bluuebunny/crossref_metadata_2025_split huggingface dataset:
Limited Song Mixing Without Genomic Gene Flow in a Contact Zone Between Two Songbird Species
Authors: Wu Lei , Dang Jing , Tang Linfang , Cheng Yalin , Song Gang , Sun Yuehua , Martens Jochen , Päckert Martin , Alström Per , Zhang Dezhi , Jia Chenxi , Lei Fumin 
Published: March 2023

AbstractSong is considered to play an important role in the maintenance of prezygotic reproductive isolation between closely related songbird species. Therefore, song mixing in a contact zone between closely related species is often considered as evidence of hybridization. The Sichuan Leaf Warbler Phylloscopus forresti and the Gansu Leaf Warbler Phylloscopus kansuensis, which diverged 2 million years ago, have formed a contact zone in the south of the Gansu Province of China, where mixed songs have been observed. In this study, we investigated the potential causes and consequences of song mixing by integrating bioacoustic, morphological, mitochondrial, and genomic data with field ecological observations. We found that the two species display no apparent morphological differences, whereas their songs differ dramatically. We demonstrated that ∼11% of the males in the contact zone sang mixed songs. Two males singing mixed song were genotyped, and both were found to be P. kansuensis. Despite the presence of mixed singers, population genomic analyses detected no signs of recent gene flow between the two species, although two possible cases of mitochondrial introgression were identified. We conclude that the rather limited song mixing does not lead to, or result from, hybridization, and hence does not result in the breakdown of reproductive barriers between these cryptic species.
Similarity and difference between systemic lupus erythematosus and NZB/W F1 mice by multi-omics analysis
Authors: Okuma Kenji , Oku Takuma , Sasaki Chiyomi , Kitagori Koji , Mimori Tsuneyo , Aramori Ichiro , Hirayama Yoshitaka , Yoshifuji Hajime 
Published: March 2023

ABSTRACTObjectivesSeveral animal disease models have been used to understand the mechanisms of systemic lupus erythematosus (SLE); however, the translation of findings from animals to humans has not been sufficiently examined in drug development. To confirm the validity of New Zealand black x New Zealand white (NZB/W) F1 mice as an SLE model, we extensively characterized SLE patients and NZB/W F1 mice by omics analysis.MethodsPeripheral blood from patients and mice and spleen and lymph node tissue from mice were analysed using cell subset analysis, cytokine panel assays, and transcriptome analysis.ResultsCD4+ effector memory T cells, plasmablasts, and plasma cells were increased in both SLE patients and NZB/W F1 mice. Levels of tumor necrosis factor-α, interferon gamma induced protein-10, and B cell activating factor in plasma were significantly higher in SLE patients and NZB/W F1 mice than in their corresponding controls. Transcriptome analysis revealed an upregulation of genes involved in the interferon signalling pathway and T-cell exhaustion signalling pathway in both SLE patients and the mouse model. In contrast, death receptor signalling genes showed changes in the opposite direction between patients and mice.ConclusionNZB/W F1 mice are a generally suitable model of SLE for analysing the pathophysiology and treatment response of T/B cells and monocytes/macrophages and their secreted cytokines.
Weak tension accelerates hybridization and dehybridization of short oligonucleotides
Authors: Hart Derek J , Jeong Jiyoun , Gumbart James C , Kim Harold D 
Published: March 2023

Abstract
The hybridization and dehybridization of DNA subject to tension is relevant to fundamental genetic processes and to the design of DNA-based mechanobiology assays. While strong tension accelerates DNA melting and decelerates DNA annealing, the effects of tension weaker than 5 pN are less clear. In this study, we developed a DNA bow assay, which uses the bending rigidity of double-stranded DNA (dsDNA) to exert weak tension on a single-stranded DNA (ssDNA) target in the range of 2–6 pN. Combining this assay with single-molecule FRET, we measured the hybridization and dehybridization kinetics between a 15 nt ssDNA under tension and a 8–9  nt oligonucleotide, and found that both the hybridization and dehybridization rates monotonically increase with tension for various nucleotide sequences tested. These findings suggest that the nucleated duplex in its transition state is more extended than the pure dsDNA or ssDNA counterpart. Based on coarse-grained oxDNA simulations, we propose that this increased extension of the transition state is due to steric repulsion between the unpaired ssDNA segments in close proximity to one another. Using linear force-extension relations verified by simulations of short DNA segments, we derived analytical equations for force-to-rate conversion that are in good agreement with our measurements.
Identification and characterization of thousands of bacteriophage satellites across bacteria
Authors: de Sousa Jorge A Moura , Fillol-Salom Alfred , Penadés José R , Rocha Eduardo P C 
Published: March 2023

AbstractBacteriophage–bacteria interactions are affected by phage satellites, elements that exploit phages for transfer between bacteria. Satellites can encode defense systems, antibiotic resistance genes, and virulence factors, but their number and diversity are unknown. We developed SatelliteFinder to identify satellites in bacterial genomes, detecting the four best described families: P4-like, phage inducible chromosomal islands (PICI), capsid-forming PICI, and PICI-like elements (PLE). We vastly expanded the number of described elements to ∼5000, finding bacterial genomes with up to three different families of satellites. Most satellites were found in Proteobacteria and Firmicutes, but some are in novel taxa such as Actinobacteria. We characterized the gene repertoires of satellites, which are variable in size and composition, and their genomic organization, which is very conserved. Phylogenies of core genes in PICI and cfPICI indicate independent evolution of their hijacking modules. There are few other homologous core genes between other families of satellites, and even fewer homologous to phages. Hence, phage satellites are ancient, diverse, and probably evolved multiple times independently. Given the many bacteria infected by phages that still lack known satellites, and the recent proposals for novel families, we speculate that we are at the beginning of the discovery of massive numbers and types of satellites.
PRRC2 proteins impact translation initiation by promoting leaky scanning
Authors: Bohlen Jonathan , Roiuk Mykola , Neff Marilena , Teleman Aurelio A 
Published: March 2023

Abstract
Roughly half of animal mRNAs contain upstream open reading frames (uORFs). These uORFs can represent an impediment to translation of the main ORF since ribosomes usually bind the mRNA cap at the 5′ end and then scan for ORFs in a 5′-to-3′ fashion. One way for ribosomes to bypass uORFs is via leaky scanning, whereby the ribosome disregards the uORF start codon. Hence leaky scanning is an important instance of post-transcriptional regulation that affects gene expression. Few molecular factors regulating or facilitating this process are known. Here we show that the PRRC2 proteins PRRC2A, PRRC2B and PRRC2C impact translation initiation. We find that they bind eukaryotic translation initiation factors and preinitiation complexes, and are enriched on ribosomes translating mRNAs with uORFs. We find that PRRC2 proteins promote leaky scanning past translation start codons, thereby promoting translation of mRNAs containing uORFs. Since PRRC2 proteins have been associated with cancer, this provides a mechanistic starting point for understanding their physiological and pathophysiological roles.
SelectBCM tool: a batch evaluation framework to select the most appropriate batch-correction methods for bulk transcriptome analysis
Authors: Mishra Madhulika , Barck Lucas , Moreno Pablo , Heger Guillaume , Song Yuyao , Thornton Janet M , Papatheodorou Irene 
Published: March 2023

AbstractBulk transcriptomes are an essential data resource for understanding basic and disease biology. However, integrating information from different experiments remains challenging because of the batch effect generated by various technological and biological variations in the transcriptome. Numerous batch-correction methods to deal with this batch effect have been developed in the past. However, a user-friendly workflow to select the most appropriate batch-correction method for the given set of experiments is still missing. We present the SelectBCM tool that prioritizes the most appropriate batch-correction method for a given set of bulk transcriptomic experiments, improving biological clustering and gene differential expression analysis. We demonstrate the applicability of the SelectBCM tool on analyses of real data for two common diseases, rheumatoid arthritis and osteoarthritis, and one example to characterize a biological state, where we performed a meta-analysis of the macrophage activation state. The R package is available at https://github.com/ebi-gene-expression-group/selectBCM.
cgRNASP: coarse-grained statistical potentials with residue separation for RNA structure evaluation
Authors: Tan Ya-Lan , Wang Xunxun , Yu Shixiong , Zhang Bengong , Tan Zhi-Jie 
Published: March 2023

AbstractKnowledge-based statistical potentials are very important for RNA 3-dimensional (3D) structure prediction and evaluation. In recent years, various coarse-grained (CG) and all-atom models have been developed for predicting RNA 3D structures, while there is still lack of reliable CG statistical potentials not only for CG structure evaluation but also for all-atom structure evaluation at high efficiency. In this work, we have developed a series of residue-separation-based CG statistical potentials at different CG levels for RNA 3D structure evaluation, namely cgRNASP, which is composed of long-ranged and short-ranged interactions by residue separation. Compared with the newly developed all-atom rsRNASP, the short-ranged interaction in cgRNASP was involved more subtly and completely. Our examinations show that, the performance of cgRNASP varies with CG levels and compared with rsRNASP, cgRNASP has similarly good performance for extensive types of test datasets and can have slightly better performance for the realistic dataset—RNA-Puzzles dataset. Furthermore, cgRNASP is strikingly more efficient than all-atom statistical potentials/scoring functions, and can be apparently superior to other all-atom statistical potentials and scoring functions trained from neural networks for the RNA-Puzzles dataset. cgRNASP is available at https://github.com/Tan-group/cgRNASP.
BaM-seq and TBaM-seq, highly multiplexed and targeted RNA-seq protocols for rapid, low-cost library generation from bacterial samples
Authors: Johnson Grace E , Parker Darren J , Lalanne Jean-Benoit , Parker Mirae L , Li Gene-Wei 
Published: March 2023

Abstract
The ability to profile transcriptomes and characterize global gene expression changes has been greatly enabled by the development of RNA sequencing technologies (RNA-seq). However, the process of generating sequencing-compatible cDNA libraries from RNA samples can be time-consuming and expensive, especially for bacterial mRNAs which lack poly(A)-tails that are often used to streamline this process for eukaryotic samples. Compared to the increasing throughput and decreasing cost of sequencing, library preparation has had limited advances. Here, we describe bacterial-multiplexed-seq (BaM-seq), an approach that enables simple barcoding of many bacterial RNA samples that decreases the time and cost of library preparation. We also present targeted-bacterial-multiplexed-seq (TBaM-seq) that allows for differential expression analysis of specific gene panels with over 100-fold enrichment in read coverage. In addition, we introduce the concept of transcriptome redistribution based on TBaM-seq that dramatically reduces the required sequencing depth while still allowing for quantification of both highly and lowly abundant transcripts. These methods accurately measure gene expression changes with high technical reproducibility and agreement with gold standard, lower throughput approaches. Together, use of these library preparation protocols allows for fast, affordable generation of sequencing libraries.
De-novoreconstruction and identification of transcriptional gene regulatory network modules differentiating single-cell clusters
Authors: Oubounyt Mhaned , Elkjaer Maria L , Laske Tanja , Grønning Alexander G B , Moeller Marcus J , Baumbach Jan 
Published: March 2023

AbstractSingle-cell RNA sequencing (scRNA-seq) technology provides an unprecedented opportunity to understand gene functions and interactions at single-cell resolution. While computational tools for scRNA-seq data analysis to decipher differential gene expression profiles and differential pathway expression exist, we still lack methods to learn differential regulatory disease mechanisms directly from the single-cell data. Here, we provide a new methodology, named DiNiro, to unravel such mechanisms de novo and report them as small, easily interpretable transcriptional regulatory network modules. We demonstrate that DiNiro is able to uncover novel, relevant, and deep mechanistic models that not just predict but explain differential cellular gene expression programs. DiNiro is available at https://exbio.wzw.tum.de/diniro/.
Genital Herpes Simplex Virus Type 2 Suppression With Valacyclovir Is Not Associated With Changes in Nugent Score or Absolute Abundance of Key Vaginal Bacteria
Authors: Babu Tara M , Srinivasan Sujatha , Magaret Amalia , Proll Sean , Karita Helen Stankiewicz , Wallis Jacqueline M , Selke Stacy , Varon Dana , Pholsena Thepthara , Fredricks David , Marrazzo Jeanne , Wald Anna , Johnston Christine 
Published: March 2023

AbstractBackgroundIn women, genital herpes simplex virus type 2 (HSV-2) infection is associated with increased risk for recurrent bacterial vaginosis (BV), but causal relationships are unclear.MethodsWomen with a self-reported history of BV and HSV-2 seropositivity self-collected vaginal and anogenital swabs for 2 nonconsecutive 28-day periods, in the absence or presence of valacyclovir suppressive therapy (500 mg daily). HSV polymerase chain reaction was performed on anogenital swabs; vaginal swabs were used for assessment of BV by Nugent score and quantification of vaginal microbiota. Days with BV, defined by Nugent score ≥7, were compared during the observational period and valacyclovir treatment.ResultsForty-one women collected swabs for a median of 28 days (range, 20–32 days) each study period. The HSV-2 shedding rate decreased from 109 of 1126 days (9.7%) presuppression to 6 of 1125 days (0.05%) during valacyclovir (rate ratio [RR], 0.06 [95% confidence interval {CI}, .02–.13]). BV occurred on 343 of 1103 days (31.1%) during observation and 302 of 1091 days (27.7%) during valacyclovir (RR, 0.90 [95% CI, .68–1.20]). The median per-person Nugent score was 3.8 during observation and 4.0 during valacyclovir. Average log10 concentrations of vaginal bacterial species did not change significantly during valacyclovir treatment.ConclusionsShort-term HSV-2 suppression with valacyclovir did not significantly affect the Nugent score or the vaginal microbiome despite potent suppression of HSV-2 shedding.
Effectiveness of Noncertified Pharmacist–Led Antimicrobial Stewardship Programs in a Medium-Sized Hospital Without an Infectious Disease Specialist: A Retrospective Pre–Post Study
Authors: Sawada Keisuke , Inose Ryo , Goto Ryota , Nakatani Takeshi , Kono Shuji , Muraki Yuichi 
Published: March 2023

AbstractBackgroundFew studies have reported the outcomes of antimicrobial stewardship programs (ASPs) implemented without infectious disease (ID) physician or pharmacist specialists. We implemented interventions that included providing antimicrobial optimization recommendations through a pharmacist-led team using prospective audit and feedback. This study evaluated different types of interventions and their impact on the outcomes of ASPs in a medium-sized hospital without ID specialists.MethodsThis retrospective pre–post study included adult inpatients treated with intravenous antimicrobials between April 2016 and March 2020. Outcome (eg, length of hospital stay [LOS], drug cost) and process measures (eg, type of intervention, length of therapy) were compared between 2 time periods: pre-ASP (April 2016–March 2018) and post-ASP (April 2018–March 2020).ResultsWe included 5419 and 5634 patients in the pre- and post-ASP periods, respectively. The most common types of interventions were adjusting length of therapy (49.5%), additional laboratory tests (27.1%), antimicrobial change (16.2%), and dosage of antimicrobial (7.1%). After ASP implementation, LOS significantly decreased (14.8 vs 13.8 days, P &lt; .01), along with the length of therapy, empirical use of antipseudomonal and anti–methicillin-resistant Staphylococcus aureus drugs, and number of days to de-escalation. No significant differences were noted in 30-day mortality, 30-day readmission, or de-escalation rates. On average, the antimicrobial cost per hospitalization decreased from US$173.03 to US$120.66.ConclusionsPharmacist-led ASP interventions that focus on the length of therapy have the potential to reduce LOS in hospitals without ID specialists. Overall, this study showed that ASPs can be effectively implemented in medium-sized hospitals without ID specialists.
Factors Associated With Adherence to First-line Antiviral Therapy Among Commercially Insured Patients With Chronic Hepatitis B
Authors: Alpern Jonathan D , Joo Heesoo , Bahr Nathan C , Leventhal Thomas M 
Published: March 2023

AbstractBackgroundNonadherence to antiviral therapy can lead to poor clinical outcomes among patients with chronic hepatitis B (CHB). We used a claims database to evaluate risk factors for nonadherence to antiviral therapy among commercially insured patients with CHB in the United States.MethodsWe obtained data for commercially insured adult patients with CHB prescribed entecavir or tenofovir disoproxil fumarate (TDF) in 2019. Primary outcomes were adherence to entecavir and adherence to TDF. Enrollees with a proportion of days covered (PDC) ≥80% were considered adherent. We presented adjusted odds ratios (AORs) from multivariate logistic regressions.ResultsEighty-three percent (n = 640) of entecavir patients were adherent, and 81% (n = 687) of TDF patients were adherent. Ninety-day supply (vs 30-day supply; AOR, 2.21; P &lt; .01), mixed supply (vs 30-day supply; AOR, 2.19; P = .04), and ever using a mail order pharmacy (AOR, 1.92, P = .03) were associated with adherence to entecavir. Ninety-day supply (vs 30-day supply; AOR, 2.51; P &lt; .01), mixed supply (vs 30-day supply; AOR, 1.82; P = .04), and use of a high-deductible health plan (vs no high-deductible health plan; AOR, 2.29; P = .01) were associated with adherence to TDF. Out-of-pocket spending of &gt;$25 per 30-day supply of TDF was associated with reduced odds of adherence to TDF (vs &lt;$5 per 30-day supply of TDF; AOR, 0.34; P &lt; .01).ConclusionsNinety-day and mixed-duration supplies of entecavir and TDF were associated with higher fill rates as compared with 30-day supplies among commercially insured patients with CHB.
Tenosynovial Giant Cell Tumor Observational Platform Project (TOPP) Registry: A 2-Year Analysis of Patient-Reported Outcomes and Treatment Strategies
Authors: Palmerini Emanuela , Healey John H , Bernthal Nicholas M , Bauer Sebastian , Schreuder Hendrik , Leithner Andreas , Martin-Broto Javier , Gouin Francois , Lopez-Bastida Julio , Gelderblom Hans , Staals Eric L , Mercier Florence , Laeis Petra , Ye Xin , van de Sande Michiel 
Published: March 2023

Abstract

Background
The Tenosynovial giant cell tumor Observational Platform Project (TOPP) registry is an international prospective study that ­previously described the impact of diffuse-type tenosynovial giant cell tumour (D-TGCT) on patient-reported outcomes (PROs) from a baseline snapshot. This analysis describes the impact of D-TGCT at 2-year follow-up based on treatment strategies.

Material and Methods
TOPP was conducted at 12 sites (EU: 10; US: 2). Captured PRO measurements assessed at baseline, 1-year, and 2-year follow-ups were Brief Pain Inventory (BPI), Pain Interference, BPI Pain Severity, Worst Pain, EQ-5D-5L, Worst Stiffness, and ­Patient-Reported Outcomes Measurement Information System. Treatment interventions were no current/planned treatment (Off-Treatment) and systemic treatment/surgery (On-Treatment).

Results
A total of 176 patients (mean age: 43.5 years) were included in the full analysis set. For patients without active treatment strategy ­(Off-Treatment) at baseline (n = 79), BPI Pain Interference (1.00 vs. 2.86) and BPI Pain Severity scores (1.50 vs. 3.00) were numerically favorable in patients remaining Off-Treatment compared with those who switched to an active treatment strategy at year 1. From 1-year to 2-year ­follow-ups, patients who remained Off-Treatment had better BPI Pain Interference (0.57 vs. 2.57) and Worst Pain (2.0 vs. 4.5) scores compared with patients who switched to an alternative treatment strategy. In addition, EQ-5D VAS scores (80.0 vs. 65.0) were higher in patients who remained ­Off-Treatment between 1-year and 2-year follow-ups compared with patients who changed treatment strategy. For patients receiving systemic treatment at baseline, numerically favorable scores were seen in patients remaining on systemic therapy at 1-year follow-up: BPI Pain Interference (2.79 vs. 5.93), BPI Pain Severity (3.63 vs. 6.38), Worst Pain (4.5 vs. 7.5), and Worst Stiffness (4.0 vs. 7.5). From 1-year to 2-year follow-up, EQ-5D VAS scores (77.5 vs. 65.0) were higher in patients who changed from systemic treatment to a different treatment strategy.

Conclusion
These findings highlight the impact D-TGCT has on patient quality of life, and how treatment strategies may be influenced by these outcome measures. (ClinicalTrials.gov number: NCT02948088)
Exercising Caution: A Case for Ethics Analysis in Physical Activity Promotion
Authors: Esmonde Katelyn 
Published: March 2023

Abstract
Despite the important role of physical activity in population health and well-being, it has received less focus in public health ethics as compared to other modifiable lifestyle factors such as smoking and diet. However, when considering the current and potential role of physical activity within public health—including interventions and policies to encourage physical activity in schools and workplaces, changes to the built environment and the equity issues associated with access to physical activity—it is a ripe territory for ethical analysis. This paper makes a case for a more sustained focus on physical activity within public health ethics by reviewing two ethical issues within physical activity and public health: physical activity inequity as a structural injustice issue, and stigma in physical activity promotion. While the benefits of physical activity for every age group and demographic are numerous, ethics oversight is encouraged to ensure that these efforts do not impose unnecessary risks or stigmatize marginalized populations.