bluuebunny/crossref_metadata_2025 huggingface dataset:
Collision avoidance for autonomous ship using deep reinforcement learning and prior-knowledge-based approximate representation
Authors: Wang Chengbo , Zhang Xinyu , Yang Zaili , Bashir Musa , Lee Kwangil
Published: January 2023

Reinforcement learning (RL) has shown superior performance in solving sequential decision problems. In recent years, RL is gradually being used to solve unmanned driving collision avoidance decision-making problems in complex scenarios. However, ships encounter many scenarios, and the differences in scenarios will seriously hinder the application of RL in collision avoidance at sea. Moreover, the iterative speed of trial-and-error learning for RL in multi-ship encounter scenarios is slow. To solve this problem, this study develops a novel intelligent collision avoidance algorithm based on approximate representation reinforcement learning (AR-RL) to realize the collision avoidance of maritime autonomous surface ships (MASS) in a continuous state space environment involving interactive learning capability like a crew in navigation situation. The new algorithm uses an approximate representation model to deal with the optimization of collision avoidance strategies in a dynamic target encounter situation. The model is combined with prior knowledge and International Regulations for Preventing Collisions at Sea (COLREGs) for optimal performance. This is followed by a design of an online solution to a value function approximation model based on gradient descent. This approach can solve the problem of large-scale collision avoidance policy learning in static-dynamic obstacles mixed environment. Finally, algorithm tests were constructed though two scenarios (i.e., the coastal static obstacle environment and the static-dynamic obstacles mixed environment) using Tianjin Port as an example and compared with multiple groups of algorithms. The results show that the algorithm can improve the large-scale learning efficiency of continuous state space of dynamic obstacle environment by approximate representation. At the same time, the MASS can efficiently and safely avoid obstacles enroute to reaching its target destination. It therefore makes significant contributions to ensuring safety at sea in a mixed traffic involving both manned and MASS in near future.
Marine ecological security assessment from the perspective of emergy ecological footprint
Authors: Wang Cui , Lin Aiyong , Liu Conghu
Published: January 2023

Introduction

Marine ecological security assessments are considered as a basis for coordinating marine economic development and ecological protection.

Methods

We propose an assessment method based on the emergy ecological footprint which first measures the emergy of the natural and economic elements of the marine ecosystem. Considering the role of economic, social and waste discharge factors in the marine ecosystem, an ecological security evaluation index is constructed, and a dynamic evaluation is conducted based on long time series data to characterize the change trend of ecological security.

Results

The Guangxi marine ecosystem was selected as the case study, and the ecological security dynamic evaluation was conducted by collecting data from 2008 to 2020. The results show that Guangxi's marine ecosystem has always been in an ecologically secure state, but since 2010, the emergy ecological footprint intensity has been increasing, indicating ecosystem deterioration. Therefore, some targeted suggestions are put forward.

Discussion

This method provides a new assessment tool for marine ecological security evaluation and offers guidance for the sustainable development and utilization of marine ecosystems.
Towards a pan-European coastal flood awareness system: Skill of extreme sea-level forecasts from the Copernicus Marine Service
Authors: Irazoqui Apecechea Maialen , Melet Angélique , Armaroli Clara
Published: January 2023

European coasts are regularly exposed to severe storms that trigger extreme water-level conditions, leading to coastal flooding and erosion. Early Warning Systems (EWS) are important tools for the increased preparedness and response against coastal flood events, hence greatly reducing associated risks. With this objective, a proof-of-concept for a European Coastal Flood Awareness System (ECFAS) was developed in the framework of the H2020 ECFAS project, which capitalizes on the Copernicus products. In this context, this manuscript evaluates for the first time the capability of the current Copernicus Marine operational ocean models to forecast extreme coastal water levels and hence to feed coastal flood awareness applications at European scale. A methodology is developed to focus the assessment on storm-driven extreme sea level events (EEs) from tide-gauge records. For the detected EEs, the event peak representation is validated, and the impact of forecast lead time is evaluated. Results show satisfactory performance but a general underprediction of peak magnitudes of 10% for water levels and 18% for surges across the detected EEs. In average, the models are capable of independently flagging 76% of the observed EEs. Forecasts show limited lead time impact up to a 4-day lead time, demonstrating the suitability of the systems for early warning applications. Finally, by separating the surge and tidal contributions to the extremes, the potential sources of the prediction misfits are discussed and consequent recommendations for the evolution of the Copernicus Marine Service forecasting models towards coastal flooding applications are provided.
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

Background

Microperimetry is a novel technology to assess macular function. The aim of the study was to explore the global research status and trends in microperimetry.

Methods

Documents 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.

Results

A 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.

Conclusion

The 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.
Autoimmune bullous diseases during COVID-19 pandemic: 2022 update on rituximab and vaccine
Authors: Pira Anna , Sinagra Jo Linda Maria , Moro Francesco , Mariotti Feliciana , Di Zenzo Giovanni
Published: January 2023

Autoimmune bullous diseases (AIBDs) are a heterogeneous group of life-threatening disorders associated with subepidermal or intraepidermal blistering. Skin barrier alterations and prolonged immunosuppressive treatments increase the risk of infections in patients with AIBDs, who are considered fragile. COVID-19 pandemic had a heavy impact on these patients. Although advances have been made in terms of prevention and treatment of COVID-19, this topic remains significant as the pandemic and its waves could last several years and, so far, a relevant proportion of the population worldwide is not vaccinated. This review is a 2022 update that summarizes and discusses the pandemic’s burden on AIBD patients mainly considering relevant studies in terms of: (i) sample dimension; (ii) quality of control populations; (iii) possible standardization by age, gender and country. The findings show that: (i) the risk of COVID-19 infection and its severe course were comparable in AIBD patients and in the general population, except for rituximab-treated patients that presented a higher risk of infection and severe disease; (ii) the mortality rate in COVID-19-infected bullous pemphigoid patients was higher than in the general population, (iii) 121 cases of AIBD onset and 185 cases of relapse or exacerbation occurred after COVID-19 vaccination and a causal relationship has not been demonstrated so far. Altogether, acquired knowledge on COVID-19 pandemic could also be important in possible, albeit undesirable, future pandemic scenarios.
Inactivation of Pseudomonas aeruginosa biofilms by thymoquinone in combination with nisin
Authors: Chen Hong , Ji Peng-Cheng , Qi Yue-Heng , Chen Shi-Jin , Wang Chang-Yao , Yang Yu-Jie , Zhao Xin-Yu , Zhou Jin-Wei
Published: January 2023

Pseudomonas aeruginosa is one of the most important foodborne pathogens that can persist in leafy green vegetables and subsequently produce biofilms. In this study, the synergistic effect of thymoquinone and nisin in reducing biofilm formation of P. aeruginosa on lettuce was evaluated, and their anti-virulence and anti-biofilm mechanisms were also investigated. At concentrations ranging from 0.5 to 2 mg/ml, thymoquinone inhibited the production of autoinducers and virulence factors, and enhanced the susceptibility of P. aeruginosa biofilms to nisin as evidenced by the scanning electron microscopy and confocal laser scanning microscopy. Integrated transcriptomics, metabolomics, and docking analyses indicated that thymoquinone treatment disrupted the quorum sensing (QS) system, altered cell membrane component, and down-regulated the expressions of genes related to virulence, efflux pump, and antioxidation. The changed membrane component and repressed efflux pump system enhanced membrane permeability and facilitated the entrance of nisin into cells, thus improving the susceptibility of biofilms to nisin. The dysfunctional QS and repressed antioxidant enzymes lead to the enhancement of oxidative stress. The enhanced oxidative stress disrupted energy metabolism and protein metabolism and ultimately attenuated the virulence and pathogenicity of P. aeruginosa PAO1. Our study indicated that thymoquinone has the potential to function as a QS-based agent to defend against foodborne pathogens in combination with nisin.
Spatiotemporal variations, assembly processes, and co-occurrence patterns of particle-attached and free-living bacteria in a large drinking water reservoir in China
Authors: Yu Bobing , Xie Guijuan , Shen Zhen , Shao Keqiang , Tang Xiangming
Published: January 2023

Particle-attached (PA) and free-living (FL) bacterial communities are sensitive to pollutant concentrations and play an essential role in biogeochemical processes and water quality maintenance in aquatic ecosystems. However, the spatiotemporal variations, assembly processes, co-occurrence patterns, and environmental interactions of PA and FL bacteria in drinking water reservoirs remain as yet unexplored. To bridge this gap, we collected samples from 10 sites across four seasons in Lake Tianmu, a large drinking water reservoir in China. Analysis of 16S rRNA gene libraries demonstrated spatiotemporal variations in bacterial diversity and identified differences in bacterial community composition (BCC) between PA and FL lifestyles. Capacity for nitrogen respiration, nitrogen fixation, and nitrate denitrification was enriched in the PA lifestyle, while photosynthesis, methylotrophy, and methanol oxidation were enriched in the FL lifestyle. Deterministic processes, including interspecies interactions and environmental filtration, dominated the assembly of both PA and FL bacterial communities. The influence of environmental filtration on the FL community was stronger than that on the PA community, indicating that bacteria in the FL lifestyle were more sensitive to environmental variation. Co-occurrence patterns and keystone taxa differed between PA and FL lifestyles. The ecological functions of keystone taxa in the PA lifestyle were associated with the supply and recycling of nutrients, while those in FL were associated with the degradation of complex pollutants. PA communities were more stable than FL communities in the face of changing environmental conditions. Nutrients (e.g., TDN and NO3–) and abiotic and biotic factors (e.g., WT and Chl-a) exerted positive and negative effects, respectively, on the co-occurrence networks of both lifestyles. These results improve our understanding of assembly processes, co-occurrence patterns, and environmental interactions within PA and FL communities in a drinking water reservoir.
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 < .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

Background

Migraine 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 analysis

This 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.

Discussion

This 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

Backgrounds

Apathy 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.

Methods

Data 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.

Results

The serum transferrin (TRF, p < 0.0024) concentration and total iron binding capacity (TIBC, p < 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).

Conclusion

Abnormal 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

Background

Frailty 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.

Methods

We 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).

Results

In 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.

Conclusion

The 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 objective

Alzheimer’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.

Methods

The 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.

Results

The 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 < 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 < 0.001). INH also inhibited enzyme activities of β-site amyloid precursor protein cleaving enzyme 1 (BACE1, p < 0.05) and monoamine oxidase B (Mao-b, p < 0.01). INH significantly increased the protrusion density in the hippocampus (p < 0.01). Immunofluorescence staining revealed that INH significantly reduced the number of activated microglia and astrocytes around the Aβ plaques (both p < 0.01).

Conclusion

Isoniazid 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.
Prescribed performance adaptive event-triggered consensus control for multiagent systems with input saturation
Authors: Yue Xia , Liu Jiarui , Chen Kairui , Zhang Yuanqing , Hu Zikai
Published: January 2023

In this paper, a prescribed performance adaptive event-triggered consensus control method is developed for a class of multiagent systems with the consideration of input dead zone and saturation. In practical engineering applications, systems are inevitably suffered from input saturation. In addition, input dead zone is widely existing. As the larger signal is limited and the smaller signal is difficult to effectively operate, system efficacious input encounters unknown magnitude limitations, which seriously impact system control performance and even lead to system instability. Furthermore, when constrained multiagent systems are required to converge quickly, the followers would achieve it with drastic and quick variation of states, which may violate the constraints and even cause security problems. To address those problems, an adaptive event-triggered consensus control is proposed. By constructing the transform function and the barrier Lyapunov function, while state constrained is guaranteed, multiagent systems quickly converge with prescribed performance. Finally, some examples are adopted to confirm the effectiveness of the proposed control method.
Circadian rhythms as modulators of brain health during development and throughout aging
Authors: Van Drunen Rachel , Eckel-Mahan Kristin
Published: January 2023

The circadian clock plays a prominent role in neurons during development and throughout aging. This review covers topics pertinent to the role of 24-h rhythms in neuronal development and function, and their tendency to decline with aging. Pharmacological or behavioral modification that augment the function of our internal clock may be central to decline of cognitive disease and to future chronotherapy for aging-related diseases of the central nervous system.
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

Background

Previous 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.

Methods

In 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.

Results

In 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.

Conclusion

Transcutaneous electrical acupoint stimulation could induce a sedative effect in healthy volunteers, and inhibition of the thalamus was among its possible mechanisms.

Clinical trial registration

www.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

Introduction

Studies 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.

Methods

We 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.

Results

Significantly 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).

Discussion

Our 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.
Drosophila melanogaster as a model for unraveling unique molecular features of epilepsy elicited by human GABA transporter 1 variants
Authors: Kasture Ameya S. , Fischer Florian P. , Kunert Lisa , Burger Melanie L. , Burgstaller Alexander C. , El-Kasaby Ali , Hummel Thomas , Sucic Sonja
Published: January 2023

Mutations in the human γ-aminobutyric acid (GABA) transporter 1 (hGAT-1) can instigate myoclonic-atonic and other generalized epilepsies in the afflicted individuals. We systematically examined fifteen hGAT-1 disease variants, all of which dramatically reduced or completely abolished GABA uptake activity. Many of these loss-of-function variants were absent from their regular site of action at the cell surface, due to protein misfolding and/or impaired trafficking machinery (as verified by confocal microscopy and de-glycosylation experiments). A modest fraction of the mutants displayed correct targeting to the plasma membrane, but nonetheless rendered the mutated proteins devoid of GABA transport, possibly due to structural alterations in the GABA binding site/translocation pathway. We here focused on a folding-deficient A288V variant. In flies, A288V reiterated its impeded expression pattern, closely mimicking the ER-retention demonstrated in transfected HEK293 cells. Functionally, A288V presented a temperature-sensitive seizure phenotype in fruit flies. We employed diverse small molecules to restore the expression and activity of folding-deficient hGAT-1 epilepsy variants, in vitro (in HEK293 cells) and in vivo (in flies). We identified three compounds (chemical and pharmacological chaperones) conferring moderate rescue capacity for several variants. Our data grant crucial new insights into: (i) the molecular basis of epilepsy in patients harboring hGAT-1 mutations, and (ii) a proof-of-principle that protein folding deficits in disease-associated hGAT-1 variants can be corrected using the pharmacochaperoning approach. Such innovative pharmaco-therapeutic prospects inspire the rational design of novel drugs for alleviating the clinical symptoms triggered by the numerous emerging pathogenic mutations in hGAT-1.
Weakly supervised learning analysis of Aβ plaque distribution in the whole rat brain
Authors: Chen Zhiyi , Zheng Weijie , Pang Keliang , Xia Debin , Guo Lingxiao , Chen Xuejin , Wu Feng , Wang Hao
Published: January 2023

Alzheimer’s disease (AD) is a great challenge for the world and hardly to be cured, partly because of the lack of animal models that fully mimic pathological progress. Recently, a rat model exhibiting the most pathological symptoms of AD has been reported. However, high-resolution imaging and accurate quantification of beta-amyloid (Aβ) plaques in the whole rat brain have not been fulfilled due to substantial technical challenges. In this paper, a high-efficiency data analysis pipeline is proposed to quantify Aβ plaques in whole rat brain through several terabytes of image data acquired by a high-speed volumetric imaging approach we have developed previously. A novel segmentation framework applying a high-performance weakly supervised learning method which can dramatically reduce the human labeling consumption is described in this study. The effectiveness of our segmentation framework is validated with different metrics. The segmented Aβ plaques were mapped to a standard rat brain atlas for quantitative analysis of the Aβ distribution in each brain area. This pipeline may also be applied to the segmentation and accurate quantification of other non-specific morphology objects.
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

Background

Neurobiological 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.

Methods

We 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.

Results

Our 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.

Conclusion

Our 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.
Segregation of D1 and D2 dopamine receptors in the striatal direct and indirect pathways: An historical perspective
Authors: Gerfen Charles R.
Published: January 2023

The direct and indirect striatal pathways form a cornerstone of the circuits of the basal ganglia. Dopamine has opponent affects on the function of these pathways due to the segregation of the D1- and D2-dopamine receptors in the spiny projection neurons giving rise to the direct and indirect pathways. An historical perspective is provided on the discovery of dopamine receptor segregation leading to models of how the direct and indirect affect motor behavior.
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

Objective

We 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 design

Sixty 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.

Results

In 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.

Conclusion

Our 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.
Quantitative omics analyses of NCOA4 deficiency reveal an integral role of ferritinophagy in iron homeostasis of hippocampal neuronal HT22 cells
Authors: Bengson Emily F. , Guggisberg Cole A. , Bastian Thomas W. , Georgieff Michael K. , Ryu Moon-Suhn
Published: January 2023

Introduction

Neurons require iron to support their metabolism, growth, and differentiation, but are also susceptible to iron-induced oxidative stress and cytotoxicity. Ferritin, a cytosolic iron storage unit, mediates cellular adaptation to fluctuations in iron delivery. NCOA4 has been characterized as a selective autophagic cargo receptor facilitating the mobilization of intracellular iron from ferritin. This process named ferritinophagy results in the degradation of ferritin and the consequent release of iron into the cytosol.

Methods

Here we demonstrate that NCOA4 is important for the adaptation of the HT22 mouse hippocampal neuronal cell line to cellular iron restriction. Additionally, we determined the pathophysiological implications of impaired ferritinophagy via functional analysis of the omics profile of HT22 cells deficient in NCOA4.

Results

NCOA4 silencing impaired ferritin turnover and was cytotoxic when cells were restricted of iron. Quantitative proteomics identified IRP2 accumulation among the most prominent protein responses produced by NCOA4 depletion in HT22 cells, which is indicative of functional iron deficiency. Additionally, proteins of apoptotic signaling pathway were enriched by those responsive to NCOA4 deficiency. Transcriptome profiles of NCOA4 depletion revealed neuronal cell death, differentiation of neurons, and development of neurons as potential diseases and bio functions affected by impaired ferritinophagy, particularly, when iron was restricted.

Discussion

These findings identify an integral role of NCOA4-mediated ferritinophagy in the maintenance of iron homeostasis by HT22 cells, and its potential implications in controlling genetic pathways of neurodevelopment and neurodegenerative diseases.
The influence of dietary and supplemental omega-3 fatty acids on the omega-3 index: A scoping review
Authors: Dempsey Meghan , Rockwell Michelle S. , Wentz Laurel M.
Published: January 2023

Introduction

The majority of the population do not consume adequate omega-3 fatty acids (n-3 FA), leading to global deficiencies, as evidenced by poor omega-3 status. An indicator of overall n-3 FA status, omega3-index (O3i) ≥8% has been associated with reduced risk of chronic disease, most notably cardiovascular disease. Thus, a synthesis of current research summarizing the effects of n-3 FA intake on O3i is warranted to develop and refine clinical recommendations. The purpose of this scoping review was to evaluate the effect of n-3 FA interventions and estimate sufficient n-3 FA intake to improve O3i to meet recommendations.

Methods

Search criteria were human studies published in English from 2004 to 2022 that assessed O3i at baseline and following an n-3 FA intervention.

Results

Fifty-eight studies that met inclusion criteria were identified. Protocols included fish consumption, fortified foods, combined eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplements, supplements of single n-3 FA (alpha linolenic acid (ALA), EPA, DHA, etc.), and supplements providing multiple n-3 FA. Dietary supplements varied in chemical composition; the most common were triglycerides or ethyl esters. The lowest supplementation protocol was 100 mg/d, and the largest was 4,400 mg/d EPA and DHA. Supplementation time period ranged from 3 weeks to 1 year. At baseline, three study samples had mean O3i >8%, although many intervention protocols successfully increased O3i.

Discussion

Generally, the lowest doses shown to be effective in raising O3i to recommended levels were >1,000 mg/d of combination DHA plus EPA for 12 weeks or longer. Supplements composed of triglycerides were more bioavailable and thus more effective than other formulas. Based on the data evaluated, practical recommendations to improve O3i to ≥8% are consumption of 1,000–1,500 mg/d EPA plus DHA as triglycerides for at least 12 weeks.
Preoperative prediction of cytokeratin-19 expression for hepatocellular carcinoma using T1 mapping on gadoxetic acid-enhanced MRI combined with diffusion-weighted imaging and clinical indicators
Authors: Zhao Yue , Tan Xiaoliang , Chen Jingmu , Tan Hongweng , Huang Huasheng , Luo Peng , Liang Yongsheng , Jiang Xinqing
Published: January 2023

Objectives

To explore the value of T1 mapping on gadoxetic acid-enhanced magnetic resonance imaging (MRI) in preoperative predicting cytokeratin 19 (CK19) expression for hepatocellular carcinoma (HCC).

Methods

This retrospective study included 158 patients from two institutions with surgically resected treatment-native solitary HCC who underwent preoperative T1 mapping on gadoxetic acid-enhanced MRI. Patients from institution I (n = 102) and institution II (n = 56) were assigned to training and test sets, respectively. univariable and multivariable logistic regression analyses were performed to investigate the association of clinicoradiological variables with CK19. The receiver operating characteristic (ROC) curve and precision-recall (PR) curve were used to evaluate the performance for CK19 prediction. Then, a prediction nomogram was developed for CK19 expression. The performance of the prediction nomogram was evaluated by its discrimination, calibration, and clinical utility.

Results

Multivariable logistic regression analysis showed that AFP>400ng/ml (OR=4.607, 95%CI: 1.098-19.326; p=0.037), relative apparent diffusion coefficient (rADC)≤0.71 (OR=3.450, 95%CI: 1.126-10.567; p=0.030), T1 relaxation time in the 20-minute hepatobiliary phase (T1rt-HBP)>797msec (OR=4.509, 95%CI: 1.301-15.626; p=0.018) were significant independent predictors of CK19 expression. The clinical-quantitative model (CQ-Model) constructed based on these significant variables had the best predictive performance with an area under the ROC curve of 0.844, an area under the PR curve of 0.785 and an F1 score of 0.778. The nomogram constructed based on CQ-Model demonstrated satisfactory performance with C index of 0.844 (95%CI: 0.759-0.908) and 0.818 (95%CI: 0.693-0.902) in the training and test sets, respectively.

Conclusions

T1 mapping on gadoxetic acid-enhanced MRI has good predictive efficacy for preoperative prediction of CK19 expression in HCC, which can promote the individualized risk stratification and further treatment decision of HCC patients.
Combined iodine-125 seed strand, portal vein stent, transarterial chemoembolization, lenvatinib and anti-PD-1 antibodies therapy for hepatocellular carcinoma and Vp4 portal vein tumor thrombus: A propensity-score analysis
Authors: Zhang Zi-Han , Hou Si-Nan , Yu Jia-Ze , Zhang Wen , Ma Jing-Qin , Yang Min-Jie , Liu Qing-Xin , Liu Ling-Xiao , Luo Jian-Jun , Qu Xu-Dong , Yan Zhi-Ping
Published: January 2023

Objective

To evaluate the safety and efficacy of interventional therapy (iodine-125[125I] seed strand and portal vein stent [PVS] implantation plus transarterial chemoembolization [TACE]) combined with systemic therapy (lenvatinib plus anti-PD-1 antibody) as first-line treatment for hepatocellular carcinoma (HCC) patients with Vp4 portal vein tumor thrombus (PVTT).

Patients and methods

From December 2018 to October 2021, 87 HCC patients with Vp4 PVTT were included in this single-center retrospective study. Forty-seven patients underwent interventional therapy combined with lenvatinib and anti-PD-1 antibody (group A), while 40 cases underwent interventional therapy combined with lenvatinib only (group B). Overall response rate (ORR), stent occlusion rates (SOR), median overall survival (OS), median progression-free survival (PFS) and median stent patency time (SPT) were compared between the 2 groups.

Results

The mean intended dose (r = 10 mm; z = 0; 240 days) was 64.9 ± 1.0 Gy and 64.5 ± 1.1 Gy in group A and B, respectively (p = 0.133). ORR and SOR were significantly different between group A and B (ORR, 55.3% vs 17.5%, p < 0.001; SOR, 12.8% vs 35.0%, p = 0.014). In the propensity-score matching (PSM) cohort, the median OS, median PFS and median SPT were significantly longer in group A compared with group B (32 PSM pairs; OS, 17.7 ± 1.7 vs 12.0 ± 0.8 months, p = 0.010; PFS, 17.0 ± 4.3 vs 8.0 ± 0.7 months, p < 0.001; SPT, not-reached vs 12.5 ± 1.1 months, p = 0.028).

Conclusion

This interventional therapy combined with lenvatinib and anti-PD-1 antibody is safe and effective for HCC patients with Vp4 PVTT.