bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applying a Reproductive Justice Lens to Enhance Research Engagement Among Systematically Underrepresented Childbearing Women
Authors: McGlothen-Bell Kelly , McGrath Jacqueline M. , Brownell Elizabeth A. , Shlafer Rebecca J. , Crawford Allison D. 
Published: December 2022

BackgroundHistorically, childbearing women from diverse and systematically hard-to-reach populations have been excluded from nursing research. This practice limits the generalizability of findings. Maximizing research strategies to meet the unique needs of these populations must be a priority.ObjectivesThe aim of this study was to provide methodological context for the comprehensive application of reproductive justice strategies to guide research methods and promote engagement of underrepresented childbearing women while decreasing systemic bias.MethodsIn this article, we use a reproductive justice lens to characterize and define strategies for enhancing ethical and equitable engagement in research involving childbearing women who are often systematically underrepresented using a case study approach. Using a specific case study exemplar, the core tenets of reproductive justice are outlined and affirm the need to advance research strategies that create ethical engagement of diverse populations, transform oppressive social structures, and shift research paradigms so research objectives intentionally highlight the strengths and resiliency inherent to the targeted communities.ResultsWe begin by describing parallels between the tenets of reproductive justice and the ethical principles of research (i.e., respect for persons, beneficence, and justice). We then apply these tenets to conceptualization, implementation (recruitment, data management, and retention), and dissemination of research conducted with childbearing women from diverse backgrounds who are systemically underrepresented. We highlight our successful research strategies from our case study example of women with histories of incarceration.DiscussionTo date, outcomes from our research indicate the need for multilevel strategies with a focus on respectful, inclusive participant and key community partner engagement; the time investment in local communities to promote equitable collaboration; encouragement of the patient's autonomous right to self-determination; and mitigation of power imbalances. Nurse researchers are well positioned to advance research justice at the intersection of reproductive justice and ethics to fully engage diverse populations in advancing health equity to support the best health outcomes.
Predictive Value of Routine White Blood Cell Count Obtained Prior to Discharge for Organ Space Infection in Children with Complicated Appendicitis: Results from the Eastern Pediatric Surgery Network
Authors: Cramm Shannon L , Graham Dionne A , Allukian Myron , Blakely Martin L , Chandler Nicole M , Cowles Robert A , Feng Christina , Kunisaki Shaun M , Russell Robert T , Rangel Shawn J ,   for the Eastern Pediatric Surgery Network (EPSN)
Published: December 2022

Background:
The objective of this study was to evaluate the clinical utility of a routine pre-discharge white blood cell count (RPD-WBC) for predicting post-discharge organ space infection (OSI) in children with complicated appendicitis.

Study Design:
This was a multicenter study using NSQIP-Pediatric data from 14 hospitals augmented with RPD-WBC data obtained through supplemental chart review. Children with fever or surgical site infection diagnosed during the index admission were excluded. Positive predictive value (PPV) for post-discharge OSI was calculated for RPD-WBC values of persistent leukocytosis (≥9.0x103 cells per microliter), increasing leukocytosis (RPD-WBC>preoperative WBC), quartiles of absolute RPD-WBC, and quartiles of relative proportional change from preoperative WBC. Logistic regression was used to calculate predictive values adjusted for patient age, appendicitis severity, and use of post-discharge antibiotics.

Results:
1264 children were included, of which 348 (27.5%) had a RPD-WBC obtained (hospital range: 0.8-100%, P<0.01). Median RPD-WBC was similar between children who did and did not develop a post-discharge OSI (9.0 vs. 8.9; p=0.57), and leukocytosis was absent in 50% of children who developed a post-discharge OSI. The PPV of RPD-WBC was poor for both persistent and increasing leukocytosis (3.9% and 9.8%, respectively), and for thresholds based on the quartiles of highest RPD-WBC values (>11.1, PPV: 6.4%) and greatest proportional change (<32% decrease from preoperative WBC; PPV: 7.8%).

Conclusions:
Routine pre-discharge WBC data have poor predictive value for identifying children at risk for post-discharge OSI following appendectomy for complicated appendicitis.
The First Insight into the Epigenetic Fusion Gene Landscape of Acute Myeloid Leukemia
Authors: Ling Fei , Zhuo Noah , Zhuo Degen 
Published: December 2022

AbstractEpigenetic fusion genes have been defined as the fusion genes produced viacis-splicing of read-through pre-mRNAs of two identical-strand neighbor genes and have been known for decades. However, they need to be adequately investigated. In this study, we analyze RNA-Seq data from 390 AML patients and identify 12,754 EFG isoforms encoded by 5,213 EFGs, one-sixth of all potential EFGs. We characterize 479 EFG isoforms whose recurrent frequencies range from 10% to 96.2% and show that most of them result from developmental interactions between recurrent inherited genetic and environmental abnormalities. Novel EFG isoforms generated during late developments reflect somatic genetic abnormalities and environmental stresses. These characteristics of EFG isoforms make it possible for clustering heatmap and counting for EFG isoforms to distinguish GTEx healthy individuals and AML patients. This study reveals that human genomes encode potential EFGs equal to the total number of human genes and pseudogenes. EFGs provide one of the most powerful and economical tools to monitor the earliest signals from somatic genetic and environmental abnormalities.
Stromal resistance to castration-induced prostate regression in a mouse model of benign prostatic hyperplasia
Authors: Zhang Renyuan , Singh Shalini , Pan Chunliu , Xu Bo , Kindblom Jon , Yeh Shu-Yuan , Chang Chawnshang , Eng Kevin H. , Krolewski John J. , Nastiuk Kent L. 
Published: December 2022

AbstractBenign prostatic hyperplasia (BPH) is a non-neoplastic proliferative disease producing lower urinary tract symptoms related to the enlarged prostate. BPH is pathologically characterized by hyperplastic growth in both epithelial and stromal compartments. Androgen signaling is essential for prostate function and androgen blockade is the second-line medical therapy to relieve symptoms of BPH. Here we examined the prostates of probasin promoter-driven prolactin (Pb-PRL) transgenic mice, a robust model of BPH that spontaneously develops prostate enlargement, to investigate prostate regression in response to surgical castration. Serial ultrasound imaging demonstrated very uniform self-limited growth of Pb-PRL prostate volume that is consistent with the benign, limited cellular proliferation characteristic of BPH and that contrasts with the highly variable, exponential growth of murine prostate cancer models. Castration elicited only a partial reduction in prostate volume, relative to castration-induced regression of the normal prostate gland. The anti-androgen finasteride induced a diminished reduction of Pb-PRL prostate volume versus castration alone. The limited extent of Pb-PRL mouse prostate volume regression correlated with the initial volume of the stromal compartment, suggesting a differential sensitivity to androgen withdrawal of the epithelial and stroma compartments. Indeed, two-dimensional morphometric analyses revealed a distinctly reduced rate of regression for the stromal compartment in Pb-PRL mice. The myofibroblast component of the Pb-PRL prostate stroma appeared normal, but contained more fibroblasts and extracellular collagen deposition. Like normal prostate, the rate of regression of the Pb-PRL prostate was partially dependent on TGFß and TNF signaling, but unlike the normal prostate, the extent of castration-induced regression was not affected by TGFß or TNF blockade. Our studies show that androgen deprivation can effectively reduce the overall volume of hyperplastic prostate, but the stromal compartment is relatively resistant, suggesting additional therapies might be required to offer an effective treatment for the clinical manifestations of BPH.
Antiviral activity of Cytomegalovirus-specific CD4+ T cells against lytically infected non-haemopoietic cells
Authors: Lim EY , Houldcroft CJ , Jackson SE , Okecha G , Wills M 
Published: December 2022

ABSTRACTHCMV establishes a lifelong latent infection in its host, eliciting a broad immune response involving both the innate and adaptive arms of immunity. In immunocompromised individuals, recovery of the HCMV-specific CD4+ T cell response is associated with a lower risk of HCMV reactivation and disease, suggesting that CD4+ T cells contribute significantly to control of viral replicationin vivo. However, most prior studies of the HCMV-specific CD4+ T cell response have been performed with the aim of either predicting those at risk for HCMV reactivation and end-organ disease, or identifying markers which are associated with higher risk of HCMV viraemia. Few studies have examined the mechanisms of viral control of CD4+ T cells in response to cells lytically infected with HCMV. In this paper, we show that CD4+ T cells from a HCMV-seropositive donor can prevent viral dissemination in autologous fibroblasts, that the secretome from these cells is also antiviral, and that IFN-γ is a key cytokine in the secretome. We also show that MHC Class II antigen presentation by monocytes was critical to driving this HCMV-specific CD4+ T cell response.
The application ofNicotiana benthamianaas a Transient Expression Host to Clone the Coding Sequences of Plant Genes
Authors: Huang Jianzhong , Jia Peng , Zhong Xiaoju , Guan Xiuying , Zhang Hongbin , Ruan Honglei 
Published: December 2022

AbstractCoding sequences (CDS) are commonly used for transient gene expression, in yeast two-hybrid screening, to verify protein interactions and in prokaryotic gene expression studies. CDS are most commonly obtained using complementary DNA (cDNA) derived from messenger RNA (mRNA) extracted from plant tissues and generated by reverse transcription. However, some CDS are difficult to acquire through this process as they are expressed at extremely low levels or have specific spatial and/or temporal expression patternsin vivo. These challenges require the development of alternative CDS cloning technologies.In this study, we found that the genomic intron-containing gene coding sequences (gDNA) fromArabidopsis thaliana, Oryza sativa, Brassica napus, andGlycine maxcan be correctly transcribed and spliced into mRNA inNicotiana benthamiana. In contrast, gDNAs fromTriticum aestivumandSorghum bicolordid not function correctly. In transient expression experiments, the target DNA sequence is driven by a constitutive promoter. Theoretically, a sufficient amount of mRNA can be extracted from theN. benthamianaleaves, making it conducive to the cloning of CDS target genes. Our data demonstrate thatN. benthamianacan be used as an effective host for the cloning CDS of plant genes.
Visualization of early RNA replication kinetics of SARS-CoV-2 by using single molecule RNA-FISH
Authors: Pathak Rajiv , Eliscovich Carolina , Mena Ignacio , Dixit Updesh , García-Sastre Adolfo , Singer Robert H , Kalpana Ganjam V. 
Published: December 2022

AbstractSARS-CoV-2 infection has caused a major global burden. Despite intensive research, the mechanism and dynamics of early viral replication are not completely understood including the kinetics of formation of plus stranded genomic and subgenomic RNAs (gRNA and sgRNA) starting from the RNA from the first virus that enters the cell. We employed single-molecule RNA-fluorescencein situhybridization (smRNA-FISH) to simultaneously detect viral gRNA and sgRNA in infected cells and carried out a time course analysis to determine the kinetics of their replication. We visualized the single molecules of gRNA within the cytoplasm of infected cells 30 minutes post-infection and detected the co-expression of gRNA and sgRNA within two hours post-infection. Furthermore, we observed the formation of a replication organelle (RO) from a single RNA, which led to the formation of multiple ROs within the same cells. Single molecule analysis indicated that while gRNA resided in the center of these ROs, the sgRNAs were found to radiate and migrate out of these structures. Our results also indicated that after the initial delay, there was a rapid but asynchronous replication, and the gRNA and sgRNAs dispersed throughout the cell within 4-5 hours post-infection forming multiple ROs that filled the entire cytoplasm. These results provide insight into the kinetics of early post-entry events of SARS-CoV-2 and the formation of RO, which will help to understand the molecular events associated with viral infection and facilitate the identification of new therapeutic targets that can curb the virus at a very early stage of replication to combat COVID-19.Author SummarySARS-CoV-2 infection continues to be a global burden. Soon after the entry, SARS-CoV-2 replicates by an elaborate process, producing genomic and subgenomic RNAs (gRNA and sgRNAs) within specialized structures called replication organelles (RO). Many questions including the timing of multiplication of gRNA and sgRNA, the generation, subcellular localization, and function of the ROs, and the mechanism of vRNA synthesis within ROs is not completely understood. Here, we have developed probes and methods to simultaneously detect the viral gRNA and a sgRNA at single cell single molecule resolution and have employed a method to scan thousands of cells to visualize the early kinetics of gRNA and sgRNA synthesis soon after the viral entry into the cell. Our results reveal that the replication is asynchronous and ROs are rapidly formed from a single RNA that enters the cell within 2 hours, which multiply to fill the entire cell cytoplasm within ~4 hours after infection. Furthermore, our studies provide a first glimpse of the gRNA and sgRNA synthesis within ROs at single molecule resolution. Our studies may facilitate the development of drugs that inhibit the virus at the earliest possible stages of replication to minimize the pathogenic impact of viral infection.
SWAMPy: Simulating SARS-CoV-2 Wastewater Amplicon Metagenomes with Python
Authors: Boulton William , Fidan Fatma Rabia , Denise Hubert , De Maio Nicola , Goldman Nick 
Published: December 2022

AbstractMotivationTracking SARS-CoV-2 variants through genomic sequencing has been an important part of the global response to the pandemic. As well as whole-genome sequencing of clinical samples, this surveillance effort has been aided by amplicon sequencing of wastewater samples, which proved effective in real case studies. Because of its relevance to public healthcare decisions, testing and benchmarking wastewater sequencing analysis methods is also crucial, which necessitates a simulator. Although metagenomic simulators exist, none are fit for the purpose of simulating the metagenomes produced through amplicon sequencing of wastewater.ResultsOur new simulation tool, SWAMPy (Simulating SARS-CoV-2WastewaterAmpliconMetagenomes withPython), is intended to provide realistic simulated SARS-CoV-2 wastewater sequencing datasets with which other programs that rely on this type of data can be evaluated and improved.AvailabilityThe code for this project is available athttps://github.com/goldman-gp-ebi/SWAMPyIt can be installed on any Unix-based operating system and is available under the GPL-v3 license.
Circadian reprogramming of adipose progenitor cells regulates intermittent fasting-mediated adipose tissue remodeling and metabolic improvement
Authors: Lee Ju Hee , Patel Yash , Yeung Joanna Lan-Hing , Pickel Lauren , Ealey Kafi N. , Togo Jacques , Kim Yun Hye , Kim Kyoung-Han , Park Jin-Gyoon , Jackson Timothy , Okrainec Allan , Kim Jae-Ryong , Park So-Young , Dash Satya , Sung Hoon-Ki 
Published: December 2022

ABSTRACTWhite adipose tissue (WAT) fibrosis is a hallmark of dysfunctional WAT that is directly linked to metabolic abnormalities. Recent studies have highlighted the role of dysfunctional adipose progenitor cells (APCs) in WAT fibrosis and impaired adaptive tissue plasticity, leading to systemic insulin resistance. However, therapeutic options for WAT fibrosis are limited. Intermittent fasting (IF) is an effective dietary regimen for weight control and metabolic improvement through various mechanisms, including healthy remodeling of WAT. However, whether IF is effective in improving age-associated WAT fibrosis and metabolic homeostasis is unknown. Here, we show that IF confers therapeutic benefits in aged and obese mice through reduction of WAT fibrosis. Single-cell analyses revealed that IF significantly reduces pro-fibrotic signatures within APCs along with upregulation of the circadian pathways, suggesting that the circadian clock of APCs mediates IF-induced WAT remodeling. Importantly, mice lacking core circadian gene exhibited increased fibrotic signatures in WAT and diminished beneficial response to IF, further supporting the importance of circadian rhythm in IF-mediated metabolic benefits. Lastly, insulin resistance in humans also presented with dysregulated circadian rhythm signatures in APC populations. Collectively, our findings highlight the novel role of the APC circadian rhythm in plasticity of WAT and metabolic response to IF.
Large-scale analysis of the N-terminal regulatory elements of the kinase domain in plant receptor-like kinase family
Authors: Fu Qiong , Liu Qian , Zhang Rensen , Chen Jia , Guo Hengchang , Ming Zhenhua , Yu Feng , Zheng Heping 
Published: December 2022

SummaryThe N-terminal regulatory element of the kinase domain (NRE), which includes juxtamembrane segment (JM) of Receptor-like kinases (RLKs) and the N-terminal extension segment of the kinase domain in RLCKs, is the key component that regulates the activities of RLKs and RLCKs. However, their feature and functions remain largely unexplored. Herein, we perform a systematic analysis of 510,233 NRE sequences in RLKs and RLCKs from 528 plants by integrating information theory and genome-wide analysis to unravel their common characteristics and diversity. Recombinant RLKs are used to explore the structural-functional relationship of the newly-discovered motifsin vitro. Most NRE segments are around 40-80 amino acids, featuring a serine-rich region and a 14-amino-acid motif ‘FSYEELEKATBNFS’ which harbors a characteristic α-helix connecting to the core kinase domain. This α-helix suppresses FERONIA’s kinase activity. Motif discovery algorithm has identified 29 motifs with known phosphorylation sites highly conserved in RLK and RLCK classes, especially the motif ‘VGPWKpTGLpSGQLQKAFVTGVP’ in LRR-VI-2 class. The NRE phosphorylation of an LRR-VI-2 member MDIS1 modulates the auto-phosphorylation of its co-receptor MIK1, indicating NRE’s potential role as a “kinase switch” in RLK activation. Consequently, the characterization of phosphorylatable NRE motifs improves the accuracy in predicting phosphorylatable serines. Altogether, our study provides an enriched and comprehensive dataset to investigate NRE segments from individual RLKs and helps understand the underlying mechanism of action of the RLK signal transduction and kinase activation processes in plant adaptation.
REASSURED diagnostics at point-of-care in sub-Saharan Africa: A scoping review
Authors: Moetlhoa Boitumelo , Maluleke Kuhlula , Mathebula Evans M , Kgarosi Kabelo , Nxele Siphesihle R , Lenonyane Bonolo , Mashamba-Thompson Tivani 
Published: December 2022

AbstractPoint-of-care (POC) diagnostics that meet the REASSURED criteria are essential in combating the rapid increase and severity of global health emergencies caused by infectious diseases. However, little is known about whether the REASSURED criteria are implemented in regions known to have a high burden of infectious diseases such as sub-Saharan Africa (SSA). This scoping review maps evidence of the use of REASSURED POC diagnostic tests in SSA. The scoping review was guided by the advanced methodological framework of Arksey and O’Malley, and Levac et al. We searched the following electronic databases for relevant literature: Scopus, Dimensions, ProQuest Central, Google Scholar, and EBSCOhost (MEDLINE, CINAHL, as well as AFRICA-WIDE). Two reviewers independently screened abstracts and full-text articles using the inclusion criteria as reference. We appraised the quality of the included studies using the mixed-method appraisal tool (MMAT) version 2018. We retrieved 138 publications, comprising 134 articles and four grey literature articles. Of these, only five articles were included following abstract and full-text screening. The five included studies were all conducted in SSA. The following themes emerged from the eligible articles: quality assurance on accuracy of REASSURED POC diagnostic tests, sustainability of REASSURED POC diagnostic tests, and local infrastructure capability for delivering REASSURED POC diagnostic tests to end users. All five articles had MMAT scores between 90% and 100%. In conclusion, our scoping review revealed limited published research on REASSURED diagnostics at POC in SSA. We recommend primary studies aimed at investigating the implementation of REASSURED POC diagnostic tests in SSA.
The key audit matters and the audit cost: does governance matter?
Authors: Elmarzouky Mahmoud , Hussainey Khaled , Abdelfattah Tarek 
Published: December 2022

Purpose
This paper aims to investigate the relationship between key audit matters (KAMs) and audit costs and whether board size and independence affect this relationship. Furthermore, this paper examines the moderating effect of corporate governance on the relationship between KAMs and audit costs.

Design/methodology/approach
The authors hypothesise that disclosing more KAMs in the audit report is positively associated with audit costs because of the greater effort. The agency theory suggests that firms with good governance will mitigate the agency conflict of interest and improve financial reporting quality. Thus, good governance might moderate the relationship between reported KAMs and audit costs. The authors use a quantitative approach. The authors are using a sample of the UK FTSE all-share non-financial firms from 2014 to 2018 for the UK Financial Times Stock Exchange all-share non-financial firms.

Findings
The authors provide evidence of a significant positive relationship between KAMs and audit costs. The relationship is relatively higher when considering the independent directors' percentage as a moderating factor. These results came consistent with the agency theory literature. However, the authors found no empirical evidence to support a moderating effect of board size on the relationship between KAMs and audit cost.

Practical implications
The finding benefits the regulatory setters to better understand the consequences of the new auditing standards. This paper has theoretical and practical implications for regulators, standard setters, professional bodies, shareholders and academics.

Originality/value
This paper contributes to the literature assessing the regulatory changes related to audit reform and adds to the debate on the impact on audit costs. This paper underlines governance factors as a moderating role in this relationship between KAMs and audit costs.