Expanding the phenotype and genotype spectrum of TAOK1 neurodevelopmental disorder and delineating TAOK2 neurodevelopmental disorder.

Purpose: The TAOK proteins are a group of serine/threonine-protein kinases involved in signalling pathways, cytoskeleton regulation, and neuronal development. TAOK1 variants are associated with a neurodevelopmental disorder (NDD) characterized by distinctive facial features, hypotonia and feeding difficulties. TAOK2 variants have been reported to be associated with autism and early-onset obesity.

A syndromic neurodevelopmental disorder caused by rare variants in PPFIA3.

PPFIA3 encodes the protein-tyrosine phosphatase, receptor-type, F-polypeptide-interacting-protein-alpha-3 (PPFIA3), which is a member of the LAR-protein-tyrosine phosphatase-interacting-protein (liprin) family involved in synapse formation and function, synaptic vesicle transport, and presynaptic active zone assembly. The protein structure and function are evolutionarily well conserved, but human diseases related to PPFIA3 dysfunction are not yet reported in OMIM. Here, we report 20 individuals with rare PPFIA3 variants (19 heterozygous and 1 compound heterozygous) presenting with developmental delay, intellectual disability, hypotonia, dysmorphisms, microcephaly or macrocephaly, autistic features, and epilepsy with reduced penetrance.

A dual decoder U-Net-based model for nuclei instance segmentation in hematoxylin and eosin-stained histological images.

Even in the era of precision medicine, with various molecular tests based on omics technologies available to improve the diagnosis process, microscopic analysis of images derived from stained tissue sections remains crucial for diagnostic and treatment decisions. Among other cellular features, both nuclei number and shape provide essential diagnostic information. With the advent of digital pathology and emerging computerized methods to analyze the digitized images, nuclei detection, their instance segmentation and classification can be performed automatically.

Professional Oversight of Emergency-Use Interventions and Monitoring Systems: Ethical Guidance From the Singapore Experience of COVID-19.

High degrees of uncertainty and a lack of effective therapeutic treatments have characterized the COVID-19 pandemic and the provision of drug products outside research settings has been controversial. International guidelines for providing patients with experimental interventions to treat infectious diseases outside of clinical trials exist but it is unclear if or how they should apply in settings where clinical trials and research are strongly regulated. We propose the Professional Oversight of Emergency-Use Interventions and Monitoring System (POEIMS) as an alternative pathway based on guidance developed for the ethical provision of experimental interventions to treat COVID-19 in Singapore.

Retinal Degeneration Associated With the G1606A Mitochondrial Mutation.

The guanine-to-adenine substitution at nucleotide 1606 (G1606A) mutation in the mitochondrial DNA transfer RNA-valine gene has been reported to cause sensorineural deafness, ataxia, myoclonus, seizures, and mental retardation. This study hereby presents a single case report of a new retinal phenotype associated with this mutation: a middle-aged woman with retinal pigment epithelium stippling, atrophy, and peripapillary (retinal pigment epithelium) dropout on fundus examination. The patient was administered an empiric trial of a mitochondrial cocktail with close monitoring of her systemic symptoms.

A Grouping Differential Evolution Algorithm Boosted by Attraction and Repulsion Strategies for Masi Entropy-Based Multi-Level Image Segmentation.

Masi entropy is a popular criterion employed for identifying appropriate threshold values in image thresholding. However, with an increasing number of thresholds, the efficiency of Masi entropy-based multi-level thresholding algorithms becomes problematic. To overcome this, we propose a novel differential evolution (DE) algorithm as an effective population-based metaheuristic for Masi entropy-based multi-level image thresholding.

Investigating the Impact of the Bit Depth of Fluorescence-Stained Images on the Performance of Deep Learning-Based Nuclei Instance Segmentation.

Nuclei instance segmentation can be considered as a key point in the computer-mediated analysis of histological fluorescence-stained (FS) images. Many computer-assisted approaches have been proposed for this task, and among them, supervised deep learning (DL) methods deliver the best performances. An important criterion that can affect the DL-based nuclei instance segmentation performance of FS images is the utilised image bit depth, but to our knowledge, no study has been conducted so far to investigate this impact.

CryoNuSeg: A dataset for nuclei instance segmentation of cryosectioned H&E-stained histological images.

Nuclei instance segmentation plays an important role in the analysis of hematoxylin and eosin (H&E)-stained images. While supervised deep learning (DL)-based approaches represent the state-of-the-art in automatic nuclei instance segmentation, annotated datasets are required to train these models. There are two main types of tissue processing protocols resulting in formalin-fixed paraffin-embedded samples (FFPE) and frozen tissue samples (FS), respectively.

Multimodal imaging of an RPGR carrier female.

: Retinitis pigmentosa GTPase regulator () gene mutations are a common cause of X-linked retinitis pigmentosa and X-linked cone-rod dystrophy. There have been no previous reports of association with crystalline retinopathy or pseudo-crystalline retinopathy.: We describe the history, clinical findings, retinal imaging, and electrodiagnostic studies of a patient with a tapetal-like reflex (TLR) and pseudo-crystalline retinopathy secondary to mutation.

"Who is watching the watchdog?": ethical perspectives of sharing health-related data for precision medicine in Singapore.

Background: We aimed to examine the ethical concerns Singaporeans have about sharing health-data for precision medicine (PM) and identify suggestions for governance strategies. Just as Asian genomes are under-represented in PM, the views of Asian populations about the risks and benefits of data sharing are under-represented in prior attitudinal research.

Methods: We conducted seven focus groups with 62 participants in Singapore from May to July 2019.

Transfer learning using a multi-scale and multi-network ensemble for skin lesion classification.

Background And Objective: Skin cancer is among the most common cancer types in the white population and consequently computer aided methods for skin lesion classification based on dermoscopic images are of great interest. A promising approach for this uses transfer learning to adapt pre-trained convolutional neural networks (CNNs) for skin lesion diagnosis. Since pre-training commonly occurs with natural images of a fixed image resolution and these training images are usually significantly smaller than dermoscopic images, downsampling or cropping of skin lesion images is required.

A Multi-Organ Nucleus Segmentation Challenge.

Generalized nucleus segmentation techniques can contribute greatly to reducing the time to develop and validate visual biomarkers for new digital pathology datasets. We summarize the results of MoNuSeg 2018 Challenge whose objective was to develop generalizable nuclei segmentation techniques in digital pathology. The challenge was an official satellite event of the MICCAI 2018 conference in which 32 teams with more than 80 participants from geographically diverse institutes participated.

Constitutive activation of the PI3K-AKT pathway and cardiovascular abnormalities in an individual with Kosaki overgrowth syndrome.

Kosaki overgrowth syndrome is a recently described syndrome characterized by distinctive facial features, brain white matter lesions, and developmental delay. Germline activating heterozygous PDGFRB mutations have been reported in this condition. Systemic connective tissue-type findings have been described in some individuals.

Fusing fine-tuned deep features for skin lesion classification.

Malignant melanoma is one of the most aggressive forms of skin cancer. Early detection is important as it significantly improves survival rates. Consequently, accurate discrimination of malignant skin lesions from benign lesions such as seborrheic keratoses or benign nevi is crucial, while accurate computerised classification of skin lesion images is of great interest to support diagnosis.

McArdle Disease Presenting With Muscle Pain in a Teenage Girl: The Role of Whole-Exome Sequencing in Neurogenetic Disorders.

We present the case of a young woman with worsening attacks of muscle pain and rhabdomyolysis beginning at age 14. Initial metabolic testing and electromyography revealed findings of a nonspecific myopathy. Diagnostic options were discussed among the members of a neurogenetics clinic team.

A parent-of-origin analysis of paternal genetic variants and increased risk of conotruncal heart defects.

The association between conotruncal heart defects (CTHDs) and maternal genetic and environmental exposures is well studied. However, little is known about paternal genetic or environmental exposures and risk of CTHDs. We assessed the effect of paternal genetic variants in the folate, homocysteine, and transsulfuration pathways on risk of CTHDs in offspring.

Distributed Task Rescheduling With Time Constraints for the Optimization of Total Task Allocations in a Multirobot System.

This paper considers the problem of maximizing the number of task allocations in a distributed multirobot system under strict time constraints, where other optimization objectives need also be considered. It builds upon existing distributed task allocation algorithms, extending them with a novel method for maximizing the number of task assignments. The fundamental idea is that a task assignment to a robot has a high cost if its reassignment to another robot creates a feasible time slot for unallocated tasks.

A novel approach in pediatric telegenetic services: geneticist, pediatrician and genetic counselor team.

PurposeOur aim was to improve access to genetic services in an underserved region by developing a collaborative telegenetic service delivery model with a pediatrician, medical geneticist, and genetics counselor (GC).MethodsProtocols for the evaluation of common genetic indications were developed. Patients referred with indications suggestive of a syndromic etiology were scheduled to see the geneticist directly via telegenetics.

Alu-mediated deletion of PIGL in a Patient with CHIME syndrome.

CHIME syndrome is a rare autosomal recessive neuroectodermal disorder associated with biallelic mutations in PIGL. To date, six molecularly confirmed cases of CHIME syndrome have been reported. Here, we report the seventh patient with biallelic PIGL mutations associated with CHIME syndrome and describe the first characterization of an intragenic deletion in PIGL.

A hybrid cost-sensitive ensemble for imbalanced breast thermogram classification.

Objectives: Early recognition of breast cancer, the most commonly diagnosed form of cancer in women, is of crucial importance, given that it leads to significantly improved chances of survival. Medical thermography, which uses an infrared camera for thermal imaging, has been demonstrated as a particularly useful technique for early diagnosis, because it detects smaller tumors than the standard modality of mammography.

Methods And Material: In this paper, we analyse breast thermograms by extracting features describing bilateral symmetries between the two breast areas, and present a classification system for decision making.

Analysis of HEp-2 images using MD-LBP and MAD-bagging.

Indirect immunofluorescence imaging is employed to identify antinuclear antibodies in HEp-2 cells which founds the basis for diagnosing autoimmune diseases and other important pathological conditions involving the immune system. Six categories of HEp-2 cells are generally considered, namely homogeneous, fine speckled, coarse speckled, nucleolar, cyto-plasmic, and centromere cells. Typically, this categorisation is performed manually by an expert and is hence both time consuming and subjective.

A newborn with complex skeletal abnormalities, joint contractures, and bilateral corneal clouding with sclerocornea.

A newborn presented to genetics with complex skeletal abnormalities, joint contractures, and bilateral corneal clouding with sclerocornea. The patient survived for 8 months before succumbing to respiratory failure. Exome sequencing revealed a compound heterozygous mutation in theB3GALT6gene.