bluuebunny/crossref_metadata_2025_split huggingface dataset:
Baseline serum HBV RNA is associated with the risk of hepatitis flare after stopping nucleoside analog therapy in HBeAg-negative participants
Authors: Thompson Alexander J. , Jackson Kathy , Bonanzinga Sara , Hall Sam A.L. , Hume Simon , Burns Gareth S. , Sundararajan Vijaya , Ratnam Dilip , Levy Miriam T. , Lubel John , Nicoll Amanda J. , Strasser Simone I. , Sievert William , Desmond Paul V. , Ngu Meng C. , Sinclair Marie , Meredith Christopher , Matthews Gail , Revill Peter A. , Littlejohn Margaret , Bowden D. Scott , Canchola Jesse A. , Torres Jason , Siew Philip , Lau Jasmin , La Brot Benjamin , Kuchta Alison , Visvanathan Kumar 
Published: July 2023

Background and Aims:
HBV RNA in peripheral blood reflects HBV cccDNA transcriptional activity and may predict clinical outcomes. The prospective Melbourne HBV-STOP trial studied nucleot(s)ide analog discontinuation in HBeAg-negative non-cirrhotic participants with long-term virological suppression. Ninety-six weeks after stopping treatment, the proportion of participants with virological relapse (HBV DNA > 2000 IU/mL), biochemical relapse (ALT > 2 × ULN and HBV DNA > 2000 IU/mL), or hepatitis flare (ALT > 5 × ULN and HBV DNA > 2000 IU/mL) was 89%, 58%, and 38%, respectively. We evaluated the ability of serum HBV RNA levels to predict these outcomes.

Approach & Results:
HBV RNA levels were measured using the Roche cobas 6800/8800 HBV RNA Investigational Assay. Sixty-five participants had baseline and longitudinal off-treatment specimens available for RNA testing. HBV RNA was detectable at baseline in 25% of participants and was associated with a higher risk of biochemical relapse (81% vs. 51%, p value 0.04) and hepatitis flare (63% vs. 31%, p value 0.04). Participants who had undetectable serum HBV RNA as well as HBsAg ≤ 100 IU/mL at baseline were less likely to experience virological relapse (4 of 9, 44%) than participants with detectable HBV RNA and HBsAg level > 100 IU/mL (15/15, 100%; p value 0.0009). Off-treatment levels of HBV RNA were correlated with HBV DNA and were associated with the risk of hepatitis flare.

Conclusions:
Serum HBV RNA may be a useful biomarker for guiding clinical decision-making before stopping nucleot(s)ide analog therapy. Baseline HBV RNA and HBsAg levels are associated with the risk of clinical relapse, hepatitis flare, and disease remission off-treatment.
In-vivo functions and regulation of polyphosphate in the vascular system
Authors: Huang Wen-Chan , Mailer Reiner K. , Renné Thomas 
Published: July 2023

Purpose of review
Polyphosphate, an inorganic polymer consisting of linearly linked phosphate subunits, is ubiquitously found in living organisms. Functions and regulation of the polymer have been analyzed in plants, bacteria and yeast; however, the roles of polyphosphate in mammals are still emerging.

Recent findings
In contrast to synthetic polyphosphate that has been extensively utilized in ex-vivo studies, natural polyphosphate is complexed with bivalent cations (mostly Ca2+) and regardless of chain length, forms microparticles that are retained on the surface of procoagulant platelets, platelet-derived microparticles and cancer extracellular vesicles. On cell surfaces, these Ca2+/polyphosphate aggregates initiate the factor XII-driven contact system, triggering proinflammatory and procoagulant reactions through the kallikrein kinin system and intrinsic pathway of coagulation, respectively. Polyphosphate inhibitors interfere with thrombosis while sparing hemostasis, replicating the effect of factor XII neutralizing agents. Furthermore, polyphosphate binds to platelet factor 4, which has implications for autoimmune thrombotic diseases, such as heparin-induced thrombocytopenia (HIT) and vaccine-induced thrombotic thrombocytopenia (VITT), potentially contributing to their pathogenesis. The metabolism and organ-specific distribution of the polymer remain incompletely defined and is the topic of ongoing research.

Summary
Polyphosphate acts as a procoagulant and proinflammatory mediator. Neutralizing polyphosphate provides well tolerated thromboprotection, mimicking the effects of factor XII deficiency.
Comparison of Urinary Tract Infection Incidence Following Intradetrusor OnabotulinumtoxinA in Office Versus Operating Room Settings
Authors: Briskin Rebeccah S. , Etta Patrick , Luck Ali M. , Raffee Samantha , Atiemo Humphrey O. 
Published: July 2023

Importance
Urinary tract infection (UTI) is a known complication of intradetrusor onabotulinumtoxinA (BTX) injection. However, whether administering intradetrusor BTX in different clinical settings affects the risk of postprocedural UTI has not been investigated.

Objectives
The objective of this study was to assess differences in the incidence of postprocedural UTI in women who received intradetrusor BTX in an outpatient office versus an operating room (OR).

Study Design
We performed a retrospective chart review of intradetrusor BTX procedures at a single institution between 2013 and 2020. Demographic data, comorbidities, and perioperative data were abstracted. The primary outcome was UTI defined as initiation of antibiotics within 30 days following BTX administration based on clinician assessment of symptoms and/or urine culture results. Univariate analysis of patients with and without UTI was performed.

Results
A total of 446 intradetrusor BTX procedures performed on female patients either in an outpatient office (n = 160 [35.9%]) or in an OR (n = 286 [64.1%]) were included in the analysis. Within 30 days of BTX administration, UTI was diagnosed after 14 BTX procedures (8.8%) in the office group and 29 BTX procedures (10.1%) in the OR group (P = 0.633). De novo postprocedural urinary retention occurred in more women who were treated in the office than in the OR (13 [9.6%] vs 3 [1.3%], P < 0.001).

Conclusions
Selecting the appropriate setting for BTX administration is dependent on multiple factors. However, the clinical setting in which intradetrusor BTX is administered may not be an important factor in the development of postprocedural UTI, and further research is warranted.
Patient-Initiated Telephone Calls Before and After Introduction of an Enhanced Recovery After Surgery Protocol for Female Pelvic Reconstructive Surgery
Authors: O'Meara Amanda , LaSala Christina , Rameseshan Aparna , O'Sullivan David M. , Tunitsky-Bitton Elena 
Published: July 2023

Importance
An evaluation of Enhanced Recovery After Surgery (ERAS) effect on perioperative patient phone calls.

Objective
The aim of this study was to compare perioperative patient phone calls before and after implementation of ERAS.

Study Design
This is a retrospective chart review of women who underwent surgery by urogynecologists where ERAS was implemented. Patients who underwent surgery were identified before the implementation and compared with the same time period after implementation. Perioperative phone calls were reviewed and categorized by reason for call. Differences between the 2 groups were compared with a Student t test if normally distributed or with a Mann-Whitney U test if not. Categorical outcomes were reported with a percentage and compared with a χ
2 test with an α level of 0.05.

Results
We reviewed 387 records. There was no difference in the percentage of patient calls before and after implementation of ERAS (preoperatively: 19.8% vs 25.1% [P = 0.21], postoperatively: 64.1% vs 61.5% [P = 0.61]). Questions about chronic home medications were the most common reasons for calling before surgery (pre-ERAS: 16 [42.1%]; post-ERAS: 12 [28.6%]). Questions related to medications, pain, and bowels were the top reasons people called postoperatively. These remained the top 3 in the post-ERAS time period; however, bowel-related questions switched with medications for the top reason.

Conclusions
Despite patient education being an essential component of ERAS with written and verbal instructions provided, our study found no difference in preoperative or postoperative calls with the implementation. By focusing on common concerns, we may be able to improve the patients experience and reduce office phone calls.
Assessment of Adverse Events in a Matched Cohort of Women Undergoing Concurrent Midurethral Sling at the Time of Minimally Invasive Benign Gynecologic Surgery
Authors: Wood Nicole , Casas-Puig Viviana , Ferrando Cecile K. 
Published: July 2023

Importance
Procedures for stress urinary incontinence and benign gynecologic surgery are often performed concurrently, and associated complication rates have previously been unexplored.

Objective
The aim of this study was to compare postoperative complication rates between women undergoing midurethral sling (MUS) placement at the time of benign gynecologic surgery and those undergoing MUS alone.

Study Design
This was a retrospective matched cohort study of women undergoing MUS with or without concurrent minimally invasive benign gynecologic surgery from January 2010 through December 2020. Eligible women undergoing concurrent surgery were matched to a cohort of women undergoing MUS placement alone. The electronic medical record was queried for demographic and perioperative/postoperative data up to 12 months after surgery.

Results
Thirty-eight women met inclusion criteria for the concurrent group, and 152 women were matched accordingly. The overall adverse event rate was 39.5% (95% confidence interval [CI], 0.25–0.55) for the concurrent group and 24.3% (95% CI, 0.18–0.32) for the MUS-only group (P = 0.05). Adverse events with Clavien-Dindo grade ≤ 2 were higher in the concurrent group (Clavien-Dindo Grade 1: 5% vs 0%, P = 0.04; Clavien-Dindo Grade 2: 16% vs 6%, P = 0.04), as was composite postoperative resource utilization (76% vs 49%, P = 0.003). Mesh exposure (P = 0.03) and sling lysis/excision rates (P = 0.02) were higher in the concurrent group. On logistic regression, concurrent surgery cases remained significantly associated with sling mesh erosion (adjusted odds ratio, 12.6; 95% CI, 1.4–116.4).

Conclusions
Midurethral sling placement at the time of minimally invasive benign gynecologic surgery is safe but is associated with a higher incidence of postoperative hospital resource utilization and sling mesh extrusion, and a need for revision.
Lysosomal Degradation Pathways Target Mutant Calreticulin and the Thrombopoietin Receptor in Myeloproliferative Neoplasms
Authors: Kaur Amanpreet , Venkatesan Arunkumar , Kandarpa Malathi , Talpaz Moshe , Raghavan Malini 
Published: July 2023

AbstractSomatic mutants of calreticulin (CRT) drive myeloproliferative neoplasms (MPNs) via binding to the thrombopoietin receptor (MPL) and aberrant activation of the JAK/STAT pathway. Compared with healthy donors, platelets from MPN patients with CRT mutations display low cell surface MPL. Co-expression of MPL with an MPN-linked CRT mutant (CRTDel52) reduces cell surface MPL expression, indicating the involvement of induced protein degradation, a better understanding of which could lead to new therapies. We show that lysosomal degradation is relevant to the turnover of both CRTDel52and MPL. Drug-mediated activation of lysosomal degradation reduces CRTDel52and MPL expression, with parallel inhibition of CRTDel52-induced cell proliferation and stem cell colony formation. Thus, reduced surface MPL, a marker of platelets from MPN patients with CRT mutations, results from mutant CRT-induced lysosomal degradation of MPL. Drug-induced activation of lysosomal degradation compromises the pathogenic effects of CRTDel52, which can be further exploited for therapeutic interventions.
Guiding Discovery of Protein Sequence-Structure-Function Modeling
Authors: Hussain Azam , Brooks Charles L. 
Published: July 2023

AbstractProtein engineering techniques are key in designing novel catalysts for a wide range of reactions. Although approaches vary in their exploration of the sequence-structure-function paradigm, they are often hampered by the labor-intensive steps of protein expression and screening. In this work, we describe the development and testing of a high throughputin silicosequence-structure-function pipeline using AlphaFold2 and Fast Fourier Transform docking that is benchmarked with enantioselectivity and reactivity predictions for an ancestral sequence library of fungal flavin-dependent monooxygenases. The predicted enantioselectivities and reactivities correlate well with previously described screens of an experimentally available subset of these proteins and capture known changes in enantioselectivity across the phylogenetic tree representing ancestorial proteins from this family. With this pipeline established as our functional screen, we apply ensemble decision tree models and explainable AI techniques to build sequence function models and extract critical residues within the binding site and the second sphere residues around this site. We demonstrate that the top-identified key residues in the control of enantioselectivity and reactivity correspond to experimentally verified residues. Thein silicosequence-to-function pipeline serves as an accelerated framework to inform protein engineering efforts.
Deep spatial proteomic exploration of severe COVID-19-related pulmonary injury in post-mortem specimens
Authors: Mao Yiheng , Chen Ying , Li Yuan , Ma Longda , Wang Xi , Wang Qi , He An , Liu Xi , Dong Tianyi , Gao Weina , Xu Yanfen , Liu Liang , Ren Liang , Liu Qian , Zhou Peng , Hu Ben , Zhou Yiwu , Tian Ruijun , Shi Zheng-Li 
Published: July 2023

ABSTRACTThe lung, as a primary target of SARS-CoV-2, exhibits heterogeneous microenvironment accompanied by various histopathological changes following virus infection. However, comprehensive insight into the protein basis of COVID-19-related pulmonary injury with spatial resolution is currently deficient. Here, we generated a region-resolved quantitative proteomic atlas of seven major pathological structures within the lungs of COVID-19 victims by integrating histological examination, laser microdissection, and ultrasensitive proteomic technologies. Over 10,000 proteins were quantified across 71 dissected FFPE post-mortem specimens. By comparison with control samples, we identified a spectrum of COVID-19-induced protein and pathway dysregulations in alveolar epithelium, bronchial epithelium, and pulmonary blood vessels, providing evidence for the proliferation of transitional-state pneumocytes. Additionally, we profiled the region-specific proteomes of hallmark COVID-19 pulmonary injuries, including bronchiole mucus plug, pulmonary fibrosis, airspace inflammation, and hyperplastic alveolar type 2 cells. Bioinformatic analysis revealed the enrichment of cell-type and functional markers in these regions (e.g. enriched TGFBI in fibrotic region). Furthermore, we identified the up-regulation of proteins associated with viral entry, host restriction, and inflammatory response in COVID-19 lungs, such as FURIN and HGF. Collectively, this study provides spatial proteomic insights for understanding COVID-19-caused pulmonary injury, and may serve as a valuable reference for improving therapeutic intervention for severe pneumonia.
Rgg2/Rgg3 quorum sensing is a determinant ofStreptococcus pyogenes-host interactions in a murine intact skin infection model
Authors: Wilkening Reid V. , Langouët-Astrié Christophe , Severn Morgan , Federle Michael J , Horswill Alexander R. 
Published: July 2023

AbstractStreptococcus pyogenesis an obligate human pathobiont associated with many disease states. Here, we present a novel model ofS. pyogenesinfection using intact murine epithelium. From this model, we were able to perform RNA sequencing to evaluate the genetic changes undertaken by both the bacterium and host at 5- and 24-hours post infection. Analysis of these genomic data demonstrate thatS. pyogenesundergoes significant genetic adaptation to successfully infect the murine epithelium, including changes to metabolism and activation of the Rgg2/Rgg3 quorum sensing (QS) system. Subsequent experiments demonstrate that an intact Rgg2/Rgg3 QS cascade is necessary to establish a stable superficial skin infection. Furthermore, activation of this pathway results in increased murine morbidity and increased bacterial burden on the skin. This phenotype is associated with gross changes to the murine skin, as well as histopathological evidence of inflammation. Taken together, these experiments offer a novel method to investigateS. pyogenes-epithelial interactions and demonstrate that a well-studied QS pathway is critical to a persistent infection.ImportanceStreptococcus pyogenesremains a pathogen of global importance, with significant total disease burden worldwide. Much of this burden is due to skin infection or sequalae thereof, yet little is currently known about the initial interactions between the organism and host skin. Here we present a new mouse model of skin infection. From this model, we were able to study gene expression by both the bacteria and the host during early infection time points. Both genetic and phenotypic data derived from these results demonstrate that a well-conservedS. pyogenescommunication network, the Rgg2/Rgg3 quorum sensing pathway, contributes to establishing and maintaining a durable skin infection. We propose that by better understanding the genetic pathways needed to colonize and adapt to new niches, new approaches to preventing and treatingS. pyogenesmay be possible.
An N-terminal delivery domain defines a new class of polymorphic T6SS effectors inEnterobacterales
Authors: Carobbi Andrea , di Nepi Simone , Bosis Eran , Salomon Dor , Sessa Guido 
Published: July 2023

AbstractThe type VI secretion system (T6SS), a widespread protein delivery apparatus, plays a role in bacterial competition by delivering toxic effectors into neighboring cells. Identifying new T6SS effectors and deciphering the mechanism that governs their secretion remain major challenges. Here, we report two orphan, antibacterial T6SS effectors in the pathogenPantoea agglomerans(Pa). These effectors share an N-terminal domain, PIX, that defines a widespread class of polymorphic T6SS effectors inEnterobacterales. We show that the PIX domain is necessary and sufficient for T6SS-mediated effector secretion and that PIX binds to a specializedPaVgrG protein, outside of its C-terminal toxic domain. Our findings underline the importance of identifying and characterizing new delivery domains in polymorphic toxin classes as a tool to reveal novel effectors and shed light on effector delivery mechanisms.
Maresin-2 Fine-tunes ULK1 O-GlcNAcylation to Improve Post Myocardial Infarction Remodeling
Authors: Zhang Jingjing , Li Chenyu , Wei Yanzhao , Jiang Shujuan , Wu Xiaolin , Zhou Qing , Yang Shuang , Hu He , Huang He , Kong Bin , Shuai Wei 
Published: July 2023

AbstractMaresin-2, a specialized pro-solving mediator of inflammation has been consolidated to be a novel cytokine fine-tuning inflammatory cascade. However, the underlying molecular basis is still largely unknown. Focused on cardiac dysfunction and remodeling, we employed in vivo- and in vitro- based genome editing methodology tools including adenosine associated virus, adenosine virus, lenti-virus, plasmid transfection, and CRISPR-Cas9 methodology for investigation. As suggested, exogenous maresin-2 supplement facilitated autophagosome formation by microtubule-associated proteins 1A/1B light chain 3B (LC3) conjugation system under the modulation of O-GlcNAcylation dependent ULK1 activation, whereas reversed by ULK1 S409A and S422A mutagenesis, showcasing the potential O-GlcNAc (O-linked β- N-acetylglucosamine) modifiable sites on ULK1. Moreover, we found that hereafter maresin-2 treatment glutamine-fructose-6-phosphate aminotransferase 1 (GFAT1) which is accessary to sense hexosamine biosynthesis influx is more likely the prime checkpoint for conjugating O-terminal β-N-acetylglucosamine motif onto ULK1, rather than O-linked N-acetylglucosaminyltransferase (OGT). Mechanistically, maresin-2 largely prohibits transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), therefore increasing the availability of TAB1 for GFAT1, which encourages O-GlcNAcylation of ULK1.
Reliability analysis for air-breathing hypersonic vehicles based on a new dynamic PHI2 method
Authors: Guo Zhongge , Wang Yuhui , He Jiale , Pang Dong 
Published: July 2023

Purpose
This paper aims to present a novel dynamic reliability model that considers the interval mixed uncertainty for the air-breathing hypersonic flight vehicle (AHFV) to guarantee flight safety and structural reliability.

Design/methodology/approach
Initially, the force condition of the fuselage is analyzed based on the longitudinal elastic model of an AHFV. Subsequently, a new high-efficiency dynamic reliability model is presented to describe the failure probability evolution of the fuselage structure. For the random uncertainty problem with interval distribution parameters, the interval PHI2 method of time-dependent reliability is used to obtain the time-dependent reliability interval of the AHFV. Finally, the key variables that affect the failure probability accumulation are determined, which provide an important reference for ensuring structural reliability and improving the life span of AHFVs.

Findings
It is demonstrated that the proposed reliability model can obtain more accurate dynamic reliability results for the fuselage, and it is confirmed the key variables that affect the failure probability accumulation. The results also provide an important reference for the reliability analysis of hypersonic vehicles.

Originality/value
The novelty of this work comes from the first application of the PHI2 method (considering the interval mixed uncertainty) in the AHFV and the development of a new reliability model for the entire body of AHFVs. The proposed analysis scheme is implemented on the dynamic model of the AHFV, which provides a more accurate reference for improving the structural reliability and life span of AHFVs.
Integrating as-built BIM model from point cloud data in construction projects
Authors: Zeng Ruochen , Shi Jonathan J.S. , Wang Chao , Lu Tao 
Published: July 2023

PurposeAs laser scanning technology becomes readily available and affordable, there is an increasing demand of using point cloud data collected from a laser scanner to create as-built building information modeling (BIM) models for quality assessment, schedule control and energy performance within construction projects. To enhance the as-built modeling efficiency, this study explores an integrated system, called Auto-Scan-To-BIM (ASTB), with an aim to automatically generate a complete Industry Foundation Classes (IFC) model consisted of the 3D building elements for the given building based on its point cloud without requiring additional modeling tools.Design/methodology/approachASTB has been developed with three function modules. Taking the scanned point data as input, Module 1 is built on the basis of the widely used region segmentation methodology and expanded with enhanced plane boundary line detection methods and corner recalibration algorithms. Then, Module 2 is developed with a domain knowledge-based heuristic method to analyze the features of the recognized planes, to associate them with corresponding building elements and to create BIM models. Based on the spatial relationships between these building elements, Module 3 generates a complete IFC model for the entire project compatible with any BIM software.FindingsA case study validated the ASTB with an application with five common types of building elements (e.g. wall, floor, ceiling, window and door).Originality/valueFirst, an integrated system, ASTB, is developed to generate a BIM model from scanned point cloud data without using additional modeling tools. Second, an enhanced plane boundary line detection method and a corner recalibration algorithm are developed in ASTB with high accuracy in obtaining the true surface planes. At last, the research contributes to develop a module, which can automatically convert the identified building elements into an IFC format based on the geometry and spatial relationships of each plan.