Miracle-dz/UniFAR-FTUs huggingface dataset:
Discovering Effective Connectivity in Neural Circuits: Analysis Based on Machine Learning Methodology

As multielectrode array technology increases in popularity, accessible analytical tools become necessary. Simultaneous recordings from multiple neurons may produce huge amounts of information. Traditional tools based on classical statistics are either insufficient to analyze multiple spike trains or sophisticated and expensive in computing terms. In this communication, we put to the test the idea that AI algorithms may be useful to gather information about the effective connectivity of neurons in local nuclei at a relatively low computing cost. To this end, we decided to explore the capacity of the algorithm C5.0 to retrieve information from a large series of spike trains obtained from a simulated neuronal circuit with a known structure. Combinatory, iterative and recursive processes using C5.0 were built to examine possibilities of increasing the performance of a direct application of the algorithm. Furthermore, we tested the applicability of these processes to a reduced dataset obtained from original biological recordings with unknown connectivity. This was obtained in house from a mouse in vitro preparation of the spinal cord. Results show that this algorithm can retrieve neurons monosynaptically connected to the target in simulated datasets within a single run. Iterative and recursive processes can identify monosynaptic neurons and disynaptic neurons under favorable conditions. Application of these processes to the biological dataset gives clues to identify neurons monosynaptically connected to the target. We conclude that the work presented provides substantial proof of concept for the potential use of AI algorithms to the study of effective connectivity.
Echocardiographic Characteristics and Outcome in Patients With COVID-19 Infection and Underlying Cardiovascular Disease

Background: The cardiac manifestations of coronavirus disease 2019 (COVID-19) patients with cardiovascular disease (CVD) remain unclear. We aimed to investigate the prognostic value of echocardiographic parameters in patients with COVID-19 infection and underlying CVD. Methods: One hundred fifty-seven consecutive hospitalized COVID-19 patients were enrolled. The left ventricular (LV) and right ventricular (RV) structure and function were assessed using bedside echocardiography. Results: Eighty-nine of the 157 patients (56.7%) had underlying CVD. Compared with patients without CVD, those with CVD had a higher mortality (22.5 vs. 4.4%, p = 0.002) and experienced more clinical events including acute respiratory distress syndrome, acute heart injury, or deep vein thrombosis. CVD patients presented with poorer LV diastolic and RV systolic function compared to those without CVD. RV dysfunction (30.3%) was the most frequent, followed by LV diastolic dysfunction (9.0%) and LV systolic dysfunction (5.6%) in CVD patients. CVD patients with high-sensitivity troponin I (hs-TNI) elevation or requiring mechanical ventilation therapy demonstrated worsening RV function compared with those with normal hs-TNI or non-intubated patients, whereas LV systolic or diastolic function was similar. Impaired RV function was associated with elevated hs-TNI level. RV function and elevated hs-TNI level were independent predictors of higher mortality in COVID-19 patients with CVD. Conclusions: Patients with COVID-19 infection and underlying CVD displayed impaired LV diastolic and RV function, whereas LV systolic function was normal in most patients. Importantly, RV function parameters are predictive of higher mortality.
New Insights Into the Pathologic Roles of the Platelet-Activating Factor System

Described almost 50 years ago, the glycerophosphocholine lipid mediator Platelet-activating factor (PAF) has been implicated in many pathologic processes. Indeed, elevated levels of PAF can be measured in response to almost every type of pathology involving inflammation and cell damage/death. In this review, we provide evidence for PAF involvement in pathologic processes, with focus on cancer, the nervous system, and in photobiology. Importantly, recent insights into how PAF can generate and travel via bioactive extracellular vesicles such as microvesicle particles (MVP) are presented. What appears to be emerging from diverse pathologies in different organ systems is a common theme where pro-oxidative stressors generate oxidized glycerophosphocholines with PAF agonistic effects, which then trigger more enzymatic PAF synthesis via the PAF receptor. A downstream consequence of PAF receptor activation is the generation and release of MVP which provide a mechanism to transmit PAF as well as other bioactive agents. The knowledge gaps which when addressed could result in novel therapeutic strategies are also discussed. Taken together, an enhanced understanding of the PAF family of lipid mediators is essential in our improved comprehension of the relationship amongst the diverse cutaneous, cancerous, neurologic and systemic pathologic processes.
The Principle of Least Effort and Comprehension of Spoken Sentences by Younger and Older Adults

There is considerable evidence that listeners’ understanding of a spoken sentence need not always follow from a full analysis of the words and syntax of the utterance. Rather, listeners may instead conduct a superficial analysis, sampling some words and using presumed plausibility to arrive at an understanding of the sentence meaning. Because this latter strategy occurs more often for sentences with complex syntax that place a heavier processing burden on the listener than sentences with simpler syntax, shallow processing may represent a resource conserving strategy reflected in reduced processing effort. This factor may be even more important for older adults who as a group are known to have more limited working memory resources. In the present experiment, 40 older adults (Mage = 75.5 years) and 20 younger adults (Mage = 20.7) were tested for comprehension of plausible and implausible sentences with a simpler subject-relative embedded clause structure or a more complex object-relative embedded clause structure. Dilation of the pupil of the eye was recorded as an index of processing effort. Results confirmed greater comprehension accuracy for plausible than implausible sentences, and for sentences with simpler than more complex syntax, with both effects amplified for the older adults. Analysis of peak pupil dilations for implausible sentences revealed a complex three-way interaction between age, syntactic complexity, and plausibility. Results are discussed in terms of models of sentence comprehension, and pupillometry as an index of intentional task engagement.
A Real-Time PCR Assay for the Diagnosis of Intestinal Schistosomiasis and Cure Assessment After the Treatment of Individuals With Low Parasite Burden

The laboratorial diagnosis of the intestinal schistosomiasis is always performed using Kato-Katz technique. However, this technique presents low sensitivity for diagnosis of individuals with low parasite burden, which constitutes the majority in low endemicity Brazilian locations for the disease. The objective of this study was developed and to validate a real-time PCR assay (qPCR) targeting 121 bp sequence to detect Schistosoma spp. DNA for the diagnosis of intestinal schistosomiasis and a sequence of the human β-actin gene as internal control. Firstly, the qPCR was standardized and next it was evaluated for diagnosis and cure assessment of intestinal schistosomiasis in the resident individuals in Tabuas and Estreito de Miralta, two locations in Brazil endemic for intestinal schistosomiasis. The qPCR assay results were compared with those of the Kato-Katz (KK) test, examining 2 or 24 slides, Saline Gradient (SG) and “reference test” (24 KK slides + SG). The cure assessment was measured by these diagnostic techniques at 30, 90, and 180 days post-treatment. In Tabuas, the positivity rates obtained by the qPCR was 30.4% (45/148) and by “reference test” was of 31.0% (46/148), with no statistical difference (p = 0.91). The presumed cure rates at 30, 90, and 180 days post-treatment were 100, 94.4, and 78.4% by the analysis of 24 KK slides, 100, 94.4, and 78.4% by the SG, and 100, 83.3, and 62.1% by the qPCR assay. In Estreito de Miralta, the positivity obtained by qPCR was 18.3% (26/142) and with “reference test” was 24.6% (35/142), with no statistical difference (p = 0.20). The presumed cure rates were 93.3, 96.9, and 96.5% by the KK, 93.3, 96.9, and 100% by the SG, and 93.3, 93.9, and 96.5% by the qPCR at 30, 90, and 180 days post-treatment, respectively. This study showed that the diagnostic techniques presented different performance in the populations from the two districts (Tabuas and Estreito de Miralta) and reinforces the need of combining techniques to improve diagnosis accuracy, increasing the detection of individuals with low parasite burden. This combination of techniques consists an important strategy for controlling the disease transmission.
Fixel-Based Analysis of White Matter Degeneration in Patients With Progressive Supranuclear Palsy or Multiple System Atrophy, as Compared to Parkinson's Disease

Introduction: White matter degeneration may contribute to clinical symptoms of parkinsonism. Objective: We used fixel-based analysis (FBA) to compare the extent and patterns of white matter degeneration in different parkinsonian syndromes—including idiopathic Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Methods: This is a retrospective interpretation of prospectively acquired data of patients recruited in previous studies during 2008 and 2019. Diffusion-weighted images were acquired on a 3-Tesla scanner (diffusion weighting b = 1000 s/mm2–applied along either 64 or 30 non-collinear directions) from 53 patients with PD (men/women: 29/24; mean age: 65.06 ± 5.51 years), 47 with MSA (men/women: 20/27; mean age: 63.00 ± 7.19 years), and 50 with PSP men/women: 20/30; mean age: 65.96 ± 3.14 years). Non-parametric permutation tests were used to detect intergroup differences in fixel-related indices—including fiber density, fiber cross-section, and their combination. Results: Patterns of white matter degeneration were significantly different between PD and atypical parkinsonisms (MSA and PSP). Compared with patients with PD, those with MSA and PSP showed a more extensive white matter involvement—noticeably descending tracts from primary motor cortex to corona radiata and cerebral peduncle. Lesions of corpus callosum were specific to PSP and absent in both MSA and PD. Discussion: FBA identified specific patterns of white matter changes in MSA and PSP patients compared to PD. Our results proved the utility of FBA in evaluation of implied biological processes of white matter changes in parkinsonism. Our study set the stage for future applications of this technique in patients with parkinsonian syndromes.
Overexpression of SlGATA17 Promotes Drought Tolerance in Transgenic Tomato Plants by Enhancing Activation of the Phenylpropanoid Biosynthetic Pathway

GATA transcription factors (TFs) are widely distributed in eukaryotes. Some GATA TFs have been shown to be related to photosynthesis, germination, circadian rhythm, and other functions in plants. Our previous study found that some members of this family have obvious responses when tomato plants are subjected to drought stress, in which the SlGATA17 gene is significantly upregulated. To further verify the function of this gene under drought stress, we constructed tomato lines with this gene overexpressed. Phenotypic and physiological indicators indicated that the SlGATA17-overexpressing plants were more drought tolerant than the wild-type plants. Transcriptomic sequencing results showed that the overexpression of the SlGATA17 gene improved the activity of the phenylpropanoid biosynthesis pathway. The PAL enzyme activity assay results confirmed that the initial activity of this pathway was enhanced in transgenic plants, especially in the initial response stage, indicating that the SlGATA17 gene regulates the drought resistance of tomato plants by regulating the activity of the phenylpropanoid biosynthesis pathway.
A Socially Assistive Robot for Long-Term Cardiac Rehabilitation in the Real World

What are the benefits of using a socially assistive robot for long-term cardiac rehabilitation? To answer this question we designed and conducted a real-world long-term study, in collaboration with medical specialists, at the Fundación Cardioinfantil-Instituto de Cardiología clinic (Bogotá, Colombia) lasting 2.5 years. The study took place within the context of the outpatient phase of patients' cardiac rehabilitation programme and aimed to compare the patients' progress and adherence in the conventional cardiac rehabilitation programme (control condition) against rehabilitation supported by a fully autonomous socially assistive robot which continuously monitored the patients during exercise to provide immediate feedback and motivation based on sensory measures (robot condition). The explicit aim of the social robot is to improve patient motivation and increase adherence to the programme to ensure a complete recovery. We recruited 15 patients per condition. The cardiac rehabilitation programme was designed to last 36 sessions (18 weeks) per patient. The findings suggest that robot increases adherence (by 13.3%) and leads to faster completion of the programme. In addition, the patients assisted by the robot had more rapid improvement in their recovery heart rate, better physical activity performance and a higher improvement in cardiovascular functioning, which indicate a successful cardiac rehabilitation programme performance. Moreover, the medical staff and the patients acknowledged that the robot improved the patient motivation and adherence to the programme, supporting its potential in addressing the major challenges in rehabilitation programmes.
Serum Neurofilament Light and GFAP Are Associated With Disease Severity in Inflammatory Disorders With Aquaporin-4 or Myelin Oligodendrocyte Glycoprotein Antibodies

Objective: To evaluate the potential of serum neurofilament light (sNfL) and serum glial fibrillary acidic protein (sGFAP) as disease biomarkers in neuromyelitis optica spectrum disorder (NMOSD) with aquaporin-4 antibody (AQP4-ab) or myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD). Methods: Patients with AQP4-ab-positive NMOSD (n = 51), MOGAD (n = 42), and relapsing-remitting multiple sclerosis (RRMS) (n = 31 for sNfL and n = 22 for sGFAP testing), as well as healthy controls (HCs) (n = 28), were enrolled prospectively. We assessed sNfL and sGFAP levels using ultrasensitive single-molecule array assays. Correlations of sNfL and sGFAP levels with clinical parameters were further examined in AQP4-ab-positive NMOSD and MOGAD patients. Results: sNfL levels were significantly higher in patients with AQP4-ab-positive NMOSD (median 17.6 pg/mL), MOGAD (27.2 pg/mL), and RRMS (24.5 pg/mL) than in HCs (7.4 pg/mL, all p < 0.001). sGFAP levels were remarkably increased in patients with AQP4-ab-positive NMOSD (274.1 pg/mL) and MOGAD (136.7 pg/mL) than in HCs (61.4 pg/mL, both p < 0.001). Besides, sGFAP levels were also significantly higher in patients with AQP4-ab-positive NMOSD compared to those in RRMS patients (66.5 pg/mL, p < 0.001). The sGFAP/sNfL ratio exhibited good discrimination among the three disease groups. sNfL levels increased during relapse in patients with MOGAD (p = 0.049) and RRMS (p < 0.001), while sGFAP levels increased during relapse in all three of the disease groups (all p < 0.05). Both sNfL and sGFAP concentrations correlated positively with Expanded Disability Status Scale scores in AQP4-ab-positive NMOSD (β = 1.88, p = 0.018 and β = 2.04, p = 0.032) and MOGAD patients (β = 1.98, p = 0.013 and β = 1.52, p = 0.008). Conclusion: sNfL and sGFAP levels are associated with disease severity in AQP4-ab-positive NMOSD and MOGAD patients, and the sGFAP/sNfL ratio may reflect distinct disease pathogenesis.
Predictive Analysis of the Neutralization Activity in Convalescent Plasmas From COVID-19 Recovered Patients in Zhejiang Province, China, January-March, 2020

Background Convalescent plasma (CP) transfusion is considered to be the priority therapeutic option for COVID-19 inpatients when no specific drugs are available for emerging infections. An alternative, simple, and sensitive method is urgently needed for clinical use to detect neutralization activity of the CP to avoid the use of inconvenient micro-neutralization assay. Method This study aims to explore optimal index in predicting the COVID-19 CP neutralization activity (neutralizing antibody titers, NAb titers) in an indirect ELISA format. Fifty-seven COVID-19-recovered patients plasma samples were subjected to anti-SARS-CoV-2 RBD, S1, and N protein IgG antibody by indirect ELISA. Results ELISA-RBD exhibited high specificity (96.2%) and ELISA-N had high sensitivity (100%); while ELISA-S1 had low sensitivity (86.0%) and specificity (73.1%). Furthermore, ELISA-RBD IgG titers and pseudovirus-based NAb titers correlated significantly, with R2 of 0.2564 (P < 0.0001). Conclusion ELISA-RBD could be a substitute for the neutralization assay in resource-limited situations to screen potential plasma donors for further plasma infusion therapy.
Transcription Factor TonEBP Stimulates Hyperosmolality-Dependent Arginine Vasopressin Gene Expression in the Mouse Hypothalamus

The hypothalamic neuroendocrine system is strongly implicated in body energy homeostasis. In particular, the degree of production and release of arginine vasopressin (AVP) in the hypothalamus is affected by plasma osmolality, and that hypothalamic AVP is responsible for thirst and osmolality-dependent water and metabolic balance. However, the osmolality-responsive intracellular mechanism within AVP cells that regulates AVP synthesis is not clearly understood. Here, we report a role for tonicity-responsive enhancer binding protein (TonEBP), a transcription factor sensitive to cellular tonicity, in regulating osmosensitive hypothalamic AVP gene transcription. Our immunohistochemical work shows that hypothalamic AVP cellular activity, as recognized by c-fos, was enhanced in parallel with an elevation in TonEBP expression within AVP cells following water deprivation. Interestingly, our in vitro investigations found a synchronized pattern of TonEBP and AVP gene expression in response to osmotic stress. Those results indicate a positive correlation between hypothalamic TonEBP and AVP production during dehydration. Promoter and chromatin immunoprecipitation assays confirmed that TonEBP can bind directly to conserved binding motifs in the 5’-flanking promoter regions of the AVP gene. Furthermore, dehydration- and TonEBP-mediated hypothalamic AVP gene activation was reduced in TonEBP haploinsufficiency mice, compared with wild TonEBP homozygote animals. Therefore, our result support the idea that TonEBP is directly necessary, at least in part, for the elevation of AVP transcription in dehydration conditions. Additionally, dehydration-induced reductions in body weight were rescued in TonEBP haploinsufficiency mice. Altogether, our results demonstrate an intracellular machinery within hypothalamic AVP cells that is responsible for dehydration-induced AVP synthesis.
Growing Up Under Constant Light: A Challenge to the Endocrine Function of the Leydig Cells

The factors influencing Leydig cell maturity and the acquisition of functional capacity are incompletely defined. Here we analyzed the constant light (LL) influence on Leydig cells’ endocrine function during reproductive maturation. Rats were exposed to LL from P21 to P90. Data were collected at juvenile (P35), peri/pubertal (P42, P49), and adult (P90) stages of life. The results proved the effect of LL on rats’ physiology by changing of bimodal voluntary activity pattern into free-running. Additionally, the peripheral clock in Leydig cells changed in LL condition, indicating disturbed rhythm: the positive element (Bmal1) increased in pre-/pubertal but decreased in the adult period, while negative elements (Per2 and Reverba) were increased. The effects of LL were most prominent in puberty: pituitary genes encoding gonadotropic hormones (Cga, Lhb, Fshb) decreased; serum corticosterone increased, while serum androgens and mass of testicular and sex accessory organs reduced; markers of Leydig cells maturity/differentiation (Insl3, Lhcgr) and steroidogenesis-related genes (Scarb1, Star, Cyp11a1, Cyp17a1) decreased; the steroidogenic and energetic capacity of the Leydig cell mitochondria decreased; the mtDNA copy number reduced, and mitochondrial dynamics markers changed: fusion decreased (Opa1 and Mfn2), and mitophagy increased (Pink1). In adults, the negative effect of LL on mitochondrial function and steroidogenic capacity persists in adult Leydig cells while other parameters reached control values. Altogether, the results indicate that LL slows down Leydig cells’ maturation by reducing the endocrine and energy capacity of cells leading to the delay of reproductive development.
White Matter Connectivity and Gray Matter Volume Changes Following Donepezil Treatment in Patients With Mild Cognitive Impairment: A Preliminary Study Using Probabilistic Tractography

The donepezil treatment is associated with improved cognitive performance in patients with mild cognitive impairment (MCI), and its clinical effectiveness is well-known. However, the impact of the donepezil treatment on the enhanced white matter connectivity in MCI is still unclear. The purpose of this study was to evaluate the thalamo-cortical white matter (WM) connectivity and cortical thickness and gray matter (GM) volume changes in the cortical regions following donepezil treatment in patients with MCI using probabilistic tractography and voxel-based morphometry. Patients with MCI underwent magnetic resonance examinations before and after 6-month donepezil treatment. Compared with healthy controls, patients with MCI showed decreased WM connectivity of the thalamo-lateral prefrontal cortex, as well as reduced thickness in the medial/lateral orbitofrontal cortices (p < 0.05). The thalamo-lateral temporal cortex connectivity in patients with MCI was negatively correlated with Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) (r = −0.76, p = 0.01). The average score of the Korean version of the mini-mental state examination (K-MMSE) in patients with MCI was improved by 7.9% after 6-months of donepezil treatment. However, the patterns of WM connectivity and brain volume change in untreated and treated patients were not significantly different from each other, resulting from multiple comparison corrections. These findings will be valuable in understanding the neurophysiopathological mechanism on MCI as a prodromal phase of Alzheimer's disease in connection with brain functional connectivity and morphometric change.