Miracle-dz/UniFAR-FTUs huggingface dataset:
Pax9 and Gbx2 Interact in the Pharyngeal Endoderm to Control Cardiovascular Development

The correct formation of the aortic arch arteries depends on a coordinated and regulated gene expression profile within the tissues of the pharyngeal arches. Perturbation of the gene regulatory networks in these tissues results in congenital heart defects affecting the arch arteries and the outflow tract of the heart. Aberrant development of these structures leads to interruption of the aortic arch and double outlet right ventricle, abnormalities that are a leading cause of morbidity in 22q11 Deletion Syndrome (DS) patients. We have recently shown that Pax9 functionally interacts with the 22q11DS gene Tbx1 in the pharyngeal endoderm for 4th pharyngeal arch artery morphogenesis, with double heterozygous mice dying at birth with interrupted aortic arch. Mice lacking Pax9 die perinatally with complex cardiovascular defects and in this study we sought to validate further potential genetic interacting partners of Pax9, focussing on Gbx2 which is down-regulated in the pharyngeal endoderm of Pax9-null embryos. Here, we describe the Gbx2-null cardiovascular phenotype and demonstrate a genetic interaction between Gbx2 and Pax9 in the pharyngeal endoderm during cardiovascular development.
Targeted Nutritional Intervention for Patients with Mild Cognitive Impairment: The Cognitive impAiRmEnt Study (CARES) Trial 1

Omega-3 fatty acids (ω-3FAs), carotenoids, and vitamin E are important constituents of a healthy diet. While they are present in brain tissue, studies have shown that these key nutrients are depleted in individuals with mild cognitive impairment (MCI) in comparison to cognitively healthy individuals. Therefore, it is likely that these individuals will benefit from targeted nutritional intervention, given that poor nutrition is one of the many modifiable risk factors for MCI. Evidence to date suggests that these nutritional compounds can work independently to optimize the neurocognitive environment, primarily due to their antioxidant and anti-inflammatory properties. To date, however, no interventional studies have examined the potential synergistic effects of a combination of ω-3FAs, carotenoids and vitamin E on the cognitive function of patients with MCI. Individuals with clinically confirmed MCI consumed an ω-3FA plus carotenoid plus vitamin E formulation or placebo for 12 months. Cognitive performance was determined from tasks that assessed global cognition and episodic memory. Ω-3FAs, carotenoids, and vitamin E were measured in blood. Carotenoid concentrations were also measured in tissue (skin and retina). Individuals consuming the active intervention (n = 6; median [IQR] age 73.5 [69.5–80.5] years; 50% female) exhibited statistically significant improvements (p < 0.05, for all) in tissue carotenoid concentrations, and carotenoid and ω-3FA concentrations in blood. Trends in improvements in episodic memory and global cognition were also observed in this group. In contrast, the placebo group (n = 7; median [IQR] 72 (69.5–75.5) years; 89% female) remained unchanged or worsened for all measurements (p > 0.05). Despite a small sample size, this exploratory study is the first of its kind to identify trends in improved cognitive performance in individuals with MCI following supplementation with ω-3FAs, carotenoids, and vitamin E.
THE TIMING OF CONFLICT AND COOPERATION AMONG COFOUNDRESSES OF THE SOCIAL WASP POLISTES FUSCATUS (HYMENOPTERA: VESPIDAE)

Field observations were made on 37 preworker, multiple-foundress colonies of the social wasp Polistes fuscatus. In total, 401.9 h of behavioural observations of cofoundresses were conducted at three different periods prior to the emergence of workers. Cofoundresses displayed a marked, significant increase in aggression at about the time in the colony cycle when reproductive-destined eggs began to be laid. Both queens and their subordinates became increasingly aggressive at this time. These empirical results support theoretical predictions that conflict among cofoundresses would intensify over the production of reproductive-destined (but not worker-destined) eggs. Cooperation in foraging to minimize nest inattendance as well as synchronicity (temporal overlap) in activity also increased significantly at the onset of the production of reproductive-destined eggs. Thus, conflict and cooperation are not necessarily antagonistic in P. fuscatus. Foundresses minimized the time that nests are unattended at a time .
Low Serum Bicarbonate and CKD Progression in Children.

BACKGROUND AND OBJECTIVES Studies of adults have demonstrated an association between metabolic acidosis, as measured by low serum bicarbonate levels, and CKD progression. We evaluated this relationship in children using data from the Chronic Kidney Disease in Children study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The relationship between serum bicarbonate and a composite end point, defined as 50% decline in eGFR or KRT, was described using parametric and semiparametric survival methods. Analyses were stratified by underlying nonglomerular and glomerular diagnoses, and adjusted for demographic characteristics, eGFR, proteinuria, anemia, phosphate, hypertension, and alkali therapy. RESULTS Six hundred and three participants with nonglomerular disease contributed 2673 person-years of follow-up, and 255 with a glomerular diagnosis contributed 808 person-years of follow-up. At baseline, 39% (237 of 603) of participants with nonglomerular disease had a bicarbonate level of ≤22 meq/L and 36% (85 of 237) of those participants reported alkali therapy treatment. In participants with glomerular disease, 31% (79 of 255) had a bicarbonate of ≤22 meq/L, 18% (14 of 79) of those participants reported alkali therapy treatment. In adjusted longitudinal analyses, compared with participants with a bicarbonate level >22 meq/L, hazard ratios associated with a bicarbonate level of <18 meq/L and 19-22 meq/L were 1.28 [95% confidence interval (95% CI), 0.84 to 1.94] and 0.91 (95% CI, 0.65 to 1.26), respectively, in children with nonglomerular disease. In children with glomerular disease, adjusted hazard ratios associated with bicarbonate level ≤18 meq/L and bicarbonate 19-22 meq/L were 2.16 (95% CI, 1.05 to 4.44) and 1.74 (95% CI, 1.07 to 2.85), respectively. Resolution of low bicarbonate was associated with a lower risk of CKD progression compared with persistently low bicarbonate (≤22 meq/L). CONCLUSIONS In children with glomerular disease, low bicarbonate was linked to a higher risk of CKD progression. Resolution of low bicarbonate was associated with a lower risk of CKD progression. Fewer than one half of all children with low bicarbonate reported treatment with alkali therapy. Long-term studies of alkali therapy's effect in patients with pediatric CKD are needed.
Retinoic acid signaling within pancreatic endocrine progenitors regulates mouse and human β cell specification

ABSTRACT Retinoic acid (RA) signaling is essential for multiple developmental processes, including appropriate pancreas formation from the foregut endoderm. RA is also required to generate pancreatic progenitors from human pluripotent stem cells. However, the role of RA signaling during endocrine specification has not been fully explored. In this study, we demonstrate that the disruption of RA signaling within the NEUROG3-expressing endocrine progenitor population impairs mouse β cell differentiation and induces ectopic expression of crucial δ cell genes, including somatostatin. In addition, the inhibition of the RA pathway in hESC-derived pancreatic progenitors downstream of NEUROG3 induction impairs insulin expression. We further determine that RA-mediated regulation of endocrine cell differentiation occurs through Wnt pathway components. Together, these data demonstrate the importance of RA signaling in endocrine specification and identify conserved mechanisms by which RA signaling directs pancreatic endocrine cell fate. Summary: This study reveals a previously unappreciated role of RA signaling within the NEUROG3-expressing endocrine progenitor population that impairs β cell differentiation and induces ectopic expression of crucial δ cell genes.
New genera and higher taxa of septate gregarines (Protozoa, Apicomplexa)

SYNOPSIS The following new taxa of septate gregarines are established: METAMERIDAE fam. nov. includes genera Metamera Duke, Deutomera Bhatia & Setna, and Cognettia gen. n. , the last with the type and only species C. legeri (Cognetti de Martiis); family GREGARINIDAE Labbe includes Degiustia gen. n. with the type and only species D. hyallela (Batten & DeGiusti); Cirrigregarina gen. n. , with the type species C. spissa (Henry) and another species, C. kamenote (Hoshide); and Molluskocystis gen. n. , with the type and only species M. pterotracheae (Stuart). Family HIRMOCYSTIDAE (Grasse) includes Arachnocystis gen. n. , with the type species A. arachnoidea (Devdhar & Gourishankar) and 3 other species A. nitida (Geus), A. oribatidae (Geus), A. scutovertexi (Erhardova). Family ACTINOCEPHALIDAE (Leger), subfamily Actinocephalinae (Leger), includes Chilogregarina gen. n. , with the type species C. striata (Leger & Duboscq) and 3 other species C. brasiliensis (Pinto), C. dujardini (Schneider), and C. stella (Leger).
Microneedle ocular patch: fabrication, characterization, and ex-vivo evaluation using pilocarpine as model drug

Abstract Context: Enhacing the ocular bioavailability of drugs after their topical application is a challenge. Objective: The objective of the study was to design, fabricate, and investigate the effectiveness of microneedle ocular patch (MOP) in delivering the model drug, pilocarpine HCl across the corneal membrane. Methods: MOP mimicked commercially available contact lens design elements having a diameter of 14.20 mm and a sagittal height of 3.85 mm with a convex curvature. The base of this patch contained an array of 25 pyramid-shaped microneedles measuring 521 ± 10 µm in length. Pilocarpine loaded MOP was prepared by micromolding technique using dissolvable polyvinyl alcohol and polyvinyl pyrrolidone matrix. MOP was characterized for physical and mechanical properties using a stereomicroscope, scanning electron microscope, and texture analyzer. Results: Histological examination after MOP application on excised human cornea showed penetration of microneedles with a required insertional force of 1.04 ± 0.17 N. Flux of pilocarpine across excised cornea was significantly (p < 0.05) greater after application of MOP (704 ± 149 µg/cm2/h) compared with solution formulation (188 ± 24 µg/cm2/h). Ex-vivo pilocarpine permeation study in porcine eye globe revealed significantly (p < 0.05) greater availability in aqueous humor within 30 min of application of MOP (249 ± 85 µg/ml) compared with solution formulation (46 ± 9 µg/ml). Conclusion: MOP can be developed as a potential ophthalmic drug delivery system.
Magnetic Resonance Imaging Alteration of the Brain in a Patient With Coronavirus Disease 2019 (COVID-19) and Anosmia.

The neurotropism of human coronaviruses has already been demonstrated in small animals, and in autoptic studies the severe acute respiratory syndrome coronavirus (SARS-CoV), which was responsible for the SARS outbreak during 2002 to 2003, was found in the brains of patients with infection.1 It has been proposed that the neuroinvasive potential of the novel SARS-CoV-2, responsible for coronavirus disease 2019 (COVID-19), may be at least partially responsible for the respiratory failure of patients with COVID-19.2 In this article, we share the magnetic resonance imaging (MRI) evidence of in vivo brain alteration presumably due to SARS-CoV-2 and demonstrate that anosmia can represent the predominant symptom in COVID-19. A 25-year-old female radiographer with no significant medical history who had been working in a COVID-19 ward presented with a mild dry cough that lasted for 1 day, followed by persistent severe anosmia and dysgeusia. She did not have a fever. She had no trauma, seizure, or hypoglycemic event. Three days later, nasal fibroscopic evaluation results were unremarkable, and noncontrast chest and maxillofacial computed tomography results were negative. On the same day, a brain MRI was also performed. On 3-dimensional and 2-dimensional fluid-attenuated inversion recovery images, a cortical hyperintensity was evident in the right gyrus rectus (Figure 1) and a subtle hyperintensity was present in the olfactory bulbs (Figure 1). Because many patients in Italy are experiencing anosmia3 and the cortical signal alteration was suggestive of viral infection, a swab test was performed and reverse transcription–polymerase chain reaction analysis yielded positive results for SARS-CoV-2. During a follow-up MRI performed 28 days later, the signal alteration in the cortex completely disappeared and the olfactory bulbs were thinner and slightly less hyperintense (Figure 24). The patient recovered from anosmia. No brain abnormalities were seen in 2 other patients with COVID-19 presenting anosmia who underwent brain MRI 12 and 25 days from symptom onset. To our knowledge, this is the first report of in vivo human brain involvement in a patient with COVID-19 showing a signal alteration compatible with viral brain invasion in a cortical region (ie, posterior gyrus rectus) that is associated with olfaction. Alternative diagnoses (eg, status epilepticus, posterior reversible encephalopathy syndrome–like alterations, other viral infections, and anti–N-methyl-D-aspartate receptor encephalitis) are unlikely given the clinical context. Based on the MRI findings, including the slight olfactory bulb changes, we can speculate that SARS-CoV-2 might invade the brain through the olfactory pathway and cause an olfactory dysfunction of sensorineural origin; cerebrospinal fluid and pathology studies are required to confirm this hypothesis. Ours and others’ observations of normal brain imaging in
AOP4EUpest: mapping of pesticides in adverse outcome pathways using a text mining tool

Abstract Motivation Exposure to pesticides may lead to adverse health effects in human populations, in particular vulnerable groups. The main long-term health concerns are neurodevelopmental disorders, carcinogenicity as well as endocrine disruption possibly leading to reproductive and metabolic disorders. Adverse outcome pathways (AOP) consist in linear representations of mechanistic perturbations at different levels of the biological organization. Although AOPs are chemical-agnostic, they can provide a better understanding of the Mode of Action of pesticides and can support a rational identification of effect markers. Results With the increasing amount of scientific literature and the development of biological databases, investigation of putative links between pesticides, from various chemical groups and AOPs using the biological events present in the AOP-Wiki database is now feasible. To identify co-occurrence between a specific pesticide and a biological event in scientific abstracts from the PubMed database, we used an updated version of the artificial intelligence-based AOP-helpFinder tool. This allowed us to decipher multiple links between the studied substances and molecular initiating events, key events and adverse outcomes. These results were collected, structured and presented in a web application named AOP4EUpest that can support regulatory assessment of the prioritized pesticides and trigger new epidemiological and experimental studies. Availability and implementation http://www.biomedicale. parisdescartes.fr/aop4EUpest/home.php. Supplementary information Supplementary data are available at Bioinformatics online.
An update on ACE2 amplification and its therapeutic potential

The renin angiotensin system (RAS) plays an important role in the pathogenesis of variety of diseases. Targeting the formation and action of angiotensin II (Ang II), the main RAS peptide, has been the key therapeutic target for last three decades. ACE‐related carboxypeptidase (ACE2), a monocarboxypeptidase that had been discovered 20 years ago, is one of the catalytically most potent enzymes known to degrade Ang II to Ang‐(1‐7), a peptide that is increasingly accepted to have organ‐protective properties that oppose and counterbalance those of Ang II. In addition to its role as a RAS enzyme ACE2 is the main receptor for SARS‐CoV‐2. In this review, we discuss various strategies that have been used to achieve amplification of ACE2 activity including the potential therapeutic potential of soluble recombinant ACE2 protein and novel shorter ACE2 variants.
Molecular characterization of the Thermomonospora curvataaglA gene encoding a thermotolerant α‐1,4‐glucosidase

The cloning, sequencing and structural characterization of a gene encoding a thermostable α‐1,4‐glucosidase from Thermomonospora curvata is described. DNA sequence analysis revealed four open reading frames designated aglA, aglR, aglE and aglF. The aglA gene encodes a thermostable α‐1,4‐glucosidase from T. curvata and is situated between two genes, aglR and aglE. Genes aglA, aglE and aglF are transcribed in the same direction, while aglR is transcribed in the opposite direction. By comparing the amino acid sequence of the α‐1,4‐glucosidase from T. curvata with other α‐glucanases, it appears that the enzyme is a member of the α‐amylase family. The proteins of this family have an (α/β)8 barrel super secondary structure. The topology of the α‐1,4‐glucosidase was predicted by computer‐assisted analysis. The topology of the secondary structures of the α‐1,4‐glucosidase resembles the structure of barley α‐amylase, but the primary structure resembles most closely the oligo‐1,6‐glucosidase from Bacillus cereus. Putative catalytic residues (D221, E281 and D343) and calcium binding residues (N116, E179, D191, H224 or G225) are proposed.
EEG Connectivity Analysis Using Denoising Autoencoders for the Detection of Dyslexia

The Temporal Sampling Framework (TSF) theorizes that the characteristic phonological difficulties of dyslexia are caused by an atypical oscillatory sampling at one or more temporal rates. The LEEDUCA study conducted a series of Electroencephalography (EEG) experiments on children listening to amplitude modulated (AM) noise with slow-rythmic prosodic (0.5-1[Formula: see text]Hz), syllabic (4-8[Formula: see text]Hz) or the phoneme (12-40[Formula: see text]Hz) rates, aimed at detecting differences in perception of oscillatory sampling that could be associated with dyslexia. The purpose of this work is to check whether these differences exist and how they are related to children's performance in different language and cognitive tasks commonly used to detect dyslexia. To this purpose, temporal and spectral inter-channel EEG connectivity was estimated, and a denoising autoencoder (DAE) was trained to learn a low-dimensional representation of the connectivity matrices. This representation was studied via correlation and classification analysis, which revealed ability in detecting dyslexic subjects with an accuracy higher than 0.8, and balanced accuracy around 0.7. Some features of the DAE representation were significantly correlated ([Formula: see text]) with children's performance in language and cognitive tasks of the phonological hypothesis category such as phonological awareness and rapid symbolic naming, as well as reading efficiency and reading comprehension. Finally, a deeper analysis of the adjacency matrix revealed a reduced bilateral connection between electrodes of the temporal lobe (roughly the primary auditory cortex) in DD subjects, as well as an increased connectivity of the F7 electrode, placed roughly on Broca's area. These results pave the way for a complementary assessment of dyslexia using more objective methodologies such as EEG.
Production and Purification of Artificial Circular RNA Sponges for Application in Molecular Biology and Medicine

Characterized by their covalently closed structure and thus an elevated stability compared to linear RNA molecules, circular RNAs (circRNAs) form a novel class of mainly non-coding RNAs. Although the biological functions of naturally occurring circRNAs are largely unknown, they were reported to act as molecular sponges, sequestering microRNAs (miRNAs), resulting in a de-repression of target mRNAs. Taking these characteristics of naturally occurring circRNAs into account, artificial circRNAs could be a potential tool in molecular biology and medicine. Using the Hepatitis C virus (HCV) as a model system, this application of artificial circular RNAs was demonstrated. The virus requires cellular miRNA miR-122 for its life cycle, and circRNAs specifically engineered to efficiently sequester this miRNA impacted viral propagation. Since in this context the production of engineered circRNA remains the limiting factor, we present a method to produce and efficiently purify artificial circRNA sponges (ciRS) in vitro. In this protocol we provide insights into a small-scale and large-scale production technique of artificial circular RNA sponges relying on in vitro transcription and RNA ligation.
A reflection on an adapted approach from face‐to‐face to telephone consultations in our Urology Outpatient Department during the COVID‐19 pandemic – a pathway for change to future practice?

The sudden and unanticipated coronavirus disease 2019 (COVID‐19) viral pandemic of 2020 and its profound impact on the NHS prompted an almost overnight change in the services we are able to offer our patients to fulfil clinical demands. From March 2020, we have changed outpatient appointments from face‐to‐face to telephone‐led consultations. We have performed an early review of this service to ensure its sustainability during the unknown duration of this current crisis and to establish its potential utility when normal services resume in the future. Our present results show a patient satisfaction of 93%, with 83% happy to have telephone follow‐up in the future, and a clinician satisfaction of 82% in the adequacy of the telephone consultation for making a clinical decision. Telephone clinics are a safe and efficient alternative to face‐to‐face outpatient consultations for many patients, particularly non‐complex benign follow‐ups.
The Mental Health Burden of the COVID-19 Pandemic on Physical Therapists

We evaluated the mental health burden of coronavirus disease (COVID-19) on physical therapists, including their stress and anxiety levels, who were at risk of developing psychological distress and other mental health symptoms. A questionnaire survey was conducted with physical therapists of three university hospitals in South Korea on 10 April 2020. The questionnaires evaluated the presence of anxiety and depression in the respondents. Among the 65 physical therapists who completed our survey, 21 (32.3%) and 12 (18.5%) physical therapists reported having symptoms of anxiety and depression, respectively. If a physical therapist was living with a ≤6-year-old infant or child, the possibility of the presence of anxiety was significantly higher. The risk of depression among those who were in their 30 s and 50 s was significantly higher than among those in their 20 s. Thus, physical therapists living with a ≤6-year-old infant or child and those in their 30 s and 50 s need special attention.
Ontogénie des périthèces d'Endocarpon pusillum (Pyrénolichen, Verrucariacées)

The comparative ontogeny of perithecia of numerous Verrucariaceae indicates that species studied to date show a peculiar, verrucariacean, stage. It is distinguished, at the time of perithecial cavity aperture opening, by short periphysoids and a domelike sporophytic apparatus. The development and structure of the perithecia of Endocarpon pusillum Hedw. are of the ascolocular type. This species is related to the genus Verrucaria, but differs from the genus Dermatocarpon, especially Dermatocarpon miniatum (L.) Mann.