bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comprehensive overview of cellular senescence from 1990 to 2021: A machine learning-based bibliometric analysis
Authors: Li Chan , Liu Zhaoya , Shi Ruizheng 
Published: January 2023

BackgroundAs a cellular process, senescence functions to prevent the proliferation of damaged, old and tumor-like cells, as well as participate in embryonic development, tissue repair, etc. This study aimed to analyze the themes and topics of the scientific publications related to cellular senescence in the past three decades by machine learning.MethodsThe MeSH term “cellular senescence” was used for searching publications from 1990 to 2021 on the PubMed database, while the R platform was adopted to obtain associated data. A topic network was constructed by latent Dirichlet allocation (LDA) and the Louvain algorithm.ResultsA total of 21,910 publications were finally recruited in this article. Basic studies (15,382, 70.21%) accounted for the most proportion of publications over the past three decades. Physiology, drug effects, and genetics were the most concerned MeSH terms, while cell proliferation was the leading term since 2010. Three senolytics were indexed by MeSH terms, including quercetin, curcumin, and dasatinib, with the accumulated occurrence of 35, 26, and 22, separately. Three clusters were recognized by LDA and network analyses. Telomere length was the top studied topic in the cluster of physiological function, while cancer cell had been a hot topic in the cluster of pathological function, and protein kinase pathway was the most popular topic in the cluster of molecular mechanism. Notably, the cluster of physiological function showed a poor connection with other clusters.ConclusionCellular senescence has obtained increasing attention over the past three decades. While most of the studies focus on the pathological function and molecular mechanism, more researches should be conducted on the physiological function and the clinical translation of cellular senescence, especially the development and application of senotherapeutics.
New onset, transient and stable motoric cognitive risk syndrome: Clinical characteristics and association with incidence of probable dementia in the NuAge cohort
Authors: Beauchet Olivier , Matskiv Jacqueline , Gaudreau Pierrette , Allali Gilles 
Published: January 2023

BackgroundMotoric cognitive risk syndrome (MCR) is a pre-dementia stage. The existence of stable and transient MCR, their related clinical characteristics and their association with incident dementia is a matter of debate.ObjectiveThis study aims to examine the clinical characteristics and the time course associated with new onset, transient and stable MCR, and their association with incidence of probable dementia in community-dwelling older adults living in the province of Quebec (Canada).DesignQuebec elderly population-based observational cohort study with 3 years of follow-up.SettingCommunity dwellers.SubjectsA subset of participants (n = 1,113) from the “Quebec Longitudinal Study on Nutrition and Successful Aging” (NuAge) cohort.MethodsParticipants with MCR were identified at baseline and after 1 year of follow-up. Socio-demographic characteristics, 30-item Geriatric depression scale (GDS) score, cardiovascular risk factors and diseases were recorded at baseline. Incidence of probable dementia was measured at annual follow-up visits over a 3-year period.ResultsOver the period of the first year of follow-up, the prevalence of MCR was 8.5% with 4.3% having new onset MCR, 2.8% transient MCR and 1.4% stable MCR. A higher 30-item GDS score was reported with new onset and transient MCR, and the highest prevalence of cerebrovascular diseases was shown with stable MCR compared to non-MCR participants (p &lt; 0.05). MCR was associated with overall incidence of probable dementia, regardless of its status (Hazard Ratio ≥ 1.86, p ≤ 0.034).ConclusionGreater prevalence of depressive symptoms and cerebrovascular diseases were reported, respectively, with new onset and transient MCR, and stable MCR. The association of MCR with incidence of probable dementia remains significant, regardless of MCR subtypes.
Protein content of blood-derived extracellular vesicles: An approach to the pathophysiology of cerebral hemorrhage
Authors: Laso-García Fernando , Piniella Dolores , Gómez-de Frutos Mari Carmen , Casado-Fernández Laura , Pérez-Mato María , Alonso-López Elisa , Otero-Ortega Laura , Bravo Susana Belén , Chantada-Vázquez María Del Pilar , Trilla-Fuertes Lucía , Fresno-Vara Juan Ángel , Fuentes Blanca , Díez-Tejedor Exuperio , Gutiérrez-Fernández María , Alonso De Leciñana María 
Published: January 2023

Introduction: Extracellular vesicles (EVs) participate in cell-to-cell paracrine signaling and can be biomarkers of the pathophysiological processes underlying disease. In intracerebral hemorrhage, the study of the number and molecular content of circulating EVs may help elucidate the biological mechanisms involved in damage and repair, contributing valuable information to the identification of new therapeutic targets.Methods: The objective of this study was to describe the number and protein content of blood-derived EVs following an intracerebral hemorrhage (ICH). For this purpose, an experimental ICH was induced in the striatum of Sprague-Dawley rats and EVs were isolated and characterized from blood at baseline, 24 h and 28 days. The protein content in the EVs was analyzed by mass spectrometric data-dependent acquisition; protein quantification was obtained by sequential window acquisition of all theoretical mass spectra data and compared at pre-defined time points.Results: Although no differences were found in the number of EVs, the proteomic study revealed that proteins related to the response to cellular damage such as deubiquitination, regulation of MAP kinase activity (UCHL1) and signal transduction (NDGR3), were up-expressed at 24 h compared to baseline; and that at 28 days, the protein expression profile was characterized by a higher content of the proteins involved in healing and repair processes such as cytoskeleton organization and response to growth factors (COR1B) and the regulation of autophagy (PI42B).Discussion: The protein content of circulating EVs at different time points following an ICH may reflect evolutionary changes in the pathophysiology of the disease.
Oligodendrogenesis and myelination tracing in a CRISPR/Cas9-engineered brain microphysiological system
Authors: Romero July Carolina , Berlinicke Cynthia , Chow Sharon , Duan Yukan , Wang Yifei , Chamling Xitiz , Smirnova Lena 
Published: January 2023

IntroductionOligodendrocytes (OLs) are the myelin-forming cells of the central nervous system (CNS). Although OLs can be differentiated from human-induced pluripotent stem cells (hiPSCs), the in vitro modeling of axon myelination in human cells remains challenging. Brain microphysiological systems (bMPS, e.g. organoids) are complex three-dimensional (3D) cultures that offer an ideal system to study this process as OLs differentiate in a more in vivo-like environment; surrounded by neurons and astrocytes, which support the myelination of axons.MethodsHere, we take advantage of CRISPR/Cas9 technology to generate a hiPSC line in which proteolipid protein 1 (PLP1), an OLs marker, is tagged with super-fold GFP (sfGFP). While generating the PLP1-sfGFP reporter, we used reverse transfection and obtained higher Knock-In (KI) efficiency compared to forward transfection (61–72 vs. 46%).ResultsAfter validation of the KI and quality control of the PLP1-sfGFP line, selected clones were differentiated into bMPS, and the fidelity, specificity, and function of the tagged PLP protein were verified in this model. We tracked different stages of oligodendrogenesis in the verified lines based on PLP1-sfGFP+ cells’ morphology, and the presence of PLP1-sfGFP surrounding axons during bMPS’ differentiation. Finally, we challenged the bMPS with cuprizone and quantified changes in both the percentage of PLP1-sfGFP expressing cells and the intensity of GFP expression.DiscussionThis work demonstrates an efficient method for generating hiPSC KI lines and the description of a new 3D model to study OL differentiation, migration, and maturation both during in vitro neurodevelopment as well as in response to environmental chemicals or disease-associated stressors.
Treadmill training of rats after sciatic nerve graft does not alter accuracy of muscle reinnervation
Authors: Barham Mohammed , Andermahr Jonas , Majczyński Henryk , Sławińska Urszula , Vogt Johannes , Neiss Wolfram F. 
Published: January 2023

Background and purposeAfter peripheral nerve lesions, surgical reconstruction facilitates axonal regeneration and motor reinnervation. However, functional recovery is impaired by aberrant reinnervation.Materials and methodsWe tested whether training therapy by treadmill exercise (9 × 250 m/week) before (run–idle), after (idle–run), or both before and after (run–run) sciatic nerve graft improves the accuracy of reinnervation in rats. Female Lewis rats (LEW/SsNHsd) were either trained for 12 weeks (run) or not trained (kept under control conditions, idle). The right sciatic nerves were then excised and reconstructed with 5 mm of a congenic allograft. One week later, training started in the run–run and idle–run groups for another 12 weeks. No further training was conducted in the run–idle and idle–idle groups. Reinnervation was measured using the following parameters: counting of retrogradely labeled motoneurons, walking track analysis, and compound muscle action potential (CMAP) recordings.ResultsIn intact rats, the common fibular (peroneal) and the soleus nerve received axons from 549 ± 83 motoneurons. In the run–idle group, 94% of these motoneurons had regenerated 13 weeks after the nerve graft. In the idle–run group, 81% of the normal number of motoneurons had regenerated into the denervated musculature and 87% in both run–run and idle–idle groups. Despite reinnervation, functional outcome was poor: walking tracks indicated no functional improvement of motion in any group. However, in the operated hindlimb of run–idle rats, the CMAP of the soleus muscle reached 11.9 mV (normal 16.3 mV), yet only 6.3–8.1 mV in the other groups.ConclusionTreadmill training neither altered the accuracy of reinnervation nor the functional recovery, and pre-operative training (run–idle) led to a higher motor unit activation after regeneration.
Longitudinal association between changes in resting-state network connectivity and cognition trajectories: The moderation role of a healthy diet
Authors: Gaynor Alexandra M. , Varangis Eleanna , Song Suhang , Gazes Yunglin , Habeck Christian , Stern Yaakov , Gu Yian 
Published: January 2023

IntroductionHealthy diet has been shown to alter brain structure and function and improve cognitive performance, and prior work from our group showed that Mediterranean diet (MeDi) moderates the effect of between-network resting-state functional connectivity (rsFC) on cognitive function in a cross-sectional sample of healthy adults. The current study aimed to expand on this previous work by testing whether MeDi moderates the effects of changes in between- and within-network rsFC on changes in cognitive performance over an average of 5 years.MethodsAt baseline and 5-year follow up, 124 adults aged 20–80 years underwent resting state fMRI to measure connectivity within and between 10 pre-defined networks, and completed six cognitive tasks to measure each of four cognitive reference abilities (RAs): fluid reasoning (FLUID), episodic memory, processing speed and attention, and vocabulary. Participants were categorized into low, moderate, and high MeDi groups based on food frequency questionnaires (FFQs). Multivariable linear regressions were used to test relationships between MeDi, change in within- and between-network rsFC, and change in cognitive function.ResultsResults showed that MeDi group significantly moderated the effects of change in overall between-network and within-network rsFC on change in memory performance. Exploratory analyses on individual networks revealed that interactions between MeDi and between-network rsFC were significant for nearly all individual networks, whereas the moderating effect of MeDi on the relationship between within-network rsFC change and memory change was limited to a subset of specific functional networks.DiscussionThese findings suggest healthy diet may protect cognitive function by attenuating the negative effects of changes in connectivity over time. Further research is warranted to understand the mechanisms by which MeDi exerts its neuroprotective effects over the lifespan.
Cognitive impairment with Type 2 Diabetes Mellitus among community-dwelling older adults in Chile: Prevalence, risk factors and cognitive characteristics
Authors: Bozanic Agnieszka , Toro Pablo , Bello-Lepe Sebastián , Hurtado-Oliva Javier , Beyle Christian , Valdés Catalina , Formiga Francesc 
Published: January 2023

IntroductionThe aim of this study is to determine prevalence and risk factors of Cognitive Impairment (CI) and its association with Type 2 Diabetes Mellitus (T2DM) in subjects aged 65 years and above. Additionally, we attempt to provide a cognitive profile for T2DM group.MethodologyA cross-sectional analytical study to assess CI was carried out. We evaluated a sample of community-dwelling residents from Chile. All participants underwent a general interview, lifestyle questionnaires and a comprehensive neuropsychological battery. Regression analyses were performed to evaluate risk of CI with T2DM and influencing factors. Results between groups in the different domains of the neuropsychological assessment were compared by Student’s t-tests and MANOVA.ResultsAmong all 358 subjects, overall T2DM prevalence were 17.3%. The prevalence of CI was higher in T2DM group compared to the healthy participants (30.7%, p &lt; 0.001). The risk of CI was 2.8 times higher in older people with T2DM compared to older people without the diagnosis. Multiple regression analysis, adjusted for age and gender, demonstrated that age, education, presence of dyslipidemia, and T2DM duration were the predictor variables significantly associated with CI. T2DM group performed worse on global cognitive performance, attention, language, verbal memory, visual memory, visual constructional ability, and executive function. After adjusting for significant covariates from multiple regression analysis, a relationship between “cognition” and T2DM is still observed. Amnesic multi-domain impairment was the specific cognitive identified pattern for T2DM group.ConclusionThe present study confirms the high prevalence of CI with T2DM among Chilean older adults in a community-based population. T2DM is significantly associated with a higher risk of CI, and age, education, presence of dyslipidemia, and duration of T2DM are risk factors. T2DM patients with CI are impaired in multiple cognitive domains, even after adjusting covariables, resulting in an amnesic multi-domain cognitive profile.
Aberrant resting-state regional activity in patients with postpartum depression
Authors: Li Bo , Zhang Shufen , Li Shuyan , Liu Kai , Hou Xiaoming 
Published: January 2023

BackgroundPostpartum depression (PPD) is a common disorder with corresponding cognitive impairments such as depressed mood, memory deficits, poor concentration, and declining executive functions, but little is known about its underlying neuropathology.MethodA total of 28 patients with PPD and 29 healthy postpartum women were recruited. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed in the fourth week after delivery. Individual local activity of PPD patients was observed by regional homogeneity (ReHo) during resting state, and the ReHo value was computed as Kendall's coecient of concordance (KCC) and analyzed for differences between voxel groups. Correlations between ReHo values and clinical variables were also analyzed.ResultCompared with healthy postpartum women, patients with PPD exhibited significantly higher ReHo values in the left precuneus and right hippocampus. ReHo value was significantly lower in the left dorsolateral prefrontal cortex (dlPFC) and right insula. Furthermore, ReHo values within the dlPFC were negatively correlated with the Edinburgh PPD scale (EPDS) score. The functional connectivity (FC) of the right hippocampus to the left precuneus and left superior frontal gyrus (SFG) was stronger in patients with PPD than that in controls.ConclusionThe present study provided evidence of aberrant regional functional activity and connectivity within brain regions in PPD, and it may contribute to further understanding of the neuropathology underlying PPD.
Comparing therapeutic modulators of the SOD1 G93A Amyotrophic Lateral Sclerosis mouse pathophysiology
Authors: Lee Albert J. B. , Kittel Tyler E. , Kim Renaid B. , Bach Thao-Nguyen , Zhang Tian , Mitchell Cassie S. 
Published: January 2023

IntroductionAmyotrophic Lateral Sclerosis (ALS) is a paralyzing, multifactorial neurodegenerative disease with limited therapeutics and no known cure. The study goal was to determine which pathophysiological treatment targets appear most beneficial.MethodsA big data approach was used to analyze high copy SOD1 G93A experimental data. The secondary data set comprised 227 published studies and 4,296 data points. Treatments were classified by pathophysiological target: apoptosis, axonal transport, cellular chemistry, energetics, neuron excitability, inflammation, oxidative stress, proteomics, or systemic function. Outcome assessment modalities included onset delay, health status (rotarod performance, body weight, grip strength), and survival duration. Pairwise statistical analysis (two-tailed t-test with Bonferroni correction) of normalized fold change (treatment/control) assessed significant differences in treatment efficacy. Cohen’s d quantified pathophysiological treatment category effect size compared to “all” (e.g., all pathophysiological treatment categories combined).ResultsInflammation treatments were best at delaying onset (d = 0.42, p &gt; 0.05). Oxidative stress treatments were significantly better for prolonging survival duration (d = 0.18, p &lt; 0.05). Excitability treatments were significantly better for prolonging overall health status (d = 0.22, p &lt; 0.05). However, the absolute best pathophysiological treatment category for prolonging health status varied with disease progression: oxidative stress was best for pre-onset health (d = 0.18, p &gt; 0.05); excitability was best for prolonging function near onset (d = 0.34, p &lt; 0.05); inflammation was best for prolonging post-onset function (d = 0.24, p &gt; 0.05); and apoptosis was best for prolonging end-stage function (d = 0.49, p &gt; 0.05). Finally, combination treatments simultaneously targeting multiple pathophysiological categories (e.g., polytherapy) performed significantly (p &lt; 0.05) better than monotherapies at end-stage.DiscussionIn summary, the most effective pathophysiological treatments change as function of assessment modality and disease progression. Shifting pathophysiological treatment category efficacy with disease progression supports the homeostatic instability theory of ALS disease progression.
Putative cause of seizure-induced cognitive alterations: The oscillatory reconfiguration of seizure network
Authors: Fan Denggui , Qi Lixue , Yang Zecheng , Luan Guoming , Wang Qingyun 
Published: January 2023

IntroductionThe dynamic reconfiguration of network oscillations is connected with cognitive processes. Changes in how neural networks and signaling pathways work are crucial to how epilepsy and related conditions develop. Specifically, there is evidence that prolonged or recurrent seizures may induce or exacerbate cognitive impairment. However, it still needs to be determined how the seizure brain configures its functional structure to shape the battle of strong local oscillations vs. slow global oscillations in the network to impair cognitive function.MethodsIn this paper, we aim to deduce the network mechanisms underlying seizure-induced cognitive impairment by comparing the evolution of strong local oscillations with slow global oscillations and their link to the resting state of healthy controls. Here, we construct a dynamically efficient network of pathological seizures by calculating the synchrony and directionality of information flow between nine patients’ SEEG signals. Then, using a pattern-based method, we found hierarchical modules in the brain’s functional network and measured the functional balance between the network’s local strong and slow global oscillations.Results and discussionAccording to the findings, a tremendous rise in strong local oscillations during seizures and an increase in slow global oscillations after seizures corresponded to the initiation and recovery of cognitive impairment. Specifically, during the interictal period, local strong and slow global oscillations are in metastable balance, which is the same as a normal cognitive process and can be switched easily. During the pre-ictal period, the two show a bimodal pattern of separate peaks that cannot be easily switched, and some flexibility is lost. During the seizure period, a single-peak pattern with negative peaks is showcased, and the network eventually transitions to a very intense strong local oscillation state. These results shed light on the mechanism behind network oscillations in epilepsy-induced cognitive impairment. On the other hand, the differential (similarity) of oscillatory reorganization between the local (non) epileptogenic network and the global network may be an emergency protective mechanism of the brain, preventing the spread of pathological information flow to more healthy brain regions.
Eighteen years’ experience with tumor treating fields in the treatment of newly diagnosed glioblastoma
Authors: Vymazal Josef , Kazda Tomas , Novak Tomas , Slanina Petr , Sroubek Jan , Klener Jan , Hrbac Tomas , Syrucek Martin , Rulseh Aaron M. 
Published: January 2023

IntroductionThe prognosis of glioblastoma remains unfavorable. TTFields utilize low intensity electric fields (frequency 150–300 kHz) that disrupt cellular processes critical for cancer cell viability and tumor progression. TTFields are delivered via transducer arrays placed on the patients’ scalp. Methods: Between the years 2004 and 2022, 55 patients (20 female), aged 21.9–77.8 years (mean age 47.3±11.8 years; median 47.6 years) were treated with TTFields for newly-diagnosed GBM, and compared to 54 control patients (20 females), aged 27.0–76.7 years (mean age 51.4±12.2 years; median 51.7 years) (p=0.08). All patients underwent gross total or partial resection of GBM. One patient had biopsy only. When available, MGMT promoter methylation status and IDH mutation was detected.ResultsPatients on TTFields therapy demonstrated improvements in PFS and OS relative to controls (hazard ratio: 0.64, p=0.031; and 0.61, p=0.028 respectively). TTFields average time on therapy was 74.8% (median 82%): median PFS of these patients was 19.75 months. Seven patients with TTFields usage ≤60% (23–60%, mean 46.3%, median 53%) had a median PFS of 7.95 months (p=0.0356). Control patients with no TTFields exposure had a median PFS of 12.45 months. Median OS of TTF patients was 31.67 months compared to 24.80 months for controls.DiscussionThis is the most extensive study on newly-diagnosed GBM patients treated with TTFields, covering a period of 18 years at a single center and presenting not only data from clinical trials but also a group of 36 patients treated with TTFields as a part of routine clinical practice.