bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced network synchronization connectivity following transcranial direct current stimulation (tDCS) in bipolar depression: effects on EEG oscillations and deep learning-based predictors of clinical remission
Authors: Xiao Wenyi , Moncy Jijomon C. , Ghazi-Noori Ali-Reza , Woodham Rachel D. , Rezaei Hakimeh , Bramon Elvira , Ritter Philipp , Bauer Michael , Young Allan H. , Fu Cynthia H.Y. 
Published: April 2024

AbstractAimTo investigate oscillatory networks in bipolar depression, effects of a home-based tDCS treatment protocol, and potential predictors of clinical response.Methods20 participants (14 women) with bipolar disorder, mean age 50.75 ± 10.46 years, in a depressive episode of severe severity (mean Montgomery-Åsberg Rating Scale (MADRS) score 24.60 ± 2.87) received home-based transcranial direct current stimulation (tDCS) treatment for 6 weeks. Clinical remission defined as MADRS score < 10. Resting-state EEG data were acquired at baseline, prior to the start of treatment, and at the end of treatment, using a portable 4-channel EEG device (electrode positions: AF7, AF8, TP9, TP10). EEG band power was extracted for each electrode and phase locking value (PLV) was computed as a functional connectivity measure of phase synchronization. Deep learning was applied to pre-treatment PLV features to examine potential predictors of clinical remission.ResultsFollowing treatment, 11 participants (9 women) attained clinical remission. A significant positive correlation was observed with improvements in depressive symptoms and delta band PLV in frontal and temporoparietal regional channel pairs. An interaction effect in network synchronisation was observed in beta band PLV in temporoparietal regions, in which participants who attained clinical remission showed increased synchronisation following tDCS treatment, which was decreased in participants who did not achieve clinical remission. Main effects of clinical remission status were observed in several PLV bands: clinical remission following tDCS treatment was associated with increased PLV in frontal and temporal regions and in several frequency bands, including delta, theta, alpha and beta, as compared to participants who did not achieve clinical remission. The highest deep learning prediction accuracy 69.45% (sensitivity 71.68%, specificity 66.72%) was obtained from PLV features combined from theta, beta, and gamma bands.ConclusionstDCS treatment enhances network synchronisation, potentially increasing inhibitory control, which underscores improvement in depressive symptoms. Baseline EEG-based measures might aid predicting clinical response.
Short-term stability of diluted treprostinil sodium for subcutaneous administration
Authors: Sketch Margaret R. , Sauerstrom Daniel , Lange Allison Marie , Diehl Jane Hall 
Published: April 2024

AbstractBackgroundThe Remunity Pump for Remodulin (treprostinil) Injection is an infusion system indicated for use with subcutaneous treprostinil.ObjectiveThe objective was to assess the stability of diluted treprostinil sodium stored in Remunity pump cassettes.MethodsTreprostinil’s chemical and physical stability were assessed over a 76-hour period at 40 degrees Celsius and 75% relative humidity after dilution to 0.01 mg/mL in sterile water for injection and 0.9% sodium chloride. Analyses were conducted via visual inspection, pH measurement, and a stability-indicating high-performance liquid chromatographic assay.ResultsAt all time points, the treprostinil samples were consistently clear, colorless, and free of visible particulate matter, with pH levels 6.0-7.0. All assays were within 90.0%-110.0% of the label claim, with minimal variation.ConclusionsTreprostinil diluted to 0.01 mg/mL was stable in Remunity pump cassettes for up to 76 hours at elevated temperature and humidity. No notable changes from label claim concentration values were observed.
Accurate cross-platform GWAS analysis via two-stage imputation
Authors: Greenberg Anya , Reynolds Kaylia , McNulty Michelle T. , Sampson Matthew G. , Kang Hyun Min , Lee Dongwon 
Published: April 2024

AbstractIn genome-wide association studies (GWAS), combining independent case-control cohorts has been successful in increasing power for meta and joint analyses. This success sparked interest in extending this strategy to GWAS of rare and common diseases using existing cases and external controls. However, heterogeneous genotyping data can cause spurious results. To harmonize data, we propose a new method, two-stage imputation (TSIM), where cohorts are imputed separately, merged on intersecting high-quality variants, and imputed again. We show that TSIM minimizes cohort-specific bias while controlling imputation-derived errors. Merging arthritis cases and UK Biobank controls using TSIM, we replicated known associations without introducing false positives. Furthermore, GWAS using TSIM performed comparably to the meta-analysis of nephrotic syndrome cohorts genotyped on five different platforms, demonstrating TSIM’s ability to harmonize heterogeneous genotyping data. With the plethora of publicly available genotypes, TSIM provides a GWAS framework that harmonizes heterogeneous data, enabling analysis of small and case-only cohorts.
Predictive Modeling and Deep Phenotyping of Obstructive Sleep Apnea and Associated Comorbidities through Natural Language Processing and Large Language Models
Authors: Ahmed Awwal , Rispoli Anthony , Wasieloski Carrie , Khurram Ifrah , Zamora-Resendiz Rafael , Morrow Destinee , Dong Aijuan , Crivelli Silvia 
Published: April 2024

AbstractObstructive Sleep Apnea (OSA) is a prevalent sleep disorder associated with serious health conditions. This project utilized large language models (LLMs) to develop lexicons for OSA sub-phenotypes. Our study found that LLMs can identify informative lexicons for OSA sub-phenotyping in simple patient cohorts, achieving wAUC scores of 0.9 or slightly higher. Among the six models studied, BioClinical BERT and BlueBERT outperformed the rest. Additionally, the developed lexicons exhibited some utility in predicting mortality risk (wAUC score of 0.86) and hospital readmission (wAUC score of 0.72). This work demonstrates the potential benefits of incorporating LLMs into healthcare.Data and Code AvailabilityThis paper uses the MIMIC-IV dataset (Johnson et al., 2023a), which is available on the PhysioNet repository (Johnson et al., 2023b). We plan to make the source code publicly available in the future.Institutional Review Board (IRB)This research does not require IRB approval.
The role of pulmonary metastasectomy (PM) for non-primary lung cancer: Umbrella review of meta-analyses
Authors: Woo Wongi , Park Brandon , Ahadi Awranoos , Chung Liam il-young , Jung Chan Mi , Bharat Ankit , Chae Young Kwang 
Published: April 2024

AbstractIntroductionDue to heterogeneous characteristics of primary cancers, the efficacy of pulmonary metastasectomy(PM) in non-primary lung cancers has not been investigated other than colorectal cancers. This study aims to investigate the clinical outcomes of PM for non-primary lung cancer.MethodsA systematic search for meta-analyses on PM for non-primary lung cancers was conducted, encompassing publications up to January 3, 2024. The analysis included seven primary cancer types: renal cell, breast, adrenocortical, head and neck cancers, melanoma, germ cell tumors, and sarcoma. Primary outcomes, overall survival, and recurrence rates post-PM were assessed using random-effect models to account for study heterogeneity.ResultsThis study included 16 systematic-review articles and 101 individual studies, involving 10,277 patients who underwent PM for non-primary lung cancer. Patients had a mean age of 48.0 years, with 68.4% being male. About half of the patients(47.1% [95%CI 40.8-53.5] presented with multiple metastatic lesions, and complete R0 resection achieved in 87.2% [95%CI 83.0-90.8]. The pooled 5-year overall survival (OS) rate post-PM was 41.2% [95%CI, 37.1-45.4%]. Patients with germ cell tumors demonstrated significantly higher survival rate than other cancers(p<0.05), while patients with melanoma exhibited the poorest outcome(p<0.05). During follow-up, 57.6%[95%CI 46.4-68.1] had recurrence; 48% of them had intrathoracic-only recurrence and 52% had extra-thoracic recurrence.ConclusionThis study underscores the survival benefits associated with PM. Overall survival rates following PM do not significantly differ based on primary cancer types, except for germ cell tumors and melanoma. These findings highlight the importance of recognizing and incorporating PM into clinical practice when appropriate.SynopsisSurgical resection for pulmonary metastasis from cancers other than lung cancer still holds a significant role in improving a patient’s prognosis. Though the recurrence rate is high, it could improve the chance of survival regardless of the primary cancer types.
Comparative gene regulatory networks modulatingAPOEexpression in microglia and astrocytes
Authors: Brase Logan , Yu Yanbo , McDade Eric ,   Dominantly Inherited Alzheimer Network (DIAN), Harari Oscar , Benitez Bruno A. 
Published: April 2024

AbstractBackgroundSingle-cell technologies have unveiled various transcriptional states in different brain cell types. Transcription factors (TFs) regulate the expression of related gene sets, thereby controlling these diverse expression states. Apolipoprotein E (APOE), a pivotal risk-modifying gene in Alzheimer’s disease (AD), is expressed in specific glial transcriptional states associated with AD. However, it is still unknown whether the upstream regulatory programs that modulate its expression are shared across brain cell types or specific to microglia and astrocytes.MethodsWe used pySCENIC to construct state-specific gene regulatory networks (GRNs) for resting and activated cell states within microglia and astrocytes based on single-nucleus RNA sequencing data from AD patients’ cortices from the Knight ADRC-DIAN cohort. We then identified replicating TF using data from the ROSMAP cohort. We identified sets of genes co-regulated withAPOEby clustering the GRN target genes and identifying genes differentially expressed after the virtual knockout of TFs regulatingAPOE. We performed enrichment analyses on these gene sets and evaluated their overlap with genes found in AD GWAS loci.ResultsWe identified an average of 96 replicating regulators for each microglial and astrocyte cell state. Our analysis identified the CEBP, JUN, FOS, and FOXO TF families as key regulators of microglial APOE expression. The steroid/thyroid hormone receptor families, including the THR TF family, consistently regulated APOE across astrocyte states, while CEBP and JUN TF families were also involved in resting astrocytes. AD GWAS-associated genes (PGRN,FCGR3A,CTSH,ABCA1,MARCKS,CTSB,SQSTM1,TSC22D4,FCER1G, and HLA genes) are co-regulated with APOE. We also uncovered that APOE-regulating TFs were linked to circadian rhythm (BHLHE40,DBP,XBP1,CREM,SREBF1,FOXO3, andNR2F1).ConclusionsOur findings reveal a novel perspective on the transcriptional regulation ofAPOEin the human brain. We found a comprehensive and cell-type-specific regulatory landscape forAPOE, revealing distinct and shared regulatory mechanisms across microglia and astrocytes, underscoring the complexity ofAPOEregulation.APOE-co-regulated genes might also affect AD risk. Furthermore, our study uncovers a potential link between circadian rhythm disruption andAPOEregulation, shedding new light on the pathogenesis of AD.
Quantitative Magnetic Resonance Cerebral Spinal Fluid Flow Properties and Executive Function Cognitive Outcomes in Congenital Heart Disease
Authors: Lee Vincent Kyu , Reynolds William T. , Wallace Julia , Beluk Nancy , Badaly Daryaneh , Lo Cecilia W , Ceschin Rafael , Panigrahy Ashok 
Published: April 2024

ABSTRACTCerebrospinal fluid (CSF) circulation has recently been shown to be important in nutrient distribution, waste removal, and neurogenesis. Increased CSF volumes are frequently observed in congenital heart disease (CHD) and are associated with neurodevelopmental deficits. This suggests prolonged perturbation to the CSF system and possible interference to its homeostatic function, which may contribute to the neurodevelopmental deficits in CHD. CSF flow has yet to be studied in CHD patients, but the pulsatile flow of CSF throughout the brain is driven mainly by cardiopulmonary circulation. Given the underlying heart defects in CHD, the cardiopulmonary circulatory mechanisms in CHD might be impaired with resultant perturbation on the CSF circulation. In this study, we determine whether CSF flow, using MRI measurements of static and dynamic pulsatile flow, is abnormal in youths with CHD compared to healthy controls in relation to executive cognitive function. CSF flow measurements were obtained on a total of 58 child and young adult participants (CHD=20, healthy controls = 38). The CSF flow was measured across the lumen of the Aqueduct of Sylvius using cardiac-gated phase-contrast MRI at 3.0T. Static pulsatility was characterized as anterograde and retrograde peak velocities, mean velocity, velocity variance measurements, and dynamic pulsatility calculated as each participant’s CSF flow deviation from the study cohort’s consensus flow measured with root mean squared deviation (RMSD) were obtained. The participants had neurocognitive assessments for executive function with focus on inhibition, cognitive flexibility, and working memory domains. The CHD group demonstrated greater dynamic pulsatility (higher overall flow RMSD over the entire CSF flow cycle) compared to controls (p=0.0353), with no difference detected in static pulsatility measures. However, lower static CSF flow pulsatility (anterograde peak velocity: p=0.0323) and lower dynamic CSF flow pulsatility (RMSD: p=0.0181) predicted poor inhibitory executive function outcome. Taken together, while the whole CHD group exhibited higher dynamic CSF flow pulsatility compared to controls, the subset of CHD subjects with relatively reduced static and dynamic CSF flow pulsatility had the worst executive functioning, specifically the inhibition domain. These findings suggest that altered CSF flow pulsatility may be central to not only brain compensatory mechanisms but can also drive cognitive impairment in CHD. Further studies are needed to investigate possible mechanistic etiologies of aberrant CSF pulsatility (i.e. primary cardiac hemodynamic disturbances, intrinsic brain vascular stiffness, altered visco-elastic properties of tissue, or glial-lymphatic disturbances), which can result in acquired small vessel brain injury (including microbleeds and white matter hyperintensities).
Safety of balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: role of the standardized definition of complications
Authors: van Leusden F.J. , Staal D.P. , van Thor M.C.J. , Rensing B.J.M.W. , van Kuijk J.P. , Mulder B.J.M. , van den Heuvel D. , Boerman S. , Boomars K.A. , Peper J. , Mager J.J. , Post M.C. 
Published: April 2024

AbstractLiterature reports high complication rates in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who undergo balloon pulmonary angioplasty (BPA), especially in patients with poor pulmonary hemodynamics. Here we describe complications of BPA based on the new definitions.All patients with CTEPH who completed BPA treatment before September 15th, 2023, were selected from the CTEPH database. Peri-procedural complications were collected and classified according to the 2023 consensus paper on BPA treatment. Complications were analyzed in subgroups of patients with pulmonary vascular resistance (PVR) ≤ or > 6.6 WU and mean pulmonary artery pressure (mPAP) ≤ or > 45 mmHg at first BPA.In this analysis, 87 patients (63% women; mean age 61.1±14.0 years; 62% on dual PH targeted medical therapy) underwent 426 (mean 4.9±1.6 per patient) BPAs. Only non-severe complications occurred in 14% of BPA treatments; in 47% of the patients; 31% patients had a thoracic complication. The thoracic complications were mild (71%) or moderate (29%). Patients with a PVR >6.6 WU (n=8) underwent more BPA treatments (6.6±1.5 versus 4.6±1.5, p=0.002), had more complications (88% versus 41% of patients, p=0.020), and more thoracic complications (17% vs 7% of BPAs, p=0.013) than patients with PVR ≤6.6 WU. Patients with mPAP >45 mmHg (n=13) also had more BPA-treatments (6.5±1.7 versus 4.6±1.4, p<0.001), more complications (77% versus 44% of patients, p=0.027) and more thoracic complications (14% versus 8% of BPAs, p=0.039) than patients with mPAP ≤45 mmHg.Complications occurred in 14% of BPAs and were mostly mild. Patients with severe pulmonary hemodynamics suffered more (thoracic) complications.What is known?BPA is an effective treatment in improving pulmonary hemodynamics in patients with CTEPH.BPAs are associated with a high complication rate.In 2023 a consensus statement was published concerning the definition of complications of BPAs.Patients with poor pulmonary hemodynamics may be more susceptible to suffer from complications.What does this study add?For the first time, complications are categorized according to the consensus statement on BPA treatments in patients with CTEPH.Thoracic complication rates in patients with severe pulmonary hemodynamics are significantly higher compared to complication rates in patients with lower pulmonary hemodynamic values.
Aurodox, a polyketide fromStreptomyces goldiniensis, inhibits transcription of the type III secretion system of multiple Gram-negative pathogens
Authors: Mark David , O’Boyle Nicky , Wale Kabo R , Tucker Samantha K , McHugh Rebecca E , Roe Andrew J 
Published: April 2024

AbstractGram-negative pathogens pose a significant threat due to their propensity for causing various infections, often coupled with formidable resistance to conventional antibiotic treatments. In light of this challenge, the development of antivirulence (AV) compounds emerges as a promising alternative strategy, aiming to disrupt key virulence mechanisms rather than directly targeting bacterial viability. One such compound, aurodox, derived fromStreptomyces goldiniensis, has exhibited promising AV properties in our prior studies. Specifically, aurodox caused a marked downregulation in the expression and function of theE. colitype 3 secretion system (T3SS), a needle-like injectosome structure which is deployed to translocate effector proteins from the cytoplasm to the host target cells.However, the broader spectrum of aurodox’s efficacy against T3SS across diverse pathogens remained unanswered, prompting the focus of this work. Using quantitative real-time PCR, we show that aurodox exerts inhibitory effects on selected T3SS in various pathogens, including Salmonella typhimurium,Yersinia pseudotuberculosis, andVibrio parahaemolyticus. However, aurodox was not a universal blocker of all secretion systems, showing selectivity in its mode-of-action, even within a single strain. This finding was verified using transcriptomics which demonstrated that aurodox selectively blocks the expression of the Salmonella typhimurium SPI-2 type T3SS whilst other pathogenicity islands, including the SPI-1 system were not inhibited. To delve deeper into the mechanisms governing aurodox’s efficacy against these pathogens, we analysed transcriptomic datasets from bothE. coliand S. Typhimurium treated with aurodox. By identifying orthologous genes exhibiting differential expression in response to aurodox treatment across these pathogens, our study sheds light on the potential mechanisms underlying the action of this rediscovered antibiotic.
A delta-tubulin/epsilon-tubulin/Ted protein complex is required for centriole architecture
Authors: Pudlowski Rachel , Xu Lingyi , Milenkovic Ljiljana , Kumar Chandan , Hemsworth Katherine , Aqrabawi Zayd , Stearns Tim , Wang Jennifer T. 
Published: April 2024

AbstractCentrioles have a unique, conserved architecture formed by three linked “triplet” microtubules arranged in nine-fold symmetry. The mechanisms by which these triplet microtubules are formed are not understood and likely involve the noncanonical tubulins delta-tubulin and epsilon-tubulin. Previously, we found that human cells deficient in delta-tubulin or epsilon-tubulin form abnormal centrioles, characterized by an absence of triplet microtubules, lack of central core protein POC5, and a futile cycle of centriole formation and disintegration (Wang et al., 2017). Here, we show that human cells lacking either of the associated proteins TEDC1 and TEDC2 have these same phenotypes. Using ultrastructure expansion microscopy, we find that mutant centrioles elongate to the same length as control centrioles in G2-phase. These mutants fail to recruit inner scaffold proteins of the central core and have an expanded proximal region. During mitosis, the mutant centrioles elongate further before fragmenting and disintegrating. All four proteins physically interact and TEDC1 and TEDC2 are capable forming a subcomplex in the absence of the tubulins. These results support an AlphaFold Multimer model of the tetramer in which delta-tubulin and epsilon-tubulin are predicted to form a heterodimer. TEDC1 and TEDC2 localize to centrosomes and are mutually dependent on each other and on delta-tubulin and epsilon-tubulin for localization. Our results demonstrate that delta-tubulin, epsilon-tubulin, TEDC1, and TEDC2 function together to promote robust centriole architecture. This work also lays the groundwork for future molecular studies of this complex, providing a basis for determining the mechanisms that underlie the assembly and interplay between the triplet microtubules and inner centriole structure.
A conserved genetic basis for commensal-host specificity through live imaging of colonization dynamics
Authors: Gutiérrez-García Karina , Aumiller Kevin , Dodge Ren , Obadia Benjamin , Deng Ann , Agrawal Sneha , Yuan Xincheng , Wolff Richard , Garud Nandita , Ludington William B 
Published: April 2024

AbstractAnimals throughout the metazoa selectively acquire specific symbiotic gut bacteria from their environment that aid host fitness. Current models of colonization suggest these bacteria use weakly specific receptors to stick to host tissues and that colonization results when they stick in a region of the host gut that overlaps with their nutritional niche. An alternative model is that unique receptor-ligand binding interactions provide specificity for target niches. Here we use live imaging of individual symbiotic bacterial cells colonizing the gut of livingDrosophila melanogasterto show thatLactiplantibacillus plantarumspecifically recognizes a distinct physical niche in the host gut. We find that recognition is controlled by a colonization island that is widely conserved in commensals and pathogens from the Lactobacillales to the Clostridia. Our findings indicate a genetic mechanism of host specificity that is broadly conserved.One-Sentence SummaryHost-symbiont specificity is encoded by a conserved colonization island that provides molecular precision to host niche access.