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The fusiform face area responds selectively to faces and is causally involved in face perception. How does face-selectivity in the fusiform arise in development, and why does it develop so systematically in the same location across individuals? Preferential cortical responses to faces develop early in infancy, yet evidence is conflicting on the central question of whether visual experience with faces is necessary. Here, we revisit this question by scanning congenitally blind individuals with fMRI while they haptically explored 3D-printed faces and other stimuli. We found robust face-selective responses in the lateral fusiform gyrus of individual blind participants during haptic exploration of stimuli, indicating that neither visual experience with faces nor fovea-biased inputs is necessary for face-selectivity to arise in the lateral fusiform gyrus. Our results instead suggest a role for long-range connectivity in specifying the location of face-selectivity in the human brain.

Congenital heart defects (CHD) are the most common birth defect and are both clinically and genetically heterogeneous. Truncus arteriosus (TA), characterized by a single arterial vessel arising from both ventricles giving rise to the coronary, pulmonary and systemic arteries, is rare and only responsible for 1% of all CHD. Two consanguineous families with TA were previously identified to have homozygous nonsense variants within the gene NKX2-6. NKX2-6 is a known downstream target of TBX1, an important transcriptional regulator implicated in the cardiac phenotype of 22q11.2 microdeletion syndrome. Herein, we report two siblings with TA presumably caused by compound heterozygous NKX2-6 variants without a history of consanguinity. Two in-house cohorts with conotruncal defects (CTD) were sequenced for variants in NKX2-6 and no additional cases of biallelic NKX2-6 variants were identified. The similar phenotype of these cases, and the clustering of variants that likely result in a truncated protein that disrupts the homeobox domain, suggest that biallelic loss of function for NKX2-6 is a rare genetic etiology for TA in particular, and possibly other types of CHD.

PURPOSE: Pediatric cardiomyopathy is rare, has a broad differential diagnosis, results in high morbidity and mortality, and has sub-optimal diagnostic yield using next generation sequencing panels. Exome sequencing has reported diagnostic yields ranging from 30-57% for neonates in intensive care units. We aimed to characterize the clinical utility of exome sequencing in infantile heart failure. METHODS: Infants diagnosed with acute heart failure prior to 1 year old over a period of 34 months at a large tertiary children’s hospital were recruited. Demographic and diagnostic information was obtained from medical records. Fifteen eligible patients were enrolled. RESULTS: Dilated cardiomyopathy was the predominant cardiac diagnosis, seen in 60% of patients. Molecular diagnosis was identified in 66.7% of patients (10/15). Of those diagnoses, 70% would not have been detected using multi-gene next generation sequencing panels focused on cardiomyopathy or arrhythmia disease genes. Genetic testing changed medical decision-making in 53% of all cases and 80% of positive cases, and was especially beneficial when testing was expedited. CONCLUSIONS: Given the broad differential diagnosis and critical status of infants with heart failure, rapid exome sequencing provides timely diagnoses, changes medical management, and should be the first-tier molecular test.

Clinical exome sequencing (CES) aids in the diagnosis of rare genetic disorders. Herein, we report the molecular diagnostic yield and spectrum of genetic alterations contributing to disease in 700 pediatric cases analyzed at the Children's Hospital of Philadelphia. The overall diagnostic yield was 23%, with three cases having more than one molecular diagnosis and 2.6% having secondary/additional findings. A candidate gene finding was reported in another 8.4% of cases. The clinical indications with the highest diagnostic yield were neurodevelopmental disorders (including seizures), whereas immune- and oncology-related indications were negatively associated with molecular diagnosis. The rapid expansion of knowledge regarding the genome's role in human disease necessitates reanalysis of CES samples. To capture these new discoveries, a subset of cases (n = 240) underwent reanalysis, with an increase in diagnostic yield. We describe our experience reporting CES results in a pediatric setting, including reporting of secondary findings, reporting newly discovered genetic conditions, and revisiting negative test results. Finally, we highlight the challenges associated with implementing critical updates to the CES workflow. Although these updates are necessary, they demand an investment of time and resources from the laboratory. In summary, these data demonstrate the clinical utility of exome sequencing and reanalysis, while highlighting the critical considerations for continuous improvement of a CES test in a clinical laboratory.

In this digital era, consumers are influenced by various intelligent computing technologies in the age of the Internet of Things (IoT) to enhance their comfort and quality of life. A Smart TV with broadcasting services is considered as an excellent illustration of the digital technologies. Smart TV applications and software are constantly developed, and it has been certified to satisfy EAL2 security requirements. These technologies understand hand movements and responds appropriately. They are, however, vulnerable to security breaches via email, cameras, internet connectivity, and media players. However, the risks can be reduced by utilizing passwords, antivirus software, secure Wi-Fi, and other methods. This research study is a review on the applications of Smart TV in an IoT driven environment. The purpose of this research is to develop and describe: (a) study architecture, (b) working (c) security issues, (d) testing, (e) advantages and (f) disadvantages.

Novel gene-disease discoveries, rapid advancements in technology, and improved bioinformatics tools all have the potential to yield additional molecular diagnoses through the reanalysis of exome sequencing data. Collaborations between clinical laboratories, ordering physicians, and researchers are also driving factors that can contribute to these new insights. Automation in ongoing natural history collection, evolving phenotype updates, advancements in processing next-generation sequencing data, and up-to-date variant-gene-disease databases are increasingly needed for systematic exome reanalysis. Here, we review some of the advantages and challenges for clinician-initiated and laboratory-initiated exome reanalysis, and we propose a model for the future that could potentially maximize the clinical utility of exome reanalysis by integrating information from electronic medical records and knowledge databases into routine clinical workflows.

Social Media is an ever-growing tool which will only continue to grow as time goes by. As the commercial applications of social media increase exponentially, interest in using AI techniques to predict the performance of posts has also increased. In this paper we have discussed four major approaches and methodologies to analyse the information present in social media posts and on the basis of the historical data obtained, predict the popularity of any future post in terms of number of likes, comments and shares. These approaches include Deep Neural Network (DNN), Multimodal approach by using the multimodal information embedded in a social media post on a given social media platform, Social Network Services (SNS) for the collection and inference of user-related data and Social Forecast method for the accurate forecast of popularity of content put up on a social media platform. All these methodologies are performed on a dataset in the form of algorithms to obtain results of predictions. These methods take into consideration textual and multimedia content such as images and videos and on the basis of data acquired from these, eventually draw results. Our hope is that this paper can provide an insight into the current state of ML approaches towards social media metrics prediction.

The advancement of precision medicine requires new methods to coordinate and deliver genetic data from heterogeneous sources to physicians and patients. The eMERGE III Network enrolled >25,000 participants from biobank and prospective cohorts of predominantly healthy individuals for clinical genetic testing to determine clinically actionable findings. The network developed protocols linking together the 11 participant collection sites and 2 clinical genetic testing laboratories. DNA capture panels targeting 109 genes were used for testing of DNA and sample collection, data generation, interpretation, reporting, delivery, and storage were each harmonized. A compliant and secure network enabled ongoing review and reconciliation of clinical interpretations, while maintaining communication and data sharing between clinicians and investigators. A total of 202 individuals had positive diagnostic findings relevant to the indication for testing and 1,294 had additional/secondary findings of medical significance deemed to be returnable, establishing data return rates for other testing endeavors. This study accomplished integration of structured genomic results into multiple electronic health record (EHR) systems, setting the stage for clinical decision support to enable genomic medicine. Further, the established processes enable different sequencing sites to harmonize technical and interpretive aspects of sequencing tests, a critical achievement toward global standardization of genomic testing. The eMERGE protocols and tools are available for widespread dissemination.

Purpose Hearing loss (HL) is the most common sensory disorder in children. Prompt molecular diagnosis may guide screening and management; especially in syndromic cases when HL is the single presenting feature. Exome sequencing (ES)is an appealing diagnostic tool for HL as the genetic causes are highly heterogeneous. Methods ES was performed on a prospective cohort of 43 probands with HL. Sequence data were analyzed for primary and secondary findings. Capture and coverage analysis was performed for genes and variants associated with HL. Results The diagnostic rate using ES was 37.2% compared to 15.8% with clinical HL panel. Secondary findings were discovered in three patients. For 247 genes associated with HL, 94.7% of the exons were targeted for capture and 81.7% of these exons were covered at 20× or greater. Further analysis of 454 randomly selected HL-associated variants showed 89% were targeted for capture and 75% were covered at a read depth of at least 20×. Conclusion ES has an improved yield to clinical testing and may capture diagnoses not initially considered due to subtle clinical phenotypes. Technical challenges were identified, including inadequate capture and coverage of HL genes. Additional considerations of ES include secondary findings, cost, and turnaround time.

Coronavirus has significantly entered the globe and has affected everyone’s life in some form or another. The identification of the coronavirus is as important as prevention. An early and precise diagnosis will have significant-good benefits for us. The Convolutional Neural Network can be implemented for virus detection, and content-adaptive progressive occlusion analysis could be used to handle occlusion. To improve precision, it is also possible to add many other classification methods accordingly, which are mentioned in this paper.

This paper explores home as a space of youth nightlife and drinking through a feminist lens. It draws on feminist geographical scholarship on home and 40 semi-structured interviews with young people aged 16–25 in Switzerland in the context of a larger interdisciplinary study. We find that the home figures as a central space of nightlife for young people beyond pre-drinking or home parties. At the same time, privacy and intimacy are important to young people when drinking alcohol outside of the home. We suggest that this preference of privacy when going out indicates an interweaving of private and public spheres in young people’s nightlives. The paper argues that the home is both a central concrete space and an important symbolic notion in young people’s nightlives. In so doing, it empirically complicates the public/private dualism and contributes to feminist geographical conceptualisations of home in the context of youth nightlife.

International audience; Purpose:CACNA1C encodes the alpha-1-subunit of a voltage-dependent L-type calcium channel expressed in human heart and brain. Heterozygous variants in CACNA1C have previously been reported in association with Timothy syndrome and long QT syndrome. Several case reports have suggested that CACNA1C variation may also be associated with a primarily neurological phenotype.Methods:We describe 25 individuals from 22 families with heterozygous variants in CACNA1C, who present with predominantly neurological manifestations.Results:Fourteen individuals have de novo, nontruncating variants and present variably with developmental delays, intellectual disability, autism, hypotonia, ataxia, and epilepsy. Functional studies of a subgroup of missense variants via patch clamp experiments demonstrated differential effects on channel function in vitro, including loss of function (p.Leu1408Val), neutral effect (p.Leu614Arg), and gain of function (p.Leu657Phe, p.Leu614Pro). The remaining 11 individuals from eight families have truncating variants in CACNA1C. The majority of these individuals have expressive language deficits, and half have autism.Conclusion:We expand the phenotype associated with CACNA1C variants to include neurodevelopmental abnormalities and epilepsy, in the absence of classic features of Timothy syndrome or long QT syndrome.

Carrier screening involves detection of carrier status for genes associated with recessive conditions. A negative carrier screening test result bears a nonzero residual risk (RR) for the individual to have an affected child. The RR depends on the prevalence of specific conditions and the detection rate (DR) of the test itself. Herein, we provide a detailed approach for calculating DR and RR. DR was calculated on the basis of the sum of disease allele frequencies (DAFs) of pathogenic variants found in published literature. As a proof of concept, DAF data for cystic fibrosis were compared with society guidelines. The DAF data calculated by this method were consistent with the published cystic fibrosis guideline. In addition, we compared DAF for four genes (ABCC8, ASPA, GAA, and MMUT) across three laboratories, and outlined the likely reasons for discrepancies between these laboratories. The utility of carrier screening is to support couples with information while making reproductive choices. Accurate development of DR and RR is therefore critical. The method described herein provides an unbiased and transparent process to collect, calculate, and report these data.

As the human brain transforms incoming sounds, it remains unclear whether semantic meaning is assigned via distributed, domain-general architectures or specialized hierarchical streams. Here we show that the spatiotemporal progression from acoustic to semantically dominated representations is consistent with a hierarchical processing scheme. Combining magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) patterns, we found superior temporal responses beginning ~80 ms post-stimulus onset, spreading to extratemporal cortices by ~130 ms. Early acoustically-dominated representations trended systematically toward semantic category dominance over time (after ~200 ms) and space (beyond primary cortex). Semantic category representation was spatially specific: vocalizations were preferentially distinguished in temporal and frontal voice-selective regions and the fusiform face area; scene and object sounds were distinguished in parahippocampal and medial place areas. Our results are consistent with an extended auditory processing hierarchy in which acoustic representations give rise to multiple streams specialized by category, including areas typically considered visual cortex.

Here we show robust face-selectivity in the lateral fusiform gyrus of congenitally blind participants during haptic exploration of 3D-printed stimuli, indicating that neither visual experience, nor fovea-biased input, nor visual expertise is necessary for face-selectivity to arise in its characteristic location. Similar resting fMRI correlation fingerprints in individual blind and sighted participants suggest a role for long-range connectivity in the specification of the cortical locus of face-selectivity.

Sifrim–Hitz–Weiss syndrome (SIHIWES) is a recently described multisystemic neurodevelopmental disorder caused by de novo variants in CHD4. In this study, we investigated the clinical spectrum of the disorder, genotype–phenotype correlations, and the effect of different missense variants on CHD4 function. We collected clinical and molecular data from 32 individuals with mostly de novo variants in CHD4, identified through next-generation sequencing. We performed adenosine triphosphate (ATP) hydrolysis and nucleosome remodeling assays on variants from five different CHD4 domains. The majority of participants had global developmental delay, mild to moderate intellectual disability, brain anomalies, congenital heart defects, and dysmorphic features. Macrocephaly was a frequent but not universal finding. Additional common abnormalities included hypogonadism in males, skeletal and limb anomalies, hearing impairment, and ophthalmic abnormalities. The majority of variants were nontruncating and affected the SNF2-like region of the protein. We did not identify genotype–phenotype correlations based on the type or location of variants. Alterations in ATP hydrolysis and chromatin remodeling activities were observed in variants from different domains. The CHD4-related syndrome is a multisystemic neurodevelopmental disorder. Missense substitutions in different protein domains alter CHD4 function in a variant-specific manner, but result in a similar phenotype in humans.

Cystic fibrosis (CF) is one of the most common genetic diseases worldwide with high carrier frequencies across different ethnicities. Next generation sequencing of the cystic fibrosis transmembrane conductance regulator (CFTR) gene has proven to be an effective screening tool to determine carrier status with high detection rates. Here, we evaluate the performance of the Swift Biosciences Accel-Amplicon CFTR Capture Panel using CFTR-positive DNA samples. This assay is a one-day protocol that allows for one-tube reaction of 87 amplicons that span all coding regions, 5′ and 3′UTR, as well as four intronic regions. In this study, we provide the FASTQ, BAM, and VCF files on seven unique CFTR-positive samples and one normal control sample (14 samples processed including repeated samples). This method generated sequencing data with high coverage and near 100% on-target reads. We found that coverage depth was correlated with the GC content of each exon. This dataset is instrumental for clinical laboratories that are evaluating this technology as part of their carrier screening program., Measurement(s)amplicon sequencingTechnology Type(s)DNA sequencingFactor Type(s)CFTR mutationsSample Characteristic - OrganismHomo sapiens Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.10060244

Contains fulltext : 215381.pdf (Publisher’s version ) (Closed access) Background: Many addictive behaviours are influenced by the context in which they occur, but methods for simultaneously capturing the characteristics of a behaviour and its context are scarce. This study describes a smartphone application developed to document young adults' nightlife and drinking behaviours and investigates its impact on participants' lives. Methods: 241 participants, aged 16-25 (46.5% women), were asked to document 10 Friday and Saturday nights over seven weekends. Using their own smartphones, they documented the beverages consumed and the social and physical context by means of questionnaires, photos, and video clips, while phone sensors (e.g., GPS, Bluetooth, accelerometer) were running in the background. Quantitative and additional qualitative data (40 in-depth interviews) were used to investigate response burden, assessment reactivity, and disruption of usual activities among three participant groups, arranged according to the number of reports submitted during the study. Results: 69% of participants documented 10 or more nights. Compared with the most frequent contributors, regular and irregular participants reported similar numbers of non-alcoholic drinks per night, but lower numbers of alcoholic drinks. Within each group, the number of drinks consumed did not change over the course of the study. Taking pictures and video clips was sometimes perceived as inappropriate and potentially disruptive to the ongoing social activities. Conclusion: The application required a high but sustainable degree of commitment and did not induce reactivity. The method might be adapted to study other context-dependent addictive behaviours. Measures to decrease response burden and disruption of usual activities are proposed. 14 p.

Contains fulltext : 216279.pdf (Publisher’s version ) (Closed access) Despite human geographers' growing recognition of the need to explore how digital technologies are increasingly co-producing geographies, the methodological implications of such forms of data production are rarely discussed. This paper explores how smartphones co-constitute fieldwork when they are used as research instruments. Drawing from a research project on young people's nightlife in Switzerland, we use Ahmed's ideas of emotions to show how smartphones are not inert research tools but emotionally entangled in the field. We argue that doing research with smartphones visibly in fieldwork has an effect on the relationships between the people, practices, and places of the field site. More specifically, we propose that these effects of emotions call for a renewed scrutiny of research ethics, particularly as smartphones increasingly become part of research designs. 8 p.