bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in research related to ophthalmic microperimetry from 1992 to 2022: A bibliometric analysis and knowledge graph study
Authors: Ming Jing , Qin Rui 
Published: January 2023

BackgroundMicroperimetry is a novel technology to assess macular function. The aim of the study was to explore the global research status and trends in microperimetry.MethodsDocuments related to microperimetry in ophthalmology from 1992 to 2022 were extracted from the Science Citation Index Expanded (SCI-E) database of the Web of Science Core Collection (WOSCC). Raw data were analyzed using the VOSviewer and CiteSpace software. Bibliometric parameters included annual publication quantity, countries, authors, journals, international cooperation, and keywords.ResultsA total of 1,217 peer-reviewed documents were retrieved. Annual research output has increased significantly since 2005, especially since 2013. Holz F, Rubin G, and Guymer R contributed most to the number of articles published about microperimetry. Rubin G, Fitzke F, and Holz F, respectively, received the most citations for their study. The countries publishing most were the USA, Italy, and the UK, while the USA, the UK, and Germany received the most citation frequency. Univ Bonn, UCL, and Moorfields Eye Hosp were the top three productive institutions for microperimetry research in the world. The top three journals that publish articles about microperimetry were Retina-The Journal of Retinal and Vitreous Diseases, Investigative Ophthalmology and Visual Science, and the American Journal of Ophthalmology. The top 10 common keywords included microperimetry, optical coherence tomography, eye, retinal sensitivity, macular degeneration, fundus autofluorescence, scanning laser ophthalmoscope, visual acuity, sensitivity, and degeneration. Keywords “optical coherence tomography angiography,” “retinitis pigmentosa,” and “internal limiting membrane” burst in the last 3 years.ConclusionThe bibliometric and knowledge graph analysis of research status and trends in microperimetry provided global researchers with valuable information to propose future cooperation and track cutting-edge progress.
Disruption of DYRK1A-induced hyperphosphorylation of amyloid-beta and tau protein in Alzheimer’s disease: An integrative molecular modeling approach
Authors: Shukla Rohit , Kumar Anuj , Kelvin David J. , Singh Tiratha Raj 
Published: January 2023

Alzheimer’s disease (AD) is a neurological disorder caused by the abnormal accumulation of hyperphosphorylated proteins. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a dual phosphorylation enzyme which phosphorylates the amyloid-β (Aβ) and neurofibrillary tangles (NFTs). A high throughput virtual screening approach was applied to screen a library of 98,071 compounds against DYRK1A using different programs including AutoDock Vina, Smina, and idock. Based on the binding affinities, we selected 330 compounds for absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis. Various pharmacokinetics parameters were predicted using the admetSAR server, and based on the pharmacokinetics results, 14 compounds were selected for cross-docking analysis using AutoDock. Cross-docking analysis revealed four compounds, namely, ZINC3843365 (−11.07 kcal/mol−1), ZINC2123081 (−10.93 kcal/mol−1), ZINC5220992 (−10.63 kcal/mol−1), and ZINC68569602 (−10.35 kcal/mol−1), which had the highest negative affinity scores compared to the 10 other molecules analyzed. Density functional theory (DFT) analysis was conducted for all the four top-ranked compounds. The molecular interaction stability of these four compounds with DYRK1A has been evaluated using molecular dynamics (MD) simulations on 100 nanoseconds followed by principal component analysis (PCA) and binding free energy calculations. The Gibbs free energy landscape analysis suggested the metastable state and folding pattern of selected docking complexes. Based on the present study outcome, we propose four antagonists, viz., ZINC3843365, ZINC2123081, ZINC5220992, and ZINC68569602 as potential inhibitors against DYRK1A and to reduce the amyloid-β and neurofibrillary tangle burden. These screened molecules can be further investigated using a number of in vitro and in vivo experiments.
Early increase in circulating carbonic anhydrase IX: A potential new predictive biomarker of preeclampsia
Authors: Galbiati Silvia , Gabellini Daniela , Ambrosi Alessandro , Soriani Nadia , Pasi Federica , Locatelli Massimo , Lucianò Roberta , Candiani Massimo , Valsecchi Luca , Zerbini Gianpaolo , Smid Maddalena 
Published: January 2023

Preeclampsia (PE) is a severe complication of pregnancy. The identification of a reliable predictive biomarker could help in setting up a specific preventive strategy. To this aim, we studied carbonic anhydrase IX (CAIX) as a marker of hypoxia (a pathway involved in PE pathogenesis) and compared the diagnostic accuracy of CAIX to that of the validated biomarker sFlt1/PlGF ratio. Fifteen women with overt PE and 38 women at a risk of developing PE, sampled at different time intervals during gestation (a total of 82 plasma samples collected), were enrolled and underwent the CAIX measurement. CAIX levels significantly increased (p &lt; .001) before the onset of the disease in women (25% of the total number) who later on developed PE when compared to women who did not, starting from 28th gestational week. The best CAIX cut-off of 68.268 pg/mL yielded a sensitivity of 100%, a specificity of 81.82%, and an AUC value of .9221. In our pilot study, when compared to the sFlt1/PlGF ratio, CAIX performed better in predicting PE before the clinical onset. Furthermore when implemented as CAIX/PlGF ratio, showed up to be comparable in the identification of women with overt early PE. In conclusion, CAIX could represent an effective predictive biomarker of PE, and larger studies are mandatory to validate this finding.
The effect of bright light therapy in migraine patients with sleep disturbance: A prospective, observational cohort study protocol
Authors: Lin Tsung-Hsing , Yang Cheng-Chia , Lee Shih-Yu , Chang Ching-Mao , Tsai I-Ju , Wei Cheng-Yu , Yang Chun-Pai 
Published: January 2023

BackgroundMigraine is a common disabling disorder, and its substantial burden is associated with a considerable negative impact on the patients’ quality of life. Moreover, aging patients with migraine have more cognitive complaints. Additionally, the elderly are more likely to have sleep disturbances, which may also predict the risk of incident dementia. Migraines are reported to be closely associated with sleep and circadian rhythms. Sleep disturbance is a well-known trigger for migraine episodes; moreover, shift work or jet lag reportedly triggers some migraines. The hypothalamus is thought to be the migraine generator; sleep and circadian activity rhythm are also controlled by the hypothalamus. Evidence suggests an influence of both sleep and circadian system on migraine. Previously, light therapy has been show to stabilize sleep architecture and further improve insomnia related to circadian rhythm disorders. However, the beneficial effect of light therapy on migraine with sleep disturbance has not yet been determined. We aim to explore the effects of light therapy for migraine combined with sleep disturbance.Methods and analysisThis project is a 2-year, randomized, double-blind, placebo-controlled clinical trial. The study design includes a 4-week monitoring period (baseline and pretest), a 4-week treatment period, and a posttest. The study participants will undergo assessments on headache frequency and severity and subjective and objective (wrist actigraphy and polysomnography) sleep disturbances, and quality of life and a series of blood tests for serum biomarkers.DiscussionThis study will establish evidence-based alternative medicine for the preventive effect of bright light therapy in migraine patients with sleep disturbances. Moreover, our data will be useful to comprehend the biochemical mechanism of light therapy in migraine prevention.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04890691.
A nomogram based on iron metabolism can help identify apathy in patients with Parkinson’s disease
Authors: Li Jiang-ting , Qu Yi , Gao Hong-ling , Li Jing-yi , Qin Qi-xiong , Wang Dan-lei , Zhao Jing-wei , Mao Zhi-juan , Min Zhe , Xiong Yong-jie , Xue Zheng 
Published: January 2023

BackgroundsApathy is common in Parkinson’s disease (PD) but difficult to identify. Growing evidence suggests that abnormal iron metabolism is associated with apathy in PD. We aimed to investigate the clinical features and iron metabolism of apathetic patients with PD, and construct a nomogram for predicting apathy in PD.MethodsData of 201 patients with PD were analyzed. Demographic data, Apathy Scale (AS) assessments, and serum iron metabolism parameters were obtained. Spearman correlations were used to assess relationships between AS scores and iron metabolism parameters, separately for male and female patients. Additionally, a nomograph for detecting apathetic patients with PD was built based on the results of logistic regression analysis.ResultsThe serum transferrin (TRF, p &lt; 0.0024) concentration and total iron binding capacity (TIBC, p &lt; 0.0024) were lower in the apathetic group after Bonferroni correction, and they were negatively associated with AS scores in male participants with PD (TRF, r = −0.27, p = 0.010; TIBC, r = −0.259, p = 0.014). The nomogram was developed by incorporating the following five parameters: age, sex, serum iron concentration, TIBC and Hamilton Depression Rating Scale (HAMD) scores, which showed good discrimination and calibration, with a consistency index of 0.799 (95% confidence interval = 0.732–0.865).ConclusionAbnormal iron metabolism may contribute to apathy in PD, especially among men. TIBC levels in combination with HAMD scores can be effectively used for the prediction of apathetic patients with PD.
Structural brain signatures of frailty, defined as accumulation of self-reported health deficits in older adults
Authors: Gutiérrez-Zúñiga Raquel , Davis James R. C. , Ruddy Kathy , De Looze Céline , Carey Daniel , Meaney James , Kenny Rose Anne , Knight Silvin Paul , Romero-Ortuno Roman 
Published: January 2023

BackgroundFrailty in older adults has been associated with reduced brain health. However, structural brain signatures of frailty remain understudied. Our aims were: (1) Explore associations between a frailty index (FI) and brain structure on magnetic resonance imaging (MRI). (2) Identify the most important FI features driving the associations.MethodsWe designed a cross-sectional observational study from a population-based study (The Irish Longitudinal Study on Aging: TILDA). Participants aged ≥50 years who underwent the wave 3 MRI sub-study were included. We measured cortex, basal ganglia, and each of the Desikan-Killiany regional volumes. Age-and sex-adjusted correlations were performed with a 32-item self-reported FI that included conditions commonly tested for frailty in research and clinical settings. A graph theory analysis of the network composed by each FI item and cortex volume was performed. White matter fiber integrity was quantified using diffusion tensor imaging (DTI).ResultsIn 523 participants (mean age 69, 49% men), lower cortex and thalamic volumes were independently associated with higher FI. Sensory and functional difficulties, diabetes, polypharmacy, knee pain, and self-reported health were the main FI associations with cortex volume. In the network analysis, cortex volume had a modest influence within the frailty network. Regionally, higher FI was significantly associated with lower volumes in both orbitofrontal and temporal cortices. DTI analyses revealed inverse associations between the FI and the integrity of some association bundles.ConclusionThe FI used had a recognizable but subtle structural brain signature in this sample. Only some FI deficits were directly associated with cortex volume, suggesting scope for developing FIs that include metrics more specifically related with brain health in future aging neuroscience studies.
Isoniazid improves cognitive performance, clears Aβ plaques, and protects dendritic synapses in APP/PS1 transgenic mice
Authors: Chen Jiacheng , Guo Ning , Ruan Yuting , Mai Yingren , Liao Wang , Feng Yanqing 
Published: January 2023

Background and objectiveAlzheimer’s disease (AD) is characterized by amyloid β (Aβ) aggregation and neuroinflammation. This study aimed to investigate the therapeutic effect of isoniazid (INH) against AD.MethodsThe APP/PS1 transgenic mouse model of AD was adopted. The APP/PS1 mice received oral INH (45 mg/kg/d) for 14 days. The cognitive capability was assessed by the Morris Water Maze test. Amyloid plaques and Aβ levels were determined by immunohistochemistry and ELISA assay. The dendritic spines were analyzed by DiOlistic labeling. Immunofluorescence staining was used to observe the microglia and astrocytes.ResultsThe Morris Water Maze test suggested that INH administration can effectively attenuate the reference memory deficit and improve the working memory of the APP/PS1 mice compared to the untreated mice (all p &lt; 0.001). INH significantly decreased the Aβ plaques in the hippocampus and cortex and reduced the levels of Aβ1-40 and Aβ1-42 in the brain homogenates, cerebrospinal fluid, and serum (all p &lt; 0.001). INH also inhibited enzyme activities of β-site amyloid precursor protein cleaving enzyme 1 (BACE1, p &lt; 0.05) and monoamine oxidase B (Mao-b, p &lt; 0.01). INH significantly increased the protrusion density in the hippocampus (p &lt; 0.01). Immunofluorescence staining revealed that INH significantly reduced the number of activated microglia and astrocytes around the Aβ plaques (both p &lt; 0.01).ConclusionIsoniazid administration effectively improved cognitive performance, cleared Aβ plaques, protected dendritic synapses, and reduced innate immune cells around the Aβ plaques, suggesting that INH could be a potential drug for AD treatment.
Transcutaneous electrical acupoint stimulation induced sedative effects in healthy volunteers: A resting-state fMRI study
Authors: Lu Zhihong , Huo Tingting , Deng Jiao , Guo Fan , Liu Kang , Liu Peng , Wang Qiang , Xiong Lize 
Published: January 2023

BackgroundPrevious studies indicated the sedative effect of acupoint stimulation. However, its mechanism remains unclear. This study aimed to investigate the sedative effect of transcutaneous electrical acupoint stimulation (TEAS) and to explore the brain regions involved in this effect in healthy volunteers using functional magnetic resonance imaging (fMRI) techniques.MethodsIn this randomized trial, 26 healthy volunteers were randomly assigned to the TEAS group (receiving 30 min of acupoint stimulation at HT7/PC4) and the control group. fMRI was conducted before and after the intervention. The primary outcome was the BIS value during the intervention. Secondary outcomes included the amplitude of low-frequency fluctuation (ALFF) and region of interest (ROI)-based functional connectivity (FC) showed by fMRI.ResultsIn healthy volunteers, compared with the control group, ALFF values in the TEAS-treated volunteers decreased in the left thalamus, right putamen, and midbrain, while they increased in the left orbitofrontal cortex. More FC existed between the thalamus and the insula, middle cingulate cortex, somatosensory cortex, amygdala, and putamen in subjects after TEAS treatment compared with subjects that received non-stimulation. In addition, ALFF values of the thalamus positively correlated with BIS in both groups.ConclusionTranscutaneous electrical acupoint stimulation could induce a sedative effect in healthy volunteers, and inhibition of the thalamus was among its possible mechanisms.Clinical trial registrationwww.ClinicalTrials.gov; identifier: NCT01896063.
Right hemisphere brain lateralization for knee proprioception among right-limb dominant individuals
Authors: Strong Andrew , Grip Helena , Arumugam Ashokan , Boraxbekk Carl-Johan , Selling Jonas , Häger Charlotte K. 
Published: January 2023

IntroductionStudies indicate that brain response during proprioceptive tasks predominates in the right hemisphere. A right hemisphere lateralization for proprioception may help to explain findings that right-limb dominant individuals perform position matching tasks better with the non-dominant left side. Evidence for proprioception-related brain response and side preference is, however, limited and based mainly on studies of the upper limbs. Establishing brain response associated with proprioceptive acuity for the lower limbs in asymptomatic individuals could be useful for understanding the influence of neurological pathologies on proprioception and locomotion.MethodsWe assessed brain response during an active unilateral knee joint position sense (JPS) test for both legs of 19 right-limb dominant asymptomatic individuals (females/males = 12/7; mean ± SD age = 27.1 ± 4.6 years). Functional magnetic resonance imaging (fMRI) mapped brain response and simultaneous motion capture provided real-time instructions based on kinematics, accurate JPS errors and facilitated extraction of only relevant brain images.ResultsSignificantly greater absolute (but not constant nor variable) errors were seen for the dominant right knee (5.22° ± 2.02°) compared with the non-dominant left knee (4.39° ± 1.79°) (P = 0.02). When limbs were pooled for analysis, significantly greater responses were observed mainly in the right hemisphere for, e.g., the precentral gyrus and insula compared with a similar movement without position matching. Significant response was also observed in the left hemisphere for the inferior frontal gyrus pars triangularis. When limbs were assessed independently, common response was observed in the right precentral gyrus and superior frontal gyrus. For the right leg, additional response was found in the right middle frontal gyrus. For the left leg, additional response was observed in the right rolandic operculum. Significant positive correlations were found between mean JPS absolute errors for the right knee and simultaneous brain response in the right supramarginal gyrus (r = 0.464, P = 0.040).DiscussionOur findings support a general right brain hemisphere lateralization for proprioception (knee JPS) of the lower limbs regardless of which limb is active. Better proprioceptive acuity for the non-dominant left compared with the dominant right knee indicates that right hemisphere lateralization may have meaningful implications for motor control.
Alteration of resting-state network dynamics in autism spectrum disorder based on leading eigenvector dynamics analysis
Authors: Wang Chaoyan , Yang Lu , Lin Yanan , Wang Caihong , Tian Peichao 
Published: January 2023

BackgroundNeurobiological models to explain the vulnerability of autism spectrum disorders (ASDs) are scarce, and previous resting-state functional magnetic resonance imaging (rs-fMRI) studies mostly examined static functional connectivity (FC). Given that FC constantly evolves, it is critical to probe FC dynamic differences in ASD patients.MethodsWe characterized recurring phase-locking (PL) states during rest in 45 ASD patients and 47 age- and sex-matched healthy controls (HCs) using Leading Eigenvector Dynamics Analysis (LEiDA) and probed the organization of PL states across different fine grain sizes.ResultsOur results identified five different groups of discrete resting-state functional networks, which can be defined as recurrent PL state overtimes. Specifically, ASD patients showed an increased probability of three PL states, consisting of the visual network (VIS), frontoparietal control network (FPN), default mode network (DMN), and ventral attention network (VAN). Correspondingly, ASD patients also showed a decreased probability of two PL states, consisting of the subcortical network (SUB), somatomotor network (SMN), FPN, and VAN.ConclusionOur findings suggested that the temporal reorganization of brain discrete networks was closely linked to sensory to cognitive systems of the brain. Our study provides new insights into the dynamics of brain networks and contributes to a deeper understanding of the neurological mechanisms of ASD.
Irisin participates in the beneficial effects of exercise in preventing gestational diabetes mellitus in overweight and obese pregnant women and a mouse model
Authors: Wang Chen , Zhang Xiaoming , Liu Minghui , Qin Shengtang , He Chengrong , Liu Yingnan , Huai Jing , Zhang Qidi , Wei Yumei , Yang Huixia 
Published: January 2023

ObjectiveWe aimed to explore whether irisin participates in the beneficial effects of exercise in preventing gestational diabetes mellitus (GDM) in overweight and obese pregnant women.Study designSixty overweight and obese pregnant women each in the exercise and control groups were randomly selected from our previous randomized controlled trial. Eighteen obese model mice were generated and divided into exercise and control groups in which body weight, abdominal circumference, anal temperature, glucose tolerance test, and insulin tolerance test were recorded. The plasma irisin level, the expression of PGC-1α/FNDC5 and brown (UCP1) and beige adipose (CD137, TMEM26, and TBX-1) marker genes were detected in muscle and adipose tissue.ResultsIn the human study, women in the exercise group had a significantly higher irisin level and lower insulin resistance level than those in the control group. Enhanced expression of beige adipose tissue marker genes (CD137, TMEM26, and TBX-1) in omental adipose tissue and the CD137 gene in subcutaneous adipose tissue were found in the exercise group compared to the control group. In a mouse model, body weight and abdominal circumference were decreased, while glucose homeostasis and insulin sensitivity were significantly improved, and anal temperature was elevated after exercise intervention. A significantly higher level of irisin was revealed in the exercise group after undergoing exercise treatment. The expression of the beige adipose marker genes CD137 and TBX-1 was significantly higher in the exercise group than in the control group in posterior subcutaneous adipose tissue from the inguinal area and interscapular adipose tissue respectively.ConclusionOur observations show that regular exercise during pregnancy can increase irisin levels, promote white fat beiging/browning, improve glucose homeostasis and enhance body energy expenditure, which may be one of the mechanisms by which exercise prevents GDM.