bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of bound ssRNA length on allostery in the Dengue Virus NS3 helicase
Authors: Amrein Fernando , Sarto Carolina , Cababie Leila A , Gonzalez Flecha F Luis , Kaufman Sergio B , Arrar Mehrnoosh 
Published: October 2023

Abstract
The presence of ATP is known to stimulate helicase activity of the Dengue Virus Non-structural protein 3 helicase (NS3h), and the presence of RNA stimulates NS3h ATPase activity, however this coupling is still mechanistically unclear. Here we use atomistic models and molecular dynamics simulations to evaluate the single-stranded RNA (ssRNA)-length dependence of the NS3h–ssRNA binding affinity and its modulation by bound ATP. Considering complexes with 7, 11, 16 and 26 nucleotides (nts), we observe that both the binding affinity and its modulation by bound ATP are augmented with increased ssRNA lengths. In models with at least 11 nts bound, the binding of ATP results in a shift from a tightly bound to a weakly bound state. We find that the weakly bound state persists during both the ADP-Pi- and ADP-bound stages of the catalytic cycle. We obtain the equilibrium association constants for NS3h binding to an ssRNA 10-mer in vitro, both in the absence and presence of ADP, which further support the alternation between tightly and weakly bound states during the catalytic cycle. The length of bound ssRNA is critical for understanding the NS3h–RNA interaction as well as how it is modulated during the catalytic cycle.
CancerProteome: a resource to functionally decipher the proteome landscape in cancer
Authors: Lv Dezhong , Li Donghao , Cai Yangyang , Guo Jiyu , Chu Sen , Yu Jiaxin , Liu Kefan , Jiang Tiantongfei , Ding Na , Jin Xiyun , Li Yongsheng , Xu Juan 
Published: October 2023

Abstract
Advancements in mass spectrometry (MS)-based proteomics have greatly facilitated the large-scale quantification of proteins and microproteins, thereby revealing altered signalling pathways across many different cancer types. However, specialized and comprehensive resources are lacking for cancer proteomics. Here, we describe CancerProteome (http://bio-bigdata.hrbmu.edu.cn/CancerProteome), which functionally deciphers and visualizes the proteome landscape in cancer. We manually curated and re-analyzed publicly available MS-based quantification and post-translational modification (PTM) proteomes, including 7406 samples from 21 different cancer types, and also examined protein abundances and PTM levels in 31 120 proteins and 4111 microproteins. Six major analytical modules were developed with a view to describe protein contributions to carcinogenesis using proteome analysis, including conventional analyses of quantitative and the PTM proteome, functional enrichment, protein–protein associations by integrating known interactions with co-expression signatures, drug sensitivity and clinical relevance analyses. Moreover, protein abundances, which correlated with corresponding transcript or PTM levels, were evaluated. CancerProteome is convenient as it allows users to access specific proteins/microproteins of interest using quick searches or query options to generate multiple visualization results. In summary, CancerProteome is an important resource, which functionally deciphers the cancer proteome landscape and provides a novel insight for the identification of tumor protein markers in cancer.
Dynamics of ribosome composition and ribosomal protein phosphorylation in immune signaling in Arabidopsis thaliana
Authors: Siodmak Anna , Martinez-Seidel Federico , Rayapuram Naganand , Bazin Jeremie , Alhoraibi Hanna , Gentry-Torfer Dione , Tabassum Naheed , Sheikh Arsheed H , Kise José Kenyi González , Blilou Ikram , Crespi Martin , Kopka Joachim , Hirt Heribert 
Published: October 2023

Abstract
In plants, the detection of microbe-associated molecular patterns (MAMPs) induces primary innate immunity by the activation of mitogen-activated protein kinases (MAPKs). We show here that the MAMP-activated MAPK MPK6 not only modulates defense through transcriptional regulation but also via the ribosomal protein translation machinery. To understand the effects of MPK6 on ribosomes and their constituent ribosomal proteins (RPs), polysomes, monosomes and the phosphorylation status of the RPs, MAMP-treated WT and mpk6 mutant plants were analysed. MAMP-activation induced rapid changes in RP composition of monosomes, polysomes and in the 60S ribosomal subunit in an MPK6-specific manner. Phosphoproteome analysis showed that MAMP-activation of MPK6 regulates the phosphorylation status of the P-stalk ribosomal proteins by phosphorylation of RPP0 and the concomitant dephosphorylation of RPP1 and RPP2. These events coincide with a significant decrease in the abundance of ribosome-bound RPP0s, RPP1s and RPP3s in polysomes. The P-stalk is essential in regulating protein translation by recruiting elongation factors. Accordingly, we found that RPP0C mutant plants are compromised in basal resistance to Pseudomonas syringae infection. These data suggest that MAMP-induced defense also involves MPK6-induced regulation of P-stalk proteins, highlighting a new role of ribosomal regulation in plant innate immunity.
FL-circAS: an integrative resource and analysis for full-length sequences and alternative splicing of circular RNAs with nanopore sequencing
Authors: Chiang Tai-Wei , Jhong Song-En , Chen Yu-Chen , Chen Chia-Ying , Wu Wei-Sheng , Chuang Trees-Juen 
Published: October 2023

Abstract
Circular RNAs (circRNAs) are RNA molecules with a continuous loop structure characterized by back-splice junctions (BSJs). While analyses of short-read RNA sequencing have identified millions of BSJ events, it is inherently challenging to determine exact full-length sequences and alternatively spliced (AS) isoforms of circRNAs. Recent advances in nanopore long-read sequencing with circRNA enrichment bring an unprecedented opportunity for investigating the issues. Here, we developed FL-circAS (https://cosbi.ee.ncku.edu.tw/FL-circAS/), which collected such long-read sequencing data of 20 cell lines/tissues and thereby identified 884 636 BSJs with 1 853 692 full-length circRNA isoforms in human and 115 173 BSJs with 135 617 full-length circRNA isoforms in mouse. FL-circAS also provides multiple circRNA features. For circRNA expression, FL-circAS calculates expression levels for each circRNA isoform, cell line/tissue specificity at both the BSJ and isoform levels, and AS entropy for each BSJ across samples. For circRNA biogenesis, FL-circAS identifies reverse complementary sequences and RNA binding protein (RBP) binding sites residing in flanking sequences of BSJs. For functional patterns, FL-circAS identifies potential microRNA/RBP binding sites and several types of evidence for circRNA translation on each full-length circRNA isoform. FL-circAS provides user-friendly interfaces for browsing, searching, analyzing, and downloading data, serving as the first resource for discovering full-length circRNAs at the isoform level.
GDPF: a data resource for the distribution of prokaryotic protein families across the global biosphere
Authors: Pan Zhuo , Li Dan-dan , Li Peng , Geng Yu , Jiang Yiru , Liu Ya , Li Yue-zhong , Zhang Zheng 
Published: October 2023

Abstract
Microorganisms encode most of the functions of life on Earth. However, conventional research has primarily focused on specific environments such as humans, soil and oceans, leaving the distribution of functional families throughout the global biosphere poorly comprehended. Here, we present the database of the global distribution of prokaryotic protein families (GDPF, http://bioinfo.qd.sdu.edu.cn/GDPF/), a data resource on the distribution of functional families across the global biosphere. GDPF provides global distribution information for 36 334 protein families, 19 734 superfamilies and 12 089 KEGG (Kyoto Encyclopedia of Genes and Genomes) orthologs from multiple source databases, covering typical environments such as soil, oceans, animals, plants and sediments. Users can browse, search and download the distribution data of each entry in 10 000 global microbial communities, as well as conduct comparative analysis of distribution disparities among multiple entries across various environments. The GDPF data resource contributes to uncovering the geographical distribution patterns, key influencing factors and macroecological principles of microbial functions at a global level, thereby promoting research in Earth ecology and human health.
Crossroads of Antimicrobial and Diagnostic Stewardship: Assessing Risks to Develop Clinical Decision Support to Combat Multidrug-Resistant Pseudomonas
Authors: Zou Iris , Abate Daniel , Newman Michelle , Heil Emily L , Leekha Surbhi , Claeys Kimberly C 
Published: October 2023

Abstract

Background
Early detection of multidrug-resistant Pseudomonas aeruginosa (MDRP) remains challenging. Existing risk prediction tools are difficult to translate to bedside application. The goal of this study was to develop a simple electronic medical record (EMR)–integrated tool for prediction of MDRP infection.

Methods
This was a mixed-methods study. We conducted a split-sample cohort study of adult critical care patients with P aeruginosa infections. Two previously published tools were validated using c-statistic. A subset of variables based on strength of association and ease of EMR extraction was selected for further evaluation. A simplified tool was developed using multivariable logistic regression. Both c-statistic and theoretical trade-off of over- versus underprescribing of broad-spectrum MDRP therapy were assessed in the validation cohort. A qualitative survey of frontline clinicians assessed understanding of risks for MDRP and potential usability of an EMR-integrated tool to predict MDRP.

Results
The 2 previous risk prediction tools demonstrated similar accuracy in the derivation cohort (c-statistic of 0.76 [95% confidence interval {CI}, .69–.83] and 0.73 [95% CI, .66–.8]). A simplified tool based on 4 variables demonstrated reasonable accuracy (c-statistic of 0.71 [95% CI, .57–.85]) without significant overprescribing in the validation cohort. The risk factors were prior MDRP infection, ≥4 antibiotics prior to culture, infection &gt;3 days after admission, and dialysis. Fourteen clinicians completed the survey. An alert providing context regarding individual patient risk factors for MDRP was preferred.

Conclusions
These results can be used to develop a local EMR-integrated tool to improve timeliness of effective therapy in those at risk of MDRP infections.
A unique cell population expressing the Epithelial-Mesenchymal Transition-transcription factor Snail moderates microglial and astrocyte injury responses
Authors: Clarkson-Paredes Cheryl , Karl Molly T , Popratiloff Anastas , Miller Robert H 
Published: October 2023

Abstract
Insults to the central nervous system (CNS) elicit common glial responses including microglial activation evidenced by functional, morphological, and phenotypic changes, as well as astrocyte reactions including hypertrophy, altered process orientation, and changes in gene expression and function. However, the cellular and molecular mechanisms that initiate and modulate such glial response are less well-defined. Here we show that an adult cortical lesion generates a population of ultrastructurally unique microglial-like cells that express Epithelial-Mesenchymal Transcription factors including Snail. Knockdown of Snail with antisense oligonucleotides results in a postinjury increase in activated microglial cells, elevation in astrocyte reactivity with increased expression of C3 and phagocytosis, disruption of astrocyte junctions and neurovascular structure, increases in neuronal cell death, and reduction in cortical synapses. These changes were associated with alterations in pro-inflammatory cytokine expression. By contrast, overexpression of Snail through microglia-targeted an adeno-associated virus (AAV) improved many of the injury characteristics. Together, our results suggest that the coordination of glial responses to CNS injury is partly mediated by epithelial-mesenchymal transition-factors (EMT-Fsl).
Diagnostic values, association with disease activity and possible risk factors of anti-PAD4 in rheumatoid arthritis: a meta-analysis
Authors: Zhang Guangyue , Xu Jiayi , Du Dongru , Liu Yi , Dai Lunzhi , Zhao Yi 
Published: October 2023

Abstract

Objective
Anti-peptidyl arginine deaminase 4 (anti-PAD4) antibody has been a subject of investigation in RA in the last two decades. This meta-analysis investigated the diagnostic values, association with disease activity and possible risk factors of anti-PAD4 antibody in rheumatoid arthritis.

Method
We searched studies from five databases up to 1 December 2022. Bivariate mixed-effect models were used to pool the diagnostic accuracy indexes, and the summary receiver operating characteristics (SROC) curve was plotted. The quality of diagnostic studies was assessed using QUADAS-2. Non-diagnostic meta-analyses were conducted using the random-effects model. Sensitivity analysis, meta-regression, subgroup analyses and Deeks’ funnel plot asymmetry test were used to address heterogeneity.

Result
Finally, 24 journal articles and one letter were included. Anti-PAD4 antibody had a good diagnostic value between RA and healthy individuals, but it might be lower between RA and other rheumatic diseases. Moreover, anti-PAD4 could slightly enhance RA diagnostic sensitivity with a combination of ACPA or ACPA/RF. Anti-PAD4 antibody was positively correlated with HLA-SE and negatively correlated with ever or current smoking in patients with RA. RA patients with anti-PAD4 antibody had higher DAS28, ESR, swollen joint count (SJC) and the possibility of having interstitial lung disease (ILD) and pulmonary fibrosis compared with those without.

Conclusion
Our study suggests that anti-PAD4 antibody is a potentially useful diagnostic biomarker and clinical indicator for RA. Further mechanistic studies are required to understand the impact of HLA-SE and smoking on the production of anti-PAD4 antibody.
What makes an entrepreneurial university? Institutional moderators of ecosystem impacts in a developing country
Authors: Schaeffer Paola Rücker , Fischer Bruno Brandão , Queiroz Sérgio , Moraes Gustavo Hermínio Salati Marcondes de 
Published: October 2023

Abstract
Entrepreneurial universities have become a key concept in debates concerning regional economic development. Yet, we still fall short of having a clear comprehension of the enablers of such localized impacts arising from academic activity. Such conditions are particularly critical for the context of developing countries, which have mostly mimicked initiatives taking place in the context of developed markets. To address these issues, we analyze the impacts generated by research-intensive universities on local innovation ecosystems. We apply a combination of econometric and case study methods for the state of São Paulo, Brazil. Results suggest that research-intensive universities, mostly public universities, positively impact their respective innovation ecosystems. Moreover, qualified research funds and the existence of a support structure (incubators and science and technology parks) significantly enhance the impacts generated by research-intensive universities. These findings highlight the relationship between the internal constraints of universities and their capacity to generate impacts on local ecosystems.
Interstitial lung diseases in inborn errors of immunity
Authors: Sullivan Neal P. , Maniam Nivethietha , Maglione Paul J. 
Published: October 2023

Purpose of review
Our goal is to review current understanding of interstitial lung disease (ILD) affecting patients with inborn errors of immunity (IEI). This includes understanding how IEI might predispose to and promote development or progression of ILD as well as how our growing understanding of IEI can help shape treatment of ILD in these patients. Additionally, by examining current knowledge of ILD in IEI, we hope to identify key knowledge gaps that can become focus of future investigative efforts.

Recent findings
Recent identification of novel IEI associated with ILD and the latest reports examining treatment of ILD in IEI are included. Of noted interest, are recent clinical studies of immunomodulatory therapy for ILD in common variable immunodeficiency.

Summary
ILD is a frequent complication found in many IEI. This article provides a guide to identifying manifestations of ILD in IEI. We review a broad spectrum of IEI that develop ILD, including antibody deficiency and immune dysregulation disorders that promote autoimmunity and autoinflammation. This work integrates clinical information with molecular mechanisms of disease and diagnostic assessments to provide an expedient overview of a clinically relevant and expanding topic.
Intraoperative Radiation Exposure in Adolescent Idiopathic and Neuromuscular Scoliosis
Authors: Fares Nicole , Levey Sarah Toner , Ashy Cody , McFadden Ryan , Barfield William , Murphy Robert F. , Dow Matthew A. , Van Nortwick Sara S. 
Published: October 2023

Background:Intraoperative imaging is often used to aid pedicle screw placement during scoliosis operations. Higher rates of cancer and death have been observed in orthopaedic surgeons and radiation technologists, including a fourfold higher rate of breast cancer in female orthopaedic surgeons. The purpose of this study was to evaluate variability in intraoperative radiation during spinal fusions for both adolescent idiopathic scoliosis (AIS) and neuromuscular scoliosis (NMS).Methods:A retrospective review of posterior spinal fusion and segmental spinal instrumentation for scoliosis performed by pediatric orthopaedic surgeons from 2017 to 2019 at a single institution was performed. Inclusion criteria included: a diagnosis of AIS or NMS and patients between 8 and 18 years of age. Exclusion criteria included: revision surgery, use of intraoperative navigation, and patients younger than 10 at the time of scoliosis onset within the AIS cohort. Data collected included: preoperative curve, body mass index (BMI), number of levels fused, number of Ponte osteotomies, and fluoroscopy time. One-way analysis of variance tests, Bonferroni post hoc tests, independentttests, and Pearson correlations were utilized with significance determined at the 95% confidence level (a= 0.05).Results:A total of 148 patients were included in the study. The average fluoroscopy time was 143 ± 67 seconds. Patients with NMS had higher average fluoroscopy times (193 ± 75 s) compared with patients with AIS (129 ± 58 s,P< 0.001). In patients with AIS, fluoroscopy time correlated to the patient’s preoperative curve (r= 0.182,P= 0.050). Patients with AIS with fewer than 12 levels fused had significantly less radiation exposure than those with 12 or more levels fused (P= 0.01). When controlling for the number of levels fused, patients with AIS with higher BMIs had significantly greater fluoroscopy times (P= 0.001). In patients with NMS, fluoroscopy time negatively correlated with BMI (r= −0.459,P= 0.009) and positively correlated with a preoperative curve (r= 0.475,P= 0.007).Conclusion:Fluoroscopy times vary greatly during adolescent spinal fusions for scoliosis. Longer fluoroscopy times are correlated with: NMS diagnosis, larger preoperative curve, BMI, and number of levels fused. Surgeons' knowledge of factors affecting fluoroscopy time will increase awareness and may be the first step in decreasing intraoperative radiation risks.Level of Evidence:Level III; Therapeutic—a retrospective study.
Depressive Symptoms in Autistic Youth with Anxiety Disorders
Authors: Greenberg Rebecca L. , Guzick Andrew G. , Schneider Sophie C. , Weinzimmer Saira A. , Kook Minjee , Perozo Garcia Amanda B. , Storch Eric A. 
Published: October 2023

Abstract:

Objective:
Anxiety and depression often coexist in youth and share overlapping symptomatology; however, little is known about the comorbidity of anxiety and depression in autistic youth. This study explores (1) the frequency of depressive symptoms among autistic children with clinically significant anxiety, (2) clinical variables that may be associated with elevated depressive symptoms, and (3) whether pretreatment depressive symptoms predict cognitive behavioral therapy (CBT) outcomes for anxiety.

Method:
Children aged 7 to 13 years (N = 87) and their parents participated in a randomized controlled trial comparing 2 versions of a parent-led, telehealth-delivered CBT program. Parents and children completed a variety of clinical assessments and self-report questionnaires before and after treatment.

Results:
Fifty-seven percent of the child sample reported experiencing elevated depressive symptoms while roughly 20% of parents reported elevated depressive symptoms in their child. A strong association between anxiety and depression was found. Heightened feelings of loneliness, per child report, and functional impairment, per parent report, were found to be uniquely associated with elevated depressive symptoms. Finally, depressive symptoms were not a significant predictor of CBT outcomes for anxiety.

Conclusion:
Findings suggest high degrees of comorbidity between anxiety and depression among autistic children and that feelings of loneliness, anxiety, and functional impairment may be early indicators of mood-related concerns. Further research is needed to determine the full extent of the association between anxiety and depression and additional options for treating depression in autistic children.
Changes in diaphragmatic ultrasonography findings and their association with postoperative complications in children undergoing pulmonary resection
Authors: Lee Ji-Hyun , Kang Pyoyoon , Park Jung-Bin , Kim Jin-Tae 
Published: October 2023

BACKGROUND
Few studies have investigated the changes in diaphragmatic function and their association with postoperative pulmonary complications (PPCs) in paediatric patients after lung resection.

OBJECTIVE
This study aimed to evaluate diaphragmatic function using ultrasound after lung resection and its influence on PCCs in children.

DESIGN
Prospective observational study.

SETTING
A tertiary children's hospital.

PATIENTS
Children aged 6 years or less who were scheduled for video-assisted thoracoscopic lung resection.

INTERVENTION
Ultrasonographic measurements of diaphragmatic excursion (DE) and thickening fraction (TF) were performed for three epochs: before anaesthesia induction (T0), 1 h postoperatively (T1) and 24 h postoperatively (T2). The thickening fraction is calculated from the thickness of the diaphragm at end expiration and end inspiration at each time point. DET1/DET0, DET2/DET0, TFT1/TFT0 and TFT2/TFT0 (%) were calculated. The incidence of PCCs was also determined.

MAIN OUTCOME MEASURES
The primary outcomes were changes in diaphragmatic excursion and thickening fraction over time, from T0 to T2. The secondary outcomes were the association between ultrasound parameters of diaphragm function and the occurrence of early PPCs within 3 days.

RESULTS
Data from 74 children were analysed. On the operated side, both diaphragmatic excursion and thickening fraction decreased at T1 and recovered slightly at T2, and were significantly lower than the T0 values. Children with PPCs had significantly lower DET2/DET0 and TFT2/TFT0 scores on the operated side than those without PPCs. According to the receiver operating characteristic analysis, the DET2/DET0 (< 61.1%) on the operated side was associated with PPCs with an area under the curve of 0.764.

CONCLUSIONS
Peri-operative diaphragmatic function assessed by ultrasonography changed after lung resection in children. The diaphragmatic excursion and thickening fraction decreased postoperatively, and a prolonged decrease in diaphragmatic excursion was associated with pulmonary complications after lung surgery in children.

CLINICAL TRIAL REGISTRY
ClinicalTrials.gov, NCT04400370