bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accessible gene borders establish a core structural unit for chromatin architecture in Arabidopsis
Authors: Lee Hongwoo , Seo Pil Joon 
Published: October 2023

Abstract
Three-dimensional (3D) chromatin structure is linked to transcriptional regulation in multicellular eukaryotes including plants. Taking advantage of high-resolution Hi-C (high-throughput chromatin conformation capture), we detected a small structural unit with 3D chromatin architecture in the Arabidopsis genome, which lacks topologically associating domains, and also in the genomes of tomato, maize, and Marchantia polymorpha. The 3D folding domain unit was usually established around an individual gene and was dependent on chromatin accessibility at the transcription start site (TSS) and transcription end site (TES). We also observed larger contact domains containing two or more neighboring genes, which were dependent on accessible border regions. Binding of transcription factors to accessible TSS/TES regions formed these gene domains. We successfully simulated these Hi-C contact maps via computational modeling using chromatin accessibility as input. Our results demonstrate that gene domains establish basic 3D chromatin architecture units that likely contribute to higher-order 3D genome folding in plants.
VarEPS-Influ:an risk evaluation system of occurred and virtual variations of influenza virus genomes
Authors: Shu Chang , Sun Qinglan , Fan Guomei , Peng Kesheng , Yu Zhengfei , Luo Yingfeng , Gao Shenghan , Ma Juncai , Deng Tao , Hu Songnian , Wu Linhuan 
Published: October 2023

Abstract
Influenza viruses undergo frequent genomic mutations, leading to potential cross-species transmission, phenotypic changes, and challenges in diagnostic reagents and vaccines. Accurately evaluating and predicting the risk of such variations remain significant challenges. To address this, we developed the VarEPS-Influ database, an influenza virus variations risk evaluation system (VarEPS-Influ). This database employs a ‘multi-dimensional evaluation of mutations’ strategy, utilizing various tools to assess the physical and chemical properties, primary, secondary, and tertiary structures, receptor affinity, antibody binding capacity, antigen epitopes, and other aspects of the variation's impact. Additionally, we consider space-time distribution, host species distribution, pedigree analysis, and frequency of mutations to provide a comprehensive risk evaluation of mutations and viruses. The VarEPS-Influ database evaluates both observed variations and virtual variations (variations that have not yet occurred), thereby addressing the time-lag issue in risk predictions. Our current one-stop evaluation system for influenza virus genomic variation integrates 1065290 sequences from 224 927 Influenza A, B and C isolates retrieved from public resources. Researchers can freely access the data at https://nmdc.cn/influvar/.
eRNAbase: a comprehensive database for decoding the regulatory eRNAs in human and mouse
Authors: Song Chao , Zhang Guorui , Mu Xinxin , Feng Chenchen , Zhang Qinyi , Song Shuang , Zhang Yuexin , Yin Mingxue , Zhang Hang , Tang Huifang , Li Chunquan 
Published: October 2023

Abstract
Enhancer RNAs (eRNAs) transcribed from distal active enhancers serve as key regulators in gene transcriptional regulation. The accumulation of eRNAs from multiple sequencing assays has led to an urgent need to comprehensively collect and process these data to illustrate the regulatory landscape of eRNAs. To address this need, we developed the eRNAbase (http://bio.liclab.net/eRNAbase/index.php) to store the massive available resources of human and mouse eRNAs and provide comprehensive annotation and analyses for eRNAs. The current version of eRNAbase cataloged 10 399 928 eRNAs from 1012 samples, including 858 human samples and 154 mouse samples. These eRNAs were first identified and uniformly processed from 14 eRNA-related experiment types manually collected from GEO/SRA and ENCODE. Importantly, the eRNAbase provides detailed and abundant (epi)genetic annotations in eRNA regions, such as super enhancers, enhancers, common single nucleotide polymorphisms, expression quantitative trait loci, transcription factor binding sites, CRISPR/Cas9 target sites, DNase I hypersensitivity sites, chromatin accessibility regions, methylation sites, chromatin interactions regions, topologically associating domains and RNA spatial interactions. Furthermore, the eRNAbase provides users with three novel analyses including eRNA-mediated pathway regulatory analysis, eRNA-based variation interpretation analysis and eRNA-mediated TF–target gene analysis. Hence, eRNAbase is a powerful platform to query, browse and visualize regulatory cues associated with eRNAs.
A task-specific encoding algorithm for RNAs and RNA-associated interactions based on convolutional autoencoder
Authors: Wang Yunxia , Pan Ziqi , Mou Minjie , Xia Weiqi , Zhang Hongning , Zhang Hanyu , Liu Jin , Zheng Lingyan , Luo Yongchao , Zheng Hanqi , Yu Xinyuan , Lian Xichen , Zeng Zhenyu , Li Zhaorong , Zhang Bing , Zheng Mingyue , Li Honglin , Hou Tingjun , Zhu Feng 
Published: October 2023

AbstractRNAs play essential roles in diverse physiological and pathological processes by interacting with other molecules (RNA/protein/compound), and various computational methods are available for identifying these interactions. However, the encoding features provided by existing methods are limited and the existing tools does not offer an effective way to integrate the interacting partners. In this study, a task-specific encoding algorithm for RNAs and RNA-associated interactions was therefore developed. This new algorithm was unique in (a) realizing comprehensive RNA feature encoding by introducing a great many of novel features and (b) enabling task-specific integration of interacting partners using convolutional autoencoder-directed feature embedding. Compared with existing methods/tools, this novel algorithm demonstrated superior performances in diverse benchmark testing studies. This algorithm together with its source code could be readily accessed by all user at: https://idrblab.org/corain/ and https://github.com/idrblab/corain/.
Ventilator Weaning and Terminal Extubation: Withdrawal of Life-Sustaining Therapy in Children. Secondary Analysis of the Death One Hour After Terminal Extubation Study
Authors: Pringle Charlene P. , Filipp Stephanie L. , Morrison Wynne E. , Fainberg Nina A. , Aczon Melissa D. , Avesar Michael , Burkiewicz Kimberly F. , Chandnani Harsha K. , Hsu Stephanie C. , Laksana Eugene , Ledbetter David R. , McCrory Michael C. , Morrow Katie R. , Noguchi Anna E. , O’Brien Caitlin E. , Ojha Apoorva , Ross Patrick A. , Shah Sareen , Shah Jui K. , Siegel Linda B. , Tripathi Sandeep , Wetzel Randall C. , Zhou Alice X. , Winter Meredith C. 
Published: October 2023

OBJECTIVE:
Terminal extubation (TE) and terminal weaning (TW) during withdrawal of life-sustaining therapies (WLSTs) have been described and defined in adults. The recent Death One Hour After Terminal Extubation study aimed to validate a model developed to predict whether a child would die within 1 hour after discontinuation of mechanical ventilation for WLST. Although TW has not been described in children, pre-extubation weaning has been known to occur before WLST, though to what extent is unknown. In this preplanned secondary analysis, we aim to describe/define TE and pre-extubation weaning (PW) in children and compare characteristics of patients who had ventilatory support decreased before WLST with those who did not.

DESIGN:
Secondary analysis of multicenter retrospective cohort study.

SETTING:
Ten PICUs in the United States between 2009 and 2021.

PATIENTS:
Nine hundred thirteen patients 0–21 years old who died after WLST.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
71.4% (n = 652) had TE without decrease in ventilatory support in the 6 hours prior. TE without decrease in ventilatory support in the 6 hours prior = 71.4% (n = 652) of our sample. Clinically relevant decrease in ventilatory support before WLST = 11% (n = 100), and 17.6% (n = 161) had likely incidental decrease in ventilatory support before WLST. Relevant ventilator parameters decreased were Fio
2 and/or ventilator set rates. There were no significant differences in any of the other evaluated patient characteristics between groups (weight, body mass index, unit type, primary diagnostic category, presence of coma, time to death after WLST, analgosedative requirements, postextubation respiratory support modality).

CONCLUSIONS:
Decreasing ventilatory support before WLST with extubation in children does occur. This practice was not associated with significant differences in palliative analgosedation doses or time to death after extubation.
Effect of combined tobacco use and type 2 diabetes mellitus on prevalent fibrosis in patients with MASLD
Authors: Balogun Oluwafemi , Wang Jeffrey Y. , Shaikh Emad S. , Liu Karine , Stoyanova Stefania , Memel Zoe N. , Schultz Hayley , Mun Lisa , Bertman Jack , Rogen Cheryl A. , Ibrahim Maryam K. , Berschback Madeline , Uche-Anya Eugenia , Wilechansky Robert , Simon Tracey G. , Corey Kathleen E. 
Published: October 2023

Background:
Several studies have investigated the independent effect of cigarette smoking or type 2 diabetes mellitus (T2DM) on MASLD. However, the interaction effect between tobacco consumption and T2DM on MASLD severity remains underexplored. In this study, we assessed the combined effect of tobacco use and T2DM on hepatic fibrosis in MASLD.

Methods:
We conducted a single-center retrospective cross-sectional analysis of eligible participants from the Mass General Brigham Fibroscan© database. The participants were divided into 3 groups: those with T2DM and a history of tobacco use (primary exposure group), those with T2DM but no history of tobacco use (secondary exposure group), and those without T2DM and no history of tobacco use (reference group). An additional model was developed, which included a fourth group, participants with a history of tobacco use but no T2DM. The likelihood of fibrosis was determined using a defined fibrosis-4 index cutoff value of 1.3. In addition, we computed the estimated marginal means for liver stiffness measurement and compared the values among the exposure groups. Bivariable and multivariable logistic regression models were used to explore the associations between the exposure groups and the risk for hepatic fibrosis.

Results:
Overall, 598 individuals were enrolled in the study. The bivariable logistic regression model revealed a significant independent association between T2DM, combined smoking and T2DM, and the outcome of interest, fibrosis. Age, sex, metabolic syndrome, aspirin use, statin use, hemoglobin A1C (A1C), and total bilirubin level were also significantly associated with fibrosis. In the adjusted fibrosis-4 multivariable model (comparing exposure groups to controls), cigarette smoking and T2DM interaction had higher odds of prevalent fibrosis (aOR, 3.04; 95% CI, 1.62–5.76), compared to those with T2DM alone (aOR 2.28; 95% CI, 1.37–3.85). The continuous liver stiffness measurement comparison across the exposure group showed an estimated marginal means of 6.26 (95% CL: 5.58–6.94), 7.54 (95% CL: 6.78–8.30), and 7.88 (6.78–8.99) for the reference group, T2DM only group, and tobacco-T2DM group, respectively. The diabetes-only group and the combined tobacco-T2DM group had statistically significant associations with liver stiffness measurement (p values: 0.013 and 0.014, respectively).

Conclusion:
Although diabetes is independently associated with hepatic fibrosis in patients with MASLD, the combination of tobacco consumption and diabetes is associated with a higher prevalence of fibrosis. Therefore, lifestyle change through tobacco use cessation in patients with diabetes could be beneficial in reducing the incidence of liver fibrosis among individuals with MASLD.
It Is All About the Angle: A Clinical and Optical Coherence Tomography Comparison of Corneal Ocular Surface Squamous Neoplasia and Corneal Pannus
Authors: Huang Jaxon J. , Locatelli Elyana V. T. , Huang Jordan J. , De Arrigunaga Sofia , Rao Pragnya , Dubovy Sander , Karp Carol L. , Galor Anat 
Published: October 2023

Purpose:
The aim of this study was to compare clinical characteristics and high-resolution optical coherence tomography (HR-OCT) findings between corneal ocular surface squamous neoplasia (OSSN) and corneal pannus.

Methods:
Retrospective study of 9 individuals, 3 with lesions histologically confirmed to be OSSN, 3 with lesions histologically confirmed to be pannus, 1 with lesions histologically confirmed to be OSSN followed by pannus, and 2 with long-standing, nonchanging lesions clinically diagnosed as pannus. All individuals presented to the Miami Veterans Affairs Medical Center eye clinic or Bascom Palmer Eye Institute between 2015 and 2023. Clinical characteristics and HR-OCT findings were evaluated and compared.

Results:
Mean age of the population was 72.8 ± 5.1 years, 100% self-identified as male, 100% as White, and 11.1% as Hispanic. Clinically, all lesions appeared as whitish, opalescent, variably vascularized opacities extending from the limbus. None of the OSSN cases had vessels that extended to the border, whereas 4 cases of pannus (67%) had at least 1 vessel that reached the border. On HR-OCT, epithelial hyperreflectivity was observed in all cases of OSSN and pannus. Epithelial thickening was observed in all cases of OSSN, but in none of the cases of pannus. An important distinction between the 2 groups was the transition between normal and abnormal epithelium. All cases of OSSN had a vertical transition, whereas all cases of pannus had an angled transition.

Conclusions:
Corneal OSSN and corneal pannus can both present with clinical findings of an opalescent lesion and may have overlapping findings on HR-OCT. Although both entities may show epithelial hyperreflectivity on HR-OCT, OSSN demonstrates an abrupt transition at a vertical, 90 degrees angle perpendicular to the Bowman layer, whereas pannus appears as an angled transition around 45 degrees. Therefore, the angle of transition between normal and abnormal epithelium can be useful in distinguishing between the 2 entities.
Comparison of direct intra-arterial pressure and ClearSight finger cuff arterial pressure measurements in elderly patients undergoing transcatheter aortic valve replacement
Authors: Yahagi Musashi , Sasaki Momoko 
Published: October 2023

Objective:
This study aimed to assess the agreement between direct intra-arterial pressure and ClearSight finger cuff arterial pressure measurements in elderly patients undergoing transcatheter aortic valve replacement (TAVR).

Methods:
A prospective observational study was conducted at Hitachi General Hospital, Japan, involving 30 patients aged 65 years and older who underwent TAVR under general anesthesia. Intra-arterial pressure and finger cuff arterial pressure measurements were recorded for 30 min after valve deployment. Bland–Altman analysis, four-quadrant plot analysis, and error grid analysis were used to assess the concordance between the two methods. Multiple regression analysis was performed to explore potential confounding factors affecting the agreement.

Results:
The bias and precision of ClearSight measurements were −4.88 ± 15.46 (mmHg) for SBP, 4.73 ± 8.95 (mmHg) for mean, and 9.53 ± 9.01 (mmHg) for DBP. The Bland–Altman analysis demonstrated acceptable agreement between intra-arterial pressure and finger cuff arterial pressure measurements. The four-quadrant plot analysis showed good trend-tracking ability, and the error grid analysis revealed that most of the observed values fell into the no-risk category. The mean BP match ratio and SBP match ratio were influenced by several factors such as age, BSA, ejection fraction, valve size, and gender.

Conclusion:
The ClearSight finger cuff arterial pressure measurement showed good agreement with direct intra-arterial pressure in elderly patients undergoing TAVR. However, factors such as age, BSA, ejection fraction, valve size, and gender may influence the agreement between the two methods.
Real-world use of antiretroviral therapy and risk of cancer among people with HIV in Texas
Authors: Horner Marie-Josephe , Shiels Meredith S. , McNeel Timothy S. , Monterosso Analise , Miller Paige , Pfeiffer Ruth M. , Engels Eric A. 
Published: October 2023

Background:
Combination antiretroviral therapy (cART) may reduce cancer risk among people with HIV (PWH), but cancer-specific associations are incompletely understood.

Methods:
We linked HIV and cancer registries in Texas to a national prescription claims database. cART use was quantified as the proportion of days covered (PDC). Cox proportional hazards models assessed associations of cancer risk with cART usage, adjusting for demographic characteristics, AIDS status, and time since HIV report.

Results:
We evaluated 63 694 PWH followed for 276 804 person-years. The median cART PDC was 21.4% (interquartile range: 0.0–59.8%). cART use was associated with reduced risk of Kaposi sarcoma [adjusted hazard ratio (aHR) 0.48, 95% confidence interval (CI) 0.34–0.68 relative to unexposed status] and non-Hodgkin lymphoma (aHR 0.41, 95% CI 0.31–0.53), liver cancer (aHR 0.61, 95% CI 0.39–0.96), anal cancer (aHR 0.65, 95% CI 0.46–0.92), and a miscellaneous group of ‘other’ cancers (aHR 0.80, 95% CI 0.66–0.98). In contrast, cART-exposed status was not associated with risk for cervical, lung, colorectal, prostate or breast cancers.

Conclusion:
In a large HIV cohort incorporating data from prescription claims, cART was associated with greatly reduced risks of Kaposi sarcoma and non-Hodgkin lymphoma, and to a lesser degree, reduced risks of liver and anal cancers. These associations likely reflect the beneficial effects of HIV suppression and improved immune control of oncogenic viruses. Efforts to increase cART use and adherence may further decrease cancer incidence among PWH.
Aurantibacillus circumpalustris gen. nov., sp. nov., the first characterized representative of the Bacteroidota candidate family env.OPS 17 and proposal of Aurantibacillaceae fam. nov.
Authors: Vieira Selma , Riedel Thomas , Geppert Alicia , Rohde Manfred , Wolf Jacqueline , Neumann-Schaal Meina , Overmann Jörg 
Published: October 2023

16S rRNA sequence types associated with the candidate family env.OPS 17 have been reported from various environments, but no representatives have been characterized and validly named. Bacteria of env.OPS 17 are affiliated with the order

Sphingobacteriales

and were first detected more than two decades ago in the vicinity of a thermal spring in Yellowstone National Park. Strain Swamp196T, isolated from the soil surrounding a swamp in Northern Germany, is the first characterized representative of candidate family env.OPS 17. Cells of strain Swamp196T are rod-shaped, non-motile, non-spore-forming, non-capsulated and stain Gram-negative. Colonies are small and orange-coloured. The strain is mesophilic and grows under aerobic or microaerophilic conditions. It grows chemo-organotrophically over a narrow range of pH and exclusively on proteinaceous substrates. The major cellular fatty acids are iso-C15 : 0, iso-C15 : 1
ω10c, C18 : 1
ω9c and C16 : 1
ω7c and the major polar lipids are two unidentified aminophospholipids, one unidentified aminolipid and one unidentified lipid. The predominant respiratory quinone is MK-7. The DNA G+C content of genomic DNA is 35.5 mol%. Strain Swamp196T is related to

Pedobacter cryophilus

AR-3-17T,

Arcticibacter pallidicorallinus

Hh36T and

Pedobacter daechungensis

Dae 13T with 16S rRNA gene sequence similarity of 84.1, 83.8 and 83.5 %, respectively. Based on our phenotypic, genomic and phylogenetic analysis, we propose the novel species Aurantibacillus circumpalustris sp. nov (type strain Swamp196T=DSM 105849T=CECT 30420T) of the novel genus Aurantibacillus gen. nov. and the novel family Aurantibacillaceae fam. nov.
AlphaMissense is better correlated with functional assays of missense impact than earlier prediction algorithms
Authors: Ljungdahl Alicia , Kohani Sayeh , Page Nicholas F. , Wells Eloise S. , Wigdor Emilie M. , Dong Shan , Sanders Stephan J. 
Published: October 2023

AbstractMissense variants that alter a single amino acid in the encoded protein contribute to many human disorders but pose a substantial challenge in interpretation. Though these variants can be reliably identified through sequencing, distinguishing the clinically significant ones remains difficult, such that “Variants of Unknown Significance” outnumber those classified as “Pathogenic” or “Likely Pathogenic.” Numerousin silicoapproaches have been developed to predict the functional impact of missense variants to inform clinical interpretation, the latest being AlphaMissense, which uses artificial intelligence methods trained on predicted protein structure. To independently assess the performance of AlphaMissense and 38 other predictors of missense severity, we compared predictions to data from multiplexed assays of variant effect (MAVE). MAVE experiments generate almost every possible individual amino acid change in a gene and measure their functional impact using a high-throughput assay. Assessing 17,696 variants across five genes (DDX3X, MSH2, PTEN, KCNQ4, andBRCA1), we find that AlphaMissense is consistently one of the top five algorithms based on correlation with functional impact and is the best-correlated algorithm for two genes. We conclude that AlphaMissense represents the current best-in-class predictor by this metric; however, the improvement over other algorithms is modest. We note that multiple missense predictors, including AlphaMissense, appear to overcall variants as pathogenic despite minimal functional impact and that substantially more high-quality training data, including consistently analyzed patient cohorts and MAVE analyses, are required to improve accuracy.
Developing small Cas9 hybrids using molecular modeling
Authors: Mangin Antoine , Dion Vincent , Menzies Georgina 
Published: October 2023

AbstractThe RNA-guided CRISPR-Cas9 fromStreptococcus pyogenesis the best characterized enzyme for gene editing. Its large size, however, precludes it from being packaged together with its single guide (sg)RNA into a single adeno-associated virus, limitingin vivoapplications. Here, we developed smaller Cas9 hybrids, made of the PAM interacting domain (PID) ofS. pyogenesand the catalytic domains of the smaller Cas9 orthologues, as well as sgRNA cognate hybrids. Molecular modeling revealed that the presence of a sgRNA stabilizes Cas9. Making the D10A mutation to turn Cas9 into a nickase dramatically alters its binding energy to the sgRNA, showing that the approach can identify functionally relevant changes. However, we found that the four Cas9/sgRNA hybrid pairs tested in human cells failed to edit target sequences. We conclude thatin silicoapproaches can identify functional changes caused by point mutations but are not sufficient for designing Cas9/sgRNA hybrids.