bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Trials Radiographers identifying priority challenges associated with implementing a national programme of clinical trials in the United Kingdom’s first proton beam therapy centre
Authors: Davies Lucy S C , McHugh Louise , Falk Sally , Bridge Jacqui , Amaro Philip F , Whiteside Lee , Bailey Rachael , Webb Julie , Eccles Cynthia L
Published: May 2024

Objectives

This article is an evaluation of the current trial processes within a national proton beam therapy (PBT) clinical trial service in the United Kingdom. The work within the article identifies priority challenges associated with the implementation of PBT trials with a view to improving patient trial processes.

Methods

The nominal group technique (NGT) was used. Five Clinical Trials Radiographers were asked the target question “what are the major challenges when implementing PBT clinical trials and facilitating PBT trial-related activities?” Participants individually and silently listed their challenges to the target question. Following this, group discussion clarified and refined responses. Participants then individually selected five challenges that they deemed most pertinent to the target question, giving a weighted score (out of 10). Individual scores were combined to provide a ranked, weighted order of challenges. Further group discussion identified improvement strategies to the highest scored challenges.

Results

After combining lists generated by participants, 59 challenges were identified. Group discussion eliminated 27 responses. Eighteen were merged, resulting in 14 challenges. The two challenges that ranked highest were: (i) lack of initial understanding of the responsibilities of teams and who the relevant stakeholders were, and (ii) that a national PBT service requires the provision of shared care across multi-disciplinary teams and sites. Improvement areas include the development of shared protocols, clarifying stakeholder responsibilities and improving communication between centres to streamline PBT trial processes.

Conclusions

This work has identified priority areas requiring development to improve the conduct of a national PBT clinical trials programme.

Advances in knowledge

This is the first publication to evaluate current clinical trial processes for the United Kingdom’s PBT service.
From skin checking to suturing: efficacy of a sequential dermatology simulation for medical students
Authors: Zaminski Devyn , Zhang Ya-Han , Engelman Jenny , Kolla Patel Avani , Pahalyants Vartan , Bawany Fatima , Himeles Jaclyn R , Mazori Daniel R
Published: May 2024

Clinical simulations have been shown to increase medical students’ understanding of and interest in dermatology. The New York University Grossman School of Medicine Dermatology Interest Group developed and evaluated a new simulation that more fully mimics the process of diagnosing pigmented lesions by emulating a dermatologist’s actual workflow. After participating in the simulation, students demonstrated increased knowledge in both short- and long-term assessments, and 96% felt that the simulation should be a mandatory part of their curriculum.
The relationship between the uptake of alveolar bone inflammation and of cervical lymph nodes on fluoro-2-deoxy-D-glucose positron emission tomography
Authors: Oda Masafumi , Koga Hirofumi , Kataoka Shota , Yoshii Shinji , Nishina Susumu , Ansai Toshihiro , Morimoto Yasuhiro
Published: May 2024

Objectives

To elucidate the relationships between the maximum standardized uptake value (SUVmax) of alveolar bone and those of lymph nodes (LNs) around the neck on 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET).

Methods

The SUVmax values of alveolar bone and of level IA, level IB, and level IIA LNs of 174 patients, including those with and without active odontogenic inflammation, on PET/CT performed for a health check were retrospectively evaluated. The upper and lower jaws were divided into four blocks (right maxilla, left maxilla, right mandible, and left mandible). The SUVmax values of each block and of the LNs were calculated. The differences in the SUVmax of each LN level between patients with and without odontogenic inflammation, and the relationship between the SUVmax values of alveolar bone and of the LNs were analysed statistically.

Results

Significant differences in SUVmax values of bilateral level IB and IIA LNs were found between patients with and without odontogenic inflammation (Mann-Whitney U test: right level IB, P = .008; left level IB, P = .006; right level IIA, P < .001; left level IIA, P = .002), but not in bilateral level IA LNs (Mann-Whitney U test: right level IA, P = .432; left level IA, P = .549). The inflammatory site with the highest SUVmax in level IB LNs was the ipsilateral mandible (multivariate analysis: right, beta = 0.398, P < .001; left, beta = 0.472, P < .001), and the highest SUVmax in level IIA LNs was the ipsilateral maxilla (multivariate analysis: right, beta = 0.223, P = .002; left, beta = 0.391, P < .001).

Conclusions

The SUVmax values of level IB and IIA LNs were associated with a tendency towards a higher SUVmax value of alveolar bone on 18F-FDG-PET.
The enigma of fine mobile structures on the aortic surface in a patient undergoing transcatheter aortic valve replacement: a case report
Authors: Cohen Gerald I , Saleb Karim , Troy Patrick , Hagspiel Klaus D , Lalonde Thomas
Published: May 2024

Background

The surface of the aorta generally does not show motion unless mobile atheroma, thrombi, vegetations, or intimal flaps are present. We previously described unusual mobile filamentous structures in the carotid artery. Here, we describe similar findings in the aorta and their possible cause.

Case summary

An 88-year-old female with progressive exertional dyspnoea and severe aortic stenosis had a successful transcatheter aortic valve replacement (TAVR). A filamentous structure was noted on the focused pre-operative 2D transoesophageal echocardiography in the proximal descending aorta and post-TAVR as long strand-like structures attached to the thickened intimal wall with a planar component on 3D imaging. These findings were not associated with symptoms or clinical sequelae on short- and long-term follow-up.

Discussion

The mobile structures that we describe are atypical for atheroma, thrombi, vegetations, and dissections in terms of their form and clinical presentation. 2D imaging showed that the filaments had focal thickening and emerged from the aortic surface. These findings suggest a relationship with the intima, perhaps from atherogenesis or injury with disruption or lifting of the intimal surface. No clinical sequelae were detected that may also relate to their position in the descending aorta and not the arch.
Diagnostic value of left ventricular layer strain and specific regional strain patterns in cardiac amyloidosis and Fabry disease
Authors: Steudel Tilman , Barzen Gina , Frumkin David , Romero-Dorta Elena , Spethmann Sebastian , Hindricks Gerhard , Stangl Karl , Knebel Fabian , Heidecker Bettina , Canaan-Kühl Sima , Pernice Helena Franziska , Hahn Katrin , Mattig Isabel , Brand Anna
Published: May 2024

Aims

Layer-specific left ventricular (LV) strain alterations have been suggested as a specific finding in Fabry disease (FD). Our study aimed to assess the diagnostic value of layer-specific radial strain (RS) indices compared to the established LV regional strain pattern in cardiac amyloidosis (CA) and FD, i.e. apical sparing and posterolateral strain deficiency (PLSD).

Methods and results

We retrospectively analysed the global, subendocardial, subepicardial LV radial strain, the corresponding strain gradient, as well as the regional and global longitudinal strain. The diagnostic accuracy of the diverse LV strain analyses was comparatively assessed using receiver operating characteristic curve and multivariable regression analyses. In 40 FD and 76 CA patients, CA featured more reduced layer strain values [global RS −12.3 (−15.6 to −9.6) in CA vs. −16.7 (−20.0 to −13.6) in FD; P < 0.001; subendocardial RS −22.3 (−27.4 to −15.9) vs. −28.3 (−31.8 to −23.6), P < 0.001; subepicardial RS −6.6 (−8.6 to −4.7) in CA vs. −8.9 (−11.7 to − 6.5) in FD; P < 0.001]. Global radial and longitudinal strain held an area under the curve (AUC) of 0.75 (0.66–0.84) and AUC 0.73 (0.63–0.83). While the apical sparing and PLSD strain pattern showed the highest accuracy as single parameters [AUC 0.87 (0.79–0.95) and 0.81 (0.72–0.89), P < 0.001], the combination of subendocardial RS and the apical sparing pattern featured the highest diagnostic accuracy [AUC 0.92 (0.87–0.97)].

Conclusion

Combining radial strain-derived parameters to the established strain pattern apical sparing and PLSD improve the diagnostic accuracy in the echocardiographic assessment in suspected storage disease.
Mechanical circulatory support in patients with congenital heart disease: a European Registry for Patients with Mechanical Circulatory Support (EUROMACS) study
Authors: Ardissino Maddalena , Morley Alec P , Lewis Clive , Bhagra Catriona , Stoll Victoria , Potapov Evegnij , Schoenrath Felix , Gummert Jan , Przybyłowski Piotr , Śliwka Joanna , Meyns Bart , de By Theo M M H , Jones Nicola , Tsui Steven
Published: May 2024

OBJECTIVES

This study aims to explore characteristics and clinical outcomes of patients with congenital heart disease (CHD) in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS).

METHODS

This is a retrospective study of EUROMACS participants receiving MCS as bridge-to-transplant, possible bridge-to-transplant, or rescue therapy/bridge-to-recovery from 2011 to 2023 (n = 5340). Adult and paediatric cohorts were analysed separately. The primary outcome was mortality on MCS; secondary outcomes included recovery, transplant and complications including bleeding, cerebrovascular events, and sepsis.

RESULTS

Among adult patients, mortality at 1-year was 33.3% among the CHD cohort vs 22.1% in the non-CHD cohort. Adult CHD patients had higher hazards of mortality within the first year after MCS implantation [hazard ratios 1.98, 95% confidence interval (CI) 1.35–2.91, P < 0.001] and bleeding events (subdistribution hazard ratios 2.10, 95% CI 1.40–3.16, P < 0.001) compared with non-CHD patients. Both associations remained significant after accounting for multiple mediators. Among paediatric patients, mortality at 1 year was 22.1% in the CHD cohort vs 17.3% in the non-CHD cohort (hazard ratios 1.39, 95% CI 0.83–2.32, P = 0.213).

CONCLUSIONS

Adult and paediatric patients with CHD on MCS have higher adverse event risk compared with non-CHD MCS patients, though children did not have greater risk of mortality. As the number of CHD patients requiring advanced heart failure management continues to grow, these findings can enhance informed decision-making.

Clinical trial registration number

Registry name: EUROMACS.
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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.
Understanding enterprise data warehouses to support clinical and translational research: impact, sustainability, demand management, and accessibility
Authors: Campion Thomas R , Craven Catherine K , Dorr David A , Bernstam Elmer V , Knosp Boyd M
Published: May 2024

Objectives

Healthcare organizations, including Clinical and Translational Science Awards (CTSA) hubs funded by the National Institutes of Health, seek to enable secondary use of electronic health record (EHR) data through an enterprise data warehouse for research (EDW4R), but optimal approaches are unknown. In this qualitative study, our goal was to understand EDW4R impact, sustainability, demand management, and accessibility.

Materials and Methods

We engaged a convenience sample of informatics leaders from CTSA hubs (n = 21) for semi-structured interviews and completed a directed content analysis of interview transcripts.

Results

EDW4R have created institutional capacity for single- and multi-center studies, democratized access to EHR data for investigators from multiple disciplines, and enabled the learning health system. Bibliometrics have been challenging due to investigator non-compliance, but one hub’s requirement to link all study protocols with funding records enabled quantifying an EDW4R’s multi-million dollar impact. Sustainability of EDW4R has relied on multiple funding sources with a general shift away from the CTSA grant toward institutional and industry support. To address EDW4R demand, institutions have expanded staff, used different governance approaches, and provided investigator self-service tools. EDW4R accessibility can benefit from improved tools incorporating user-centered design, increased data literacy among scientists, expansion of informaticians in the workforce, and growth of team science.

Discussion

As investigator demand for EDW4R has increased, approaches to tracking impact, ensuring sustainability, and improving accessibility of EDW4R resources have varied.

Conclusion

This study adds to understanding of how informatics leaders seek to support investigators using EDW4R across the CTSA consortium and potentially elsewhere.
Environmental Materialities and the History of Pandemics
Authors: Webster Emily
Published: May 2024

Over the last several decades, a growing group of environmental and medical historians have argued that engagement with the materiality of disease is critical to eroding the false boundaries between environment and health, and especially to the historical study of major epidemics and pandemics. This article evaluates the ways in which environmental and medical historians have engaged materiality when thinking through questions of infectious disease. It argues that far from eschewing cultural constructions of disease and analysis of medical systems, these works demonstrate that engagement with materiality in the study of disease articulates the stakes of medical regimes and practices of healing, and renders legible the multiple scales at which epidemics occur. Addressing key controversies in the use of sources, it provides examples of works that incorporate material objects, biological ideas and actors, and non-humans without falling prey to the extremes of “biological determinism” or “constructivism.” It argues that commonalities in the methods employed by these works – utilization of scientific frameworks and data, multispecies analysis, attention to scale, and spatial thinking – reveal unseen and untold aspects of past pandemics. It concludes with a brief example of how these frameworks come together in practice through a case study on the history of enteric fever in Dublin, Ireland.
Post-traumatic renal arteriovenous malformation failed endovascular embolization
Authors: Alyami Ali , Alothman Ali , Balaraj Faisal , Alomairi Mohanned , Ghazwani Yahya , Albqami Nasser
Published: May 2024

Renal arteriovenous malformations (AVMs) are abnormal connections between the renal arteries and venous system. Arteriovenous fistulas account for 70%–80% of renal arteriovenous abnormalities, often resulting from iatrogenic injuries. While most renal AVMs are asymptomatic, hematuria is a common symptom caused by AVM rupture into the renal calyces. Angiography is the gold standard for diagnosis, but noninvasive imaging techniques like ultrasound, computed tomography, or magnetic resonance imaging are commonly used for initial evaluation. Most renal AVMs are managed conservatively. Symptomatic patients typically undergo endovascular embolization, the preferred treatment, while surgery is reserved for unstable patients or those with complex vascular anatomy. We present a case of a 32-year-old man with renal AVMs following a motor vehicle accident. The patient initially received unsuccessful endovascular embolization but achieved successful treatment through open fistula ligation. This case highlights the challenges in managing renal AVMs and the importance of considering alternative interventions when initial treatments prove ineffective.
Omental infarction following robotic-assisted laparoscopic inguinal hernia repair
Authors: Hassanesfahani Maryam , Tian Jane , Keating Luke , Khan Noman , Louis Martine A , Malhotra Rajinder
Published: May 2024

Omental infarction (OI) is a rare condition with an overall incidence of less than 0.3%. It can occur spontaneously or can be secondary to trauma, surgery, and inflammation. While previously a diagnosis of exclusion, due to development in imaging technology, OI can now be identified based on CT findings. OI symptoms can mimic an acute abdomen, prompting potentially unnecessary surgical exploration. Treatment options range from conservative management to interventional radiology or surgical resection of the infarcted omentum. We are presenting the first case of OI following robotic-assisted inguinal hernia repair. This case highlights the importance of considering OI in differential diagnoses for patients presenting with acute abdominal pain, the utility of imaging workup in identifying OI, and guidance for conservative treatment approaches to reduce unnecessary surgical intervention.
Pure laparoscopic bilateral arcuate line hernia repair (with video)
Authors: Rappoport J , Carrasco J , Gamez B
Published: May 2024

An arcuate line hernia is a generally asymptomatic, ascending protrusion of intraperitoneal structures over the linea arcuata. Arcuate line herniae are scarcely reported in the literature. Only a few publications were found. No clear descriptions of the techniques for repair have been published either. We aim to provide diagnostic images and illustrate our method to repair this hernia.
Partitioning seasonal stem carbon dioxide efflux into stem respiration, bark photosynthesis, and transport-related flux in Scots pine
Authors: Dukat Paulina , Hölttä Teemu , Oren Ram , Salmon Yann , Urbaniak Marek , Vesala Timo , Aalto Juho , Lintunen Anna
Published: May 2024

Stem CO2 efflux is an important component of the carbon balance in forests. The efflux is considered to principally reflect the net result of two dominating and opposing processes: stem respiration and stem photosynthesis. In addition, transport of CO2 in xylem sap is thought to play an appreciable role in affecting the net flux. This work presents an approach to partition stem CO2 efflux among these processes using sap-flux data and CO2-exchange measurements from dark and transparent chambers placed on mature Scots pine (Pinus sylvestris) trees. Seasonal changes and monthly parameters describing the studied processes were determined. Respiration contributed most to stem net CO2 flux, reaching up to 79% (considering the sum of the absolute values of stem respiration, stem photosynthesis, and flux from CO2 transported in xylem sap to be 100%) in June, when stem growth was greatest. The contribution of photosynthesis accounted for up to 13% of the stem net CO2 flux, increasing over the monitoring period. CO2 transported axially with sap flow decreased towards the end of the growing season. At a reference temperature, respiration decreased starting around midsummer, while its temperature sensitivity increased during the summer. A decline was observed for photosynthetic quantum yield around midsummer together with a decrease in light-saturation point. The proposed approach facilitates modeling net stem CO2 flux at a range of time scales.
Expect the unexpected: endocarditis caused by Legionella feeleii
Authors: Moran Angelica , Otero Espinal Dennise E , Parilla Megan , Beavis Kathleen G , Mullane Kathleen M , Tesic Vera
Published: May 2024

We report a fatal case of Legionella feeleii endocarditis in a post–lung transplant patient. The diagnosis was delayed, as routine microbiological testing of nonrespiratory specimens does not account for extrapulmonary Legionella, and urine antigen testing only reliably detects Legionella pneumophila serogroup 1. This case also illustrates the utility of molecular sequencing for blood culture–negative endocarditis.
Gliese 12 b, a temperate Earth-sized planet at 12 parsecs discovered with TESS and CHEOPS
Authors: Dholakia Shishir , Palethorpe Larissa , Venner Alexander , Mortier Annelies , Wilson Thomas G , Huang Chelsea X , Rice Ken , Van Eylen Vincent , Nabbie Emma , Cloutier Ryan , Boschin Walter , Ciardi David , Delrez Laetitia , Dransfield Georgina , Ducrot Elsa , Essack Zahra , Everett Mark E , Gillon Michaël , Hooton Matthew J , Kunimoto Michelle , Latham David W , López-Morales Mercedes , Li Bin , Li Fan , McDermott Scott , Murphy Simon J , Murray Catriona A , Seager Sara , Timmermans Mathilde , Triaud Amaury , Turner Daisy A , Twicken Joseph D , Vanderburg Andrew , Wang Su , Wittenmyer Robert A , Wright Duncan
Published: May 2024

We report on the discovery of Gliese 12 b, the nearest transiting temperate, Earth-sized planet found to date. Gliese 12 is a bright (V = 12.6 mag, K = 7.8 mag) metal-poor M4V star only 12.162 ± 0.005 pc away from the Solar system with one of the lowest stellar activity levels known for M-dwarfs. A planet candidate was detected by TESS based on only 3 transits in sectors 42, 43, and 57, with an ambiguity in the orbital period due to observational gaps. We performed follow-up transit observations with CHEOPS and ground-based photometry with MINERVA-Australis, SPECULOOS, and Purple Mountain Observatory, as well as further TESS observations in sector 70. We statistically validate Gliese 12 b as a planet with an orbital period of 12.76144 ± 0.00006 d and a radius of 1.0 ± 0.1 R⊕, resulting in an equilibrium temperature of ∼315 K. Gliese 12 b has excellent future prospects for precise mass measurement, which may inform how planetary internal structure is affected by the stellar compositional environment. Gliese 12 b also represents one of the best targets to study whether Earth-like planets orbiting cool stars can retain their atmospheres, a crucial step to advance our understanding of habitability on Earth and across the galaxy.
Hypothermia, bradycardia, and hypotension during glucocorticoid or cyclosporine A therapy in a boy with Kikuchi-Fujimoto disease
Authors: Hiramatsu Yasuyoshi , Takahashi Kazuki , Shimomura Masaki , Taniguchi Kota , Okura Yuka , Nawate Mitsuru , Takahashi Yutaka , Kobayashi Ichiro
Published: May 2024

Kikuchi-Fujimoto disease (KFD) is an inflammatory disease of unknown aetiology characterised by fever and cervical lymphadenopathy. Although KFD is a self-limiting disease, patients with severe or long-lasting course require glucocorticoid therapy. We presently report a 17-year-old boy with KFD who had seven relapses since the onset at 4 years old. He suffered from hypothermia, bradycardia, and hypotension during the treatment with prednisolone or methylprednisolone. All of his vital signs recovered after cessation of the drug in addition to fluid replacement and warming. Thus, glucocorticoid was effective but could not be continued because of the adverse event. Although hypothermia developed during the treatment with 5 mg/kg/day of cyclosporine A (CsA) at his second relapse, he was successfully treated with lower-dose CsA (3 mg/kg/day). Thereafter, he had five relapses of KFD until the age of 12 years and was treated by 1.3–2.5 mg/kg/day of CsA. Hypothermia accompanied by bradycardia and hypotension developed soon after concomitant administration of ibuprofen at his fifth and sixth relapses even during low-dose CsA therapy. Conclusively, glucocorticoid, standard dose of CsA, or concomitant use of non-steroidal anti-inflammatory drugs may cause hypothermia, bradycardia, and hypotension and needs special attention. Low-dose CsA could be a choice for such cases with KFD.