bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and electroencephalographic findings prior to the onset of juvenile myoclonic epilepsy: A case series
Authors: Hiraiwa Akiko , Kobayashi Yu , Hojo Moemi , Tohyama Jun 
Published: March 2023

AbstractThe purpose of this study was to investigate the timing of generalized electroencephalographic abnormalities in patients with juvenile myoclonic epilepsy who were followed up long term before the onset of juvenile myoclonic epilepsy. We enrolled juvenile myoclonic epilepsy patients whose course of epilepsy had been observed for >5 years before the onset of juvenile myoclonic epilepsy, those who had undergone electroencephalogram recording more than twice before the onset of juvenile myoclonic epilepsy, and those who had terminated antiseizure medications for at least 2 years before the onset of juvenile myoclonic epilepsy. Patients who had transitioned from childhood absence epilepsy to juvenile myoclonic epilepsy were excluded. We retrospectively reviewed the medical records and neurophysiological data of the patients. Four patients met the inclusion criteria. One patient was diagnosed with febrile seizures during childhood, and the remaining three had transitioned to juvenile myoclonic epilepsy from other epileptic disorders, such as self‐limited epilepsy with autonomic seizures, genetic epilepsy with febrile seizure plus, or nonspecific genetic generalized epilepsy. All patients exhibited generalized spike–wave discharges or photoparoxysmal responses for >2 years before the onset of juvenile myoclonic epilepsy. The four patients had transitioned to juvenile myoclonic epilepsy from other epileptological preconditions. Patients with juvenile myoclonic epilepsy may show generalized electroencephalographic abnormality many years prior to the onset of symptoms. Generalized spike–waves on the electroencephalogram during the course of any type of epilepsy or febrile seizure may be a risk factor for developing juvenile myoclonic epilepsy.
Importance of Dietary Uptake for in Situ Bioaccumulation of Systemic Fungicides Using Gammarus pulex as a Model Organism
Authors: Raths Johannes , Schnurr Jacob , Bundschuh Mirco , Pinto Fernanda E. , Janfelt Christian , Hollender Juliane 
Published: March 2023

Abstract
Bioaccumulation of organic contaminants from contaminated food sources might pose an underestimated risk toward shredding invertebrates. This assumption is substantiated by monitoring studies observing discrepancies of predicted tissue concentrations determined from laboratory-based experiments compared with measured concentrations of systemic pesticides in gammarids. To elucidate the role of dietary uptake in bioaccumulation, gammarids were exposed to leaf material from trees treated with a systemic fungicide mixture (azoxystrobin, cyprodinil, fluopyram, and tebuconazole), simulating leaves entering surface waters in autumn. Leaf concentrations, spatial distribution, and leaching behavior of fungicides were characterized using liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-HRMS/MS) and matrix-assisted laser desorption ionization-mass spectrometric imaging. The contribution of leached fungicides and fungicides taken up from feeding was assessed by assembling caged (no access) and uncaged (access to leaves) gammarids. The fungicide dynamics in the test system were analyzed using LC-HRMS/MS and toxicokinetic modeling. In addition, a summer scenario was simulated where water was the initial source of contamination and leaves contaminated by sorption. The uptake, translocation, and biotransformation of systemic fungicides by trees were compound-dependent. Internal fungicide concentrations of gammarids with access to leaves were much higher than in caged gammarids of the autumn scenario, but the difference was minimal in the summer scenario. In food choice and dissectioning experiments gammarids did not avoid contaminated leaves and efficiently assimilated contaminants from leaves, indicating the relevance of this exposure pathway in the field. The present study demonstrates the potential impact of dietary uptake on in situ bioaccumulation for shredders in autumn, outside the main application period. The toxicokinetic parameters obtained facilitate modeling of environmental exposure scenarios. The uncovered significance of dietary uptake for detritivores warrants further consideration from scientific as well as regulatory perspectives. Environ Toxicol Chem 2023;42:1993–2006. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Abstract
Schematic overview of systemic fungicide fluxes along a vegetated riparian buffer stripe. Runoff, plant uptake, and bioconcentration in aquatic organisms are dominant fate processes in summer. In autumn systemic fungicides incorporated into foliage may be an important fate process, resulting in leaching and biomagnification processes in adjacent water bodies
Sex differences, asymmetry, and age‐related white matter development in infants and 5‐year‐olds as assessed with tract‐based spatial statistics
Authors: Kumpulainen Venla , Merisaari Harri , Silver Eero , Copeland Anni , Pulli Elmo P. , Lewis John D. , Saukko Ekaterina , Shulist Satu J. , Saunavaara Jani , Parkkola Riitta , Lähdesmäki Tuire , Karlsson Linnea , Karlsson Hasse , Tuulari Jetro J. 
Published: March 2023

AbstractThe rapid white matter (WM) maturation of first years of life is followed by slower yet long‐lasting development, accompanied by learning of more elaborate skills. By the age of 5 years, behavioural and cognitive differences between females and males, and functions associated with brain lateralization such as language skills are appearing. Diffusion tensor imaging (DTI) can be used to quantify fractional anisotropy (FA) within the WM and increasing values correspond to advancing brain development. To investigate the normal features of WM development during early childhood, we gathered a DTI data set of 166 healthy infants (mean 3.8 wk, range 2–5 wk; 89 males; born on gestational week 36 or later) and 144 healthy children (mean 5.4 years, range 5.1–5.8 years; 76 males). The sex differences, lateralization patterns and age‐dependent changes were examined using tract‐based spatial statistics (TBSS). In 5‐year‐olds, females showed higher FA in wide‐spread regions in the posterior and the temporal WM and more so in the right hemisphere, while sex differences were not detected in infants. Gestational age showed stronger association with FA values compared to age after birth in infants. Additionally, child age at scan associated positively with FA around the age of 5 years in the body of corpus callosum, the connections of which are important especially for sensory and motor functions. Lastly, asymmetry of WM microstructure was detected already in infants, yet significant changes in lateralization pattern seem to occur during early childhood, and in 5‐year‐olds the pattern already resembles adult‐like WM asymmetry.
Associations between everyday activities and arterial spin labeling‐derived cerebral blood flow: A longitudinal study in community‐dwelling elderly volunteers
Authors: Sanders Anne‐Marthe , Richard Geneviève , Kolskår Knut , Ulrichsen Kristine M. , Alnæs Dag , Beck Dani , Dørum Erlend S. , Engvig Andreas , Lund Martina Jonette , Nordhøy Wibeke , Pedersen Mads L. , Rokicki Jaroslav , Nordvik Jan Egil , Westlye Lars T. 
Published: March 2023

AbstractCerebral blood flow (CBF) is critical for brain metabolism and function. Age‐related changes in CBF are associated with increased risk of neurocognitive disorders and vascular events such as stroke. Identifying correlates and positive modifiers of age‐related changes in CBF before the emergence of incipient clinical decline may inform public health advice and clinical practice. Former research has been inconclusive regarding the association between regular physical activity and CBF, and there is a lack of studies on the association between level of everyday activities and CBF, in older adults. To investigate these relationships, 118 healthy community‐dwelling adults (65–89 years) underwent pseudo‐continuous arterial spin labeling (ASL) MRI, neurocognitive, physical, and activity assessments at baseline. Eighty‐six participants completed a follow‐up ASL MRI, on average 506 (SD = 113) days after the baseline scan. Cross‐sectional analysis revealed credible evidence for positive associations between time spent on low intensity physical activity and CBF in multiple cortical and subcortical regions, time spent on moderate to vigorous intensity physical activity and accumbens CBF, participation in social activity and CBF in multiple cortical regions, and between reading and thalamic CBF, indicating higher regional CBF in more active adults. Longitudinal analysis revealed anecdotal evidence for an interaction between time and baseline level of gardening on occipital and parietal CBF, and baseline reading on pallidum CBF, indicating more change in CBF in adults with lower level of activity. The findings support that malleable lifestyle factors contribute to healthy brain aging, with relevance for public health guidelines.
Drug repurposing for Mpox: Discovery of small molecules as potential inhibitors against DNA‐dependent RNA polymerase using molecular modeling approach
Authors: Dutt Mansi , Kumar Anuj , Rout Madhusmita , Dehury Budheswar , Martinez Gustavo , Ndishimye Pacifique , Kelvin Alyson A. , Kelvin David J. 
Published: March 2023

AbstractMpox (formerly Monkeypox), a zoonotic illness caused by the Mpox virus, belongs to the Orthopoxvirus genus in the family Poxviridae. To design and develop effective antiviral therapeutics against DNA viruses, the DNA‐dependent RNA polymerase (DdRp) of poxviruses has emerged as a promising drug target. In the present study, we modeled the three‐dimensional (3D) structure of DdRp using a template‐based homology approach. After modeling, virtual screening was performed to probe the molecular interactions between 1755 Food and Drug Administration‐approved small molecule drugs (≤500 molecular weight) and the DdRp of Mpox. Based on the binding affinity and molecular interaction patterns, five drugs, lumacaftor (−11.7 kcal/mol), conivaptan (−11.7 kcal/mol), betulinic acid (−11.6 kcal/mol), fluspirilene (−11.3 kcal/mol), and imatinib (−11.2 kcal/mol), have been ranked as the top drug compounds interacting with Mpox DdRp. Complexes of these shortlisted drugs with DdRp were further evaluated using state‐of‐the‐art all‐atoms molecular dynamics (MD) simulations on 200 nanoseconds followed by principal component analysis (PCA). MD simulations and PCA results revealed highly stable interactions of these small drugs with DdRp. After due validation in wet‐lab using available in vitro and in vivo experiments, these repurposed drugs can be further utilized for the treatment of contagious Mpox virus. The outcome of this study may establish a solid foundation to screen repurposed and natural compounds as potential antiviral therapeutics against different highly pathogenic viruses.
Training the next generation of delivery science researchers: 10‐year experience of a post‐doctoral research fellowship program within an integrated care system
Authors: Grant Richard W , Schmittdiel Julie A , Liu Vincent X , Estacio Karen R , Chen Yi‐Fen Irene , Lieu Tracy A 
Published: March 2023

AbstractIntroductionLearning health systems require a workforce of researchers trained in the methods of identifying and overcoming barriers to effective, evidence‐based care. Most existing postdoctoral training programs, such as NIH‐funded postdoctoral T32 awards, support basic and epidemiological science with very limited focus on rigorous delivery science methods for improving care. In this report, we present the 10‐year experience of developing and implementing a Delivery Science postdoctoral fellowship embedded within an integrated health care delivery system.MethodsIn 2012, the Kaiser Permanente Northern California Division of Research designed and implemented a 2‐year postdoctoral Delivery Science Fellowship research training program to foster research expertise in identifying and addressing barriers to evidence‐based care within health care delivery systems.ResultsSince 2014, 20 fellows have completed the program. Ten fellows had PhD‐level scientific training, and 10 fellows had clinical doctorates (eg, MD, RN/PhD, PharmD). Fellowship alumni have graduated to faculty research positions at academic institutions (9), and research or clinical organizations (4). Seven alumni now hold positions in Kaiser Permanente's clinical operations or medical group (7).ConclusionsThis delivery science fellowship program has succeeded in training graduates to address delivery science problems from both research and operational perspectives. In the next 10 years, additional goals of the program will be to expand its reach (eg, by developing joint research training models in collaboration with clinical fellowships) and strengthen mechanisms to support transition from fellowship to the workforce, especially for researchers from underrepresented groups.
LncRNA ENST00000370438 promotes cell proliferation by upregulating DHCR24 in breast cancer
Authors: Yan Liang , Wu Xu , Zhang Yuan , Tan Qiuyu , Xu Jinwen , Wang Ying , Wang Ruodan , Li Yulei , Zhao Jun 
Published: March 2023

AbstractLong noncoding RNAs (lncRNAs) are critically involved in the occurrence and development of breast cancer (BC). In this study, we performed RNA sequencing, and the results revealed an increase in the expression level of novel lncRNA ENST00000370438 in tissues of patients with BC. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) results showed an increase in lncRNA ENST00000370438 expression level in 23 pairs of BC tissues. Next, we determined the effect of ENST00000370438 on BC cell proliferation, and the results showed that ENST00000370438 promotes cell proliferation in BC. The proteomic analysis showed a decrease in DHCR24 expression level in BC cells transfected with ENST00000370438 small interfering RNA. Western blot and qRT‐PCR assay results showed that ENST00000370438 regulated DHCR24 expression. Furthermore, the rescue experiment showed that the interference with ENST00000370438 expression could restore the effect of DHCR24 overexpression on BC cell proliferation, demonstrating that ENST00000370438 could promote cell proliferation by upregulating DHCR24. Finally, we showed that lncRNA ENST000000370438 could promote tumor growth by overexpressing DHCR24 in nude mice. Our results demonstrated that lncRNA ENST00000370438 promotes BC cell proliferation by upregulating DHCR24 expression.
Limb Preference Changes after Focused‐Ultrasound Thalamotomy for Tremor
Authors: Swytink‐Binnema Catherine A. , Rockel Conrad P. , Martino Davide , Dukelow Sean P. , Pike G. Bruce , Kiss Zelma H.T. 
Published: March 2023

AbstractBackgroundMagnetic resonance‐guided focused‐ultrasound (MRgFUS) thalamotomy is an effective treatment for essential and other tremors. It targets the ventrointermedius (Vim) nucleus, which is the thalamic relay in a proprioceptive pathway, and contains kinesthetic cells. Although MRgFUS thalamotomy reduces some risks associated with more invasive surgeries, it still has side effects, such as balance and gait disturbances; these may be caused by the lesion impacting proprioception.ObjectivesOur aim was to quantitatively measure the effects of MRgFUS on proprioception and limb use in essential tremor patients. We hypothesized that this thalamotomy alters proprioception, because the sensorimotor Vim thalamus is lesioned.MethodsProprioception was measured using the Kinarm exoskeleton robot in 18 patients. Data were collected pre‐operatively, and then 1 day, 3 months, and 1 year after surgery. Patients completed four tasks, assessing motor coordination and postural control, goal‐directed movement and bimanual planning, position sense, and kinesthesia.ResultsImmediately after surgery there were changes in posture speed (indicating tremor improvement), and in bimanual hand use, with the untreated limb being preferred. However, these measures returned to pre‐operative baseline over time. There were no changes in parameters related to proprioception. None of these measures correlated with lesion size or lesion‐overlap with the dentato‐rubro‐thalamic tract.ConclusionsThis is the first quantitative assessment of proprioception and limb preference following MRgFUS thalamotomy. Our results suggest that focused‐ultrasound lesioning of the Vim thalamus does not degrade proprioception but alters limb preference. This change may indicate a required “relearning” in the treated limb, because the effect is transient. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Regulation of beta‐amyloid for the treatment of Alzheimer's disease: Research progress of therapeutic strategies and bioactive compounds
Authors: Qiu Weimin , Liu Hui , Liu Yijun , Lu Xin , Wang Lei , Hu Yanyu , Feng Feng , Li Qi , Sun Haopeng 
Published: March 2023

AbstractAlzheimer's disease (AD) is a progressive neurodegenerative disease that is difficult to treat. Extracellular amyloid is the principal pathological criterion for the diagnosis of AD. Amyloid β (Aβ) interacts with various receptor molecules on the plasma membrane and mediates a series of signaling pathways that play a vital role in the occurrence and development of AD. Research on receptors that interact with Aβ is currently ongoing. Overall, there are no effective medications to treat AD. In this review, we first discuss the importance of Aβ in the pathogenesis of AD, then summarize the latest progress of Aβ‐related targets and compounds. Finally, we put forward the challenges and opportunities in the development of effective AD therapies.
Cell division factor ZapE regulates Pseudomonas aeruginosa biofilm formation by impacting the pqs quorum sensing system
Authors: Liu Xi , Jia Minlu , Wang Jing , Cheng Hang , Cai Zhao , Yu Zhaoxiao , Liu Yang , Ma Luyan Z. , Zhang Lianhui , Zhang Yingdan , Yang Liang 
Published: March 2023

AbstractPseudomonas aeruginosa is one of the leading nosocomial pathogens that causes both severe acute and chronic infections. The strong capacity of P. aeruginosa to form biofilms can dramatically increase its antibiotic resistance and lead to treatment failure. The biofilm resident bacterial cells display distinct gene expression profiles and phenotypes compared to their free‐living counterparts. Elucidating the genetic determinants of biofilm formation is crucial for the development of antibiofilm drugs. In this study, a high‐throughput transposon‐insertion site sequencing (Tn‐seq) approach was employed to identify novel P. aeruginosa biofilm genetic determinants. When analyzing the novel biofilm regulatory genes, we found that the cell division factor ZapE (PA4438) controls the P. aeruginosa pqs quorum sensing system. The ∆zapE mutant lost fitness against the wild‐type PAO1 strain in biofilms and its production of 2‐heptyl‐3‐hydroxy‐4(1H)‐quinolone (PQS) had been reduced. Further biochemical analysis showed that ZapE interacts with PqsH, which encodes the synthase that converts 2‐heptyl‐4‐quinolone (HHQ) to PQS. In addition, site‐directed mutagenesis of the ATPase active site of ZapE (K72A) abolished the positive regulation of ZapE on PQS signaling. As ZapE is highly conserved among the Pseudomonas group, our study suggests that it is a potential drug target for the control of Pseudomonas infections.
Serum nuclear magnetic resonance metabolomics analysis of human metastatic colorectal cancer: Biomarkers and pathway analysis
Authors: Tristán Ana Isabel , González‐Flores Encarnación , Salmerón Ana del Mar , Abreu Ana Cristina , Caba Octavio , Jiménez‐Luna Cristina , Melguizo Consolación , Prados José , Fernández Ignacio 
Published: March 2023

AbstractWe describe the use of nuclear magnetic resonance metabolomics to analyze blood serum samples from healthy individuals (n = 26) and those with metastatic colorectal cancer (CRC; n = 57). The assessment, employing both linear and nonlinear multivariate data analysis techniques, revealed specific metabolite changes associated with metastatic CRC, including increased levels of lactate, glutamate, and pyruvate, and decreased levels of certain amino acids and total fatty acids. Biomarker ratios such as glutamate‐to‐glutamine and pyruvate‐to‐alanine were also found to be related to CRC. The study also found that glutamate was linked to progression‐free survival and that both glutamate and 3‐hydroxybutyrate were risk factors for metastatic CRC. Additionally, gas chromatography coupled to flame‐ionization detection was utilized to analyze the fatty acid profile and pathway analysis was performed on the profiled metabolites to understand the metabolic processes involved in CRC. A correlation was also found between the presence of certain metabolites in the blood of CRC patients and certain clinical features.
Polyglycerol‐modified polyvinyl alcohol with improved stability during thermoplastic processing
Authors: Zeng Shulong , Li Li , Wang Qi 
Published: March 2023

AbstractPolyvinyl alcohol (PVA), which can be synthesized via a non‐petroleum route, is a multi‐hydroxyl polymer with good comprehensive properties and environmental friendliness. However, poor thermal processability impedes its development. Herein, polyglycerol (PGL) was firstly adopted to substitute parts of glycerin as one of the plasticizers to prepare modified PVA with greater thermal stability. FTIR spectra revealed the strong hydrogen‐bonding interaction between PGL and PVA which would be destroyed during heating, indicating that PGL was suitable for plasticizing PVA. The introduction of PGL weakened the volatilization of plasticizer as T5% of modified PVA was remarkably improved from 174.7°C to 245.8°C with the addition of 20 wt% PGL. The effects of PGL content on the crystallization behaviors, melting characteristics, dynamic rheological behaviors, and mechanical properties of PVA were investigated. It revealed that the substitution of PGL for glycerin did not influence the final crystalline structure and crystallinity of PVA, but shortened the crystallization time, improved the tensile strength and decreased the melt index owing to the entanglement between PVA and PGL molecules. Dynamic oscillatory rheological measurement showed that the lowest complex viscosity was obtained when 10 wt% PGL was incorporated, which is beneficial for practical processing and film forming. Under proper processing conditions, the production and application of this hot‐blown PVA film were realized at an experimental scale. This work sheds light on the exploitation of new plasticizers with high plasticizing efficiency and thermal stability during processing of PVA.