Miracle-dz/UniFAR-FTUs huggingface dataset:
Apathy in small vessel cerebrovascular disease is associated with deficits in effort-based decision making

Abstract Patients with small vessel cerebrovascular disease frequently suffer from apathy, a debilitating neuropsychiatric syndrome, the underlying mechanisms of which remain to be established. Here we investigated the hypothesis that apathy is associated with disrupted decision making in effort-based decision making, and that these alterations are associated with abnormalities in the white matter network connecting brain regions that underpin such decisions. Eighty-two patients with MRI evidence of small vessel disease were assessed using a behavioural paradigm as well as diffusion weighted MRI. The decision-making task involved accepting or rejecting monetary rewards in return for performing different levels of physical effort (hand grip force). Choice data and reaction times were integrated into a drift diffusion model that framed decisions to accept or reject offers as stochastic processes approaching a decision boundary with a particular drift rate. Tract-based spatial statistics were used to assess the relationship between white matter tract integrity and apathy, while accounting for depression. Overall, patients with apathy accepted significantly fewer offers on this decision-making task. Notably, while apathetic patients were less responsive to low rewards, they were also significantly averse to investing in high effort. Significant reductions in white matter integrity were observed to be specifically related to apathy, but not to depression. These included pathways connecting brain regions previously implicated in effort-based decision making in healthy people. The drift rate to decision parameter was significantly associated with both apathy and altered white matter tracts, suggesting that both brain and behavioural changes in apathy are associated with this single parameter. On the other hand, depression was associated with an increase in the decision boundary, consistent with an increase in the amount of evidence required prior to making a decision. These findings demonstrate altered effort-based decision making for reward in apathy, and also highlight dissociable mechanisms underlying apathy and depression in small vessel disease. They provide clear potential brain and behavioural targets for future therapeutic interventions, as well as modelling parameters that can be used to measure the effects of treatment at the behavioural level.
Neuronal Network Excitability in Alzheimer’s Disease: The Puzzle of Similar versus Divergent Roles of Amyloid β and Tau

Abstract Alzheimer’s disease (AD) is the most frequent neurodegenerative disorder that commonly causes dementia in the elderly. Recent evidence indicates that network abnormalities, including hypersynchrony, altered oscillatory rhythmic activity, interneuron dysfunction, and synaptic depression, may be key mediators of cognitive decline in AD. In this review, we discuss characteristics of neuronal network excitability in AD, and the role of Aβ and tau in the induction of network hyperexcitability. Many patients harboring genetic mutations that lead to increased Aβ production suffer from seizures and epilepsy before the development of plaques. Similarly, pathologic accumulation of hyperphosphorylated tau has been associated with hyperexcitability in the hippocampus. We present common and divergent roles of tau and Aβ on neuronal hyperexcitability in AD, and hypotheses that could serve as a template for future experiments.
COVID-19 Impacts on Families of Color and Families of Children With Asthma

Abstract Objective This cross-sectional study quantified differences in (a) social determinants of health (SDOH) and perceived changes in SDOH during the 2019 novel coronavirus (COVID-19) pandemic and (b) COVID-19 psychosocial impacts across four groups: (a) non-Hispanic White (NHW) parents of children with asthma, (b) Black, Indigenous, or other People of Color (BIPOC) parents of healthy children, (c) BIPOC parents of children with asthma, and (d) NHW parents of healthy children (referent). The NIMHD Framework was used to identify SDOHs that may change for families during COVID-19. Methods Parents were recruited via Prolific (N = 321) and completed questions about COVID-19 family impacts on employment, income, access to food and healthcare, and psychosocial functioning, including discrimination. It was hypothesized that NHW families of children with asthma and BIPOC families would endorse greater negative outcomes relative to NHW parents of healthy children. Results BIPOC families experienced greater food insecurity and discrimination relative to NHW parents of healthy children. When compared with the NHW healthy group, COVID-19 resulted in greater parent-reported resource losses for both BIPOC groups and greater reductions in healthcare access for both asthma groups. Children with asthma and BIPOC children had greater distress surrounding COVID-19. BIPOC and NHW parents of children with asthma reported greater worries about resource losses due to COVID-19. Conclusions The pandemic is widening inequities for BIPOC families, especially for families of children with asthma. These results highlight the need for interventions that address the needs of underserved communities, providing the infrastructure, policies, and supports needed to reduce health inequities during and after COVID-19.
Hidden hearing loss is associated with loss of ribbon synapses of cochlea inner hair cells

Abstract The present study aimed to observe the changes in the cochlea ribbon synapses after repeated exposure to moderate-to-high intensity noise. Guinea pigs received 95 dB SPL white noise exposure 4 h a day for consecutive 7 days (we regarded it a medium-term and moderate-intensity noise, or MTMI noise). Animals were divided into four groups: Control, 1DPN (1-day post noise), 1WPN (1-week post noise), and 1MPN (1-month post noise). Auditory function analysis by auditory brainstem response (ABR) and compound action potential (CAP) recordings, as well as ribbon synapse morphological analyses by immunohistochemistry (Ctbp2 and PSD95 staining) were performed 1 day, 1 week, and 1 month after noise exposure. After MTMI noise exposure, the amplitudes of ABR I and III waves were suppressed. The CAP threshold was elevated, and CAP amplitude was reduced in the 1DPN group. No apparent changes in hair cell shape, arrangement, or number were observed, but the number of ribbon synapse was reduced. The 1WPN and 1MPN groups showed that part of ABR and CAP changes recovered, as well as the synapse number. The defects in cochlea auditory function and synapse changes were observed mainly in the high-frequency region. Together, repeated exposure in MTMI noise can cause hidden hearing loss (HHL), which is partially reversible after leaving the noise environment; and MTMI noise-induced HHL is associated with inner hair cell ribbon synapses.
Perspectives on Social Media from Adolescents and Young Adults with Cancer

Background: Adolescents and young adults (AYAs) with cancer use social media in unique ways throughout treatment. The purpose of this article is to describe the social media experiences of AYAs with cancer as a means of exploring the potential impact of social media on AYA psychosocial development after diagnosis and throughout cancer treatment. Methods: Seven AYAs treated for cancer, aged 15–20 years, completed a semi-structured interview regarding their social media preferences and habits. Each interview was transcribed verbatim and de-identified. Data were coded and themes were identified via latent thematic analysis. Results: Four themes emerged regarding social media experiences for AYAs with cancer: (1) changes in audience and feedback after diagnosis; (2) attitudes about body image and peer support; (3) control over personal, familial, and societal messages about illness; and (4) maintaining normalcy despite hospital stressors. Discussion: Social media appear especially useful for promoting social and identity development as AYAs undergo cancer treatment. Specifically, social media provide spaces to negotiate body image and sense of self, to manage peer relationships, to reclaim control and independence, and to maintain normalcy. Understanding these experiences will prepare healthcare providers and caregivers to assess ongoing psychosocial development and adjustment throughout cancer treatment.
MicroRNA-125a Correlates with Decreased Psoriasis Severity and Inflammation and Represses Keratinocyte Proliferation

Background: Psoriasis has a complex etiology related to inflammation and dysregulated immune system. MicroRNA (miR)-125a is a miRNA intimately related to inflammation and immunity; therefore, we presumed that it might play a role in the pathogenesis of psoriasis. This study aimed to investigate the correlation of miR-125a with disease severity and inflammation in psoriasis patients, and the effect of miR-125a on proliferation, apoptosis as well as its target signaling pathway in keratinocytes. Methods: Sixty psoriasis patients were consecutively recruited, then lesional and non-lesional skin tissue samples were collected. miR-125a in lesional and non-lesional skin tissues, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-17 mRNA expressions in lesional skin tissues were detected. Then, miR-125a overexpression, control overexpression, miR-125a knockdown and control knockdown plasmids were transfected into HaCaT cells. Subsequently, cell proliferation, apoptosis, IL-23R, JAK2, and STAT3 expressions were assessed. Results: miR-125a was reduced in lesional skin tissue compared with non-lesional skin tissue (p < 0.001), and it distinguished lesional skin tissue from non-lesional skin tissue with a high area under curve of 0.917 (95% CI 0.866–0.968). Negative association of miR-125a in lesional skin tissue with lesional body surface area (p = 0.037) and psoriasis area and severity index score (p < 0.001) was found. Additionally, miR-125a was negatively correlated with TNF-α (p = 0.001), IL-1β (p = 0.014), and IL-17 (p = 0.003) in lesional skin tissue. In cellular experiments, miR-125a overexpression inhibited proliferation and promoted apoptosis, while miR-125a knockdown enhanced proliferation and repressed apoptosis in HaCaT cells. Additionally, miR-125a negatively regulated the IL-23R/JAK2/STAT3 pathway in HaCaT cells. Conclusion: miR-125a could facilitate the disease monitoring and probably has the potential to be a therapeutic target in psoriasis.
A switch from noncanonical to canonical Wnt signaling stops neuroblast migration through a Slt–Robo and RGA-9b/ARHGAP–dependent mechanism

Significance Cell migration is a central process in development, homeostasis, and disease. Among the extracellular signaling molecules that control this process are members of the Wnt family of secreted glycoproteins, which trigger distinct canonical and noncanonical pathways in responding cells. Studies in vertebrates have shown that these pathways can antagonistically regulate migration, but how they functionally interact is not known. Using the migration of the C. elegans QR neuroblast descendants as a tractable model system, we found that the two pathways converge on activators and inhibitors of the Rho family of small GTPases that mediate cell migration. Our results show that through this cross-talk mechanism, Wnt pathways can interact to tightly regulate the migration of cells to their final destinations. Members of the Wnt family of secreted glycoproteins regulate cell migration through distinct canonical and noncanonical signaling pathways. Studies of vertebrate development and disease have shown that these pathways can have opposing effects on cell migration, but the mechanism of this functional interplay is not known. In the nematode Caenorhabditis elegans, a switch from noncanonical to canonical Wnt signaling terminates the long-range migration of the QR neuroblast descendants, providing a tractable system to study this mechanism in vivo. Here, we show that noncanonical Wnt signaling acts through PIX-1/RhoGEF, while canonical signaling directly activates the Slt–Robo pathway component EVA-1/EVA1C and the Rho GTPase–activating protein RGA-9b/ARHGAP, which are required for migration inhibition. Our results support a model in which cross-talk between noncanonical and canonical Wnt signaling occurs through antagonistic regulation of the Rho GTPases that drive cell migration.
Baicalin regulates the development of pediatric asthma via upregulating microRNA-103 and mediating the TLR4/NF-κB pathway

Abstract Pediatric asthma seriously endangers the well-being and health of children worldwide. Baicalin (BA) protects against diverse disorders, including asthma. Therefore, this study explored the mechanism of BA in pediatric asthma. The ovalbumin (OVA)-induced asthmatic mouse model was established to evaluate BA efficacy from aspects of oxidative stress, inflammation, blood cells in bronchoalveolar lavage fluid (BALF) and collagen deposition. Differentially expressed microRNAs (miRs) in BA-treated mice were analyzed. Effects of BA on PDGF-BB-induced smooth muscle cells (SMCs) were assessed. miR downstream mRNA and the related pathway were predicted and verified, and their effects on asthmatic mice were evaluated. BA effectively reversed OVA-induced oxidative stress and inflammation, as well as decreased the number of total cells, eosinophils and neutrophils in BALF, and collagen deposition. miR-103 was significantly upregulated after BA treatment. BA inhibited the abnormal proliferation of PDGF-BB-induced SMCs, which was prevented by miR-103 knockdown. miR-103 targeted TLR4 and regulated the extent of NF-κB phosphorylation. In vivo, miR-103 inhibition weakened the alleviating effects of BA on asthma, which was then reversed after silencing of TLR4. We highlighted that BA has the potency to halt the pediatric asthma progression via miR-103 upregulation and the TLR4/NF-κB axis inhibition.
Allergic rhinitis is associated with atmospheric SO2: Follow-up study of children from elementary schools in Ulsan, Korea

Objectives The purpose of this study was to examine the association of allergic rhinitis with air pollutant concentrations using the follow-up data of elementary school children in Ulsan, Korea. Methods All students of four elementary schools in Ulsan, South Korea were surveyed at two-year intervals. The survey used data collected five times, over a nine-year period from June 2009 to April 2018. The questionnaire used in the survey was a modified version of the ISAAC (International society of asthma and allergy of children) questionnaire. A skin prick test (SPT) was performed with 24 standard antigens. To estimate the levels of exposure to outdoor air pollution, the concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO), and particulate matter 10 μm or less in diameter (PM10) were used. As a dependent variable, a history of allergic rhinitis diagnosed by a doctor during the last 1-year was considered. Logistic regression analysis was used to select variables suitable for the statistical model. The selected variables were then used to assess their association with the dependent variable using the generalized estimation equation. Results Among environmental factors, SO2 was associated with a high risk and PM10 was associated with a low risk of allergic rhinitis. The risk of allergic rhinitis from living in a house built within the last year was high, and the risk from living in a multi-family house or apartment was higher than that from living in a segregated house. History of allergic diseases in the family was a high-risk factor for allergic rhinitis. There was a relationship between a history of bronchiolitis at less than 2 years of age and a high risk of allergic rhinitis. Boys were at a higher risk than girls. Conclusion From the follow-up data of elementary school students in Ulsan, Korea, the concentration of SO2, which is an indicator of the degree of industrialization, was related to the prevalence of allergic rhinitis. Among all the risk factors, history of allergic disease in the parents was the most important factor, and the study reconfirmed the results of the previous studies.
Perception-Action Integration Is Modulated by the Catecholaminergic System Depending on Learning Experience

Abstract Background The process underlying the integration of perception and action is a focal topic in neuroscientific research and cognitive frameworks such as the theory of event coding have been developed to explain the mechanisms of perception-action integration. The neurobiological underpinnings are poorly understood. While it has been suggested that the catecholaminergic system may play a role, there are opposing predictions regarding the effects of catecholamines on perception-action integration. Methods Methylphenidate (MPH) is a compound commonly used to modulate the catecholaminergic system. In a double-blind, randomized crossover study design, we examined the effect of MPH (0.25 mg/kg) on perception-action integration using an established “event file coding” paradigm in a group of n = 45 healthy young adults. Results The data reveal that, compared with the placebo, MPH attenuates binding effects based on the established associations between stimuli and responses, provided participants are already familiar with the task. However, without prior task experience, MPH did not modulate performance compared with the placebo. Conclusions Catecholamines and learning experience interactively modulate perception-action integration, especially when perception-action associations have to be reconfigured. The data suggest there is a gain control–based mechanism underlying the interactive effects of learning/task experience and catecholaminergic activity during perception-action integration.
Spatial and temporal dynamics of space use by free-ranging domestic dogs Canis familiaris in rural Africa.

Variation in the spatial ecology of animals influences the transmission of infections and so understanding host behaviour can improve the control of diseases. Despite the global distribution of free-ranging domestic dogs Canis familiaris and their role as reservoirs for zoonotic diseases, little is known about the dynamics of their space use. We deployed GPS loggers on owned but free-ranging dogs from six villages in rural Chad, and tracked the movements of 174 individuals in the dry season and 151 in the wet season. We calculated 95% and core home ranges using auto-correlated kernel density estimates (AKDE95 and AKDEcore ), determined the degree to which their movements were predictable, and identified correlates of movement patterns. The median AKDE95 range in the dry season was 0.54km2 and in the wet season was 0.31km2 , while the median AKDEcore range in the dry season was 0.08km2 and in the wet season was 0.04km2 . Seasonal variation was, in part, related to owner activities; Dogs from hunting households had ranges that were five times larger in the dry season. At least 70% of individuals were more predictably 'at home' (<50m from the household) throughout the day in the dry season. 80% of dogs demonstrated periodicity in activity levels (speed) and just over half the dogs exhibited periodicity in location (repeated space use). In the wet season, dogs mostly exhibited 24-hour cycles in activity and location, with peaks at midday. In the dry season, dogs exhibited both 12 and 24-hour cycles, with either a single peak at midday, or one peak between 6am and 12 noon and a second between 6 and 10pm. Strategies to control canine-mediated zoonoses can be improved by tailoring operations to the local spatial ecology of free-ranging dogs. Interventions using a door-to-door strategy in rural Chad would best conduct operations during the dry season, when access to dogs around their household more reliably exceeds 70% throughout the day. Given the importance of use in hunting for explaining variation in dog space-use, targeting approaches to disease control at the household level on the basis of owner activities offers potential to improve access to dogs.
Paclitaxel increases axonal localization and vesicular trafficking of Nav1.7

See Silagi and Segal (doi:10.1093/brain/awab196) for a scientific commentary on this article. The chemotherapy drug paclitaxel induces an increase in Nav1.7 channel expression in sensory neurons, enhancing their excitability. Akin et al. use live imaging to visualize trafficking and surface localization of Nav1.7 channels in sensory axons after exposure to paclitaxel, and reveal a role for inflammation in this process.
Care Delivery Impact of the COVID-19 Pandemic on Breast Cancer Care

PURPOSE: COVID-19 has altered healthcare delivery. Previous work has focused on patients with cancer and COVID-19, but little has been reported on healthcare system changes among patients without COVID-19. METHODS: We performed a retrospective study of patients with breast cancer (BC) in New York City between February 1, 2020, and April 30, 2020. New patients were included as were patients scheduled to receive intravenous or injectable therapy. Patients with COVID-19 were excluded. Demographic and treatment information were obtained by chart review. Delays and/or changes in systemic therapy, surgery, radiation, and radiology related to the pandemic were tracked, along with the reasons for delay and/or change. Univariate and multivariable analysis were used to identify factors associated with delay and/or change. RESULTS: We identified 350 eligible patients, of whom 149 (42.6%) experienced a delay and/or change, and practice reduction (51.0%) was the most common reason. The patients who identified as Black or African American, Asian, or Other races were more likely to experience a delay and/or change compared with White patients (Black, 44.4%; Asian, 47.1%; Other, 55.6%; White, 31.4%; P = .001). In multivariable analysis, Medicaid compared with commercial insurance (odds ratio [OR], 3.04; 95% CI, 1.32 to 7.27) was associated with increased odds of a delay and/or change, whereas stage II or III BC compared with stage I (OR, 0.38; 95% CI, 0.15 to 0.95; and OR, 0.28; 95% CI, 0.08 to 0.092, respectively) was associated with decreased odds of a delay and/or change. CONCLUSION: Almost half of the patients with BC without COVID-19 had a delay and/or change. We found racial and socioeconomic disparities in the likelihood of a delay and/or change. Further studies are needed to determine the impact these care alterations have on BC outcomes.
Towards realizing the vision of precision medicine: AI based prediction of clinical drug response

See Chen et al. (doi:10.1093/brain/awab199) for a scientific commentary on this article. De Jong et al. present a retrospectively validated machine learning model linking drug mechanism of action and patients' genetic/clinical/demographic background to anti-epileptic drug response. They identify determinants of poor response and explore their potential utility in clinical trial design for precision medicine.