Miracle-dz/UniFAR-FTUs huggingface dataset:
Whole-Brain Mapping of Direct Inputs to Dopamine D1 and D2 Receptor-Expressing Medium Spiny Neurons in the Posterior Dorsomedial Striatum

Abstract The posterior dorsomedial striatum (pDMS) is mainly composed of medium spiny neurons (MSNs) expressing either dopamine D1 receptors (D1Rs) or D2Rs. Activation of these two MSN types produces opposing effects on addictive behaviors. However, it remains unclear whether pDMS D1-MSNs or D2-MSNs receive afferent inputs from different brain regions or whether the extrastriatal afferents express distinct dopamine receptors. To assess whether these afferents also contained D1Rs or D2Rs, we generated double transgenic mice, in which D1R-expressing and D2R-expressing neurons were fluorescently labeled. We used rabies virus-mediated retrograde tracing in these mice to perform whole-brain mapping of direct inputs to D1-MSNs or D2-MSNs in the pDMS. We found that D1-MSNs preferentially received inputs from the secondary motor, secondary visual, and cingulate cortices, whereas D2-MSNs received inputs from the primary motor and primary sensory cortices, and the thalamus. We also discovered that the bed nucleus of the stria terminalis (BNST) and the central nucleus of the amygdala (CeA) contained abundant D2R-expressing, but few D1R-expressing, neurons in a triple transgenic mouse model. Remarkably, although limited D1R or D2R expression was observed in extrastriatal neurons that projected to D1-MSNs or D2-MSNs, we found that cortical structures preferentially contained D1R-expressing neurons that projected to D1-MSNs or D2-MSNs, while the thalamus, substantia nigra pars compacta (SNc), and BNST had more D2R-expressing cells that projected to D2-MSNs. Taken together, these findings provide a foundation for future understanding of the pDMS circuit and its role in action selection and reward-based behaviors.
Using Mobile Phone Data Collection Tool, Surveda, for Noncommunicable Disease Surveillance in Five Low- and Middle-income Countries.

Objectives The Noncommunicable Disease (NCD) Mobile Phone Survey, a component of the Bloomberg Philanthropies Data for Health Initiative, determines the prevalence of NCDs and their associated risk factors and demonstrates the use of mobile phone administered surveys to supplement periodic national household surveys. The NCD Mobile Phone Survey uses Surveda to administer the survey; Surveda is an open-source, multi-modal software specifically developed for the project. The objective of the paper is to describe Surveda, review data collection methods used in participating countries and discuss how Surveda and similar approaches can improve public health surveillance. Methods Surveda features full-service survey design and implementation through a web application and collects data via Short Messaging Service (SMS), Interactive Voice Response (IVR) and/or mobile web. Surveda's survey design process employs five steps: creating a project, creating questionnaires, designing and starting a survey, monitoring survey progress, and exporting survey results. Results The NCD Mobile Phone Survey has been successfully conducted in five countries, Zambia (2017), Philippines (2018), Morocco (2019), Malawi (2019), and Sri Lanka (2019), with a total of 23,682 interviews completed. Discussion This approach to data collection demonstrates that mobile phone surveys can supplement face-to-face data collection methods. Furthermore, Surveda offers major advantages including automated mode-switch, question randomization and comparison features. Conclusion Accurate and timely survey data informs a country's abilities to make targeted policy decisions while prioritizing limited resources. The high acceptance of Surveda demonstrates that the use of mobile phones for surveillance can deliver accurate and timely data collection.
Elaboração e aceitabilidade de biscoitos enriquecidos com aveia e farinha de bagaço de uva

The growing demand for healthy food is accompanied by a search for processes that generate low volumes of solid waste, or which provide for its reuse. This paper proposes the development and evaluation of the acceptability of cookies enriched with oat and grape pomace flour. The grape pomace flour, produced as an alternative to the use of large volumes of waste generated by the wine industry, represents a great source of fibre and natural antioxidants at low cost. It was obtained by grinding the dry pomace and subsequent granulometric standardization. The oat flour, a source of food fibres, was obtained by grinding oat flakes. To prepare the cookies, three formulations with different percentages of replacement of the wheat flour by wholemeal oat flour and grape pomace flour were used, defined as Formulations A, B and C with 30%, 40% and 50% replacement respectively. The experiment was carried out using a completely randomized design, the results submitted to an analysis of variance and the means compared by the Tukey test at 5% significance. The results demonstrated that the cookies presented acceptable sensory properties and the percentage of substitution used in this study was accepted by the judges for all the attributes evaluated. The use of oat provided an increase in food fibre and the grape pomace flour was an alternative ingredient for the reuse of a product normally discarded.
Walnut Consumption, Plasma Metabolomics, and Risk of Type 2 Diabetes and Cardiovascular Disease.

BACKGROUND Walnut consumption is associated with lower risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, it is unknown whether plasma metabolites related to walnut consumption are also associated with lower risk of cardiometabolic diseases. OBJECTIVES The study aimed to identify plasma metabolites associated with walnut consumption and evaluate the prospective associations between the identified profile and risk of T2D and CVD. METHODS The discovery population included 1833 participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) study with available metabolomics data at baseline. The study population included 57% women (baseline mean BMI (in kg/m2): 29.9; mean age: 67 y). A total of 1522 participants also had available metabolomics data at year 1 and were used as the internal validation population. Plasma metabolomics analyses were performed using LC-MS. Cross-sectional associations between 385 known metabolites and walnut consumption were assessed using elastic net continuous regression analysis. A 10-cross-validation (CV) procedure was used, and Pearson correlation coefficients were assessed between metabolite weighted models and self-reported walnut consumption in each pair of training-validation data sets within the discovery population. We further estimated the prospective associations between the identified metabolite profile and incident T2D and CVD using multivariable Cox regression models. RESULTS A total of 19 metabolites were significantly associated with walnut consumption, including lipids, purines, acylcarnitines, and amino acids. Ten-CV Pearson correlation coefficients between self-reported walnut consumption and the plasma metabolite profile were 0.16 (95% CI: 0.11, 0.20) in the discovery population and 0.15 (95% CI: 0.10, 0.20) in the validation population. The metabolite profile was inversely associated with T2D incidence (HR per 1 SD: 0.83; 95% CI: 0.71, 0.97; P = 0.02). For CVD incidence, the HR per 1-SD was 0.71 (95% CI: 0.60, 0.85; P < 0.001). CONCLUSIONS A metabolite profile including 19 metabolites was associated with walnut consumption and with a lower risk of incident T2D and CVD in a Mediterranean population at high cardiovascular risk.
Antihypertensive effects of exercise involve reshaping of gut microbiota and improvement of gut-brain axis in spontaneously hypertensive rat

ABSTRACT Exercise (Ex) has long been recognized to produce beneficial effects on hypertension (HTN). This coupled with evidence of gut dysbiosis and an impaired gut-brain axis led us to hypothesize that reshaping of gut microbiota and improvement in impaired gut-brain axis would, in part, be associated with beneficial influence of exercise. Male spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were randomized into sedentary, trained, and detrained groups. Trained rats underwent moderate-intensity exercise for 12 weeks, whereas, detrained groups underwent 8 weeks of moderate-intensity exercise followed by 4 weeks of detraining. Fecal microbiota, gut pathology, intestinal inflammation, and permeability, brain microglia and neuroinflammation were analyzed. We observed that exercise training resulted in a persistent decrease in systolic blood pressure in the SHR. This was associated with increase in microbial α diversity, altered β diversity, and enrichment of beneficial bacterial genera. Furthermore, decrease in the number of activated microglia, neuroinflammation in the hypothalamic paraventricular nucleus, improved gut pathology, inflammation, and permeability were also observed in the SHR following exercise. Interestingly, short-term detraining did not abolish these exercise-mediated improvements. Finally, fecal microbiota transplantation from exercised SHR into sedentary SHR resulted in attenuated SBP and an improved gut-brain axis. These observations support our concept that an impaired gut-brain axis is linked to HTN and exercise ameliorates this impairment to induce antihypertensive effects.
Microglia Elimination Increases Neural Circuit Connectivity and Activity in Adult Mouse Cortex

Microglia have crucial roles in sculpting synapses and maintaining neural circuits during development. To test the hypothesis that microglia continue to regulate neural circuit connectivity in adult brain, we have investigated the effects of chronic microglial depletion, via CSF1R inhibition, on synaptic connectivity in the visual cortex in adult mice of both sexes. Microglia have crucial roles in sculpting synapses and maintaining neural circuits during development. To test the hypothesis that microglia continue to regulate neural circuit connectivity in adult brain, we have investigated the effects of chronic microglial depletion, via CSF1R inhibition, on synaptic connectivity in the visual cortex in adult mice of both sexes. We find that the absence of microglia dramatically increases both excitatory and inhibitory synaptic connections to excitatory cortical neurons assessed with functional circuit mapping experiments in acutely prepared adult brain slices. Microglia depletion leads to increased densities and intensities of perineuronal nets. Furthermore, in vivo calcium imaging across large populations of visual cortical neurons reveals enhanced neural activities of both excitatory neurons and parvalbumin-expressing interneurons in the visual cortex following microglia depletion. These changes recover following adult microglia repopulation. In summary, our new results demonstrate a prominent role of microglia in sculpting neuronal circuit connectivity and regulating subsequent functional activity in adult cortex. SIGNIFICANCE STATEMENT Microglia are the primary immune cell of the brain, but recent evidence supports that microglia play an important role in synaptic sculpting during development. However, it remains unknown whether and how microglia regulate synaptic connectivity in adult brain. Our present work shows chronic microglia depletion in adult visual cortex induces robust increases in perineuronal nets, and enhances local excitatory and inhibitory circuit connectivity to excitatory neurons. Microglia depletion increases in vivo neural activities of both excitatory neurons and parvalbumin inhibitory neurons. Our new results reveal new potential avenues to modulate adult neural plasticity by microglia manipulation to better treat brain disorders, such as Alzheimer's disease.
A comparative study on the anti-inflammatory effect of angiotensin-receptor blockers & statins on rheumatoid arthritis disease activity

Background & objectives: Rheumatoid artherits (RA) is a refractory disease and the imbalance between pro- and anti-inflammatory cytokines in favor of pro-inflammatory cytokines has been implicated in pathogenesis of RA. In this context, the aim of the present study was to compare the anti-inflammatory and antioxidant effects of candesartan, an angiotensin-receptor blocker, and atorvastatin in RA patients. Methods: In this single-blinded parallel randomized placebo controlled study, the patients recruited between December 2017 and May 2018 were categorized into three groups: group 1 included 15 RA patients who served as control group and received traditional therapy (+ placebo); group 2 included 15 RA patients who received traditional therapy + candesartan (8 mg/day); and group 3 included 15 patients who received traditional therapy + atorvastatin (20 mg/day) for three months. Clinical status in RA patients was evaluated by Disease Activity Score 28 (DAS28), Health Assessment Questionnaire-Disability Index (HAQ-DI) and morning stiffness before and three months after treatment. All groups were subjected to biochemical analysis of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), tumour necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and malondialdehyde (MDA) before and three months after treatment. Results: Both candesartan and atorvastatin treated groups showed significant decrease in serum levels IL-1β and TNF-α, acute-phase reactants (CRP and ESR), number of swollen joint and patient global assessment. This was also associated with improvement in disease activity and quality of life regarding DAS28 and HAQ-DI as compared to baseline data and the control group. Atorvastatin group showed significant decrease in the serum level of oxidative stress marker (MDA). Interpretation & conclusions: Both candesartan and atorvastatin showed anti-inflammatory effect and immunomodulatory effects leading to improvement in clinical status and disease activity in RA patients. However, atorvastatin was superior to candesartan through its anti-oxidant effect.
The Role of Gamma Oscillations in the Pathophysiology of Substance Use Disorders

Substance use disorders (SUDs) are a major public health problem—with over 200 million people reporting drug use in 2016. Electroencephalography (EEG) is a powerful tool that can provide insights into the impact of SUDs on cognition. Specifically, modulated gamma activity may provide an index of the pathophysiology of SUDs. Thus, the purpose of this review was to investigate the impact of alcohol, tobacco, cannabis, cocaine, and amphetamine on gamma activity, among pre-clinical and clinical populations during acute and chronic exposure and withdrawal states. We searched multiple databases for key terms related to SUDs, EEG, and gamma and ensured rigorous methods by using a standardized review reporting tool. We included 30 studies in this review and found that all substances were associated with modulation of gamma activity, across states and in both preclinical and clinical populations. Gamma oscillations appeared to be differentially modulated in clinical versus preclinical populations and had the most complex relationship with alcohol, indicating that it may act differently than other substances. The findings of this review offer insights into the pathophysiology of SUDs, providing a potential window into novel treatments for SUDs via modulation of gamma activity.
Changes in accommodative function following small-incision lenticule extraction for high myopia

Purpose To examine whether the amplitude of accommodation, the accommodative response, and the accommodative facility is affected and correlated with changes in higher-order aberrations for patients with high myopia surgically treated with small-incision lenticule extraction (SMILE). Methods 35 highly myopic eyes (myopic spherical equivalent of at least 6 diopters) of 35 patients treated with SMILE were included. Assessments were made before and 3 months after surgery. Donders push-up-method was used to measure the amplitude of accommodation. The accommodative response was assessed using an open-field autorefractor”Grand Seiko WAM-5500” (Grand Seiko Co. Ltd., Hiroshima, Japan) in combination with a Badal optometer and stimuli of accommodation at 0.0, 0.5, 1.25, 2.0, 3.0, and 4.0 D, respectively. Accommodative facility was measured at 40 cm with ±2,00D flipper lenses. All measurements of accommodation were performed monocularly with the refractive error corrected with soft contact lenses. Results The amplitude of accommodation did not change statistically significantly (mean difference -0.24 D (SD 0.98), 95% CI of mean difference -0.58 D to 0.11 D, paired-sample t(34) = -1.39; P = 0.17). The accommodative responses at 0.0, 0.5, 1.25, 2.0, 3.0, and 4.0 D did not statistically significantly change either (F(6,29) = 1.15; P = . 36). Finally, the accommodative facility was also unchanged with a mean difference of 1.11 cycles per minute (SD 5.11, 95% CI of mean difference -0.64 to 2.87, paired-sample t(34) = 1.29; P = 0.21). No clinically significant associations between changes in accommodation and higher-order aberrations were found. Conclusions SMILE does not alter the amplitude of accommodation, the accommodative response, nor the accommodative facility for highly myopic patients, and the surgically induced corneal higher-order aberrations do not affect the accommodative function.
Prone Positioning in Moderate to Severe Acute Respiratory Distress Syndrome Due to COVID-19: A Cohort Study and Analysis of Physiology

Background: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS) but it is unknown whether prone positioning improves outcomes in mechanically ventilated patients with moderate to severe ARDS due to COVID-19. Methods: A cohort study at a New York City hospital at the peak of the early pandemic in the United States, under crisis conditions. The aim was to determine the benefit of prone positioning in mechanically ventilated patients with ARDS due to COVID-19. The primary outcome was in-hospital death. Secondary outcomes included changes in physiologic parameters. Fine-Gray competing risks models with stabilized inverse probability treatment weighting (sIPTW) were used to determine the effect of prone positioning on outcomes. In addition, linear mixed effects models (LMM) were used to assess changes in physiology with prone positioning. Results: Out of 335 participants who were intubated and mechanically ventilated, 62 underwent prone positioning, 199 met prone positioning criteria and served as controls and 74 were excluded. The intervention and control groups were similar at baseline. In multivariate-adjusted competing risks models with sIPTW, prone positioning was significantly associated with reduced mortality (SHR 0.61, 95% CI 0.46-0.80, P < 0.005). Using LMM to evaluate the impact of positioning maneuvers on physiological parameters, the oxygenation-saturation index was significantly improved during days 1-3 (P < 0.01) whereas oxygenation-saturation index (OSI), oxygenation-index (OI) and arterial oxygen partial pressure to fractional inspired oxygen (PaO2: FiO2) were significantly improved during days 4-7 (P < 0.05 for all). Conclusions: Prone positioning in patients with moderate to severe ARDS due to COVID-19 is associated with reduced mortality and improved physiologic parameters. One in-hospital death could be averted for every 8 patients treated. Replicating results and scaling the intervention are important, but prone positioning may represent an additional therapeutic option in patients with ARDS due to COVID-19.
In Situ Separation and Analysis of Lipids by Paper Spray Ionization Mass Spectrometry

Paper spray ionization (PSI) is an extractive ambient ionization technique for mass spectrometry (MS), whereby a triangular paper tip serves as the sampling base and the electrospray tip. During PSI, analytes are extracted and transported to the edge of the paper tip by the applied spraying solvent. Analytes can be purified from a sample matrix and separated from each other by this transportation process. In this study, we investigated and utilized the analyte transportation process of PSI for the in situ separation and analysis of lipid mixtures. We found that differential transport of phosphatidylcholine (PC) and triacylglycerol (TAG), the two most abundant lipid classes in animals, occurred during PSI. We also found that the order in which these lipids moved strongly depended on how the spraying solvent was applied to the paper base. The more polar PC moved faster than the less polar TAG during PSI, when a polar solvent was slowly fed into a paper tip, whereas TAG was transported faster than PC when excess solvent was applied to the tip at once. In addition, we achieved a complete separation and detection of PC and TAG by slowly supplying a nonpolar solvent to a PSI tip.
Surround inhibition in patients with juvenile myoclonic epilepsy

ABSTRACT Objective In healthy subjects, there is a reduction in the amplitudes of somatosensory-evoked potentials (SEPs) after the simultaneous stimulation of two nerves compared to the sum of separate stimulations. This reduction is due to the inhibition of one area in the cortex after stimulation of the neighboring area, which results from the surround inhibition (SI) phenomenon. In this study, we aimed to investigate whether there was a decrease in SI of SEP in patients with juvenile myoclonic epilepsy (JME). Methods We included 17 patients with JME and 18 healthy subjects. Groups were similar in terms of age and gender. We recorded SEPs after stimulating (i) median nerve (mSEP), (ii) ulnar nerve (uSEP), (iii) median and ulnar nerves simultaneously (muSEP) at wrist. The arithmetic sum (aSEP) of amplitudes of mSEP and uSEP was compared with the amplitudes of muSEP. We also calculated SI%. Results The amplitudes of SEPs were significantly higher in the JME group than in the healthy subjects (mSEP, p = 0.005; uSEP, p = 0.032; muSEP, p = 0.014). In healthy subjects and the JME group, the amplitude of muSEP was significantly lower than the aSEP (p = 0.014; p = 0.001, respectively). However, SI% was significantly higher in the JME group (p = 0.010). Significance Although the SI is maintained in JME patients, the higher SI% indicates an impairment relative to healthy subjects.