EEFSEC deficiency: A selenopathy with early-onset neurodegeneration.

Inborn errors of selenoprotein expression arise from deleterious variants in genes encoding selenoproteins or selenoprotein biosynthetic factors, some of which are associated with neurodegenerative disorders. This study shows that bi-allelic selenocysteine tRNA-specific eukaryotic elongation factor (EEFSEC) variants cause selenoprotein deficiency, leading to progressive neurodegeneration. EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures.

Novel phenotype associated with homozygous likely pathogenic variant in the POP1 gene.

The biallelic variants of the POP1 gene are associated with the anauxetic dysplasia (AAD OMIM 607095), a rare skeletal dysplasia, characterized by prenatal rhizomelic shortening of limbs and generalized joint hypermobility. Affected individuals usually have normal neurodevelopmental milestones. Here we present three cases from the same family with likely pathogenic homozygous POP1 variant and a completely novel phenotype: a girl with global developmental delay and autism, microcephaly, peculiar dysmorphic features and multiple congenital anomalies.

Juvenile mucopolysaccharidosis plus disease caused by a missense mutation in VPS33A.

A rare and fatal disease resembling mucopolysaccharidosis in infants, is caused by impaired intracellular endocytic trafficking due to deficiency of core components of the intracellular membrane-tethering protein complexes, HOPS, and CORVET. Whole exome sequencing identified a novel VPS33A mutation in a patient suffering from a variant form of mucopolysaccharidosis. Electron and confocal microscopy, immunoblotting, and glycosphingolipid trafficking experiments were undertaken to investigate the effects of the mutant VPS33A in patient-derived skin fibroblasts.

Ties that Bind: The Effects of Transgender Contact on Transphobia.

Allport's Theory of Interpersonal Contact suggests that coming into contact with a member of an outgroup should increase support for that outgroup. Previous studies find mixed results when applying Allport's theory to reported contact with transgender people. We posit that this is due to imprecise and aggregated measures of contact and a lack of attention to the differences between contact that is ephemeral or ongoing and voluntary or obligatory.

Major brain malformations: corpus callosum dysgenesis, agenesis of septum pellucidum and polymicrogyria in patients with BCORL1-related disorders.

Objective: BCORL1, a transcriptional co-repressor, has a role in cortical migration, neuronal differentiation, maturation, and cerebellar development. We describe BCORL1 as a new genetic cause for major brain malformations.

Methods And Results: We report three patients from two unrelated families with neonatal onset intractable epilepsy and profound global developmental delay.

Artificial Intelligence for Rapid Meta-Analysis: Case Study on Ocular Toxicity of Hydroxychloroquine.

Background: Rapid access to evidence is crucial in times of an evolving clinical crisis. To that end, we propose a novel approach to answer clinical queries, termed rapid meta-analysis (RMA). Unlike traditional meta-analysis, RMA balances a quick time to production with reasonable data quality assurances, leveraging artificial intelligence (AI) to strike this balance.

Context and Approach in Reporting Evaluations of Electronic Health Record-Based Implementation Projects.

Electronic health records (EHRs) are ubiquitous yet still evolving, resulting in a moving target for determining the effects of context (features of the work environment, such as organization, payment systems, user training, and roles) on EHR implementation projects. Electronic health records have become instrumental in effecting quality improvement innovations and providing data to evaluate them. However, reports of studies typically fail to provide adequate descriptions of contextual details to permit readers to apply the findings.

Corrigendum to "The significant cost of systematic reviews and meta-analyses: A call for greater involvement of machine learning to assess the promise of clinical trials" [Contemp. Clin. Trials Commun. 16 (2019) 100443].

[This corrects the article DOI: 10.1016/j.conctc.

Infantile onset progressive cerebellar atrophy and anterior horn cell Degeneration-A novel phenotype associated with mutations in the PLA2G6 gene.

Pontocerebellar hypoplasia (PCH) encompasses a group of neurodegenerative disorders. There are ten known subtypes with common characteristics of pontine and cerebellar hypoplasia or atrophy, neocortical atrophy, and microcephaly. PCH is associated with anterior horn cell degeneration in PCH1a and PCH1b due to mutations in the VRK1 and EXOSC3 genes.

The significant cost of systematic reviews and meta-analyses: A call for greater involvement of machine learning to assess the promise of clinical trials.

Background: More than 90% of clinical-trial compounds fail to demonstrate sufficient efficacy and safety. To help alleviate this issue, systematic literature review and meta-analysis (SLR), which synthesize current evidence for a research question, can be applied to preclinical evidence to identify the most promising therapeutics. However, these methods remain time-consuming and labor-intensive.

Familial Intracranial Hypertension in 2 Brothers With Mutation: Expansion of the Phenotypic Spectrum.

(Phosphatase and Tensin Homolog on chromosome TEN) encodes a vastly expressed tumor suppressor protein that antagonizes the PI3 K signaling pathway and alters the MTOR pathway. Mutations in have been described in association with a number of syndromes including hamartoma-tumor syndrome, macrocephaly/autism, and juvenile polyposis of infancy. Although there is a wide variability in the clinical and radiologic presentations of -related phenotypes, the most consistent features include macrocephaly and increased tumorigenesis.

A Deep Learning Method to Automatically Identify Reports of Scientifically Rigorous Clinical Research from the Biomedical Literature: Comparative Analytic Study.

Background: A major barrier to the practice of evidence-based medicine is efficiently finding scientifically sound studies on a given clinical topic.

Objective: To investigate a deep learning approach to retrieve scientifically sound treatment studies from the biomedical literature.

Methods: We trained a Convolutional Neural Network using a noisy dataset of 403,216 PubMed citations with title and abstract as features.

Taste disturbances - are there any effective treatments?

Data sourcesSeveral electronic databases were searched such as Cochrane Oral Health's Trials, Cochrane Library, Medline Ovid, CINAHL EBSCO and AMED Ovid and ongoing registered clinical trials in clinicaltrials.gov and in the World Health Organization International Clinical Trials Registry Platform. No restriction was placed on language and date of publication.

Phylogenetic patterns of trait and trait plasticity evolution: Insights from amphibian embryos.

Environmental variation favors the evolution of phenotypic plasticity. For many species, we understand the costs and benefits of different phenotypes, but we lack a broad understanding of how plastic traits evolve across large clades. Using identical experiments conducted across North America, we examined prey responses to predator cues.

Optical Coherence Tomography Reflective Drusen Substructures Predict Progression to Geographic Atrophy in Age-related Macular Degeneration.

Purpose: Structural and compositional heterogeneity within drusen comprising lipids, carbohydrates, and proteins have been previously described. We sought to detect and define phenotypic patterns of drusen heterogeneity in the form of optical coherence tomography-reflective drusen substructures (ODS) and examine their associations with age-related macular degeneration (AMD)-related features and AMD progression.

Design: Retrospective analysis in a prospective study.

Discordant circulating fetal DNA and subsequent cytogenetics reveal false negative, placental mosaic, and fetal mosaic cfDNA genotypes.

Background: The American College of Obstetrics and Gynecology (ACOG) and Maternal Fetal Medicine (MFM) Societies recommended that abnormal cfDNA fetal results should be confirmed by amniocentesis and karyotyping. Our results demonstrate that normal cfDNA results inconsistent with high-resolution abnormal ultrasounds should be confirmed by karyotyping following a substantial frequency of incorrect cfDNA results.

Methods: Historical review of our ~4,000 signed prenatal karyotypes found ~24% of reported abnormalities would not have been detected by cfDNA.

Molecular and functional studies of retinal degeneration as a clinical presentation of SACS-related disorder.

Background: ARSACS (autosomal-recessive spastic ataxia of Charlevoix-Saguenay) is a neurodegenerative disorder caused by SACS gene mutations and characterized by a triad of symptoms: early-onset cerebellar ataxia, spasticity and peripheral neuropathy. A characteristic retinal nerve fiber hypertrophy has been reported in several individuals with ARSACS.

Methods: We describe a patient with a unique clinical presentation of ataxia, nystagmus, dysarthria, hearing impairment, and retinal degeneration.

Paroxysmal tonic upward gaze as a presentation of de-novo mutations in CACNA1A.

Objective: Paroxysmal tonic upward gaze was initially described as a benign phenomenon with negative investigations and eventual complete resolution of symptoms. Later publications demonstrated that a similar clinical picture may arise from structural brain lesions, channelopathies, neurotransmitter disorders, and epileptic seizures. CACNA1A related disorders manifest as a wide spectrum of paroxysmal neurological disorders: episodic ataxia 2, hemiplegic migraine, benign paroxysmal torticollis of infancy, and paroxysmal vertigo.

A newly recognized syndrome of severe growth deficiency, microcephaly, intellectual disability, and characteristic facial features.

Genetic syndromes with proportionate severe short stature are rare. We describe two sisters born to nonconsanguineous parents with severe linear growth retardation, poor weight gain, microcephaly, characteristic facial features, cutaneous syndactyly of the toes, high myopia, and severe intellectual disability. During infancy and early childhood, the girls had transient hepatosplenomegaly and low blood cholesterol levels that normalized later.

The impact of overall radiotherapy treatment time and delay in initiation of radiotherapy on local control and distant metastases in gastric cancer.

Objectives: To study the impact of time factors on local and distant metastases in stomach cancer.

Methods: 67 patients with gastric cancer who received adjuvant treatment were reviewed for the time to initiation of radiotherapy, overall duration of RT and the events of first local recurrence or distant metastasis.

Results: The risk probability of local recurrence is increased by 10% (HR=1.

Delineation of the interstitial 6q25 microdeletion syndrome: refinement of the critical causative region.

Interstitial deletions of the long arm of chromosome 6 are rare. Clinically, this is a recognizable microdeletion syndrome associated with intellectual disability (ID), acquired microcephaly, typical dysmorphic features, structural anomalies of the brain, and nonspecific multiple organ anomalies. Most of the reported cases have cytogenetically visible interstitial deletions or subtelomeric microdeletions.