Robust correlation estimation and UMAP assisted topological analysis of omics data for disease subtyping.

Deciphering information hidden in the gene expression assays for identifying disease subtypes has significant importance in precision medicine. However, computational limitations thwart this process due to the intricacy of the biological networks and the curse of dimensionality of gene expression data. Therefore, clustering in such scenarios often becomes the first choice of exploratory data analysis to identify natural structures and intrinsic patterns in the data. However, sparse and high dimensional nature of omics data prevents conventional clustering algorithms to discover subtypes that are clinically relevant and statistically significant. Hence, non-linear dimensionality reduction techniques coupled with clustering in such scenarios often becomes imperative to improve the clustering results. In this study, we present a robust pipeline to discover disease subtypes with clinical relevance. Specifically, we focus on discovering patient sub-groups that have a residual life patterns remarkably different from other sub-groups. This is significant because by refining prognosis, subtyping can reduce uncertainty in approximating patients expected outcome. The methodology present is based on robust correlation estimation, UMAP- a non-linear dimensionality reduction method and mapper- a tool from topology. Notably, we suggest a method for improving the robustness of the correlation matrix of gene expression data for improving the clustering results. The performance of the model is evaluated by applying to five cancer datasets obtained through TCGA and comparisons are performed with some state of the art methods of NEMO, RSC-OTRI and SNF with regard to log-rank test and Restricted Life Expectancy Difference. For example in GBM dataset, the minimum separation for any two discovered subtypes is 221 days which is significantly higher than the other methodologies. We also compared the results without using the robust correlation based estimate and observed that robust correlation improves separability between survival curves significantly. From the results we infer that our methodology performs better compared to other methodologies with regard to separating survival curves of patient sub-groups despite using single omics profiles of patients compared to multiple omics profiles of SNF and NEMO. Pathway over-representation analysis is performed on the final clustering results to investigate the biological underpinnings characterizing each subtype.

The Impact of Post-traumatic Stress of SARS-CoV-2 Affliction on Psychological and Mental Health of Student Survivors: Cross Sectional Study.

Background: COVID-19 survivor's population is often associated with a long term impact on mental and psychological health. Recent included studies have also stated affliction of mental health due to fear of virus and preventive policies among the college students. Objectives: The research was conducted to find the psychological and mental impacts of SARS-CoV-2 affliction among the students' survivors in the university. Methods: The study design of the experiment was cross-sectional, sampling technique was non probability and sampling method being applied was convenience sampling. IBM Statistical Package for the Social Sciences version 20 was used for analyses. Descriptive data was examined and results were showed as mean and standard deviations, percentages, frequencies for continuous variables of IES-R scale (Intrusion, Avoidance, and Hyperarousal) using the total sample of n = 34. Results: Out of 34 only 24 student survivors responded to the online survey post COVID-19 recovery, with an overall participation level of 71%. Grading was given for the total IES-R score which was subdivided into a predefined range. Out of 24 participants, 9 (38%) participants showed the symptoms of mild (n = 2)-severe (n = 7) psychological impacts. On correlation of factors total IES-R score and taste and sense of smell were moderately correlated. The ordinal regression for complete loss of sense of taste and smell was also significant. Conclusion: The results from IES-R evaluation clearly outlines the presence of psychological sequels post recovery of COVID-19 episodes among the young college survivors. Complete loss of sense of smell and taste may be an indicator of psychological sequelae as compared to reduce sense of smell.

Mortality among healthcare workers in Indonesia during 18 months of COVID-19.

The impact of SARS-CoV-2 infections upon Indonesian health care workers (HCWs) is unknown due to the lack of systematic collection and analysis of mortality data specific to HCWs in this setting. This report details the results of a systematic compilation, abstraction and analysis of HCW fatalities in Indonesia during the first 18 months of COVID-19. HCW who passed away between March 2020 and July 2021 were identified using Pusara Digital, a community-based digital cemetery database dedicated to HCW. We calculated the mortality rates and death risk ratio of HCWs versus the general population. The analysis indicates that at least 1,545 HCWs died during the study period. Death rates among males and females HCWs were nearly equivalent (51% vs. 49%). The majority were physicians and specialists (535, 35%), nurses (428, 28%), and midwives (359, 23%). Most deaths occurred between the ages of 40 to 59 years old, with the median age being 50 years (IQR: 39-59). At least 322 deaths (21%) occurred with pre-existing conditions, including 45 pregnant women. During the first 18 months of COVID-19 in Indonesia, we estimated a minimum HCW mortality rate of 1.707 deaths per 1,000 HCWs. The provincial rates of HCW mortality ranged from 0.136 (West Sulawesi) to 5.32 HCW deaths per 1,000 HCWs (East Java). The HCW mortality rate was significantly higher than that of the general population (RR = 4.92, 95% CI 4.67-5.17). The COVID-19 pandemic in Indonesia resulted in the loss of many hundreds of HCWs, the majority of whom were senior healthcare workers. The HCW mortality rate is five times that of the general population. A national systematic surveillance of occupational mortality is urgently needed in this setting.

Genome sequence of Dichelobacter nodosus JKS-07B isolate from J&K, India associated with virulent footrot of sheep.

INTRODUCTION: Virulent footrot of sheep caused by Dichelobacter nodosus is associated with tremendous economic losses due to recurrent treatment costs and increased culling rates. This organism being a fastidious anaerobe is difficult to isolate on ordinary media that does not support its growth. The D. nodosus serogroup B isolate described in the present study has been used in the preparation of the whole-cell killed vaccine against footrot in India. D. nodosus serogroup B is the predominant serogroup involved in virulent footrot (lesion score 4) in India as well as in many sheep-rearing countries of the globe. METHODS: Genomic DNA was extracted using wizard Genomic DNA purification kit. The whole genome of the D. nodosus strain B was sequenced using an Illumina HiSeq 2500 platform and annotated according to functional gene categories. Annotations were performed using in-house developed Perl scripts using Nr/Nt database, uniprot, Pfam, KEGG, Panther DB, and GO database. RESULT: The assembled genome size is 1.311,533 Mb and GC content is 44.38. A total of 1215 protein-coding genes, 44tRNA and 7 rRNA were identified. The genome shows 98.63% sequence homology with the reference genome. However, 21 new genes have been identified in this genome. The information will provide insights into the various genes and regulators necessary for D. nodosus growth and survival. DISCUSSION: The genome information of this serogroup B of D. nodosus isolate involved in 85-90% cases of virulent footrot of sheep in India provides further insights for improvement of the killed vaccine (B serogroup) developed recently in India. For the development of an efficacious vaccine against virulent footrot, it is essential to know the serological diversity as well as the virulent status of the strains of the D. nodosus. This serogroup isolate is a potential vaccine candidate to mitigate ovine footrot in India as the majority of virulent footrot cases belong to serogroup B of D. nodosus.

Comparison Between Three Molecular Diagnostics for the Identification of Heterozygous Hemoglobin E.

BACKGROUND AND OBJECTIVES: Hemoglobin E is a variant hemoglobin caused due to the base substitution G→A at codon 26 in the ß-globin-coding gene that is followed by the alteration of glutamic acid (GAG) to lysine (AAG). Various types of molecular analysis methods such as tetra-primer amplification refractory mutation system (T-ARMS-PCR), Tm-shift real-time polymerase chain reaction (Tm-shift qPCR) and high-resolution melting analysis (HRMA) are commonly used to detect several mutations in the ß-globin-coding gene. This study was conducted to compare the detection result of Cd 26 (G→A) mutation in the ß-globin-coding gene of heterozygous HbE between the above-mentioned methods. MATERIALS AND METHODS: DNA samples were isolated from blood archive of heterozygous HbE and analyzed for the detection of the mutation using HRMA and Tm-shift on a real-time PCR instrument, whereas T-ARMS analysis was performed on a conventional PCR equipment. High resolution melt v3.1 software and Bio-Rad CFX Manager software were used to analyze the result of HRMA and Tm-shift qPCR, whereas the T-ARMS-PCR result was analyzed by observing the number and size of DNA bands on gel electrophoresis. RESULTS: Among 21 samples, the Cd 26 mutation was detected in numbers 18, 19 and 21 by HRMA, Tm-shift qPCR and T-ARMS-PCR. DNA Sequencing confirmed Cd 26 mutation on 5 ambiguous samples and revealed two homozygous mutation. CONCLUSION: The Cd 26 (G→A) mutation was detected in proportions 100, 91 and 86% by T-ARMS-PCR, Tm-shift qPCR and HRMA, respectively.

Anterior mediastinal neurofibrosarcoma-a rare manifestation of neurofibromatosis type-1.

Anterior mediastinal neurofibroma and neurofibrosarcoma form a rare class of tumors seen in patients of neurofibromatosis. We describe a case of anterior mediastinal neurofibrosarcoma in a known case of neurofibromatosis type-1.

Imidacloprid induced histomorphological changes and expression of TLR-4 and TNFα in lung.

The imidacloprid is used worldwide as a pesticide and has been linked with endocrine disturbances and reduced pulmonary function. However, effects of imidacloprid alone or in combination with microbial molecules on lungs are not fully understood. Because the pulmonary effects of interactions of endotoxins with imidacloprid are unknown, we designed a study to investigate that in a mouse model. Mice (N=14) were given imidacloprid orally @ 1/20(th) of LD50 dissolved in corn oil for 30days. After the treatments, six animals from each group were challenged with E. coli lipopolysaccharide (LPS) @ 80µg/animal via intranasal route and remaining animals were challenged with normal saline solution @ 80µl/animal via same route. Imidacloprid in combination with LPS led to significant increase in total cell and neutrophil counts in BAL and peripheral blood. Semi-quantitative histopathology revealed lung injury in imidacloprid treatment group and injury was more marked in animal receiving both imidacloprid and LPS. There was no change (p<0.05) in the expression of TLR-4 and TNF-α both at mRNA and protein levels following exposure to imidacloprid alone or in combination with LPS. The data show that imidacloprid alone or in combination with LPS resulted changes in lung morphology without altering the expression of TLR-4 and TNF-α. Furthermore, pre-treatment with imidacloprid didn't affect response to LPS.

Achieving crop stress tolerance and improvement--an overview of genomic techniques.

The inexorable exposure of plants to the combinations of abiotic stresses has affected the worldwide food supply. The crop improvement against these abiotic stresses has been captivating approach to increase the yield and enhance the stress tolerance. By using traditional and modern breeding methods, the characters that confer tolerance to these stresses were accomplished. No doubt genetic engineering and molecular breeding have helped in comprehending the intricate nature of stress response. Understanding of abiotic stress-involved cellular pathways provides vital information on such responses. On the other hand, genomic research for crop improvement has raised new assessments in breeding new varieties against abiotic stresses. Interpretation of responses of the crop plants under stress is of great significance by studying the main role of crops in food and biofuel production. This review presents genomic-based approaches revealing the complex networks controlling the mechanisms of abiotic stress tolerance, and the possible modes of assimilating information attained by genomic-based approaches due to the advancement in isolation and functional analysis of genes controlling the yield and abiotic stress tolerance are discussed.

A Review on Pharmacological Properties of Zingerone (4-(4-Hydroxy-3-methoxyphenyl)-2-butanone).

Humans have been using natural products for medicinal use for ages. Natural products of therapeutic importance are compounds derived from plants, animals, or any microorganism. Ginger is also one of the most commonly used condiments and a natural drug in vogue. It is a traditional medicine, having some active ingredients used for the treatment of numerous diseases. During recent research on ginger, various ingredients like zingerone, shogaol, and paradol have been obtained from it. Zingerone (4-(4-hydroxy-3-methoxyphenyl)-2-butanone) is a nontoxic and inexpensive compound with varied pharmacological activities. It is the least pungent component of Zingiber officinale. Zingerone is absent in fresh ginger but cooking or heating transforms gingerol to zingerone. Zingerone closely related to vanillin from vanilla and eugenol from clove. Zingerone has potent anti-inflammatory, antidiabetic, antilipolytic, antidiarrhoeic, antispasmodic, and so forth properties. Besides, it displays the property of enhancing growth and immune stimulation. It behaves as appetite stimulant, anxiolytic, antithrombotic, radiation protective, and antimicrobial. Also, it inhibits the reactive nitrogen species which are important in causing Alzheimer's disease and many other disorders. This review is written to shed light on the various pharmacological properties of zingerone and its role in alleviating numerous human and animal diseases.