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Epithelial cancers are typically heterogeneous with primary prostate cancer being a typical example of histological and genomic variation. Prior studies of primary prostate cancer tumour genetics revealed extensive inter and intra-patient genomic tumour heterogeneity. Recent advances in machine learning have enabled the inference of ground-truth genomic single-nucleotide and copy number variant status from transcript data. While these inferred SNV and CNV states can be used to resolve clonal phylogenies, however, it is still unknown how faithfully transcript-based tumour phylogenies reconstruct ground truth DNA-based tumour phylogenies. We sought to study the accuracy of inferred-transcript to recapitulate DNA-based tumour phylogenies. We first performed in-silico comparisons of inferred and directly resolved SNV and CNV status, from single cancer cells, from three different cell lines. We found that inferred SNV phylogenies accurately recapitulate DNA phylogenies (entanglement = 0.097). We observed similar results in iCNV and CNV based phylogenies (entanglement = 0.11). Analysis of published prostate cancer DNA phylogenies and inferred CNV, SNV and transcript based phylogenies demonstrated phylogenetic concordance. Finally, a comparison of pseudo-bulked spatial transcriptomic data to adjacent sections with WGS data also demonstrated recapitulation of ground truth (entanglement = 0.35). These results suggest that transcript-based inferred phylogenies recapitulate conventional genomic phylogenies. Further work will need to be done to increase accuracy, genomic, and spatial resolution.

Abstract Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer and current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal prostate cancer, we created virtual biopsy models that mimic conventional biopsy placement and core size. We then analysed the gene expression of different prognostic signatures (OncotypeDx®, Decipher®, Prostadiag®) using a step-wise approach with increasing resolution from pseudo-bulk analysis of the whole biopsy, to differentiation by tissue subtype (benign, stroma, tumour), followed by distinct tumour grade and finally clonal resolution. The gene expression profile of virtual tumour biopsies revealed clear differences between grade groups and tumour clones, compared to a benign control, which were not reflected in bulk analyses. This suggests that bulk analyses of whole biopsies or tumour-only areas, as used in clinical practice, may provide an inaccurate assessment of gene profiles. The type of tissue, the grade of the tumour and the clonal composition all influence the gene expression in a biopsy. Clinical decision making based on biopsy genomics should be made with caution while we await more precise targeting and cost-effective spatial analyses.

Previous studies have shown the vulnerability of hematological patients with the Coronavirus disease of 2019 (COVID-19). We aimed to compare the outcomes and risk factors for poor survival in patients with hematological conditions hospitalized with COVID-19 infection. Single centre, retrospective, cohort study included all patients with a hematological condition admitted to Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India between 1 April 2020 and 31 May 2021. Of a total of 154 patients, 81 were in the pre-delta group and 73 were in the delta group out of which 21 (25.97%) in the pre-delta group and 24 (33.88%) patients in the delta group died. Haematological characteristics—age > 60 years, progressive hematological cancer, more than two lines of anti-cancer therapy, and active chemo-immunotherapy or targeted therapy were associated with higher mortality in the delta group. COVID-19 characteristics associated with higher mortality during the delta wave were severity of COVID infection, higher oxygen requirements, and COVID plasma therapy There were no deaths in individuals (n = 15) within the delta group who received COVID-19 vaccination. This study adds to the evidence that patients with hematological diseases are a particularly vulnerable group and the delta variant of the virus is associated with higher mortality. We could identify patient characteristics and features related to COVID-19 infection and underlying hematological conditions that were associated with poor outcomes in the delta sub-group. Vaccination was found to be an effective strategy for overcoming mortality and morbidity in these patients.

Context Nilotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia (CML). Aims We aim to evaluate the responses and safety of upfront Nilotinib therapy in Indian CML patients. Setting and Design We retrospectively reviewed the medical records of CML patients who received Nilotinib as an upfront treatment at our center between January 1, 2011 and October 15, 2019.The follow-up was taken till March 31, 2020. Results Forty One patients (n = 36 chronic phase and five accelerated-phase CML) received frontline Nilotinib. Median age was 39 years (21–63) with male-to-female ratio of 1.1: 1. At 3 months, 96.9% patients achieved BCR-ABL of ≤10% at international scale. By the end of 12 months, 71.5% patients achieved major molecular response (BCR-ABL ≤0.1%) and 91.4% patients achieved complete cytogenetic response assessed by BCR-ABL polymerase chain reaction of ≤1%. Common toxicities observed were weight gain, thrombocytopenia, corrected QT prolongation, and elevated serum amylase in 14 (34.1%), 7(17.07%), 4(9.7%), and 4(9.7%) patients, respectively. Overall, five patients had loss of response with further progression and death in three patients. At a median of 43.7 months, 38 patients survived with estimated 3 year event-free survival and overall survival of 65 ± 9 and 93 ± 5%. Conclusion This study showed remarkable good response with upfront Nilotinib in Indian patients with CML.

Abstract Prostate cancer (PCa) is the most common non-cutaneous cancer in men and a notable cause of cancer mortality when it metastasises. The unfolded protein response (UPR) can be cytoprotective but when acutely activated can lead to cell death. In this study, we sought to enhance the acute activation of the UPR using radiation and ONC201, an UPR activator. Treating PCa cells with ONC201 quickly increased the expression of all the key regulators of the UPR and reduced the oxidative phosphorylation, with cell death occurring 72 h later. We exploited this time lag to sensitize prostate cancer cells to radiation through short-term treatment with ONC201. To understand how priming occurred, we performed RNA-Seq analysis and found that ONC201 suppressed the expression of cell cycle and DNA repair factors. In conclusion, we have shown that ONC201 can prime enhanced radiation response.

Background: Lack of male spouse involvement can affect the delays in the decision to take health care facilities, these are the main contributing factor for increasing maternal mortality and child death ratio. Men involvement in reproductive and sexual health including child health is important in reducing teenage pregnancy, maternal mortality, infant mortality, risky abortions, and total fertility rate. This study aimed to assess the awareness and practices of male spouse in maternal care services in rural areas. Methods: This is a community-based and cross-sectional study which was undertaken in randomly selected four villages of Kashi Vidyapeeth block, Varanasi. Total enumeration of women from the selected villages delivered within last 3 years was done and their husbands were interviewed by using a pre-designed, pretested interview schedule. Data on socioeconomic and demographic characteristics, awareness of various aspects and antenatal and postnatal care were collected and analyzed with SPSS 20 trial version. Results: Out of the total 130 interviewed male spouse (respondents), only 9.8% knows about minimum four antenatal visits. 26.9% were aware about the health related problems during pregnancy and only 7.7% were aware about the danger signs. Janani Suraksha Yojna was known to 11.5% only. 22.4% respondents accompanied their wife for antenatal registration and36.2% for T. T vaccination but 70.2% were present in the hospital during delivery. Logistic regression analysis shows that education of respondents is a key determinant of their involvement during pregnancy. Conclusions: This study identified overall low awareness of male spouse about antenatal visits and involvement during antenatal care. Therefore, there is a strong need to re-strategize the involvement of male spouse in reproductive health including antenatal period.

Prostate cancer is a high-incidence cancer, often detected late in life. The prostate gland is an accessory gland that secretes citrate; an impaired citrate secretion reflects imbalances in the activity of enzymes in the TCA Cycle in mitochondria. Profiling studies on prostate tumours have identified significant metabolite, proteomic, and transcriptional modulations with an increased mitochondrial metabolic activity associated with localised prostate cancer. Here, we focus on the androgen receptor, c-Myc, phosphatase and tensin Homolog deleted on chromosome 10 (PTEN), and p53 as amongst the best-characterised genomic drivers of prostate cancer implicated in metabolic dysregulation and prostate cancer progression. We outline their impact on metabolic function before discussing how this may affect metabolite pools and in turn chromatin structure and the epigenome. We reflect on some recent literature indicating that mitochondrial mutations and OGlcNAcylation may also contribute to this crosstalk. Finally, we discuss the technological challenges of assessing crosstalk given the significant differences in the spatial sensitivity and throughput of genomic and metabolomic profiling approaches.

Abstract Background Recent adva1nces in whole genome sequencing (WGS) based technologies have facilitated multi-step applications for predicting antimicrobial resistance (AMR) and investigating the molecular epidemiology of Neisseria gonorrhoeae. However, generating full scaffolds of N. gonorrhoeae genomes from short reads, and the assignment of molecular epidemiological information (NG-MLST, NG-MAST, and NG-STAR) to multiple assembled samples, is challenging due to required manual tasks such as annotating antimicrobial resistance determinants with standard nomenclature for a large number of genomes. Results We present Gen2Epi, a pipeline that assembles short reads into full scaffolds and automatically assigns molecular epidemiological and AMR information to the assembled genomes. Gen2Epi is a command-line tool integrating third-party software and tailored specifically for N. gonorrhoeae. For its evaluation, the Gen2Epi pipeline successfully assembled the WGS short reads from 1484 N. gonorrhoeae samples into full-length genomes for both chromosomes and plasmids and was able to assign in silico molecular determinant information to each dataset automatically. The assemblies were generated using raw as well as trimmed short reads. The median genome coverage of full-length scaffolds and “N” statistics (N50, NG50, and NGA50) were higher than, or comparable to, previously published results and the scaffolding process improved the quality of the draft genome assemblies. Molecular antimicrobial resistant (AMR) determinants identified by Gen2Epi reproduced information for the 1484 samples as previously reported, including NG-MLST, NG-MAST, and NG-STAR molecular sequence types. Conclusions Gen2Epi can be used to assemble short reads into full-length genomes and assign accurate molecular marker and AMR information automatically from NG-STAR, NG-MAST, and NG-MLST. Gen2Epi is publicly available under “CC BY-NC 2.0 CA” Creative Commons licensing as a VirtualBox image containing the constituent software components running on the LINUX operating system (CentOS 7). The image and associated documentation are available via anonymous FTP at ftp://www.cs.usask.ca/pub/combi or ftp://ftp.cs.usask.ca/pub/combi

Abstract Sialic acids (SAs) are nine carbon acidic amino sugars, found at the outermost termini of glycoconjugates performing various physiological and pathological functions. SA synthesis is regulated by UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) that catalyzes rate limiting steps. Mutations in GNE result in rare genetic disorders, GNE myopathy and Sialuria. Recent studies indicate an alternate role of GNE in cell apoptosis and adhesion, besides SA biosynthesis. In the present study, using a HEK cell-based model for GNE myopathy, the role of Insulin-like Growth Factor Receptor (IGF-1R) as cell survival receptor protein was studied to counter the apoptotic effect of non-functional GNE. In the absence of functional GNE, IGF-1R was hyposialylated and transduced a downstream signal upon IGF-1 (IGF-1R ligand) treatment. IGF-1 induced activation of IGF-1R led to AKT (Protein Kinase B) phosphorylation that may phosphorylate BAD (BCL2 Associated Death Promoter) and its dissociation from BCL2 to prevent apoptosis. However, reduced ERK (Extracellular signal-regulated kinases) phosphorylation in GNE deficient cells after IGF-1 treatment suggests downregulation of the ERK pathway. A balance between the ERK and AKT pathways may determine the cell fate towards survival or apoptosis. Our study suggests that IGF-1R activation may rescue apoptotic cell death of GNE deficient cell lines and has potential as therapeutic target.

Objective: To assess the association of vitamin D (VD) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Method: Literature search was conducted for studies assessing the association of VD and DR. Total 9 studies have a sum total of 1741 patients were included for final analysis. Results: The concentration of VD in controls ranged from 17.5±3.6 to 31.9±12.9 ng/ml, while for T2DM patients without retinopathy it ranged from 11.94±4.21 to 23.10±6.12 ng/ml. T2DM patients with retinopathy had the lowest concentration, ranging from 10.02±5.61 to 19.25±7.86 ng/ml. Ahigher percentage of T2DM patients without (50.7% to 68.80%) and with (31.2% to 79.63%) retinopathy had VD deficiency (VDD). Discussion: An inverse association between VD levels and DR was observed. The concentration of VD decreases as the stage of DR advances. VD seems to be an easily modifiable risk factor for DR. Thus, VD supplementation should be encouraged in population at higher risk for diabetic complications.

Unicellular social amoebae aggregate to form a multicellular life stage, making them a model system for the evolution of multicellularity. Here, Glöckner et al.use a comparative genomic and transcriptomic approach to determine the origin of the genes essential for multicellularity in the social amoebae.

ObjectivesEfficient identification of subject experts or expert communities is vital for the growth of any organization. Most of the available expert finding systems are based on self-nomination, which can be biased, and are unable to rank experts. Thus, the objective of this work was to develop a robust and unbiased expert finding system which can quantitatively measure expertise.MethodsMedical Subject Headings (MeSH) is a controlled vocabulary developed by the National Library of Medicine (NLM) for indexing research publications, articles and books. Using the MeSH terms associated with peer-reviewed articles published from India and indexed in PubMed, we developed a Web-based program which can be used to identify subject experts and subjects associated with an expert.ResultsWe have extensively tested our system to identify experts from India in various subjects. The system provides a ranked list of experts where known experts rank at the top of the list. The system is general; since it uses information available with the PubMed, it can be implemented for any country.ConclusionsThe expert finding system is able to successfully identify subject experts in India. Our system is unique because it allows the quantification of subject expertise, thus enabling the ranking of experts. Our system is based on peer-reviewed information. Use of MeSH terms as subjects has standardized the subject terminology. The system matches requirements of an ideal expert finding system.