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Abstract The present paper deals with the problem of estimation of finite population mean of study variable using two auxiliary variables in two-phase sampling scheme using predictive approach in case of missing values of the study variable and unknown population mean of first auxiliary variable. Four classes of such estimators have been proposed using this predictive approach. The expressions of bias and mean square errors are derived up to first order of approximation. The optimal values of the constants involved in the proposed classes of estimators have been obtained and thus minimum mean square errors of the proposed classes are obtained in this study. The empirical and graphical comparisons with regression type estimators (under single phase and double phase sampling scheme) and also among themselves have been made for evaluating the performance of the proposed classes for different choices of non-responding units. Five real data sets and three simulated data sets following normal distribution have been used to evaluate the performance of the proposed classes. Numerical findings confirm the theoretical results obtained regarding superiority of proposed classes of estimators over the conventional regression type estimators in terms of percent relative efficiencies.

Serotonin transporter (SERT) deficiency has been implicated in metabolic syndrome, intestinal inflammation, and microbial dysbiosis. Interestingly, changes in microbiome metabolic capacity and several alterations in host gene expression, including lipid metabolism, were previously observed in SERT−/− mice ileal mucosa. However, the precise host or microbial metabolites altered by SERT deficiency that may contribute to the pleiotropic phenotype of SERT KO mice are not yet understood. This study investigated the hypothesis that SERT deficiency impacts lipid and microbial metabolite abundances in the ileal mucosa, where SERT is highly expressed. Ileal mucosal metabolomics was performed by Metabolon on wild-type (WT) and homozygous SERT knockout (KO) mice. Fluorescent-activated cell sorting (FACS) was utilized to measure immune cell populations in ileal lamina propria to assess immunomodulatory effects caused by SERT deficiency. SERT KO mice exhibited a unique ileal mucosal metabolomic signature, with the most differentially altered metabolites being lipids. Such changes included increased diacylglycerols and decreased monoacylglycerols in the ileal mucosa of SERT KO mice compared to WT mice. Further, the ileal mucosa of SERT KO mice exhibited several changes in microbial-related metabolites known to play roles in intestinal inflammation and insulin resistance. SERT KO mice also had a significant reduction in the abundance of ileal group 3 innate lymphoid cells (ILC3). In conclusion, SERT deficiency induces complex alterations in the ileal mucosal environment, indicating potential links between serotonergic signaling, gut microbiota, mucosal immunity, intestinal inflammation, and metabolic syndrome.

Improper disposal of waste poses a grave environmental threat, contributing to pollution of air, water, and soil. It is necessary to address this issue in order to mitigate the adverse effects of solid waste on both the environment and public health. In many developing nations, municipal authorities of bigger cities are enduring significant challenges in proper management of waste. The present study evaluates the impacts of various waste management alternative scenarios for environmental impacts for the selected study locations using Life Cycle Assessment (LCA) methodology. The methodology comprised of five different scenarios of waste management including an existing baseline scenario. In this context, the environmental impact categories analyzed were Global Warming potential (GWP), Acidification potential (AP), Eutrophication potential (EP) and Human Toxicity potential (HTP). The results indicated that amongst all the proposed scenarios, Scenario 1 and 4 exhibited the maximum and minimum environmental impacts respectively. The study revealed that least greenhouse gas emissions, acidification potential, eutrophication potential and human toxicity potential were comparatively lesser for scenario 4 varying from 5.65 to 11.36 kg CO2eq t−1; 1.24–3.345 kg SO2eq t−1, EP 0.19–0.68 kg PO4eq t−1, and 0.35–4.22 kg 1,4-DBeq t−1 respectively. Further, a sensitivity analysis was also performed to evaluate the influence of recycling rate of valuable resources in all the considered scenarios. The sensitivity analysis indicated an inversely proportional relation between change in recycling rate and total environmental burdens.

The present research focuses on two-dimensional deformation in a functionally graded thermoelastic micro-elongated medium. It is supposed that the non-homogeneous properties (thermal and mechanical) of FGM are in the x-direction. The normal mode technique is used to acquire the analytic expression for displacement components, stress, micro-elongation and temperature. The cause and effect relationship of non-homogeneity and physical quantities is shown through graphical results.

Abstract Background Differentiated thyroid cancer (DTC) affects thousands of lives worldwide each year. Typically, DTC is a treatable disease with a good prognosis. Yet, some patients are subjected to partial or total thyroidectomy and radioiodine therapy to prevent local disease recurrence and metastasis. Unfortunately, thyroidectomy and/or radioiodine therapy often worsen(s) quality of life and might be unnecessary in indolent DTC cases. On the other hand, the lack of biomarkers indicating a potential metastatic thyroid cancer imposes an additional challenge to managing and treating patients with this disease. Aim The presented clinical setting highlights the unmet need for a precise molecular diagnosis of DTC and potential metastatic disease, which should dictate appropriate therapy. Materials and methods In this article, we present a differential multi‐omics model approach, including metabolomics, genomics, and bioinformatic models, to distinguish normal glands from thyroid tumours. Additionally, we are proposing biomarkers that could indicate potential metastatic diseases in papillary thyroid cancer (PTC), a sub‐class of DTC. Results Normal and tumour thyroid tissue from DTC patients had a distinct yet well‐defined metabolic profile with high levels of anabolic metabolites and/or other metabolites associated with the energy maintenance of tumour cells. The consistency of the DTC metabolic profile allowed us to build a bioinformatic classification model capable of clearly distinguishing normal from tumor thyroid tissues, which might help diagnose thyroid cancer. Moreover, based on PTC patient samples, our data suggest that elevated nuclear and mitochondrial DNA mutational burden, intra‐tumour heterogeneity, shortened telomere length, and altered metabolic profile reflect the potential for metastatic disease. Discussion Altogether, this work indicates that a differential and integrated multi‐omics approach might improve DTC management, perhaps preventing unnecessary thyroid gland removal and/or radioiodine therapy. Conclusions Well‐designed, prospective translational clinical trials will ultimately show the value of this integrated multi‐omics approach and early diagnosis of DTC and potential metastatic PTC.

The BRCA1-PALB2-BRCA2 axis, or the BRCA pathway, plays key roles in genome stability maintenance and suppression of breast and several other cancers. Due to frequent p53 mutations in human BRCA1 breast cancers and mouse mammary tumors from Brca1, Brca2 and Palb2 conditional knockout models, it is often thought that p53 inactivation accelerates BRCA1/2 and PALB2-associated tumorigenesis. Here, we studied tumor development in mice with a mutation in Palb2 that disengages the PALB2-BRCA1 interaction in different Trp53 backgrounds. Rather than mammary tumors, Palb2 and Trp53 compound mutant mice developed, with greatly reduced latencies, lymphomas and sarcomas that are typically associated with germline Trp53 inactivation. Whole exome sequencing failed to identify any significant differences in genomic features between the same tumor types of Trp53 single mutant and Palb2;Trp53 compound mutant mice. These results suggest that loss of the BRCA pathway accelerates p53-associated tumor development, possibly without altering the fundamental tumorigenic processes.

Abstract Background Psychological morbidities are high among undergraduate medical students. They experience the transition between pre/para-clinical and clinical training as a stressful period and cope differently. Research from India in this regard are lacking. The aim of this study is to assess and compare the prevalence of psychological morbidities, associated factors and coping styles between pre/para-clinical and clinical undergraduate medical students. This institution-based cross-sectional observational design study was conducted among pre/para-clinical and clinical group of undergraduate medical students (a total of 382) by using a questionnaire in the period between April and June 2021. Stratified random sampling technique was used to select the study participants. The survey included standard self-administered questionnaires like GHQ-28 and Lin-Chen’s coping inventory to assess psychological morbidities and coping styles, respectively. Associated factors for psychological morbidities, and coping styles between two groups, were compared using chi-square test, independent t-test and binary logistic regression analysis. Results Out of the 382 responders, psychological morbidities (GHQ-28 score > 23) were found in 61% participants. Both groups reported high level, a slightly higher preponderance in clinical (61.5%) than pre/para-clinical students (60.6%) and with nonsignificant difference of psychological morbidities. Compared to pre/para-clinical group, clinical group was found to have more substance consumption behavior (p < 0.001), dissatisfaction with academic performance (p < 0.001), sought psychiatric consultation (p < 0.004) and currently on psychiatric treatment (p < 0.04). Overall, coping was found to be average and good among the participants. Active problem coping behavior was more significantly used by pre/para-clinical group, while passive problem coping and passive emotional coping behaviors were positively significantly correlated with psychological morbidities in clinical group. Conclusions This study established a significant correlation between psychological morbidities and passive coping styles in clinical group. These students need interventions to encourage the use of more active coping styles during the training to provide advances in future career. A strong correlation with dissatisfied academic performance may be a call for an efficient and more student-friendly curriculum.

Diet–microbiota interactions are emerging as important contributors in the pathogenesis of inflammatory bowel diseases (IBD), characterized by chronic inflammation of the GI tract. The aryl hydrocarbon receptor (AhR) transcription factor regulates xenobiotic metabolism and is activated by exogenous ligands, including indole-3-carbinole (I3C), which is found in cruciferous vegetables. However, studies investigating the impact of dietary I3C and AhR in preclinical models resembling human IBD are lacking. Mice (WT or AhR KO in IECs, 6–8 weeks) or SAMP/YitFC and AKR/J control (4 weeks, m/f) were fed an AhR ligand-depleted or I3C (200 ppm)-supplemented diet. There were increased levels of LPS and exacerbated inflammation, resulting in increased mortality in AhRΔIEC mice fed the AhR ligand-depleted diet in response to chronic DSS. The mechanisms underlying the protective effects of I3C supplementation during colonic colitis involved amelioration of intestinal inflammation and restoration of the altered gut microbiota, particularly the families of clostridicae and lachnospriaceae. Furthermore, the AhR-depleted diet led to the emergence of pathobiont Parvibacter caecicola in WT mice. SAMP/YitFc mice with spontaneous ileitis showed significant recovery in epithelial abnormalities when fed dietary I3C. These data demonstrate the critical role of AhR and the mechanisms of dietary I3C in maintaining epithelial homeostasis and ameliorating inflammation.

Inflammatory bowel diseases (IBD) involve complex interactions among genetic factors, aberrant immune activation, and gut microbial dysbiosis. While metabolomic studies have focused on feces and serum, fewer investigations have examined the intestinal mucosa despite its crucial role in metabolite absorption and transport. The goals of this study were twofold: to test the hypothesis that gut microbial dysbiosis from chronic intestinal inflammation leads to mucosal metabolic alterations suitable for therapeutic targeting, and to address gaps in metabolomic studies of intestinal inflammation that have overlooked the mucosal metabolome. The chronic DSS colitis was induced for five weeks in 7–9-week-old wild-type C57BL/6J male mice followed by microbial profiling with targeted 16srRNA sequencing service. Mucosal metabolite measurements were performed by Metabolon (Morrisville, NC). The data were analyzed using the bioinformatic tools Pathview, MetOrigin, and Metaboanalyst. The novel findings demonstrated increases in several host- and microbe-derived purine, pyrimidine, endocannabinoid, and ceramide metabolites in colitis. Origin analysis revealed that microbial-related tryptophan metabolites kynurenine, anthranilate, 5-hydroxyindoleacetate, and C-glycosyltryptophan were significantly increased in colon mucosa during chronic inflammation and strongly correlated with disease activity. These findings offer new insights into the pathophysiology of IBD and provide novel potential targets for microbial-based therapeutics.

Background and Aim: The servicing and framework for mental health care accessible to population have been affected during the unprecedented times of the coronavirus disease (COVID-19) pandemic. The new and almost exclusive method to maintain a therapeutic alliance with these patients has been the recently evolving telepsychiatry services. The main aim of the study is to assess and compare the mental health status of patients seeking psychiatry facilities in prelockdown and postlockdown period during the COVID-19 pandemic. Materials and Methods: This was a ambirespective study which was conducted in a tertiary care hospital in a hilly region of North India in which the registered data were analyzed between January 1, 2020 and March 21, 2020 (prelockdown phase) and from May 3, 2020 to September 30, 2020 (postlockdown phase, after the resumption of outpatient department services in the institute), to gather the information of patients about sociodemographic profile and clinical diagnosis on the basis of International Classification of Diseases-10. A total sample size of 1000 patients was included. Chi-square test and Student's t-test were used to compare the patient presentation before and after the lockdown periods. Results: Majority of the patients were male (66%) and within 19–60 years of age (85%–90%). The average age of the patients (39.17 years, standard deviation = 14.37) was significantly higher in postlockdown phase. As compared to prelockdown period (499 patients), a significantly (P < 0.001) lower number of patients diagnosed with substance use disorders and a significantly (P < 0.001) higher number of patients diagnosed with psychotic disorders along with anxiety disorders, availed the available psychiatry services in the period of COVID-19 pandemic (501 patients). Conclusions: Sudden cessation of the psychiatry services further precipitated the deterioration of mental health of the patients. There is an urgent demand for services to adapt to changing scenarios with emphasis on practical approaches to help the mentally ill people, especially in geographically difficult hilly areas.

Background: The servicing and framework for mental health care accessible to population have been affected during the unprecedented times of coronavirus disease (COVID-19) pandemic. The new and almost exclusive method to maintain a therapeutic alliance with these patients has been the recently evolving telepsychiatry services. Aim and Objectives: The main aim of the study was to assess and compare the mental health status of patients seeking available psychiatry facilities in pre-lockdown and post-lockdown period during COVID-19 pandemic. Methodology: This was a retrospective cross-sectional study that was conducted in a tertiary care hospital in a hilly region of North India. The registered data was analyzed between January 1, 2020 to March 21, 2020 to gather the information of patients about sociodemographic profile and clinical diagnosis on the basis of International Classification of Diseases-10. The retrieved data constituted 499 new consecutive patients during this period. Then in the post-lockdown phase after the resumption of OPD services in the institute (May 3, 2020), the data collection was initiated to collect a similar sample size of new consecutive patients (501). These data were collected over 151 days (May 3, 2020 to September 30, 2020). Results: A total number of 1000 patients were analyzed. Majority of the patients were male (66%) and within 19 to 60 years of age (85–90%). The average number of patients (3.31) seen per day was less and the average age of the patients (39.17 years, standard deviation = 14.37) was significantly higher in the post-lockdown phase. The most common diagnostic group consisted of neurotic/stress-related/somatoform disorders. As compared to the pre-lockdown period, a significantly (P < 0.001) lower number of patients diagnosed with substance use disorders and a significantly (P < 0.001) higher number of patients diagnosed with psychotic disorders along with anxiety disorders availed the available psychiatry services in the period of COVID-19 pandemic. Conclusion: Sudden cessation of the psychiatry services further precipitated the deterioration of mental health of the patients. There is an urgent demand for services to adapt to changing scenarios with emphasis on practical approaches to help the mentally ill people especially in geographically difficult hilly areas.

Mutations in the homologous recombination proteins BRCA1 and BRCA2 can sensitize cells to treatment with inhibitors of poly-ADP-ribose polymerase 1 (PARPi), but resistance to the treatment can occur. Here the authors by genome-wide CRISPR knockout and activation screens reveal novel pathways of PARPi resistance in BRCA2-deficient cells.

Objectives: Alzheimer's disease (AD) is the most common cause of dementia worldwide in the older population. There is no disease-modifying therapy available for AD. The current standard of care drug therapy for AD is cholinesterase inhibitors, including donepezil. Bacopa monnieri or brahmi is used in traditional Indian medicine for memory loss. We conducted a phase 2b randomized controlled trial (RCT) to find out the efficacy of brahmi and donepezil in AD and mild cognitive impairment (MCI). Patients and Methods: The study was planned as a 52 week, randomized, double-blind, parallel-group, phase-2 single-center clinical trial comparing the efficacy and safety of Bacopa monnieri (brahmi) 300 mg OD and donepezil 10 mg OD for 12 months in 48 patients with AD and MCI-AD including cognitive and quality of life outcomes. The primary outcome was differences in the change from baseline of the neuropsychological tests [Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog) and postgraduate institute (PGI) memory scale] at 12 months between the intervention group (brahmi) and active comparison group (donepezil). Results: The study was terminated after 3 years and 9 months, after recruiting 34 patients, because of slow recruitment and a high dropout rate. Intention to treat analysis after adjusting for baseline confounders showed no difference in the rate of change in ADAS-Cog score from baseline at any time point, including the last follow-up. There was no difference in the rate of change in PGI Memory scale (PGIMS) at 3, 6, and 9 months. In the last follow-up, there was a significant difference in the change in total PGIMS score between brahmi and donepezil, while there was no difference in individual scores of the PGI memory scale. Conclusion: This phase-2 RCT on the efficacy of brahmi vs. donepezil showed no significant difference between them after 1 year of treatment. Larger phase-3 trials, preferably multicentric, are required to find the superiority of brahmi over donepezil.

Antero-medial temporo-sphenoidal encephaloceles are rarest type of basal encephaloceles with bony defects in lateral sphenoid, and are termed as spontaneous when they occur in the absence of predisposing factors . They most commonly present as CSF rhinorrhea, headache or with signs of meningitis. Imaging play an important role in establishing diagnosis and for preoperative evaluation. Surgery through transnasal /transcranial route is the definite management.

With growing interest in monitoring mutational processes in normal tissues, tumor heterogeneity, and cancer evolution under therapy, the ability to accurately and economically detect ultra-rare mutations is becoming increasingly important. However, this capability has often been compromised by significant sequencing, PCR and DNA preparation error rates. Here, we describe FERMI (Fast Extremely Rare Mutation Identification) - a novel method designed to eliminate the majority of these sequencing and library-preparation errors in order to significantly improve rare somatic mutation detection. This method leverages barcoded targeting probes to capture and sequence DNA of interest with single copy resolution. The variant calls from the barcoded sequencing data are then further filtered in a position-dependent fashion against an adaptive, context-aware null model in order to distinguish true variants. As a proof of principle, we employ FERMI to probe bone marrow biopsies from leukemia patients, and show that rare mutations and clonal evolution can be tracked throughout cancer treatment, including during historically intractable periods like minimum residual disease. Importantly, FERMI is able to accurately detect nascent clonal expansions within leukemias in a manner that may facilitate the early detection and characterization of cancer relapse.

Abstract Purpose The study presents the physico-chemical, heavy metal and spectral characterization of aerobic compost to assess the suitability of its use for different purposes generated from two different municipal solid waste dumpsites located in the cities of Solan and Mandi in Himachal Pradesh. Methods The spectral characteristics of the compost material were determined using Scanning Electron Microscope (SEM), Energy Dispersive Spectroscopy (EDS) and X-ray Diffraction (XRD) technique. The heavy metal analysis of compost material was analyzed through atomic absorption spectroscopy (AAS). The study also focused on the determination of the qualitative nature of compost by utilizing an indexing method based on Fertilizer Control Order (FCO) Standards. The utility of the compost was characterized on the values of ‘Fertility Index’ and ‘Clean Index’. Results The Fertility Index (FI) of compost for Solan and Mandi was observed 3.5 and 3.6, respectively, whereas Clean Index (CI) of compost for both regions was observed 4.0 and 5.0 at the 60th day of sampling, respectively, with the former being classified as category D and the second being classified as category A of high fertilizing potential. Conclusions The MSW compost of Solan cannot be used as fertilizer due to its low fertilizing potential. The heavy metal concentration for the study regions has been found within the permissible limits of the fertility control order standards. It is concluded from the study that aerobic composting is a suitable option for processing of waste as well as it can reduce the weight of organic waste in the dumpsite.

Abstract Editing in microRNAs, particularly in seed can significantly alter the choice of their target genes. We show that out of 13 different human tissues, different regions of brain showed higher adenosine to inosine (A-to-I) editing in mature miRNAs. These events were enriched in seed sequence (73.33%), which was not observed for cytosine to uracil (17.86%) editing. More than half of the edited miRNAs showed increased stability, 72.7% of which had ΔΔG values less than −6.0 Kcal/mole and for all of them the edited adenosines mis-paired with cytosines on the pre-miRNA structure. A seed-editing event in hsa-miR-411 (with A – C mismatch) lead to increased expression of the mature form compared to the unedited version in cell culture experiments. Further, small RNA sequencing of GBM patients identified significant miRNA hypoediting which correlated with downregulation of ADAR2 both in metadata and qRT-PCR based validation. Twenty-two significant (11 novel) A-to-I hypoediting events were identified in GBM samples. This study highlights the importance of specific sequence and structural requirements of pre-miRNA for editing along with a suggestive crucial role for ADAR2. Enrichment of A-to-I editing in seed sequence highlights this as an important layer for genomic regulation in health and disease, especially in human brain.

Summary: Impacts of genetic and non-genetic intra-tumor heterogeneity (ITH) on tumor phenotypes and evolvability remain debated. We analyze ITH in lung squamous cell carcinoma at the levels of genome, transcriptome, and tumor-immune interactions and histopathological characteristics by multi-region bulk and single-cell sequencing. Genomic heterogeneity alone is a weak indicator of intra-tumor non-genetic heterogeneity at immune and transcriptomic levels that impact multiple cancer-related pathways, including those related to proliferation and inflammation, which in turn contribute to intra-tumor regional differences in histopathology and subtype classification. Tumor subclones have substantial differences in proliferation score, suggestive of non-neutral clonal dynamics. Proliferation and other cancer-related pathways also show intra-tumor regional differences, sometimes even within the same subclones. Neo-epitope burden negatively correlates with immune infiltration, indicating immune-mediated purifying selection on somatic mutations. Taken together, our observations suggest that non-genetic heterogeneity is a major determinant of heterogeneity in histopathological characteristics and impacts evolutionary dynamics in lung cancer. : Sharma et al. show that in non-small-cell lung cancer, genetic heterogeneity is moderate and does not sufficiently reflect the extent of non-genetic heterogeneity at immune and transcriptomic levels, which contributes to regional differences in histopathological characteristics. Non-genetic heterogeneity also influences subclonal dynamics, shaping the trajectory of tumor evolution.

Somatic variation in DNA can cause cells to deviate from the preordained genomic path in both disease and healthy conditions. Here, using exome sequencing of paired tissue samples, we show that the normal human brain harbors somatic single base variations measuring up to 0.48% of the total variations. Interestingly, about 64% of these somatic variations in the brain are expected to lead to non-synonymous changes, and as much as 87% of these represent G:C>T:A transversion events. Further, the transversion events in the brain were mostly found in the frontal cortex, whereas the corpus callosum from the same individuals harbors the reference genotype. We found a significantly higher amount of 8-OHdG (oxidative stress marker) in the frontal cortex compared to the corpus callosum of the same subjects (pT:A transversions in the cortex. We found significant enrichment for axon guidance and related pathways for genes harbouring somatic variations. This could represent either a directed selection of genetic variations in these pathways or increased susceptibility of some loci towards oxidative stress. This study highlights that oxidative stress possibly influence single nucleotide somatic variations in normal human brain.

We present a case of a 56-year-old male who developed Capgras syndrome following hyponatremia consequent to dehydration. He was a previously healthy male who eventually developed secondary systematized delusions due to misidentification syndrome. This case highlights the need for evaluating the role of toxic/medical etiology in the causation of this syndrome that is more often encountered in schizophrenia.

The experiment was conducted in the experimental field of Department of Horticulture, College of Agriculture, Rewa under Jawaharlal Nehru Krishi Vishwa Vidyalaya, Jabalpur during the rabi season 2009-2010. The results showed that morphological characters of cauliflower (Brassica oleracea var botrytis L.) increased significantly with the different levels of boron and molybdenum at every stage of observation. At 60 DAT, the maximum plant height (34.35 cm), number of leaves/plant (19.45), leaf length (32.02 cm), leaf width (28.31 cm) and stem girth (5.14 cm) were recorded in treatment T9, whereas the minimum plant height (32.50 cm), number of leaves/plant (16.49), leaf length (29.07 cm), leaf width (25.72 cm) and stem girth (4.50 cm) were observed in control treatment T1. Yield and quality parameters were also influenced significantly due to various treatments of boron and molybdenum. The highest curd diameter (18.41 cm), fresh- weight of curd (1.24 kg), yield/ha (400.29 q) and dry matter of curd (11.37 %) were recorded in treatment T9, whereas the lowest curd diameter (15.52 cm), fresh weight of curd (0.69 kg), yield/ha (218.28 q) and dry matter of curd (0.69 %) were found in control treatment T1. The treatment T9 was found significantly superior over all the treatments. The treatment T8 registered the maximum ‘A’ grade curds (52.54%) as well as ‘B’ grade curds (35.20%) and the lowest ‘C’ grade curds (12.26%). This was equally followed by T7 and T9 treatments. The lowest ‘A’ grade curds 46.57% were found in case of control treatment T1, this was followed by T2 giving 46.64% ‘A’ grade curds, 33.09% ‘B’ grade curds and 20.01% C grade curds.

Somatic variation in DNA can cause cells to deviate from the preordained genomic path in both disease and healthy conditions. Here, using exome sequencing of paired tissue samples, we show that the normal human brain harbors somatic single base variations measuring up to 0.48% of the total variations. Interestingly, about 64% of these somatic variations in the brain are expected to lead to non-synonymous changes, and as much as 87% of these represent G:C>T:A transversion events. Further, the transversion events in the brain were mostly found in the frontal cortex, whereas the corpus callosum from the same individuals harbors the reference genotype. We found a significantly higher amount of 8-OHdG (oxidative stress marker) in the frontal cortex compared to the corpus callosum of the same subjects (pT:A transversions in the cortex. We found significant enrichment for axon guidance and related pathways for genes harbouring somatic variations. This could represent either a directed selection of genetic variations in these pathways or increased susceptibility of some loci towards oxidative stress. This study highlights that oxidative stress possibly influence single nucleotide somatic variations in normal human brain.