Reasons for Utilizing Telemedicine during and after the COVID-19 Pandemic: An Internet-Based International Study

The COVID-19 pandemic challenges healthcare services. Concomitantly, this pandemic had a stimulating effect on technological expansions related to telehealth and telemedicine. We sought to elucidate the principal patients’ reasons for using telemedicine during the COVID-19 pandemic and the propensity to use it thereafter. Our primary objective was to identify the reasons of the survey participants’ disparate attitudes toward the use of telemedicine. We performed an online, multilingual 30-question survey for 14 days during March–April 2021, focusing on the perception and usage of telemedicine and their intent to use it after the pandemic. We analyzed the data to identify the attributes influencing the intent to use telemedicine and built decision trees to highlight the most important related variables. We examined 473 answers: 272 from Israel, 87 from Uruguay, and 114 worldwide. Most participants were women (64.6%), married (63.8%) with 1–2 children (52.9%), and living in urban areas (84.6%). Only a third of the participants intended to continue using telemedicine after the COVID-19 pandemic. Our main findings are that an expected substitution effect, technical proficiency, reduced queueing times, and peer experience are the four major factors in the overall adoption of telemedicine. Specifically, (1) for most participants, the major factor influencing their telemedicine usage is the implicit expectation that such a visit will be a full substitute for an in-person appointment; (2) another factor affecting telemedicine usage by patients is their overall technical proficiency and comfort level in the use of common web-based tools, such as social media, while seeking relevant medical information; (3) time saving as telemedicine can allow for asynchronous communications, thereby reducing physical travel and queuing times at the clinic; and finally (4) some participants have also indicated that telemedicine seems more attractive to them after watching family and friends (peer experience) use it successfully

CpG sites with continuously increasing or decreasing methylation from early to late human fetal brain development

Normal human brain development is dependent on highly dynamic epigenetic processes for spatial and temporal gene regulation. Recent work identified wide-spread changes in DNA methylation during fetal brain development. We profiled CpG methylation in frontal cortex of 27 fetuses from gestational weeks 12-42, using Illumina 450K methylation arrays. Sites showing genome-wide significant correlation with gestational age were compared to a publicly available data set from gestational weeks 3-26. Altogether, we identified 2016 matching developmentally regulated differentially methylated positions (m-dDMPs): 1767 m-dDMPs were hypermethylated and 1149 hypomethylated during fetal development. M-dDMPs are underrepresented in CpG islands and gene promoters, and enriched in gene bodies. They appear to cluster in certain chromosome regions. M-dDMPs are significantly enriched in autism-associated genes and CpGs. Our results promote the idea that reduced methylation dynamics during fetal brain development may predispose to autism. In addition, m-dDMPs are enriched in genes with human-specific brain expression patterns and/or histone modifications. Collectively, we defined a subset of dDMPs exhibiting constant methylation changes from early to late pregnancy. The same epigenetic mechanisms involving methylation changes in cis-regulatory regions may have been adopted for human brain evolution and ontogeny

Epigenetic dysregulation in the developing Down syndrome cortex

<p>Using Illumina 450K arrays, 1.85% of all analyzed CpG sites were significantly hypermethylated and 0.31% hypomethylated in fetal Down syndrome (DS) cortex throughout the genome. The methylation changes on chromosome 21 appeared to be balanced between hypo- and hyper-methylation, whereas, consistent with prior reports, all other chromosomes showed 3–11 times more hyper- than hypo-methylated sites. Reduced <i>NRSF/REST</i> expression due to upregulation of <i>DYRK1A</i> (on chromosome 21q22.13) and methylation of REST binding sites during early developmental stages may contribute to this genome-wide excess of hypermethylated sites. Upregulation of <i>DNMT3L</i> (on chromosome 21q22.4) could lead to <i>de novo</i> methylation in neuroprogenitors, which then persists in the fetal DS brain where <i>DNMT3A</i> and <i>DNMT3B</i> become downregulated. The vast majority of differentially methylated promoters and genes was hypermethylated in DS and located outside chromosome 21, including the protocadherin gamma (<i>PCDHG</i>) cluster on chromosome 5q31, which is crucial for neural circuit formation in the developing brain. Bisulfite pyrosequencing and targeted RNA sequencing showed that several genes of <i>PCDHG</i> subfamilies A and B are hypermethylated and transcriptionally downregulated in fetal DS cortex. Decreased <i>PCDHG</i> expression is expected to reduce dendrite arborization and growth in cortical neurons. Since constitutive hypermethylation of <i>PCDHG</i> and other genes affects multiple tissues, including blood, it may provide useful biomarkers for DS brain development and pharmacologic targets for therapeutic interventions.</p

Next-generation sequencing reveals germline mutations in an infant with synchronous occurrence of nephro- and neuroblastoma

<p>Although neuro- and nephroblastoma are common solid tumors in children, the simultaneous occurrence is very rare and is often associated with syndromes. Here, we present a unique case of synchronous occurrence of neuro- and nephroblastoma in an infant with no signs of congenital anomalies or a syndrome. We performed genetic testing for possible candidate genes as underlying mutation using the next-generation sequencing (NGS) approach to target 94 genes and 284 single-nucleotide polymorphisms (SNPs) involved in cancer. We uncovered a novel heterozygous germline missense mutation p.F58L (c.172T→C) in the anaplastic lymphoma kinase (<i>ALK</i>) gene and one novel heterozygous rearrangement Q418Hfs^*11 (c.1254_1264delins TTACTTAGTACAAGAACTG) in the Fanconi anemia gene <i>FANCD2</i> leading to a truncated protein. Besides, several SNPs associated with the occurrence of neuroblastoma and/or nephroblastoma or multiple primary tumors were identified. The next-generation sequencing approach might in the future be useful not only in understanding tumor etiology but also in recognizing new genetic markers and targets for future personalized therapy.</p

GD2 Expression in Medulloblastoma and Neuroblastoma for Personalized Immunotherapy: A Matter of Subtype

Neuroblastoma (NBL) and medulloblastoma (MB) are aggressive pediatric cancers which can benefit from therapies targeting gangliosides. Therefore, we compared the ganglioside profile of 9 MB and 14 NBL samples by thin layer chromatography and mass spectrometry. NBL had the highest expression of GD2 (median 0.54 nmol GD2/mg protein), and also expressed complex gangliosides. GD2-low samples expressed GD1a and were more differentiated. MB mainly expressed GD2 (median 0.032 nmol GD2/mg protein) or GM3. Four sonic hedgehog-activated (SHH) as well as one group 4 and one group 3 MBs were GD2-positive. Two group 3 MB samples were GD2-negative but GM3-positive. N-glycolyl neuraminic acid-containing GM3 was neither detected in NBL nor MB by mass spectrometry. Furthermore, a GD2-phenotype predicting two-gene signature (ST8SIA1 and B4GALNT1) was applied to RNA-Seq datasets, including 86 MBs and validated by qRT-PCR. The signature values were decreased in group 3 and wingless-activated (WNT) compared to SHH and group 4 MBs. These results suggest that while NBL is GD2-positive, only some MB patients can benefit from a GD2-directed therapy. The expression of genes involved in the ganglioside synthesis may allow the identification of GD2-positive MBs. Finally, the ganglioside profile may reflect the differentiation status in NBL and could help to define MB subtypes

Extreme Methylation Values of Imprinted Genes in Human Abortions and Stillbirths

Imprinted genes play an important role in fetal and placental development. Using quantitative bisulfite pyrosequencing assays, we determined the DNA methylation levels at two paternally methylated (H19 and MEG3) and four maternally methylated (LIT1, NESP55, PEG3, and SNRPN) imprinted regions in fetal muscle samples from abortions and stillbirths. Two of 55 (4%) spontaneous abortions and 10 of 57 (18%) stillbirths displayed hypermethylation in multiple genes. Interestingly, none of 34 induced abortions had extreme methylation values in multiple genes. All but two abortions/stillbirths with multiple methylation abnormalities were male, indicating that the male embryo may be more susceptible to excess methylation. Hypermethylation of multiple imprinted genes is consistent with stochastic failures of the mechanism, which normally protects the hypomethylated allele from de novo methylation after fertilization. Two of six informative abortions/stillbirths with H19 hypermethylation revealed significant biallelic expression of the autocrine growth factor IGF2. In two other cases hypermethylation of MEG3 was associated with transcriptional down-regulation. We propose that primary epimutations resulting in inappropriate methylation and expression patterns of imprinted genes may contribute to both normal human variation and disease, in particular spontaneous pregnancy loss