Optimizing viral genome subsampling by genetic diversity and temporal distribution (TARDiS) for phylogenetics.

Summary: TARDiS is a novel phylogenetic tool for optimal genetic subsampling. It optimizes both genetic diversity and temporal distribution through a genetic algorithm.

Availability And Implementation: TARDiS, along with example datasets and a user manual, is available at https://github.

Epilepsy in "Sunflower syndrome": electroclinical features, therapeutic response, and long-term follow-up.

Background: Sunflower syndrome (SFS) is a rare childhood-onset generalized epilepsy characterized by photosensitivity, heliotropism, and drug-resistant stereotyped seizures maybe self-induced by hand-waving maneuvers. Data on the long-term prognosis are scantly and evidence over best treatment strategies is lacking.

Methods: We retrospectively describe the electroclinical features, and therapeutic response in a group of 21 patients with SFS, without intellectual disability.

Acute Posterior Ocular Toxoplasmosis: An Optical Coherence Tomography Angiography and Dye Angiography Study.

Purpose: To compare Indocyanine Green (ICGA) and fundus fluorescein angiography (FFA) with Optical Coherence Tomography Angiography (OCTA) findings in toxoplasmic chorioretinitis (TCR).

Methods: Patients affected by active TCR were included. FFA, ICGA, and OCTA images were analyzed and lesions were compared between different modalities.

Anthocran® Phytosome®: Prevention of Recurring Urinary Infections and Symptoms after Catheterization.

In this preliminary pilot registry study, we investigated the effects of the oral supplementation of a standardized cranberry extract (Anthocran® Phytosome®, Indena) delivered by a lecithin-based system, for the prophylactic management of recurrent-urinary tract infections (R-UTIs). We included 64 otherwise healthy subjects who underwent a surgical procedure and required post-surgical urinary catheterization for high-risk UTIs or a previous history of R-UTIs. Patients were given supplementation with the standardized cranberry extract at the dose of either 120 mg/day ( = 12) or 240 mg/day ( = 12) or assigned to a control group consisting of standard management (SM;  = 18) or nitrofurantoin administration ( = 22) for 4 weeks.

Prominent and Regressive Brain Developmental Disorders Associated with Nance-Horan Syndrome.

Nance-Horan syndrome (NHS) is a rare X-linked developmental disorder caused mainly by loss of function variants in the gene. NHS is characterized by congenital cataracts, dental anomalies, and distinctive facial features, and a proportion of the affected individuals also present intellectual disability and congenital cardiopathies. Despite identification of at least 40 distinct hemizygous variants leading to NHS, genotype-phenotype correlations remain largely elusive.

Complex Neurological Phenotype Associated with a De Novo Mutation in a Boy with Intellectual Disability, Refractory Epilepsy, and Movement Disorder.

Mutations in the gene (MIM: 617836), encoding a subunit of dehydrodolichyl diphosphate synthase complex, have been recently implicated in very rare neurodevelopmental diseases. In total, five individuals carrying two mutations in have been reported so far, but genotype-phenotype correlations remain elusive. We reported a boy with a mutation in (NM_205861.

Rapid Emergence and Spread of Severe Acute Respiratory Syndrome Coronavirus 2 Gamma (P.1) Variant in Haiti.

After an initial wave of coronavirus disease 2019 (COVID-19) in Haiti in summer 2020 (primarily lineage B.1), seropositivity for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) was ~40%. Variant P.

Examination of CA1 Hippocampal DNA Methylation as a Mechanism for Closing of Estrogen's Critical Window.

There is a critical window for estrogen replacement therapy, beyond which estradiol (E2) fails to enhance cognition and N-methyl-D-aspartate (NMDA) receptor function, and E2-responsive transcription decreases. Much less attention has been given to the mechanism for closing of the critical window, which is thought to involve the decline in estrogen signaling cascades, possibly involving epigenetic mechanisms, including DNA methylation. This study investigated changes in DNA methylation in region CA1 of the hippocampus of ovariectomized female rats over the course of brain aging and in response to E2-treatment, using whole genome bisulfite sequencing.

PRC2 Inhibitors Overcome Glucocorticoid Resistance Driven by Mutation in Pediatric Acute Lymphoblastic Leukemia.

Mutations in epigenetic regulators are common in relapsed pediatric acute lymphoblastic leukemia (ALL). Here, we uncovered the mechanism underlying the relapse of ALL driven by an activating mutation of the histone methyltransferase (p.E1099K).

Broad betacoronavirus neutralization by a stem helix-specific human antibody.

The spillovers of betacoronaviruses in humans and the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants highlight the need for broad coronavirus countermeasures. We describe five monoclonal antibodies (mAbs) cross-reacting with the stem helix of multiple betacoronavirus spike glycoproteins isolated from COVID-19 convalescent individuals. Using structural and functional studies, we show that the mAb with the greatest breadth (S2P6) neutralizes pseudotyped viruses from three different subgenera through the inhibition of membrane fusion, and we delineate the molecular basis for its cross-reactivity.

The Italian version of the Reflective Functioning Questionnaire: Validity within a sample of adolescents and associations with psychological problems and alexithymia.

Objectives: This study aims to test the psychometric proprieties of the Reflective Functioning Questionnaire (RFQ) applied to younger (13-16 years) and older (17-20 years) Italian adolescents examining (1) the factorial structure of RFQ; (2) its invariance across age and sex; (3) correlations between RFQ subscale scores, as well as the associations of the RFQ with (4) psychological problems and alexithymia dimensions.

Methods: A cross-sectional study was conducted with 593 adolescents between the ages of 13 and 20 years old recruited from the community within Italy. These participants completed the RFQ, Symptom Checklist-90, and Toronto Alexithymia Scale.

Copper as Dietary Supplement for Bone Metabolism: A Review.

While in vitro and animal studies of osteoblastic and osteoclastic activity as well as bone resistance for copper are numerous, and the results encouraging in terms of regulation, human studies are scarce. The aim of this narrative review was to investigate the correlation of blood copper, daily copper intake, and copper supplementation with bone mineral density. This review included 10 eligible studies: five studies concerned copper blood levels, one study concerned daily copper intake, and four studies concerned copper supplementation.

UHPLC-MS/MS Analysis of Cannabidiol and Its Metabolites in Serum of Patients with Resistant Epilepsy Treated with CBD Formulations.

Cannabidiol (CBD) is a promising therapeutic agent with analgesic, myorelaxant, and anti-epileptic actions. Recently, a purified form of CBD (Epidiolex) has been approved by the European Medicines Agency (EMA) for the treatment of two highly-refractory childhood-onset epilepsies (Dravet and Lennox-Gastaut syndrome). Given the interindividual response and the relationship between the dose administered and CBD blood levels, therapeutic drug monitoring (TDM) is a valuable support in the clinical management of patients.

Coenzyme Q10 Phytosome Formulation Improves CoQ10 Bioavailability and Mitochondrial Functionality in Cultured Cells.

Coenzyme Q10 (CoQ10) is a lipid-soluble molecule with a dual role: it transfers electrons in the mitochondrial transport chain by promoting the transmembrane potential exploited by the ATPase to synthesize ATP and, in its reduced form, is a membrane antioxidant. Since the high CoQ10 hydrophobicity hinders its bioavailability, several formulations have been developed to facilitate its cellular uptake. In this work, we studied the bioenergetic and antioxidant effects in I407 and H9c2 cells of a CoQ10 phytosome formulation (UBIQSOME, UBQ).

Potential Clinical Benefits of Quercetin in the Early Stage of COVID-19: Results of a Second, Pilot, Randomized, Controlled and Open-Label Clinical Trial.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing global pandemic known as COVID-19. Based on the potential antiviral role of quercetin, and on its described anti-blood clotting, anti-inflammatory and antioxidant properties, we hypothesize that subjects with mild COVID-19 treated with Quercetin Phytosome (QP), a novel bioavailable form of quercetin, may have a shorter time to virus clearance, a milder symptomatology, and higher probabilities of a benign earlier resolution of the disease.

Methods: In our 2-week, randomized, open-label, and controlled clinical study, we have enrolled 42 COVID-19 outpatients.

A new sensitive and fast assay for the detection of EGFR mutations in liquid biopsies.

Background: A major perspective for the use of circulating tumor DNA (ctDNA) in the clinical setting of non-small cell lung cancer (NSCLC) is expected as predictive factor for resistance and response to EGFR TKI therapy and, especially, as a non-invasive alternative to tissue biopsy. However, ctDNA is both highly fragmented and mostly low concentrated in plasma and serum. On this basis, it is important to use a platform characterized by high sensitivity and linear performance in the low concentration range.

Possible Therapeutic Effects of Adjuvant Quercetin Supplementation Against Early-Stage COVID-19 Infection: A Prospective, Randomized, Controlled, and Open-Label Study.

Background: Quercetin, a well-known naturally occurring polyphenol, has recently been shown by molecular docking, in vitro and in vivo studies to be a possible anti-COVID-19 candidate. Quercetin has strong antioxidant, anti-inflammatory, immunomodulatory, and antiviral properties, and it is characterized by a very high safety profile, exerted in animals and in humans. Like most other polyphenols, quercetin shows a very low rate of oral absorption and its clinical use is considered by most of modest utility.

Methylscaper: an R/Shiny app for joint visualization of DNA methylation and nucleosome occupancy in single-molecule and single-cell data.

Summary: Differential DNA methylation and chromatin accessibility are associated with disease development, particularly cancer. Methods that allow profiling of these epigenetic mechanisms in the same reaction and at the single-molecule or single-cell level continue to emerge. However, a challenge lies in jointly visualizing and analyzing the heterogeneous nature of the data and extracting regulatory insight.

Virtual Residency Interviews: What Variables Can Applicants Control?

Due to the ongoing coronavirus disease 2019 (COVID-19) pandemic, almost all residency programs have adopted virtual interviewing for the National Residency Matching Program® (NRMP) or The Match® 2021. Hence, applicants have had to adapt quickly to this process, since the interviewers and the applicants were mostly inexperienced regarding this process. To date, program directors have had a successful experience on this new modality, and since the pandemic continues to limit in-person meetings and given the benefits that virtual interviews provide in terms of transportation, booking, and cost, there is a high chance that interviews for The Match 2022 will also be conducted in the same, virtual way.