bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of appropriateness in clinical practice: data from a single-centre nuclear cardiology laboratory
Authors: Liga Riccardo , Grassini Dario , Giorgetti Assuero , Grasso Enrico , Dalmiani Stefano , Gimelli Alessia 
Published: November 2023

Abstract

Aims
To verify the level of appropriateness of referral to our nuclear cardiology laboratory for stress myocardial perfusion imaging (MPI) and explore the correlation between test appropriateness patterns and ischaemia.

Methods and results
In 1870 consecutive patients (mean age 73 ± 12 years; 33% female) undergoing MPI, the level of imaging test appropriateness was evaluated according to the 2023 Appropriate Use Criteria (AUC) and the current European Society of Cardiology (ESC) guidelines for the management of chronic coronary syndromes. The evidence of moderate-to-severe ischaemia (i.e. summed difference score &gt;7) was recorded. According to the AUC criteria, the MPI of 1638 (88%), 130 (7%), and 102 (5%) patients could be classified as ‘appropriate’, ‘inappropriate’, and ‘uncertain’, respectively. Similarly, in 1685 (90%) patients, the referral to MPI was adherent to ESC guidelines, while in 185 (10%), it was not. The majority of appropriate MPI tests showed the presence of moderate-to-severe ischaemia (55%), while only a limited number (10%; P &lt; 0.05) of MPI tests with uncertain clinical appropriateness or clearly inappropriate indications did not. In patients managed adherently to ESC guidelines, invasive coronary angiography more frequently showed obstructive coronary artery disease (CAD) (93 vs. 47%, P &lt; 0.001) and led to coronary revascularization (65 vs. 23%, P &lt; 0.001) compared with patients managed non-adherently.

Conclusion
In a single-centre, single-national, single-modality population, the current rate of appropriate MPI tests is high. Appropriate referrals are associated with a higher probability of moderate-to-severe ischaemia and better downstream resource utilization than inappropriate ones.
Therapeutic management of congenital forms of endocrine hypertension
Authors: Charoensri Suranut , Auchus Richard J 
Published: November 2023

Abstract
Congenital forms of endocrine hypertension are rare and potentially life-threatening disorders, primarily caused by genetic defects affecting adrenal steroid synthesis and activation pathways. These conditions exhibit diverse clinical manifestations, which can be distinguished by their unique molecular mechanisms and steroid profiles. Timely diagnosis and customized management approach are crucial to mitigate unfavorable outcomes associated with uncontrolled hypertension and other related conditions. Treatment options for these disorders depend on the distinct underlying pathophysiology, which involves specific pharmacological therapies or surgical adrenalectomy in some instances. This review article summarizes the current state of knowledge on the therapeutic management of congenital forms of endocrine hypertension, focusing on familial hyperaldosteronism (FH), congenital adrenal hyperplasia, apparent mineralocorticoid excess, and Liddle syndrome. We provide an overview of the genetic and molecular pathogenesis underlying each disorder, describe the clinical features, and discuss the various therapeutic approaches available and their risk of adverse effects, aiming to improve outcomes in patients with these rare and complex conditions.
Environment predicts the maintenance of reproductive isolation in a mosaic hybrid zone of rubber rabbitbrush
Authors: Faske Trevor M , Agneray Alison C , Jahner Joshua P , Osuna-Mascaró Carolina , Sheta Lana M , Richardson Bryce A , Leger Elizabeth A , Parchman Thomas L 
Published: November 2023

Abstract
Widely distributed plants of western North America experience divergent selection across environmental gradients, have complex histories shaped by biogeographic barriers and distributional shifts and often illustrate continuums of reproductive isolation. Rubber rabbitbrush (Ericameria nauseosa) is a foundational shrub species that occurs across diverse environments of western North America. Its remarkable phenotypic diversity is currently ascribed to two subspecies—Ericameria nauseosa nauseosa and Ericameria nauseosa consimilis—and 22 named varieties. To understand how genetic variation is partitioned across subspecies, varieties, and environments, we used high throughput sequencing of reduced representation libraries. We found clear evidence for divergence between the two subspecies, despite largely sympatric distributions. Numerous locations exhibiting admixed ancestry were not geographically localized but were widely distributed across a mosaic hybrid zone. The occurrence of hybrid and subspecific ancestries was strongly predicted by environmental variables as well as the proximity to major ecotones between ecoregions. Although this repeatability illustrates the importance of environmental factors in shaping reproductive isolation, variability in the prevalence of hybridization also indicates these factors likely differ across ecological contexts. There was mixed evidence for the evolutionary cohesiveness of varieties, but several genetically distinct and narrow endemic varieties exhibited admixed subspecific ancestries, hinting at the possibility for transgressive hybridization to contribute to phenotypic novelty and the colonization of new environments in E. nauseosa.
Enterococcus faecium R-026 combined with Bacillus subtilis R-179 alleviate hypercholesterolemia and modulate the gut microbiota in C57BL/6 mice
Authors: Huang Jinli , Xu Yafang , Wang Minghao , Yu Shu , Li Yixuan , Tian Haoxin , Zhang Caihua , Li Huajun 
Published: November 2023

Abstract
Probiotics have been demonstrated to lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in individuals with mild hypercholesterolemia. Our previous study found that intervention with Bacillus subtilis R-179 and Enterococcus faecium R-026, well-known probiotics, improved obesity-associated dyslipidemia through ameliorating the gut microbiota, but similar studies on hypercholesterolemia have not been reported to date. Here, we investigated the therapeutic effect of live combined B. subtilis R-179 and E. faecium R-026 (LCBE) in a C57BL/6 mouse model of hypercholesterolemia. A total of 40 mice were administered with a high-cholesterol diet (containing 1.2% cholesterol) to establish a state of hypercholesterolemia for 4 weeks. Then, mice were divided into one model group (group M) and three treatment groups (n = 10 per group), which were administered with LCBE at 0.023 g/mouse/day (group L) or 0.230 g/mouse/day (group H), or atorvastatin 0.010 g/kg/day (group A), for 5 weeks while on a high-cholesterol diet. LCBE at high doses significantly alleviated the symptoms of group M and reduced serum TC, LDL-C, and lipopolysaccharide (LPS). LCBE improved liver steatosis and adipocyte enlargement caused by a high-cholesterol diet. In addition, the administration of LCBE regulated the change in gut microbiota and diversity (Shannon index). Compared with group M, the relative abundance of Actinobacteriota, Colidextribacter, and Dubosiella dramatically decreased in the treatment groups, which were positively correlated with serum TC and LPS. These findings indicated that the mechanism of action of LCBE in treating hypercholesterolemia may be modulation of the gut microbiota. In conclusion, LCBE ameliorated lipid accumulation, reduced inflammation, and alleviated the gut microbiota imbalance in hypercholesterolemic mice. These findings support the probiotic role of LCBE as a clinical candidate for the treatment of hypercholesterolemia.
Developing the improved Community Health Fund in Tanzania: was it a fair process?
Authors: Binyaruka Peter , Mtei Gemini , Maiba John , Gopinathan Unni , Dale Elina 
Published: November 2023

AbstractTanzania developed its 2016–26 health financing strategy to address existing inequities and inefficiencies in its health financing architecture. The strategy suggested the introduction of mandatory national health insurance, which requires long-term legal, interministerial and parliamentary procedures. In 2017/18, improved Community Health Fund (iCHF) was introduced to make short-term improvements in coverage and financial risk protection for the informal sector. Improvements involved purchaser–provider split, portability of services, uniformity in premium and risk pooling at the regional level. Using qualitative methods and drawing on the policy analysis triangle framework (context, content, actors and process) and criteria for procedural fairness, we examined the decision-making process around iCHF and the extent to which it met the criteria for a fair process. Data collection involved a document review and key informant interviews (n = 12). The iCHF reform was exempt from following the mandatory legislative procedures, including processes for involving the public, for policy reforms in Tanzania. The Ministry of Health, leading the process, formed a technical taskforce to review evidence, draw lessons from pilots and develop plans for implementing iCHF. The taskforce included representatives from ministries, civil society organizations and CHF implementing partners with experience in running iCHF pilots. However, beneficiaries and providers were not included in these processes. iCHF was largely informed by the evidence from pilots and literature, but the evidence to reduce administrative cost by changing the oversight role to the National Health Insurance Fund was not taken into account. Moreover, the iCHF process lacked transparency beyond its key stakeholders. The iCHF reform provided a partial solution to fragmentation in the health financing system in Tanzania by expanding the pool from the district to regional level. However, its decision-making process underscores the significance of giving greater consideration to procedural fairness in reforms guided by technical institutions, which can enhance responsiveness, legitimacy and implementation.
A Universal Heat Semigroup Characterisation of Sobolev and BV Spaces in Carnot Groups
Authors: Garofalo Nicola , Tralli Giulio 
Published: November 2023

Abstract
In sub-Riemannian geometry there exist, in general, no known explicit representations of the heat kernels, and these functions fail to have any symmetry whatsoever. In particular, they are not a function of the control distance, nor they are for instance spherically symmetric in any of the layers of the Lie algebra. Despite these unfavourable aspects, in this paper we establish a new heat semigroup characterisation of the Sobolev and $BV$ spaces in a Carnot group by means of an integral decoupling property of the heat kernel.
From context adaptation to context restoration: strategies, motivations, and decision rules of managing context collapse on WeChat
Authors: Li Pengxiang , Cho Hichang , Shen Cuihua , Kong Hangchen 
Published: November 2023

AbstractContext collapse occurs on social media platforms when different groups are mixed into one audience. To advance the understanding of the extensive and complex coping strategies people use to address context collapse, this study makes a conceptual distinction between passively adapting by sharing context-free, general information (context adaptation) and rebuilding contexts to satisfy the diverse needs of impression management (context restoration). This study in-depth interviewed 51 WeChat users (30 working professionals and 21 college students) in urban China. The results identified strategies for context restoration through reconstructing contextual boundaries on psychological, relational, spatial, and temporal dimensions. These findings highlight individual (effort minimization, self-consciousness, and privacy concerns) and audience factors (the heterogeneity and activeness of the audience) in determining the adoption of specific strategies. This study emphasizes the subjectivity and agency of users in relation to the social media ecosystem and develops a theoretical spectrum systematically situating users’ coping behaviors for mitigating context collapse.
Improved 13C metabolic flux analysis in Escherichia coli metabolism: application of a high-resolution MS (GC–EI–QTOF) for comprehensive assessment of MS/MS fragments
Authors: Richter Chris , Grafahrend-Belau Eva , Ziegler Jörg , Raorane Manish L , Junker Björn H 
Published: November 2023

Abstract

Gas chromatography–tandem mass spectrometry with electron ionization (GC–EI–MS/MS) provides rich information on stable-isotope labeling for 13C-metabolic flux analysis (13C-MFA). To pave the way for the routine application of tandem MS data for metabolic flux quantification, we aimed to compile a comprehensive library of GC–EI–MS/MS fragments of tert-butyldimethylsilyl (TBDMS) derivatized proteinogenic amino acids. First, we established an analytical workflow that combines high-resolution gas chromatography-quadrupole time-of-flight mass spectrometry and fully 13C-labeled biomass to identify and structurally elucidate tandem MS amino acid fragments. Application of the high-mass accuracy MS procedure resulted into the identification of 129 validated precursor–product ion pairs of 13 amino acids with 30 fragments being accepted for 13C-MFA. The practical benefit of the novel tandem MS data was demonstrated by a proof–of–concept study, which confirmed the importance of the compiled library for high-resolution 13C-MFA.

One sentence summary
An analytical workflow that combines high-resolution mass spectrometry (MS) and fully 13C-labeled biomass to identify and structurally elucidate tandem MS amino acid fragments, which provide positional information and therefore offering significant advantages over traditional MS to improve 13C-metabolic flux analysis.
Education, epistemic justice, and truthfulness: Miranda Fricker interviewed by A. C. Nikolaidis and Winston C. Thompson
Authors: Nikolaidis A C , Thompson Winston C , Fricker Miranda 
Published: November 2023

Abstract
In her groundbreaking book, Epistemic Injustice, renowned moral philosopher and social epistemologist Miranda Fricker coined the term epistemic injustice to draw attention to the pervasive impact of epistemic oppression on marginalized social groups. Fricker’s account spurred a flurry of scholarship regarding the discriminatory impact of epistemic injustice and gave birth to a domain of philosophical inquiry that has extended far beyond the disciplinary boundaries of philosophy. In this interview, Fricker responds to questions posed by A. C. Nikolaidis and Winston C. Thompson that address the ways in which epistemic injustice intersects with education as a human endeavour and social institution. In doing so, Fricker reflects on her motivations in writing her book more than fifteen years ago and explicitly addresses some of the most significant contributions of the concept of epistemic injustice as a tool for analysing issues in education. She also offers insights on the purpose of education, outlines educational manifestations of epistemic injustice, and discusses the virtues that educators must exhibit and inculcate in their students in order for epistemic justice to obtain.
Controlling the false discovery rate in transformational sparsity: Split Knockoffs
Authors: Cao Yang , Sun Xinwei , Yao Yuan 
Published: November 2023

AbstractControlling the False Discovery Rate (FDR) in a variable selection procedure is critical for reproducible discoveries, and it has been extensively studied in sparse linear models. However, it remains largely open in scenarios where the sparsity constraint is not directly imposed on the parameters but on a linear transformation of the parameters to be estimated. Examples of such scenarios include total variations, wavelet transforms, fused LASSO, and trend filtering. In this paper, we propose a data-adaptive FDR control method, called the Split Knockoff method, for this transformational sparsity setting. The proposed method exploits both variable and data splitting. The linear transformation constraint is relaxed to its Euclidean proximity in a lifted parameter space, which yields an orthogonal design that enables the orthogonal Split Knockoff construction. To overcome the challenge that exchangeability fails due to the heterogeneous noise brought by the transformation, new inverse supermartingale structures are developed via data splitting for provable FDR control without sacrificing power. Simulation experiments demonstrate that the proposed methodology achieves the desired FDR and power. We also provide an application to Alzheimer’s Disease study, where atrophy brain regions and their abnormal connections can be discovered based on a structural Magnetic Resonance Imaging dataset.
Adaptive bootstrap tests for composite null hypotheses in the mediation pathway analysis
Authors: He Yinqiu , Song Peter X K , Xu Gongjun 
Published: November 2023

Abstract
Mediation analysis aims to assess if, and how, a certain exposure influences an outcome of interest through intermediate variables. This problem has recently gained a surge of attention due to the tremendous need for such analyses in scientific fields. Testing for the mediation effect (ME) is greatly challenged by the fact that the underlying null hypothesis (i.e. the absence of MEs) is composite. Most existing mediation tests are overly conservative and thus underpowered. To overcome this significant methodological hurdle, we develop an adaptive bootstrap testing framework that can accommodate different types of composite null hypotheses in the mediation pathway analysis. Applied to the product of coefficients test and the joint significance test, our adaptive testing procedures provide type I error control under the composite null, resulting in much improved statistical power compared to existing tests. Both theoretical properties and numerical examples of the proposed methodology are discussed.
An intronic RNA element modulates Factor VIII exon-16 splicing
Authors: Tse Victor , Chacaltana Guillermo , Gutierrez Martin , Forino Nicholas M , Jimenez Arcelia G , Tao Hanzhang , Do Phong H , Oh Catherine , Chary Priyanka , Quesada Isabel , Hamrick Antonia , Lee Sophie , Stone Michael D , Sanford Jeremy R 
Published: November 2023

Abstract
Pathogenic variants in the human Factor VIII (F8) gene cause Hemophilia A (HA). Here, we investigated the impact of 97 HA-causing single-nucleotide variants on the splicing of 11 exons from F8. For the majority of F8 exons, splicing was insensitive to the presence of HA-causing variants. However, splicing of several exons, including exon-16, was impacted by variants predicted to alter exonic splicing regulatory sequences. Using exon-16 as a model, we investigated the structure–function relationship of HA-causing variants on splicing. Intriguingly, RNA chemical probing analyses revealed a three-way junction structure at the 3′-end of intron-15 (TWJ-3–15) capable of sequestering the polypyrimidine tract. We discovered antisense oligonucleotides (ASOs) targeting TWJ-3–15 partially rescue splicing-deficient exon-16 variants by increasing accessibility of the polypyrimidine tract. The apical stem loop region of TWJ-3–15 also contains two hnRNPA1-dependent intronic splicing silencers (ISSs). ASOs blocking these ISSs also partially rescued splicing. When used in combination, ASOs targeting both the ISSs and the region sequestering the polypyrimidine tract, fully rescue pre-mRNA splicing of multiple HA-linked variants of exon-16. Together, our data reveal a putative RNA structure that sensitizes F8 exon-16 to aberrant splicing.
RefSeq and the prokaryotic genome annotation pipeline in the age of metagenomes
Authors: Haft Daniel H , Badretdin Azat , Coulouris George , DiCuccio Michael , Durkin A Scott , Jovenitti Eric , Li Wenjun , Mersha Megdelawit , O’Neill Kathleen R , Virothaisakun Joel , Thibaud-Nissen Françoise 
Published: November 2023

Abstract
The Reference Sequence (RefSeq) project at the National Center for Biotechnology Information (NCBI) contains over 315 000 bacterial and archaeal genomes and 236 million proteins with up-to-date and consistent annotation. In the past 3 years, we have expanded the diversity of the RefSeq collection by including the best quality metagenome-assembled genomes (MAGs) submitted to INSDC (DDBJ, ENA and GenBank), while maintaining its quality by adding validation checks. Assemblies are now more stringently evaluated for contamination and for completeness of annotation prior to acceptance into RefSeq. MAGs now account for over 17000 assemblies in RefSeq, split over 165 orders and 362 families. Changes in the Prokaryotic Genome Annotation Pipeline (PGAP), which is used to annotate nearly all RefSeq assemblies include better detection of protein-coding genes. Nearly 83% of RefSeq proteins are now named by a curated Protein Family Model, a 4.7% increase in the past three years ago. In addition to literature citations, Enzyme Commission numbers, and gene symbols, Gene Ontology terms are now assigned to 48% of RefSeq proteins, allowing for easier multi-genome comparison. RefSeq is found at https://www.ncbi.nlm.nih.gov/refseq/. PGAP is available as a stand-alone tool able to produce GenBank-ready files at https://github.com/ncbi/pgap.
A novel program of infiltrative control in astrocytomas: ADAM23 depletion promotes cell invasion by activating γ-secretase complex
Authors: Jandrey Elisa Helena Farias , Barnabé Gabriela Filoso , Maldaun Marcos , Asprino Paula Fontes , dos Santos Natália Cristina , Inoue Lilian Tiemi , Rozanski Andrei , Galante Pedro Alexandre Favoretto , Marie Suely Kazue Nagahashi , Oba-Shinjo Sueli Mieko , dos Santos Tiago Góss , Chammas Roger , Lancellotti Carmen Lucia Penteado , Furnari Frank B , Camargo Anamaria Aranha , Costa Érico Tosoni 
Published: November 2023

Abstract

Background
Infiltration is a life-threatening growth pattern in malignant astrocytomas and a significant cause of therapy resistance. It results in the tumor cell spreading deeply into the surrounding brain tissue, fostering tumor recurrence and making complete surgical resection impossible. We need to thoroughly understand the mechanisms underlying diffuse infiltration to develop effective therapies.

Methods
We integrated in vitro and in vivo functional assays, RNA sequencing, clinical, and expression information from public data sets to investigate the role of ADAM23 expression coupling astrocytoma’s growth and motility.

Results
ADAM23 downregulation resulted in increased infiltration, reduced tumor growth, and improved overall survival in astrocytomas. Additionally, we show that ADAM23 deficiency induces γ-secretase (GS) complex activity, contributing to the production and deposition of the Amyloid-β and release of NICD. Finally, GS ablation in ADAM23-low astrocytomas induced a significant inhibitory effect on the invasive programs.

Conclusions
Our findings reveal a role for ADAM23 in regulating the balance between cell proliferation and invasiveness in astrocytoma cells, proposing GS inhibition as a therapeutic option in ADAM23 low-expressing astrocytomas.