bluuebunny/crossref_metadata_2025_split huggingface dataset:
Photoreceptor outer segment reflectivity with ultrahigh resolution visible light optical coherence tomography in systemic hydroxychloroquine use
Authors: Garg Anupam K. , Wang Jingyu , Alonzo Bailee , Yi Ji , Kashani Amir H. 
Published: September 2024

AbstractPurposeTo evaluate outer retinal organization in normal subjects and those using hydroxychloroquine (HCQ) with ultrahigh resolution visible light optical coherence tomography (VIS-OCT).MethodsForty eyes of 22 adult subjects were recruited from a tertiary care retina practice including controls (20 eyes, 12 subjects, mean age 40±22yrs, mean logMAR BCVA 0.19, 90% female) and subjects with a history of HCQ use (20 eyes, 10 subjects, mean age 62±17yrs, mean logMAR BCVA 0.03, 67% female). Each subject was imaged using a custom-built VIS-OCT device (axial resolution 1.3μm) and FDA-approved OCT devices.ResultsUsing VIS-OCT, control subjects demonstrate 5 and 6 hyperreflective bands in the foveal and parafoveal regions, respectively, between the outer nuclear layer and Bruch’s membrane. These bands demonstrate intensity profiles complementary to the known histopathologic distribution of rods and cones. In comparison to controls, subjects taking HCQ demonstrate blunting of all bands, particularly bands 2-4. In all cases of suspected or known toxicity, VIS-OCT demonstrated attenuation of band 3i and in no cases was there attenuation of other bands that was more severe than band 3i, suggesting that changes in the reflectivity of Band 3i may be the earliest identifiable sign of HCQ toxicity.ConclusionsVIS-OCT of the outer retina demonstrates a unique outer retinal banding pattern corresponding to photoreceptor density profiles. There is a notable attenuation of the photoreceptor outer segment reflectivity profile associated with early HCQ toxicity. This finding may be an early, and possibly reversible, sign of HCQ toxicity, primarily impacting the cones.
Deuterium metabolic imaging of the human abdomen at clinical field strength
Authors: Wodtke Pascal , McLean Mary A , Horvat-Menih Ines , Birchall Jonathan R , Zamora-Morales Maria J , Grimmer Ashley , Latimer Elizabeth , Wylot Marta , Schulte Rolf F , Gallagher Ferdia A 
Published: September 2024

AbstractBackgroundThe Warburg effect is a hallmark of cancer and is characterized by increased glucose consumption and lactate formation. Deuterium metabolic imaging (DMI) is an emerging non-invasive MRI method for probing this metabolic reprogramming in the field of neuroimaging. Here we show the feasibility of the technique for abdominal imaging using a routine 3 T MRI system, which has previously presented significant technical challenges.PurposeThis study aimed to translate abdominal DMI to clinical field strength by optimizing the radiofrequency coil setup, the administered dose of deuterium (2H)-labelled glucose, and the data processing pipeline for quantitative characterization of DMI signals over time in the kidney and liver, establishing a basis for routine clinical studies in the future.Materials and MethodsFive healthy volunteers were recruited and imaged on 2 or 3 occasions, with different2H-glucose doses (totalling 13 DMI scan sessions). DMI was performed at 3 T using a flexible 20 x 30 cm22H-tuned transmit-receive surface coil. We have defined three novel quantitative parameters as metrics of metabolism and compared these between doses and organs.ResultsThe careful positioning of a dedicated surface coil minimized unwanted gastric signals while maintaining excellent hepatic and renal measurements. The timecourses derived from the liver and kidney were reproducible and comparable across different doses, with a trend towards lower quantitative measurements with decreasing dose. An increase in the2H-water signal over time particularly in the liver, could be used as an indirect measure of metabolism.ConclusionDMI of the human abdomen is feasible using a routine MRI system and the metabolism measured in the kidney and liver can serve as a reference for future clinical studies. The2H-glucose dose can be reduced from 0.75 to 0.25 g/kg to minimize gastric signal without substantially affecting the reliability of organ quantification.
Phenotypic Findings Associated with Variation in Elastin
Authors: Justice Anne , Kelly Melissa A. , Bellus Gary , Green Joshua D. , Zaidi Raza , Kerrins Taylor , Josyula Navya , Luperchio Teresa R. , Kozel Beth A. , Williams Marc S. 
Published: September 2024

AbstractVariation in the elastin gene (ELN) may contribute to connective tissue disease beyond the known disease associations of Supravalvar Aortic Stenosis and Cutis Laxa. Exome data from MyCode Community Health Initiative participants were analyzed forELNrare variants (mean allele frequency <1%, not currently annotated as benign). Participants with variants of interest underwent phenotyping by dual chart review using a standardized abstraction tool. Additionally, all rare variants that met inclusion criteria were collapsed into anELNgene burden score to perform a Phenome-wide Association Study (PheWAS). Two hundred and ninety-six eligible participants with relevantELNvariants were identified from 184,293 MyCode participants. One hundred and three of 254 living participants (41%) met phenotypic criteria, most commonly aortic hypoplasia, arterial dilation, aneurysm, and dissection, and connective tissue abnormalities.ELNvariation was significantly (P <2.8×10−5) associated with “arterial dissection” in the PheWAS and two connective tissue Phecodes approached significance. Variation inELNis associated with connective tissue pathology beyond classic phenotypes.eTOC BlurbCarriers of variants of interest in the elastin gene (ELN) were evaluated for presence of findings that could be associated with the variation. Chart review and Phenome-wide Association Studies were used. Results are consistent with variation inELNbeing associated with findings affecting elastic tissues beyond classic phenotypes.
EFFECTS OF LIFESTYLE ACTIVITY LEVEL ON ANTICIPATORY LOCOMOTOR ADJUSTMENTS FOR PEDESTRIAN CIRCUMVENTION
Authors: Boulo Joris , Simon Margaux , McFadyen Bradford J. , Blanchette Andreanne K. 
Published: September 2024

AbstractNavigating public environments requires adjustments to one’s walking patterns to avoid stationary and moving obstacles. It is known that physical inactivity induces alterations in motor capacities, but the impact of inactivity on anticipatory locomotor adjustments (ALA) has not been studied. The purpose of the present study was to compare ALAs and related muscle co-contraction during a pedestrian circumvention task between active (AA) and inactive young adults (IA). Thirteen AA and thirteen IA were placed in a virtual environment simulating a public park. Participants circumvented virtual pedestrians walking towards them. Walking speed, onset of deviation, clearance, foot placement strategies and muscle co-contraction were analysed. IA exhibited slower walking speeds compared to the AA during circumvention condition but not during unobstructed walking condition. The distance at the onset of trajectory deviation was larger for IA. Both groups increased co-contraction for pedestrian circumvention at the ankle and left hip and IA displayed greater ankle co-contraction overall. No significant group differences were observed in minimum clearance. This study suggests that an inactive lifestyle influences ALAs by inducing a cautious behavior during pedestrian circumvention.
Network biology and bioinformatics-based framework to identify the impacts of SARS-CoV-2 infections on lung cancer and tuberculosis
Authors: Waaje Abdul , Sarkar Md Sumon , Islam Md Zahidul 
Published: September 2024

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a coronavirus variation responsible for COVID-19, the respiratory disease that triggered the COVID-19 pandemic. The primary aim of our study is to elucidate the complex network of interactions between SARS-CoV-2, tuberculosis, and lung cancer employing a bioinformatics and network biology approach. Lung cancer is the leading cause of significant illness and death connected to cancer worldwide. Tuberculosis (TB) is a prevalent medical condition induced by the Mycobacterium bacteria. It mostly affects the lungs but may also have an influence on other areas of the body. Coronavirus disease (COVID-19) causes a risk of respiratory complications between lung cancer and tuberculosis. SARS-CoV-2 impacts the lower respiratory system and causes severe pneumonia, which can significantly increase the mortality risk in individuals with lung cancer. We conducted transcriptome analysis to determine molecular biomarkers and common pathways in lung cancer, TB, and COVID-19, which provide understanding into the association of SARS-CoV-2 to lung cancer and tuberculosis. Based on the compatible RNA-seq data, our research employed GREIN and NCBI’s Gene Expression Omnibus (GEO) to perform differential gene expression analysis. Our study exploited three RNA-seq datasets from the Gene Expression Omnibus (GEO)—GSE171110, GSE89403, and GSE81089—to identify distinct relationships between differentially expressed genes (DEGs) in SARS-CoV-2, tuberculosis, and lung cancer. We identified 30 common genes among SARS-CoV-2, tuberculosis, and lung cancer (25 upregulated genes and 5 downregulated genes). We analyzed the following five databases: WikiPathway, KEGG, Bio Carta, Elsevier Pathway and Reactome. Using Cytohubba’s MCC and Degree methods, We determined the top 15 hub genes resulting from the PPI interaction. These hub genes can serve as potential biomarkers, leading to novel treatment strategies for disorders under investigation. Transcription factors (TFs) and microRNAs (miRNAs) were identified as the molecules that control the differentially expressed genes (DEGs) of interest, either during transcription or after transcription. We identified 35 prospective therapeutic compounds that form significant differentially expressed genes (DEGs) in SARS-CoV-2, lung cancer, and tuberculosis, which could potentially serve as medications. We hypothesized that the potential medications that emerged from this investigation may have therapeutic benefits.
Rapamycin alters the feeding preference for amino acids and sugar in femaleDrosophila
Authors: Yu Guixiang , Yang Qihao , Wu Qi 
Published: September 2024

AbstractPharmacological interventions targeting the aging process hold significant promise for improving the quality of life in the elderly and reducing healthcare costs. Rapamycin, in particular, has exhibited significant anti-aging and lifespan-extending effects across multiple model organisms. However, chronic rapamycin administration may also lead to various adverse reactions since it reshapes energy metabolism. Here, usingDrosophila melanogasteras a model, we show that life-prolonging doses of rapamycin significantly modify animal feeding behavior. Long-term administration of rapamycin decreased protein preference in females while enhancing their sugar intake. Utilizing a chemically defined diet, we identified that changes in amino acid and sugar feeding preferences emerged as early as the second day of rapamycin treatment, preceding any detectable decline in fecundity. However, rapamycin-induced changes in macronutrient feeding preferences were not observed in males and sterile mutant females. Overall, our study suggests that the modification of feeding behavior could be a non-negligible side effect of rapamycin treatment, which is influenced by both sex and reproductive status.
Genetic deletion of NAPE-PLD induces context-dependent dysregulation of anxiety-like behaviors, stress responsiveness, and HPA-axis functionality in mice
Authors: Woodward Taylor J. , Dimen Diana , Sizemore Emily Fender , Stockman Sarah , Kazi Fezaan , Luquet Serge , Mackie Ken , Katona Istvan , Hohmann Andrea G. 
Published: September 2024

AbstractThe endocannabinoid (eCB) system regulates stress responsiveness and hypothalamic-pituitary-adrenal (HPA) axis activity. The enzymeN-acyl phosphatidylethanolamine phospholipase-D (NAPE-PLD) is primarily responsible for the synthesis of the endocannabinoid signaling molecule anandamide (AEA) and other structurally related lipid signaling molecules known asN-acylethanolamines (NAEs). However, little is known about how activity of this enzyme affects behavior. As AEA plays a regulatory role in stress adaptation, we hypothesized that reducing synthesis of AEA and other NAEs would dysregulate stress reactivity. To test this hypothesis, we evaluated wild type (WT) and NAPE-PLD knockout (KO) mice in behavioral assays that assess stress responsiveness and anxiety-like behavior. NAPE-PLD KO mice exhibited anxiety-like behaviors in the open field test and the light-dark box test after a period of single housing. NAPE-PLD KO mice exhibited a heightened freezing response to the testing environment that was further enhanced by exposure to 2,3,5-trimethyl-3-thiazoline (TMT) predator odor. NAPE-PLD KO mice exhibited an exaggerated freezing response at baseline but blunted response to TMT when compared to WT mice. NAPE-PLD KO mice also exhibited a context-dependent dysregulation of HPA axis in response to TMT in the paraventricular hypothalamic nucleus at a neuronal level, as measured by c-Fos immunohistochemstry. Male, but not female, NAPE-PLD knockout mice showed higher levels of circulating corticosterone relative to same-sex wildtype mice in response to TMT exposure, suggesting a sexually-dimorphic dysregulation of the HPA axis at the hormonal level. Together, these findings suggest the enzymatic activity of NAPE-PLD regulates emotional resilience and recovery from both acute and sustained stress.Significance StatementThe endocannabinoid anandamide (AEA) regulates stress responsiveness and activity of the hypothalamic-pituitary-adrenal (HPA) axis. Currently, little is known about how an enzyme (i.e.N-acylphosphatidylethanolamine phospholipase-D (NAPE-PLD)) involved in thesynthesisof AEA affects behavior. We hypothesized that genetic deletion of NAPE-PLD would dysregulate responsiveness to stress at a behavioral and neuronal level. Our studies provide insight into potential vulnerabilities to stress and anxiety that may result from dysregulation of the enzyme NAPE-PLD in people.
Identification of 16 novel Alzheimer’s disease susceptibility loci using multi-ancestry meta-analyses of clinical Alzheimer’s disease and AD-by-proxy cases from four whole genome sequencing datasets
Authors: Willett Julian Daniel Sunday , Waqas Mohammad , Choi Younjung , Ngai Tiffany , Mullin Kristina , Tanzi Rudolph E. , Prokopenko Dmitry 
Published: September 2024

AbstractAlzheimer’s disease (AD) is the most prevalent form of dementia. While many AD-associated genetic determinants have been previously identified, few studies have analyzed individuals of non-European ancestry. Here, we describe a multi-ancestry genome-wide association study of clinically-diagnosed AD and AD-by-proxy using whole genome sequencing data from NIAGADS, NIMH, UKB, and All of Us (AoU) consisting of 49,149 cases (12,074 clinically-diagnosed and 37,075 AD-by-proxy) and 383,225 controls. Nearly half of NIAGADS and AoU participants are of non-European ancestry. For clinically-diagnosed AD, we identified 14 new loci - five common (FBN2,/SCL27A6, AC090115.1, DYM, KCNG1/AL121785.1, TIAM1) and nine rare (VWA5B1, RNU6-755P/LMX1A, MOB1A, MORC1-AS1, LINC00989, PDE4D, RNU2-49P/CDO1, NEO1,andSLC35G3/AC022916.1). Meta-analysis of UKB and AoU AD-by-proxy cases yielded two new rare loci (RPL23/LASP1andCEBPA/AC008738.6) which were also nominally significant in NIAGADS. In summary, we provide evidence for 16 novel AD loci and advocate for more studies using WGS-based GWAS of diverse cohorts.
Impact of Respiratory Syncytial Virus (RSV) in adults 60 years and older in Spain
Authors: Jimeno S. , Peláez A. , Calle Á. , Villarreal M. , Natalini S. 
Published: September 2024

AbstractRespiratory illnesses frequently lead to hospitalisation in adults aged 60 and older, especially due to respiratory virus infectious (RVIs). This study investigates hospitalisation patterns and characteristics of RVIs at HM Hospitals from October 2023 to March 2024.We retrospectively explored hospitalisations of patients aged 60 years and older with RVIs, gathering data on demographics, clinical profiles, comorbidities, and treatments. Outcomes included hospitalisation, ICU admissions, and mortality, independent factors associated with outcomes were identified using a multi-state model.From October 2023 to March 2024, from a total of 3,258 hospitalisation, 1,933 (59.3%) were identified as positive for RVIs. Overall, SARS-CoV-2 was the most prevalent (52.6%), followed by influenza (32.7%) and RSV (11.8%). Most RVIs involved single infections (88.2%). Hospitalisation rates increased with age for SARS-CoV-2, influenza, and RSV, with SARS-CoV-2 showing the highest rate, followed by influenza and RSV.In the multi-state model, RSV infection significantly increased ICU admission risk (HR: 2.1, 95%,p= 0.037). Age on admission (HR: 1.1, 95%, p < 0.001) and Charlson score (HR: 1.4, 95%,p= 0.001) were associated with transitioning from admission to death. ICU to death risks included age at admission (HR: 1.7, 95%,p< 0.001).RVIs in adults 60 years and older are associated with high hospitalisation and mortality rates, primarily driven by influenza and SARS-CoV-2, followed by RSV. Age and comorbidities significantly impact disease severity, emphasising the need for targeted prevention and management strategies for RSV in this vulnerable population.FundingThis studio received no funding.
WearGait-PD: An Open-Access Wearables Dataset for Gait in Parkinson’s Disease and Age-Matched Controls
Authors: Anderson Anthony J. , Eguren David , Gonzalez Michael A. , Khan Naima , Watkinson Sophia , Caiola Michael , Hirczy Siegfried S , Zabetian Cyrus P. , Mills Kelly , Moukheiber Emile , Moro-Velazquez Laureano , Dehak Najim , Motely Chelsie , Muir Brittney C. , Butala Ankur , Kontson Kimberly 
Published: September 2024

AbstractWearable movement sensors are powerful tools for objectively characterizing and quantifying movement. They enhance the precise characterization of gait, balance, and motor symptoms in Parkinson’s disease and related disorders, facilitating in-clinic and remote assessments, disease management, and therapeutic intervention development. Access to high-quality data from these sensors can accelerate discoveries in this clinical population. The WearGait-PD open-access dataset contains raw inertial measurement unit (IMU) and sensorized insole data from individuals with PD and age-matched controls, synchronized to a gait walkway reference system. IMU data include 3-degree of freedom (DOF) acceleration, rotational velocity, magnetic field strength, and orientation for each of 13 sensors on the participant’s body. Sensor insole data include absolute pressure from 16 sensors in each insole and 3-DOF acceleration and rotational velocity. Walkway data include 2D position and relative pressure for each active sensor during every footfall. Frame-by-frame annotation of participant actions during gait and balance tasks was incorporated using synchronized video cameras. All data were associated with demographic information and clinical evaluations (e.g., medications, DBS-status, MDS-UPDRS scores).
Effect of Fathers in Preemie Prep for Parents (P3) Program on Couple’s Preterm Birth Preparedness
Authors: Basir Mir A. , McDonnell Siobhan M. , Brazauskas Ruta , Kim U. Olivia , Ahamed S. Iqbal , McIntosh Jennifer J. , Pizur-Barnekow Kris , Pitt Michael B. , Kruper Abbey , Leuthner Steven R. , Flynn Kathryn E. 
Published: September 2024

ABSTRACTObjectiveEvaluate the effect of fathers’ participation in the Preemie Prep for Parents (P3) program on maternal learning and fathers’ preterm birth knowledge.MethodsMothers with preterm birth predisposing medical condition(s) enrolled with or without the baby’s father and were randomized to the P3 intervention (text-messages linking to animated videos) or control (patient education webpages). Parent Prematurity Knowledge Questionnaire assessed knowledge, including unmarried fathers’ legal neonatal decision-making ability.Results104 mothers reported living with the baby’s father; 50 participated with the father and 54 participated alone. In the P3 group, mothers participating with the father (n=33) had greater knowledge than mothers participating alone (n=21), 85% correct responses vs. 76%,p=0.033. However, there was no difference in knowledge among the control mothers, 67% vs. 60%,p=0.068. P3 fathers (n=33) knowledge scores were not different than control fathers (n=17), 77% vs. 68%,p=0.054. Parents who viewed the video on fathers’ rights (n=58) were more likely than those who did not (n=96) to know unmarried fathers’ legal inability to decide neonatal treatments, 84% vs. 41%,p<0.001.ConclusionsAmong opposite-sex cohabitating couples, fathers’ participation in the P3 program enhanced maternal learning.Practice ImplicationsThe P3 program’s potential to educate fathers may benefit high-risk pregnancies.
A survey of Large Language Model use in a hospital, research, and teaching campus
Authors: Gasparini Loretta , Phillipson Nitya , Capurro Daniel , Rosenberg Revital , Buttery Jim , Howley Jayne , Ranganathan Sarath , Quinlan Catherine , Selvadurai Niloufer , Wildenauer Michael , South Michael , Dimaguila Gerardo Luis 
Published: September 2024

AbstractBackgroundThe use of Large Language Models (LLMs) has exploded since November 2022 but there is sparse evidence regarding LLM use in health, medical and research contexts.ObjectiveTo summarise the current uses of and attitudes towards LLMs across the clinical, research and teaching contexts in our campus.DesignWe administered a survey about LLM uses and attitudes. We conducted summary quantitative analysis and inductive qualitative analysis of free text responses.SettingIn August-September 2023, we circulated the survey amongst all staff and students across our campus (approximately n=7500), a fully integrated paediatric academic hospital and research institute.ParticipantsWe received 281 anonymous survey responses.Main outcome measuresWe asked about participants’ knowledge of LLMs, their current use of LLMs in professional or learning contexts, and perspectives on possible future uses, opportunities, and risks of LLM use.ResultsOver 90% of respondents have heard of LLM tools and about two-thirds have used them in their work on our campus. Respondents reported using LLMs for a range of uses, including for generating or editing text and exploring ideas. Many, but not necessarily all, respondents seem aware of the limitations and potential risks of LLMs, including privacy and security risks. Various respondents expressed enthusiasm about opportunities of LLM use, including increased efficiency.ConclusionsOur findings show LLM tools are already widely used on our campus. Guidelines and governance are needed to keep up with practice. We have developed recommendations for the use of LLMs on our campus using insights from this survey.What is knownThe known:The use of Large Language Models (LLMs) has increased rapidly since the introduction of ChatGPT in November 2022.The new:Most survey respondents are aware of, if not using, LLMs in their work across our hospital, research, and university campus. Diverse uses were reported, including generating or editing text and exploring ideas. There were varying attitudes towards LLMs. Perceived risks included privacy and security risks. A key perceived opportunity was increased efficiency.The implications:LLM tools are already widely used on our campus, highlighting the need for guidelines and governance to keep up with practice.