bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transient peripheral blood transcriptomic response to ketamine treatment in children with ADNP syndrome
Authors: Buxbaum Grice Ariela S. , Sloofman Laura , Levy Tess , Walker Hannah , Ganesh Gauri , Rodriguez de los Santos Miguel , Armini Pardis , Buxbaum Joseph D. , Kolevzon Alexander , Kostic Ana , Breen Michael S. 
Published: January 2024

ABSTRACTActivity-dependent neuroprotective protein (ADNP) syndrome is a rare neurodevelopmental disorder resulting in intellectual disability, developmental delay and autism spectrum disorder (ASD) and is due to mutations in theADNPgene. Ketamine treatment has emerged as a promising therapeutic option for ADNP syndrome, showing safety and apparent behavioral improvements in a first open label study. However, the molecular perturbations induced by ketamine remain poorly understood. Here, we investigated the longitudinal effect of ketamine on the blood transcriptome of 10 individuals with ADNP syndrome. Transcriptomic profiling was performed before and at multiple time points after a single low-dose intravenous ketamine infusion (0.5mg/kg). We show that ketamine triggers immediate and profound gene expression alterations, with specific enrichment of monocyte-related expression patterns. These acute alterations encompass diverse signaling pathways and co-expression networks, implicating up-regulation of immune and inflammatory-related processes and down-regulation of RNA processing mechanisms and metabolism. Notably, these changes exhibit a transient nature, returning to baseline levels 24 hours to 1 week after treatment. These findings enhance our understanding of ketamine’s molecular effects and lay the groundwork for further research elucidating its specific cellular and molecular targets. Moreover, they contribute to the development of therapeutic strategies for ADNP syndrome and potentially, ASD more broadly.
Impact of Pre-reperfusion Left Ventricle Unloading on ST-segment-elevation Myocardial Infarction According to the Onset-to-Unloading Time
Authors: Okamoto Naotaka , Egami Yasuyuki , Abe Masaru , Osuga Mizuki , Nohara Hiroaki , Kawanami Shodai , Kawamura Akito , Ukita Kohei , Yasumoto Koji , Tsuda Masaki , Matsunaga-Lee Yasuharu , Yano Masamichi , Nishino Masami ,   J-PVAD investigators
Published: January 2024

AbstractBackgroundImpella in the left ventricle (LV) with delaying reperfusion reduces the infarction size in animal models. However, the onset-to-unloading time in real-world practice can frequently be longer than that in animal experiments. It is unclear whether the impact of pre-reperfusion Impella use is sustained throughout all periods from the onset. This study aimed to evaluate the association between the onset-to-unloading time and the effect of pre-reperfusion Impella on the survival of patients with ST-segment-elevation myocardial infarction (STEMI).MethodsThis study is a post-hoc analysis of the J-PVAD registry. Among all patients registered in J-PVAD between February 2020 and December 2021, patients with STEMI and treated with Impella alone support were selected. Two cohorts were provided based on whether the onset-to-unloading time was less than 6 hours. The patients were divided into two groups according to pre- or post-reperfusion use of Impella in each cohort. The primary outcome was an 80-day survival rate. The independent factors of survival were identified with a multivariable Cox proportional hazard regression analysis after adjusting for the variables that were statistically significant in the univariable analysis.ResultsPatients with pre-reperfusion unloading had a significantly higher 80-day survival rate than patients with post-reperfusion unloading (81.6% vs. 59.5%, p=0.02) in the cohort with an onset-to-unloading time ≥6 hours, while patients with pre- and post-reperfusion unloading had similar 80-day survival rates (85.3% vs. 91.2%, p=0.38) in the cohort with an onset-to-unloading time <6 hours. A multivariable analysis revealed that pre-reperfusion use of Impella was an independent factor of survival (hazard ratio 0.184 [95% confidence interval 0.045-0.746], p=0.02) in the onset-to-unloading time ≥6 hours cohort.ConclusionsPre-reperfusion LV unloading could be a crucial treatment to improve the short-term survival rate when the onset-to-LV unloading was more than 6 hours.
A CRISPR-Nonhomologous End-Joining-based strategy for rapid and efficient gene disruption inMycobacterium abscessus
Authors: Zeng Sanshan , Ju Yanan , Alam Md Shah , Lu Ziwen , Hameed H.M. Adnan , Li Lijie , Tian Xirong , Fang Cuiting , Fang Xiange , Ding Jie , Wang Xinyue , Hu Jinxing , Wang Shuai , Zhang Tianyu 
Published: January 2024

AbstractMycobacterium abscessus, a fast-growing, non-tuberculous mycobacterium resistant to most antimicrobial drugs, causes many types of serious infections in humans, posing a significant public health challenge. Currently, effective genetic manipulation tools forM. abscessusare still being developed, which hampers research and therapeutic development. However, the clustered regularly interspaced short palindromic repeats (CRISPR) - associated protein (Cas) systems have emerged as promising methods for generating highly specific double-strand breaks (DSBs) in its genome. These DSBs can be repaired by the error-prone nonhomologous end joining (NHEJ) mechanism, facilitating targeted gene editing. Here, our study marks a pioneering application of the CRISPR-NHEJ strategy inM. abscessus. Additionally, we discovered that NrgA fromMycobacterium marinumis crucial for the repair of DSBs caused by the CRISPR-Cas system inM. abscessus. Finally, contrary to previous findings, our study also indicates that inhibiting or overexpressing homologous recombination/single-strand annealing significantly decreases the efficiency of NHEJ repair inM. abscessus. This discovery challenges established perspectives and suggests that the NHEJ repair inM. abscessusmay require the involvement of components from homologous recombination and single-strand annealing, demonstrating the complex interactions among the three DSB repair pathways inM. abscessus.Impact statementThere are still very few genetic manipulation tools available forMycobacterium abscessus. Here we report the successful application of CRISPR-Cas12a-assisted nonhomologous end joining (NHEJ) in efficient gene editing inM. abscessus. Contrary to previous research suggesting that homologous recombination (HR) inhibition may enhance such editing efficiency in other Mycobacterium species, our results showed that disruption or overexpression of either HR or single-strand annealing not only failed to enhance but also significantly reduced the gene editing efficiency inM. abscessus. This suggests that NHEJ repair inM. abscessusmay require components from both HR and single-strand annealing, highlighting a complex interaction among the DSB repair pathways inM. abscessus.
In-silicoDrug Repurposing Pipeline for Epilepsy: Integrating Deep Learning and Structure-based Approaches
Authors: Lv Xiaoying , Wang Jia , Yuan Ying , Pan Lurong , Guo Jinjiang 
Published: January 2024

AbstractDue to considerable global prevalence and high recurrence rate, the pursuit of effective new medication for epilepsy treatment remains an urgent and significant challenge. Drug repurposing emerges as a cost-effective and efficient strategy to combat this disorder. This study leverages the transformer-based deep learning methods coupled with molecular binding affinity calculation to develop a novelin-silicodrug repurposing pipeline for epilepsy. The number of candidate inhibitors against 24 target proteins encoded by gain-of-function (GOF) genes implicated in epileptogenesis ranged from zero to several hundreds. Our pipeline has repurposed the medications with most anti-epileptic drugs (AEDs) and nearly half psychiatric medications, highlighting the effectiveness of our pipeline. Furthermore, Lomitapide, a cholesterol-lowering drug, first emerged as particularly noteworthy, exhibiting high binding affinity for 10 targets and verified by molecular dynamics (MD) simulation and mechanism analysis. These findings provided a novel perspective on therapeutic strategies for other central nervous system (CNS) disease.
Disease resistance ofBrassica junceatoSclerotinia sclerotiorumis established through the induction of indole glucosinolate biosynthesis
Authors: Zhang Jinze , Yang Xu , Jiang Yingfen , Jin Hairun , Yu Kunjiang , Xiao Lijing , Ouyang Qingjing , Tian Entang 
Published: January 2024

AbstractSclerotinia stem rot (SSR), caused bySclerotinia sclerotiorum, is the main disease threat to oilseeds in Brassiceae, causing significant yield losses and reduction in oil content and quality. The studies onS. sclerotiorumrequire a great focus and extensive research onB. junceacompared to those onB. napusandB. oleracea. Transcriptome analysis revealed a large number of defense-related genes and response processes inB. napusandB. oleracea. However, similarities and differences in the defense responses toS. sclerotiorumonB. junceaare rarely reported. In the present study, we reported aB. junceabreeding line of H83 with highS. sclerotiorumresistance, which was used for transcriptome analysis compared to L36 with low resistance. A novel regulatory network was proposed to defend againstS. sclerotioruminvasion inB. juncea. Upon infection ofS. sclerotiorum, a series of auxin and MAPK signaling pathways were initiated within 12 h, and then defenses were activated to restrict the development and spread ofS. sclerotiorumby inducing the massive synthesis of indole glucosinolates after 24 h. Twelve hub genes involved in the network were identified by the weighted gene co-expression network (WGCNA), which are involved in plant-pathogen interaction, signaling pathway genes, indole glucosinolate biosynthesis and cell wall formation. The hub genes were further validated by qRT-PCR. The research revealed a new resistant line of H83 againstS. sclerotiorumand a different regulatory network inB. juncea, which would be beneficial for the future effective breeding of Sclerotinia-resistant varieties.
The usefulness of Nanopore Sequencing in Whole-Genome Sequencing-Based Genotyping ofListeria monocytogenesandSalmonella entericaserovar Enteritidis
Authors: Hong Yu-Ping , Chen Bo-Han , Wang You-Wun , Teng Ru-Hsiou , Wei Hsiao Lun , Chiou Chien-Shun 
Published: January 2024

ABSTRACTBacterial genotyping through whole-genome sequencing plays a crucial role in disease surveillance and outbreak investigations in public health laboratories. This study assessed the effectiveness of Nanopore Oxford Technologies (ONT) sequencing in the genotyping ofListeria monocytogenesandSalmonella entericaserovar Enteritidis. Our results indicated that ONT sequences, generated with the R10.4.1 flow cell and basecalled using the Dorado 0.5.0 Super Accurate 4.3 model, exhibited comparable accuracy to Illumina sequences, effectively discriminating among bacterial strains from outbreaks. These findings suggest that ONT sequencing has the potential to be a promising tool for rapid whole-genome sequencing of bacterial pathogens in public health laboratories for epidemiological investigations.
In turkeys, unlike chickens, the non-structural NS1 protein does not play a significant role in the replication and tissue tropism of the H7N1 avian influenza virus
Authors: Kuryshko Maryna , Landmann Maria , Luttermann Christine , Ulrich Reiner , Abdelwhab Elsayed M. 
Published: January 2024

AbstractThe economic losses caused by high pathogenicity (HP) avian influenza viruses (AIV) in poultry industry worldwide are enormous. Although chickens and turkeys are two closely related Galliformes, turkeys are thought to be a bridging host for the adaptation of AIV from wild birds to poultry because of their high susceptibility to AIV infections. HPAIV evolve from low pathogenicity (LP) AIV after circulation in poultry through mutations in different viral proteins, including the non-structural protein (NS1), a major interferon (IFN) antagonist of AIV. At present, it is largely unknown whether the virulence determinants of HPAIV are the same in turkeys and chickens. Previously, we showed that mutations in the NS1 of HPAIV H7N1 significantly reduced viral replication in chickens in vitro and in vivo. Here, we investigated the effect of NS1 on the replication and virulence of HPAIV H7N1 in turkeys after inoculation with recombinant H7N1 carrying a naturally truncated wild-type NS1 (with 224 amino-acid “aa” in length) or an extended NS1 with 230-aa similar to the LP H7N1 ancestor. There were no significant differences in multiple-cycle viral replication or in the efficiency of NS1 to block IFN induction in cell culture. Similarly, all viruses were highly virulent in turkeys and replicated at similar levels in various organs and swabs collected from inoculated turkeys. These results suggest that NS1 does not play a role in the virulence or replication of HPAIV H7N1 in turkeys and further indicate that the genetic determinants of HPAIV differ in these two closely related galliform species.
miR-26 deficiency causes alterations in lens transcriptome and results in adult-onset cataract
Authors: Upreti Anil , Hoang Thanh V. , Li Minghua , Tangeman Jared A. , Dierker David S. , Wagner Brad D. , Tsonis Panagiotis A. , Liang Chun , Lachke Salil A. , Robinson Michael L. 
Published: January 2024

AbstractPurposeDespite strong evidence demonstrating that normal lens development requires regulation governed by miRNAs, the functional role of specific miRNAs in mammalian lens development remains largely unexplored.MethodsA comprehensive analysis of miRNA transcripts in the newborn mouse lens, exploring both differential expression between lens epithelial cells and lens fiber cells and overall miRNA abundance was conducted by miRNA-seq. Mouse lenses lacking each of three abundantly expressed lens miRNAs: miR-184, miR-26 and miR-1 were analyzed to explore the role of these miRNAs in lens development.ResultsMice lacking all three copies ofmiR-26(miR-26TKO) developed postnatal cataracts as early as 4-6 weeks of age. RNA-seq analysis of neonatal lenses frommiR-26TKOmice exhibited abnormal reduced expression of a cohort of genes found to be lens-enriched and linked to cataract (e.g. Foxe3,Hsf4,Mip,Tdrd7,and numerous crystallin genes), and abnormal elevated expression of genes related to neural development (Lhx3, Neurod4, Shisa7, Elavl3), inflammation (Ccr1, Tnfrsf12a, Csf2ra), the complement pathway, and epithelial to mesenchymal transition (Tnfrsf1a, Ccl7, Stat3, Cntfr).ConclusionmiR-1, miR-184 and miR-26 are each dispensable for normal embryonic lens development. However, loss of miR-26 causes lens transcriptome changes and drives cataract formation.
Mitochondrial DNA copy number reduction viain vitro TFAMknockout remodels the nuclear epigenome and transcriptome
Authors: Nguyen Julia , Win Phyo W. , Nagano Tyler Shin , Shin Elly H. , Newcomb Charles , Arking Dan E. , Castellani Christina A. 
Published: January 2024

AbstractMitochondrial DNA copy number (mtDNA-CN) is associated with several age-related chronic diseases and is a predictor of all-cause mortality. Here, we examine site-specific differential nuclear DNA (nDNA) methylation and differential gene expression resulting fromin vitroreduction of mtDNA-CN to uncover shared genes and biological pathways mediating the effect of mtDNA-CN on disease. Epigenome and transcriptome profiles were generated for three independent human embryonic kidney (HEK293T) cell lines harbouring a mitochondrial transcription factor A (TFAM) heterozygous knockout generated via CRISPR-Cas9, and matched control lines. We identified 4,242 differentially methylated sites, 228 differentially methylated regions, and 179 differentially expressed genes associated with mtDNA-CN. Integrated analysis uncovered 381 Gene-CpG pairs. GABAAreceptor genes and related pathways, the neuroactive ligand receptor interaction pathway, ABCD1/2 gene activity, and cell signalling processes were overrepresented, providing insight into the underlying biological mechanisms facilitating these associations. We also report evidence implicating chromatin state regulatory mechanisms as modulators of mtDNA-CN effect on gene expression. We demonstrate that mitochondrial DNA variation signals to the nuclear DNA epigenome and transcriptome and may lead to nuclear remodelling relevant to development, aging, and complex disease.
The human claustrum tracks slow waves during sleep
Authors: Lamsam Layton , Liang Mingli , Gu Brett , Sun George , Hirsch Lawrence J. , Pittenger Christopher , Kaye Alfred P. , Krystal John H. , Damisah Eyiyemisi C. 
Published: January 2024

AbstractSlow waves are a distinguishing feature of non-rapid-eye-movement (NREM) sleep, an evolutionarily conserved process critical for brain function. Non-human studies posit that the claustrum, a small subcortical nucleus, coordinates slow waves. We recorded claustrum neurons in humans during sleep. In contrast to neurons from other brain regions, claustrum neurons increased their activity and tracked slow waves during NREM sleep suggesting that the claustrum plays a role in human sleep architecture.
Effects of APOE e4 and Neuropathological Diagnoses on Neuropsychiatric Symptoms: Mediation Analyses and Likely Causation in an Integrated NACC Database
Authors: Goldberg Terry E. , Devanand D.P. , Fang Zhiqian , Kim Hyun , Rueppel Elizabeth , Tucker Aren , Carlson Scott , Lee Seonjoo 
Published: January 2024

AbstractBackgroundOur goal in this study was to identify paths from APOE e4 to neurobehaviors itemized on a neuropsychiatric inventory that involved neuropathologies associated with e4 (amyloid, tau, cerebral amyloid angiopathy, and Lewy bodies) or cognition mediators (memory or global cognitive status), as well as direct paths from e4 to cognition or neurobehaviors.MethodsA total of 1199 cases with available neurobehavioral, cognition and neuropathological data were included. We then conducted a series of causal mediation analyses in R in which e4 always served as the independent variable and Neuropsychiatric Inventory (NPI) neurobehavioral items, when included in the mediation, the outcome. Neuropathologies or cognition served as mediators.ResultsMultiple significant indirect paths from e4 through neuropathologies to neurobehaviors were identified. More refined analyses indicated that neuritic plaques and Braak stage, but not extent of diffuse amyloid plaques, drove the findings. A significant direct effect of e4 to memory was also identified. Additionally, Lewy body disease, when treated as an exposure, had a direct effect on hallucinations in keeping with known features of the disease.ConclusionsWe found strong evidence for partial mediation of NPI symptoms by cognition, suggesting that cognitive limitations that may have influenced understanding (or misunderstanding) the environment with impacts on maladaptive behavior. In addition, neuritic amyloid plaque levels and Braak stage, but not diffuse amyloid plaque extent, were key in NPI mediated associations suggesting the possibility that synaptic failure play an important role in multiple neurobehavioral symptoms in dementia, including psychosis. Last, we found strong evidence that e4 may have direct effects on cognition when we used verbal episodic memory as an outcome, suggesting that medial temporal regions that support memory may be sensitive to non-amyloidogenic and non-tau related pathophysiological processes.
Assessing the Impact of Non-exhaust Emissions on the Asthmatic Airway (IONA) Protocol for a randomised three exposure crossover study
Authors: Scales James , Hajmohammadi Hajar , Priestman Max , McIlvenna Luke C. , de Boer Ingrid E. , Hassan Haneen , Tremper Anja H. , Chen Gang , Wood Helen E. , Green David C. , Katsouyanni Klea , Mudway Ian S. , Griffiths Christopher 
Published: January 2024

AbstractBackgroundPeople living with asthma are disproportionately affected by air pollution, with increased symptoms, medication usage, hospital admissions and the risk of death. To date there has been a focus on exhaust emissions, but traffic-related air pollution (TRAP) can also arise from the mechanical abrasion of tyres, brakes, and road surfaces. Non-exhaust emissions (NEE) currently make up a greater proportion of TRAP by mass than exhaust emissions. With the increasing weight of vehicle fleets due to electrification, and increasing uptake of larger vehicles, it is likely that NEE will continue to be an increasing health challenge.These NEE remain unregulated and underexplored in terms of their health impacts, particularly in vulnerable groups such as people living with asthma. To date, few real-world studies have attempted to explore the impacts of non-exhaust emissions on human health. We therefore created a study with the aim of investigating the acute impacts of NEE on the lung function and airway immune status of asthmatic adults.MethodsThe IONA study will expose adults with asthma in random order at three locations in London selected to provide the greatest contrast in the NEE components within TRAP. Health responses will be assessed before and after each exposure, with lung function measured by spirometry as the primary outcome variable.DiscussionCollectively this study will provide us with valuable information on the health effects of NEE components within ambient PM2.5and PM10, whilst establishing a biological mechanism to help contextualise current epidemiological observations.Trial registrationIRAS Number 320784 athttps://clinicaltrials.gov/
Using routine primary care data to assess Sudden Cardiac Arrest risk in people with type 2 diabetes: a proof-of-concept case-control study
Authors: Harms Peter P. , van Dongen Laura H , Oosterbaan Nicky I.C. , Bennis Frank C. , Beulens Joline WJ , Swart Karin M.A. , Hoogendoorn Mark , Tan Hanno L. , Elders Petra P.J.M. , Blom Marieke T. 
Published: January 2024

AbstractBackgroundApproximately 50% of out-of-hospital Sudden Cardiac Arrest (SCA) occurs in people with unrecognized SCA-risk and no preceding cardiologic care records. General practitioner (GP) records include these people, specifically people with type 2 diabetes (T2D) with increased SCA-risk. We aimed to provide a proof-of-concept for using routine primary care data to study SCA-risk in people with T2D.MethodsThis case-control study, identified SCA cases through the AmsteRdam REsuscitation STudies (ARREST) registry of out-of-hospital SCA in the Dutch region of Noord-Holland (2005-2019). We included cases with presumed cardiac cause and T2D registered at participating GP practices from the PHARMO Data Network and the academic network of general practice Amsterdam UMC (ANHA). Cases were matched (age, sex, T2D, GP-practice) with up to five non-SCA controls. From their GP files, we collected clinical measurements, medication use and medical history. Associations with SCA were analysed using univariable and multivariable conditional logistic regression (Odds Ratios, 95% confidence intervals).ResultsWe included 247 cases and 1,143 controls. In the multivariable model, high fasting glucose (1.08 (1.01-1.16) per 1 mmol/L), high cholesterol ratio (1.17 (1.03-1.34)), moderate albuminuria (2.77 (1.84-4.16)), severe albuminuria (2.96 (1.44-6.08)), dyslipidaemia (0.53 (0.33-0.86)) and a history of cardiovascular disease (1.72 (1.23-2.17)) were significantly associated with SCA. Current smoking behaviour, decreased eGFR, insulin use, hypertension and microvascular complications were close to significantly associated with SCA.ConclusionsThe relatively strong associations in our small sample are consistent with those found in cardiologic care populations, indicating that GP file data can be useful to study SCA-risk.