rudyvdbrink/CitationDatabase huggingface dataset:
Robust parallel decision-making in neural circuits with nonlinear inhibition.
Proceedings of the National Academy of Sciences of the United States of America, 2020

An elemental computation in the brain is to identify the best in a set of options and report its value. It is required for inference, decision-making, optimization, action selection, consensus, and foraging. Neural computing is considered powerful because of its parallelism; however, it is unclear whether neurons can perform this max-finding operation in a way that improves upon the prohibitively slow optimal serial max-finding computation (which takes [Formula: see text] time for N noisy candidate options) by a factor of N, the benchmark for parallel computation. Biologically plausible architectures for this task are winner-take-all (WTA) networks, where individual neurons inhibit each other so only those with the largest input remain active. We show that conventional WTA networks fail the parallelism benchmark and, worse, in the presence of noise, altogether fail to produce a winner when N is large. We introduce the nWTA network, in which neurons are equipped with a second nonlinearity that prevents weakly active neurons from contributing inhibition. Without parameter fine-tuning or rescaling as N varies, the nWTA network achieves the parallelism benchmark. The network reproduces experimentally observed phenomena like Hick's law without needing an additional readout stage or adaptive N-dependent thresholds. Our work bridges scales by linking cellular nonlinearities to circuit-level decision-making, establishes that distributed computation saturating the parallelism benchmark is possible in networks of noisy, finite-memory neurons, and shows that Hick's law may be a symptom of near-optimal parallel decision-making with noisy input.
The physio-metabolic effects of time-restricting liquid sugar intake to six-hour windows during the mouse active phase: The effects of active phase liquid sugar consumption.
Physiology & behavior, 2020

Obesity is a major public health concern and overconsumption of unhealthy fats and sugary beverages are contributing factors. Time-restricted feeding can reduce obesity-associated pathophysiological parameters by limiting the time of food consumption; however, the effects of time-restricted sugary water consumption are unknown. To examine whether liquid calorie restriction impacts metabolic health, we measured metabolic parameters in mice provided liquid sugar at various intervals during the active phase. The control (Con) group received tap water, the adlibitum fructose-glucose (ALFG) group received ad libitumsugar water and the early fructose-glucose (EFG) and late fructose-glucose (LFG) groups received liquid sugar during the first and last six hours of the active period, respectively. Each group was given free access to chow. Zeitgeber time (ZT) notation was used to set all experimental time points to lights on as ZT 0. The ALFG group exhibited elevated body and adipose tissue weights compared to the other groups and increased hepatic steatosis compared to the Con group. The ALFG group consumed more calories than the other groups during ZT 6-11, indicating that this window may be critical in the promotion of weight gain from liquid sugar consumption. The EFG group exhibited higher levels of energy expenditure than the Con and LFG groups during the first half of the active period (ZT 12-17); however, there was no difference among the groups during the second half of the active period (ZT18-23). In contrast, the EFG group exhibited lower respiratory exchange ratio than other groups during the inactive period as well as the second half of the active period, indicating that the EFG group had greater metabolic flexibility and utilized lipids when carbohydrates from liquid sugar were not available. Additionally, the EFG group was more insulin tolerant than the ALFG and Con groups. Our results support the hypothesis that time-restricted liquid calorie restriction aids in reducing the detrimental metabolic effects of sugary drink consumption.
A reliable indirect cell-labelling protocol for optical imaging allows ex vivo visualisation of mesenchymal stem cells after transplantation.
Archives italiennes de biologie, 2013

We set out to assess the feasibility of exploiting expression of the mCherry gene, after lentiviral infection, in order visualise bone marrow-derived human mesenchymal stem cells (hMSCs) by optical imaging, and to provide proof of principle of this approach as a method for cell tracking and quantification in pre-clinical models. Commercial hMSCs were infected with a lentiviral vector carrying the mCherry gene under the control of the phosphoglycerate kinase promoter. After extensive in vitro culture, infected hMSCs were analysed for viability, morphology, differentiation capability, and maintenance of fluorescence. Thereafter, mCherry-positive cells were transplanted into unilaterally 6-hydroxy-dopamine lesioned rats (an experimental model of Parkinson's disease). Our analysis showed that hMSCs can be efficiently transduced with the lentiviral vector, retaining their biological features even in the long term. Intrastriatally transplanted mCherry-positive hMSCs can be detected ex vivo by a sensitive cooled CCD camera, both in the whole brain and in serial slices, and relatively quantified. Our protocol was found to be a reliable means of studying the viability of implanted hMSCs. mCherry labelling appears to be readily applicable in the post-transplantation tracking of stem cells and could favour the rapid development of new therapeutic targets for clinical treatments.
Translating Knowledge of Sexual Configurations Theory via Instructional Videos.
Archives of sexual behavior, 2021

Gender/sex and sexual diversity are increasingly understood by the public as complex. But, scientific frameworks that address the complexity of gender/sex and sexual diversity are few and not well situated for the public. Sexual configurations theory (SCT; van Anders, 2015) is one approach that provides a visual framework for understanding and measuring gender/sex and sexual diversity. But how might knowledge users and creators actually use it? To make SCT more accessible to researchers, educators, clinicians, and the general public, we created three instructional videos (individual gender/sex, gender/sex sexuality, and partner number sexuality) that explained SCT and demonstrated how to use its diagrams. Participants (N = 242) of diverse gender/sex and sexual identities, including professionals who work in gender/sex- and sexuality-related fields, watched one of the three videos, filled out the diagrams, and evaluated the video and diagrams via scaled and open-ended questions. Results demonstrated that the SCT videos were sufficient for most participants to fill out the diagrams. Participants evaluated the video generally positively, with some variation by condition, identity group, and professional status. These results indicate that instructional videos are able to translate SCT, potentially facilitating uptake of SCT by clinicians, researchers, and educators as well as increasing awareness of gender/sex and sexual diversity more broadly within the public.
Homeostatic state of microglia in a rat model of chronic sleep restriction.
Sleep, 2020

Chronic sleep restriction (CSR) negatively impacts brain functions. Whether microglia, the brain's resident immune cells, play any role is unknown. We studied microglia responses to CSR using a rat model featuring slowly rotating wheels (3 h on/1 h off), which was previously shown to induce both homeostatic and adaptive responses in sleep and attention. Adult male rats were sleep restricted for 27 or 99 h. Control rats were housed in locked wheels. After 27 and/or 99 h of CSR, the number of cells immunoreactive for the microglia marker ionized calcium-binding adaptor molecule-1 (Iba1) and the density of Iba1 immunoreactivity were increased in 4/10 brain regions involved in sleep/wake regulation and cognition, including the prelimbic cortex, central amygdala, perifornical lateral hypothalamic area, and dorsal raphe nucleus. CSR neither induced mitosis in microglia (assessed with bromodeoxyuridine) nor impaired blood-brain barrier permeability (assessed with Evans Blue). Microglia appeared ramified in all treatment groups and, when examined quantitatively in the prelimbic cortex, their morphology was not affected by CSR. After 27 h, but not 99 h, of CSR, mRNA levels of the anti-inflammatory cytokine interleukin-10 were increased in the frontal cortex. Pro-inflammatory cytokine mRNA levels (tumor necrosis factor-α, interleukin-1β, and interleukin-6) were unchanged. Furthermore, cortical microglia were not immunoreactive for several pro- and anti-inflammatory markers tested, but were immunoreactive for the purinergic P2Y12 receptor. These results suggest that microglia respond to CSR while remaining in a physiological state and may contribute to the previously reported homeostatic and adaptive responses to CSR.
Structural rearrangement of amyloid-β upon inhibitor binding suppresses formation of Alzheimer's disease related oligomers.
eLife, 2020

The formation of oligomers of the amyloid-β peptide plays a key role in the onset of Alzheimer's disease. We describe herein the investigation of disease-relevant small amyloid-β oligomers by mass spectrometry and ion mobility spectrometry, revealing functionally relevant structural attributes. In particular, we can show that amyloid-β oligomers develop in two distinct arrangements leading to either neurotoxic oligomers and fibrils or non-toxic amorphous aggregates. Comprehending the key-attributes responsible for those pathways on a molecular level is a pre-requisite to specifically target the peptide's tertiary structure with the aim to promote the emergence of non-toxic aggregates. Here, we show for two fibril inhibiting ligands, an ionic molecular tweezer and a hydrophobic peptide that despite their different interaction mechanisms, the suppression of the fibril pathway can be deduced from the disappearance of the corresponding structure of the first amyloid-β oligomers.
Suicidal ideation among Bangladeshi university students early during the COVID-19 pandemic: Prevalence estimates and correlates.
Children and youth services review, 2020

Lockdown, social isolation, and interruption of daily life during the COVID-19 period have impacted many lives. University students are particularly vulnerable to such disruptions and may be particularly disposed to suicidal ideation, potentially creating a new public health crisis. This study aimed to assess suicidal ideation and associated factors among university students in Bangladesh during the early stages of the COVID-19 pandemic. A cross-sectional online survey was conducted using the Google form (Google survey tool) from April to May 2020. Initially, 3366 respondents voluntarily completed the survey form. Finally, 3331 surveys were included in the final analyses after removing incomplete surveys. The data ware reviewed, rechecked, and analyzed with SPSS (25.0 version) software. A total of 1979 (59.4%) males and 1352 (40.6%) females participated. Respondents were between the ages of 18 to 28 years (mean age 21.4 years [SD = 1.9]). The prevalence estimate of suicidal ideation was 12.8%. Potential risk factors included less sleep, excess sleep, cigarette smoking, past suicidal thoughts, suicide attempt history, family history of suicidality, depression, anxiety, and stress. Potential protective factors included being male, having lower SES, living in rural areas, regular physical exercise, and satisfactory study. Suicidal ideation was prevalent among Bangladeshi university students during the onset of the COVID-19 pandemic. Understanding the correlates of suicidal ideation may aid to develop targeted strategies to support students during and after the COVID-19 pandemic.
Locomotor-related V3 interneurons initiate and coordinate muscles spasms after spinal cord injury.
Journal of neurophysiology, 2019

Spinal cord injury leads to a devastating loss of motor function and yet is accompanied by a paradoxical emergence of muscle spasms, which often involve complex muscle activation patterns across multiple joints, reciprocal muscle timing, and rhythmic clonus. We investigated the hypothesis that spasms are a manifestation of partially recovered function in spinal central pattern-generating (CPG) circuits that normally coordinate complex postural and locomotor functions. We focused on the commissural propriospinal V3 neurons that coordinate interlimb movements during locomotion and examined mice with a chronic spinal transection. When the V3 neurons were optogenetically activated with a light pulse, a complex coordinated pattern of motoneuron activity was evoked with reciprocal, crossed, and intersegmental activity. In these same mice, brief sensory stimulation evoked spasms with a complex pattern of activity very similar to that evoked by light, and the timing of these spasms was readily reset by activation of V3 neurons. Given that V3 neurons receive abundant sensory input, these results suggest that sensory activation of V3 neurons is alone sufficient to generate spasms. Indeed, when we silenced V3 neurons optogenetically, sensory evoked spasms were inhibited. Also, inhibiting general CPG activity by blocking N-methyl-d-aspartate (NMDA) receptors inhibited V3 evoked activity and associated spasms, whereas NMDA application did the opposite. Furthermore, overwhelming the V3 neurons with repeated optogenetic stimulation inhibited subsequent sensory evoked spasms, both in vivo and in vitro. Taken together, these results demonstrate that spasms are generated in part by sensory activation of V3 neurons and associated CPG circuits. NEW & NOTEWORTHY We investigated whether locomotor-related excitatory interneurons (V3) play a role in coordinating muscle spasm activity after spinal cord injury (SCI). Unexpectedly, we found that these neurons not only coordinate reciprocal motor activity but are critical for initiating spasms, as well. More generally, these results suggest that V3 neurons are important in initiating and coordinating motor output after SCI and thus provide a promising target for restoring residual motor function.
Sex-specific pathways among tri-allelic serotonin transporter polymorphism, trait neuroticism and generalized anxiety disorder.
Journal of psychiatry & neuroscience : JPN, 2020

Neuroticism personality trait is recognized as an important endophenotypic predictor of generalized anxiety disorder (GAD). Furthermore, endophenotype-based pathway approaches have recently been shown to have greater advantages for gene-finding strategies than traditional case-control studies. In the present study, in addition to conventional case-control methods, we used pathway analyses to test whether the tri-allelic serotonin transporter promoter polymorphism (combining 5-HTTLPR and rs25531) is associated with risk of GAD through its effects on trait neuroticism.
Superficial Temporal Artery Perforator Flap: Indications, Surgical Outcomes, and Donor Site Morbidity.
Dentistry journal, 2020

The aim of this retrospective case series was to discuss indications, surgical outcomes, and donor site morbidity in the use of superficial temporal artery perforator (STAP) flaps in intra-oral or extra-oral facial reconstruction. This study involved 9 patients treated with a STAP flap at the Maxillo-Facial Surgery Unit of the University of Campania "Luigi Vanvitelli", Naples. A STAP flap was used alone or in combination with other local flaps, for the coverage of facial soft tissue defects, after the resection of craniofacial malignant tumors (
Metabolic rerouting via SCD1 induction impacts X-linked adrenoleukodystrophy.
The Journal of clinical investigation, 2021

X-linked adrenoleukodystrophy (ALD) is a progressive neurodegenerative disease caused by mutations in ABCD1, the peroxisomal very long-chain fatty acid (VLCFA) transporter. ABCD1 deficiency results in accumulation of saturated VLCFAs. A drug screen using a phenotypic motor assay in a zebrafish ALD model identified chloroquine as the top hit. Chloroquine increased expression of stearoyl-CoA desaturase-1 (scd1), the enzyme mediating fatty acid saturation status, suggesting that a shift toward monounsaturated fatty acids relieved toxicity. In human ALD fibroblasts, chloroquine also increased SCD1 levels and reduced saturated VLCFAs. Conversely, pharmacological inhibition of SCD1 expression led to an increase in saturated VLCFAs, and CRISPR knockout of scd1 in zebrafish mimicked the motor phenotype of ALD zebrafish. Importantly, saturated VLCFAs caused ER stress in ALD fibroblasts, whereas monounsaturated VLCFA did not. In parallel, we used liver X receptor (LXR) agonists to increase SCD1 expression, causing a shift from saturated toward monounsaturated VLCFA and normalizing phospholipid profiles. Finally, Abcd1-/y mice receiving LXR agonist in their diet had VLCFA reductions in ALD-relevant tissues. These results suggest that metabolic rerouting of saturated to monounsaturated VLCFAs may alleviate lipid toxicity, a strategy that may be beneficial in ALD and other peroxisomal diseases in which VLCFAs play a key role.
Cannabis vapor self-administration elicits sex- and dose-specific alterations in stress reactivity in rats.
Neurobiology of stress, 2020

Cannabis users frequently report stress relief as their primary reason for use. Recent studies indicate that human cannabis users exhibit blunted stress reactivity; however, it is unknown whether this is a cause or a consequence of chronic cannabis use.
Risk factors for pediatric cerebral sinovenous thrombosis: A case-control study with case validation.
Thrombosis research, 2020

Cerebral sinovenous thrombosis (CSVT) represents the second most common type of venous thromboembolism (VTE) in children. Current literature includes limited evidence on risk factors for CSVT, particularly in the pediatric population. We sought to determine risk factors for CSVT in pediatric patients through a single-institutional case-control study. In addition, we evaluated thrombophilias, treatments and outcomes in CSVT among cases.
New light on cortical neuropeptides and synaptic network plasticity.
Current opinion in neurobiology, 2020

Neuropeptides, members of a large and evolutionarily ancient family of proteinaceous cell-cell signaling molecules, are widely recognized as extremely potent regulators of brain function and behavior. At the cellular level, neuropeptides are known to act mainly via modulation of ion channel and synapse function, but functional impacts emerging at the level of complex cortical synaptic networks have resisted mechanistic analysis. New findings from single-cell RNA-seq transcriptomics now illuminate intricate patterns of cortical neuropeptide signaling gene expression and new tools now offer powerful molecular access to cortical neuropeptide signaling. Here we highlight some of these new findings and tools, focusing especially on prospects for experimental and theoretical exploration of peptidergic and synaptic networks interactions underlying cortical function and plasticity.
Ecological momentary assessment versus retrospective assessment for measuring change in health-related quality of life following cardiac intervention.
Journal of patient-reported outcomes, 2020

Measuring change in health-related quality-of-life (HRQoL) is important to assess the impact of disease and/or treatment. Ecological momentary assessment (EMA) comprises the repeated assessment of momentary HRQoL in the natural environment and is particularly suited to capture daily experiences. Our objective was to study whether change in momentary measures or retrospective measures of HRQoL are more strongly associated with criterion measures of change in HRQoL. Twenty-six coronary artery disease patients completed momentary and retrospective HRQoL questionnaires before and after coronary revascularization. Momentary HRQoL was assessed with 14 items which were repeatedly presented 9 times a day for 7 consecutive days. Each momentary assessment period was followed by a retrospective HRQoL questionnaire that used the same items, albeit phrased in the past tense and employing a one-week time frame. Criterion measures of change comprised the New York Heart Association functioning classification system and the Subjective Significance Change Questionnaire. Regression analysis was used to determine the association of momentary and retrospective HRQoL change with the criterion measures of change.
Obstructive sleep apnoea and cognitive decline in mild-to-moderate Alzheimer's disease.
The European respiratory journal, 2020

We evaluated the influence of untreated obstructive sleep apnoea (OSA) on the magnitude of cognitive decline and on several cognitive subdomains in patients with mild-to-moderate Alzheimer's disease.In this single-centre study, 144 patients were recruited prospectively from a cognitive impairment unit and underwent overnight polysomnography.The mean±sd change in the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) score at 12 months was 3.19±5.61 in the non-OSA group and 0.08±5.62 in the OSA group, with an intergroup difference of -3.36 (95% CI 0.19-0.16; p=0.002). We did not observe a significant difference in any cognitive subdomains at 12 months. Regarding Mini-Mental State Examination scores at 36 months, the mean change was 1.69 (95% CI -1.26-4.64; p=0.445). No significant differences were found among different OSA severity groups.We observed that ADAS-cog scores were better in the OSA group than in the non-OSA group by a statistically but not clinically significant margin. We did not find differences in the different cognitive subdomains after 1 year or in global cognition after 3 years of follow-up.
Neighborhood socioeconomic status and racial disparities in schizophrenia: An exploration of domains of functioning.
Schizophrenia research, 2020

Black Americans are disproportionately diagnosed with schizophrenia and experience worse objective functional outcomes (e.g., hospitalizations) than their White counterparts. However, we have a limited understanding of the psychological pathways through which Black Americans with schizophrenia reach worse outcomes. This study assessed race and domains of functioning (e.g., neurocognition, functional capacity) known to be associated with objective outcomes in a sample of 108 non-Hispanic Black and 61 non-Hispanic White individuals with schizophrenia-spectrum disorders from the Social Cognition Psychometric Evaluation (SCOPE) study. Three primary findings emerged: First, Black participants showed lower scores than White participants on measures of neurocognition(NC), social cognition(SC), and everyday living skills, but not social skills or community functioning. Second, neighborhood socioeconomic status (SES) explained 21% of the relationship between race and NC but did not mediate the relationship between race and SC or everyday living skills. Finally, prior research has established that NC, SC, social skills, and everyday living skills predict community functioning in individuals. Finally, prior research has established that NC, SC, social skills, and everyday living skills predict community functioning in individuals with schizophrenia. In our sample, after controlling for neighborhood SES, race did not moderate the relationships of NC, SC, social skills, or everyday living skills to community functioning. This indicates that relationships between these domains are comparably strong across Black and White Americans. Taken together, these findings show that NC, SC, and everyday living skills may be important areas to explore in regards to racial disparities in schizophrenia. More research, especially incorporating nuanced race- and SES-related variables, is needed to understand how to best intervene and improve real-world outcomes for Black Americans with schizophrenia.