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IntroductionThe unprecedented impact of the coronavirus pandemic (COVID-19) has had profound implications on the ASD community, including disrupting daily life, increasing stress and emotional dysregulation in autistic children, and worsening individual and family well-being.MethodsThis study used quantitative and qualitative survey data from parents in Qatar (n=271), to understand the impact of the COVID-19 pandemic on autistic children and their families in Qatar. The questionnaire was a combination of open-ended (qualitative) and closed-ended (quantitative) questions to explore patterns in the experiences of the different families, as well as to contrive themes. The survey was created in a way to evaluate the psychological, academic/intervention, economic, and other impacts of the pandemic related measures on a sample of multicultural families residing in the State of Qatar during the peak period of confinement and physical distancing in 2020. Data acquisition involved the utilization of Google Forms. Subsequent quantitative analysis employed the SPSS software and chi-square analysis for numerical examination, enabling the characterization of the studied population and exploration of associations between parental stress levels and variables such as employment status, therapy accessibility, presence of hired assistance, and alterations in their childs skills. Concurrently, qualitative data from written responses underwent thorough categorization, encompassing themes such as emotional isolation, mental or financial challenges, and difficulties in obtaining support.ResultsParents expressed distress and disturbance in their daily lives, including profound disruptions to their childrens access to treatment, education, and activities. Most parents reported deteriorations in their childrens sleep (69.4%), behavioral regulation (52.8%), and acquired skills across multiple domains (54.2%). Parents also reported decreased access to family and social support networks, as well as decreased quality of clinical and community support. Qualitative analysis of parental responses revealed that child developmental regression was an important source of parental stress.Discussion and conclusionThe greater impact of the pandemic on autistic children and their families emphasizes the need for accessible and affordable health, education, and family services to manage their special needs.

It is now evident that DNA forms an organized nuclear architecture, which is essential to maintain the structural and functional integrity of the genome. Chromatin organization can be systematically studied due to the recent boom in chromosome conformation capture technologies (e.g., 3C and its successors 4C, 5C and Hi-C), which is accompanied by the development of computational pipelines to identify biologically meaningful chromatin contacts in such data. However, not all tools are applicable to all experimental designs and all structural features. Capture Hi-C (CHi-C) is a method that uses an intermediate hybridization step to target and select predefined regions of interest in a Hi-C library, thereby increasing effective sequencing depth for those regions. It allows researchers to investigate fine chromatin structures at high resolution, for instance promoter-enhancer loops, but it introduces additional biases with the capture step, and therefore requires specialized pipelines. Here, we compare multiple analytical pipelines for CHi-C data analysis. We consider the effect of retaining multi-mapping reads and compare the efficiency of different statistical approaches in both identifying reproducible interactions and determining biologically significant interactions. At restriction fragment level resolution, the number of multi-mapping reads that could be rescued was negligible. The number of identified interactions varied widely, depending on the analytical method, indicating large differences in type I and type II error rates. The optimal pipeline depends on the project-specific tolerance level of false positive and false negative chromatin contacts.

Somatic cells are reprogrammed with reprogramming factors to generate induced pluripotent stem cells (iPSCs), offering a promising future for disease modeling and treatment by overcoming the limitations of embryonic stem cells. However, this process remains inefficient since only a small percentage of transfected cells can undergo full reprogramming. Introducing miRNAs, such as miR-294 and miR302/3667, with reprogramming factors, has shown to increase iPSC colony formation. Previously, we identified five transcription factors, GBX2, NANOGP8, SP8, PEG3, and ZIC1, which may boost iPSC generation. In this study, we performed quantitative miRNAome and small RNA-seq sequencing and applied our previously identified transcriptome to identify the potential miRNA–mRNA regulomics and regulatory network of other ncRNAs. From each fibroblast (N = 4), three iPSC clones were examined (N = 12). iPSCs and original fibroblasts expressed miRNA clusters differently and miRNA clusters were compared to mRNA hits. Moreover, miRNA, piRNA, and snoRNAs expression profiles in iPSCs and original fibroblasts were assessed to identify the potential role of ncRNAs in enhancing iPSC generation, pluripotency, and differentiation. Decreased levels of let-7a-5p showed an increase of SP8 as described previously. Remarkably, the targets of identifier miRNAs were grouped into pluripotency canonical pathways, on stemness, cellular development, growth and proliferation, cellular assembly, and organization of iPSCs.

Stress granules (SGs) are assemblies of selective messenger RNAs (mRNAs), translation factors, and RNA-binding proteins in small untranslated messenger ribonucleoprotein (mRNP) complexes in the cytoplasm. Evidence indicates that different types of cells have shown different mechanisms to respond to stress and the formation of SGs. In the present work, we investigated how human-induced pluripotent stem cells (hiPSCs/IMR90-1) overcome hyperosmotic stress compared to a cell line that does not harbor pluripotent characteristics (SH-SY5Y cell line). Gradient concentrations of NaCl showed a different pattern of SG formation between hiPSCs/IMR90-1 and the nonpluripotent cell line SH-SY5Y. Other pluripotent stem cell lines (hiPSCs/CRTD5 and hESCs/H9 (human embryonic stem cell line)) as well as nonpluripotent cell lines (BHK-21 and MCF-7) were used to confirm this phenomenon. Moreover, the formation of hyperosmotic SGs in hiPSCs/IMR90-1 was independent of eIF2α phosphorylation and was associated with low apoptosis levels. In addition, a comprehensive proteomics analysis was performed to identify proteins involved in regulating this specific pattern of hyperosmotic SG formation in hiPSCs/IMR90-1. We found possible implications of microtubule organization on the response to hyperosmotic stress in hiPSCs/IMR90-1. We have also unveiled a reduced expression of tubulin that may protect cells against hyperosmolarity stress while inhibiting SG formation without affecting stem cell self-renewal and pluripotency. Our observations may provide a possible cellular mechanism to better understand SG dynamics in pluripotent stem cells.

The diversity of RNA viruses dictates their evolution in a particular host, community or environment. Here, we reported within- and between-host pH1N1virus diversity at consensus and sub-consensus levels over a three-year period (2015−2017) and its implications on disease severity. A total of 90 nasal samples positive for the pH1N1 virus were deep-sequenced and analyzed to detect low-frequency variants (LFVs) and haplotypes. Parallel evolution of LFVs was seen in the hemagglutinin (HA) gene across three scales: among patients (33%), across years (22%), and at global scale. Remarkably, investigating the emergence of LFVs at the consensus level demonstrated that within-host virus evolution recapitulates evolutionary dynamics seen at the global scale. Analysis of virus diversity at the HA haplotype level revealed the clustering of low-frequency haplotypes from early 2015 with dominant strains of 2016, indicating rapid haplotype evolution. Haplotype sharing was also noticed in all years, strongly suggesting haplotype transmission among patients infected during a specific influenza season. Finally, more than half of patients with severe symptoms harbored a larger number of haplotypes, mostly in patients under the age of five. Therefore, patient age, haplotype diversity, and the presence of certain LFVs should be considered when interpreting illness severity. In addition to its importance in understanding virus evolution, sub-consensus virus diversity together with whole genome sequencing is essential to explain variabilities in clinical outcomes that cannot be explained by either analysis alone.

Introduction: The unprecedented impact of the coronavirus pandemic (COVID- 19) has had profound implications on the ASD community, including disrupting daily life, increasing stress and emotional dysregulation in autistic children, and worsening individual and family well-being. Methods: This study used quantitative and qualitative survey data from parents in Qatar (n=271), to understand the impact of the COVID-19 pandemic on autistic children and their families in Qatar. The questionnaire was a combination of open-ended (qualitative) and closed-ended (quantitative) questions to explore patterns in the experiences of the different families, as well as to contrive themes. The survey was created in a way to evaluate the psychological, academic/ intervention, economic, and other impacts of the pandemic related measures on a sample of multicultural families residing in the State of Qatar during the peak period of confinement and physical distancing in 2020. Data acquisition involved the utilization of Google Forms. Subsequent quantitative analysis employed the SPSS software and chi-square analysis for numerical examination, enabling the characterization of the studied population and exploration of associations between parental stress levels and variables such as employment status, therapy accessibility, presence of hired assistance, and alterations in their childs skills. Concurrently, qualitative data from written responses underwent thorough categorization, encompassing themes such as emotional isolation, mental or financial challenges, and difficulties in obtaining support. Results: Parents expressed distress and disturbance in their daily lives, including profound disruptions to their childrens access to treatment, education, and activities. Most parents reported deteriorations in their childrens sleep (69.4%), behavioral regulation (52.8%), and acquired skills across multiple domains (54.2%). Parents also reported decreased access to family and social support networks, as well as decreased quality of clinical and community support. Qualitative analysis of parental responses revealed that child developmental regression was an important source of parental stress. Discussion and conclusion: The greater impact of the pandemic on autistic children and their families emphasizes the need for accessible and affordable health, education, and family services to manage their special needs. [ABSTRACT FROM AUTHOR]

Abnormal eye gaze is a hallmark characteristic of autism spectrum disorder (ASD). The primary aim of the present research was to develop an Arabic version of an objective measure of ASD, the "autism index" (AI), based on eye gaze tracking to social and nonsocial stimuli validated initially in the United States. The initial phase of this study included the translation of English language eye‐tracking stimuli into stimuli appropriate for an Arabic‐speaking culture. During the second phase, we tested it on a total of 144 children with ASD, and 96 controls. The AI had excellent internal consistency and test–retest reliability. Moreover, the AI showed good differentiation of ASD from control cases (AUC = 0.730, SE = 0.035). The AI was significantly positively correlated with SCQ total raw scores (r = 0.46, p < 0.001). ADOS‐2 scores were only available in the ASD group and did not show a significant relationship with AI scores (r = 0.10, p = 0.348), likely due to the restricted range. The AI, when implemented using Arabic‐translated stimuli in a Qatari sample, showed good diagnostic differentiation and a strong correlation with parent‐reported ASD symptoms. Thus, the AI appears to have cross‐cultural validity and may be useful as a diagnostic aide to inform clinical judgment and track ASD symptom levels as part of the evaluation process. Lay Summary: This study aimed to create an Arabic version of a tool called the "autism index" (AI), which uses eye gaze tracking to assess autism spectrum disorder (ASD). The researchers translated the AI's eye‐tracking tests into Arabic and tested it on children with ASD (n = 144), non‐autistic children (n = 84), and children with developmental delays (n = 12). The AI proved to be reliable and effectively distinguished children with ASD from the control groups and demonstrated cross‐cultural validity. It also showed a strong correlation with parent‐reported ASD symptoms. In conclusion, the Arabic version of the AI showed promise as a valuable cross‐cultural objective tool for screening, diagnosing, and tracking ASD symptoms. [ABSTRACT FROM AUTHOR]

Somatic cells are reprogrammed with reprogramming factors to generate induced pluripotent stem cells (iPSCs), offering a promising future for disease modeling and treatment by overcoming the limitations of embryonic stem cells. However, this process remains inefficient since only a small percentage of transfected cells can undergo full reprogramming. Introducing miRNAs, such as miR-294 and miR302/3667, with reprogramming factors, has shown to increase iPSC colony formation. Previously, we identified five transcription factors, GBX2, NANOGP8, SP8, PEG3, and ZIC1, which may boost iPSC generation. In this study, we performed quantitative miRNAome and small RNA-seq sequencing and applied our previously identified transcriptome to identify the potential miRNA–mRNA regulomics and regulatory network of other ncRNAs. From each fibroblast (N = 4), three iPSC clones were examined (N = 12). iPSCs and original fibroblasts expressed miRNA clusters differently and miRNA clusters were compared to mRNA hits. Moreover, miRNA, piRNA, and snoRNAs expression profiles in iPSCs and original fibroblasts were assessed to identify the potential role of ncRNAs in enhancing iPSC generation, pluripotency, and differentiation. Decreased levels of let-7a-5p showed an increase of SP8 as described previously. Remarkably, the targets of identifier miRNAs were grouped into pluripotency canonical pathways, on stemness, cellular development, growth and proliferation, cellular assembly, and organization of iPSCs. [ABSTRACT FROM AUTHOR]

It is now evident that DNA forms an organized nuclear architecture, which is essential to maintain the structural and functional integrity of the genome. Chromatin organization can be systematically studied due to the recent boom in chromosome conformation capture technologies (e.g., 3C and its successors 4C, 5C and Hi-C), which is accompanied by the development of computational pipelines to identify biologically meaningful chromatin contacts in such data. However, not all tools are applicable to all experimental designs and all structural features. Capture Hi-C (CHi-C) is a method that uses an intermediate hybridization step to target and select predefined regions of interest in a Hi-C library, thereby increasing effective sequencing depth for those regions. It allows researchers to investigate fine chromatin structures at high resolution, for instance promoter-enhancer loops, but it introduces additional biases with the capture step, and therefore requires specialized pipelines. Here, we compare multiple analytical pipelines for CHi-C data analysis. We consider the effect of retaining multi-mapping reads and compare the efficiency of different statistical approaches in both identifying reproducible interactions and determining biologically significant interactions. At restriction fragment level resolution, the number of multi-mapping reads that could be rescued was negligible. The number of identified interactions varied widely, depending on the analytical method, indicating large differences in type I and type II error rates. The optimal pipeline depends on the project-specific tolerance level of false positive and false negative chromatin contacts. [ABSTRACT FROM AUTHOR]

Stress granules (SGs) are assemblies of selective messenger RNAs (mRNAs), translation factors, and RNA-binding proteins in small untranslated messenger ribonucleoprotein (mRNP) complexes in the cytoplasm. Evidence indicates that different types of cells have shown different mechanisms to respond to stress and the formation of SGs. In the present work, we investigated how human-induced pluripotent stem cells (hiPSCs/IMR90-1) overcome hyperosmotic stress compared to a cell line that does not harbor pluripotent characteristics (SH-SY5Y cell line). Gradient concentrations of NaCl showed a different pattern of SG formation between hiPSCs/IMR90-1 and the nonpluripotent cell line SH-SY5Y. Other pluripotent stem cell lines (hiPSCs/CRTD5 and hESCs/H9 (human embryonic stem cell line)) as well as nonpluripotent cell lines (BHK-21 and MCF-7) were used to confirm this phenomenon. Moreover, the formation of hyperosmotic SGs in hiPSCs/IMR90-1 was independent of eIF2α phosphorylation and was associated with low apoptosis levels. In addition, a comprehensive proteomics analysis was performed to identify proteins involved in regulating this specific pattern of hyperosmotic SG formation in hiPSCs/IMR90-1. We found possible implications of microtubule organization on the response to hyperosmotic stress in hiPSCs/IMR90-1. We have also unveiled a reduced expression of tubulin that may protect cells against hyperosmolarity stress while inhibiting SG formation without affecting stem cell self-renewal and pluripotency. Our observations may provide a possible cellular mechanism to better understand SG dynamics in pluripotent stem cells. [ABSTRACT FROM AUTHOR]