bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Photon-Counting CT Enters the Field of Cochlear Implantation: Comparison to Angiography DynaCT and Conventional Multislice CT
Authors: Rak Kristen , Spahn Bjoern , Müller-Graff Franz-Tassilo , Engert Jonas , Voelker Johannes , Hackenberg Stephan , Hagen Rudolf , Petritsch Bernhard , Grunz Jan-Peter , Bley Thorsten , Neun Tilmann , Huflage Henner 
Published: June 2024

Introduction
Cochlear duct length (CDL) measurement plays a role in the context of individualized cochlear implant (CI) surgery regarding an individualized selection and implantation of the CI electrode carrier and an efficient postoperative anatomy-based fitting process. The level of detail of the preoperative temporal bone CT scan depends on the imaging modality with major impact on CDL measurements and CI electrode contact position determination. The aim of this study was to evaluate the accuracy of perioperative CDL measurements and electrode contact determination in photon-counting CT (PCCT).

Methods
Ten human fresh-frozen petrous bone specimens were examined with a first-generation PCCT. A clinically applicable radiation dose of 27.1 mGy was used. Scans were acquired before and after CI insertion. Postoperative measurement of the CDL was conducted using an otological planning software and 3D-curved multiplanar reconstruction. Investigation of electrode contact position was performed by two respective observers. Measurements were compared with a conventional multislice CT and to a high-resolution flat-panel volume CT with secondary reconstructions.

Results
Pre- and postoperative CDL measurements in PCCT images showed no significant difference to high-resolution flat-panel volume CT. Postoperative CI electrode contact determination was also as precise as the flat-panel CT-based assessment. PCCT and flat-panel volume CT were equivalent concerning interobserver variability.

Conclusion
CDL measurement with PCCT was equivalent to flat-panel volume CT with secondary reconstructions. PCCT enabled highly precise postoperative CI electrode contact determination with substantial advantages over conventional multislice CT scanners.
The Sexual Health Clinic Role in Vaccine and Treatment Access During the 2022 Mpox Outbreak in King County, Washington
Authors: Karmarkar Ellora N. , Cannon Chase A. , Golden Matthew R. , Thibault Christina S. , Zinsli Kaitlin , Kim Joong , Pogosjans Sargis , Chow Eric J. , Herrmann Susannah O. , Ocbamichael Negusse , Ramchandani Meena S. , Dombrowski Julia C. 
Published: June 2024

Background
Sexual health clinics (SHCs) were frontline providers in the 2022 US mpox public health response, although data on clinic-based mpox vaccine scale-up, diagnoses, and treatment are limited. We describe the role of a public health SHC in King County's mpox response between May 23, 2022, and October 31, 2022.

Methods
In July 2022, the SHC implemented a dedicated vaccine clinic and presumptive tecovirimat treatment (before laboratory confirmation) with on-site dispensation. We describe SHC's vaccine scale-up and contribution to clinical care by calculating the weekly number of vaccines administered by SHC and the total number of patients diagnosed and treated for mpox within SHC, and by comparing with countywide data. We calculated time from symptom onset to testing and time from testing to treatment, and assessed temporal changes in these metrics using linear regression.

Results
The SHC provided ≥1 vaccine doses to 7442 individuals (10,295 doses), administering 42% of the 24,409 vaccine doses provided countywide, with the greatest contribution in the first week of August (n = 1562, 58% of countywide vaccinations that week). Of 598 patients evaluated for mpox and tested, 178 (30%) tested positive (37% of countywide cases), and 152 (85% of SHC patients with mpox) received tecovirimat (46% of treatment countywide). Median time from symptom onset to testing decreased from 12 to 6 days (P = 0.045); time from testing to treatment decreased from 4.5 to 0 days (P < 0.001).

Conclusions
The SHC was central to mpox vaccination and treatment scale-up, particularly in the first months of the 2022 epidemic.
Integrating HIV Cluster Analysis in Everyday Public Health Practice: Lessons Learned From a Public Health–—Academic Partnership
Authors: Fulton John , Novitsky Vladimir , Gillani Fizza , Guang August , Steingrimsson Jon , Khanna Aditya , Hague Joel , Dunn Casey , Hogan Joseph , Howe Katharine , MacAskill Meghan , Bhattarai Lila , Bertrand Thomas , Bandy Utpala , Kantor Rami 
Published: June 2024

Background:
The use of molecular HIV cluster analysis to supplement public health contact tracing has shown promise in addressing HIV outbreaks. However, the potential of HIV cluster analysis as an adjunct to daily, person-by-person HIV prevention efforts remains unknown. We documented lessons learned within a unique public health–academic partnership while guiding workaday HIV prevention efforts with near–real-time molecular cluster analysis.

Setting:
A public health-academic partnership in the State of Rhode Island, the United States.

Methods:
We recorded perceptions of our team of academicians and public health practitioners that were encountered in an 18-month study evaluating the integration of molecular cluster analysis with HIV contact tracing for public health benefit. The focus was on monthly conferences where molecular clustering of each new statewide diagnosis was discussed to facilitate targeted interventions and on attempted reinterviews of all newly HIV-diagnosed persons statewide whose HIV sequences clustered to increase partner naming.

Results:
Three main themes emerged: First, multidisciplinary conferences are substantially beneficial for gleaning actionable inferences from integrating molecular cluster analysis and public health data. Second, universal reinterviews were perceived to potentially have negative consequences but may be selectively beneficial. Third, the translation of cluster analysis into public health action is hampered by jurisdictional surveillance boundaries and within-jurisdictional data silos, across which data sharing is problematic.

Conclusions:
Insights from a statewide public health–academic partnership support integration of molecular HIV cluster analyses with public health efforts, which can guide public health activities to prevent transmission while identifying substantial barriers to integration, informing continued research.
Traumatic Thoracic Aortic Coarctation after Blunt Thoracic Aortic Injury Mandates Emergent Thoracic Endovascular Aortic Repair
Authors: Bhatt Maunil N. , Byerly Saskya , Filiberto Dina M. , Afzal Muhammad O. , Fabian Timothy C. , Croce Martin A. , Mitchell Erica L. 
Published: June 2024

Objective:
This study sought to elucidate clinical and imaging findings predictive for malperfusion syndrome after blunt thoracic aortic injury (BTAI).

Background:
There is limited literature on malperfusion syndrome after BTAI, and the timing of thoracic endovascular aortic repair (TEVAR) in patients with this condition has not been defined.

Methods:
A retrospective analysis of prospectively collected data of patients with BTAI treated between January 2021 and October 2023. Clinical and thoracic aortic (TA) imaging data, time to TEVAR, in-hospital death, and malperfusion/reperfusion sequelae (paraplegia, renal/visceral/limb ischemia, and compartment syndromes) were assessed. Correlations between clinical and imaging findings, time to TEVAR, and outcomes were evaluated.

Results:
Of the 19,203 trauma patients evaluated, 13,717 (71%) had blunt injuries and 77 (0.6%) had BTAI. The majority (67.5%) were male, with a median age of 40 years (IQR: 33–55). TEVAR was performed in 42 (54.5%) patients. Seven (9.1%) patients presented with clinical and TA imaging criteria for traumatic thoracic aortic coarctation (TTAC), including diminished/absent femoral pulses and TA luminal narrowing of 50% to 99%. The median time to TEVAR was 9 (IQR: 5–32), 11, and 4 hours for all non-TTAC and TTAC BTAI patients, respectively (P=0.037). Only TTAC patients presented/developed malperfusion/reperfusion sequelae. In-hospital mortality rates were 7.8%, 5.8%, and 29% for all non-TTAC and TTAC BTAI patients, respectively (P=0.09). Aortic-related mortality occurred in only 2 (2.6%) TTAC patients.

Conclusions:
Patients with clinical and TA imaging manifestations of TTAC are predisposed to malperfusion/reperfusion sequelae if TEVAR is delayed. We recommend the emergent repair of all BTAIs with TTAC.
Solitary Lung Cavities on CT Imaging: Differentiating Malignant and Non-Malignant Diseases
Authors: Cosgun Zeliha 
Published: June 2024

AbstractBackgroundThis study aims to explore how radiological findings contribute to distinguishing between benign and malignant diseases in patients with solitary cavitary lesions detected on CT.MethodsWe retrospectively assessed lesion size, cavity wall thickness, and additional parenchymal findings in diagnosing benign or malignant disease in these patients. Our study investigated the incidence and etiology of solitary pulmonary cavities. CT scans were reviewed by a single radiologist with expertise in thoracic radiology. The study was conducted using two 64-multidetector CT systems, and measurements of lesion size and cavity wall thickness were recorded on axial images. Consolidation and centrilobular nodules were assessed based on predefined criteria. Receiver operating characteristic curves were generated to determine optimal cut-off points for distinguishing between malignant and non-malignant lesions based on cavity wall thickness.ResultsNon-malignant lesions accounted for 47.9% of cases, with active pulmonary tuberculosis being the most common diagnosis. In the malignant group, primary lung cancer predominated, squamous cell carcinoma being the most prevalent subtypes. Significant differences were noted between malignant and non-malignant cases regarding average maximum wall thickness and lesion diameter. Presence of perilesional consolidation or centrilobular nodules favored non-malignant diagnoses. Maximum wall thickness thresholds of 7.2 mm or 23 mm were most accurate in suggesting non-malignant and malignant etiologies, respectively.ConclusionsIn conclusion, CT findings revealed significant distinctions between malignant and non-malignant solitary lung cavities; benign lesions generally exhibited smaller and thinner cavity walls, with accompanying perilesional parenchymal findings observed in benign lesions of infectious origin but not in malignant lesions.
How well it works: Benchmarking performance of GPT models on medical natural language processing tasks
Authors: Rough Kathryn , Feng Hui , Milligan Paul B , Tombini Francesco , Kwon Tom , Zine El Abidine Khaldoun , Mack Christina D , Hughes Benjamin 
Published: June 2024

AbstractImportanceThe ability of large language models (LLMs) to generate high-quality, human-like text has been accompanied with speculation about their application in healthcare, alongside ethical and safety concerns.ObjectiveEvaluate LLM performance on medical natural language processing (NLP) tasks, benchmarked against other commercially available tools.DesignObservational study to evaluate and compare model performance. All models were commercially available and were evaluated without modification.SettingThe Text Analysis Coding (TAC) 2017 challenge was used to assess ability to perform medical coding using standard MedDRA preferred terms. Text from 55 publicly available de-identified medical transcription reports were annotated to identify pre-defined medical concepts (age, disease/symptom, body structure, medication name, and medication dosage).ParticipantsPublicly available, de-identified adverse event and medical transcription reports were used for evaluation.ExposuresFor each task, general LLMs (GPT-3.5-turbo, GPT-4) were compared to commercially available healthcare NLP tools (Microsoft Text Analytics for Health, Amazon Comprehend Medical, IQVIA API Marketplace).Main Outcomes and MeasuresFor each NLP task, sensitivity, positive predictive value (PPV) and F1 score were calculated. Because GPT models had variable outputs, the range of metrics over 5 trials is reported.ResultsFor MedDRA coding, GPT-4 had similar F1 score performance to healthcare NLP algorithms (GPT-4: 0.67 to 0.73; Microsoft Text Analytics for Health: 0.66, IQVIA API Marketplace: 0.72), while GPT-3.5-turbo had considerably lower performance (0.50 to 0.51). For medical information extraction, LLM performance varied widely across differing medical concepts; the highest F1 scores were for age (GPT-3.5-turbo: 0.82 to 0.83, GPT-4: 0.84 to 0.87) and medication name (GPT-3.5-turbo: 0.55 to 0.59, GPT-4: 0.70 to 0.76), while F1 scores for disease/symptom, body structure, and medication dosage were lower than those observed for the healthcare NLP tools. GPT-3.5-turbo and GPT-4 generally had lower sensitivity than comparators.Conclusions and RelevanceIn the absence of domain-specific fine tuning, GPT-4 performed similarly to healthcare-specific NLP tools on some tasks and less accurately on others; GPT-3.5-turbo was consistently less accurate than comparators. To maximize benefit and reduce risk of harm, robust quantitative evaluation for specific tasks should be performed prior to implementing LLMs in medical contexts.
Thymic self-recognition-mediated TCR signal strength modulates antigen-specific CD8+T cell pathogenicity in non-obese diabetic mice
Authors: Ho Chia-Lo , Yeh Li-Tzu , Liu Yu-Wen , Dong Jia-Ling , Sytwu Huey-Kang 
Published: June 2024

AbstractOur understanding of autoimmune diabetes underscores the critical involvement of CD8+T cells recognizing islet-specific antigens. However, the influence of thymic positive selection on diabetogenic CD8+T cell development remains unclear. Using CD5 marker representing T-cell receptor (TCR) signal strength, we illustrated that naïve CD5hiCD8+T cells of non-obese diabetic (NOD) mice with enhanced TCR signals displayed predisposed differentiated/memory T cell traits with increased activation and proliferation upon TCR stimulation, compared to CD5locounterparts. Additionally, CD5hiCD8+T cells exhibited gene expression landscape similar to effector T cells and exacerbated disease in transfer model. Interestingly, the protective effects of transgenic phosphatase Pep expression, which lowers TCR signaling and diabetes incidence, were abolished in NOD strain 8.3 with high CD5 expression linked to increased thymic positive selection. Strikingly, TCR repertoire analysis identified higher frequencies of autoimmune disease-related clonotypes in naïve CD5hiCD8+cells, supporting that distinct effector functions arise from intrinsic TCR repertoire differences. Overall, CD5hiCD8+clones may be potential targets for autoimmune diabetes treatment.
The spatial organization of ascending auditory pathway microstructural maturation from infancy through adolescence using a novel fiber tracking approach
Authors: Lynch Kirsten M. , Bodison Stefanie C. , Cabeen Ryan P. , Toga Arthur W. , Voelker Courtney C.J. 
Published: June 2024

AbstractAuditory perception is established through experience-dependent stimuli exposure during sensitive developmental periods; however, little is known regarding the structural development of the central auditory pathway in humans. The present study characterized the regional developmental trajectories of the ascending auditory pathway from the brainstem to the auditory cortex from infancy through adolescence using a novel diffusion MRI-based tractography approach and along-tract analyses. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to quantify the magnitude and timing of auditory pathway microstructural maturation. We found spatially varying patterns of white matter maturation along the length of the tract, with inferior brainstem regions developing earlier than thalamocortical projections and left hemisphere tracts developing earlier than the right. These results help to characterize the processes that give rise to functional auditory processing and may provide a baseline for detecting abnormal development.HighlightsWe characterize the microstructural maturation of the auditory pathwayWe show structural development of the auditory pathway is dynamic and heterogeneousDiffusion metrics AD, RD and MD reach adult-like levels earlier than FA and NDIBrainstem microstructure matures earlier than the subcortical white matterMaturation of the right auditory pathway continues later than the left
Maternal Immunoglobulin A regulates the development of the neonatal microbiota and intestinal microbiota-specific CD4+ T cell responses
Authors: Abbott Darryl A. , Rai Ali T. , Yang Aaron , Cai Yixuan , Fabre Shelcie , Frazer Austin J. , Deschepper Jacob D. , Poholek Amanda C. , Hand Timothy W. 
Published: June 2024

AbstractBreast milk is a complex mixture of nutrients and bioactives that promote infant development and decrease the incidence of chronic inflammatory disease. We investigated the role of one milk-derived bioactive, Immunoglobulin A (IgA) on the developing small intestinal microbiota and immune system. We demonstrate that early in life, milk-derived IgA suppressed colonization of the small intestine byEnterobacteriaceaeand regulated the maturation of the small intestinal epithelium and the development of intestinal IL-17-producing CD4+T cells.Enterobacteriaceae- specific CD4+T cells, induced in the first weeks of life in the absence of milk-derived IgA, persisted in the intestine as memory T cells that can contribute to inflammatory disease later in life. Our study suggests that milk-derived IgA shapes mucosal immunity by regulating the neonatal microbiota thus preventing the development of long-lived intestinal microbiota-specific T cells.
Genetically diverse Mycobacterium tuberculosis isolates manipulate inflammasome activation and IL-1β secretion independently of macrophage metabolic rewiring
Authors: Fernandes Ana Isabel , Pinto Alexandre Jorge , Silvério Diogo , Zedler Ulrike , Ferreira Carolina , Duarte Iola F. , Silvestre Ricardo , Dorhoi Anca , Saraiva Margarida 
Published: June 2024

AbstractThe natural diversity ofMycobacterium tuberculosisis gaining relevance in dictating the outcome of tuberculosis (TB). We previously revealed a link between TB severity andM. tuberculosis-driven evasion of the macrophage cytosolic surveillance systems, with isolates from severe TB cases reducing inflammasome activation and interleukin (IL)-1β production by infected cells. IL-1β production and inflammasome activation are commonly associated with the metabolic reprogramming of stimulated macrophages. Thus, we questioned whether the differential modulation of the inflammasome and IL-1β byM. tuberculosisisolates depended on distinct macrophage metabolic reprogramming. Using metabolic inhibitors, mice deficient for key metabolic regulators, and a metabolomics approach, we found that the macrophage metabolic landscape was similar regardless of the infectingM. tuberculosisisolate. Paralleling single-TLR activated macrophages, inhibition of glycolysis during infection impaired IL-1β secretion. However, departing from TLR based models, inM. tuberculosis-infected macrophages IL-1β secretion was independent of macrophage mitochondrial metabolic changes and the transcription factor hypoxia-inducible factor (HIF)-1α. Additionally, we found a previously unappreciated impact of host metabolic inhibitors on the pathogen, and show that inhibition of the mycobacteria metabolism dampened both inflammasome activation and IL-1β production. Collectively, our study raises awareness of the potential confounding effect of host metabolic inhibitors acting on the pathogen itself and demonstrates that the modulation of the inflammasome byM. tuberculosismay be uncoupled from the host metabolic reprogramming.Author SummaryMycobacterium tuberculosisis the causative agent of tuberculosis and one of the top infectious killers in the world, with around 1.3 million deaths reported annually. The genetic variability of this pathogen can shape its interaction with the host and modulate disease outcomes. We previously found thatM. tuberculosisclinical isolates from patients with severe forms of tuberculosis evade cytosolic surveillance systems in macrophages. Here, we explored whether this evasion tactic was linked to metabolic alterations in the infected macrophages. We found that differentM. tuberculosisisolates induced similar metabolic changes in infected macrophages. Additionally, we demonstrate that both host glycolysis and pathogen’s metabolism were pivotal for maximum IL-1β production. These findings highlight the complexity of macrophage-pathogen interactions and emphasize that bacterial metabolism should be considered in metabolic studies and may be amenable to therapeutic intervention against tuberculosis.
A Mechanistic Approach to Optimize Combination Antibiotic Therapy
Authors: Clarelli F. , Ankomah P. O. , Weiss H. , Conway J. M. , Forsdahl G. , Wiesch P. Abel zur 
Published: June 2024

AbstractAntimicrobial resistance is one of the most significant healthcare challenges of our times. Multidrug or combination therapies are sometimes required to treat severe infections; for example, the current protocols to treat pulmonary tuberculosis combine four antibiotics. However, combination therapy is usually based on lengthy empirical trials and it is difficult to predict its efficacy. We propose a new tool to identify antibiotic synergy or antagonism and optimize combination therapies. Our model explicitly incorporates the mechanisms of individual drug action and estimates their combined effect using a mechanistic approach. By quantifying the impact on growth and death of a bacterial population, we can identify optimal combinations of multiple drugs. Our approach also allows for the investigation of the drugs’ actions and the testing of theoretical hypotheses.We demonstrate the utility of this tool with in vitroEscherichia colidata using a combination of ampicillin and ciprofloxacin. In contrast to previous interpretations, our model finds a slight synergy between the antibiotics. Our mechanistic model allows investigating possible causes of the synergy.
Sensitive tumor detection, accurate quantification, and cancer subtype classification using low-pass whole methylome sequencing of plasma DNA
Authors: Paoli Marta , Galardi Francesca , Nardone Agostina , Biagioni Chiara , Romagnoli Dario , Donato Samantha Di , Franceschini Gian Marco , Livraghi Luca , Pestrin Marta , Sanna Giuseppina , Risi Emanuela , Migliaccio Ilenia , Moretti Erica , Malorni Luca , Biganzoli Laura , Demichelis Francesca , Benelli Matteo 
Published: June 2024

AbstractThe analysis of circulating tumor DNA (ctDNA) is increasingly used for monitoring disease in patients with metastatic cancer. Here, we introduce a robust and reproducible strategy combining low-pass whole methylome sequencing of plasma DNA with METER, a novel computational tool. Engaging prediction models trained on independent available datasets, METER enables the detection and quantification of tumor content (TC) and performs molecular cancer subtyping. Applied to plasma methylomes from early metastatic breast cancer patients, our method demonstrated reliable quantification, sensitive tumor detection below 3% of TC, and the ability to perform accurate Estrogen Receptor (ER) subtyping. METER provided clinically relevant predictions, underscored by associations with relevant prognostic factors, robust correlation with matched circulating tumor cells, and highly correlated with patients’ outcomes in challenging scenarios as TC<3%. Our strategy provides comprehensive and sensitive analysis of plasma samples, serving as a valuable yet cost-effective precision oncology tool.