bluuebunny/crossref_metadata_2025_split huggingface dataset:
TraumaICDBERT, A Natural Language Processing Algorithm to Extract Injury ICD-10 Diagnosis Code from Free Text
Authors: Choi Jeff , Chen Yifu , Sivura Alexander , Vendrow Edward B. , Wang Jenny , Spain David A. 
Published: September 2023

Objective:
To develop and validate TraumaICDBERT, a natural language processing algorithm to predict injury ICD-10 diagnosis codes from trauma tertiary survey notes.

Summary Background Data:
The adoption of ICD-10 diagnosis codes in clinical settings for injury prediction is hindered by the lack of real-time availability. Existing natural language processing algorithms have limitations in accurately predicting injury ICD-10 diagnosis codes.

Methods:
Trauma tertiary survey notes from hospital encounters of adults between January 2016 and June 2021 were used to develop and validate TraumaICDBERT, an algorithm based on BioLinkBERT. The performance of TraumaICDBERT was compared to Amazon Web Services Comprehend Medical, an existing natural language processing tool.

Results:
A dataset of 3,478 tertiary survey notes with 15,762 4-character injury ICD-10 diagnosis codes was analyzed. TraumaICDBERT outperformed Amazon Web Services Comprehend Medical across all evaluated metrics. On average, each tertiary survey note was associated with 3.8 (standard deviation: 2.9) trauma registrar-extracted 4-character injury ICD-10 diagnosis codes.

Conclusions:
TraumaICDBERT demonstrates promising initial performance in predicting injury ICD-10 diagnosis codes from trauma tertiary survey notes, potentially facilitating the adoption of downstream prediction tools in clinical settings.
An RNA foundation model enables discovery of disease mechanisms and candidate therapeutics
Authors: Celaj Albi , Gao Alice Jiexin , Lau Tammy T.Y. , Holgersen Erle M. , Lo Alston , Lodaya Varun , Cole Christopher B. , Denroche Robert E. , Spickett Carl , Wagih Omar , Pinheiro Pedro O. , Vora Parth , Mohammadi-Shemirani Pedrum , Chan Steve , Nussbaum Zach , Zhang Xi , Zhu Helen , Ramamurthy Easwaran , Kanuparthi Bhargav , Iacocca Michael , Ly Diane , Kron Ken , Verby Marta , Cheung-Ong Kahlin , Shalev Zvi , Vaz Brandon , Bhargava Sakshi , Yusuf Farhan , Samuel Sharon , Alibai Sabriyeh , Baghestani Zahra , He Xinwen , Krastel Kirsten , Oladapo Oladipo , Mohan Amrudha , Shanavas Arathi , Bugno Magdalena , Bogojeski Jovanka , Schmitges Frank , Kim Carolyn , Grant Solomon , Jayaraman Rachana , Masud Tehmina , Deshwar Amit , Gandhi Shreshth , Frey Brendan J. 
Published: September 2023

AbstractAccurately modeling and predicting RNA biology has been a long-standing challenge, bearing significant clinical ramifications for variant interpretation and the formulation of tailored therapeutics. We describe a foundation model for RNA biology, “BigRNA”, which was trained on thousands of genome-matched datasets to predict tissue-specific RNA expression, splicing, microRNA sites, and RNA binding protein specificity from DNA sequence. Unlike approaches that are restricted to missense variants, BigRNA can identify pathogenic non-coding variant effects across diverse mechanisms, including polyadenylation, exon skipping and intron retention. BigRNA accurately predicted the effects of steric blocking oligonucleotides (SBOs) on increasing the expression of 4 out of 4 genes, and on splicing for 18 out of 18 exons across 14 genes, including those involved in Wilson disease and spinal muscular atrophy. We anticipate that BigRNA and foundation models like it will have widespread applications in the field of personalized RNA therapeutics.
Exploring the effects of Dasatinib, Quercetin, and Fisetin on DNA methylation clocks: a longitudinal study on senolytic interventions
Authors: Lee Edwin , Carreras-Gallo Natàlia , Lopez Leilani , Turner Logan , Lin Aaron , Mendez Tavis L. , Went Hannah , Tomusiak Alan , Verdin Eric , Corley Michael , Ndhlovu Lishomwa , Smith Ryan , Dwaraka Varun B. 
Published: September 2023

AbstractSenolytics, small molecules targeting cellular senescence, have emerged as potential therapeutics to enhance health span. However, their impact on epigenetic age remains unstudied. This study aimed to assess the effects of Dasatinib and Quercetin (DQ) senolytic treatment on DNA methylation (DNAm), epigenetic age, and immune cell subsets. In a Phase I pilot study, 19 participants received DQ for 6 months, with DNAm measured at baseline, 3 months, and 6 months. Significant increases in epigenetic age acceleration were observed in first-generation epigenetic clocks and mitotic clocks at 3 and 6 months, along with a notable decrease in telomere length. However, no significant differences were observed in second and third-generation clocks. Building upon these findings, a subsequent investigation evaluated the combination of DQ with Fisetin (DQF), a well-known antioxidant and antiaging senolytic molecule. After one year, 19 participants (including 10 from the initial study) received DQF for 6 months, with DNAm assessed at baseline and 6 months. Remarkably, the addition of Fisetin to the treatment resulted in non-significant increases in epigenetic age acceleration, suggesting a potential mitigating effect of Fisetin on the impact of DQ on epigenetic aging. Furthermore, our analyses unveiled notable differences in immune cell proportions between the DQ and DQF treatment groups, providing a biological basis for the divergent patterns observed in the evolution of epigenetic clocks. These findings warrant further research to validate and comprehensively understand the implications of these combined interventions.
Quantitative Assessment of Morphological Changes in Lipid Droplets and Lipid-Mito Interactions with Aging in Brown Adipose
Authors: Crabtree Amber , Neikirk Kit , Pinette Julia , Whiteside Aaron , Shao Bryanna , McKenzie Jessica , Vue Zer , Vang Larry , Le Han , Dermici Mert , Ahmad Taseer , Owens Trinity Celeste , Oliver Ashton , Zeleke Faben , Beasley Heather K. , Lopez Edgar Garza , Scudese Estevão , Rodman Taylor , Kabugi Kinuthia , Koh Alice , Navarro Suzanne , Lam Jacob , Kirk Ben , Mungai Margaret , Sweetwyne Mariya , Koh Ho-Jin , Zaganjor Elma , Damo Steven M. , Gaddy Jennifer A. , Kirabo Annet , Murray Sandra A. , Cooper Anthonya , Williams Clintoria , McReynolds Melanie R. , Marshall Andrea G. , Hinton Antentor 
Published: September 2023

ABSTRACTThe physical characteristics of brown adipose tissue (BAT) are defined by the presence of multilocular lipid droplets (LD) within the brown adipocytes and a high abundance of iron-containing mitochondria, which give it its characteristic color. Normal mitochondrial function is, in part, regulated by organelle-to-organelle contacts. Particularly, the contact sites that mediate mitochondria-LD interactions are thought to have various physiological roles, such as the synthesis and metabolism of lipids. Aging is associated with mitochondrial dysfunction, and previous studies show that there are changes in mitochondrial structure and proteins that modulate organelle contact sites. However, how mitochondria-LD interactions change with aging has yet to be fully clarified. Therefore, we sought to define age-related changes in LD morphology and mitochondria-lipid interactions in BAT. We examined the three-dimensional morphology of mitochondria and LDs in young (3-month) and aged (2-year) murine BAT using serial block face-scanning electron microscopy and the Amira program for segmentation, analysis, and quantification. Analysis showed reductions in LD volume, area, and perimeter in aged samples compared to young samples. Additionally, we observed changes in LD appearance and type in aged samples compared to young samples. Notably, we found differences in mitochondrial interactions with LDs, which could implicate that these contacts may be important for energetics in aging. Upon further investigation, we also found changes in mitochondrial and cristae structure for mitochondria interacting with LD lipids. Overall, these data define the nature of LD morphology and organelle-organelle contacts during aging and provide insight into LD contact site changes that interconnect biogerontology and mitochondrial functionality, metabolism, and bioactivity in aged BAT.Abstract FigureGraphical AbstractWorkflow highlighting the process of murine interscapular BAT extraction, processing and imaging serial block facing-scanning electron microscopy and using Amira software for 3D reconstruction of LDs and mitochondrial lipid contact sites to elucidate their structure across aging.
Research ethics review during the COVID-19 pandemic: An international study
Authors: Salamanca-Buentello Fabio , Katz Rachel , Silva Diego S. , Upshur Ross E.G. , Smith Maxwell J. 
Published: September 2023

ABSTRACTResearch ethics review committees (ERCs) worldwide faced daunting challenges during the COVID-19 pandemic. There was a need to balance rapid turnaround with rigorous evaluation of high-risk research protocols in the context of considerable uncertainty. This study explored the experiences and performance of ERCs during the pandemic.We conducted an anonymous, cross-sectional, global online survey of chairs (or their delegates) of ERCs who were involved in the review of COVID-19-related research protocols after March 2020. The survey ran from October 2022 to February 2023 and consisted of 50 items, with opportunities for open text responses.Two hundred and three participants [130 from high-income countries (HICs) and 73 from low-and middle-income countries (LMICs)] completed our survey. Respondents came from diverse entities and organizations from 48 countries (19 HICs and 29 LMICs) in all World Health Organization regions. Responses show little of the increased global funding for COVID-19 research was allotted to the operation of ERCs. Few ERCs had pre-existing internal policies to address operation during public health emergencies, but almost half used existing guidelines. Most ERCs modified existing procedures or designed and implemented new ones but had not evaluated the success of these changes. Participants overwhelmingly endorsed permanently implementing several of them. Few ERCs added new members but non-member experts were consulted; quorum was generally achieved. Collaboration among ERCs was infrequent, but reviews conducted by external ERCs were recognized and validated. Review volume increased during the pandemic, with COVID-19-related studies being prioritized. Most protocol reviews were reported as taking less than three weeks. One-third of respondents reported external pressure on their ERCs from different stakeholders to approve or reject specific COVID-19-related protocols.ERC members faced significant challenges to keep their committees functioning during the pandemic. Our findings can inform ERC approaches towards future public health emergencies. To our knowledge, this is the first international, COVID-19-related study of its kind.
How demographic factors matter for antimicrobial resistance – quantification of the patterns and impact of variation in prevalence of resistance by age and sex
Authors: Waterlow Naomi R , Cooper Ben S , Robotham Julie V , Knight Gwenan M 
Published: September 2023

AbstractBackgroundAntibiotic usage, contact with high transmission healthcare settings as well as changes in immune system function all vary by a patient’s age and sex. Yet, most analyses of antimicrobial resistance (AMR) ignore demographic indicators and provide only country level resistance prevalence values.In this work we use routine surveillance data on serious infections in Europe to characterise the importance of age and sex on incidence and resistance prevalence patterns for 33 different bacteria and antibiotic combinations. We fit Bayesian multilevel regression models to quantify these effects and provide estimates of country-, bacteria- and drug-family effect variation.ResultsAt the European level, we find distinct patterns in resistance prevalence by age that have previously not been explored in detail. Trends often vary more within an antibiotic family than within a bacterium: clear resistance increases by age for methicillin resistantS. aureus(MRSA) contrast with a peak in resistance to several antibiotics at ∼30 years of age forP. aeruginosa.This diverges from the known, clear exponential increase in infection incidence rates by age, which are higher for males except forE. coliat ages 15-40.At the country-level, the patterns are highly context specific with national and subnational differences accounting for a large amount of resistance variation (∼38%) and a range of associations between age and resistance prevalence. We explore our results in greater depths for two of the most clinically important bacteria–antibiotic combinations. For MRSA, age trends were mostly positive, with 72% of countries seeing an increased resistance between males aged 1 and 100 and more resistance in males. This compares to age trends for aminopenicillin resistance inE. coliwhich were mostly negative (males: 93% of countries see decreased resistance between ages 1 and 100) with more resistance in females. A change in resistance prevalence between ages 1 and 100 ranged up to ∼0.46 (95% CI 0.37 – 0.51, males) for MRSA but varied between 0.16 (95% CI 0.23-0.3, females) to -0.27 (95%CI -0.4 - - 0.15, males) across individual countries for aminopenicillin resistance inE. coli.ConclusionPrevalence of resistance in infection varies substantially by the age and sex of the individual revealing gaps in our understanding of AMR epidemiology. These context-specific patterns should now be exploited to improve intervention targeting as well as our understanding of AMR dynamics.
BMP signaling pathway member expression is enriched in enteric neural progenitors and required for zebrafish enteric nervous system development
Authors: Moore Joshua A. , Noah Arielle S. , Singleton Eileen W. , Uribe Rosa A. 
Published: September 2023

AbstractThe vertebrate enteric nervous system (ENS) consists of a series of interconnected ganglia within the gastrointestinal (GI) tract, formed during development following the migration of enteric neural crest cells (ENCCs) into the primitive gut tube. Much work has been done to unravel the complex nature of extrinsic and intrinsic factors that regulate processes that direct the migration, proliferation, and differentiation of ENCCs. However, ENS development is a complex process and we still have much to learn regarding the signaling factors that regulate ENCC development. Here in zebrafish, through transcriptomic,in situtranscript expression, immunohistochemical analysis, and chemical attenuation, we identified a time-dependent role for bone morphogenetic protein (BMP) in the maintenance of Phox2bb+enteric progenitor numbers and/or time of differentiation of the progenitor pool. In support of ourin silicotranscriptomic analysis, we identified expression of a novel ENS ligand-encoding transcript,bmp5,within developmental regions of ENCCs. Through generation of a novel mutantbmp5wmr2,we identified a functional role for BMP5 in proper GI tract colonization, wherebyphox2bb+enteric progenitor numbers were reduced. Altogether, this work has identified time-dependent roles for BMP signaling and identification of a novel extrinsic factor, BMP5, that is necessary for proper formation of vertebrate ENS.
Recruitment, Consent and DNA Sample Acquisition in a U.S. Precision Health Cohort During the COVID-19 Pandemic
Authors: Derry Allyson M. , Strong Yvette , Schioppo Davia , Cotter Joni , Wilkins Geisa M. , Siqueiros Laura I. , Ouyang Andrea , Hulseman Kathleen , Petrosino Joseph , Liang Lorrin , Stevenson Megan , Aguilera Tiffany Elianne , Soto Alexandria L. , Meurer Katherine , Herman Alison L. , Cohen Inessa , Falcone Guido J. , Longbrake Erin E. , Chaar Cassius I. Ochoa , Anastasio Kelly M. , Murray Michael F. 
Published: September 2023

AbstractAimThe Yale Generations Project (YGP) is a precision health cohort initiative that began enrollment in New Haven Connecticut USA in July 2019. In March 2020, after nine months of operation, pandemic restrictions prompted abrupt changes to staff availability as well as changes to the project’s recruitment, consenting, and sample acquisition. This manuscript describes the successful addition of remote recruitment, consenting, and DNA sampling to YGP workflows during the initial 27-months of pandemic restrictions ending June 30, 2022.MethodsThe initial YGP protocol established face-to-face workflow for recruiting, consenting and peripheral blood collection. A telemedicine consent protocol was initiated in April of 2020, and a remote saliva collection was established in October of 2020. De-identified data was extracted from YGP dataset and reported here.ResultsAt the completion of YGP’s initial 36 months (9-months pre-pandemic and 27-months pandemic) YGP enrolled N=4949 volunteers. There were N=1,950 (216.7 per month) volunteers consented pre-pandemic and N=2,999 (111.1 per month) during pandemic. The peak consenting month was February 2020 with N=428. DNA sample acquisition peaked in the pre-pandemic month of February 2020 with N=291 peripheral blood draws, and in the pandemic period the peak DNA acquisition month was November 2020 with N=176 (N=68 peripheral blood draws and N=108 saliva samples).ConclusionThe YGP successfully transitioned from pre-pandemic recruiting, consenting and sample acquisition model that was exclusively face-to-face, to pandemic model that was predominantly remote. The added value of remote recruiting, consenting, and sampling has led to plans for an optimized hybrid model post-pandemic.
Noninvasive Quantification of Radiation-Induced Lung Injury using a Targeted Molecular Imaging Probe
Authors: Abston Eric , Zhou Iris Y. , Saenger Jonathan A. , Shuvaev Sergey , Akam Eman , Esfahani Shadi A. , Hariri Lida P. , Rotile Nicholas J. , Crowley Elizabeth , Montesi Sydney B. , Humblet Valerie , Arabasz Grae , Catana Ciprian , Fintelmann Florian J. , Caravan Peter , Lanuti Michael 
Published: September 2023

AbstractRationaleRadiation-induced lung injury (RILI) is a progressive inflammatory process commonly seen following irradiation for lung cancer. The disease can be insidious, often characterized by acute pneumonitis followed by chronic fibrosis with significant associated morbidity. No therapies are approved for RILI, and accurate disease quantification is a major barrier to improved management.ObjectiveTo noninvasively quantify RILI, utilizing a molecular imaging probe that specifically targets type 1 collagen in mouse models and patients with confirmed RILI.MethodsUsing a murine model of lung radiation, mice were imaged with EP-3533, a type 1 collagen probe to characterize the development of RILI and to assess disease mitigation following losartan treatment. The human analog probe targeted against type 1 collagen,68Ga-CBP8, was tested on excised human lung tissue containing RILI and quantified via autoradiography. Finally,68Ga-CBP8 PET was used to assess RILIin vivoin six human subjects.ResultsMurine models demonstrated that probe signal correlated with progressive RILI severity over six-months. The probe was sensitive to mitigation of RILI by losartan. Excised human lung tissue with RILI had increased binding vs unirradiated control tissue and68Ga-CBP8 uptake correlated with collagen proportional area. Human imaging revealed significant68Ga-CBP8 uptake in areas of RILI and minimal background uptake.ConclusionsThese findings support the ability of a molecular imaging probe targeted at type 1 collagen to detect RILI in preclinical models and human disease, suggesting a role for targeted molecular imaging of collagen in the assessment of RILI.Clinical trial registered withwww.clinicaltrials.gov(NCT04485286,NCT03535545)
Voice-Enabled Response Analysis Agent (VERAA): Leveraging Large Language Models to Map Voice Responses in SDoH Survey
Authors: Krishnamoorthy Rishivardhan , Nagarajan Vishal , Pour Hayden , Shashikumar Supreeth P. , Boussina Aaron , Farcas Emilia , Nemati Shamim , Josef Christopher S. 
Published: September 2023

AbstractSocial Determinants of Health (SDoH) have been shown to have profound impacts on health-related outcomes, yet this data suffers from high rates of missingness in electronic health records (EHR). Moreover, limited English proficiency in the United States can be a barrier to communication with health care providers. In this study, we have designed a multilingual conversational agent capable of conducting SDoH surveys for use in healthcare environments. The agent asks questions in the patient’s native language, translates responses into English, and subsequently maps these responses via a large language model (LLM) to structured options in a SDoH survey. This tool can be extended to a variety of survey instruments in either hospital or home settings, enabling the extraction of structured insights from free-text answers. The proposed approach heralds a shift towards more inclusive and insightful data collection, marking a significant stride in SDoH data enrichment for optimizing health outcome predictions and interventions.
An assessment of census-tract level socioeconomic position as a modifier of the relationship between PM 2.5 concentrations and cardiovascular emergency department visits in Missouri
Authors: McCann Zachary H. , Chang Howard H. , D’Souza Rohan , Scovronick Noah , Ebelt Stefanie 
Published: September 2023

AbstractAmbient PM2.5 exposure elevates the risk for cardiovascular disease morbidity (CVDM). The aim of this study is to characterize which area-level measures of socioeconomic position (SEP) modify the relationship between PM2.5 exposure and CVDM in Missouri at the census-tract (CT) level. We use individual level Missouri emergency department (ED) admissions data (n = 3,284,956), modeled PM2.5 data, and yearly census tract data from 2012-2016 to conduct a two-stage analysis. Stage one uses a case-crossover approach with conditional logistic regression to establish the baseline risk of ED visits associated with interquartile range (IQR) changes in PM2.5. In the second stage, we use multivariate meta-regression to examine how census tract level SEP modifies the relationship between ambient PM2.5 exposure and CVDM. We find that overall, ambient PM2.5 exposure is associated with increased risk for CVDM. We test effect modification in statewide and urban census tracts, and in the warm-season only. Effect modification results suggest that among SEP measures, poverty is most consistently associated with increased risk for CVDM. For example, across Missouri the highest poverty CTs are at an elevated risk for CVDM [OR = 1.010 (95% CI 1.007, 1.014)] compared to the lowest poverty CTs [OR = 1.004 (95% CI 1.000, 1.008)]. Other SEP modifiers generally display an inconsistent or null effect. Overall, we find some evidence that area-level SEP modifies the relationship between ambient PM2.5 exposure and CVDM, and suggest that the relationship between air-pollution, area-level SEP, and CVDM may be sensitive to spatial scale.