bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucagon-Like Peptide-1 Receptor–Targeted PET/CT With 68Ga-HBED-CC-Exendin-4 in Localizing Insulinoma
Authors: Li Linlin , Wang Guochang , Wang Jiarou , Ma Heng , Chen Jingci , Wang Rongxi , Pan Qingqing , Hong Haiyan , Jin Wenbin , Kung Hank F. , Zhu Lin , Luo Yaping , Zhu Zhaohui 
Published: November 2024

Purpose
Modifying glucagon-like peptide-1 receptor (GLP-1R)–targeted PET agent to achieve faster renal clearance and preserved high affinity to GLP-1R is clinically relevant. The aim of this study is to assess the performance of a newly developed GLP-1R–targeted agent, 68Ga-HBED-CC-exendin-4 in localizing insulinoma, and its biodistribution, as compared with previously introduced 68Ga-NOTA-exendin-4.

Patients and Methods
Nineteen patients with endogenous hyperinsulinemic hypoglycemia were enrolled and referred for 68Ga-HBED-CC-exendin-4 PET/CT and 68Ga-NOTA-exendin-4 PET/CT within 2 consecutive days. Diagnostic performance of the 2 tracers in localizing insulinoma was evaluated, and SUV of the lesion, normal pancreas background, kidneys, and bladder were measured.

Results

68Ga-HBED-CC-exendin-4 and 68Ga-NOTA-exendin-4 PET/CT exhibited an equivalent efficacy in detection rate (both sensitivity of 100%). Although SUVmax of the tumor in 68Ga-HBED-CC-exendin-4 was significantly lower than that in 68Ga-NOTA-exendin-4 (20.01 ± 9.41 vs 31.78 ± 15.46, P < 0.001) at 50 minutes postinjection, there was no significant difference in the tumor-to-background ratio between the 2 agents (8.61 ± 3.57 vs 8.18 ± 3.38, P = 0.326), and the lesions could be visible as early as 4 minutes postinjection for both agents in patients who underwent dynamic PET/CT. In addition, 68Ga-HBED-CC-exendin-4 exhibited approximately 30% decrease of the renal accumulation compared with 68Ga-NOTA-exendin-4 (SUVmean, 42.21 ± 5.79 vs 58.58 ± 10.06 at 50 minutes, P < 0.001).

Conclusions

68Ga-HBED-CC-exendin-4 is an effective agent for localizing insulinoma showing similar detectability and tumor-to-background ratio compared with 68Ga-NOTA-exendin-4. Notably, 68Ga-HBED-CC-exendin-4 exhibits significantly lower renal uptake than 68Ga-NOTA-exendin-4, which might potentially benefit the detection of the tumors adjacent to the left kidneys.
General practice antibiotic prescriptions attributable to Respiratory Syncytial Virus by age and antibiotic class: An ecological analysis of the English population
Authors: Miller Lucy , Beaney Thomas , Hope Russel , Cunningham Mark , Robotham Julie V. , Pouwels Koen B. , Costelloe Cèire E. 
Published: November 2024

AbstractBackgroundRespiratory syncytial virus (RSV) may contribute to a substantial volume of antibiotic prescriptions in primary care. However, data on the type of antibiotics prescribed for such infections is only available for children <5 years in the UK. Understanding the contribution of RSV to antibiotic prescribing would facilitate predicting the impact of RSV preventative measures on antibiotic use and resistance.ObjectivesTo estimate the proportion of antibiotic prescriptions in English general practice attributable to RSV by age and antibiotic class.MethodsGeneralised additive models examined associations between weekly counts of general practice antibiotic prescriptions and laboratory-confirmed respiratory infections from 2015 to 2018, adjusting for temperature, practice holidays and remaining seasonal confounders. We used general practice records from the Clinical Practice Research Datalink and microbiology tests for RSV, influenza, rhinovirus, adenovirus, parainfluenza, human Metapneumovirus,Mycoplasma pneumoniaeandStreptococcus pneumoniaefrom England’s Second Generation Surveillance System.ResultsAn estimated 2.1% of antibiotics were attributable to RSV, equating to an average of 640,000 prescriptions annually. Of these, adults ≥75 years contributed to the greatest volume, with an annual average of 149,078 (95% credible interval: 93,733-206,045). Infants 6-23 months had the highest average annual rate at 6,580 prescriptions per 100,000 individuals (95% credible interval: 4,522-8,651). Most RSV-attributable antibiotic prescriptions were penicillins, macrolides or tetracyclines. Adults ≥65 years had a wider range of antibiotic classes associated with RSV compared to younger age groups.ConclusionsInterventions to reduce the burden of RSV, particularly in older adults, could complement current strategies to reduce antibiotic use in England.
Genome sequence of the medicinal plantTropaeolum majusprovides insights into flavonoid biosynthesis
Authors: Friedhoff Ronja , Wittstock Ute , Pucker Boas 
Published: November 2024

AbstractTropaeolum majusis a very popular species around the world with an enormous number of commercially available varieties displaying various flower color patterns and growth characteristics. It is rich in phytochemicals such as glucotropaeolin, hydroxycinnamic acid derivatives, and flavonol glycosides. Here, we report a highly continuous genome sequence ofT. majusand a comprehensive annotation of protein encoding genes suitable for comparative genomics. The potential for the exploration of individual gene functions in this valuable plant is demonstrated by an analysis of the flavonoid biosynthesis genes and their transcriptional regulators. Important players of the flavonol biosynthesis, including structural genes and a transcription factor, were identified that are required to produce precursors of phytomedically relevant flavonol glycosides. The genome sequence does not reveal an ortholog of the leucoanthocyanidin reductase encoding gene (LAR), which aligns with previous reports about the absence of this gene in many Brassicales species.
Genomic, phenomic, and geographic associations of leukocyte telomere length in the United States
Authors: Nakao Tetsushi , Koyama Satoshi , Truong Buu , Uddin Md Mesbah , Misra Anika , Patel Aniruddh P. , Bhatnagar Aarushi , Viscosi Victoria , Vlasschaert Caitlyn , Bick Alexander G. , Nelson Christopher P. , Codd Veryan , Samani Nilesh J. , Hornsby Whitney , Ellinor Patrick T. , Natarajan Pradeep 
Published: November 2024

AbstractLeukocyte telomere length (LTL) is associated with multiple conditions, including cardiovascular diseases and neoplasms, yet their differential associations across diverse individuals are largely unknown. We estimated LTL from blood-derived whole genome sequences in theAll of UsResearch Program (n=242,494) with diverse backgrounds across the United States. LTL was associated with lifestyle, socioeconomic status, biomarkers, cardiometabolic diseases, and neoplasms with heterogeneity across genetic ancestries and sexes. Geographical analysis revealed that significantly longer LTL clustered in the West Coast and Central Midwest, while significantly shorter LTL clustered in the Southeast in the United States, accounting for age, sex, and genetic ancestry. Genome-wide association study and meta-analysis with the UK Biobank (n=679,972) found 234 non-overlapping loci, of which 36 were novel. We identified 4 novel loci unique to non-European-like populations and one specific to females. Rare variant analysis uncovered 7 novel genes, providing new functional insights. Our study highlighted previously underappreciated contextual heterogeneities of phenomic and genomic associations with LTL.
The Society of Radiologists in Training (SRT) 2024 Training Survey on the impact of recent changes to training and non-radiologist roles
Authors: Kilic Yakup , Colman Jordan , Kiandee Miraen , Shyamanur Bhavana , Ngu Wee Ping , Watura Emma 
Published: November 2024

AbstractIntroductionIn 2016, the Royal College of Radiologists (RCR) launched an initiative to address the radiology workforce crisis in the UK, focusing on increasing the number of training places. To address this, the RCR advocated for the introduction of skill mix and expanded imaging training academies. The NHS’s 2023 long-term workforce plan proposed increased integration of medical associate professions (MAPs) in radiology, although this has raised concerns regarding regulation and training quality.MethodsWe conducted an online survey targeting UK radiologists to gather insights on their perceptions of training quality, recent modifications to training, and views on non-radiologist roles. The purpose of the study was to evaluate the ways in which these elements affect their training experiences and general contentment.ResultsA total of 227 responses were collected, predominantly from residents across all UK training deaneries. 63.9% of trainees expressed satisfaction with their training although this varied, with trainees in new/hybrid academies reporting lower satisfaction. Concerns about training quality were prevalent, attributed to numerous factors such as consultants working from home and increased training numbers. Although opinions on the new curriculum were divided, many commented on the challenges of meeting the new IR competences, and the greater focus on general training was perceived more adversely. Career prospects in radiology were often bleak.ConclusionThe survey results highlighted a multifaceted array of perceptions and concerns amongst radiology residents regarding several factors negatively impacting their training, such as changes to the curriculum and growth of non-radiologist roles.
A Multimodal Foundation Model for Discovering Genetic Associations with Brain Imaging Phenotypes
Authors: Machado Reyes Diego , Burch Myson , Parida Laxmi , Bose Aritra 
Published: November 2024

AbstractDue to the intricate etiology of neurological disorders, finding interpretable associations between multi-omics features can be challenging using standard approaches. We proposeCOMICAL, a contrastive learning approach leveraging multi-omics data to generate associations between genetic markers and brain imaging-derived phenotypes.COMICALjointly learns omic representations utilizing transformer-based encoders with custom tokenizers. Our modality-agnostic approach uniquely identi-fies many-to-many associations via self-supervised learning schemes and cross-modal attention encoders.COMICALdiscovered several significant associations between genetic markers and imaging-derived phenotypes for a variety of neurological disorders in the UK Biobank as well as predicting across diseases and unseen clinical outcomes from the learned representations. Source code ofCOMICALalong with pre-trained weights, enabling transfer learning is available athttps://github.com/IBM/comical.
The open-closed mod-minimizer algorithm
Authors: Koerkamp Ragnar Groot , Liu Daniel , Pibiri Giulio Ermanno 
Published: November 2024

AbstractSampling algorithms that deterministically select a subset ofk-mers are an important building block in bioinformatics applications. For example, they are used to index large textual collections, like DNA, and to compare sequences quickly. In such applications, a sampling algorithm is required to select onek-mer out of every window ofwconsecutivek-mers. The folklore and most used scheme is therandom minimizerthat selects the smallestk-mer in the window according to some random order. This scheme is remarkably simple and versatile, and has adensity(expected fraction of selectedk-mers) of 2/(w+ 1). In practice, lower density leads to faster methods and smaller indexes, and it turns out that the random minimizer is not the best one can do. Indeed, some schemes are known to approach optimal density 1/wwhenk → ∞, like the recently introducedmod-minimizer(Groot Koerkamp and Pibiri, WABI 2024).In this work, we study methods that achieve low density whenk ≤ w. In this small-kregime, a practical method with provably better density than the random minimizer is theminiception(Zheng et al., Bioinformatics 2021). This method can be elegantly described as sampling the smallestclosed sycnmer(Edgar, PeerJ 2021) in the window according to some random order. We show that extending the miniception to prefer samplingopensyncmers yields much better density. This new method – theopen-closedminimizer – offers improved density for smallk ≤ wwhile being as fast to compute as the random minimizer. Compared to methods based on decycling sets, that achieve very low density in the small-kregime, our method has comparable density while being computationally simpler and intuitive.Furthermore, we extend the mod-minimizer to improve density of any scheme that works well for smallkto also work well whenk > wis large. We hence obtain theopen-closed mod-minimizer, a practical method that improves over the mod-minimizer for allk.
Biobank-scale characterization of Alzheimer’s disease and related dementias identifies potential disease-causing variants, risk factors, and genetic modifiers across diverse ancestries
Authors: Khani Marzieh , Akçimen Fulya , Grant Spencer M. , Akerman S. Can , Lee Paul Suhwan , Faghri Faraz , Leonard Hampton , Kim Jonggeol Jeffrey , Makarious Mary B. , Koretsky Mathew J. , Rothstein Jeffrey D , Blauwendraat Cornelis , Nalls Mike A. , Singleton Andrew , Bandres-Ciga Sara 
Published: November 2024

AbstractAlzheimer’s disease and related dementias (AD/ADRDs) pose a significant global public health challenge, underscored by the intricate interplay of genetic and environmental factors that differ across ancestries. To effectively implement equitable, personalized therapeutic interventions on a global scale, it is essential to identify disease-causing mutations and genetic risk and resilience factors across diverse ancestral backgrounds. Exploring genetic-phenotypic correlations across the globe enhances the generalizability of research findings, contributing to a more inclusive and universal understanding of disease. This study leveraged biobank-scale data to conduct the largest multi-ancestry whole-genome sequencing characterization of AD/ADRDs. We aimed to build a valuable catalog of potential disease-causing, genetic risk and resilience variants impacting the etiology of these conditions. We thoroughly characterized genetic variants from key genes associated with AD/ADRDs across 11 genetic ancestries, utilizing data from All of Us, UK Biobank, 100,000 Genomes Project, Alzheimer’s Disease Sequencing Project, and the Accelerating Medicines Partnership in Parkinson’s Disease, including a total of 25,001 cases and 93,542 controls. We prioritized 116 variants possibly linked to disease, including 18 known pathogenic and 98 novel variants. We detected previously described disease-causing variants among controls, leading us to question their pathogenicity. Notably, we showed a higher frequency ofAPOEε4/ε4 carriers among individuals of African and African Admixed ancestry compared to other ancestries, confirming ancestry-driven modulation ofAPOE-associated AD/ADRDs. A thorough assessment ofAPOErevealed a disease-modifying effect conferred by theTOMM40:rs11556505,APOE:rs449647,19q13.31:rs10423769,NOCT:rs13116075,CASS4:rs6024870, andLRRC37A:rs2732703 variants amongAPOEε4 carriers across different ancestries. In summary, we compiled the most extensive catalog of established and novel genetic variants in known genes increasing risk or conferring resistance to AD/ADRDs across diverse ancestries, providing clinical insights into their genetic-phenotypic correlations. The findings from this investigation hold significant implications for potential clinical trials and therapeutic interventions on a global scale. Finally, we present an accessible and user-friendly platform for the AD/ADRDs research community to help inform and support basic, translational, and clinical research on these debilitating conditions (https://niacard.shinyapps.io/MAMBARD_browser/).
Obsessive-compulsive disorder is characterised by metacognitive deficits resistant to subthalamic stimulation
Authors: Kist Audrey , Pereira Michael , Msheik Ramla , Goueytes Dorian , Pouchon Arnaud , Chabardès Stephan , Bastin Julien , Polosan Mircea , Faivre Nathan 
Published: November 2024

AbstractMost human studies on perceptual decision-making are correlational, and few addressed the causal role of the neural markers they identify. Here, we took the opportunity offered by deep brain stimulation to study the causal role of subthalamo-cortical networks on perceptual decision-making and perceptual monitoring. To this end, we asked participants with obsessive-compulsive disorder (OCD) treated with subthalamic stimulation to detect visual stimuli and provide confidence reports while we recorded scalp electroencephalography. Following a preregistered plan, we compared behavioural and neural results between patients off-stimulation and matched healthy controls and among patients on and off-stimulation to identify the effect of subthalamic stimulation on perceptual choices and metacognitive judgments. Our results indicate that patients off-stimulation detected visual stimuli similarly to matched healthy controls but provided poorer confidence judgments indicative of a metacognitive deficit. Moreover, chronic subthalamic stimulation significantly reduced clinical symptoms, but acute stimulation changes did not impact visual detection, confidence, or corresponding event-related potentials at the scalp level. We conclude that acute changes in subthalamic stimulation are insufficient to alleviate metacognitive deficits observed in OCD.
Machine learning predicts liver cancer risk from routine clinical data: a large population-based multicentric study
Authors: Clusmann Jan , Koop Paul-Henry , Zhang David Y. , van Haag Felix , El Nahhas Omar S. M. , Seibel Tobias , Žigutytė Laura , Kaewdech Apichat , Calderaro Julien , Tacke Frank , Luedde Tom , Truhn Daniel , Bruns Tony , Schneider Kai Markus , Kather Jakob N. , Schneider Carolin V. 
Published: November 2024

AbstractBackground and aimsHepatocellular carcinoma (HCC) is a highly fatal tumor, for which early detection and risk stratification is crucial, yet remains challenging. We aimed to develop an interpretable machine-learning framework for HCC risk stratification based on routinely collected clinical data.MethodsWe leverage data obtained from over 900,000 individuals and 983 cases of HCC across two large-scale population-based cohorts: the UK Biobank study and the “All Of Us Research Program”. For all of these patients, clinical data from timepoints years before diagnosis of HCC was available. We integrate data modalities including demographics, electronic health records, lifestyle, routine blood tests, genomics and metabolomics to offer a unique, multi-modal perspective on HCC risk.ResultsOur random-forest-based model significantly outperforms all publicly available state-of-the-art risk-scores, with an AUROC of 0.88 both for internal and external test sets. We demonstrate robustness of our model across ethnic subgroups, a major advance over previous models with variable performance by ethnicity. Further, we perform extensive feature-importance analysis, showcasing our approach as an interpretable framework. We provide all model weights and an open-source web calculator to facili-tate further validation of our model.ConclusionOur study presents a robust and interpretable machine-learning framework for HCC risk stratification, which offers the potential to improve early detection and could ultimately reduce disease burden through targeted interventions.Lay summaryFinding liver cancer early is crucial for successful treatment. Therefore, screening with abdominal ultra-sound can be performed. However, it is not clear who should receive ultrasound screening, as with the current standard of screening only patients with liver cirrhosis, a severe liver disease, many patients are diagnosed with liver cancer in late stages. Therefore, we trained a machine learning model, acting like many decision trees at the same time, to detect patients with high risk of liver cancer by looking at patterns of almost 1000 cases of liver cancer in a population of 900.000 individuals. In a separate set of patients, which the model has not seen during training, our model worked better than all available models. Additionally, we investigated 1. how the model comes to its prediction, 2. whether it works in males and females alike and 3. which data is most relevant for the model. Like this, our model can help sort patients into categories like “high-risk”, “medium-risk” and “low-risk”, via which screening strategies can then be decided, to help improve early detection of liver cancer.
Involvement of the Posterior Visual Pathway Correlates with Higher-Order Visual Impairment in Childhood Stroke Patients detected by Virtual Reality/Eye Tracking Paradigm
Authors: Da Cruz Emily , Tambala Diana , Lynch Anna , Manley Claire , Bambery Melissa , Kelly Daniel , Chui Carrie , Alhadid Kenda , Sullivan Alyssa W. , Grieco Julie , Ondeck Benjamin , Lauer Arne , Merabet Lotfi B. , Musolino Patricia L. 
Published: November 2024

Background/ObjectiveCerebral injury due to stroke in childhood increases the risk of higher-order visual processing (HOVP) deficits, like cerebral visual impairment (CVI), which can lead to severe behavioral and learning disabilities if left untreated. Using a virtual reality-based search task and structural Magnetic Resonance Imaging analysis, we assess the extent of functional vision deficits in childhood stroke patients and potential anatomical correlates.Methods20 childhood stroke patients and 38 healthy controls completed a dynamic visual search task using a virtual reality/eye-tracking (VR/ET) paradigm to quantify functional vision abilities between 2021 to 2024 (average 7.34 years after stroke). Virtual reality assessment measures, stroke imaging characteristics (visual pathway involvement) and neuropsychological outcomes were analyzed between cohorts using statistical comparison methods and linear regression model.ResultsAll childhood stroke patients could complete the VR/ET task, whose metrics were associated with neuropsychological testing measures of visual attention and processing speed, as demonstrated by success rates and task compliance in equal measure to controls. However, less accurate search and slower fixation rates together with less sensitivity to changes in task load and greater impairment in initiating a response to a target were observed in our patient cohort. On MRI lesion analysis injury involving the posterior visual pathways, specifically the optic radiations, inferior longitudinal fasciculus, or superior longitudinal fasciculus, correlated with slower reaction time to fixation on a target when controlling for age at time of VR testing.ConclusionsBedside VR/ET assessment in children affected by stroke can detect signs of HOVP deficits as confirmed by neuropsychological testing. Imaging demonstrating involvement of the posterior visual pathway at the time of diagnosis is strongly correlated with development of impaired visual tracking abilities later in life. While detection of HOVP deficits relies on current standard clinical and neuropsychological evaluations between 3 to 6 years of age, our study demonstrates that injury pattern on imaging at stroke onset can help identify children at risk of HOVP deficits. This may enable early monitoring and timely accommodations facilitating functional vision development, critical to learning and skill acquisition.