Tag: nevin manimala

Sci Rep. 2021 May 24;11(1):10760. doi: 10.1038/s41598-021-90118-5.

ABSTRACT

In 2020, the world experienced its very first pandemic of the globalized era. A novel coronavirus, SARS-CoV-2, is the causative agent of severe pneumonia and has rapidly spread through many nations, crashing health systems and leading a large number of people to death. In Brazil, the emergence of local epidemics in major metropolitan areas has always been a concern. In a vast and heterogeneous country, with regional disparities and climate diversity, several factors can modulate the dynamics of COVID-19. What should be the scenario for inner Brazil, and what can we do to control infection transmission in each of these locations? Here, a mathematical model is proposed to simulate disease transmission among individuals in several scenarios, differing by abiotic factors, social-economic factors, and effectiveness of mitigation strategies. The disease control relies on keeping all individuals’ social distancing and detecting, followed by isolating, infected ones. The model reinforces social distancing as the most efficient method to control disease transmission. Moreover, it also shows that improving the detection and isolation of infected individuals can loosen this mitigation strategy. Finally, the effectiveness of control may be different across the country, and understanding it can help set up public health strategies.

PMID:34031456 | DOI:10.1038/s41598-021-90118-5

Sci Rep. 2021 May 24;11(1):10740. doi: 10.1038/s41598-021-89938-2.

ABSTRACT

The robust detection of disease-associated splice events from RNAseq data is challenging due to the potential confounding effect of gene expression levels and the often limited number of patients with relevant RNAseq data. Here we present a novel statistical approach to splicing outlier detection and differential splicing analysis. Our approach tests for differences in the percentages of sequence reads representing local splice events. We describe a software package called Bisbee which can predict the protein-level effect of splice alterations, a key feature lacking in many other splicing analysis resources. We leverage Bisbee’s prediction of protein level effects as a benchmark of its capabilities using matched sets of RNAseq and mass spectrometry data from normal tissues. Bisbee exhibits improved sensitivity and specificity over existing approaches and can be used to identify tissue-specific splice variants whose protein-level expression can be confirmed by mass spectrometry. We also applied Bisbee to assess evidence for a pathogenic splicing variant contributing to a rare disease and to identify tumor-specific splice isoforms associated with an oncogenic mutation. Bisbee was able to rediscover previously validated results in both of these cases and also identify common tumor-associated splice isoforms replicated in two independent melanoma datasets.

PMID:34031440 | DOI:10.1038/s41598-021-89938-2

Sci Rep. 2021 May 24;11(1):10809. doi: 10.1038/s41598-021-89448-1.

ABSTRACT

Karst rocky desertification (KRD) is a type of land deterioration, resulting in the degraded soil and a delicate ecosystem. Previous studies focused on the influence of KRD on the animals and plants, the impact of KRD on microorganisms, especially soil fungi remains to be discovered. This study reveals the change in the soil fungal community in response to KRD progression in southwest China. Illumina HiSeq was used to survey the soil fungal community. Results showed that the soil fungal community in the severe KRD (SKRD) was noticeably different from that in other KRD areas. Statistical analyses suggested that soil TN was the primary factor associated with the fungal community, followed by pH. Phylum Ascomycota was significantly abundant in non-degraded soils; whereas Basidiomycota predominated in SKRD. The ratio of Ascomycota/Basidiomycota significantly decreased along with KRD progression, which might be used as an indicator of KRD severity. Phylum Basidiomycota was sensitive to changes in all the soil properties but AP. Genus Sebacina might have the potential to promote vegetation and land restoration in KRD areas. This study fills a gap of knowledge on changes in soil fungal communities in accordance with KRD progression.

PMID:34031439 | DOI:10.1038/s41598-021-89448-1

Transl Psychiatry. 2021 May 24;11(1):310. doi: 10.1038/s41398-021-01431-6.

ABSTRACT

Gene expression has provided promising insights into the pathophysiology of post-traumatic stress disorder (PTSD); however, specific regulatory transcriptomic mechanisms remain unknown. The present study addressed this limitation by performing transcriptome-wide RNA-Seq of whole-blood samples from 226 World Trade Center responders. The investigation focused on differential expression (DE) at the gene, isoform, and for the first time, alternative splicing (AS) levels associated with the symptoms of PTSD: total burden, re-experiencing, avoidance, numbing, and hyperarousal subdimensions. These symptoms were associated with 76, 1, 48, 15, and 49 DE genes, respectively (FDR < 0.05). Moreover, they were associated with 103, 11, 0, 43, and 32 AS events. Avoidance differed the most from other dimensions with respect to DE genes and AS events. Gene set enrichment analysis (GSEA) identified pathways involved in inflammatory and metabolic processes, which may have implications in the treatment of PTSD. Overall, the findings shed a novel light on the wide range of transcriptomic alterations associated with PTSD at the gene and AS levels. The results of DE analysis associated with PTSD subdimensions highlights the importance of studying PTSD symptom heterogeneity.

PMID:34031375 | DOI:10.1038/s41398-021-01431-6

Nat Commun. 2021 May 24;12(1):3051. doi: 10.1038/s41467-021-23094-z.

ABSTRACT

The vast preponderance of somatic mutations in a typical cancer are either extremely rare or have never been previously recorded in available databases that track somatic mutations. These constitute a hidden genome that contrasts the relatively small number of mutations that occur frequently, the properties of which have been studied in depth. Here we demonstrate that this hidden genome contains much more accurate information than common mutations for the purpose of identifying the site of origin of primary cancers in settings where this is unknown. We accomplish this using a projection-based statistical method that achieves a highly effective signal condensation, by leveraging DNA sequence and epigenetic contexts using a set of meta-features that embody the mutation contexts of rare variants throughout the genome.

PMID:34031376 | DOI:10.1038/s41467-021-23094-z

Nat Commun. 2021 May 24;12(1):3042. doi: 10.1038/s41467-021-22417-4.

ABSTRACT

Controlling off-target editing activity is one of the central challenges in making CRISPR technology accurate and applicable in medical practice. Current algorithms for analyzing off-target activity do not provide statistical quantification, are not sufficiently sensitive in separating signal from noise in experiments with low editing rates, and do not address the detection of translocations. Here we present CRISPECTOR, a software tool that supports the detection and quantification of on- and off-target genome-editing activity from NGS data using paired treatment/control CRISPR experiments. In particular, CRISPECTOR facilitates the statistical analysis of NGS data from multiplex-PCR comparative experiments to detect and quantify adverse translocation events. We validate the observed results and show independent evidence of the occurrence of translocations in human cell lines, after genome editing. Our methodology is based on a statistical model comparison approach leading to better false-negative rates in sites with weak yet significant off-target activity.

PMID:34031394 | DOI:10.1038/s41467-021-22417-4

Med J Malaysia. 2021 May;76(3):401-413.

ABSTRACT

INTRODUCTION: Internet Addiction Disorder (IAD) is an umbrella term for various types of Internet-based behavioural addiction, whereas Internet Gaming Disorder (IGD) addresses a specific type of IAD that is postulated to be due to a lack of control in impulse inhibition. IGD is an area of concern in the Diagnostic and Statistics Manual of Mental Disorders (DSM-5), which can be objectively assessed by dysfunctional behaviour and the increasing time of being online, particularly during the COVID-19 pandemic. Electroencephalography (EEG) identifies amplitude changes in the evoked response potential (ERP) among IGDs, correlated with underlying comorbidities.

MATERIALS AND METHODS: A scoping review was performed to elaborate on the research regarding resting-state EEG and task-based EEG, particularly for Go/No-go paradigms pertaining to subjects with IAD or specifically IGD. The role of EEG was identified in its diagnostic capability to identify the salient changes that occurred in the response to reward network and the executive control network, using restingstate and task-based EEG. The implication of using EEG in monitoring the therapy for IAD and IGD was also reviewed.

RESULTS: EEG generally revealed reduced beta waves and increased theta waves in addicts. IGD with depression demonstrated increased theta and decreased alpha waves. Whereas increased P300, a late cognitive ERP component, was frequently associated with impaired excessive allocation of attentional resources of the IAD towards addiction-specific cues. IGD had increased whole brain delta waves at baseline, which showed significant reduction post therapy.

CONCLUSION: EEG can identify distinct neurophysiological changes among Internet Addiction Disorder and Internet Gaming Disorder that are akin to substance abuse disorders.

PMID:34031341

Transl Psychiatry. 2021 May 24;11(1):311. doi: 10.1038/s41398-021-01437-0.

ABSTRACT

Posttraumatic stress disorder (PTSD) is associated with shortened lifespan and healthspan, which suggests accelerated aging. Emerging evidence suggests that methylation age may be accelerated in PTSD. It is important to examine whether transcriptional age is also accelerated because transcriptome is highly dynamic, associated with age-related outcomes, and may offer greater insight into the premature aging in PTSD. This study is the first reported investigation of the relationship between transcriptional age and PTSD. Using RNA-Seq data from our previous study on 324 World Trade Center responders (201 never had PTSD, 81 with current PTSD, and 42 with past PTSD), as well as a transcriptional age calculator (RNAAgeCalc) recently developed by our group, we found that responders with current PTSD, compared with responders without a PTSD diagnosis, showed accelerated transcriptional aging (p = 0.0077) after adjustment for chronological age and race. We compared our results to the epigenetic aging results computed from several epigenetic clock calculators on matching DNA methylation data. GrimAge methylation age acceleration was also associated with PTSD diagnosis (p = 0.0097), and the results remained significant after adjustment for the proportions of immune cell types. PhenoAge, Hannum, and Horvath methylation age acceleration were not reliably related to PTSD. Both epigenetic and transcriptional aging may provide biological insights into the mechanisms underpinning aging in PTSD.

PMID:34031357 | DOI:10.1038/s41398-021-01437-0

Med J Malaysia. 2021 May;76(3):360-368.

ABSTRACT

INTRODUCTION: The effective connectivity (EC) when the brain is resting and how a neuronal system exerts influence over other regions of the brain, in different groups of subjects are still being investigated. Limited information was seen about the relationship between precuneus (PRE) which is a wellknown resting state hub with supramarginal gyrus (SMG) in healthy subjects (HS) and temporal lobe epilepsy (TLE) participants.

MATERIALS AND METHODS: Fourteen HS and 14 TLE patients with age and gender matched underwent resting state functional magnetic resonance imaging (rsfMRI) scanning using a 3-Tesla MRI machine to investigate the EC and percentage of amplitude fluctuation (PerAF) involving SMG and PRE. The rsfMRI data were analysed using Statistical Parametric Mapping (SPM12) and Spectral Dynamic Causal Modelling (spDCM) from which causal models were specified, estimated and inferred.

RESULTS: Model with bidirectional connections between PRE and SMG was chosen as the winning model. The EC from PRE to SMG is positive but the EC from SMG to PRE is negative in both hemispheres and in HS and TLE. Based on the findings from the EC analysis, there is an excitatory effect shown by PRE to SMG connection indicating a dominant role of PRE over SMG in both groups.

CONCLUSION: There is important evidence showing that PRE might also have influence on areas outside resting state network and the influence changes in the presence of brain abnormality.

PMID:34031335

Med J Malaysia. 2021 May;76(3):369-374.

ABSTRACT

INTRODUCTION: Twenty-seven adult patients, skin type III -V with mild to moderate acne, were recruited. IPL at wavelengths range of 420 – 600nm with triple pulses was administered every two weeks for a total of 3 sessions. Assessment of acne severity and improvement of treatment was based on Global Acne Grading System (GAGS), scoring before and after treatment for each session and patient satisfaction’s using a 5-item Likert scale range at the end of session three.

RESULTS: Of the 27 patients, 77.8% were female. Their ages group ranged from 18 to 35 years, and all patients had skin type III or IV. There were 14 mild acne patients and 13 moderate ones. There was a statistically significant improvement in mean acne severity score from 18.1± 4.3 at baseline to 14.3 ± 4.6 after two weeks post-IPL and 12.3 ± 4.9 after four weeks post-IPL. The result on satisfaction level of patients showed ‘satisfied’ in 3 patients, “very satisfied” in 5 patients; and, half of the patients (11) answered “fair” at the end of the study. Most patients tolerated well the procedure, and only 5 patients developed either post-inflammatory hyperpigmentation or skin hyperpigmentation.

CONCLUSION: The IPL of wavelength of 400-600nm offers effective, safe, and well-tolerated treatment of mild to moderate acne lesions in Malaysians with skin types III-IV. The majority of subjects had a fair score on treatment satisfaction. It is recommended that reasonable expectations for clinical results be addressed with patients before hands to prevent over-expectation.

PMID:34031336