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Adenylate kinase (AK) deficiency is a rare erythroenzymopathy associated with hereditary nonspherocytic haemolytic anaemia along with mental/psychomotor retardation in few cases. Diagnosis of AK deficiency depends on the decreased level of enzyme activity in red cell and identification of a mutation in the AK1 gene. Until, only eight mutations causing AK deficiency have been reported in the literature. We are reporting two novel missense mutation (c.71A > G and c.413G > A) detected in the AK1 gene by next-generation sequencing (NGS) in a 6-year-old male child from India. Red cell AK enzyme activity was found to be 30% normal. We have screened a total of 32 family members of the patient and showed reduced red cell enzyme activity and confirm mutations by Sanger’s sequencing. On the basis of Sanger sequencing, we suggest that the proband has inherited a mutation in AK1 gene exon 4 c.71A > G (p.Gln24Arg) from paternal family and exon 6 c.413G > A (p.Arg138His) from maternal family. Bioinformatics tools, such as SIFT, Polymorphism Phenotyping v.2, Mutation Taster, MutPred, also confirmed the deleterious effect of both the mutations. Molecular modelling suggests that the structural changes induced by p.Gln24Arg and p.Arg138His are pathogenic variants having a direct impact on the structural arrangement of the region close to the active site of the enzyme. In conclusion, NGS will be the best solution for diagnosis of very rare disorders leading to better management of the disease. This is the first report of the red cell AK deficiency from the Indian population.

Primary renal involvement by T lymphoblasts is rare among adults with T acute lymphoblastic leukaemia. We report a 28‐year‐old man presenting with acute renal failure due to infiltration by T lymphoblasts and his response to paediatric‐inspired modified BFM‐90 protocol. The patient achieved an initial complete remission (CR) but developed central nervous system relapse. He achieved CR2 with cranial irradiation and intrathecal chemotherapy. He underwent a haploidentical transplant in CR2 and remains in remission post‐transplant day 330. An early kidney biopsy helped confirm the diagnosis. Such presentations remain responsive to modified BFM‐90. An early allotransplant in CR2 remains the standard of care.

The present study revisits the vertical distribution of suspended sediment concentration in an open channel flow analytically with a special attention to sediment diffusion coefficient. If turbulent diffusivity is considered to follow a parabolic-type profile, the diffusivity coefficient is zero at the bed and very small near the bed; so alone it may not be enough to diffuse the particles from bed-load layer to suspension region. Due to the hydrodynamic interactions between solid particles, a type of diffusion namely shear-induced diffusion arises. This work considers the Hunt diffusion equation incorporating the concept of shear-induced diffusion and reinvestigates the vertical sediment concentration profile. One of the primary objectives of this work is to show the application of homotopy analysis method (HAM) in determining a convergent series solution for a highly non-linear differential equation governing the vertical sediment concentration distribution for both dilute and high concentrated sediment-laden flows. To that end, HAM efficiently produces an accurate approximate solution to the problem, which is shown by verifying it with the corresponding numerical solution and validating the model with available experimental data. The implementation plan of the method and supporting theorems are provided to have a better understanding on the methodology. On the other hand, the behaviour of the shear-induced diffusion coefficient with vertical distance and varying particle diameters, have also been interpreted physically. In addition, the effects of important turbulent factors such as inverse of Schmidt number, hindered settling on concentration profile, have been investigated considering relevant sets of experimental data.

A new, simple, sensitive, precise and robust high-performance thin layer chromatographic (HPTLC) method was developed for the estimation of andrographolide in herbal extracts and pharmaceutical dosage forms. Analysis of andrographolide was performed on TLC aluminium plates pre-coated with silica gel 60F-254 as stationary phase. Linear ascending development was carried out in twin trough glass chamber saturated with chloroform:toluene:methanol (66:26:8, v/v/v) at room temperature (25 ± 2 °C). The Rf value of andrographolide was found to be 0.49. Camag TLC scanner III was used for spectrodensitometric scanning and analysis in absorbance mode at 229 nm. The system was found to give compact spots for andrographolide (Rf value of 0.49). The data for calibration plots showed good linear relationship with r2 = 0.9986 in the concentration range of 200 ng to 1000 ng with respect to peak area. The present method was validated by precision, recovery, robustness and reproducibility according to ICH guidelines. The limits of detection and quantification were determined and it was found to be 3.5 and 11.7 ng, respectively. Statistical analysis of the data showed that the method is reproducible and selective for estimation of andrographolide.

The well-known Rouse equation is the most widely used equation to determine the vertical distribution of suspended sediment concentration in an open-channel flow. The exponent of Rouse equation, known as Rouse number, contains the parameter β defined by the ratio of sediment diffusion coefficient to turbulent diffusion coefficient. As such to measure sediment concentration accurately, an appropriate expression for β is essentially needed. The present study, therefore, focuses on the derivation of depth-averaged β through modified expressions of sediment and turbulent diffusion coefficients. A regression analysis is done to establish the relation between β and normalized settling velocity, and the relation is used to determine suspension concentration.

Common variable immunodeficiency (CVID) causes a chronic debilitating syndrome in affected patients and often leads to high morbidity and mortality. Among its several presentations, chronic enteropathy leading to malabsorption syndrome continues to offer a major diagnostic dilemma. Lately, higher testing for norovirus infection in patients with CVID enteropathy has correlated its presence to chronic diarrhoeas, severe villous atrophy and malabsorption syndromes. There have been no such reports of its clinical and histopathological manifestations in CVID from India. Here, we demonstrate the significance of testing for norovirus in the gut with multiplex PCRs in an adult patient with a chronic undiagnosed CVID enteropathy and its response to monthly intravenous immunoglobulin (IVIG) therapy. Our patient responded after three cycles of monthly IVIG with a complete clinical recovery of his bowel functions, leading to a significant improvement in his quality of life and performance status.

Common Variable Immunodeficiency (CVID) is a heterogeneous disorder characterized by impaired antibody production and recurrent infections. In this study we investigated the clinical and immunological features of CVID in Indian patients and develops a machine learning model for predicting disease severity. We retrospectively analyzed 150 patients diagnosed with CVID over a decade at a tertiary care center in India. The median age of diagnosis was 18 years, with a male predominance (62%). The majority of patients (66.6%) had a severe phenotype, with recurrent respiratory tract infections being the most common clinical manifestation (84.2%). Gastrointestinal complications were observed in 45% of patients, while autoimmune manifestations were seen in 21%. All patients exhibited hypogammaglobulinemia. IgA levels varied, with 7.8% normal and 14.5% undetectable. IgM levels were decreased in 85.5% of patients. B-cell analysis revealed 64.4% had reduced class-switched memory B cells, with 21.7% showing very low levels. Nine adult patients presented with late-onset combined immunodeficiency. Genetic testing, performed on 52 patients, identified underlying monogenic causes in 29 pediatric and 15 adult patients. LRBA deficiency was the most common genetic defect, found in seven pediatric and three adult patients. We developed a novel machine learning-based severity prediction model for CVID patients, utilizing readily available lymphocyte subsets, class-switched memory B cell counts, and serum immunoglobulin levels to provide an accessible and robust tool for predicting disease severity using Ameratunga’s clinical severity score. Random Forest outperformed other models across all metrics, achieving an accuracy of 0.853 (95% CI: 0.840–0.866). Feature importance analysis across all models identified Th-Tc ratio, CD19, and IgM levels as the most influential predictors for severity prediction. Our study highlights the diverse clinical and immunological features of CVID in Indian patients, emphasizing the need for early diagnosis and individualized management strategies. The machine learning model developed using commonly available immune parameters provide a robust tool for predicting disease severity, potentially guiding treatment strategies to improve patient outcomes.

Talicabtagene autoleucel (tali-cel) is the first humanized CD19-directed CAR-T cell therapy approved in India for relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) and B-cell non-Hodgkin lymphoma (B-NHL). Here, we integrated clinical and manufacturing operations through a centralized coordination unit (CCU) and evaluated tali-cel implementation. Patients with r/r B-ALL (n = 105) and r/r B-NHL (n = 145) who underwent leukapheresis between 15 November 2023 and 31 January 2025 across 56 treatment centers were included. The CCU enabled timely delivery, with manufacturing slot allocation within one week of slot request and a median vein-to-vein time of 29 days (range, 16-102), independent of geographic location. In r/r B-ALL patients, the median follow-up was 14 months, and the median overall survival (OS) not reached, and progression-free survival (PFS) was 18 months (range: 9-NR). The 12-month OS and PFS were 64% (95% CI: 53-72) and 55% (95% CI: 45-65). In r/r B-NHL, the median follow-up was 13 months and the median PFS was 11 months (range:7-16) and OS was not reached. The 12-month OS and PFS were 63% (95% CI: 54-71) and 47% (95% CI: 38-56). No patients underwent consolidative stem cell transplantation. Grade 3/4 cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and Immune Effector Cell-associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS) occurred in 6%, 4%, and 23% of r/r B-ALL and 6%, 3%, and 18% of r/r B-NHL patients, respectively. These findings demonstrate the successful implementation of tali-cel across multiple centers in a large cohort, which might contribute towards improving CAR-T access globally.