bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA editing in plant mitochondria and chloroplasts
Authors: Bock Ralph 
Published: November 2023

Abstract
In plants, genetic information is distributed among three cellular compartments: the nucleus, mitochondria and plastids. Each of these compartments carries its own genome and, consequently, expresses heritable traits. Plastids and mitochondria do not obey Mendelian rules and are often transmitted uniparentally to the next generation, a phenomenon early recognized as being one of the characteristics of extranuclear inheritance (1).
Adenosine-to-inosine RNA editing: substrates and consequences
Authors: Emeson Ronald B 
Published: November 2023

Abstract
The conversion of adenosine to inosine (A→I) by RNA editing is an increasingly recognized RNA processing event by which multiple RNA and protein isoforms can be generated from a single genomic locus. This type of modification was first observed in yeast tRNAs (1, 2), but has since been identified in multiple viral RNA transcripts and cellular mRNA species (3–5). Since inosine preferentially base-pairs with cytidine, an inosine within RNA transcripts is read as guanosine during translation, often resulting in specific change(s) in the amino acid coding potential of the mRNA, which can dramatically alter the functional properties of the encoded protein product. In several instances, A→I editing events have also been described in untranslated RNA species (e.g. tRNAs) (6, 7) and non-coding regions of mRNA transcripts (8–11), suggesting that such modifications may also affect other aspects of RNA function including translation, splicing and stability.
Point mutations and chimeric receptors in studies of ligand binding domains and second messenger activation of α1-adrenoceptors
Authors: Perez Dianne M , Zuscik Michael J , Ross Sean A , Waugh David J J 
Published: November 2023

Abstract
The creation of point mutations or the generation of chimeric receptors is a valuable model system for the evaluation of structure-function relationships of G protein-coupled receptors (GPCRs). One can essentially mutate any area in the receptor structure and then determine the functional and/or binding consequences of that mutation; thus, interpreting the importance of the original amino acid in receptor structure. This chapter will outline two basic techniques to generate mutations, how to transfect into mammalian cells, then to analyse the effects of the mutations by either binding or function.
A Systematic Review and Meta-Analysis of Mapping Biopsy for Primary Extramammary Paget’s Disease in Reducing Recurrence Following Surgical Excision
Authors: Murugan Thirrisha , Wong Louis Choon Kit , Ong Xing-Yi Sarah , Tan Sze Huey , Tan Joey Wee-Shan , Liu Ying , Shannon Nicholas B. , Chiang Jianbang , Poon Eileen , Chan Jason Yongsheng , Yang Valerie Shiwen , Somasundaram Nagavalli , Farid Mohamad , Wong Ru Xin , Nei Wen Long , Kwek Jin Wei , Thng Choon Hua , Hennedige Tiffany , Tang Po Yin , Selvarajan Sathiyamoorthy , Tay Kae Jack , Abdul Mohamed Rezal , Wong Jolene Si Min , Seo Chin Jin , Soo Khee Chee , Chia Claramae Shulyn , Ong Chin-Ann Johnny 
Published: November 2023

Objective:
To examine the association between the performance of mapping biopsies and surgical outcomes postexcision of extramammary Paget’s disease (EMPD).

Background:
Primary EMPD is a rare entity associated with poorly defined surgical margins and difficult-to-access sites of lesions. Surgical resection with clear margins remains the preferred management method. The use of mapping biopsies might be beneficial, particularly in lowering disease recurrence.

Methods:
Available literature was reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology before a fixed-effect meta-analysis was performed to identify the presence of a correlation between performing mapping biopsies and positive margins on permanent sections as well as disease-free survival. Additional study results not included in the quantitative assessment were qualitatively assessed and reported.

Results:
A total of 12 studies were shortlisted for final analysis. 294 patients who underwent mapping biopsies and 48 patients who did not undergo mapping biopsies were included in the assessment. Forest plot analysis revealed a pooled rate ratio of 0.50 (95% CI, 0.32–0.77) in the prevalence of positive margins in patients with mapping biopsies performed as compared to patients without. The pooled rate ratio of the prevalence of disease-free survival in patients with mapping biopsies performed as compared to patients without was 1.38 (95% CI, 1.03–1.84). Qualitative assessment of the remaining selected studies revealed equivocal results.

Conclusions:
Mapping biopsies are able to improve EMPD surgical excision outcomes but given the rarity of the disease and heterogeneity of mapping biopsy procedures, further confirmation with randomized controlled trials or a larger patient pool is necessary.
A Network Meta-analysis of the Efficacy and Safety of Targeted Drug Combinations in the Treatment of Pulmonary Arterial Hypertension
Authors: Wang Rui , Wei Meng , Wang Jie , Huang Xiang , Yan Qianzhi , Wang Shichao , Wu Yun 
Published: November 2023

Objective:
This network meta-analysis aims to compare the efficacy and safety of different targeted drug combination treatment for pulmonary arterial hypertension (PAH).

Methods:
Searches were conducted in Cochrane, PubMed, EMBASE, China National Knowledge Infrastructure, China Biomedical Literature Database, Wanfang Database, and VIP Chinese Science and Technology Journal Data to identify both published and unpublished randomized controlled trials from inception until January 1, 2022. The risk of bias in the included studies was assessed in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. A network meta-analysis was performed using Stata 16.0 software. The efficacy and safety of different targeted drugs combined treatment for PAH were evaluated based on forest plot, funnel plot, and surface under the cumulative ranking.

Results:
A total of 29 randomized controlled trails with 4,448 patients treated with 10 different types of targeted drug combinations were included in this study. The results of the surface under the cumulative ranking showed that the combination regimen was the best clinical option to improve symptoms and delay progression in patients with pulmonary artery hypertension compared with monotherapy. Sildenafil in combination with ambrisentan significantly improved the 6-minute walk distance and reduced N-terminal pro-brain natriuretic peptide levels. Bosentan in combination with sildenafil significantly reduced mean pulmonary artery pressure, whereas bosentan in combination with epoprostenol was more effective than other combinations in reducing pulmonary vascular resistance. Bosentan in combination with tadalafil significantly improved the Borg dyspnea score, and bosentan in combination with iloprost was the best combination for improving World Health Organization functional class/New York Heart Association functional class. In terms of safety, there was no significant reduction in the incidence of adverse events, hospitalizations, or all-cause mortality for combination therapy compared with monotherapy. Bosentan combined with sildenafil significantly reduced the risk of serious adverse events, but the risk of discontinuation due to an adverse event was higher than monotherapy. Sildenafil combined with epoprostenol reduced the risk of clinical worsening in patients with PAH.

Conclusion:
Compared with monotherapy, targeted drug combinations for PAH significantly improves exercise tolerance, pulmonary hemodynamic parameters, and reduces the risk of serious adverse events and clinical worsening in patients. Bosentan in combination with sildenafil and bosentan in combination with iloprost are combinations of targeted agents with significant efficacy and better safety profile than monotherapy for the treatment of PAH. Sildenafil in combination with epoprostenol has a low risk of clinical worsening in PAH.
STAT3-CD163 cross-talk exhibits promising biomarkers for a progressive ischemic cardiomyopathy: integrative computational and gene expression profiling based on Gene Expression Omnibus datasets
Authors: Mohareb Mina W. , Kariem Mohammed A. , Tohamy Aly , Gamal Noha M. , Mosaad Rehab M. , Esmaiel Nora N. , Fayez Alaaeldin G. 
Published: November 2023

Background and purpose:
Ischemic heart disease frequently leads to heart failure, often resulting in death. In this study, we aimed to identify common hub mRNAs and pathways involved in the pathological progression of ischemic cardiomyopathy (ICM).

Methods:
Validation quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was carried out on peripheral blood and left ventricle specimens from patients in three groups with stable coronary artery disease (CAD), myocardial infarction (MI), and ICM and compared with corresponding controls. qRT-PCR was preceded by computational analysis of eight high-throughput RNA sequencing and microarray datasets from 499 patients and 233 controls, to determine possible common biologically meaningful differentially expressed genes (DEGs). To determine the potential pathological pathways, we performed Gene Ontology functional annotation, pathway enrichment analysis, protein–protein interaction (PPI) analysis, and constructed transcriptional factor/miRNA regulatory networks. Finally, approved drugs were screened.

Results:
Fifteen common DEGs with P < 0.01 were identified. STAT3, CEBPD, GLUL, and CD163 were hub-enriched mRNAs with an interaction score ≥ 0.50. Our qRT-PCR analysis showed an increased expression of STAT3 in all three patient groups and CD163, mainly in cardiac samples, in a remarkably ascending manner. Interaction modules showed co-regulators supporting high STAT3-CD163 connectivity, suggesting a potential role for STAT3-CD163 cross-talk-mediated inflammatory responses in ICM progression.

Conclusions:
Our results provided a novel perspective for understanding the underlying mechanisms of ICM progression and exploring new therapeutic agents.

Clinical trial registration:
URL: www.clinicaltrials.gov. Unique identifier: NCT05508269.
Travel for abortion care: implications for clinical practice
Authors: Lerma Klaira , Coplon Leah , Goyal Vinita 
Published: November 2023

Purpose of review
Traveling long distances to obtain abortion care due to restrictions and scarce availability is associated with significant obstacles. We review clinical strategies that can facilitate abortion access and outline considerations to ensure person-centered and equitable care.

Recent findings
Establishing a patient's gestational duration prior to travel may be beneficial to ensure they are eligible for their desired abortion method at the preferred facility or to determine if a multiday procedure is required. If a local ultrasound cannot be obtained prior to travel, evidence demonstrates people can generally estimate their gestational duration accurately. If unable to provide care, clinicians should make timely referrals for abortion. Integration of telemedicine into abortion care is safe and well regarded by patients and should be implemented into service delivery where possible to reduce obstacles to care. Routine in-person follow-up care is not necessary. However, for those who want reassurance, formalized pathways to care should be established to ensure people have access to care in their community. To further minimize travel-related burdens, facilities should routinely offer information about funding and practical support, emotional support, and legal resources.

Summary
There are many opportunities to optimize clinical practice to support those traveling for abortion care.
Risk stratification of papillary thyroid cancers using multidimensional machine learning
Authors: Li Yuanhui , Wu Fan , Ge Weigang , Zhang Yu , Hu Yifan , Zhao Lingqian , Gou Wanglong , Shi Jingjing , Ni Yeqin , Li Lu , Fu Wenxin , Lin Xiangfeng , Yu Yunxian , Han Zhijiang , Chen Chuanghua , Xu Rujun , Zhang Shirong , Zhou Li , Pan Gang , Peng You , Mao Linlin , Zhou Tianhan , Zheng Jusheng , Zheng Haitao , Sun Yaoting , Guo Tiannan , Luo Dingcun 
Published: November 2023

Background:
Papillary thyroid cancer (PTC) is one of the most common endocrine malignancies with different risk levels. However, preoperative risk assessment of PTC is still a challenge in the worldwide. Here, we first report a Preoperative Risk Assessment Classifier for PTC (PRAC-PTC) by multidimensional features including clinical indicators, immune indices, genetic feature, and proteomics.

Materials and methods:
The 558 patients collected from June 2013 to November 2020 were allocated to three groups: discovery set (274 patients, 274 FFPE), retrospective test set (166 patients, 166 FFPE) and prospective test set (118 patients, 118 FNA). Proteomic profiling was conducted by formalin-fixed paraffin-embedded (FFPE) and fine-needle aspiration (FNA) tissues from the patients. Preoperative clinical information and blood immunological indices were collected. The BRAF
V600E mutation were detected by the amplification refractory mutation system (ARMS).

Results:
We developed a machine learning model of 17 variables based on multidimensional features of 274 PTC patients from a retrospective cohort. The PRAC-PTC achieved areas under the curve (AUC) of 0.925 in the discovery set and validated externally by blinded analyses in a retrospective cohort of 166 PTC patients (0.787 AUC) and a prospective cohort of 118 PTC patients (0.799 AUC) from two independent clinical centres. Meanwhile, the preoperative predictive risk effectiveness of clinicians was improved with the assistance of PRAC-PTC, and the accuracies reached at 84.4% (95% CI 82.9-84.4) and 83.5% (95% CI 82.2-84.2) in the retrospective and prospective test sets, respectively.

Conclusion:
This study demonstrated that the PRAC-PTC that integrating clinical data, gene mutation information, immune indices, high-throughput proteomics and machine learning technology in multi-centre retrospective and prospective clinical cohorts can effectively stratify the preoperative risk of PTC and may decrease unnecessary surgery or overtreatment.
Bronchoscopic lung volume reduction in emphysema: a review
Authors: Ravikumar Nakul , Wagh Ajay , Holden Van K. , Hogarth D. Kyle 
Published: November 2023

Purpose of review
Chronic obstructive pulmonary disease (COPD) poses a substantial burden on the healthcare system and is currently considered the sixth leading cause of death in the United States. Emphysema, as evidenced by severe air-trapping in patients with COPD, leads to significant dyspnea and morbidity. Lung volume reduction via surgery or minimally invasive endobronchial interventions are currently available, which improve lung function and quality of life.

Recent findings
Newer studies have noted a survival benefit in patients post bronchoscopic lung volume reduction vs. those subjected to standard of care. The presence of collateral ventilation is one of the most common impeding factors to placing endobronchial valves, and if placed, these patients might not achieve lobar atelectasis; however, there are newer modalities that are now available for patients with collateral ventilation which we have described.

Summary
Combining standard of care treatment that includes smoking cessation, bronchodilators, preventive care including vaccinations, pulmonary rehabilitation, and endobronchial treatment using various interventions in decreasing hyperinflation improves quality of life and may improve survival and hence significantly reduce the burden of COPD on healthcare.
The HIV-2 proviral landscape is dominated by defective proviruses
Authors: Koofhethile Catherine K. , Gao Ce , Chang Charlotte , Lian Xiaodong , Shapiro Roger , Yu Xu G. , Lichterfeld Mathias , Kanki Phyllis J. 
Published: November 2023

Background:
Compared with HIV-1 infection, HIV-2 infection is associated with a slower progression to AIDS. Understanding the persistence of HIV-2 infection might inform the mechanisms responsible for differences in the pathogenicity of HIV-2 versus HIV-1.

Methods:
In this study, we analyzed the genetic composition of the proviral reservoir in archived blood samples collected from 13 untreated HIV-2-infected adults from Senegal. We used single-genome, near-full-length individual proviral sequencing (FLIP-Seq) to assess the relative frequency of intact and defective proviruses.

Results:
Ten out of 13 (77%) study participants demonstrated virologic suppression (<90 HIV RNA copies/ml) while the remaining 3 (23%) had detectable HIV RNA. We obtained 363 proviral sequences from peripheral blood mononuclear cells (PBMCs) from the 13 study participants. Within these sequences, 342 (94%) defective proviruses were detected. Twenty-one (6%) intact proviruses were detected from three study participants, with one study participant displaying a large clone consisting of 16 genome-intact sequences.

Conclusion:
This data suggests that similar to HIV-1 infection, the proviral landscape of HIV-2 is dominated by defective proviruses.
Parasite-mediated predation determines the infection in a complex predator-prey system
Authors: Híjar-Islas Ana C. , Milne Amy , Eizaguirre Christophe , Huang Weini 
Published: November 2023

AbstractThe interplay of host-parasite and predator-prey interactions is critical in ecological dynamics because both predators and parasites play an important role in regulating populations and communities. But what is the prevalence of infected prey and predators when a parasite is transmitted through trophic interactions, particularly when stochastic fluctuations of demographical changes are allowed arising from individual-level dynamics? Here, we analysed the system stability and the frequency of infected and uninfected host subpopulations in a complex predator-prey-parasite system, where infection happens through trophic interactions transmitting parasites from prey to predators. We varied the parasite virulence implemented as reproductive costs imposed on infected hosts and the probabilities of parasites infecting the hosts per encounter, to investigate how those important evolutionary factors will determine the species coexistence and population composition. We further explored the role of stochasticity in our system by comparing our deterministic analysis with stochastic simulations. Our results show that parasites go extinct when the infection probabilities of either host are small. The success in infecting the final host (the predator) is more critical for the survival of the parasite species, as the threshold for infection probability of the predator is higher than that of the prey for three-species coexistence. While our stochastic simulations agree with deterministic predictions well in most parameter regions. However, in the border parameter regions between coexistence and extinction typically with high infection probabilities, while only one possible outcome in deterministic dynamics, both coexistence and extinction can happen in stochastic repeats under the same parameter values. This illustrates the importance of stochasticity and demographic fluctuations in species coexistence. In addition, the proportion of infected individuals increases with the infection probabilities in our deterministic analysis and stochastic simulations as expected. Interestingly, we found that in some parameter space, the relative frequencies of infected and uninfected individuals are different between the intermediate host (prey) and the final host (predator) populations. This counterintuitive observation shows that the interplay of host-parasite and predator-prey interactions lead to more complex dynamics than a simple resource-consumer relationship.
What has changed in 20 years? Structure and function of soft-sediment macrofauna in a subarctic embayment, Newfoundland (Canada)
Authors: Komendić Ivana , de Moura Neves Bárbara , Ramey-Balci Patricia A. 
Published: November 2023

AbstractUnderstanding how natural and anthropogenic disturbances affect the structure and functioning of marine ecosystems and their associated services is central to predicting future dynamics. Placentia Bay is an Ecologically and Biologically Significant Area (EBSA) in the north Atlantic exposed to multiple stressors. To investigate changes in the community and functional structure of soft-sediment macrofauna as well as environmental drivers of observed variation, we compared contemporary (2019–2020) and historical (1998) samples at eight stations (n=77) collected 21 years apart. Although community and functional structure significantly differed between these two time points, functional traits were maintained (i.e., no loss of 36 trait modalities). Thirty-seven percent of species/taxa where only observed in either the historical or contemporary community, and the contemporary community exhibited a lower density of macrofauna but had similar richness, resulting in higher evenness and diversity. Highly tolerant subsurface deposit feeders having small body sizes (<10mm) and direct development dominated the historical community, whereas the contemporary community had nearly equal proportions of surface and subsurface deposit feeders with small to medium body sizes (<10–50 mm) with pelagic larvae, and the proportion of highly tolerant species/taxa was reduced. These changes likely reflect the large reduction in polychaetes (91 vs. 58%) and increased bivalves (4 vs. 25%) relative to the historical time point. Community variation was driven by changes in the sedimentary habitat. Contemporary versus historical sediments were ∼4.5x coarser and had higher levels of sedimentary organic matter. This work contributes to advancing our understanding of relationships between benthic macrofauna, functional traits, and the sedimentary habitat in coastal environments.
FoxA1/2-dependent epigenomic reprogramming drives lineage switching in lung adenocarcinoma
Authors: Gillis Katherine , Orellana Walter A. , Wilson Emily , Parnell Timothy J. , Fort Gabriela , Dadzie Headtlove Essel , Zhang Xiaoyang , Snyder Eric L. 
Published: November 2023

ABSTRACTThe ability of cancer cells to alter their identity is essential for tumor survival and progression. Loss of the pulmonary lineage specifier NKX2-1 within KRAS-driven lung adenocarcinoma (LUAD) enhances tumor progression and results in a pulmonary-to-gastric lineage switch that is dependent upon the activity of pioneer factors FoxA1 and FoxA2; however, the underlying mechanism remains largely unknown. Here, we show that FoxA1/2 reprogram the epigenetic landscape of NKX2-1-negative LUAD to facilitate a gastric identity. AfterNkx2-1deletion, FoxA1/2 mediate demethylation of gastric-defining genes through recruitment of TET3, an enzyme that induces DNA demethylation. H3K27ac ChIP-seq and HiChIP show that FoxA1/2 also control the activity of regulatory elements and their 3D interactions at gastric loci. Furthermore, oncogenic KRAS is required for the FoxA1/2-dependent epigenetic reprogramming. This work demonstrates the role of FoxA1/2 in rewiring the methylation and histone landscape and cis-regulatory dynamics of NKX2-1-negative LUAD to drive cancer cell lineage switching.