Novel UBE3B mutations: report of eight patients with Kaufman oculocerebrofacial syndrome with additional clinical findings from a highly consanguineous population.

Biallelic mutations in UBE3B cause Kaufman oculocerebrofacial syndrome (KOS; OMIM 244450) with a wide range of clinical manifestations. In this study, we employed genetic analyses including homozygosity mapping, candidate gene sequencing, whole exome sequencing, and confirmatory Sanger sequencing on eight patients from three unrelated consanguineous families. Our analysis yielded three different novel variants in UBE3B : a missense substitution [NM_130466.

Postoperative Management of Kahook Dual Blade Goniotomy with Phacoemulsification Cataract Extraction.

Aim: To review the efficacy and safety of two common postoperative regimens following Kahook Dual Blade goniotomy with phacoemulsification cataract extraction (KDB-CE).

Materials And Methods: This is a retrospective review of eyes undergoing KDB-CE from May 2016 to 2018 by a single surgeon. Almost 12-month follow-up data were assessed for two common postop regimens-treatment with (1) topical prednisolone acetate 1% with pilocarpine 1% (pred-pilo) or (2) difluprednate 0.

Integration of green economy concepts for sustainable biosurfactant production - A review.

The link between increasing global population, food demand, industrialization, and agricultural waste is strong. Decomposing by-products from food cycles can introduce harmful toxic heavy metals, active degrading microbes, and enzymes to the environment. Additionally, high greenhouse gas emissions from the decomposing wastes contribute to global change and a high carbon economy.

The algorithmic turn in conservation biology: Characterizing progress in ethically-driven sciences.

As a discipline distinct from ecology, conservation biology emerged in the 1980s as a rigorous science focused on protecting biodiversity. Two algorithmic breakthroughs in information processing made this possible: place-prioritization algorithms and geographical information systems. They provided defensible, data-driven methods for designing reserves to conserve biodiversity that obviated the need for largely intuitive and highly problematic appeals to ecological theory at the time.

Gene Expression and Transcriptome Profiling of Changes in a Cancer Cell Line Post-Exposure to Cadmium Telluride Quantum Dots: Possible Implications in Oncogenesis.

Cadmium telluride quantum dots (CdTe-QDs) are acquiring great interest in terms of their applications in biomedical sciences. Despite earlier sporadic studies on possible oncogenic roles and anticancer properties of CdTe-QDs, there is limited information regarding the oncogenic potential of CdTe-QDs in cancer progression. Here, we investigated the oncogenic effects of CdTe-QDs on the gene expression profiles of Chang cancer cells.

Transcriptome analysis of neratinib treated HER2 positive cancer model vs untreated cancer unravels the molecular mechanism of action of neratinib.

Human estrogen receptor positive cancer cells have mutations and make an excess of the HER2 protein and are far more aggressive than others cancers. Neratinib, an irreversible tyrosine kinase inhibitor is used to treat HER2 positive cancers. Neratinib targets HER2 and blocks its signal transduction resulting in inhibition of cell proliferation and induction of apoptosis without any information about the molecular mechanism involved.

Comprehensive Genomic Analysis of Noonan Syndrome and Acute Myeloid Leukemia in Adults: A Review and Future Directions.

Acute myeloid leukemia (AML) in the setting of Noonan syndrome (NS) has been reported before without clear guidelines for treatment or prognosis in these subgroups of patients, most likely due to its rarity and incomplete understanding of the pathogenesis of both diseases. In the current era of next-generation sequencing-based genomic analysis, we can better identify patients with NS with more accurate AML-related prognostic markers. Germline mutations in PTPN11 are the most common cause of NS.

Efficacy and safety of a single-use dual blade goniotomy: 18-month results.

Purpose: To compare the 18-month efficacy and safety of Kahook Dual Blade goniotomy (KDB) in combination with cataract surgery (combined group) or as a standalone procedure (standalone group).

Setting: Single surgeon practice.

Design: Retrospective review study.

Interleukin-8 Dedifferentiates Primary Human Luminal Cells to Multipotent Stem Cells.

During aging, cellular plasticity and senescence play important roles in tissue regeneration and the pathogenesis of different diseases, including cancer. We have recently shown that senescent breast luminal cells can activate their adjacent stromal fibroblasts. In the present report, we present clear evidence that these senescence-related active fibroblasts can dedifferentiate proliferating primary human luminal cells to multipotent stem cells in an interleukin-8 (IL-8)-dependent manner.

A novel nonsense mutation in the STS gene in a Pakistani family with X-linked recessive ichthyosis: including a very rare case of two homozygous female patients.

Background: X-linked ichthyosis (XLI; OMIM# 308100) is a recessive keratinization disorder characterized by the presence of dark brown, polygonal, adherent scales on different parts of the body surface. It almost exclusively affects males and the estimated prevalence ranges from 1:2000-6000 in males worldwide. Extracutaneous manifestations are frequent including corneal opacities, cryptorchidism, neuropsychiatric symptoms or others.

New Insights into the Impact of Genome-Wide Copy Number Variations on Complex Congenital Heart Disease in Saudi Arabia.

Congenital heart diseases (CHDs) are complex traits that manifest in diverse clinical phenotypes such as the Tetralogy of Fallot (TOF), valvular and ventricular/atrial septal defects. Genetic mechanisms of CHDs have remained largely unclear to date. Copy number variations (CNVs) have been implicated in many complex diseases but their impact has not been examined extensively in various forms of CHD lesions.

Human Versus Machine: Comparing a Deep Learning Algorithm to Human Gradings for Detecting Glaucoma on Fundus Photographs.

Purpose: To compare the diagnostic performance of human gradings vs predictions provided by a machine-to-machine (M2M) deep learning (DL) algorithm trained to quantify retinal nerve fiber layer (RNFL) damage on fundus photographs.

Design: Evaluation of a machine learning algorithm.

Methods: An M2M DL algorithm trained with RNFL thickness parameters from spectral-domain optical coherence tomography was applied to a subset of 490 fundus photos of 490 eyes of 370 subjects graded by 2 glaucoma specialists for the probability of glaucomatous optical neuropathy (GON), and estimates of cup-to-disc (C/D) ratios.

Associations of autozygosity with a broad range of human phenotypes.

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F) for >1.

Telomerase reverse transcriptase promoter mutations in cancers derived from multiple organ sites among middle eastern population.

Sanger Sequencing and immunohistochemistry was employed to investigate the TERT promoter mutations and TERT protein expression with their association to clinicopathological characteristics in over 2200 samples of Middle Eastern origin from 13 different types of cancers. The TERT promoter mutations were most frequently present in bladder cancer (68.6%), followed by central nervous system tumors (28.

Truncating ARL6IP1 variant as the genetic cause of fatal complicated hereditary spastic paraplegia.

Background: Mutations in ARL6IP1, which encodes a tetraspan membrane protein localized to the endoplasmic reticulum (ER), have been recently described in a large family with a complicated form of hereditary spastic paraplegia (HSP).

Case Presentation: We sought to expand the HSP phenotype associated with ARL6IP1 variants by examining a Saudi kindred with a clinically more severe presentation, which resulted in spontaneous neonatal death of both affected siblings. Clinical features encompassed not only spastic paraplegia but also developmental delay, microcephaly, cerebral atrophy, periventricular leukoencephalopathy, hypotonia, seizures, spasticity, jejunal stricture, gastrointestinal reflux, neuropathy, dysmorphism and respiratory distress.

Update on hereditary, autosomal dominant cathepsin-A-related arteriopathy with strokes and leukoencephalopathy (CARASAL).

Cathepsin-A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) is an acronym that describes an ultra-rare, hereditary, cerebral small vessel disease. The aim is to summarize current knowledge and recent findings concerning phenotype, genotype, pathogenesis, diagnoses, and treatment options of CARASAL. The method used in the study is a systematic literature review.

First report of two successive deletions on chromosome 15q13 cytogenetic bands in a boy and girl: additional data to 15q13.3 syndrome with a report of high IQ patient.

15q13.3 syndrome is associated with a wide spectrum of neurological disorders. Among a cohort of 150 neurodevelopmental cases, we identified two patients with two close proximity interstitial hemizygous deletions on chromosome 15q13.

Familial, long-term pollakisuria as initial manifestation of HSP4 due to the SPAST variant c.683-2A>C.

Objective: Hereditary spastic paraplegia type-IV (HSP4) is the most common of the autosomal-dominant HSPs. Though urinary dysfunction is a frequent phenotypic feature, long-term pollakisuria as the initial manifestation of HSP4 has not been reported.

Case Report: The patient is a 56yo female with an uneventful history until age 46y, when she developed pollakisuria.

Transcranial Blade Injuries and Principles of Their Safe Extraction.

Retained cranial blade injuries are uncommon events lacking standardized recommendations for appropriate surgical extraction. The authors present a case of a 30-year-old male who sustained a penetrating blade injury of the left orbit with intracranial extension through the skull base into the temporal lobe. The patient walked to the emergency room and remained alert.

Combining CDKN1A gene expression and genome-wide SNPs in a twin cohort to gain insight into the heritability of individual radiosensitivity.

Individual variability in response to radiation exposure is recognised and has often been reported as important in treatment planning. Despite many efforts to identify biomarkers allowing the identification of radiation sensitive patients, it is not yet possible to distinguish them with certainty before the beginning of the radiotherapy treatment. A comprehensive analysis of genome-wide single-nucleotide polymorphisms (SNPs) and a transcriptional response to ionising radiation exposure in twins have the potential to identify such an individual.

Pattern Recognition Receptor Polymorphisms as Predictors of Oxaliplatin Benefit in Colorectal Cancer.

Background: Constitutional loss of function (LOF) single nucleotide polymorphisms (SNPs) in pattern recognition receptors FPR1, TLR3, and TLR4 have previously been reported to predict oxaliplatin benefit in colorectal cancer. Confirmation of this association could substantially improve patient stratification.

Methods: We performed a retrospective biomarker analysis of the Short Course in Oncology Therapy (SCOT) and COIN/COIN-B trials.

Exome Sequencing: Mutilating Sensory Neuropathy with Spastic Paraplegia due to a Mutation in FAM134B Gene.

Hereditary sensory and autonomic neuropathies (HSANs) are a clinically and genetically heterogeneous group of disorders involving various sensory and autonomic dysfunctions. The most common symptoms of HSANs include loss of sensations of pain and temperature that frequently lead to chronic ulcerations in the feet and hands of the patient. In this case study, we present the clinical features and genetic characteristics of two affected individuals from two unrelated Saudi families presenting mutilating sensory loss and spastic paraplegia.

Bi-allelic TMEM94 Truncating Variants Are Associated with Neurodevelopmental Delay, Congenital Heart Defects, and Distinct Facial Dysmorphism.

Neurodevelopmental disorders (NDD) are genetically and phenotypically heterogeneous conditions due to defects in genes involved in development and function of the nervous system. Individuals with NDD, in addition to their primary neurodevelopmental phenotype, may also have accompanying syndromic features that can be very helpful diagnostically especially those with recognizable facial appearance. In this study, we describe ten similarly affected individuals from six unrelated families of different ethnic origins having bi-allelic truncating variants in TMEM94, which encodes for an uncharacterized transmembrane nuclear protein that is highly conserved across mammals.