bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine Learning-Based Sample Misidentification Error Detection in Clinical Laboratory Tests: A Retrospective Multicenter Study
Authors: Seok Hyeon Seok , Yu Shinae , Shin Kyung-Hwa , Lee Woochang , Chun Sail , Kim Sollip , Shin Hangsik 
Published: August 2024

Abstract

Background
In clinical laboratories, the precision and sensitivity of autoverification technologies are crucial for ensuring reliable diagnostics. Conventional methods have limited sensitivity and applicability, making error detection challenging and reducing laboratory efficiency. This study introduces a machine learning (ML)-based autoverification technology to enhance tumor marker test error detection.

Methods
The effectiveness of various ML models was evaluated by analyzing a large data set of 397 751 for model training and internal validation and 215 339 for external validation. Sample misidentification was simulated by random shuffling error-free test results with a 1% error rate to achieve a real-world approximation. The ML models were developed with Bayesian optimization for tuning. Model validation was performed internally at the primary institution and externally at other institutions, comparing the ML models’ performance with conventional delta check methods.

Results
Deep neural networks and extreme gradient boosting achieved an area under the receiver operating characteristic curve of 0.834 to 0.903, outperforming that of conventional methods (0.705 to 0.816). External validation by 3 independent laboratories showed that the balanced accuracy of the ML model ranged from 0.760 to 0.836, outperforming the balanced accuracy of 0.670 to 0.773 of the conventional models.

Conclusions
This study addresses limitations regarding the sensitivity of current delta check methods for detection of sample misidentification errors and provides versatile models that mitigate the operational challenges faced by smaller laboratories. Our findings offer a pathway toward more efficient and reliable clinical laboratory testing.
Clinical Course of Bio Naive Ulcerative Colitis Patients Five Years After Initiation of Adalimumab in a Nationwide Cohort
Authors: Sundararajan Ramaswamy , Patel Manthankumar , Bahirwani Janak , Trivedi Chinmay , Mahmud Nadim , Khan Nabeel 
Published: August 2024

Abstract

Background
There is limited data on the long-term clinical outcomes of bio-naïve ulcerative colitis (UC) patients who are initiated on adalimumab (ADA). Our study aims to evaluate the clinical course of a nationwide cohort of bio naïve UC patients who were started on ADA, and then followed for 5 years after initiation of the drug.

Methods
We conducted a retrospective cohort study using the US Veteran Affairs Healthcare System (VAHS). Bio naïve UC patients were followed for 5 years after initiation of ADA. The primary outcome was to determine the time to discontinuation of ADA and if patients achieved endoscopic remission by the end of follow-up.

Results
A total of 387 patients were included among whom 193 (49.87%) had pancolitis. The highest rate of ADA discontinuation was within the first year, with the elderly having a higher rate of discontinuation (HR 1.67, 95% CI: 1.14–2.45) and those on concomitant immunomodulators having a lower rate of discontinuation (HR 0.70, 95% CI: 0.48–1.03). In total, 125 (32.30%) patients remained on ADA at the end of their maximum follow-up. 54 (43.90%) achieved endoscopic remission.

Conclusion
Among bio-naive UC patients who were started on ADA, a third were still on the drug at the end of 5 years and half had endoscopic remission. The rate of discontinuation was highest within the first year of initiation, but patients continued to stop the drug over the course of follow-up.
Smooth muscle-specific deletion of cellular communication network factor 2 causes severe aorta malformation and atherosclerosis
Authors: Larsen Jannik H , Hegelund Julie S , Pedersen Matilde K , Andersson Cecilie M , Lindegaard Caroline A , Hansen Didde R , Stubbe Jane , Lindholt Jes S , Hansen Camilla S , Grentzmann Andrietta , Bloksgaard Maria , Jensen Boye L , Rodriguez-Díez Raúl R , Ruiz-Ortega Marta , Albinsson Sebastian , Pasterkamp Gerard , Mokry Michal , Leask Andrew , Goldschmeding Roel , Pilecki Bartosz , Sorensen Grith L , Pyke Charles , Overgaard Martin , Beck Hans C , Ketelhuth Daniel F J , Rasmussen Lars M , Steffensen Lasse B 
Published: August 2024

Abstract

Aims
Cellular communication network factor 2 (CCN2) is a matricellular protein implicated in fibrotic diseases, with ongoing clinical trials evaluating anti-CCN2-based therapies. By uncovering CCN2 as abundantly expressed in non-diseased artery tissue, this study aimed to investigate the hypothesis that CCN2 plays a pivotal role in maintaining smooth muscle cell (SMC) phenotype and protection against atherosclerosis.

Methods and results
Global- and SMC-specific Ccn2 knockout mouse models were employed to demonstrate that Ccn2 deficiency leads to SMC de-differentiation, medial thickening, and aorta elongation under normolipidaemic conditions. Inducing hyperlipidaemia in both models resulted in severe aorta malformation and a 17-fold increase in atherosclerosis formation. Lipid-rich lesions developed at sites of the vasculature typically protected from atherosclerosis development by laminar blood flow, covering 90% of aortas and extending to other vessels, including coronary arteries. Evaluation at earlier time points revealed medial lipid accumulation as a lesion-initiating event. Fluorescently labelled LDL injection followed by confocal microscopy showed increased LDL retention in the medial layer of Ccn2 knockout aortas, likely attributed to marked proteoglycan enrichment of the medial extracellular matrix. Analyses leveraging data from the Athero-Express study cohort indicated the relevance of CCN2 in established human lesions, as CCN2 correlated with SMC marker transcripts across 654 transcriptomically profiled carotid plaques. These findings were substantiated through in situ hybridization showing CCN2 expression predominantly in the fibrous cap.

Conclusion
This study identifies CCN2 as a major constituent of the normal artery wall, critical in regulating SMC differentiation and aorta integrity and possessing a protective role against atherosclerosis development. These findings underscore the need for further investigation into the potential effects of anti-CCN2-based therapies on the vasculature.
Complete pathologic response in esophageal adenocarcinoma: does it make a difference?
Authors: Donato Britton B , Campany Megan E , Brady Justin T , Jenkins J Asher , Armstrong Valerie , Butterfield Richard , Reck dos Santos Pedro , D’Cunha Jonathan 
Published: August 2024

SUMMARY
Advancements in neoadjuvant regimens for esophageal adenocarcinoma have enabled some patients to achieve complete pathologic response at time of esophagectomy. There are currently limited data detailing this trend or the implications of complete pathologic response on survival. The National Cancer Database was used to identify 16,169 patients with esophageal adenocarcinoma that received trimodal therapy including esophagectomy between 2006 and 2020. Of these, 11.4% had complete pathologic response at esophagectomy. Patient factors, staging characteristics, and survival trends were evaluated. In patients diagnosed between 2016 and 2020, the rate of complete pathologic response was 17.5%. Female sex (OR 1.295, 95% CI 1.134–1.481, p = 0.0001), Black race (OR 1.729, 95% CI 1.362–2.196, p = 0.0002), Hispanic ethnicity (OR 1.418, 95% CI 1.073–1.875, p = 0.0141), and later era of diagnosis (2016–2020 OR 2.898, 95% CI 2.508–3.349, p &lt; 0.0001) were independent predictors of complete pathologic response. Clinical stage II disease was associated with an increased probability of complete pathologic response (OR 1.492, 95% CI 1.19–1.871) while clinical stage III disease had a decreased probability of complete pathologic response (OR 0.762, 95% CI 0.621–0.936, p &lt; 0.0001). Complete pathologic response conveyed a strong survival benefit, with a median survival of 86.4 months (95% CI 73.9–102.1) versus 30.7 months (95% CI 29.8–31.7, p &lt; 0.0001) in those without complete pathologic response. Four-year median survival was also higher in those with complete pathologic response (63.3%, 95% CI 60.8–66.0% vs. 39.2%, 95% CI 38.4–40.1%, p &lt; 0.0001). In summary, complete pathologic response is associated with a profound survival advantage in patients with esophageal adenocarcinoma. Such knowledge carries implications for patient counseling, prognostication, and surveillance and demonstrates a need for improved identification of complete clinical response prior to esophagectomy.
The chicken or the egg? Mycoplasma pneumoniae complicated by left ventricle thrombus and anterior myocardial infarction: a case report
Authors: Balac Nina , Nelson Kyle F , Naib Tara , El-Eshmawi Ahmed , Goldman Martin E 
Published: August 2024

Abstract

Background
Mycoplasma pneumoniae can be associated with extrapulmonary manifestations, including vasculitis, myocarditis, and thrombosis. In rare cases, it has also been implicated in intracardiac thrombus formation.

Case Summary
A previously healthy 25-year-old male presented with worsening abdominal pain, an episode of acute chest pain, new lightheadedness, and gait instability in the setting of M. pneumoniae. Initial blood tests were notable for mild coagulopathy, thrombocytosis, transaminitis, and elevated high-sensitivity troponin. Further, workup revealed systematic emboli to the cerebellum, kidneys, spleen, anterior myocardial infarction, and a left ventricular multilobular mural mass. Due to the unknown composition of the mass with concern for further embolic events, the patient underwent successful surgical excision with the mass ultimately defined as a thrombus. Hypercoagulable workup was notably inconclusive and intraoperative myocardial biopsies revealed organizing infarction without inflammation or healed myocarditis. Post-operative course was complicated by left ventricular dysfunction and acute kidney injury, both with eventual improvement. Patient has remained on guideline-directed medical therapy and prophylactic anticoagulation.

Discussion
We presume that the formation of the ventricular thrombus in this case was a result of transient thrombophilia in the setting of M. pneumonia resulting in coronary obstruction and subsequent myocardial injury. This case underscores the challenge of determining the pathophysiological sequence of events in patients with mycoplasma who develop systemic embolism and the management of a large residual thrombus, particularly in regard to surgical consideration.
Successful treatment of acute left main coronary artery disease with a drug-coated balloon under left ventricular unloading using Impella: a case report
Authors: Kamada Kazuhiro , Joko Kensuke , Otaka Naoya , Matsusaka Hidenori , Morishige Kunio 
Published: August 2024

Abstract

Background
Although the efficacy and safety of drug-coated balloons (DCBs) for acute left main coronary artery (LMCA) disease have not yet been proven, stentless percutaneous coronary intervention with a DCB is preferred for patients with high bleeding risk requiring a shorter duration of dual antiplatelet therapy. Mechanical circulatory support may improve haemodynamics in patients with cardiogenic shock caused by acute LMCA disease.

Case summary
A 74-year-old man diagnosed with acute congestive heart failure underwent emergency coronary angiography (CAG) at our hospital owing to ischaemic changes on the electrocardiogram (ECG), indicating acute LMCA disease. Coronary angiography revealed severe LMCA ostial stenosis. Immediately after CAG, mechanical circulatory support was initiated using Impella CP® for haemodynamic collapse with abrupt ST-segment elevation in the precordial leads. The haemodynamics stabilized with a dramatic improvement in the ECG. We treated the culprit ostial lesion with inflation of a cutting balloon followed by DCB delivery because of an episode of haematochezia. Subsequently, his cardiac function recovered fully.

Discussion
A case of acute LMCA disease was successfully treated with a DCB under haemodynamic support using Impella CP. The left ventricular (LV) unloading with Impella was indicated to contribute to stable haemodynamics, even during long inflation with the DCB, and the immediate recovery of LV function. Haemodynamic support using Impella may be effective, especially in cases requiring repeated and longer inflation of balloon catheters accompanied by extensive myocardial ischaemia.
Life's Essential 8 and the risk of cardiovascular disease: a systematic review and meta-analysis
Authors: Sebastian Sneha Annie , Shah Yash , Paul Haris , Arsene Camelia 
Published: August 2024

Abstract

Aims
The benefits of achieving optimal cardiovascular health (CVH) through Life's Simple 7 (LS7) are well-documented across diverse populations. In this study, we assess the updated metrics, Life's Essential 8 (LE8), and its association with long-term cardiovascular disease (CVD) outcomes and mortality.

Methods and results
We conducted a comprehensive systematic review, searching PubMed, Google Scholar, Cochrane Library, and ScienceDirect from January 2022 until June 2024, focusing on studies that specifically assessed the impact of LE8 on CVH. The statistical analysis used RevMan 5.4 and applied a random effects model to synthesize hazard ratios (HRs) for primary and secondary outcomes. This study is registered in PROSPERO (CRD42024558493). Our final analysis comprised 34 observational studies, encompassing 1 786 664 participants aged 18–80 years, with an average follow-up of approximately 11.6 years. Pooled analysis revealed a statistically significant decrease in the risk of CVD among individuals with higher LE8 scores compared with those with lower scores, with an HR of 0.47 (95% CI: 0.39–0.56, P &lt; 0.00001). Higher LE8 scores were also associated with significant reductions in both all-cause mortality (HR: 0.54, 95% CI: 0.43–0.69, P &lt; 0.00001) and CVD-related mortality (HR: 0.37, 95% CI: 0.26–0.52, P &lt; 0.00001. Moreover, individuals with high LE8 scores have a 56% lower risk of coronary heart disease and a 48% lower risk of stroke.

Conclusion
LE8 has a strong inverse association with CVD risk and mortality, with higher LE8 scores corresponding to significantly lower risk levels.
Candida species-specific colonization in the healthy and impaired human gastrointestinal tract as simulated using the Mucosal Ileum-SHIME® model
Authors: Marsaux Benoît , Moens Frédéric , Vandevijver Gies , Marzorati Massimo , van de Wiele Tom 
Published: August 2024

Abstract
Candida species primarily exist as harmless commensals in the gastrointestinal tract of warm-blooded animals. However, they can also cause life-threatening infections, which are often associated with gut microbial dysbiosis. Identifying the microbial actors that restrict Candida to commensalism remains a significant challenge. In vitro models could enable a mechanistic study of the interactions between Candida and simulated colon microbiomes. Therefore, this study aimed to elucidate the spatial and temporal colonization kinetics of specific Candida, including C. albicans, C. tropicalis, and C. parapsilosis, and their relative Nakaseomyces glabratus, by using an adapted SHIME® model, simulating the ileum, and proximal and distal colons. We monitored fungal and bacterial colonization kinetics under conditions of eubiosis (commensal lifestyle) and antibiotic-induced dysbiosis (pathogenic lifestyle). Our findings highlighted the variability in the colonization potential of Candida species across different intestinal regions. The ileum compartment proved to be the most favourable environment for C. albicans and C. parapsilosis under conditions of eubiosis. Antibiotic-induced dysbiosis resulted in resurgence of opportunistic Candida species, especially C. tropicalis and C. albicans. Future research should focus on identifying specific bacterial species influencing Candida colonization resistance and explore the long-term effects of antibiotics on the mycobiome and bacteriome.
The Party Politics of Military Intervention in Australia and Executive Prerogatives: Ideology Meets Strategy and Culture
Authors: Ostermann Falk 
Published: August 2024

Abstract
As an adjusted Westminster-style system with large executive room for maneuver in matters of foreign, security, and defense policies, Australia’s parliament does not have a formal say in sending troops abroad despite the continental nation’s constant military deployments, i.e., alongside its major ally, the United States. Past efforts from Democrats and Greens to push legislation giving parliament ex ante voting rights have been stymied by Labor-Liberal bipartisanism opposing it. However, given increasing political fragmentation and the politicization of military deployments, post-Cold War politics gives testament to dissent on the use of force, decision-making on it, and the reach of oversight between political parties. Linking the Australian case to contemporary scholarship on the party politics of security and defense policy, this article focuses on the party-political component of contestation and explores patterns of dissent and consensus on the use of force, decision-making, and oversight. Using voting, debate, interview data, and taking stock of the most recent parliamentary inquiry into war powers, the article demonstrates Australian parallels with party-political contestation in other countries. However, it also highlights that debate and agency in Australia do only follow those in other Westminster systems to some extent, while Australian parties put an even higher emphasis on decision-making efficiency in an insecure strategic environment.
Transcriptional repression and enhancer decommissioning silence cell cycle genes in postmitotic tissues
Authors: Fogarty Elizabeth A , Buchert Elli M , Ma Yiqin , Nicely Ava B , Buttitta Laura A 
Published: August 2024

Abstract
The mechanisms that maintain a non-cycling status in postmitotic tissues are not well understood. Many cell cycle genes have promoters and enhancers that remain accessible even when cells are terminally differentiated and in a non-cycling state, suggesting their repression must be maintained long term. In contrast, enhancer decommissioning has been observed for rate-limiting cell cycle genes in the Drosophila wing, a tissue where the cells die soon after eclosion, but it has been unclear if this also occurs in other contexts of terminal differentiation. In this study, we show that enhancer decommissioning also occurs at specific, rate-limiting cell cycle genes in the long-lived tissues of the Drosophila eye and brain, and we propose this loss of chromatin accessibility may help maintain a robust postmitotic state. We examined the decommissioned enhancers at specific rate-limiting cell cycle genes and showed that they encode for dynamic temporal and spatial expression patterns that include shared, as well as tissue-specific elements, resulting in broad gene expression with developmentally controlled temporal regulation. We extend our analysis to cell cycle gene expression and chromatin accessibility in the mammalian retina using a published dataset and find that the principles of cell cycle gene regulation identified in terminally differentiating Drosophila tissues are conserved in the differentiating mammalian retina. We propose a robust, non-cycling status is maintained in long-lived postmitotic tissues through a combination of stable repression at most cell cycle genes, alongside enhancer decommissioning at specific rate-limiting cell cycle genes.
The Effect of Axenic Dietary Restriction on the Age-Related Changes in Caenorhabditis elegans
Authors: Wu Ping , Vandemeulebroucke Lieselot , Claeys Myriam , Bert Wim , Braeckman Bart P 
Published: August 2024

Abstract
Axenic dietary restriction (ADR) is highly effective in extending lifespan of Caenorhabditis elegans, but its effects on healthspan improvement are less well characterized. Using transmission electron microscopy, morphometric analyses, and functional assays, we found ADR can preserve tissue ultrastructure, including the cuticle, epidermis, and intestinal lumen, and reduce age-associated pathologies like gonad degeneration, uterine tumor clusters, pharyngeal deterioration, and intestinal atrophy. However, there was no notable improvement in behavioral and functional metrics. Our results underscore that lifespan extension through ADR does not inherently translate to broad healthspan improvements.
Sialylated keratan sulfates on MUC5B are Siglec-8 ligands in the human esophagus
Authors: Li T August , Gonzalez-Gil Anabel , Awol Abduselam K , Ackerman Steven J , Orsburn Benjamin C , Schnaar Ronald L 
Published: August 2024

Abstract
Human sialic acid-binding immunoglobulin-like lectins (Siglecs) are expressed on subsets of immune cells. Siglec-8 is an immune inhibitory Siglec on eosinophils and mast cells, which are effectors in allergic disorders including eosinophilic esophagitis. Inhibition occurs when Siglec-8 is crosslinked by multivalent Siglec ligands in target tissues. Previously we discovered a high-affinity Siglec-8 sialoglycan ligand on human airways composed of terminally sialylated keratan sulfate chains carried on a single protein, DMBT1. Here we extend that approach to another allergic inflammatory target tissue, human esophagus. Lectin overlay histochemistry revealed that Siglec-8 ligands are expressed predominantly by esophageal submucosal glands, and are densely packed in submucosal ducts leading to the lumen. Expression is tissue-specific; esophageal glands express Siglec-8 ligand whereas nearby gastric glands do not. Extraction and resolution by gel electrophoresis revealed a single predominant human esophageal Siglec-8 ligand migrating at &gt;2 MDa. Purification by size exclusion and affinity chromatography, followed by proteomic mass spectrometry, revealed the protein carrier to be MUC5B. Whereas all human esophageal submucosal cells express MUC5B, only a portion convert it to Siglec-8 ligand by adding terminally sialylated keratan sulfate chains. We refer to this as MUC5B S8L. Material from the esophageal lumen of live subjects revealed MUC5B S8L species ranging from ~1–4 MDa. We conclude that MUC5B in the human esophagus is a protein canvas on which Siglec-8 binding sialylated keratan sulfate chains are post-translationally added. These data expand understanding of Siglec-8 ligands and may help us understand their roles in allergic immune regulation.
Integrating firearm storage and safety devices into health care
Authors: Cogle Christopher R , Venkatesh Anirudh B , Hall Jaclyn M 
Published: August 2024

Abstract
Millions of US children and adolescents live in homes with loaded firearms, with only half of these homes securing their guns. Firearm-related deaths among youth have doubled over the past decade, making firearms the leading cause of death for children and adolescents in the United States. The recent advisory by the US Surgeon General, identifying firearm violence as a public health crisis, underscores the urgent need for responsible firearm ownership, including safe firearm storage. However, the healthcare community currently lacks durable medical equipment (DME) codes for firearm storage devices, limiting the ability of healthcare providers to support responsible gun ownership. We propose the establishment of DME codes for firearm storage and safety devices, which would facilitate insurance coverage of these vital prevention measures. Durable medical equipment codes would empower physicians and other healthcare providers to integrate anticipatory guidance and lethal means counseling of firearm safety into routine care and support hospital- and community-based efforts to prevent firearm-related injuries and deaths among children and adolescents.