack of canonical 3′ end processing was highly predictive of NEXT targets. Other associated features, such as promoter-proximal G/C content and 5′ splice sites, were informative, but only for distinguishing NEXT and not PAXT targets. Finally, we discovered predictive features not previously associated with exosome targeting, in particular RNA helicase DDX3X binding sites. Overall, our results demonstrate that nucleoplasmic exosome targeting is to a large degree predictable, and our approach can assess the predictive power of previously known and new features in an unbiased way.
Harmonizing Surveillance Methodologies for Group A Streptococcal Diseases
Authors: Moore Hannah C , Miller Kate M , Carapetis Jonathan R , Van Beneden Chris A 
Published: September 2022

Abstract
Group A Streptococcus (Strep A) is responsible for a significant global health and economic burden. The recent prioritization of Strep A vaccine development by the World Health Organization has prompted global research activities and collaborations. To progress this prioritization, establishment of robust surveillance for Strep A to generate updated regional disease burden estimates and to establish platforms for future impact evaluation is essential. Through the activities of the Strep A Vaccine Global Consortium (SAVAC), we have refined and harmonized surveillance protocols for 7 Strep A disease endpoints with a view that these will form part of surveillance standards for ongoing research and public health activities.
Standardization of Epidemiological Surveillance of Acute Rheumatic Fever
Authors: Scheel Amy , Beaton Andrea Z , Katzenellenbogen Judith , Parks Tom , Miller Kate M , Cherian Thomas , Van Beneden Chris A , Cannon Jeffrey W , Moore Hannah C , Bowen Asha C , Carapetis Jonathan R 
Published: September 2022

Abstract
Acute rheumatic fever (ARF) is a multiorgan inflammatory disorder that results from the body’s autoimmune response to pharyngitis or a skin infection caused by Streptococcus pyogenes (Strep A). Acute rheumatic fever mainly affects those in low- and middle-income nations, as well as in indigenous populations in wealthy nations, where initial Strep A infections may go undetected. A single episode of ARF puts a person at increased risk of developing long-term cardiac damage known as rheumatic heart disease. We present case definitions for both definite and possible ARF, including initial and recurrent episodes, according to the 2015 Jones Criteria, and we discuss current tests available to aid in the diagnosis.
We outline the considerations specific to ARF surveillance methodology, including discussion on where and how to conduct active or passive surveillance (eg, early childhood centers/schools, households, primary healthcare, administrative database review), participant eligibility, and the surveillance population. Additional considerations for ARF surveillance, including implications for secondary prophylaxis and follow-up, ARF registers, community engagement, and the impact of surveillance, are addressed. Finally, the core elements of case report forms for ARF, monitoring and audit requirements, quality control and assurance, and the ethics of conducting surveillance are discussed.
Standardization of Epidemiological Surveillance of Group A Streptococcal Cellulitis
Authors: Miller Kate M , Lamagni Theresa , Hay Roderick , Cannon Jeffrey W , Marks Michael , Bowen Asha C , Kaslow David C , Cherian Thomas , Seale Anna C , Pickering Janessa , Daw Jessica N , Moore Hannah C , Van Beneden Chris , Carapetis Jonathan R , Manning Laurens 
Published: September 2022

Abstract
Cellulitis is an acute bacterial infection of the dermis and subcutaneous tissue usually found complicating a wound, ulcer, or dermatosis. This article provides guidelines for the surveillance of cellulitis. The primary objectives of cellulitis surveillance are to (1) monitor trends in rates of infection, (2) describe the demographic and clinical characteristics of patients with cellulitis, (3) estimate the frequency of complications, and (4) describe the risk factors associated with primary and recurrent cellulitis. This article includes case definitions for clinical cellulitis and group A streptococcal cellulitis, based on clinical and laboratory evidence, and case classifications for an initial and recurrent case. It is expected that surveillance for cellulitis will be for all-cause cellulitis, rather than specifically for Strep A cellulitis. Considerations of the type of surveillance are also presented, including identification of data sources and surveillance type. Minimal surveillance necessary for cellulitis is facility-based, passive surveillance. Prospective, active, facility-based surveillance is recommended for estimates of pathogen-specific cellulitis burden. Participant eligibility, surveillance population, and additional surveillance considerations such as active follow-up of cases, the use of International Classification of Disease diagnosis codes, and microbiological sampling of cases are discussed. Finally, the core data elements to be collected on case report forms are presented.
Standardization of Epidemiological Surveillance of Invasive Group A Streptococcal Infections
Authors: Miller Kate M , Lamagni Theresa , Cherian Thomas , Cannon Jeffrey W , Parks Tom , Adegbola Richard A , Pickering Janessa , Barnett Tim , Engel Mark E , Manning Laurens , Bowen Asha C , Carapetis Jonathan R , Moore Hannah C , Barth Dylan D , Kaslow David C , Van Beneden Chris A 
Published: September 2022

Abstract
Invasive group A streptococcal (Strep A) infections occur when Streptococcus pyogenes, also known as beta-hemolytic group A Streptococcus, invades a normally sterile site in the body. This article provides guidelines for establishing surveillance for invasive Strep A infections. The primary objective of invasive Strep A surveillance is to monitor trends in rates of infection and determine the demographic and clinical characteristics of patients with laboratory-confirmed invasive Strep A infection, the age- and sex-specific incidence in the population of a defined geographic area, trends in risk factors, and the mortality rates and rates of nonfatal sequelae caused by invasive Strep A infections.
This article includes clinical descriptions followed by case definitions, based on clinical and laboratory evidence, and case classifications (confirmed or probable, if applicable) for invasive Strep A infections and for 3 Strep A syndromes: streptococcal toxic shock syndrome, necrotizing fasciitis, and pregnancy-associated Strep A infection.
Considerations of the type of surveillance are also presented, noting that most people who have invasive Strep A infections will present to hospital and that invasive Strep A is a notifiable disease in some countries. Minimal surveillance necessary for invasive Strep A infection is facility-based, passive surveillance. A resource-intensive but more informative approach is active case finding of laboratory-confirmed Strep A invasive infections among a large (eg, state-wide) and well defined population.
Participant eligibility, surveillance population, and additional surveillance components such as the use of International Classification of Disease diagnosis codes, follow-up, period of surveillance, seasonality, and sample size are discussed. Finally, the core data elements to be collected on case report forms are presented.
Polymicrobial Foot Infection Patterns Are Common and Associated With Treatment Failure
Authors: Barshes Neal R , Clark Nicholas J , Bidare Deeksha , Dudenhoeffer J H , Mindru Cezarina , Rodriguez-Barradas Maria C 
Published: September 2022

Abstract

Background
That foot infections are predominately polymicrobial has long been recognized, but it is not clear if the various species co-occur randomly or in patterns. We sought nonrandom species co-occurrence patterns that might help better predict prognosis or guide antimicrobial selection.

Methods
We analyzed tissue (bone, skin, and other soft tissue), fluid, and swab specimens collected from initial foot infection episodes during a 10-year period using a hospital registry. Nonrandom co-occurrence of microbial species was identified using simple pairwise co-occurrence rates adjusted for multiple comparisons, Markov and conditional random fields, and factor analysis. A historical cohort was used to validate pattern occurrence and identify clinical significance.

Results
In total, 156 unique species were identified among the 727 specimens obtained from initial foot infection episodes in 694 patients. Multiple analyses suggested that Staphylococcus aureus is negatively associated with other staphylococci. Another pattern noted was the co-occurrence of alpha-hemolytic Streptococcus, Enterococcus fecalis, Klebsiella, Proteus, Enterobacter, or Escherichia coli, and absence of both Bacteroides and Corynebacterium. Patients in a historical cohort with this latter pattern had significantly higher risk-adjusted rates of treatment failure.

Conclusions
Several nonrandom microbial co-occurrence patterns are frequently seen in foot infection specimens. One particular pattern with many Proteobacteria species may denote a higher risk for treatment failure. Staphylococcus aureus rarely co-occurs with other staphylococci.
Improving refugee resettlement: insights from market design
Authors: Hadad Justin , Teytelboym Alexander 
Published: September 2022

AbstractThe current refugee resettlement system is inefficient because there are too few resettlement places and because refugees are resettled to locations where they might not thrive. We outline how ideas from market design can lead to better resettlement practices. In particular, we discuss how market design can incentivize participation of countries in resettlement and improve the matching of refugees at international and local levels; some of these insights have already put into practice. Finally, we highlight several further applications of market design in refugee resettlement, including cardinal preference submission and matching with transfers.
Born Again but Not Evangelical?
Authors: Margolis Michele F 
Published: September 2022

AbstractPublic opinion research often identifies evangelical Christians based on a double-barreled, yes-or-no, question asking respondents whether they are an evangelical or born-again Christian. This paper uses a survey experiment to demonstrate the implications of this measurement strategy. Among White Americans, more than one-third of those whom researchers classify as evangelical using the standard double-barreled question actually eschew the evangelical label; the same is true for just under two-thirds of African Americans. Additionally, these born-again non-evangelical Christians hold less conservative political outlooks compared to the self-identified evangelicals with whom they are grouped, and, in fact, oftentimes more closely resemble those who reject both the evangelical and born-again labels. Despite this, the double-barreled identification question produces a White “evangelical or born-again” group that looks politically similar to a composite “evangelical” or “born-again” group based on two questions asking about each identity separately. Finally, important differences appear across race, suggesting that religious and political histories affect how people interpret and respond to double-barreled questions.