bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cabergoline targets multiple pathways to inhibit PRL secretion and increases stromal fibrosis
Authors: Zhang Dongyun , Hugo Willy , Bergsneider Marvin , Wang Marilene B , Kim Won , Han Karam , Vinters Harry V , Heaney Anthony P 
Published: May 2024

Abstract

Objective
Unravel the potential mechanism(s) of the on- and off-target actions of dopamine agonist therapy in both human prolactinoma tumors and neighboring stromal and immune cells.

Design and Methods
Five surgically resected prolactinomas (PRLomas) from 3 cabergoline (CBG)-treated patients and 2 treatment-naive patients were analyzed by using single-cell RNA sequencing (scRNA-seq) to compare the cellular composition and transcriptional landscape.

Results
Six major cell populations, namely tumor (88.2%), immune (5.6%), stromal (4.9%), progenitor cells (0.6%), proliferating cells (0.4%), and erythrocytes (0.2%), were observed. Tumor cells from CBG-treated patients expressed lower levels of genes that regulated hormone secretion, such as SCG2, VGF, TIMP1, NNAT, and CALD1, consistent with the inhibitory effects of CBG on hormone processing and secretion. Interestingly, we also observed an increased number of CD8+ T cells in the CBG-treated tissues. These cytotoxic CD8+ T cells expressed killing granule components such as perforin and the granzymes GZMB, GNLY, and KLRD1 as well as the inflammatory cytokine CCL5. Immune cell activation of these CD8+ T cells was further analyzed in a compartment-specific manner, and increased CD25 (IL2R) expression was noted in the CD8+ T cells from the CBG-treated samples. Additionally, and confirming prior reports, we noted a higher stromal cell population in the CBG-treated samples.

Conclusions
Our scRNA-seq studies revealed key differences in the transcriptomic features of CBG-treated and CBG-untreated PRLomas in both tumor and microenvironment cellular constituents, and for the first time, describe the previously unknown activation of CD8+ T cells following CBG treatment, which may play a role in the tumoricidal actions of CBG.
De Novo Genome Assembly and Annotation of Leptosia nina Provide New Insights into the Evolutionary Dynamics of Genes Involved in Host-Plant Adaptation of Pierinae Butterflies
Authors: Okamura Yu , Vogel Heiko 
Published: May 2024

Abstract
In interactions between plants and herbivorous insects, the traits enabling phytophagous insects to overcome chemical defenses of their host plants have evolved multiple times. A prominent example of such adaptive key innovations in herbivorous insects is nitrile specifier proteins (NSPs) that enabled Pierinae butterflies to colonize Brassicales host plants that have a glucosinolate–myrosinase defense system. Although the evolutionary aspects of NSP-encoding genes have been studied in some Pierinae taxa (especially among Pieris butterflies), the ancestral evolutionary state of NSPs is unclear due to the limited genomic information available for species within Pierinae. Here, we generate a high-quality genome assembly and annotation of Leptosia nina, a member of a small tribe, Leptosiaini. L. nina uses as its main host Capparaceae plants, one of the ancestral hosts within Pierinae. By using ∼90-fold coverage of Oxford Nanopore long reads and Illumina short reads for subsequent polishing and error correction, we constructed a final genome assembly that consisted of 286 contigs with a total of 225.8 Mb and an N50 of 10.7 Mb. Genome annotation with transcriptome hints predicted 16,574 genes and covered 98.3% of BUSCO genes. A typical NSP gene is composed of three tandem domains found in Pierinae butterflies; unexpectedly, we found a new NSP-like gene in Pierinae composed of only two tandem domains. This newly found NSP-like gene in L. nina provides important insights into the evolutionary dynamics of domain and gene duplication events relating to host-plant adaptation in Pierinae butterflies.
How group structure impacts the numbers at risk for coronary artery disease: polygenic risk scores and nongenetic risk factors in the UK Biobank cohort
Authors: Zhao Jinbo , O’Hagan Adrian , Salter-Townshend Michael 
Published: May 2024

Abstract
The UK Biobank (UKB) is a large cohort study that recruited over 500,000 British participants aged 40–69 in 2006–2010 at 22 assessment centers from across the United Kingdom. Self-reported health outcomes and hospital admission data are 2 types of records that include participants’ disease status. Coronary artery disease (CAD) is the most common cause of death in the UKB cohort. After distinguishing between prevalence and incidence CAD events for all UKB participants, we identified geographical variations in age-standardized rates of CAD between assessment centers. Significant distributional differences were found between the pooled cohort equation scores of UKB participants from England and Scotland using the Mann–Whitney test. Polygenic risk scores of UKB participants from England and Scotland and from different assessment centers differed significantly using permutation tests. Our aim was to discriminate between assessment centers with different disease rates by collecting data on disease-related risk factors. However, relying solely on individual-level predictions and averaging them to obtain group-level predictions proved ineffective, particularly due to the presence of correlated covariates resulting from participation bias. By using the Mundlak model, which estimates a random effects regression by including the group means of the independent variables in the model, we effectively addressed these issues. In addition, we designed a simulation experiment to demonstrate the functionality of the Mundlak model. Our findings have applications in public health funding and strategy, as our approach can be used to predict case rates in the future, as both population structure and lifestyle changes are uncertain.
The lithospheric structure of Greenland from a stepwise forward and inverse modelling approach
Authors: Wansing A , Ebbing J , Moorkamp M 
Published: May 2024

SUMMARY
Greenland’s tectonic history is complex, and the resulting lithospheric structure is, although extensively researched, not well constrained. In this study, we model the lithospheric structure of Greenland in a consistent, integrated framework with three steps. First, we build a lithospheric background model by forward modelling, adjusted to gravity gradient data and shear wave velocities from a regional tomography model. Subsequently, we jointly invert for the upper crustal density and susceptibility structure by minimizing the gravity residuals and magnetic total field anomaly misfit. The last modelling step searches for upper crustal thermal parameters to fit our model to the most recent geothermal heat flow predictions for Greenland. Finally, we present 3-D models of the density, temperature and velocity structure for the lithosphere as well as thermal parameters and susceptibilities for the upper crust. Our model also includes the depth of the Moho and LAB in Greenland. A comparison between inverted crustal parameters and surface geology shows a clear correlation. The novelty of our model is that all these results are consistent with each other and simultaneously explain a wide range of observed data.
Multi-cancer early detection (MCED) tests: prioritizing equity from bench to bedside
Authors: Miller Sarah J , Sly Jamilia R , Rolfo Christian , Mack Philip , Villanueva Augusto , Mazor Melissa , Weber Ellerie , Lin Jenny J , Smith Cardinale B , Taioli Emanuela 
Published: May 2024

Abstract
Multi-cancer early detection (MCED) tests are blood-based tests designed to screen for signals of multiple cancers. There is growing interest and investment in examining the potential benefits and applications of MCED tests. If MCED tests are shown to have clinical utility, it is important to ensure that all people—regardless of their demographic or socioeconomic background—equitably benefit from these tests. Unfortunately, with health care innovation, such considerations are often ignored until after inequities emerge. We urge for-profit companies, scientists, clinicians, payers, and government agencies to prioritize equity now—when MCEDs are still being developed and researched. In an effort to avoid creating and exacerbating cancer inequities, we propose 9 equity considerations for MCEDs.
Mitochondrial DNA release and sensing in innate immune responses
Authors: VanPortfliet Jordyn J , Chute Cole , Lei Yuanjiu , Shutt Timothy E , West A Phillip 
Published: May 2024

Abstract
Mitochondria are pleiotropic organelles central to an array of cellular pathways including metabolism, signal transduction, and programmed cell death. Mitochondria are also key drivers of mammalian immune responses, functioning as scaffolds for innate immune signaling, governing metabolic switches required for immune cell activation, and releasing agonists that promote inflammation. Mitochondrial DNA (mtDNA) is a potent immunostimulatory agonist, triggering pro-inflammatory and type I interferon responses in a host of mammalian cell types. Here we review recent advances in how mtDNA is detected by nucleic acid sensors of the innate immune system upon release into the cytoplasm and extracellular space. We also discuss how the interplay between mtDNA release and sensing impacts cellular innate immune endpoints relevant to health and disease.
Decoding the Enigma: Translation Termination in Human Mitochondria
Authors: Krüger Annika , Kovalchuk Daria , Shiriaev Dmitrii , Rorbach Joanna 
Published: May 2024

Abstract
Mitochondrial translation is a complex process responsible for the synthesis of essential proteins involved in oxidative phosphorylation, a fundamental pathway for cellular energy production. Central to this process is the termination phase, where dedicated factors play a pivotal role in ensuring accurate and timely protein production. This review provides a comprehensive overview of the current understanding of translation termination in human mitochondria, emphasizing structural features and molecular functions of two mitochondrial termination factors mtRF1 and mtRF1a.
Central dogma rates in human mitochondria
Authors: McShane Erik , Churchman L Stirling 
Published: May 2024

Abstract
In human cells, the nuclear and mitochondrial genomes engage in a complex interplay to produce dual-encoded oxidative phosphorylation (OXPHOS) complexes. The coordination of these dynamic gene expression processes is essential for producing matched amounts of OXPHOS protein subunits. This review focuses on our current understanding of the mitochondrial central dogma rates, highlighting the striking differences in gene expression rates between mitochondrial and nuclear genes. We synthesize a coherent model of mitochondrial gene expression kinetics, highlighting the emerging principles and emphasizing where more precise measurements would be beneficial. Such an understanding is pivotal for grasping the unique aspects of mitochondrial function and its role in cellular energetics, and it has profound implications for aging, metabolic disorders, and neurodegenerative diseases.
RNA degradation in human mitochondria: the journey is not finished
Authors: Santonoceto Giulia , Jurkiewicz Aneta , Szczesny Roman J 
Published: May 2024

Abstract
Mitochondria are vital organelles present in almost all eukaryotic cells. Although most of the mitochondrial proteins are nuclear-encoded, mitochondria contain their own genome, whose proper expression is necessary for mitochondrial function. Transcription of the human mitochondrial genome results in the synthesis of long polycistronic transcripts that are subsequently processed by endonucleases to release individual RNA molecules, including precursors of sense protein-encoding mRNA (mt-mRNA) and a vast amount of antisense noncoding RNAs. Because of mitochondrial DNA (mtDNA) organization, the regulation of individual gene expression at the transcriptional level is limited. Although transcription of most protein-coding mitochondrial genes occurs with the same frequency, steady-state levels of mature transcripts are different. Therefore, post-transcriptional processes are important for regulating mt-mRNA levels. The mitochondrial degradosome is a complex composed of the RNA helicase SUV3 (also known as SUPV3L1) and polynucleotide phosphorylase (PNPase, PNPT1). It is the best-characterized RNA-degrading machinery in human mitochondria, which is primarily responsible for the decay of mitochondrial antisense RNA. The mechanism of mitochondrial sense RNA decay is less understood. This review aims to provide a general picture of mitochondrial genome expression, with a particular focus on mitochondrial RNA (mtRNA) degradation.
Molecular and cellular consequences of mitochondrial DNA double-stranded breaks
Authors: Yu Chenxiao , Asadian Samieh , Tigano Marco 
Published: May 2024

Abstract
Mitochondria are subcellular organelles essential for life. Beyond their role in producing energy, mitochondria govern various physiological mechanisms, encompassing energy generation, metabolic processes, apoptotic events, and immune responses. Mitochondria also contain genetic material that is susceptible to various forms of damage. Mitochondrial double-stranded breaks (DSB) are toxic lesions that the nucleus repairs promptly. Nevertheless, the significance of DSB repair in mammalian mitochondria is controversial. This review presents an updated view of the available research on the consequences of mitochondrial DNA DSB from the molecular to the cellular level. We discuss the crucial function of mitochondrial DNA damage in regulating processes such as senescence, integrated stress response, and innate immunity. Lastly, we discuss the potential role of mitochondrial DNA DSB in mediating the cellular consequences of ionizing radiations, the standard of care in treating solid tumors.
Origins of tissue and cell-type specificity in mitochondrial DNA (mtDNA) disease
Authors: Burr Stephen P , Chinnery Patrick F 
Published: May 2024

Abstract
Mutations of mitochondrial (mt)DNA are a major cause of morbidity and mortality in humans, accounting for approximately two thirds of diagnosed mitochondrial disease. However, despite significant advances in technology since the discovery of the first disease-causing mtDNA mutations in 1988, the comprehensive diagnosis and treatment of mtDNA disease remains challenging. This is partly due to the highly variable clinical presentation linked to tissue-specific vulnerability that determines which organs are affected. Organ involvement can vary between different mtDNA mutations, and also between patients carrying the same disease-causing variant. The clinical features frequently overlap with other non-mitochondrial diseases, both rare and common, adding to the diagnostic challenge. Building on previous findings, recent technological advances have cast further light on the mechanisms which underpin the organ vulnerability in mtDNA diseases, but our understanding is far from complete. In this review we explore the origins, current knowledge, and future directions of research in this area.
Challenges in IBD Research 2024: Pragmatic Clinical Research
Authors: Allegretti Jessica R , Bordeianou Liliana G , Damas Oriana M , Eisenstein Samuel , Greywoode Ruby , Minar Phillip , Singh Siddharth , Harmon Sabrina , Lisansky Eugene , Malone-King Myisha , Litwin Nicole S , Weaver Alandra , Heller Caren A , Moss Alan C , Adler Jeremy 
Published: May 2024

Abstract
Pragmatic clinical research is 1 of the 5 focus areas of the Challenges in IBD Research 2024, a multidisciplinary effort by scientists, clinicians, patients, and funders to identify priorities for patient-centric research. This summary provides a comprehensive overview of current gaps in inflammatory bowel disease (IBD) clinical research and actionable approaches to address them. This review is focused on identifying research that is needed to achieve the best outcomes for patients in clinical practice. Research gaps include understanding the needs of understudied patient groups and addressing barriers to care so all patients receive optimal care, validating and using biomarkers to enable early diagnosis and result in better outcomes for adults and children with IBD, and determining the optimal sequencing of treatments (medical, surgical, adjunct) in children and adults. Inclusive pragmatic research is needed to address these gaps and lead to improvements in patient care and outcomes for all populations of patients with IBD.
Challenges in IBD Research 2024: Environmental Triggers
Authors: Ananthakrishnan Ashwin N , Gerasimidis Kostantinos , Ho Shuk-Mei , Mayer Emeran , Pollock Jennifer , Soni Shefali , Wu Gary D , Benyacoub Jalil , Ali Basmah , Favreau Alex , Smith Denise Elsbree , Oh Ji-eun , Heller Caren , Hurtado-Lorenzo Andres , Moss Alan , Croitoru Ken 
Published: May 2024

Abstract
Environmental factors play an important role in inflammatory bowel diseases (IBD; Crohn’s disease, [CD], ulcerative colitis [UC]). As part of the Crohn’s & Colitis Challenges 2024 agenda, the Environmental Triggers workgroup summarized the progress made in the field of environmental impact on IBD since the last Challenges cycle in this document. The workgroup identified 4 unmet gaps in this content area pertaining to 4 broad categories: (1) Epidemiology; (2) Exposomics and environmental measurement; (3) Biologic mechanisms; and (4) Interventions and Implementation. Within epidemiology, the biggest unmet gaps were in the study of environmental factors in understudied populations including racial and ethnic minority groups and in populations witnessing rapid rise in disease incidence globally. The workgroup also identified a lack of robust knowledge of how environmental factors may impact difference stages of the disease and for different disease-related end points. Leveraging existing cohorts and targeted new prospective studies were felt to be an important need for the field. The workgroup identified the limitations of traditional questionnaire-based assessment of environmental exposure and placed high priority on the identification of measurable biomarkers that can quantify cross-sectional and longitudinal environmental exposure. This would, in turn, allow for identifying the biologic mechanisms of influence of environmental factors on IBD and understand the heterogeneity in effect of such influences. Finally, the working group emphasized the importance of generating high-quality data on effective environmental modification on an individual and societal level, and the importance of scalable and sustainable methods to deliver such changes.
Descending necrotizing mediastinitis caused by a minor whiplash injury
Authors: Bikoi Yem Michel Landry , Decker Georges 
Published: May 2024

Abstract
We describe a case of descending necrotizing mediastinitis from a very unusual origin, caused by cervical oesophageal perforation by osteophytes after an apparently minor whiplash injury. Diagnosis was delayed by atypical and predominantly neurological clinical presentation. Despite late presentation, minimally invasive access surgical debridement of mediastinum and cervical injury site lead to full recovery.
Can physics-informed neural networks beat the finite element method?
Authors: Grossmann Tamara G , Komorowska Urszula Julia , Latz Jonas , Schönlieb Carola-Bibiane 
Published: May 2024

Abstract
Partial differential equations (PDEs) play a fundamental role in the mathematical modelling of many processes and systems in physical, biological and other sciences. To simulate such processes and systems, the solutions of PDEs often need to be approximated numerically. The finite element method, for instance, is a usual standard methodology to do so. The recent success of deep neural networks at various approximation tasks has motivated their use in the numerical solution of PDEs. These so-called physics-informed neural networks and their variants have shown to be able to successfully approximate a large range of PDEs. So far, physics-informed neural networks and the finite element method have mainly been studied in isolation of each other. In this work, we compare the methodologies in a systematic computational study. Indeed, we employ both methods to numerically solve various linear and nonlinear PDEs: Poisson in 1D, 2D and 3D, Allen–Cahn in 1D, semilinear Schrödinger in 1D and 2D. We then compare computational costs and approximation accuracies. In terms of solution time and accuracy, physics-informed neural networks have not been able to outperform the finite element method in our study. In some experiments, they were faster at evaluating the solved PDE.
The role of information systems in emergency department decision-making—a literature review
Authors: Born Cornelius , Schwarz Romy , Böttcher Timo Phillip , Hein Andreas , Krcmar Helmut 
Published: May 2024

Abstract

Objectives
Healthcare providers employ heuristic and analytical decision-making to navigate the high-stakes environment of the emergency department (ED). Despite the increasing integration of information systems (ISs), research on their efficacy is conflicting. Drawing on related fields, we investigate how timing and mode of delivery influence IS effectiveness. Our objective is to reconcile previous contradictory findings, shedding light on optimal IS design in the ED.

Materials and methods
We conducted a systematic review following PRISMA across PubMed, Scopus, and Web of Science. We coded the ISs’ timing as heuristic or analytical, their mode of delivery as active for automatic alerts and passive when requiring user-initiated information retrieval, and their effect on process, economic, and clinical outcomes.

Results
Our analysis included 83 studies. During early heuristic decision-making, most active interventions were ineffective, while passive interventions generally improved outcomes. In the analytical phase, the effects were reversed. Passive interventions that facilitate information extraction consistently improved outcomes.

Discussion
Our findings suggest that the effectiveness of active interventions negatively correlates with the amount of information received during delivery. During early heuristic decision-making, when information overload is high, physicians are unresponsive to alerts and proactively consult passive resources. In the later analytical phases, physicians show increased receptivity to alerts due to decreased diagnostic uncertainty and information quantity. Interventions that limit information lead to positive outcomes, supporting our interpretation.

Conclusion
We synthesize our findings into an integrated model that reveals the underlying reasons for conflicting findings from previous reviews and can guide practitioners in designing ISs in the ED.