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- ArticleNarrow doorways alter brain connectivity and step patterns in isolated REM sleep behaviour disorder.Ehgoetz Martens KA, Matar E, Phillips JR, Shine JM, Grunstein RR, Halliday GM, Lewis SJG.Neuroimage Clin. 2022;33:102958.BACKGROUND: Motor impairments in those with isolated REM sleep behaviour disorder (iRBD) significantly increases the likelihood of developing Lewy body disease (e.g. Parkinson's disease and Dementia with Lewy Bodies).
OBJECTIVE: This study sought to explore the prodromal process of neurodegeneration by examining the neural signature underlying motor deficits in iRBD patients.
METHODS: A virtual reality (VR) gait paradigm (which has previously been shown to elicit adaptive changes in gait performance whilst navigating doorways in Parkinson's Disease - PD) was paired with fMRI to investigate whether iRBD patients demonstrated worsened motor performance and altered connectivity across frontoparietal, motor and basal ganglia networks compared to healthy controls. Forty participants (23 iRBD and 17 healthy controls) completed the virtual reality gait task whilst in the MRI scanner, and an additional cohort of 19 Early PD patients completed the behavioural virtual reality gait task.
RESULTS: As predicted, iRBD patients demonstrated slower and more variable stepping compared to healthy control participants and demonstrated an exaggerated response when navigating narrow compared to wide doorways, a phenomenon characteristically seen in PD. The iRBD patients also demonstrated less BOLD signal change in the left posterior putamen and right mesencephalic locomotor region, as well as reduced functional connectivity between the frontoparietal network and the motor network, when navigating narrow versus wide doorways compared to healthy control participants.
CONCLUSIONS: Taken together, this study demonstrates that iRBD patients have altered task-related brain connectivity, which may represent the neural underpinnings of early motor impairments that are evident in iRBD. - ArticleDey A, Pramanik PK, Dwivedi SKD, Neizer-Ashun F, Kiss T, Ganguly A, Rice H, Mukherjee P, Xu C, Ahmad M, Csiszar A, Bhattacharya R.Redox Biol. 2023 12;68:102958.Astrocytic dysfunction is central to age-related neurodegenerative diseases. However, the mechanisms leading to astrocytic dysfunction are not well understood. We identify that among the diverse cellular constituents of the brain, murine and human astrocytes are enriched in the expression of CBS. Depleting CBS in astrocytes causes mitochondrial dysfunction, increases the production of reactive oxygen species (ROS) and decreases cellular bioenergetics that can be partially rescued by exogenous H2S supplementation or by re-expressing CBS. Conversely, the CBS/H2S axis, associated protein persulfidation and proliferation are decreased in astrocytes upon oxidative stress which can be rescued by exogenous H2S supplementation. Here we reveal that in the aging brain, the CBS/H2S axis is downregulated leading to decreased protein persulfidation, together augmenting oxidative stress. Our findings uncover an important protective role of the CBS/H2S axis in astrocytes that may be disrupted in the aged brain.
- ArticleZhou XD, Chen QF, Yang W, Zuluaga M, Targher G, Byrne CD, Valenti L, Luo F, Katsouras CS, ... Show More Thaher O, Misra A, Ataya K, Oviedo RJ, Pik-Shan Kong A, Alswat K, Lonardo A, Wong YJ, Abu-Abeid A, Al Momani H, Ali A, Molina GA, Szepietowski O, Jumaev NA, Kızılkaya MC, Viveiros O, Toro-Huamanchumo CJ, Yen Kok KY, Ospanov O, Abbas SI, Robertson AG, Fouad Y, Mantzoros CS, Zhang H, Méndez-Sánchez N, Sookoian S, Chan WK, Treeprasertsuk S, Adams L, Ocama P, Ryan JD, Perera N, Sharara AI, Al-Busafi SA, Opio CK, Garcia M, Lim-Loo MC, Ruiz-Úcar E, Prasad A, Casajoana A, Abdelbaki TN, Zheng MH.EClinicalMedicine. 2024 Dec;78:102958.[This corrects the article DOI: 10.1016/j.eclinm.2024.102848.].
- ArticleVijayKumar S, Borja M, Neff N, Royer LA, Lange M.MethodsX. 2024 Dec;13:102958.Single-cell sequencing has revolutionized our understanding of cellular heterogeneity and cell state, enabling investigations across diverse fields such as developmental biology, immunology, and cancer biology. However, obtaining a high-quality single-cell suspension is still challenging, particularly when starting with limited materials like Zebrafish embryos, a powerful animal model for studying developmental processes and human diseases. Here, we present an optimized protocol for isolating single cells from individual zebrafish embryos, offering a valuable resource for researchers interested in working with limited starting material. The protocol facilitates unique investigations utilizing individual embryos, such as inter-individual genetic differences and embryo-specific lineage tracing analysis. Using a refined single-cell isolation protocol alongside zebrafish as a model organism, researchers can access a resource for exploring the emergence of all types and states of cells, advancing our understanding of cellular processes and disease mechanisms.
- ArticleLi M, Klungland A.DNA Repair (Amst). 2020 12;96:102958.R-loops are tripartite structures consisting of an RNA:DNA hybrid and a displaced single-stranded DNA [1]. They are widespread and occupy up to 5 % of the mammalian genomes [2]. R-loops have a key role in genome stability, and known functions associated with gene regulation, DNA replication, chromatin patterning, immunoglobuline gene recombination and DNA Double-strand break repair [3-7]. Novel methodology, including the application of the S9.6 antibody, have more recently led to detailed knowledge on the genome-wide distribution of the R-loops as well as the identification of the R-loop interactome [8-10]. The regulation of R-loops was recently shown to also depend on dynamic RNA-methylation, including METTL3/14 dependent 6-methylAdenines (m6As) and METTL8 dependent 3-methylCytosines (m3Cs) [11-13].
- ArticlePicard-Deland C, Pastor M, Solomonova E, Paquette T, Nielsen T.Conscious Cogn. 2020 08;83:102958.Despite a high prevalence and broad interest in flying dreams, these exceptional experiences remain infrequent. Our study aimed to (1) induce flying dreams using a custom-built virtual reality (VR) flying task, (2) examine their phenomenological correlates and (3) investigate their relations to participant state and trait factors. 137 participants underwent VR-flying followed by a morning nap. They also completed home dream journals for 5 days before and 10 days after the VR exposure. VR-flying successfully increased the reporting of flying dreams during the laboratory nap and on the following morning compared to both baseline frequencies and a control cohort. Flying dreams were also changed qualitatively, exhibiting higher levels of Lucid-control and emotional intensity, after VR exposure. Factors such as prior dream-flying experiences and level of VR sensory immersion modulated flying dream induction. Findings are consistent with a new vection-based explanation of dream-flying and may facilitate development of dream flight-induction technologies.
- ArticleKahana-Rojkind AH, McCarroll TR, Kuhns BD, Parsa A, Quesada-Jimenez R, Domb BG.Arthrosc Tech. 2024 May;13(5):102958.Retracted full-thickness tears of the gluteus medius tendon are a well-recognized cause of disabling weakness and pain that significantly impact patients' quality of life. We present an efficient knotless parachute technique for dermal allograft augmentation in open gluteal abductor tendon repairs. Our technique reinforces the suture-tendon interface by incorporating a robust biological scaffold into a knotless double-row fixation. This approach capitalizes on the increased pressure and contact area achieved between the greater trochanter and the dermal allograft/gluteus medius tendon construct without the prominence of knotted sutures.
- ArticleZhao Q, Liu X, Liu Z.Health Place. 2023 01;79:102958.Emerging evidence has shown the association between ambient air pollution exposure and comorbid chronic diseases, which can subsequently impair physical function. However, less is known about the causal and contextual effect of air pollution on physical disability. Using data from the China Health and Retirement Longitudinal Study (CHARLS), this study employs a geographical regression discontinuity design based on the Huai River Policy to estimate the impact of ambient air pollution on physical disability in activities of daily living (ADL) in China. We find that a 10 μg/m3 increase in particulate matter [particulate matter smaller than 10 μm (PM10)] leads to a 5.4% increase in the incidence of physical disability among middle-aged and older adults. This result is robust to using alternative measurement of key variables, different bandwidths and polynomial functions, and adjustment for a set of sociodemographic covariates. Stroke might be one of the potential pathological pathways linking air pollution and physical disability, with a 10 μg/m3 increase in PM10 leading to a 4.7% increase in the incidence of stroke. In heterogeneity analyses, we find that older adults, males, urban residents, and people with lower socioeconomic status are more vulnerable to air pollution. These results contribute to the limited evidence on the causal and contextual effect of air pollution on physical health, and further provide policy implications for air quality control and health protection for vulnerable populations.
- ArticleLin Q, Fathi P, Chen X.EBioMedicine. 2020 Sep;59:102958.Nanomedicine has proven promising in preclinical studies. However, only few formulations have been successfully translated to clinical use. A thorough understanding of how nanoparticles interact with cells in vivo is essential to accelerate the clinical translation of nanomedicine. Intravital imaging is a crucial tool to reveal the mechanisms of nanoparticle transport in vivo, allowing for the development of new strategies for nanomaterial design. Here, we first review the most recent progress in using intravital imaging to answer fundamental questions about nanoparticle delivery in vivo. We then elaborate on how nanoparticles interact with different cell types and how such interactions determine the fate of nanoparticles in vivo. Lastly, we discuss ways in which the use of intravital imaging can be expanded in the future to facilitate the clinical translation of nanomedicine.
- ArticleLin H, Ye SQ, Xu ZH, Penaloza JS, Aljuhani M, Vetter T, Zhao MT, McBride KL.Stem Cell Res. 2022 12;65:102958.Epstein-Barr virus (EBV) immortalized lymphoblastoid cell lines (LCLs) are widely used for banking. This bioresource could be leveraged for creating human iPSC lines to model diseases including CHD. We generated an LCL-derived iPSC line (NCHi001-A) from a patient with congenital aortic valve stenosis. NCHi001-A was EBV and transgenes free, exhibited stem cell-like morphology, expressed pluripotency markers, has a normal karyotype, and could be differentiated into cells of three germ layers in vitro. Relationship inference via a microarray-based analysis showed NCHi001-A is identical to the parental cell line. NCHi001-A can be used for disease modeling, drug discovery, and cell therapy development.
- ArticleSun J, He W, Liu HY, Qin J, Ye CL.Bioorg Chem. 2019 07;88:102958.A series of novel 1,4-benzodioxane thiazolidinedione piperazine derivatives targeting FabH were designed and synthesized. The compounds exhibited better inhibitory activity against Gram-negative bacteria by computer-assisted screening, antibacterial activity test and E. coli FabH inhibitory activity test, wherein compound 6j exhibited the most significant inhibitory activity (MIC = 1.80 μΜ for P. aeruginosa, MIC = 1.56 μΜ for E. coli). Besides, compound 6j still showed the best E. coli FabH inhibitory activity (IC50 = 0.06 μΜ). Moreover, the antibacterial activities of all compounds were strongly correlated with the inhibitory ability of FabH, with a correlation coefficient of 0.954. Computational docking studies also showed that compound 6j has interacting with FabH key residues in the active site.
- ArticleJacobs PJ, Oosthuizen MK, Mitchell C, Blount JD, Bennett NC.J Therm Biol. 2021 May;98:102958.Modelling of anthropogenic induced climate suggests more frequent and severe heatwaves in the future, which are likely to result in the mass die-off of several species of organisms. Oxidative stress induced by severe heat stress has previously been associated with a reduction in animal cognitive performance, depressed reproduction and lower life expectancy. Little is known about the non-lethal consequences of species should they survive extreme heat exposure. We investigated the oxidative stress experienced by the Namaqua rock mouse, a nocturnal rodent, using two experimental heat stress protocols, a 6 hour acute heat stress protocol without access to water and a 3-day heatwave simulation with ad libitum water. Oxidative stress was determined in the liver, kidney and brain using malondialdehyde (MDA) and protein carbonyl (PC) as markers of oxidative damage, and superoxide dismutase (SOD) and total antioxidant capacity (TAC) as markers of antioxidant defence. Incubator heat stress (heat and dehydration stress) was brought about by increasing the body temperatures of animals to 39-40.8 °C for 6 hours. Following incubator heat stress, significantly higher levels of MDA were observed in the liver. Dehydration did not explain the variation in oxidative markers and is likely a combined effect of thermal and dehydration stress. Individual body mass was significantly negatively correlated to kidney SOD and lipid peroxidation. A heatwave was simulated using a temperature cycle that would naturally occur during a heatwave in the species' local habitat, with a maximal ambient temperature of 38 °C. Following the simulated heatwave, SOD activity of the kidney demonstrated significantly lowered activity suggesting oxidative stress. Current heat waves in this species have the potential of causing oxidative stress. Heat and dehydration stress following exacerbated temperatures are likely to incur significant oxidative stress in multiple tissues demonstrating the importance of water availability to allow for rehydration to prevent oxidative stress.
- ArticleMammucari C.Cell Calcium. 2024 Dec;124:102958.Mitochondrial Ca2+ plays a positive role in regulating pyruvate dehydrogenase, as well as the TCA cycle enzymes isocitrate dehydrogenase and α-ketoglutarate dehydrogenase. This regulation boosts the production of reducing equivalents that fuel the electron transport chain, ultimately driving ATP production. The Mitochondrial Calcium Uniporter (MCU) is the highly selective channel responsible for mitochondrial Ca2+ uptake when local Ca2+ levels reach the threshold for channel activation. In a recent study, LaMoia et al. used an innovative [13C5]glutamine-based metabolic flux analysis method (Q-flux) to measure in vivo hepatic metabolic fluxes in liver-specific MCU-/- mice. Surprisingly, they observed increased flux through isocitrate dehydrogenase and α-ketoglutarate dehydrogenase. Metabolic pathways are continuously reorganized in response to intrinsic cellular signals, as well as hormonal and nutritional inputs. Integrating metabolic flux analysis into complex systems can provide deeper insights into how metabolic adaptations occur under different conditions.
- ArticleBarra J, Pallier C, New B.Acta Psychol (Amst). 2020 Jan;202:102958.A novel illusion entitled "the letter height superiority effect" has been demonstrated. This shows that letters are perceived as being taller than pseudoletters, while in reality their objective sizes are identical. An explanation of this illusion has been proposed in the framework of the Interactive Activation Model. Indeed, we postulated that the more a feature is activated, the taller a stimulus is perceived as being. The objective of the current study was to test this postulate by manipulating feature activation through signal-to-noise ratio. We presented gray stimuli (low signal-to-noise ratio) or black ones (high signal-to-noise ratio). In a first experiment, participants judged the size of pairs of either letters or pseudoletters presented as black or gray. In a second experiment we presented pairs consisting of a letter and a pseudoletter, of identical or different colors. In a third experiment, we presented pairs of letters or pseudoletters of identical or different colors by block to test the possible effect of previous exposure on perceptual judgments. The results showed that for identical objective size, participants perceive black stimuli to be taller than gray ones and that the effects of the nature of the stimuli and their color are cumulative. The results also indicated that the effects were not due to previous exposure to color or sizes. These results confirm the Interactive Activation Model as a credible explanation for the letter height superiority effect.
- ArticleSevinc V, Berkman MI.Appl Ergon. 2020 Jan;82:102958.Cybersickness, i.e. visually induced motion sickness, remains as a negative effect that is detrimental to the user experience of VEs (virtual environments) developed for VR (virtual reality) consumers. As the VR technology evolves, it is rather triggered by application aspects rather than hardware limitations. For this reason, there is still a need for a measurement method to assess and compare VEs for cybersickness effects. SSQ (Simulation Sickness Questionnaire) is used for measuring users' level of sickness symptoms and is highly appreciated in VR research. However, it is criticized for its psychometric qualities and applicability in VR, as a measure of cybersickness. Recently, two variants of SSQ were offered for measuring cybersickness, CSQ (Cybersickness Questionnaire) and VRSQ (Virtual Reality Sickness Questionnaire). There is also another variant with a different factor structure, which we call FSSQ, that is based on French translation of SSQ. Our study compares SSQ and these variants for their psychometric qualities; construct validity, discriminant validity, internal reliability, test-retest reliability and sensitivity to distinguish application aspects of VEs that are related to cybersickness. Using a within-subjects experiment design, we evaluated 7 different VEs with 32 participants through 9 sessions, resulting with 288 responses to the 16-item SSQ. Results suggested that both VRSQ and CSQ were valid and reliable measures of cybersickness, as well as being sensitive to application aspects such as translational and rotational movements required by users for navigation in VEs. Compared to SSQ and FSSQ; the cybersickness questionnaires, CSQ and VRSQ, revealed better indicators of validity. On the other hand, we assume that the development of the two cybersickness scales had limitations in sample size to represent VR consumers and limitations in stimuli to represent the applications aspects of consumer VEs. We suggest further evaluation of cybersickness symptoms with larger samples and broader range of applications to identify the symptoms and the construct of a subjective measurement tool.
- ArticleAnkle inversion proprioception measured during stair descent can identify chronic ankle instability.Wang X, Wang Z, Adams R, Ganderton C, Lyu J, Han J.Musculoskelet Sci Pract. 2024 08;72:102958.BACKGROUND: Individuals with chronic ankle instability (CAI) may experience recurrent ankle sprains and symptoms during daily activities such as stair descent, where the associated proprioceptive deficit is largely unevaluated.
OBJECTIVES: To evaluate the reliability and validity of an ankle inversion discrimination apparatus for stair descent, and examine whether proprioceptive scores from this apparatus are associated with patient-reported symptoms.
DESIGN: Cross-sectional study.
METHOD: Sixty-six participants volunteered in this study. The ankle inversion discrimination apparatus was purpose-built to assess ankle proprioception across four positions of ankle inversion (10°, 12°, 14°, and 16°) during stair descent. The Area Under the Receiver Operating Curve (AUC) was employed as the ankle proprioceptive discrimination score.
RESULTS: Test-retest reliability ICC (3,1) for the whole group was 0.825, with 0.747 for the non-CAI group (95%CI = 0.331-0.920) and 0.701 for CAI (95%CI = 0.242-0.904). The CAI group performed at a significantly lower level than non-CAI on the ankle inversion discrimination apparatus for stair descent assessment (0.769 ± 0.034 vs. 0.830 ± 0.035, F = 33.786, p < 0.001). CAIT scores were strongly and significantly correlated with scores from this apparatus (Spearman's rho = 0.730, p < 0.001).
CONCLUSIONS: The ankle inversion discrimination apparatus for stair descent is reliable and valid for assessing task-specific ankle proprioceptive impairments in CAI. The strong and significant relationship found between ankle proprioception during stair descent and the severity of CAI suggests that rehabilitation programs focusing on deficits in ankle inversion proprioception during stair descent may improve self-reported instability in CAI. - ArticleAljarad Z, Mobayed BB.Ann Med Surg (Lond). 2021 Nov;71:102958.BACKGROUND: acute upper gastrointestinal bleeding (UGIB) is a common medical condition that results in substantial morbidity, mortality, and medical care cost. The mortality rate for patients with acute upper gastrointestinal (GI) bleeding is 5-10%, and it has not changed much since 1945, despite the development in medicines, endoscopy, intensive care units (ICU), and surgical management. We conduct this study to observe some of the factors that predict death in these patients.
MATERIALS AND METHODS: The Study was conducted at the Internal Medicine Department, Digestive Division, Aleppo University Hospital, between July 2018 and June 2020. The study included all patients with acute upper GI bleeding who were admitted to the digestive division during the study period, or who were admitted by other departments requesting an upper GI endoscopy.
RESULTS: This study involved 234 patients, 137 males (58.55%), 97 females (41.45%).The patients' ages ranged between 17 and 81 years old, and the mean age value ± standard deviation was 57.15 ± 22.89 years old.The number of deaths reached 22, at a rate of 9.40%, 14 male deaths (10.22%), 8 female deaths (8.25%).
CONCLUSIONS: in this study we found a moderate inverse relationship between the hemoglobin value at admission and the incidence of death; the lower the hemoglobin value at admission, the higher the probability of patient's death. Also, there is a very significant direct relationship between the number of blood units transfused and the incidence of death, noting that all patients who died had received blood transfusions. Finally, we found a moderate inverse relationship between the arterial blood pressure value at admission and the incidence of death. - ArticleGaillochet M, Desrosiers C, Lombaert H.Med Image Anal. 2023 Dec;90:102958.The performance of learning-based algorithms improves with the amount of labelled data used for training. Yet, manually annotating data is particularly difficult for medical image segmentation tasks because of the limited expert availability and intensive manual effort required. To reduce manual labelling, active learning (AL) targets the most informative samples from the unlabelled set to annotate and add to the labelled training set. On the one hand, most active learning works have focused on the classification or limited segmentation of natural images, despite active learning being highly desirable in the difficult task of medical image segmentation. On the other hand, uncertainty-based AL approaches notoriously offer sub-optimal batch-query strategies, while diversity-based methods tend to be computationally expensive. Over and above methodological hurdles, random sampling has proven an extremely difficult baseline to outperform when varying learning and sampling conditions. This work aims to take advantage of the diversity and speed offered by random sampling to improve the selection of uncertainty-based AL methods for segmenting medical images. More specifically, we propose to compute uncertainty at the level of batches instead of samples through an original use of stochastic batches (SB) during sampling in AL. Stochastic batch querying is a simple and effective add-on that can be used on top of any uncertainty-based metric. Extensive experiments on two medical image segmentation datasets show that our strategy consistently improves conventional uncertainty-based sampling methods. Our method can hence act as a strong baseline for medical image segmentation. The code is available on: https://github.com/Minimel/StochasticBatchAL.git.
- ArticleDitye T, Sartorio M, Welleschik L.J Anxiety Disord. 2025 Jan;109:102958.Emerging evidence suggests that certain individuals are unable to address others by name, presumably owing to anxiety experienced in social situations. This fear of using personal names has been termed alexinomia and occurs in all forms of relationships and communication. The symptoms of alexinomia show large overlap with the symptoms typically associated with social anxiety, raising the question of whether social anxiety could be the main driving factor of this type of name avoidance. Here, we investigated the relationship between alexinomia and social anxiety by testing name avoidance behavior in a sample of 190 participants with varying degrees of social anxiety. Results showed a strong positive relationship between these two variables. High levels of social anxiety, as measured by two independent standardized psychological instruments (i.e., the Social Interaction Anxiety Scale and the Liebowitz Social Anxiety Scale), were associated with higher degrees of fear-based name avoidance. This was shown by regression analysis as well as analyses of group differences. The findings indicate that alexinomia could be a common symptom in socially anxious individuals that so far has not been discussed in the psychological literature on social anxiety.
- ArticleRossi CM, Lenti MV, Merli S, Santacroce G, Di Sabatino A.Autoimmun Rev. 2022 Jan;21(1):102958.Allergic disorders target a young population, are increasing in both incidence and prevalence and are associated with significant disease burden. They result from the complex interplay between (epi)genetic and environmental factors, resulting in a Th2 inflammatory process targeting the epithelium of the respiratory tract (allergic rhinitis and asthma), skin (atopic dermatitis), and gastrointestinal tract (food allergy). Although the exact pathogenic mechanisms remain elusive, an altered immune system response in the gut is increasingly recognized as a relevant step. Allergic and gastrointestinal autoimmune disorders share several epidemiological, pathogenic and risk factors and several treatment modalities. Here we revise the current literature and show that allergic disorders are highly prevalent in gastrointestinal autoimmune diseases, including celiac disease, inflammatory bowel disease, autoimmune pancreatitis, and autoimmune cholangiopathies. No data are available for some autoimmune diseases, such as autoimmune gastritis and autoimmune enteropathy. To ensure the comprehensive care of patients with autoimmune gastrointestinal disorders, along with disease-specific factors, the presence of allergic disorders should be evaluated and treated when present, possibly targeting shared molecular pathways. Future studies are needed to define the exact pathogenic mechanisms underpinning the association between allergic and autoimmune diseases of the gastrointestinal tract.