bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating racial disparities in emergency general surgery
Authors: Ben-Michael Eli , Feller Avi , Kelz Rachel , Keele Luke 
Published: September 2024

Abstract
Research documents that Black patients experience worse general surgery outcomes than White patients in the U.S. In this paper, we focus on an important but less-examined category: the surgical treatment of emergency general surgery (EGS) conditions, which refers to medical emergencies where the injury is internal, such as a burst appendix. Our goal is to assess racial disparities in outcomes after EGS treatment using administrative data. We also seek to understand the extent to which differences are attributable to patient-level risk factors vs. hospital-level factors, as well as to the decision to operate on EGS patients. To do so, we develop a class of linear weighting estimators that reweight White patients to have a similar distribution of baseline characteristics to Black patients. This framework nests many common approaches, including matching and linear regression, but offers important advantages over these methods in terms of controlling imbalance between groups, minimizing extrapolation, and reducing computation time. Applying this approach to the claims data, we find that disparities estimates that adjust for the admitting hospital are substantially smaller than estimates that adjust for patient baseline characteristics only, suggesting that hospital-specific factors are important drivers of racial disparities in EGS outcomes.
The transition state for coupled folding and binding of a disordered DNA binding domain resembles the unbound state
Authors: Kuravsky Mikhail , Kelly Conor , Redfield Christina , Shammas Sarah L 
Published: September 2024

Abstract
The basic zippers (bZIPs) are one of two large eukaryotic families of transcription factors whose DNA binding domains are disordered in isolation but fold into stable α-helices upon target DNA binding. Here, we systematically disrupt pre-existing helical propensity within the DNA binding region of the homodimeric bZIP domain of cAMP-response element binding protein (CREB) using Ala-Gly scanning and examine the impact on target binding kinetics. We find that the secondary structure of the transition state strongly resembles that of the unbound state. The residue closest to the dimerization domain is largely folded within both unbound and transition states; dimerization apparently propagates additional helical propensity into the basic region. The results are consistent with electrostatically-enhanced DNA binding, followed by rapid folding from the folded zipper outwards. Fly-casting theory suggests that protein disorder can accelerate binding. Interestingly however, we did not observe higher association rate constants for mutants with lower levels of residual structure in the unbound state.
Switch-like phosphorylation of WRN integrates end-resection with RAD51 metabolism at collapsed replication forks
Authors: Palermo Valentina , Malacaria Eva , Semproni Maurizio , Camerini Serena , Casella Marialuisa , Perdichizzi Benedetta , Valenzisi Pasquale , Sanchez Massimo , Marini Federica , Pellicioli Achille , Franchitto Annapaola , Pichierri Pietro 
Published: September 2024

Abstract
Replication-dependent DNA double-strand breaks are harmful lesions preferentially repaired by homologous recombination (HR), a process that requires processing of DNA ends to allow RAD51-mediated strand invasion. End resection and subsequent repair are two intertwined processes, but the mechanism underlying their execution is still poorly appreciated. The WRN helicase is one of the crucial factors for end resection and is instrumental in selecting the proper repair pathway. Here, we reveal that ordered phosphorylation of WRN by the CDK1, ATM and ATR kinases defines a complex regulatory layer essential for correct long-range end resection, connecting it to repair by HR. We establish that long-range end resection requires an ATM-dependent phosphorylation of WRN at Ser1058 and that phosphorylation at Ser1141, together with dephosphorylation at the CDK1 site Ser1133, is needed for the proper metabolism of RAD51 foci and RAD51-dependent repair. Collectively, our findings suggest that regulation of WRN by multiple kinases functions as a molecular switch to allow timely execution of end resection and repair at replication-dependent DNA double-strand breaks.
Effective requesting method to detect fusion transcripts in chronic myelomonocytic leukemia RNA-seq
Authors: Rufflé Florence , Reboul Jérôme , Boureux Anthony , Guibert Benoit , Bessière Chloé , Silva Raissa , Jourdan Eric , Gaillard Jean-Baptiste , Boland Anne , Deleuze Jean-François , Sénamaud-Beaufort Catherine , Selimoglu-Buet Dorothée , Solary Eric , Gilbert Nicolas , Commes Thérèse 
Published: September 2024

Abstract
RNA sequencing technology combining short read and long read analysis can be used to detect chimeric RNAs in malignant cells. Here, we propose an integrated approach that uses k-mers to analyze indexed datasets. This approach is used to identify chimeric RNA in chronic myelomonocytic leukemia (CMML) cells, a myeloid malignancy that associates features of myelodysplastic and myeloproliferative neoplasms. In virtually every CMML patient, new generation sequencing identifies one or several somatic driver mutations, typically affecting epigenetic, splicing and signaling genes. In contrast, cytogenetic aberrations are currently detected in only one third of the cases. Nevertheless, chromosomal abnormalities contribute to patient stratification, some of them being associated with higher risk of poor outcome, e.g. through transformation into acute myeloid leukemia (AML). Our approach selects four chimeric RNAs that have been detected and validated in CMML cells. We further focus on NRIP1-MIR99AHG, as this fusion has also recently been detected in AML cells. We show that this fusion encodes three isoforms, including a novel one. Further studies will decipher the biological significance of such a fusion and its potential to improve disease stratification. Taken together, this report demonstrates the ability of a large-scale approach to detect chimeric RNAs in cancer cells.
Comparative analysis of single-cell pathway scoring methods and a novel approach
Authors: Wang Ruoqiao H , Thakar Juilee 
Published: September 2024

Abstract
Single-cell gene set analysis (scGSA) provides a useful approach for quantifying molecular functions and pathways in high-throughput transcriptomic data, facilitating the biological interpretation of complex human datasets. However, various factors such as gene set size, quality of the gene sets and the dropouts impact the performance of scGSA. To address these limitations, we present a single-cell Pathway Score (scPS) method to measure gene set activity at single-cell resolution. Furthermore, we benchmark our method with six other methods: AUCell, AddModuleScore, JASMINE, UCell, SCSE and ssGSEA. The comparison across all the methods using two different simulation approaches highlights the effect of cell count, gene set size, noise, condition-specific genes and zero imputation on their performance. The results of our study indicate that the scPS is comparable with other single-cell scoring methods and detects fewer false positives. Importantly, this work reveals critical variables in the scGSA.
Exploring the impact of sequence context on errors in SNP genotype calling with whole genome sequencing data using AI-based autoencoder approach
Authors: Kotlarz Krzysztof , Mielczarek Magda , Biecek Przemysław , Guldbrandtsen Bernt , Szyda Joanna 
Published: September 2024

Abstract
A critical step in the analysis of whole genome sequencing data is variant calling. Despite its importance, variant calling is prone to errors. Our study investigated the association between incorrect single nucleotide polymorphism (SNP) calls and variant quality metrics and nucleotide context. In our study, incorrect SNPs were defined in 20 Holstein–Friesian cows by comparing their SNPs genotypes identified by whole genome sequencing with the IlluminaNovaSeq6000 and the EuroGMD50K genotyping microarray. The dataset was divided into the correct SNP set (666 333 SNPs) and the incorrect SNP set (4 557 SNPs). The training dataset consisted of only the correct SNPs, while the test dataset contained a balanced mix of all the incorrectly and correctly called SNPs. An autoencoder was constructed to identify systematically incorrect SNPs that were marked as outliers by a one-class support vector machine and isolation forest algorithms. The results showed that 59.53% (±0.39%) of the incorrect SNPs had systematic patterns, with the remainder being random errors. The frequent occurrence of the CGC 3-mer was due to mislabelling a call for C. Incorrect T instead of A call was associated with the presence of T in the neighbouring downstream position. These errors may arise due to the fluorescence patterns of nucleotide labelling.
Multidisciplinary team approach for CKD-associated osteoporosis
Authors: Hansen Ditte , Jørgensen Hanne Skou , Andersen Thomas Levin , Ferreira Ana Carina , Ferreira Aníbal , de Jongh Renate , Keronen Satu , Kröger Heikki , Lafage-Proust Marie Hélène , Martola Leena , Poole Kenneth E S , Tong Xiaoyu , Evenepoel Pieter , Haarhaus Mathias 
Published: September 2024

ABSTRACT
Chronic kidney disease–mineral and bone disorder (CKD-MBD) contributes substantially to the burden of cardiovascular disease and fractures in patients with CKD. An increasing arsenal of diagnostic tools, including bone turnover markers and bone imaging, is available to support clinicians in the management of CKD-associated osteoporosis. Although not mandatory, a bone biopsy remains useful in the diagnostic workup of complex cases. In this special report, the European Renal Osteodystrophy (EUROD) initiative introduces the concept of a kidney–bone multidisciplinary team (MDT) for the diagnosis and clinical management of challenging cases of CKD-associated osteoporosis. In 2021, the EUROD initiative launched virtual clinical-pathological case conferences to discuss challenging cases of patients with CKD-associated osteoporosis, in whom a bone biopsy was useful in the diagnostic workup. Out of these, we selected four representative cases and asked a kidney–bone MDT consisting of a nephrologist, an endocrinologist and a rheumatologist to provide comments on the diagnostic and therapeutic choices. These cases covered a broad spectrum of CKD-associated osteoporosis, including bone fracture in CKD G5D, post-transplant bone disease, disturbed bone mineralization, severely suppressed bone turnover and severe hyperparathyroidism. Comments from the MDT were, in most cases, complementary to each other and additive to the presented approach in the cases. The MDT approach may thus set the stage for improved diagnostics and tailored therapies in the field of CKD-associated osteoporosis. We demonstrate the clinical utility of a kidney-bone MDT for the management of patients with CKD-MBD and recommend their establishment at local, national, and international levels.
Actionable alterations in glioblastoma: Insights from the implementation of genomic profiling as the standard of care from 2016 to 2023
Authors: Fougner Vincent , Urup Thomas , Poulsen Hans Skovgaard , Grunnet Kirsten , Westmose Christina Yde , Melchior Linea Cecilie , Larsen Karen Bonde , Højgaard Martin , Spanggaard Iben , Belcaid Laila , Rohrberg Kristoffer Staal , Lassen Ulrik , Hasselbalch Benedikte , Nørøxe Dorte Schou 
Published: September 2024

Abstract

Background
In 2016, genomic profiling was implemented for patients with grade 4 primary brain tumors at Rigshospitalet, Denmark. The aim of this study was to discover actionable alterations and to match these with targeted therapies.

Methods
Between January 2016 and December 2023, 483 brain tumor patients were profiled. We retrieved clinical data and molecular data. Whole exome, whole genome, or panel sequencing, along with SNP array analyses, and RNA-seq were performed on resected primary tumor tissue. Alterations were classified according to the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) following the European Association of Neuro-Oncology (EANO) guideline on rational molecular testing.

Results
A total of 200 (41.4%) patients’ tumors harbored an alteration of interest according to the EANO guideline. Twenty (4.1%) patients had an ESCAT high-tier alteration (tier I or II), while 155 patients (32.1%) had an alteration corresponding to ESCAT IIIA. Thirty-five patients (7.2%) had an actionable alteration, and 15 (3.1%) received targeted therapy. The treated targets were BRAFV600E mutations, FGFR alterations, NTRK fusions, PDGFRA fusions, PTPRZ1-MET fusions, and TMB-high. The overall response rate was 20%, with a median duration of response of 12 months, and 47% achieved stable disease as the best response.

Conclusions
Genomic profiling uncovers alterations of interest in a substantial number of patients, but only a minority are considered by the Danish National Molecular Tumor Board to have actionable alterations, and even fewer receive targeted therapy. Nevertheless, factors, such as promising targets and the increasing availability of trials, may contribute to a future increase in the number of patients benefiting from targeted therapies based on genomic profiling.
(Digital) Things as Objects of Property Rights: What Can Crypto Learn From Comparative Law?
Authors: Held Amy 
Published: September 2024

Abstract
This review article engages critically with Christian von Bar’s proposed definition of things as objects of property rights and their proposed place as one category in a tripartite taxonomy of the objects of private law; both expounded as part of a broader aim of bringing together the property laws of the Member States of the European Union and the UK as part of a single picture. The article first contextualises these proposals against the background of the UNIDROIT Principles on Digital Assets and the ongoing debates in England and Wales as to the property status of cryptoassets such as bitcoin; then offers a primer for both common law and civilian law readers on the structure, content and objectives of the book. After setting out the proposed taxonomy and the core theses upon which it is premised, the article then evaluates von Bar’s proposals and illustrates how they can inform and guide the debates as international and domestic laws grapple with the challenges posed by new and novel objects of economic value. The book under review is an abridged version of the first two parts of Gemeineuropäisches Sachenrecht, originally published in German by CH Beck in 2015, which were translated into English by Jason Grant Allen and reworked into a standalone text published by OUP in 2023.
Cultivating long-term well-being through transformative undergraduate education
Authors: White Holly C , Allen Debra M , Buffinton Keith , Humphrey Dana , Malpiede Marjorie , Miller Richard K , Volin John C 
Published: September 2024

Abstract
Despite the growing body of research suggesting certain pedagogical approaches that can support student well-being, higher education has not fully embraced these approaches and typically still does not view well-being as a high priority in comparison with other metrics such as retention or GPA. Here, we contend that universities must play an active role in supporting lifelong well-being in their student populations by expanding their definitions of student success and providing opportunities and programs that support elements related to well-being. We propose a student well-being nexus, which comprises a sense of belonging, agency, purpose, identity, civic engagement, and financial well-being. This article provides a perspective on the importance of each element to well-being and which pedagogical practices have been shown to support various dimensions of well-being in undergraduate education, such as service learning, undergraduate research, and mentoring. In addition, it showcases 6 exceptional initiatives from various universities that aim to support one or more of the student well-being nexus dimensions, which can serve as models for other universities. Finally, several guiding principles are outlined for higher education institutions to support the implementation of student well-being initiatives and transformational learning opportunities. These include assessment of initiatives, embedding initiatives into the curriculum, and avoidance of creating additional financial burdens for students. These efforts can promote well-being on college campuses and beyond graduation.
Forage conservation is a neglected nitrous oxide source
Authors: Yang Seongmin , Mahmood Maheen , Baral Rudra , Wu Hui , Almloff Marc , Stanton Lauren E , Min Doohong , Smiley Brenda K , Iiams J Chris , Yu Jisang , Im Jeongdae 
Published: September 2024

Abstract
Agricultural activities are the major anthropogenic source of nitrous oxide (N2O), an important greenhouse gas and ozone-depleting substance. However, the role of forage conservation as a potential source of N2O has rarely been studied. We investigated N2O production from the simulated silage of the three major crops—maize, alfalfa, and sorghum—used for silage in the United States, which comprises over 90% of the total silage production. Our findings revealed that a substantial N2O could be generated, potentially placing forage conservation as the third largest N2O source in the agricultural sector. Notably, the application of chlorate as an additive significantly reduced N2O production, but neither acetylene nor intermittent exposure to oxygen showed any impact. Overall, the results highlight that denitrifiers, rather than nitrifiers, are responsible for N2O production from silage, which was confirmed by molecular analyses. Our study reveals a previously unexplored source of N2O and provides a crucial mechanistic understanding for effective mitigation strategies.
A model of dyadic merging interactions explains human drivers’ behavior from control inputs to decisions
Authors: Siebinga Olger , Zgonnikov Arkady , Abbink David A 
Published: September 2024

Abstract
Safe and socially acceptable interactions with human-driven vehicles are a major challenge in automated driving. A good understanding of the underlying principles of such traffic interactions could help address this challenge. Particularly, accurate driver models could be used to inform automated vehicles in interactions. These interactions entail complex dynamic joint behaviors composed of individual driver contributions in terms of high-level decisions, safety margins, and low-level control inputs. Existing driver models typically focus on one of these aspects, limiting our understanding of the underlying principles of traffic interactions. Here, we present a Communication-Enabled Interaction model based on risk perception, that does not assume humans are rational and explicitly accounts for communication between drivers. Our model can explain and reproduce observed human interactions in a simplified merging scenario on all three levels. Thereby improving our understanding of the underlying mechanisms of human traffic interactions and posing a step towards interaction-aware automated driving.
Vasovagal syncope with asystole
Authors: Middleton Hayden T. , Bachman Maria J. , Strelow Brittany A. 
Published: September 2024

ABSTRACT
Although vasovagal episodes are a common cause of syncope, vasovagal syncope can be cardioinhibitory in nature, resulting in a severe heart block or asystole. This case report focuses on a young man with a history of seizures and frequent syncopal episodes who required an extensive clinical workup and treatment for cardioinhibitory syncope.
Airway obstruction secondary to vocal cord polyp
Authors: Filarski Carolyn F. , Donald Carrlene B. , Mendez Anthony P. , Lott David G. 
Published: September 2024

ABSTRACT
Patients with vocal cord polyps commonly present with symptoms of hoarseness. Although rare, large polyps can cause shortness of breath and stridor and should be included in the differential for patients with airway obstruction. Dysphonia or hoarseness can be a symptom of underlying disease, such as head and neck cancer. This case illustrates the importance of prompt and accurate diagnosis in a patient with persistent symptoms and a history of smoking. Obtaining a laryngoscopy is crucial to appropriately evaluate the larynx. Proper visualization of the laryngeal structures will help direct patient care toward further diagnostic imaging and medical or surgical intervention if indicated.
Challenges in professional development of anaesthesiology trainees
Authors: Dow Olivia , Kustura Antonia , Lior Yotam , Berger-Estilita Joana , Morais Diogo , De Hert Stefan , Abramovich Igor 
Published: September 2024

BACKGROUND
The coronavirus disease (COVID-19) pandemic disrupted training in anaesthesiology. The global shortage of healthcare workers has also negatively affected training opportunities.

OBJECTIVE
To evaluate the current experiences, challenges and professional development of anaesthesiology trainees across Europe.

DESIGN
An online cross-sectional survey of anaesthesiology trainees.

PARTICIPANTS
Anaesthesiology trainees from the 42 European Society of Anaesthesiology and Intensive Care (ESAIC)-affiliated countries.

MAIN OUTCOME MEASURES
Quality of training supervision and program structure; the impact of COVID-19 on training and practical learning, trainee support systems, financial challenges and professional development, involvement in the ESAIC Exchange Program and career mobility insights.

RESULTS
Seven hundred and seventy-one participants from 35 ESAIC-affiliated European countries highlighted several aspects of anaesthesiology training. Approximately 30.5% of trainees reported being able to independently anaesthetise patients with ASA class 1 and 2 within 3 months, whereas independence for ASA 3 and 4 patients under indirect supervision was achieved by 24.3% between 6 and 9 months. Half of the respondents attained an independent working capacity in the ICU after 1.5 years. Although 51.3% reported receiving adequate training and supervision, only 30.1% received employer financial support for educational activities. The COVID-19 pandemic led to 40.2% being redeployed, primarily to ICUs, with 45.2% experiencing negative training effects. Career-wise, 12.5% engaged in international exchange programs, and 49.1% considered relocating for better career opportunities and work–life balance.

CONCLUSION
The findings provide valuable insights into the current state of anaesthesiology training in Europe, highlighting the need for adaptive strategies in medical education and training to meet evolving challenges and ensure continual professional growth.