Pediatric neurological disorders include neurodegenerative diseases causing cognitive impairment and vision loss. They are one of the important causes of morbidity and mortality in children with diverse etiologies. Diagnosis is difficult despite genetic work, and a final diagnosis can be achieved in only 60

Metatranscriptomic analyses offer unprecedented insights into the interplay between SARS-CoV-2 and human hosts, shedding light on distinct differentially expressed genes (DEGs) and their implications. The global significance of wastewater as a resource underscores its potential for disease surveillance and public health. Leveraging wastewater-based epidemiology (WBE) and advanced sequencing technologies, this study aims to elucidate DEGs between SARS-CoV-2 and human hosts. The introduction of high-throughput sequencing techniques has revolutionized our ability to detect and monitor viral pathogens in wastewater, presenting a cost-effective and comprehensive approach to epidemiological surveillance. By employing both, short-read Illumina whole transcriptome shotgun sequencing (WTSS) and long-read Oxford Nanopore Technologies (ONT), this study reveals DEGs associated with SARS-CoV-2 pathogenesis, providing valuable insights into viral-host interactions. The analysis identifies distinct alpha diversity clades between WBE and clinical microbiomes, offering potential clues to concurrent infections and underlying pathways. Host transcriptional signatures associated with COVID-19, such as those observed in MCP signal and ABC transporters, hold promise for elucidating the role of DEGs in the infectious cycle. This pioneering metatranscriptome analysis represents a significant step towards understanding the molecular basis of SARS-CoV-2 pathogenesis and highlights the potential of wastewater-based surveillance in combating infectious diseasesFunding: This work was partially funded under the SERB special project grant CVD/2022/000021 titled "Early Detection, Surveillance, and prevention of Communicable Viral diseases in Jaipur city: a Wastewater-Based Epidemiological study for COVID-19 (DISCOVER-WBE)".Declaration of Interest: None.Ethical Approval: All experimental protocols were approved by the institutional ethics Committee with informed consents taken from all the patients.

Hemoglobinopathies are a group of disorders in which the hemoglobin molecule has abnormal production or structure. The hemoglobin molecules in red blood cells (RBC) are impacted by the blood disease known as sickle cell disease (SCD), and Thalassemia is one of the major monogenic disorders that reduces hemoglobin production( Kohne et al ., 2011). This disorder results in a large number of red blood cells being destroyed, leading to anemia. India bears a huge burden of hemoglobinopathies; thalassemia is the most prevalent (Mondal SK et al., 2016). A key component of thalassemia prevention is a successful screening procedure to identify Thalassemia carriers. Effective screening programs have numerous obstacles, especially in environments with limited resources. Machine learning (ML) has been used to solve technical and domain-specific problems in a variety of prognostic and diagnostic medical jobs. In this work, we aimed to identify and analyze the most common mutation of β--thalassemia and sickle cell disease from the north Indian population by employing Machine learning-based algorithms. To accurately predict the carrier state from a simple blood test, and to predict pathogenic hemoglobin variants in a group of individuals, these results demonstrate the application of integrated bioinformatics and machine learning approaches. This study contributes to the validation of the models based on data from several individuals and hemoglobinopathies.

Background: Early screening, diagnosis and management program can contribute in reducing the burden of genetic disorders which can lead to early neonatal death or long-term disability in the vulnerable areas. UMMID (Unique Methods of Management and treatment of Inherited Disorders) and NIDAN (National Inherited Diseases Administration), aimed at developing a community level program for need assessment and to evaluate the feasibility of basic screening for some genetic/endocrine disorders in high-risk population. Methods: UMMID was carried out at the aspirational district Ranchi, Jharkhand for 3 years (2019-2022) to perform newborn screening (NBS) in <7 days old newborn babies for 5 metabolic disorders and to screen antenatal mothers for prevention of thalassemia and other hemoglobinopathies. Results: G6PD deficiency being more prevalent in Ranchi district out of five metabolic disorders screened. 13.6% of screen positive cases were confirmed positive for hemoglobinopathies. c.20 A>T is the most common mutation found among carriers. Conclusions: This initiative underscores the need of such screening programs in aspirational districts to manage and prevent these disorders effectively.

Over the last 34 months, at least 10 severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) distinct variants have evolved. Among these, some were more infectious while others were not. These variants may serve as candidates for identification of the signature sequences linked to infectivity and viral transgressions. Based on our previous hijacking and transgression hypothesis, we aimed to investigate whether SARS-CoV-2 sequences associated with infectivity and trespassing of long noncoding RNAs (lncRNAs) provide a possible recombination mechanism to drive the formation of new variants. This work involved a sequence and structure-based approach to screen SARS-CoV-2 variants in silico, taking into account effects of glycosylation and links to known lncRNAs. Taken together, the findings suggest that transgressions involving lncRNAs may be linked with changes in SARS-CoV-2-host interactions driven by glycosylation events.

Point-of-care SARS-CoV-2 rapid antigen tests have proven to be useful over the years and have become more apparent to the public eye during COVID-19 pandemic due to their ease of use, rapid processing and result times, and low cost. Here, we have assessed the effectiveness and accuracy of rapid antigen tests in comparison to the standard real-time polymerase chain reaction analyses of the same samples.

Background and Aim: Insufcient data exists on the prevalence and types of individual visible birth defects (VBDs) in live-born babies in India. This initiative addressed this gap by reporting on VBDs in live births in Delhi. Data on VBDs for live born babies was Material and Methods: collected from November 2021 to July 2023, across 31 hospitals under Mission NEEV (Neonatal Early Evaluation Vision). Pediatricians conrmed diagnoses using ICD10 coding, and prevalence rate was calculated. showed 818 Results babies with VBDs among 193,587 screened live births, resulting in an overall prevalence of 0.43% (840 VBDs among 818 live babies). Of these, 310 were minor, and 530 were major, with a higher incidence in male babies (56% vs. 41%). Consanguinity was observed in 7.15% of parents of malformed babies. Among the 818 babies, 798 (97.5%) had isolated and 20 (2.44%) had multiple anomalies. Musculoskeletal VBDs were the most common (663 per 1000 births). The most common anomaly among all VBDs was CTEV (Congenital talipes equinovarus) (48.8%). In conclusion, the prevalence of VBDs among live births was 0.43%, with musculoskeletal system deformities being the most common, especially in male babies. Early newborn surveillance for VBDs is essential for identifying associated anomalies and early intervention.

We explore three cases of pediatric neurological diseases, viz. Arthrogryposis, congenital bilateral cataract and Autism by analyzing clinical exomes. As genetic variation attributing to pathogenesis is a significant bottleneck, we attempted to understand and validate them using Sanger validation. We further employ our CONVEX pipeline to infer pathogenic variants and discern the candidate genes for phenotype correlation.

Ameloblastoma is a benign odontogenic tumor that is locally destructive. The most common treatment option is surgery, which often results in disfigurement of the face. BRAFV600E is the common gene mutation associated with its pathogenesis. Therefore, this paper hypothesizes the use of targeted drug therapy against this mutated gene.

We report the sequencing of SARS-CoV-2 Omicron variants from 75 patients, using nanopore long-read sequencing chemistry. These data show a range of mutations in spike glycoprotein that are both unique and common to other populations.

The mitochondrial permeability transition pore (mtPTP) plays a vital role in altering the structure and function of mitochondria. Cyclophilin D (CypD) is a mitochondrial protein that regulates mtPTP function and a known drug target for therapeutic studies involving mitochondria. While the effect of aromatase inhibition on the mtPTP has been studied previously, the effect of anastrozole on the mtPTP has not been completely elucidated. The role of anastrozole in modulating the mtPTP was evaluated by docking, molecular dynamics and network-guided studies using human CypD data. The peripheral blood mononuclear cells (PBMCs) of patients with mitochondrial disorders and healthy controls were treated with anastrozole and evaluated for mitochondrial permeability transition pore (mtPTP) function and apoptosis using a flow cytometer. Spectrophotometry was employed for estimating total ATP levels. The anastrozole-CypD complex is more stable than cyclosporin A (CsA)-CypD. Anastrozole performed better than cyclosporine in inhibiting mtPTP. Additional effects included inducing mitochondrial membrane depolarization and a reduction in mitochondrial swelling and superoxide generation, intrinsic caspase-3 activity and cellular apoptosis, along with an increase in ATP levels. Anastrozole may serve as a potential therapeutic agent for mitochondrial disorders and ameliorate the clinical phenotype by regulating the activity of mtPTP. However, further studies are required to substantiate our preliminary findings.Communicated by Ramaswamy H. Sarma.

In developing countries, awareness about genetic conditions like Down syndrome, congenital defects, thalassemia, and inborn errors of metabolism is limited. We conducted a survey using a 19-question questionnaire to assess awareness of newborn, thalassemia, and pregnancy screening and whether these tests should be recommended or not among junior doctors, senior clinicians, MBBS students, and the general population. Results showed that only 60% of junior doctors knew about thalassemia screening. 50-70% of doctors and 60% of students supported invasive pregnancy testing. Approximately 35% of students were unaware of thalassemia carrier screening but 80% of them were open to routine testing. 90% of students recognized the importance of genetic screening awareness in current health scanario. About 40-60% of the general public lacked awareness about screening tests and the distinction between screening and diagnostic tests. Nearly 50% - 60% of people understood the importance of thalassemia screening. Although many clinicians and students acknowledged the benets of screening tests, yet, increased awareness and attitude change, along with improved genetic education in medical curricula is needed.

Inborn errors of ketogenesis are rare disorders that result in acute and fulminant decompensation during lipolytic stress, particularly in infants and children. These include mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase (HMGCS) deficiency and HMG-CoA lyase (HMGCL) deficiency. In this series, we describe the clinical, biochemical, and molecular profiles of four patients along with dietary interventions and their outcomes on a long-term follow-up. Two patients each of HMGCS and HMGCL deficiency were evaluated with clinical history, biochemical investigations, including tandem mass spectrometry (TMS) and urine gas chromatography-mass spectrometry (GCMS). Molecular analysis was performed by whole-exome sequencing, as well as exon array validated by long-range polymerase chain reaction. All individuals were diagnosed with acute metabolic decompensation in the early infancy period except one with HMGCL deficiency who had the first presentation at 5 years of age. Central nervous system manifestations, severe metabolic acidosis, hyperammonemia, hypoglycemia with a normal lactate, and absence of urinary ketones were observed in all the affected individuals. The disorder was life-threatening in three individuals and one succumbed to the illness. TMS was nonspecific and urine GCMS revealed dicarboxylic aciduria in HMGCS deficiency. Both the patients with HMGCL deficiency demonstrated elevated 3 hydroxyisovaleryl carnitine levels in TMS and metabolites of leucine degradation in urine GCMS. We identified five novel variants that included a large deletion involving exon 2 in HMGCL gene. There was no evidence of long-term neurological sequelae in the living individuals. Diet with moderation of fat intake was followed in two individuals with HMGCS deficiency. Low leucine and protein diet with moderation of fat intake was followed in the individual with HMGCL deficiency. All affected individuals are thriving well with no further major metabolic decompensation.

Aims: Hematopoietic acute radiation syndrome (H-ARS) can cause lethality, and therefore, the necessity of a safe radioprotector. The present study was focused on investigating the role of melatonin in granulocytes colony-stimulating factor (G-CSF) and related mechanisms underlying the reduction of DNA damage in hematopoietic system of irradiated mice. Main methods: C57BL/6 male mice were exposed to 2, 5, and 7.5Gy of whole-body irradiation (WBI), 30 min after intra-peritoneal administration of melatonin with different doses. Mice were sacrificed at different time intervals after WBI, and bone marrow, splenocytes, and peripheral blood lymphocytes were isolated for studying various parameters including micronuclei (MN), cell cycle, comet, gamma-H2AX, gene expression, amino acid profiling, and hematology. Key findings: Melatonin100mg/kg ameliorated radiation (7.5Gy and 5Gy) induced MN frequency and cell death in bone marrow without mortality. At 24 h of post-WBI (2Gy), the frequency of micronucleated polychromatic erythrocytes (mnPCE) with different melatonin doses revealed 20 mg/kg as optimal i.p. dose for protecting the hematopoietic system against radiation injury. In comet assay, a significant reduction in radiation-induced % DNA tail (p <= 0.05) was observed at this dose. Melatonin reduced gamma-H2AX foci/cell and eventually reached to the control level. Melatonin also decreased blood arginine levels in mice after 24 h of WBI. The gene expression of GCSF, Bcl-2-associated X protein (BAX), and Bcl2 indicated the role of melatonin in G-CSF regulation and downstream pro-survival pathways along with anti-apoptotic activity. Significance: The results revealed that melatonin recovers the hematopoietic system of irradiated mice by inducing G-CSF mediated radioprotection.

Background Salivary gland tumor frequency in the head and neck region is quite less and mostly benign. However, pathogenesis is associated with oxidative stress in the mitochondria. Hence, we are aiming to identify single nucleotide polymorphisms (SNP)/single nucleotide variants (SNV) in the mitochondrial DNA D-loop region of salivary gland tumors (SGT). We analyzed 19 biopsied tissue (formalin-fixed paraffin-embedded) tumors, i.e., pleomorphic adenoma-5, mucoepidermoid carcinoma-6, adenoid cystic carcinoma-5, and polymorphous low-grade adenocarcinoma-3. This extracted DNA was amplified to visualize the entire D-loop region of the mitochondrial genome of SGT. Results The three hotspot mutation were noticed at 16,519 (thymine-cytosine) (number = 10), 73 (adenine-guanine) (number = 8), and 195 (thymine-adenine) (number = 4) in the D-loop in salivary gland tumors. We observed novel synonymous mutation in the 195 region of mitochondrial D-loop, which is a novel as per Mitomap (a human mitochondrial genomic database). Conclusions We hypothesized that the biological behavior of SGT is majorly dependent upon the stress level at mitochondria in the D-loop region. SNPs noted in mt-DNA should be noted as a pivotal biomarker for the progression or metastasis of SGT in individuals at risk.

Biallelic PRKG2 (Protein Kinase, cGMP dependent Type-2) mutations cause a novel acromesomelic dysplasia PRKG2 type. We report generation of induced pluripotent stem cell line from lymphoblastoid cell lines of the patient carrying the reported frameshift mutation (p.Asn164Lysfs*2). The derived iPSC line exhibits all the features of pluripotency, free of major genetic alterations due to reprogramming process and has the capability to differentiate into three germ layers. This iPSC cell line may provide an opportunity to investigate the effect of PRKG2 mutations upon FGF (fibroblast-growth-factor) induced MAPK signalling involved in chondrocyte proliferation in-vitro and may aid in possible therapeutic screening of novel biomolecules.

Background: Duchenne Muscular Dystrophy (DMD) is an X-linked recessive muscular dystrophy that affects young boys and is caused by mutation of the dystrophin gene located over X chromosome. Materials and Methods: In this prospective study, 120 clinically diagnosed DMD patients were tested for exon deletions, duplication or point mutation. Results: Of the 120 clinically suspected DMD patients, the diagnosis of DMD was confirmed by the genetic study or muscle biopsy in 116 patients. The mean age of onset was 3.2 years and the mean age at presentation was 7.2 years. 110/120 cases were confirmed by genetic testing and six were by absence of staining for dystrophin on muscle biopsy. DMD gene deletion was present in 78.5%, duplication in 5.3% and point mutation in 11.2% cases. 70.3% of patients had deletion located at a distal hot spot region. Single exon deletion was found in 16.5%. Distal hotspot exons 47, 48 and 50 were the commonly deleted exons. Conclusions: In our study, 94.8% cases showed genetic change in the DMD gene. Muscle biopsy was the choice of investigation in earlier days. Detection of DMD by DNA based method eliminates the need to do an invasive procedure for diagnosis. Hence the genetic testing should be the investigation of choice in suspected cases of DMD. The pattern of deletion, obtained in the population of Rajasthan was similar when compared with other ethnic groups of the Indian population. It would be helpful for researchers to develop drugs specific to exons or for ongoing mutation-specific therapies.

Authors declare no conflict of interest. The peer review history for this article is available at https://publons.com/publon/10.1111/pai.13451.